AI-assisted literature exploration of innovative Chinese medicine formulas.

Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives. Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations. Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang's 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs. Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.

Transcriptomic analysis of lipoteichoic acid­treated undifferentiated and neutrophil­like differentiated HL­60 cells.

Toll-like receptor 2 (TLR2) is an important sensor for innate immune cells, including neutrophils, for the recognition of pathogen infection. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is a TLR2 ligand. LTA-induced TLR2 signaling pathways are well established in neutrophils. However, experimental studies regarding transcriptional regulation and the molecular mechanisms in primary human neutrophils are limited due to their short lifespan. The promyelocytic leukemia cell line, HL-60, can differentiate into a neutrophil-like phenotype following treatment with dimethyl sulfoxide. The aim of the present study was to investigate whether differentiated HL-60 (dHL-60) cells induced a similar gene expression profile upon LTA treatment as that previously determined for primary human neutrophils. After 4 or 24 h of Staphylococcus aureus LTA treatment, undifferentiated HL-60 (uHL-60) and dHL-60 cells were collected for RNA sequencing. The results demonstrated that hundreds of identical differentially expressed genes (DEGs) were observed in 1 and 10 µg/ml LTA-treated dHL-60 cells following 4 and 24 h of incubation, while almost no DEGs between LTA-treated HL-60 and dHL-60 cells were observed. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG), it was noted that the pathways of shared DEGs between the 1 and 10 µg/ml LTA-treated dHL-60 cells at both time points were significantly enriched in immune and inflammatory response-related pathways, such as cellular response to tumor necrosis factor, interleukin-1, interferon γ, neutrophil chemotaxis, the NF-κB signaling pathway and the Toll-like receptor signaling pathway. In addition, when comparing the effect of 1 and 10 µg/ml LTA treatment on dHL60 cells, it was found that all enriched GO and KEGG pathways were associated with the TLR signaling pathways of neutrophils. The results of the present study provided important information for the implementation of mRNA profiling in LTA-treated dHL-60 cells and may indicate the feasibility of using dHL-60 cells as a research model for TLR2 signaling in human neutrophils.

A novel goose-origin Tembusu virus exhibits pathogenicity in day-old chicks with evidence of direct contact transmission.

In late 2020, an outbreak of Tembusu virus (TMUV)-associated disease occurred in a 45-day-old white Roman geese flock in Taiwan. Here, we present the identification and isolation of a novel goose-origin TMUV strain designated as NTU/C225/2020. The virus was successfully isolated using minimal-pathogen-free duck embryos. Phylogenetic analysis of the polyprotein gene showed that NTU/C225/2020 clustered together with the earliest isolates from Malaysia and was most closely related to the first Taiwanese TMUV strain, TP1906. Genomic analysis revealed significant amino acid variations among TMUV isolates in NS1 and NS2A protein regions. In the present study, we characterized the NTU/C225/2020 culture in duck embryos, chicken embryos, primary duck embryonated fibroblasts, and DF-1 cells. All host systems were susceptible to NTU/C225/2020 infection, with observable lesions. In addition, animal experiments showed that the intramuscular inoculation of NTU/C225/2020 resulted in growth retardation and hyperthermia in day-old chicks. Gross lesions in the infected chicks included hepatomegaly, hyperemic thymus, and splenomegaly. Viral loads and histopathological damage were displayed in various tissues of both inoculated and naïve co-housed chicks, confirming the direct chick-to-chick contact transmission of TMUV. This is the first in vivo study of a local TMUV strain in Taiwan. Our findings provide essential information for TMUV propagation and suggest a potential risk of disease outbreak in chicken populations.

Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies.

Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors. Hence, identifying the crucial pathways and biomarkers for the treatment of GBM is of prime importance. We conducted this study to identify the pathways associated with GBM. We used The Cancer Genome Atlas (TCGA) GBM genomic dataset to identify differentially expressed genes (DEGs). We investigated the prognostic values of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) family of genes in GBM using a Chinese Glioma Genome Atlas (CGGA) dataset. Within this dataset, we observed the association in the tumor microenvironment between the gene expression of GNAI subunit 3 (GNAI3) and a poor prognosis. MetaCore and gene ontology (GO) analyses were conducted to explore the role of GNAI3 in co-expressed genes and associated signaling pathways using a transcript analysis. Notable pathways included "Cytoskeleton remodeling regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases" and "Immune response B cell antigen receptor (BCR) pathway". A single-cell analysis was used to assess GNAI3 expression in GBM. The results demonstrated that GNAI family genes, specifically GNAI3, were significantly associated with carcinogenesis and malignancy in GBM patients. Our findings suggest that the GNAI3 gene holds potential as a prognostic biomarker for GBM.

Isolation, full sequence analysis, and in situ hybridization of pigeon paramyxovirus-1 genotype VI.2.1.1.2.2 from oriental turtle doves (Streptopelia orientalis).

Pigeon paramyxovirus-1 (PPMV-1), a genetic variant of avian paramyxovirus-1 (APMV-1), has been identified in Columbiformes and is the primary cause of diseases in captive and free-ranging pigeons. However, it has also been reported that PPMV-1 can infect chickens naturally and experimentally, thus posing a potential threat to the poultry industry. This study investigated a lethal outbreak of paramyxovirus infection that occurred among 16 oriental turtle doves (Streptopelia orientalis) in a walk-in aviary at a zoo from March to April 2021. Necropsies were performed, and histopathological findings revealed mild to moderate lymphoplasmacytic infiltration in several organs, such as the pancreas, liver, kidneys, and lungs. Reverse transcription polymerase chain reaction (RT-PCR) using formalin-fixed paraffin-embedded tissue blocks, virus isolation from fresh tissue, and in situ hybridization against the fusion (F) protein confirmed the diagnosis for PPMV-1 infection. The isolated strain NTU/C239/21 was fully sequenced by next-generation sequencing, and the results of phylogenetic analyses revealed that the F protein of NTU/C239/21 shared 98.8% nucleotide sequence identity with Pigeon/Taiwan/AHRI121/2017, which was isolated from a feral pigeon in Taiwan. The present study is the first to identify PPMV-1 infection in Streptopelia orientalis and suggests that Streptopelia orientalis may also play an important role in spreading the infection, similar to pigeons in APMV-1 spreading.

Novel pH-activatable NIR fluorogenic spray mediated near-instant and precise tumor margins identification in human cancer tissues for surgical resection.

Rationale: Challenges such as developing a universal tumor-specific probe for tumor margin identification in diverse tumors with an easy-operative and fast-imaging pattern still exist. Hence, in the present study, a rapidly "off-on" near-infrared (NIR) fluorescent probe NBD with pH-activatable fluorescence and a large Stokes shift was constructed for spray mediated near-instant and precise clinical tumor margins identification. Methods: NBD was designed and synthesized by introducing both diphenyl amino group and benzo[e]indolium to ß-carboline at C-6 and C-3 positions respectively. The optical properties of NBD was characterized by absorption spectra, fluorescence spectra. Subsequently, we investigated its pH-dependent mechanism by 1H NMR and density functional theory (DFT) calculation. NBD was further under deeper investigation into its imaging performance in nude mice models (subcutaneous, orthotopic, metastatic tumor), and clinical tissues from patients with three clinically representative tumors (liver cancer, colon cancer, and lung cancer). Results: It was found that NBD had NIR fluorescence (742 nm), a large Stokes shift (160 nm), and two-photon absorbance (1040 nm). Fluorescence quantum yield (ФF) increased by 5.5-fold when pH decreased from 7.4 to 4.0, to show pH-dependent property. Furthermore, NBD could not only selectively light up all four cancer cell lines, but also delineate xenograft tumor and orthotopic microtumor to guide surgical tumor resection, and track metastatic tissues. Particularly, after simple topical spray (three minutes later), NBD could rapidly and precisely distinguish the boundary ranges of three kinds of clinical cancer specimens including liver, colon, and lung cancers, with high tumor-to-normal tissue signal ratios (6.48~9.80). Conclusions: Therefore, the proposed fluorescent probe NBD may serve as a versatile NIR fluorogenic spray for the near-instant visualization of tumor margins and assisting surgeons in surgerical resection of clinical cancers.

