May 2025
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4 Reads
Food Chemistry
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May 2025
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4 Reads
Food Chemistry
February 2025
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37 Reads
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1 Citation
Communications Biology
The correlation between persistent human cytomegalovirus (HCMV) infection and poor prognosis in colorectal cancer (CRC) patients has garnered increasing attention. UL82 is a tegument protein of HCMV, and our previous research indicated that the presence of UL82 is significantly associated with reduced overall survival in CRC patients. However, the mechanism by which UL82 affects the prognosis of CRC patients remains unclear. In this study, we investigated the role of UL82 in CRC progression through both in vitro and in vivo experiments, and revealed its downstream regulatory pathways by integrating transcriptomics, metabolomics, and proteomics. Our findings first revealed that UL82 significantly promoted CRC cell proliferation by increasing the proportion of cells in the S phase of the cell cycle. Additionally, UL82 enhanced the expression of the oncogene AGR2, while knockdown of AGR2 abolished the proliferative effect of UL82. Interestingly, UL82 interacted with the transcription factor DDX5, which transcriptionally inhibited AGR2 expression. Furthermore, this UL82-AGR2 axis promoted nucleotide metabolism in CRC cells by enhancing the levels of nucleotide synthesis enzymes DTYMK, RRM2, and TYMS. In conclusion, our study suggests that the UL82/DDX5 complex may promote nucleotide metabolism and cell cycle progression of CRC by upregulating AGR2 and UL82 may serve as a potential prognostic biomarker for CRC patients.
February 2025
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8 Reads
BIO-PROTOCOL
Tuberculosis (TB) remains the leading cause of human mortality in infectious diseases. Drug-resistant TB, particularly multidrug-resistant TB and extensively drug-resistant TB, poses a pressing clinical and public health challenge. The main causative agents of TB are known as Mycobacterium tuberculosis (MTB), which exhibits a highly complex drug resistance profile. Traditional culture-based phenotypic drug susceptibility testing is time-consuming, and PCR-based assays are restricted to detecting known mutational hotspots. In this study, we present a protocol leveraging high-throughput nanopore sequencing technology in conjunction with multiplex PCR, termed targeted nanopore sequencing, for the identification of MTB and analysis of its drug resistance. Our method for MTB drug resistance assessment offers the benefits of being culture-free, efficient, high-throughput, and highly accurate, which could significantly aid in clinical patient management and the control of TB infections. Key features • Targeted nanopore sequencing detects 18 genes simultaneously linked to antibiotic resistance in MTB. • The method provides broad drug resistance profiles for 14 first- and second-line anti-TB drugs without bacterial culture. • The expedited turnaround time of the process is approximately 7.5 h with a detection limit of 10² bacteria/mL.
January 2025
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7 Reads
October 2024
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76 Reads
Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m³ for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.
July 2024
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8 Reads
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3 Citations
Food Chemistry
May 2024
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44 Reads
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5 Citations
Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is one of the urgent clinical problems and public health challenges. Culture-based phenotypic drug susceptibility testing (pDST) is time-consuming, and PCR-based assays are limited to hotspot mutations. In this study, we developed and validated a convenient and efficient approach based on high-throughput nanopore sequencing technology combined with multiplex PCR, namely nanopore targeted sequencing (NTS), to simultaneously sequence 18 genes associated with antibiotic resistance in Mycobacterium tuberculosis (MTB). The analytical performance of NTS was evaluated, and 99 clinical samples were collected to assess its clinical performance. The NTS results showed that MTB and its drug resistance were successfully identified in approximately 7.5 h. Furthermore, compared to the pDST and Xpert MTB/RIF assays, NTS provided much more drug resistance information, covering 14 anti-TB drugs, and it identified 20 clinical cases of drug-resistant MTB. The mutations underlying these drug-resistant cases were all verified using Sanger sequencing. Our approach for this TB drug resistance assay offers several advantages, including being culture-free, efficient, high-throughput, and highly accurate, which would be very helpful for clinical patient management and TB infection control.
