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1.
Sci Total Environ ; 806(Pt 1): 150498, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563908

RESUMO

Sediment microbial communities play critical roles in the health of fish and the biogeochemical cycling of elements in aquaculture ecosystems. However, the response of microbial communities to temporal and spatial variations in interconnected aquaculture pond and ditch systems remains unclear. In this study, 61 sediment bacterial samples were collected over one year from 11 sites (including five ponds and six ditches) in a 30-year-old fish aquaculture farm. The 16S rRNA approach was used to determine the relative abundances of microbial communities in the sediment samples. The relationships among nutrients, heavy metals, and abundant microorganisms were analyzed. Our results showed that Proteobacteria, Bacteroides and Chloroflexi were the predominant phyla in the sediments of aquaculture pond, with average abundances of 36.33%, 18.60%, and 14.58%, respectively. The microbial diversity in aquaculture sediments was negatively correlated (P < 0.05) with the concentrations of total nitrogen and total phosphorus in sediments, indicating that the microbial diversity is highly associated with the remediation of nutrients in sediments. The sediment samples with high similarities were discovered by the t-distributed stochastic neighbor embedding (t-SNE) method. The site-specific correlations between specific microorganisms and heavy metals were explored. The network analysis revealed that the microbial diversities in aquaculture ponds were more stable than that in aquaculture ditches. The network analysis also illustrated that the microbial genera with low relative abundances may become key groups of microbial communities in sediment ecosystems. Our work deepens the understanding of the relationships between microbial communities and the spatiotemporal characteristics of surface water and sediments in aquaculture farms.


Assuntos
Microbiota , Lagoas , Animais , Aquicultura , Sedimentos Geológicos , RNA Ribossômico 16S/genética
2.
Environ Res ; 203: 111894, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34418448

RESUMO

The Tibetan Plateau (TP) has a variety of vegetation types that range from alpine tundra to tropic evergreen forest, which play an important role in the global carbon (C) cycle and is extremely vulnerable to climate change. The vegetation C uptake is crucial to the ecosystem C sequestration. Moreover, net reduction in vegetation C uptake (NRVCU) will strongly affect the C balance of terrestrial ecosystem. Until now, there is limited knowledge on the recovery process of vegetation net C uptake and the spatial-temporal patterns of NRVCU after the disturbance that caused by climate change and human activities. Here, we used the MODIS-derived net primary production to characterize the spatial-temporal patterns of NRVCU. We further explored the influence factors of the net reduction rate in vegetation C uptake (NRRVCU) and recovery processes of vegetation net C uptake across a unique gradient zone on the TP. Results showed that the total net reduction amount of vegetation C uptake gradually decreased from 2000 to 2015 on the TP (Slope = -0.002, P < 0.05). Specifically, an increasing gradient zone of multi-year average of net reduction rate in vegetation carbon uptake (MYANRRVCU) from east to west was observed. In addition, we found that the recovery of vegetation net C uptake after the disturbance caused by climate change and anthropogenic disturbance in the gradient zone were primarily dominated by precipitation and temperature. The findings revealed that the effects of climate change on MYANRRVCU and vegetation net C uptake recovery differed significantly across geographical space and vegetation types. Our results highlight that the biogeographic characteristics of the TP should be considered for combating future climate change.