Fully automated film mounting in dental radiography: a deep learning model.

BACKGROUND: Dental film mounting is an essential but time-consuming task in dental radiography, with manual methods often prone to errors. This study aims to develop a deep learning (DL) model for accurate automated classification and mounting of both intraoral and extraoral dental radiography. METHOD: The present study employed a total of 22,334 intraoral images and 1,035 extraoral images to train the model. The performance of the model was tested on an independent internal dataset and two external datasets from different institutes. Images were categorized into 32 tooth areas. The VGG-16, ResNet-18, and ResNet-101 architectures were used for pretraining, with the ResNet-101 ultimately being chosen as the final trained model. The model's performance was evaluated using metrics of accuracy, precision, recall, and F1 score. Additionally, we evaluated the influence of misalignment on the model's accuracy and time efficiency. RESULTS: The ResNet-101 model outperformed VGG-16 and ResNet-18 models, achieving the highest accuracy of 0.976, precision of 0.969, recall of 0.984, and F1-score of 0.977 (p < 0.05). For intraoral images, the overall accuracy remained consistent across both internal and external datasets, ranging from 0.963 to 0.972, without significant differences (p = 0.348). For extraoral images, the accuracy consistently achieved the highest value of 1 across all institutes. The model's accuracy decreased as the tilt angle of the X-ray film increased. The model achieved the highest accuracy of 0.981 with correctly aligned films, while the lowest accuracy of 0.937 was observed for films exhibiting severe misalignment of ± 15° (p < 0.001). The average time required for the tasks of image rotation and classification for each image was 0.17 s, which was significantly faster than that of the manual process, which required 1.2 s (p < 0.001). CONCLUSION: This study demonstrated the potential of DL-based models in automating dental film mounting with high accuracy and efficiency. The proper alignment of X-ray films is crucial for accurate classification by the model.

A versatile supramolecular nanoagent for three-pronged boosting chemodynamic therapy.

Chemodynamic therapy (CDT) utilizing toxic hydroxyl radicals (·OH) to kill cancer cells exhibits huge potentiality in antitumor treatment. However, inadequate acidity, insufficient hydrogen peroxide (H2O2) amount, and overexpressed reduced glutathione (GSH) inside cancer cells severely restrict the efficacy of CDT. Although numerous efforts have been made, fabricating a versatile CDT material for surmounting these obstacles simultaneously is still a great challenge, especially for supramolecular materials owing to lacking an active metal unit for the Fenton reaction. Here, we intriguingly proposed a powerful supramolecular nanoagent (GOx@GANPs) based on the host-guest interaction between pillar[6]arene and ferrocene for all-sided boosting CDT efficacy via in situ cascade reactions. GOx@GANPs could stimulate intracellular glucose conversion into H+ and H2O2 to optimize the in situ Fenton reaction conditions and continuously produce sufficient •OH. Meanwhile, consumption of the original intracellular GSH pool and inhibition of GSH regeneration were synchronously achieved through the GSH-responsive gambogic acid prodrug and cutting off adenosine triphosphate (ATP) supply for GSH resynthesis, respectively. This complete GSH exhausting characteristic of GOx@GANPs effectively suppressed •OH elimination, ultimately resulting in a superior CDT effect. Furthermore, GOx@GANPs also produced synergistic effects of starvation therapy, chemotherapy, and CDT, exhibiting low toxicity toward normal tissues. Thus, this work introduces a valuable way for optimizing and elevating CDT efficiency and synergistic treatment of tumors.

Acidic tumor microenvironment-activatable fluorescent diagnostic probe for the rapid identification and resection of human tumors via spraying.

