Single-cell sequencing provides promising information in tumor evolution and heterogeneity. Even with the recent advances in circulating tumor cell (CTC) technologies, it remains a big challenge to ...precisely and effectively isolate CTCs for downstream analysis. The Cell Reveal
system integrates an automatic CTC enrichment and staining machine, an AI-assisted automatic CTC scanning and identification system, and an automatic cell picking machine for CTC isolation. H1975 cell line was used for the spiking test. The identification of CTCs and the isolation of target CTCs for genetic sequencing were performed from the peripheral blood of three cancer patients, including two with lung cancer and one with both lung cancer and thyroid cancer. The spiking test revealed a mean recovery rate of 81.81% even with extremely low spiking cell counts with a linear relationship between the spiked cell counts and the recovered cell counts (Y = 0.7241 × X + 19.76, R
= 0.9984). The three cancer patients had significantly higher TTF-1
CTCs than healthy volunteers. All target CTCs were successfully isolated by the Cell Picker machine for a subsequent genetic analysis. Six tumor-associated mutations in four genes were detected. The present study reveals the Cell Reveal
platform can precisely identify and isolate target CTCs and then successfully perform single-cell sequencing by using commercially available genetic devices.
Electrochemically converting nitrate, a widespread water pollutant, back to valuable ammonia is a green and delocalized route for ammonia synthesis, and can be an appealing and supplementary ...alternative to the Haber-Bosch process. However, as there are other nitrate reduction pathways present, selectively guiding the reaction pathway towards ammonia is currently challenged by the lack of efficient catalysts. Here we report a selective and active nitrate reduction to ammonia on Fe single atom catalyst, with a maximal ammonia Faradaic efficiency of ~ 75% and a yield rate of up to ~ 20,000 μg h
mg
(0.46 mmol h
cm
). Our Fe single atom catalyst can effectively prevent the N-N coupling step required for N
due to the lack of neighboring metal sites, promoting ammonia product selectivity. Density functional theory calculations reveal the reaction mechanisms and the potential limiting steps for nitrate reduction on atomically dispersed Fe sites.
Background and Aims
Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer‐specific survival in various BTC subtypes, including gallbladder ...cancer, ampulla of Vater cancer, and cholangiocarcinoma.
Approach and Results
Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose–response relationship. Cox’s proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow‐up of 1.59 years, the 5‐year survival rate was 27.4%. The multivariate‐adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC‐specific death. Adjusted HRs for BTC‐specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose–response trend (P < 0.001; nonusers as a reference). Cancer‐specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes.
Conclusions
The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC‐specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin’s efficacy in BTC.
Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short‐term ...exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild‐type and mutant), while long‐term exposure of lung cancer cells to PM2.5 for 90 days persistently promoted EGFR activation, cell proliferation, anchorage‐independent growth, and tumor growth in a xenograft mouse model in EGFR‐driven H1975 cancer cells. We showed that PM2.5 activated AhR to translocate into the nucleus and promoted EGFR activation. AhR further interacted with the promoter of TMPRSS2, thereby upregulating TMPRSS2 and IL18 expression to promote cancer progression. Depletion of TMPRSS2 in lung cancer cells suppressed anchorage‐independent growth and xenograft tumor growth in mice. The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long‐term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2‐IL18 pathway.
Synopsis
PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18.
Exposure to PM2.5 activates EGFR pathway and promotes lung cancer progression.
Long‐term exposure to PM2.5 increases lung cancer cell proliferation, anchorage‐independent growth, and xenograft tumor growth in mice.
PM2.5 activates AhR to translocate into the nucleus and upregulates the expression of TMPRSS2.
Depletion of TMPRSS2 in lung cancer cells suppresses anchorage‐independent growth and xenograft tumor growth in mice.
TMPRSS2 upregulates IL I8 expression and promotes lung cancer progression.
PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18.
Yes‐associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an ...inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin‐producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy‐resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2‐induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2‐to‐YAP pathway that drives GC growth, progression and therapy‐resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy‐resistant GC.