May 2024
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27 Reads
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1 Citation
BMC Cancer
Background Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. Methods Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. Results This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. Conclusion Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.
March 2024
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57 Reads
Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-CoV-2 and various respiratory viruses with a sensitivity of 10 copies/mL. When seamlessly integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single molecule spatial resolution of 0.83 copies/m ³ for airborne virus surveillance. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.
November 2023
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9 Reads
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2 Citations
Sensors and Actuators B Chemical
... By utilizing such therapies, it is possible to minimize the risk of off-target side effects, making it a highly promising avenue for research. Some studies have investigated the effects of inhibiting Agr2 using short hairpin RNA (shRNA) or small interfering RNA (siRNA) molecules [144,145]. In a colorectal cancer cell model, silencing Agr2 contributed to metformin-dependent sensitization of cells to chemotherapy [80]. ...
February 2025
Communications Biology
... 6 WGS has emerged as a transformative approach in pathogen diagnostics, providing high-resolution genotyping and precise pathogen identification. 7,8 Unlike traditional DST methods, WGS provides a comprehensive analysis of MTB genomic DNA to prediction of drug resistance mechanisms across multiple antimicrobials. 9 While WGS has primarily been applied in economically developed regions with low TB burden, its potential in determining resistance to first-line drugs is increasingly being recognized. ...
May 2024
... ENO2, primarily located in mature neurons, was the first enzyme identified in mammals and has been reported to show elevated expression in tumors like glioblastoma (36), neuroendocrine prostate carcinoma (37), and renal cell carcinoma (38). Recent evidence also supports ENO2's role in shaping the tumor immune microenvironment, particularly through neutrophil recruitment (39). In contrast to prior studies, our data reveal that ENO2's association with dendritic cell infiltration in COAD may enhance antigen presentation, providing a mechanistic rationale for its inclusion in mRNA vaccine design. ...
May 2024
BMC Cancer
... 34 However, one tube can detect only one target at a time, whether for EVs or EV-A71. 35 Furthermore, when performing LAMP-CRISPR detection in two steps, opening the tube can allow the target virus that might be present in the air to enter the sample or reaction system, leading to false positive results. The limitation underscores the need for advancements in multiplex capabilities and specificity to enhance diagnostic potential. ...
October 2023
ACS Infectious Diseases
... MAVS mainly participates in the IFN signaling pathway [22] . Mfn1, Mfn2 [23] , TOM70 [24] , VDAC1 [25] , TRADD, FADD [26] , Atg5 and Atg12 [27] regulate innate immunity through the modulation of MAVS-mediated signaling. Speci cally, Mfn1 and Mfn2 regulate mitochondrial fusion [28] . ...
March 2023
Microbiology Spectrum
... Recent advances include the integration of machine learning (ML) and deep learning (DL) models to analyze factors influencing pancreatic fistula rates and INP-related mortality, enhancing risk stratification and personalized management [56,77,78]. Recent advances in ML research have demonstrated that random forest-based models exhibit superior predictive performance for severe acute pancreatitis and have the potential to facilitate personalized therapeutic strategies [79]. Furthermore, ML models utilizing gradient boosting decision trees surpass conventional clinical scoring systems, including the systemic inflammatory response syndrome score and bedside index for severity in acute pancreatitis score, in predicting sepsis among acute pancreatitis patients, thereby may serve as an effective tool for early identification of high-risk patients and timely clinical intervention optimization [80]. ...
January 2023
Journal of Gastroenterology and Hepatology
... The cell atlas was visualized using Uniform Manifold Approximation and Projection (UMAP) by "RunUMAP" [40]. 16:188 Cell cluster annotation Distinct cell clusters were identified and annotated using established cell markers from the literature [18,[41][42][43][44][45]. The COSG method (v0.9.0), based on cosine similarity, was employed for accurate and efficient marker gene identification [46]. ...
February 2022