Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. Despite the long‐standing recognition of the crosstalk between carcinoma‐associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment, how CAFs may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that lncRNA CCAL (colorectal cancer‐associated lncRNA) promotes oxaliplatin (Oxa) resistance of CRC cells. RNA‐ISH shows higher CCAL expressed in the tumor stroma compared to cancer nests of CRC tissues. Functional studies reveal that CCAL is transferred from CAFs to the cancer cells via exosomes, where it suppresses CRC cell apoptosis, confers chemoresistance and activates β‐catenin pathway in vitro and in vivo. Mechanistically, CCAL interacts directly with mRNA stabilizing protein HuR (human antigen R) to increase β‐catenin mRNA and protein levels. Our findings indicate that CCAL expressed by CAFs of the colorectal tumor stroma contributes to tumor chemoresistance and CCAL may serve as a potential therapeutic target for Oxa resistance.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1–10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.

Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with a strong tendency for metastasis and recurrence. Finding effective biomarkers for the early diagnosis of HNSCC is critical for the early treatment and prognosis of patients.Methods: RNA sequencing data including long non-coding RNAs (lncRNAs), messenger RNA (mRNAs) and microRNAs (miRNAs) of 141 HNSCC and 44 adjacent normal tissues were obtained from the TCGA. Differentially expressed genes were analyzed using the R package DESeq. GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. A competing endogenous RNAs (ceRNA) network was constructed. The most differentially expressed genes in the main ceRNA network were chosen for nasopharyngeal carcinoma (NPC) cell lines and NPEC2 Bmi-1 cell line verification. A receiver operating characteristic (ROC) curve was constructed for 141 specimens of HNSCC tissues from 44 control samples.Results: In our study, 79 HNSCC-associated abnormally expressed lncRNAs , 86 abnormally expressed miRNAs and 324 abnormally expressed mRNAs were identified. The public microarray results showed that LINC00958 and HOXC13-AS expression levels were upregulated in HNSCC tissues compared with the adjacent normal tissues in this study (p < 0.0001). LINC00958 and HOXC13-AS expression levels in NPC cell lines were higher than those in the NPEC2 Bmi-1 cell line (p < 0.05). The results showed that the area under the ROC curve (AUC) of LINC00958 reached up to 0.906 at a cutoff value of 7.96, with a sensitivity and specificity of 80.85% and 90.91%, respectively. The AUC of HOXC13-AS reached up to 0.898 at a cutoff value of 0.695, with sensitivity and specificity values of 86.23% and 83.78%, respectively.Conclusion: The current study indicates that LINC00958 and HOXC13-AS are new candidate diagnostic biomarkers for HNSCC patients.

Pseudomonas aeruginosa (PA) is a common Gram‑negative bacterium and can cause serious infections, including hospital‑acquired pneumonia, suppurative bacterial keratitis and acute burn wound infection. The pathogenesis of PA infections is closely associated with excessive inflammatory responses and bacterial virulence factors. Wingless‑type MMTV integration site family, member 3A (Wnt3a), an upstream mediator in the canonical Wnt signaling pathway, has been implicated as a regulator of inflammation. However, its role in PA‑induced inflammation and bacterial clearance remains unknown. In the present study, the efficacy of Wnt3a conditioned media (Wnt3a‑CM) was assessed using western blotting and immunofluorescence, which showed that β‑catenin, a downstream molecule of Wnt3a, was upregulated and translocated to the nucleus following exposure to 50% Wnt3a‑CM for 6 h. To explore the role of Wnt3a in PA‑induced inflammation, the mRNA levels of pro‑inflammatory cytokines and apoptosis in macrophages were measured using reverse transcription‑quantitative polymerase chain reaction and flow cytometry, respectively. This indicated that Wnt3a suppressed inflammation by reducing the production of pro‑inflammatory cytokines and by promoting apoptosis in macrophages. Furthermore, the mechanism of macrophage‑mediated bacterial killing was investigated, and the results indicated that Wnt3a enhanced macrophage‑mediated intracellular bacterial killing via the induction of the production of cathelicidin‑related antimicrobial peptide and β‑defensins 1. Taken together, the current study explored the role of Wnt3a in inflammation and bacterial invasion, which may provide an improved understanding of host resistance to PA infection.

Background: We aimed to evaluate the analytical performance of five commercial RT‐PCR kits (Genekey, Daan, BioGerm, Liferiver, and Yaneng) commonly used in China, since such comparison data are lacking.Methods: A total of 20 COVID‐19 confirmed patients and 30 negative nasopharyngeal swab specimens were analyzed by five kits. The detection ability of five RT‐PCR kits was evaluated with 5 concentration gradients diluted by a single positive sample. The limit of detection was evaluated by N gene fragment solid standard. Two positive clinical specimens were used to evaluate the repeatability and imprecision. Finally, we used six human coronaviruses plasmid and four respiratory pathogens plasmid to check for cross‐reactivity.Results: The positive detection rate was 100% for Genekey, Daan, and BioGerm,and 90% for Liferiver and Yaneng in 20 clinical SARS‐CoV‐2 infection. The coincidence rate of five kits in 10 negative samples was 100%. The detection rate of target genes for Daan, BioGerm, Liferiver, and Yaneng was 100% from Level 1 to Level 3. In Level 4, only Daan detection rate was 100%. In Level 5, five kits presented poor positive rate. The limit of detection declared by each manufacturer was verified. The repeatability for target genes was less than 5% and so did the total imprecision. There is no cross‐reactivity of five kits with six human coronaviruses and four respiratory pathogens for ORF1ab and N gene.Conclusions: Five RT‐PCR kits assessed in this study showed acceptable analytical performance characteristics and are useful tools for the routine diagnosis of SARS‐CoV‐2.

The high sensitivity and specificity of terahertz (THz) biosensing are both promising and challenging in DNA sample detection. This study produced and refined a flexible THz MM biosensor for ultrasensitive detection of HBV in clinical serum samples based on a gold magnetic nanoparticle-mediated rolling circle amplification (GMNPs@RCA) sandwich assay under isothermal conditions. Typically, solid-phase RCA reactions mediated by circular padlock probes (PLPs) are triggered under isothermal conditions in the presence of HBV DNA, resulting in long single-stranded DNA (ssDNA) with high fidelity and specificity. Then, the resultant ssDNA was conjugated with detection probes (DPs) immobilized on gold nanoparticles (DP@AuNPs) to form GMNPs-RCA-AuNPs sandwich complexes. The HBV DNA concentrations were quantified by introducing GMNPs-RCA-AuNPs complexes into the metasurface of a flexible THz metamaterial-based biosensor chip and resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 1.27E + 02 IU/ml of HBV DNA from clinical serum samples. The HBV DNA concentration was linearly correlated with the frequency shift of the THz metamaterials within the range of 1.27E + 02∼1.27E + 07 IU/ml, illustrating the applicability and accuracy of our assay in real clinical samples. This strategy constitutes a promising THz sensing method to identify virus DNA. In the future, it is hoped it can assist with pathogen identification and clinical diagnosis.