What's new?
The discovery of novel molecular targets is fundamental to the continued advance of therapeutic agents for gastric cancer (GC). In this study, the authors identify a pathway involving interaction between EphA2, a member of the erythropoietin‐producing hepatocellular receptor family, and yes‐associated protein (YAP) as a promising therapeutic target for GC. In GC cells, EphA2 phosphorylation of YAP protein resulted in YAP stabilization, translocation to the nucleus, and activation. Increased YAP stabilization and nuclear concentration in GC cells and mouse models was further associated with EphA2‐induced chemoresistance. In patients, EphA2 overexpression and nuclear YAP accumulation was related to GC relapse.
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•WO3/CdIn2S4 hybrid exhibits highly efficient activity for TCH degradation.•WO3/CdIn2S4 hybrid possess excellent photostability during TCH degradation.•The improved catalytic activity ...was ascribed to effective charge separation.•Step-scheme charge separation mechanism in WO3/CdIn2S4 was verified.
Photocatalytic degradation is an ideal choice for the treatment of antibiotic contaminant in water environment because of the characters of environmental-benign and sustainable. In this work, the visible-light-driven WO3/CdIn2S4 hybrid photocatalysts with different WO3 content were successfully fabricated by hydrothermal method. The phase structure, surface composition, optical properties, specific surface areas and charge separation were systematically by a series of measurements. The photocatalytic activity of resultant WO3/CdIn2S4 hybrid photocatalysts was evaluated by photocatalytic degradation for removal of tetracycline hydrochloride (TCH) and the results reveal that optimized photocatalytic efficiency in WO3/CdIn2S4 hybrid photocatalysts can be achieved by modulating the weight ratio of WO3 to CdIn2S4. The 70 wt% WO3/CdIn2S4 hybrid photocatalyst exhibited the best photodegradation activity. Significant enhancement of photocatalytic activity in WO3/CdIn2S4 hybrid photocatalysts is ascribed to effective charge separation due to the construction of step-scheme heterojunction. The photocatalytic mechanism involving charge transfer and separation, and degradation path using step-scheme WO3/CdIn2S4 hybrid photocatalysts were in-depth investigated and discussed. It is anticipated that our current investigation could open an avenue for design and preparation of step-scheme hybrid photocatalysts for environmental remediation.
Escherichia coli has been engineered to produce isobutanol, with titers reaching greater than the toxicity level. However, the specific effects of isobutanol on the cell have never been fully ...understood. Here, we aim to identify genotype–phenotype relationships in isobutanol response. An isobutanol‐tolerant mutant was isolated with serial transfers. Using whole‐genome sequencing followed by gene repair and knockout, we identified five mutations (acrA, gatY, tnaA, yhbJ, and marCRAB) that were primarily responsible for the increased isobutanol tolerance. We successfully reconstructed the tolerance phenotype by combining deletions of these five loci, and identified glucosamine‐6‐phosphate as an important metabolite for isobutanol tolerance, which presumably enhanced membrane synthesis. The isobutanol‐tolerant mutants also show increased tolerance to n‐butanol and 2‐methyl‐1‐butanol, but showed no improvement in ethanol tolerance and higher sensitivity to hexane and chloramphenicol than the parental strain. These results suggest that C4, C5 alcohol stress impacts the cell differently compared with the general solvent or antibiotic stresses. Interestingly, improved isobutanol tolerance did not increase the final titer of isobutanol production.
Background
To assess the association of cirrhosis and hepatocellular carcinoma (HCC) with the use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) versus long‐acting insulins (LAIs), which are ...the two commonly prescribed injectable glucose‐lowering agents (GLAs) for patients with type 2 diabetes (T2D) after the failure of multiple oral GLAs.
