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Background and aims Improving the rate of polyp detection is an important measure to prevent colorectal cancer (CRC). Real-time automatic polyp detection systems, through deep learning methods, can learn and perform specific endoscopic tasks previously performed by endoscopists. The purpose of this study was to explore whether a high-performance, real-time automatic polyp detection system could improve the polyp detection rate (PDR) in the actual clinical environment. Methods The selected patients underwent same-day, back-to-back colonoscopies in a random order, with either traditional colonoscopy or artificial intelligence (AI)-assisted colonoscopy performed first by different experienced endoscopists (> 3000 colonoscopies). The primary outcome was the PDR. It was registered with clinicaltrials.gov . (NCT047126265). Results In this study, we randomized 150 patients. The AI system significantly increased the PDR (34.0% vs 38.7%, p < 0.001). In addition, AI-assisted colonoscopy increased the detection of polyps smaller than 6 mm (69 vs 91, p < 0.001), but no difference was found with regard to larger lesions. Conclusions A real-time automatic polyp detection system can increase the PDR, primarily for diminutive polyps. However, a larger sample size is still needed in the follow-up study to further verify this conclusion. Trial Registration clinicaltrials.gov Identifier: NCT047126265

A meta‐analysis was performed to compare the effects of laparoscopic splenectomy (LS) and open splenectomy (OS) for splenic rupture on postoperative surgical site wound infections and postoperative complications. A comprehensive computerised search was conducted for studies comparing LS with OS for the treatment of splenic rupture in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases, with the search including studies published in any language between the creation of the databases and August 2023. Two researchers independently screened the literature and extracted the data. Literature quality was assessed using the Newcastle‐Ottawa Scale, and the included data were collated and analysed using Stata 17.0 software for meta‐analysis. Twenty‐two studies involving 1545 patients were included. LS was superior to OS in the following aspects: reduced risk of postoperative surgical site wound infection (OR = 0.19, 95% CI: 0.11–0.34, p  = 0.000), shortened hospital stay (standardised mean difference = −1.73, 95% CI: −2.05 to −1.40, p  = 0.000), and reduced postoperative complication rate (OR = 0.22, 95% CI: 0.16–0.31, p  = 0.000). Compared with OS, LS has a lower rate of postoperative wound infection, shorter hospital stay, and reduced rate of postoperative complications. LS is safe and effective for the treatment of splenic rupture and can be promoted clinically.

A meta‐analysis was performed to compare the effects of laparoscopic splenectomy (LS) and open splenectomy (OS) for splenic rupture on postoperative surgical site wound infections and postoperative complications. A comprehensive computerised search was conducted for studies comparing LS with OS for the treatment of splenic rupture in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases, with the search including studies published in any language between the creation of the databases and August 2023. Two researchers independently screened the literature and extracted the data. Literature quality was assessed using the Newcastle‐Ottawa Scale, and the included data were collated and analysed using Stata 17.0 software for meta‐analysis. Twenty‐two studies involving 1545 patients were included. LS was superior to OS in the following aspects: reduced risk of postoperative surgical site wound infection (OR = 0.19, 95% CI: 0.11–0.34, p = 0.000), shortened hospital stay (standardised mean difference = −1.73, 95% CI: −2.05 to −1.40, p = 0.000), and reduced postoperative complication rate (OR = 0.22, 95% CI: 0.16–0.31, p = 0.000). Compared with OS, LS has a lower rate of postoperative wound infection, shorter hospital stay, and reduced rate of postoperative complications. LS is safe and effective for the treatment of splenic rupture and can be promoted clinically.

A novel system for enhancing the properties of P( N -isopropylacrylamide- co -poly(ethylene glycol)diacrylate) (P(NIPAM- co -PEGDA)) temperature-sensitive hybrid hydrogels by incorporating acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) was developed in this study. Inorganic/organic hybrid P(NIPAM- co -PEGDA) hydrogels based on MAPOSS were synthesized via free radical polymerization. Environmental scanning electron microscopy images showed that hydrogels with different feed ratios exhibited significant changes in the porous structure and average pore size. The heterogeneous and irregular network was caused mainly by MAPOSS aggregation. The rigid cage-like nanostructure of MAPOSS had dual opposite effects on polymer thermal properties; this effect was proven through differential scanning calorimetry and thermogravimetric analysis. The mechanical behaviors of the swollen hydrogels investigated through compression test showed that MAPOSS incorporation enhanced the yield strength. Swelling, deswelling and reswelling behaviors of hydrogels with different feed ratios were systematically examined and compared. The increase in MAPOSS provided the hydrogels with improved deswelling rate because of its cage-like nanostructure and hydrophobicity.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

Exonuclease-mediated RNA decay in plants is known to be involved primarily in endogenous RNA degradation, and several RNA decay components have been suggested to attenuate RNA silencing possibly through competing for RNA substrates. In this paper, we report that overexpression of key cytoplasmic 5'-3' RNA decay pathway gene-encoded proteins (5'RDGs) such as decapping protein 2 (DCP2) and exoribonuclease 4 (XRN4) in Nicotiana benthamiana fails to suppress sense transgene-induced post-transcriptional gene silencing (S-PTGS). On the contrary, knock-down of these 5'RDGs attenuates S-PTGS and supresses the generation of small interfering RNAs (siRNAs). We show that 5'RDGs degrade transgene transcripts via the RNA decay pathway when the S-PTGS pathway is disabled. Thus, RNA silencing and RNA decay degrade exogenous gene transcripts in a hierarchical and coordinated manner. Moreover, we present evidence that infection by turnip mosaic virus (TuMV) activates RNA decay and 5'RDGs also negatively regulate TuMV RNA accumulation. We reveal that RNA silencing and RNA decay can mediate degradation of TuMV RNA in the same way that they target transgene transcripts. Furthermore, we demonstrate that VPg and HC-Pro, the two known viral suppressors of RNA silencing (VSRs) of potyviruses, bind to DCP2 and XRN4, respectively, and the interactions compromise their antiviral function. Taken together, our data highlight the overlapping function of the RNA silencing and RNA decay pathways in plants, as evidenced by their hierarchical and concerted actions against exogenous and viral RNA, and VSRs not only counteract RNA silencing but also subvert RNA decay to promote viral infection.