3.
Cancer Med ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741449

RESUMO

Cancer stem cells (CSCs) have been shown to accelerate tumor recurrence, radiotherapy, and chemotherapy resistance. Immunotherapy is a powerful anticancer treatment that can significantly prolong the overall survival of patients with lung adenocarcinoma (LUAD). However, little is known about the function of genes related to tumor stemness and immune infiltration in LUAD. After integrating the tumor stemness index based on mRNA expression (mRNAsi), immune score, mRNA expression, and clinical information from the TCGA database, we screened 380 tumor stemness and immune (TSI)-related genes and constructed a five TSI-specific-gene (CPS1, CCR2, NT5E, ANLN, and ABCC2) signature (TSISig) using a machine learning method. Survival analysis indicated that TSISig could stably predict the prognosis of patients with LUAD. Comparison of mRNAsi and immune score between high- and low-TSISig groups suggested that TSISig characterized tumor stemness and immune infiltration. In addition, enrichment of immune subpopulations showed that the low-TSISig group held more immune subpopulations. GSEA revealed that TSISig had a strong association with the cell cycle and human immune response. Further analysis revealed that TSISig not only had a good predictive ability for prognosis but could also serve as an excellent predictor of tumor recurrence and response to radiotherapy and immunotherapy in LUAD patients. TSISig might regulate the development of LUAD by coordinating tumor stemness and immune infiltration. Finally, a connectivity map (CMap) analysis demonstrated that the HDAC inhibitor could target TSISig.

4.
Mikrochim Acta ; 188(12): 412, 2021 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741664

RESUMO

Solid-state carbon dots (SCDs) have been widely investigated by scholars owing to their stability, environmental friendliness, and their good optical properties. The current studies on carbon dots (CDs) are mainly focused on the solutions of CDs, while the researches on SCDs are relatively few in comparison. Nowadays, the fabrication and design of high-performance SCDs have attracted much interest. However, due to resonance energy transfer and π-π interactions, CDs undergo aggregation-induced quenching (ACQ) phenomena. This poses an obstacle to the acquisition of SCDs and affects their luminescence performance. Publications of the past 5 years are reviewed on how to suppress the ACQ phenomenon and improve the fluorescence and phosphorescence emission of CDs (Ref. 87) and about the mechanism of achieving the luminescence of SCDs. Then, the applications of SCDs in the fields of luminescent devices, anti-counterfeiting, and detection are outlined. The concluding section analyzes the current challenges faced by SCDs and provides an outlook. Mechanism of photoluminescence from solid state carbon dots.

5.
J Control Release ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748870

RESUMO

Bone tissues are the main metastatic sites of many cancers, and bone metastasis is an important cause of death. When bone metastasis occurs, dynamic interactions between tumor cells and bone tissues promote changes in the tumor-bone microenvironments that are conducive to tumor growth and progression, which also promote several related diseases, including pathological fracture, bone pain, and hypercalcemia. Accordingly, it has obvious clinical benefits for improving the cure rate and reducing the occurrence of related diseases through targeting bone microenvironments for the treatment and early detection of cancer bone metastasis niches. In this review, we briefly analyzed the relationship between bone microstructures and tumor metastasis, as well as microenvironmental changes in osteoblasts, osteoclasts, immune cells, and extracellular and bone matrixes caused when metastatic tumor cells colonize bones. We also discuss novel designs in nanodrugs for inhibiting tumor proliferation and migration through targeting to tumor bone metastases and abnormal bone-microenvironment components. In addition, related researches on the early detection of bone and multi-organ metastases by nanoprobes are also introduced. And we look forward to provide some useful proposals and enlightenments on nanotechnology-based drug delivery and probes for the treatment and early detection of bone metastasis.

