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Nanoscale metal−organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs' applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N 3 was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide−alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N 3 was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin + ) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) in vivo, the positron-emitting zirconium-89 ( 89 Zr) was incorporated into UiO-66-N 3 . Similar PEGylation and F3 peptide conjugation resulted in the formation of 89 Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of 89 Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.

Grainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

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Background: Both patency maintenance and neoangiogenesis contribute to cerebrovascular bypass efficacy. However, the combined impact of the aforementioned two indicators on postoperative revascularization following superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass has been less well elucidated. Meanwhile, there is a paucity of evidence with conflicting results about postoperative aspirin therapy.Objective: The objective of the study was to investigate the correlation between aspirin use and STA-MCA bypass efficacy, including patency, postoperative neoangiogenesis, and follow-up outcomes.Methods: A total of 181 MMD patients (201 procedures) undergoing STA-MCA bypass at our institution (2017–2019) were retrospectively reviewed. The bypass efficacy level and postoperative complications were compared between aspirin and non-aspirin groups.Results: Among 95 PS-matched pairs, the aspirin group presented a significantly more favorable bypass efficacy than the non-aspirin group [odds ratio (OR) 2.23, 95% confidence interval (CI) 1.11–4.61; p = 0.026]. Multivariate logistic regression analysis confirmed the profound impact of aspirin as an independent predictor of bypass efficacy [adjusted OR 2.91, 95% CI 1.34–6.68; p = 0.009]. A remarkable negative correlation was found between bypass efficacy and the rate of ischemic complications (Phi = −0.521). Postoperative aspirin therapy was associated with a non-significant trend toward a lower incidence of ischemic events [OR 0.73, 95% CI 0.23–2.19; p = 0.580]. No significant difference in bleeding rates was observed between aspirin and control groups [OR 1.00, 95% CI 0.12–8.48; p = 1.000].Conclusion: Among patients undergoing STA-MCA bypass procedures, bypass efficacy is a good predictor of follow-up outcomes. Postoperative aspirin therapy can improve patency, neoangiogenesis, and overall bypass efficacy, thereby protecting against postoperative ischemic complications.Clinical Trial Registration:http://www.chictr.org.cn/, identifier CTR2100046178.

Quantifying the importance of the key sites on haemagglutinin in determining the selection advantage of influenza virus: Using A/H3N2 as an example Dear Editor , Authors' contributionsSZ and MHW conceived the study. SZ carried out the analysis, and drafted the first manuscript. SZ and MHW discussed the results. All authors read, revised the manuscript, and gave final approval for publication. Declaration of Competing InterestMHW is a shareholder of Beth Bioinformatics Co., Ltd, and BCYZ is a shareholder of Beth Bioinformatics Co., Ltd and Health View Bioanalytics Ltd. Declarations Ethics approval and consent to participateThe ethical approval or individual consent was not applicable. Availability of data and materialsAll influenza viruses sequence data were collected via the influenza virus database (IVD) of the National center for Biotechnology Information (NCBI). Please see the online supporting information for details. Consent for publicationNot applicable.

ObjectiveChronic internal carotid artery occlusion (CICAO) can cause transient ischemic attack (TIA) and ischemic stroke. Carotid artery stenting (CAS) with embolic protection devices and hybrid surgery combining carotid endarterectomy and endovascular treatment are effective methods for carotid revascularization. The objective of this study was to evaluate and compare the effect and safety of the two surgical procedures.MethodsThis was a single-center retrospective study. In this study, 44 patients who underwent hybrid surgery and 35 who underwent endovascular intervention (EI) at our center were enrolled consecutively between May 2016 and March 2022. All patients were classified into four groups (A-D), as described by Hasan et al. We recorded and analyzed clinical data, angiographic characteristics, technical success rate, perioperative complications, and follow-up data.ResultsThere was no significant difference in baseline characteristics between hybrid surgery group and EI group, except for plasma high density lipoproteins (HDL) levels (median [interquartile range]: hybrid surgery, 0.99 [0.88–1.18] vs. EI, 0.85 [0.78–0.98] mmol/L, P = 0.001). The technical success rate of hybrid surgery was higher than that of EI (37/44 [84.1%] vs. 18/35 [51.4%], P = 0.002; type A: 15/16 [93.8%] vs. 10/11 [90.9%], P = 1.000; type B: 9/10 [90.0%] vs. 5/7 [71.4%], P = 0.537; type C: 12/15 [80.0%] vs. 3/12 [25.0%], P = 0.004; type D: 1/3 [33.3%] vs. 0/5 [0%], P = 0.375). No significant difference was observed in the incidence of perioperative complications between the two procedures (hybrid surgery: 7/44 [15.9%] vs. EI: 6/35 [17.1%], P = 0.883). In addition, there were no significant differences in the rates of stroke and restenosis during follow-up.ConclusionsFor patients with symptomatic CICAO, hybrid surgery may have an advantage over EI in successfully recanalizing occluded segments. There was no significant difference in safety and restenosis between hybrid surgery and EI.