A fluorescent diagnostic probe for real-time intraoperative image-guided tumor resection can significantly improve the efficiency and quality of oncological therapy, but their development is challenging. Herein, a novel fluorescent diagnostic probe called HLTC based on ß-carboline was designed and synthesized. HLTC was found to show a ∼10-fold enhancement of fluorescence quantum field with pH from 7.4 to 4.0, indicating its imaging potential in acid environment which is a typical hallmark of the tumor microenvironment (TME). Following fluorescence microscopy imaging showed HLTC could emit specific signals in cancer cells and sections, by both one-photon excitation and two-photon excitation. Importantly, HLTC enabled the precise and rapid delineation of both transplanted tumor and clinical tumor tissues within several minutes of simple topical spray. The tumor-to-background ratio (TBR) was up to 10.2 ± 1.0 at clinical liver cancer tissues and 9.9 ± 0.3 at clinical colon cancer tissues, allowing precise tumor margin identification and the effective guidance of surgical tumor resection. Furthermore, CCK8 assay, pharmacokinetic evaluation, blood analysis and H&E staining were performed, which verified high biocompatibility and biosafety of HLTC at working concentration. These results reveal the exciting potential of this small-molecule fluorescent diagnostic probe for real-time fluorescence-based navigation during surgical tumor resection.

An exploration of the connotation of clinical dental radiology education for medical radiation students in Taiwan in 2022.

Background/purpose: In Taiwan, the dental radiology has a history of more than 100 years. However, medical radiation schools or teaching hospitals have not yet established a set of standard learning content for dental radiology internship. Materials and methods: We used the observational method and dental radiology teaching survey to explore the connotation of clinical dental radiology education for medical radiation students in Taiwan. Results: There were 64 dental departments of hospitals with their own independent dental radiology departments in Taiwan in 2022. Among them, 58 (90.63%) were in the teaching hospitals. Of the 58 dental radiology departments in the teaching hospitals, 40 (68.97%) had medical radiation interns in their dental radiology departments. There was a complete set of seven training items for dental radiology internship. The mean training items in the medical centers (4.94) was significantly higher than that in the regional hospital (3.9) (P < 0.05). No matter what level of hospital, it is the most common way to implement the training mode with preclinical exercises and then clinical practice. Conclusion: In Taiwan, the current status of dental radiology teachers in the teaching hospital is indeed seriously insufficient. It is necessary to establish a standard dental radiology education system, including setting one common dental radiology subject for medical radiation students, and the relevant regulations to formulate the basic requirements of the training items and training hours for dental radiology internship. Thus, medical radiation interns can acquire the operation skills related to dental X-ray machines after completing the internship training.

Facile and Unplugged Surface Plasmon Resonance Biosensor with NIR-Emitting Perovskite Nanocomposites for Fast Detection of SARS-CoV-2.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic prompted researchers to develop portable biosensing platforms, anticipating to detect the analyte in a label-free, direct, and simple manner, for deploying on site to prevent the spread of the infectious disease. Herein, we developed a facile wavelength-based SPR sensor built with the aid of a 3D printing technology and synthesized air-stable NIR-emitting perovskite nanocomposites as the light source. The simple synthesis processes for the perovskite quantum dots enabled low-cost and large-area production and good emission stability. The integration of the two technologies enabled the proposed SPR sensor to exhibit the characteristics of lightweight, compactness, and being without a plug, just fitting the requirements of on-site detection. Experimentally, the detection limit of the proposed NIR SPR biosensor for refractive index change reached the 10-6 RIU level, comparable with that of state-of-the-art portable SPR sensors. In addition, the bio-applicability of the platform was validated by incorporating a homemade high-affinity polyclonal antibody toward the SARS-CoV-2 spike protein. The results demonstrated that the proposed system was capable of discriminating between clinical swab samples collected from COVID-19 patients and healthy subjects because the used polyclonal antibody exhibited high specificity against SARS-CoV-2. Most importantly, the whole measurement process not only took less than 15 min but also needed no complex procedures or multiple reagents. We believe that the findings disclosed in this work can open an avenue in the field of on-site detection for highly pathogenic viruses.

A structural analysis of physician agency and pharmaceutical demand.