6.
J Appl Biomed ; 19(2): 113-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754259

RESUMO

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

7.
Front Microbiol ; 12: 721399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759897

RESUMO

Dicer proteins are mainly responsible for generating small RNAs (sRNAs), which are involved in gene silencing in most eukaryotes. In previous research, two DCL proteins in Valsa mali, the pathogenic fungus causing apple tree Valsa canker, were found associated with both the pathogenicity and generation of sRNAs. In this study, the differential expression of small interfering RNAs (siRNAs) and miRNA-like RNAs (milRNAs) was analyzed based on the deep sequencing of the wild type and Vm-DCL2 mutant, respectively. Overall, the generation of 40 siRNAs and 18 milRNAs was evidently associated with Vm-DCL2. The target genes of milRNAs were then identified using degradome sequencing; according to the prediction results, most candidate targets are related to pathogenicity. Further, expression of Vm-PC-3p-92107_6 was confirmed in the wild type but not in the Vm-DCL2 mutant. Moreover, the pathogenicity of Vm-PC-3p-92107_6 deletion mutants (ΔVm-PC-3p-92107_6) and the over-expression transformants (Vm-PC-3p-92107_6-OE) was significantly increased and decreased, respectively. Based on those degradome results, vacuolar protein sorting 10 (Vm-VPS10) was identified as the target of Vm-PC-3p-92107_6. Co-expression analysis in tobacco leaves further confirmed that Vm-PC-3p-92107_6 could suppress the expression of Vm-VPS10. Meanwhile, the expression levels of Vm-PC-3p-92107_6 and Vm-VPS10 displayed divergent trends in ΔVm-PC-3p-92107_6 and Vm-PC-3p-92107_6-OE, respectively. Perhaps most importantly, ΔVm-VPS10 featured a significant reduction in pathogenicity. Taken together, our results indicate that a DCL2-dependent milRNA Vm-PC-3p-92107_6 plays roles in pathogenicity by regulating the expression of Vm-VPS10. This study lays a foundation for the comprehensive analysis of pathogenic mechanisms of V. mali and deepens our understanding of the generation and function of fungal sRNA.

8.
Front Pharmacol ; 12: 765790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733164

RESUMO

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

9.
ACS Synth Biol ; 10(11): 2833-2841, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34734710

RESUMO

Efficient enabling technology is required for synthetic biology in Streptomyces due to its natural product reservoir. Though the CRISPR-Cas9 system is powerful for genome editing in this genus, the proposed Cas9 toxicity has limited its application. Here on the basis of previous inducible Cas9 expression at the transcriptional and translational levels coupled with atpD overexpression, a Cas9 cognate inhibitor AcrIIA4 was further introduced to fine-tune the Cas9 activity. In both laboratory and industrial Streptomyces species, we showed that, compared to the constitutively expressed Cas9, incorporating AcrIIA4 increased the conjugation efficiency from 700- to 7000-fold before induction, while a comparable 65%-90% editing efficiency was obtained even on multiple loci for simultaneous deletion after Cas9 expression was induced, along with no significant off-targets. Thus, AcrIIA4 could be a modulator to control Cas9 activity to significantly improve genome editing, and this new toolkit would be widely adaptable and fasten genetic engineering in Streptomyces.

10.
Nat Commun ; 12(1): 6698, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795245

RESUMO

Photoelectrochemical cells are emerging as powerful tools for organic synthesis. However, they have rarely been explored for C-H halogenation to produce organic halides of industrial and medicinal importance. Here we report a photoelectrocatalytic strategy for C-H halogenation using an oxygen-vacancy-rich TiO2 photoanode with NaX (X=Cl-, Br-, I-). Under illumination, the photogenerated holes in TiO2 oxidize the halide ions to corresponding radicals or X2, which then react with the substrates to yield organic halides. The PEC C-H halogenation strategy exhibits broad substrate scope, including arenes, heteroarenes, nonpolar cycloalkanes, and aliphatic hydrocarbons. Experimental and theoretical data reveal that the oxygen vacancy on TiO2 facilitates the photo-induced carriers separation efficiency and more importantly, promotes halide ions adsorption with intermediary strength and hence increases the activity. Moreover, we designed a self-powered PEC system and directly utilised seawater as both the electrolyte and chloride ions source, attaining chlorocyclohexane productivity of 412 µmol h-1 coupled with H2 productivity of 9.2 mL h-1, thus achieving a promising way to use solar for upcycling halogen in ocean resource into valuable organic halides.

