BackgroundBiomarker-targeted molecular imaging holds promise for early detection of pancreatic cancer. The aim of this study was to design and evaluate a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer imaging.Methods1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-amino(polyethylene glycol) (DSPE-PEG-NH2)-modified superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) were conjugated with plectin-1 antibody and/or Cy7 to create the multi-functional targeted nanoparticle targeted probe (Plectin-SPION-Cy7) or non-targeted probe (SPION-Cy7). Pancreatic carcinoma cell lines expressing plectin-1 were cultured with the targeted or control probes and then were imaged using confocal laser scanning microscopy and magnetic resonance imaging (MRI). Accumulations of the nanoparticles in pancreatic tumor xenografted mice were determined by MRI and fluorescence imaging.ResultsIn vitro optical imaging and MRI showed that the targeted nanoparticles were highly accumulated in MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells, which was further confirmed by Prussian blue staining. In vivo MRI showed a significant T2 signal reduction. Prussian blue staining further confirmed that the plectin-1 targeted nanoparticles were highly accumulated in the tumor mass but not in normal pancreatic tissues, or in the liver and kidney, and few nanoparticles were observed in the tumors of mice injected with SPION-Cy7.ConclusionsOur data demonstrate that plectin-1 targeted fluorescence and MR dual-functional nanoparticle can visualize pancreatic cancer, and it has great potential to be used with various imaging devices for pancreatic cancer detection.

Developing an MRI-based radiomics model to effectively and accurately predict the predominant histopathologic growth patterns (HGPs) of colorectal liver metastases (CRLMs). Materials and Methods: In this study, 182 resected and histopathological proven CRLMs of chemotherapy-naive patients from two institutions, including 123 replacement CRLMs and 59 desmoplastic CRLMs, were retrospectively analyzed. Radiomics analysis was performed on two regions of interest (ROI), the tumor zone and the tumor-liver interface (TLI) zone. Decision tree (DT) algorithm was used for radiomics modeling on each MR sequence, and fused radiomics model was constructed by combining the radiomics signature of each sequence. The clinical and combination models were developed through multivariate logistic regression method. The performance of the developed models was assessed by receiver operating characteristic (ROC) curves with indicators of area under curve (AUC), accuracy, sensitivity, and specificity. A nomogram was constructed to evaluate the discrimination, calibration, and usefulness. Results: The fused radiomics tumor and radiomics TLI models showed better performance than any single sequence and clinical model. In addition, the radiomics TLI model exhibited better performance than radiomics tumor model (AUC of 0.912 vs. 0.879) in internal validation cohort. The combination model showed good discrimination, and the AUC of nomogram was 0.971, 0.909, and 0.905 in the training, internal validation, and external validation cohorts, respectively. Han et al. Radiomics in CRLM's HGP Prediction Conclusion: MRI-based radiomics method has high potential in predicting the predominant HGPs of CRLM. Preoperative non-invasive identification of predominant HGPs could further explore the ability of HGPs as a potential biomarker for clinical treatment strategy, reflecting different biological pathways.

Successful and efficient delivery of Cas9 protein and gRNA into cells is critical for genome editing and its therapeutic application. In this study, we developed an improved supercharged polypeptide (SCP) mediated delivery system based on dithiocyclopeptide linker to realize the effective genome editing in tumor cells. The fusion protein Cas9-linker-SCP (Cas9-LS) forms positively charged complexes with gRNA in vitro to provide possibilities for gRNA delivery into cells. Under the microenvironment of tumor cells, the dithiocyclopeptide linker, containing matrix metalloproteinase 2 (MMP-2) sensitive sequence and an intramolecular disulfide bond, can be completely disconnected to promote the release of Cas9 protein with the nuclear localization sequence (NLS) in the cytoplasm and transfer to the cell nucleus for highly efficient genome editing, resulting in an obvious increase of indel efficiency in comparison to fusion protein without dithiocyclopeptide linker (Cas9-SCP). Furthermore, Cas9-LS shows no significant cytotoxicity and minimal hemolytic activity. We envision that the microenvironment-responsive Cas9 protein delivery system can facilitate more efficient genome editing in tumor cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