This paper examines the significance of physician agency in medical providers' prescription choices. Physician agency is considered as medical providers' responses to the price and markup percentage of prescription drugs. Their preferences are allowed to be heterogeneous using a random coefficient logit model. Using a sample of anti-diabetic prescriptions with metformin from a population-based database in Taiwan, empirical results reveal that physician owners, privately-owned medical providers, small medical providers and the medical providers facing less competition are more likely to prescribe drugs with higher profit margins. The aggregate pharmaceutical demand is also found to increase with the markup, which is allowed to be endogenous in the estimation. Price elasticity estimates suggest medical providers are quite responsive to pharmaceutical price changes in Taiwan. Counterfactual analysis reveals the potential impact of physician agency is economically significant. Removing markups and lowering pharmaceutical prices are found to be more welfare enhancing than restricting physicians' dispensing services.

Investigation of the keratinocyte transcriptome altered in high-glucose environment: An in-vitro model system for precision medicine.

BACKGROUND: Impaired wound healing is a serious diabetes complication compromising patients' quality of life. However, the pathogenesis of diabetic wounds (DWs) remains incompletely understood. Human epidermal keratinocyte (HEK) is the sentinel cell that initiates healing processes after the epidermal integrity has been disrupted. OBJECTIVE: This study aimed to investigate the functional roles of HEKs in wound healing and to identify candidate genes, signaling pathways and molecular signatures contributing to the DWs. METHODS: HEKs were cultured in normal or high-glucose environment, followed by scratch, to mimic the microenvironment of normal wounds and DWs. Subsequently, we performed RNA sequencing and systematically analyzed the expression profiles by bioinformatics approaches. RESULTS: High-glucose environment altered the keratinocyte transcriptome responses to wounding. In experimental model of DWs, we found that TNF, CYP24A1, NR4A3 and GGT1 were key overexpressed genes in keratinocytes and were implicated in multiple cellular responses. Further analysis showed that wounding in high-glucose environment activated G-protein-coupled receptor (GPCR) signaling, cAMP response element-binding protein (CREB) signaling, and adrenomedullin signaling in keratinocytes, while dysregulated skin development and immune responses as compared to their counterpart in normal glucose settings. CONCLUSION: This simplified in-vitro model serves as a valuable tool to gain insights into the molecular basis of DWs and to facilitate establishment of personalized therapies in clinical practice.

Prognostic and Immune Infiltration Value of Proteasome Assembly Chaperone (PSMG) Family Genes in Lung Adenocarcinoma.

The complexity of lung adenocarcinoma (LUAD) including many interacting biological processes makes it difficult to find therapeutic biomarkers for treatment. Previous studies demonstrated that PSMG (proteasome assembly chaperone) family members regulate the degradation of abnormal proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. Therefore, we used a holistic bioinformatics approach to explore PSMG genes involved in LUAD patients by integrating several high-throughput databases and tools including The Cancer Genome Atlas (TCGA), and Kaplan-Meier plotter database. These data demonstrated that PSMG3 and PSMG4 were expressed at significantly higher levels in neoplastic cells than in normal lung tissues. Notably, increased expressions of these proteins were correlated with poor prognoses of lung cancer patients, which probably confirmed their fundamental roles in the staging of LUAD tumors. Meanwhile, it was also indicated that there were positive correlations between PSMG family genes and the immune response, metabolism of ubiquinone, cell cycle regulatory pathways, and heat shock protein 90 (HSP90)/phosphatidylinositol 3-kinase (PI3K)/Wnt signaling. Experimental data also confirmed that the knockdown of PSMG4 in LUAD cell lines decreased cell proliferation and influenced expressions of downstream molecules. Collectively, this study revealed that PSMG family members are novel prognostic biomarkers for LUAD progression, which also provide new therapeutic targets of LUAD patients.

Inhibition of lncRNA RPPH1 activity decreases tumor proliferation and metastasis through down-regulation of inflammation-related oncogenes.

OBJECTIVE: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood. METHODS: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells. RESULTS: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells. CONCLUSION: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development.