Autophagy emerges as an essential immunity defense against intracellular pathogens. Here we report that turnip mosaic virus (TuMV) infection activates autophagy in plants and that Beclin1 (ATG6), a core component of autophagy, inhibits virus replication. Beclin1 interacts with NIb, the RNA-dependent RNA polymerase (RdRp) of TuMV, via the highly conserved GDD motif and the interaction complex is targeted for autophagic degradation likely through the adaptor protein ATG8a. Beclin1-mediated NIb degradation is inhibited by autophagy inhibitors. Deficiency of Beclin1 or ATG8a enhances NIb accumulation and promotes viral infection and vice versa. These data suggest that Beclin1 may be a selective autophagy receptor. Overexpression of a Beclin1 truncation mutant that binds to NIb but lacks the ability to mediate NIb degradation also inhibits virus replication. The Beclin1–RdRp interaction further extends to several RNA viruses. Thus Beclin1 restricts viral infection through suppression and also likely autophagic degradation of the viral RdRp. Plant DNA virus replication is inhibited by autophagy, but the interplay between plant RNA viruses and autophagy is less clear. Here, Li et al. show that turnip mosaic virus infection activates autophagy and that Beclin1, a core autophagy component, binds the viral polymerase and inhibits virus replication.

Sumoylation is a transient, reversible dynamic posttranslational modification that regulates diverse cellular processes including plant-pathogen interactions. Sumoylation of NPR1, a master regulator of basal and systemic acquired resistance to a broad spectrum of plant pathogens, activates the defense response. Here, we report that NIb, the only RNA-dependent RNA polymerase of Turnip mosaic virus (TuMV) that targets the nucleus upon translation, interacts exclusively with and is sumoylated by SUMO3 (SMALL UBIQUITIN-LIKE MODIFIER3), but not the three other Arabidopsis thaliana SUMO paralogs. TuMV infection upregulates SUMO3 expression, and the sumoylation of NIb by SUMO3 regulates the nuclear-cytoplasmic partitioning of NIb. We identified the SUMO-interacting motif in NIb that is essential for its sumoylation and found that knockout or overexpression of SUMO3 suppresses TuMV replication and attenuates viral symptoms, suggesting that SUMO3 plays dual roles as a host factor of TuMV and as an antiviral defender. Sumoylation of NIb by SUMO3 is crucial for its role in suppressing the host immune response. Taken together, our findings reveal that sumoylation of NIb promotes TuMV infection by retargeting NIb from the nucleus to the cytoplasm where viral replication takes place and by suppressing host antiviral responses through counteracting the TuMV infection-induced, SUMO3-activated, NPR1-mediated resistance pathway.

A recently characterized calmodulin-like protein is an endogenous RNA silencing suppressor that suppresses sense-RNA induced post-transcriptional gene silencing (S-PTGS) and enhances virus infection, but the mechanism underlying calmodulin-like protein-mediated S-PTGS suppression is obscure. Here, we show that a calmodulin-like protein from Nicotiana benthamiana (NbCaM) interacts with Suppressor of Gene Silencing 3 (NbSGS3). Deletion analyses showed that domains essential for the interaction between NbSGS3 and NbCaM are also required for the subcellular localization of NbSGS3 and NbCaM suppressor activity. Overexpression of NbCaM reduced the number of NbSGS3-associated granules by degrading NbSGS3 protein accumulation in the cytoplasm. This NbCaM-mediated NbSGS3 degradation was sensitive to the autophagy inhibitors 3-methyladenine and E64d, and was compromised when key autophagy genes of the phosphatidylinositol 3-kinase (PI3K) complex were knocked down. Meanwhile, silencing of key autophagy genes within the PI3K complex inhibited geminivirus infection. Taken together these data suggest that NbCaM acts as a suppressor of RNA silencing by degrading NbSGS3 through the autophagy pathway.

Pepper fluorescent RNAs are a recently reported bright, stable and multicolor fluorogenic aptamer tag that enable imaging of diverse RNAs in live cells. To investigate the molecular basis of the superior properties of Pepper, we determined the structures of complexes of Pepper aptamer bound with its cognate HBC or HBC-like fluorophores at high resolution by X-ray crystallography. The Pepper aptamer folds in a monomeric non-G-quadruplex tuning-fork-like architecture composed of a helix and one protruded junction region. The near-planar fluorophore molecule intercalates in the middle of the structure and is sandwiched between one non-G-quadruplex base quadruple and one noncanonical G·U wobble helical base pair. In addition, structure-based mutational analysis is evaluated by in vitro and live-cell fluorogenic detection. Taken together, our research provides a structural basis for demystifying the fluorescence activation mechanism of Pepper aptamer and for further improvement of its future application in RNA visualization. Structural analysis of the Pepper aptamer in complex with its cognate HBC or HBC-like color variants reveals that it binds fluorophore molecules via one non-G-quadruplex base quadruple and one noncanonical G·U base pair.