Methods
We emulated a target trial using the nationwide data of a Taiwanese cohort with T2D. Incident new users of GLP‐1RAs and LAIs during 2013–2018 were identified, and propensity score (PS) matching was applied to ensure between‐group comparability in baseline patient characteristics. The primary outcome was the composite liver disease including cirrhosis or HCC. Each patient was followed until the occurrence of a study outcome, death, or the end of 2019, whichever came first. Subdistribution hazard models were employed to assess the treatment‐outcome association. Sensitivity (e.g., stabilized inverse probability of treatment weighting analysis, time‐dependent analysis), E‐value, and negative control outcome analyses were performed to examine the robustness of study findings.
Results
We included 7171 PS‐matched pairs of GLP‐1RA and LAI users with no significant between‐group differences at baseline. Compared with LAIs, the use of GLP‐1RAs was associated with significantly reduced risks of composite liver disease (subdistribution hazard ratio 95% confidence interval: 0.56 0.42–0.76), cirrhosis (0.59 0.43–0.81), and HCC (0.47 0.24–0.93). Results were consistent across sensitivity analyses and among patients with different baseline characteristics.
Conclusion
Among T2D patients who require injectable GLAs, the use of GLP‐1RAs versus LAIs was associated with lower risks of cirrhosis and HCC.
Hepatocellular carcinoma (HCC) is a disease with unique management complexity because it displays high heterogeneity of molecular phenotypes. We herein aimed to characterize the molecular features of ...HCC by the development of a classification system that was based on the gene expression profile of metabolic genes. Integrative analysis was performed with a metadata set featuring 371 and 231 HCC human samples from the Cancer Genome Atlas and the International Cancer Genome Consortium, respectively. All samples were linked with clinical information. RNA sequencing data of 2752 previously characterized metabolism‐related genes were used for non‐negative matrix factorization clustering, and three subclasses of HCC (C1, C2, and C3) were identified. We then analyzed the metadata set for metabolic signatures, prognostic value, transcriptome features, immune infiltration, clinical characteristics, and drug sensitivity of subclasses, and compared the resulting subclasses with previously published classifications. Subclass C1 displayed high metabolic activity, low α‐fetoprotein (AFP) expression, and good prognosis. Subclass C2 was associated with low metabolic activities and displayed high expression of immune checkpoint genes, demonstrating drug sensitivity toward cytotoxic T‐lymphocyte‐associated protein‐4 inhibitors and the receptor tyrosine kinase inhibitor cabozantinib. Subclass C3 displayed intermediate metabolic activity, high AFP expression level, and bad prognosis. Finally, a 90‐gene classifier was generated to enable HCC classification. This study establishes a new HCC classification based on the gene expression profiles of metabolic genes, thereby furthering the understanding of the genetic diversity of human HCC.
Based on the gene expression profile of metabolic genes, patients with hepatocellular carcinoma (HCC) were divided into three subclasses: C1, C2, and C3. Each subclass had a different prognosis, clinicopathological characteristics, molecular characteristics, and potential therapies. Besides, this classification was associated with previously reported HCC molecular subclasses, including Boyault's classification, Chiang's classification, Hoshida's classification, Désert's classification, and the Cancer Genome Atlas's classification.
Two-photon excited near-infrared fluorescence materials have garnered considerable attention because of their superior optical penetration, higher spatial resolution, and lower optical scattering ...compared with other optical materials. Herein, a convenient and efficient supramolecular approach is used to synthesize a two-photon excited near-infrared emissive co-crystalline material. A naphthalenediimide-based triangular macrocycle and coronene form selectively two co-crystals. The triangle-shaped co-crystal emits deep-red fluorescence, while the quadrangle-shaped co-crystal displays deep-red and near-infrared emission centered on 668 nm, which represents a 162 nm red-shift compared with its precursors. Benefiting from intermolecular charge transfer interactions, the two co-crystals possess higher calculated two-photon absorption cross-sections than those of their individual constituents. Their two-photon absorption bands reach into the NIR-II region of the electromagnetic spectrum. The quadrangle-shaped co-crystal constitutes a unique material that exhibits two-photon absorption and near-infrared emission simultaneously. This co-crystallization strategy holds considerable promise for the future design and synthesis of more advanced optical materials.
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