Boosting the detection performance of severe acute respiratory syndrome coronavirus 2 test through a sensitive optical biosensor with new superior antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in late 2019 leading to the COVID-19 disease pandemic that triggered socioeconomic turmoil worldwide. A precise, prompt, and affordable diagnostic assay is essential for the detection of SARS-CoV-2 as well as its variants. Antibody against SARS-CoV-2 spike (S) protein was reported as a suitable strategy for therapy and diagnosis of COVID-19. We, therefore, developed a quick and precise phase-sensitive surface plasmon resonance (PS-SPR) biosensor integrated with a novel generated anti-S monoclonal antibody (S-mAb). Our results indicated that the newly generated S-mAb could detect the original SARS-CoV-2 strain along with its variants. In addition, a SARS-CoV-2 pseudovirus, which could be processed in BSL-2 facility was generated for evaluation of sensitivity and specificity of the assays including PS-SPR, homemade target-captured ELISA, spike rapid antigen test (SRAT), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Experimentally, PS-SPR exerted high sensitivity to detect SARS-CoV-2 pseudovirus at 589 copies/ml, with 7-fold and 70-fold increase in sensitivity when compared with the two conventional immunoassays, including homemade target-captured ELISA (4 × 103 copies/ml) and SRAT (4 × 104 copies/ml), using the identical antibody. Moreover, the PS-SPR was applied in the measurement of mimic clinical samples containing the SARS-CoV-2 pseudovirus mixed with nasal mucosa. The detection limit of PS-SPR is calculated to be 1725 copies/ml, which has higher accuracy than homemade target-captured ELISA (4 × 104 copies/ml) and SRAT (4 × 105 copies/ml) and is comparable with qRT-PCR (1250 copies/ml). Finally, the ability of PS-SPR to detect SARS-CoV-2 in real clinical specimens was further demonstrated, and the assay time was less than 10 min. Taken together, our results indicate that this novel S-mAb integrated into PS-SPR biosensor demonstrates high sensitivity and is time-saving in SARS-CoV-2 virus detection. This study suggests that incorporation of a high specific recognizer in SPR biosensor is an alternative strategy that could be applied in developing other emerging or re-emerging pathogenic detection platforms.

Comprehensive analysis of prognostic significance of cadherin (CDH) gene family in breast cancer.

Breast cancer is one of the leading deaths in all kinds of malignancies; therefore, it is important for early detection. At the primary tumor site, tumor cells could take on mesenchymal properties, termed the epithelial-to-mesenchymal transition (EMT). This process is partly regulated by members of the cadherin (CDH) family of genes, and it is an essential step in the formation of metastases. There has been a lot of study of the roles of some of the CDH family genes in cancer; however, a holistic approach examining the roles of distinct CDH family genes in the development of breast cancer remains largely unexplored. In the present study, we used a bioinformatics approach to examine expression profiles of CDH family genes using the Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), cBioPortal, MetaCore, and Tumor IMmune Estimation Resource (TIMER) platforms. We revealed that CDH1/2/4/11/12/13 messenger (m)RNA levels are overexpressed in breast cancer cells compared to normal cells and were correlated with poor prognoses in breast cancer patients' distant metastasis-free survival. An enrichment analysis showed that high expressions of CDH1/2/4/11/12/13 were significantly correlated with cell adhesion, the extracellular matrix remodeling process, the EMT, WNT/beta-catenin, and interleukin-mediated immune responses. Collectively, CDH1/2/4/11/12/13 are thought to be potential biomarkers for breast cancer progression and metastasis.

A Single-Arm Phase Ib/II Study of Lenvatinib plus Eribulin in Advanced Liposarcoma and Leiomyosarcoma.

PURPOSE: Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin. METHODS: LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter platform. RESULTS: Thirty patients were enrolled (leiomyosarcoma 21, liposarcoma 9); the median age was 59. One patient had to temporarily stop lenvatinib due to grade 2 arthritis in the first cycle, meeting DLT criteria. Four of 6 patients had to decrease the dose of lenvatinib to 14 mg between cycles two and three. RP2D was determined at lenvatinib 14 mg/day and eribulin 1.1 mg/m2. The confirmed ORR was 20%, and the ORR was not significantly different between phase Ib/II cohorts (P = 0.23). The median progression-free survival was 8.56 months (95% confidence interval, 4.40-not reached). Translational studies suggested increased dendritic cells in the tumor microenvironment (TME) after treatment. CONCLUSIONS: Lenvatinib plus eribulin has a manageable safety profile and exhibits promising efficacy for treating advanced leiomyosarcoma and liposarcoma.