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Although the probability of pancreatic cystic neoplasms (PCNs) being detected is raising year by year, their differential diagnosis and individualized treatment are still a challenge in clinical work. PCNs are tumors containing cystic components with different biological behaviors, and their clinical manifestations, epidemiology, imaging features, and malignant risks are different. Some are benign [e.g., serous cystic neoplasms (SCNs)], with a barely possible that turning into malignant, while others display a low or higher malignant risk [e.g., solid pseudopapillary neoplasms (SPNs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs)]. PCN management should concentrate on preventing the progression of malignant tumors while preventing complications caused by unnecessary surgical intervention. Clinically, various advanced imaging equipment are usually combined to obtain a more reliable preoperative diagnosis. The challenge for clinicians and radiologists is how to accurately diagnose PCNs before surgery so that corresponding surgical methods and follow-up strategies can be developed or not, as appropriate. The objective of this review is to sum up the clinical features, imaging findings and management of the most common PCNs according to the classic literature and latest guidelines.

Background: Rearranged during transfection (RET) is one of the rare driver genes of non-small-cell lung cancer (NSCLC), having a gene fusion incidence of 1-2% in NSCLC. Before the emergence of specific RET inhibitors, multikinase inhibitors such as cabozantinib and vandetanib were tried for RET fusionpositive NSCLC, but their efficacies were poor, and the U.S. Food and Drug Administration did not approve the application of these drugs for such patients. In the phase I/II ARROW clinical trial, pralsetinib significantly improved the overall remission rate and disease progression-free survival (PFS) of RET fusionpositive NSCLC patients. In the clinic, it is necessary to conduct adequate molecular screening of patients to guide drug choices. With the wide application of second-generation sequencing technology in clinical practice, many RET fusion partners have been discovered. It is rare for one patient with two RET fusions. Case Description: This paper reports a rare case of RET dual fusion in an advanced NSCLC patient who had coronary heart disease. After the failure of first-line treatment with platinum-based chemotherapy and post-line treatment with small-molecule targeted therapy of anlotinib and alectinib, the application of pralsetinib (400 mg, qd) reduced the tumor volume by 79% and achieved partial remission (based on the evaluation criteria of the World Health Organization) or reduced tumor volume by 17% (based on the Response Evaluation Criteria in Solid Tumors). It had an overall manageable safety profile. Conclusions: This patient with two different RET fusions was sensitive to pralsetinib. Patients with wellcontrolled coronary heart disease and recurrent myocardial infarction might benefit from pralsetinib. The pathogenesis of RET-dual-fusion NSCLC and its clinical impact need to be further studied to provide a theoretical basis for personalized treatment.

Background: Endoscopic mucosal dissection (EMD) is a new treatment method. Whether its clinical efficacy and safety are superior to surgical resection is still controversial. The sample size of previous studies on EMD for the treatment of early cancer of digestive tract is small, and there is no reliable evidence at present. Therefore, it is necessary to evaluate the efficacy and safety of EMD based on the evidence of evidence-based medicine. Methods:The PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, cqvip.com (VIP), websites and citation searching were searched to obtain relevant literature on EMD for early cancer and precancerous lesions of digestive tract. The retrieval time was from the establishment of the database to November 29th, 2022. Literature was screened according to inclusion and exclusion criteria and data and data were extracted. The final included literature was assessed by Cochrane risk of bias tool, and publication bias was assessed by Egger's test.Results: A total of 10 articles were included, with a total of 1,165 patients. Among these, 585 cases were treated with EMD and 580 cases were in the control group. The literature quality evaluation found that 5 articles had low risk of bias and 5 articles had unclear risk of bias. The results showed that the complete resection rate in the observation group was higher than that in the control group [risk ratio (RR) =1.25, 95% confidence interval (CI): 1.15-1.35, P<0.01]. Cumulative intraoperative blood loss (P<0.01), operation time (P<0.01), postoperative complications (P<0.01), hospital stay (P<0.01), and hospitalization expenses (P<0.01) in the observation group were lower than those in the control group.Conclusions: EMD for early gastrointestinal cancer and precancerous lesions can improve the complete resection rate of tumors; reduce intraoperative blood loss, complications, operation time, and hospitalization time and cost. However, due to the small number of literatures included in this paper, the quality of literatures is not high, and some results have heterogeneous interference, the conclusion needs to include more high-treatment studies for further study.