12.
Chemistry ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34791739

RESUMO

Transcatheter arterial embolization (TAE) is wildly used in clinical treatments. However, the online monitoring of the thrombosis formation is limited due to the challenges of the direct visualization of embolic agents and the real-time monitoring of dynamic blood flow. Thus, we developed a photochemical afterglow implant with strong afterglow intensity and a long lifetime for embolization and imaging. The liquid pre-implant injected into the abdominal aorta of mice was rapidly transformed into a hydrogel in situ to embolize the blood vessel. The vascular embolism position can be observed by the enhanced afterglow of the fixed implant, and the long lifetime of afterglow can also be used to monitor the effect of embolization. This provides an excellent candidate in bio-imaging to avoid the autofluorescence interference from continuous light excitation. The study suggests the potential usefulness of the implant as an embolic agent in TAE and artery imaging during a surgical procedure.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34793675

RESUMO

MXene aerogels with a porous microstructure are a promising electromagnetic interference (EMI) shielding material due to its low density and excellent electrical conductivity, which has attracted widespread attention. Compared with traditional EMI shielding materials that rely on reflection as the primary mechanism, MXene aerogels with absorption as the dominant mechanism have greater potential for development as a novel EMI shielding material because of its ability to reduce environmental contamination from reflected electromagnetic (EM) waves from materials. In this study, a novel Ti3C2Tx MXene/PEDOT:PSS hybrid aerogel was presented by freeze-drying and thermal annealing using few-layered Ti3C2Tx MXene and the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). PEDOT:PSS not only improved the gelling ability of Ti3C2Tx but also successfully established a conductive bridge between MXene nanosheets. The experimental results demonstrated that the hybrid aerogel exhibited an obvious porous microstructure, which was beneficial for the multiple scattering of EM waves within the materials. The EMI shielding effectiveness and specific shielding effectiveness reached up to 59 dB and 10,841 dB·cm2·g-1, respectively, while the SER/SET ratio value was only 0.05, indicating superior wave absorption performance. Furthermore, the good impedance matching, due to the electrical conductance loss and polarization loss effect of the composites, plays a critical role in their excellent wave absorption and EMI shielding performance. Therefore, this work provides a practical approach for designing and fabricating lightweight absorption-dominated EMI shielding materials.

14.
Cancer Manag Res ; 13: 8535-8550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803402

RESUMO

Purpose: The occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS. Methods: We comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples. Results: We found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P<0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells. Conclusion: AGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.

15.
Adv Sci (Weinh) ; : e2103373, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837482

RESUMO

The requirement of a large input amount (500 ng) for Nanopore direct RNA-seq presents a major challenge for low input transcriptomic analysis and early pathogen surveillance. The high RNA input requirement is attributed to significant sample loss associated with library preparation using solid-phase reversible immobilization (SPRI) beads. A novel solid-phase catalysis strategy for RNA library preparation to circumvent the need for SPRI bead purification to remove enzymes is reported here. This new approach leverages concurrent processing of non-polyadenylated transcripts with immobilized poly(A) polymerase and T4 DNA ligase, followed by directly loading the prepared library onto a flow cell. Whole transcriptome sequencing, using a human pathogen Listeria monocytogenes as a model, demonstrates this new method displays little sample loss, takes much less time, and generates higher sequencing throughput correlated with reduced nanopore fouling compared to the current library preparation for 500 ng input. Consequently, this approach enables Nanopore low-input direct RNA-seq, improving pathogen detection and transcript identification in a microbial community standard with spike-in transcript controls. Besides, as evident in the bioinformatic analysis, the new method provides accurate RNA consensus with high fidelity and identifies higher numbers of expressed genes for both high and low input RNA amounts.