Comparison of Transcriptomic Signatures between Monkeypox-Infected Monkey and Human Cell Lines.

Monkeypox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus of the family Poxviridae. Unlike smallpox with no animal reservoir identified and patients suffering from milder symptoms with less mortality, several animals were confirmed to serve as natural hosts of MPV. The reemergence of a recently reported monkeypox epidemic outbreak in nonendemic countries has raised concerns about a global outburst. Since the underlying mechanism of animal-to-human transmission remains largely unknown, comprehensive analyses to discover principal differences in gene signatures during disease progression have become ever more critical. In this study, two MPV-infected in vitro models, including human immortal epithelial cancer (HeLa) cells and rhesus monkey (Macaca mulatta) kidney epithelial (MK2) cells, were chosen as the two subjects to identify alterations in gene expression profiles, together with co-regulated genes and pathways that are affected during monkeypox disease progression. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and MetaCore analyses, we discovered that elevated expression of genes associated with interleukins (ILs), G protein-coupled receptors (GPCRs), heat shock proteins (HSPs), Toll-like receptors (TLRs), and metabolic-related pathways play major roles in disease progression of both monkeypox-infected monkey MK2 and human HeLa cell lines. Interestingly, our analytical results also revealed that a cluster of differentiation 40 (CD40), plasmin, and histamine served as major regulators in the monkeypox-infected monkey MK2 cell line model, while interferons (IFNs), macrophages, and neutrophil-related signaling pathways dominated the monkeypox-infected human HeLa cell line model. Among immune pathways of interest, apart from traditional monkeypox-regulated signaling pathways such as nuclear factor- (NF-κB), mitogen-activated protein kinases (MAPKs), and tumor necrosis factors (TNFs), we also identified highly significantly expressed genes in both monkey and human models that played pivotal roles during the progression of monkeypox infection, including CXCL1, TNFAIP3, BIRC3, IL6, CCL2, ZC3H12A, IL11, CSF2, LIF, PTX3, IER3, EGR1, ADORA2A, and DUOX1, together with several epigenetic regulators, such as histone cluster family gene members, HIST1H3D, HIST1H2BJ, etc. These findings might contribute to specific underlying mechanisms related to the pathophysiology and provide suggestions regarding modes of transmission, post-infectious sequelae, and vaccine development for monkeypox in the future.

QTc Interval is Associated with Atrial Fibrillation in Individuals with Metabolic Syndrome Phenotype.

Purpose: Manifestations of metabolic syndrome (MetS) carry risks for atrial fibrillation (AF). The study determined whether any electrocardiographic parameter can reflect increased AF risk in individuals with MetS. Patients and Methods: From our University Hospital database, we examined the presence of AF and its correlation with MetS manifestations, renal function, lipid profiles, and electrocardiographic parameters (P wave duration, PR interval, QRS width, and QTc intervals). Between January 2008 and December 2015, data from 4479 adults (women 41.6% vs men 58.4%) were identified. Results: The overall prevalence of AF was 12.4%, without sex differences (women, 12.8% vs men, 12.1%). Patients with AF were older (age 73.9 ± 11.8 vs non-AF 67 ± 13.5 years), with lower lipid levels (TG, total cholesterol, and LDL-cholesterol, all p < 0.0001), and at lower eGFR level (64.1 ± 30.9 vs non-AF 68.8 ± 41.4 mL/min/1.73m2, p < 0.0001). Besides, sex differences were present in all electrocardiographic parameters (all p < 0.05). Hypertension had the highest odds ratio (1.33; p = 0.026) for AF. Comparing AF to non-AF, the QTc of quartiles was significantly different (p < 0.0089). The shortest and longest QTc quartiles had an increased incidence of AF. Conclusion: AF risk in patients with MetS phenotypes can be reflected by QTc quartiles.