16.
Trials ; 22(1): 847, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823569

RESUMO

BACKGROUND: Diabetic cognitive impairment (DCI) is a serious chronic complication caused by diabetes. The pathogenesis of DCI is complex, but brain nerve injury and brain nerve cell apoptosis are important pathological changes. Multimodal brain imaging is one of the most important techniques to study the neural mechanism of the brain. For the clinical treatment of DCI, there is no effective targeted Western medicine and a lack of clear drug intervention methods. Therefore, there is an urgent need to find effective complementary and alternative methods and clarify their mechanism. This research seeks to explore the multimodal brain imaging effect of "Adjust Zang-fu and Arouse Spirit" electroacupuncture for DCI. METHODS: This clinical research will be a randomized, sham-controlled pilot trial. Eligible participants will be randomly assigned to the intervention group (n = 60) and the control group (n = 30). The intervention group will be divided into the "Adjust Zang-fu and Arouse Spirit" electroacupuncture group (n = 30) and sham electroacupuncture group (n = 30). All participants will continue to receive routine hypoglycemic therapy. The treatment period is the same in both groups. The primary outcomes include functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), Montreal Cognitive Assessment Scale (MoCA), and Clinical Dementia Rating (CDR). The secondary outcomes include blood glucose and blood lipid tests, Instrumental Activities of Daily Living Scale (IADL), Hachinski Ischemic Scale (HIS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Outcomes will be assessed at baseline and before and after treatment, and adverse events will be examined. Inter- and intragroup analyses will be performed. DISCUSSION: This randomized controlled study, combined with multimodal brain imaging techniques and a clinical evaluation scale, was designed to explore the mechanism of "Adjust Zang-fu and Arouse Spirit" electroacupuncture in improving the central nervous system in DCI. TRIAL REGISTRATION: Chinese Clinical Trial Registration ChiCTR2000040268 . Registered on 26 November 2020.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Eletroacupuntura , Atividades Cotidianas , Encéfalo/diagnóstico por imagem , Humanos , Neuroimagem , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
J Phys Condens Matter ; 34(7)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34753113

RESUMO

Zr-Rh metallic glass has enabled its many applications in vehicle parts, sports equipment and so on due to its outstanding performance in mechanical property, but the knowledge of the microstructure determining the superb mechanical property remains yet insufficient. Here, we develop a deep neural network potential of Zr-Rh system by using machine learning, which breaks the dilemma between the accuracy and efficiency in molecular dynamics simulations, and greatly improves the simulation scale in both space and time. The results show that the structural features obtained from the neural network method are in good agreement with the cases inab initiomolecular dynamics simulations. Furthermore, we build a large model of 5400 atoms to explore the influences of simulated size and cooling rate on the melt-quenching process of Zr77Rh23. Our study lays a foundation for exploring the complex structures in amorphous Zr77Rh23, which is of great significance for the design and practical application.

18.
Front Cardiovasc Med ; 8: 763469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820430

RESUMO

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

19.
Endoscopy ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823258

RESUMO

BACKGROUND AND STUDY AIMS: Tandem colonoscopy studies have found that about one in five adenomas are missed at colonoscopy. It is still debatable whether the combination of a computer-aided detection (CADe) system for colorectal polyp detection with a computer-aided quality improvement (CAQ) system for real-time withdrawal speed monitoring may result in additional benefits in the task of adenoma detection or if the synergetic effect may be harmed due to excessive visual burden resulting from the information overload. This study aims to evaluate the interaction effect on improving the adenoma detection rate (ADR). PATIENTS AND METHODS: This is a single-center, randomized, four-group parallel controlled study, performed in Renmin Hospital of Wuhan University. Between July 1, 2020 and Oct 15, 2020, 1076 participants were randomly allocated into four treatment groups [control: 271, CADe: 268, CAQ: 269 and CADe plus CAQ (COMBO): 268]. The primary outcome was the ADR. RESULTS: The average ADR in the control, CADe, CAQ and COMBO groups was 14.76% (95% C.I. 10.54-18.98), 21.27% (95% C.I. 16.37-26.17), 24.54% (95% C.I. 19.39-29.68) and 30.6% (95% C.I. 25.08-36.11), respectively. The ADR was higher in the COMBO group compared with the CADe group but not compared with the CAQ group (21.27% VS 30.6%, P=0.024, OR 1.284, 95%C.I. 1.033-1.596; 24.54%vs. 30.6%, P = 0.213, OR = 1.309, 95% C.I. 0.857-2, respectively). CONCLUSIONS: CAQ significantly improved the efficacy of CADe in a four-group parallel controlled study. No significant difference in the ADR or PDR was found between the CAQ and COMBO groups.

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