Laparoscopic ileocecal-sparing vs traditional right hemicolectomy for cancer of the hepatic flexure or proximal transverse colon: a dual-center propensity score-matched study.

Background: Traditional right hemicolectomy (TRH) is the standard treatment for patients with nonmetastatic right colon cancer. However, the ileocecum, a vital organ with mechanical and immune functions, is removed in these patients regardless of the tumor location. This study aimed to evaluate the technical and oncological safety of laparoscopic ileocecal-sparing right hemicolectomy (LISH). Method: Patients who underwent LISH at two tertiary medical centers were matched 1:2 with patients who underwent TRH by propensity score matching based on sex, age, body mass index, tumor location, and disease stage. Data on surgical and perioperative outcomes were collected. Oncological safety was evaluated in a specimen-oriented manner. Lymph nodes (LNs) near the ileocolic artery (ICA) were examined independently in the LISH group. Disease outcomes were recorded for patients who completed one year of follow-up. Results: In all, 34 patients in the LISH group and 68 patients in the TRH group were matched. LISH added 8 minutes to the dissection of LNs around the ileocolic vessels (groups 201/201d, 202, and 203 LNs), without affecting the total operation time, blood loss, or perioperative adverse event rate. Compared with TRH, LISH had a comparable lymphadenectomy quality, specimen quality, and safety margin while preserving a more functional bowel. The LISH group had no cases of LN metastasis near the ICA. No difference was detected in the recurrence rate at the 1-year follow-up time point between the two groups. Conclusion: In this dual-center study, LISH presented comparable surgical and oncological safety for patients with hepatic flexure or proximal transverse colon cancer.

Correction: Enterovirus 71 Protease 2Apro Targets MAVS to Inhibit Anti-Viral Type I Interferon Responses.

[This corrects the article DOI: 10.1371/journal.ppat.1003231.].

Impacts of environmental factors on the aetiological diagnosis and disease severity of community-acquired pneumonia in China: a multicentre, hospital-based, observational study.

Environmental exposures are known to be associated with pathogen transmission and immune impairment, but the association of exposures with aetiology and severity of community-acquired pneumonia (CAP) are unclear. A retrospective observational study was conducted at nine hospitals in eight provinces in China from 2014 to 2019. CAP patients were recruited according to inclusion criteria, and respiratory samples were screened for 33 respiratory pathogens using molecular test methods. Sociodemographic, environmental and clinical factors were used to analyze the association with pathogen detection and disease severity by logistic regression models combined with distributed lag nonlinear models. A total of 3323 CAP patients were included, with 709 (21.3%) having severe illness. 2064 (62.1%) patients were positive for at least one pathogen. More severe patients were found in positive group. After adjusting for confounders, particulate matter (PM) 2.5 and 8-h ozone (O3-8h) were significant association at specific lag periods with detection of influenza viruses and Klebsiella pneumoniae respectively. PM10 and carbon monoxide (CO) showed cumulative effect with severe CAP. Pollutants exposures, especially PM, O3-8h, and CO should be considered in pathogen detection and severity of CAP to improve the clinical aetiological and disease severity diagnosis.

The EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction.

SETD3 is an essential host factor for the replication of a variety of enteroviruses that specifically interacts with viral protease 2A. However, the interaction between SETD3 and the 2A protease has not been fully characterized. Here, we use X-ray crystallography and cryo-electron microscopy to determine the structures of SETD3 complexed with the 2A protease of EV71 to 3.5 Å and 3.1 Å resolution, respectively. We find that the 2A protease occupies the V-shaped central cleft of SETD3 through two discrete sites. The relative positions of the two proteins vary in the crystal and cryo-EM structures, showing dynamic binding. A biolayer interferometry assay shows that the EV71 2A protease outcompetes actin for SETD3 binding. We identify key 2A residues involved in SETD3 binding and demonstrate that 2A's ability to bind SETD3 correlates with EV71 production in cells. Coimmunoprecipitation experiments in EV71 infected and 2A expressing cells indicate that 2A interferes with the SETD3-actin complex, and the disruption of this complex reduces enterovirus replication. Together, these results reveal the molecular mechanism underlying the interplay between SETD3, actin, and viral 2A during virus replication.

Urchin-Like Mesoporous TiN Hollow Sphere Enabling Promoted Electrochemical Kinetics of Bromine-Based Flow Batteries.

Bromine-based flow batteries (BFB) have always suffered from poor kinetics due to the sluggish Br3 -/Br- redox, hindering their practical applications. Developing cathode materials with high catalytic activity is critical to address this challenge. Herein, the in-depth investigation for the free energy of the bromine redox electrode is conducted initially through DFT calculations, establishing the posterior desorption during oxidation as the rate-determining step. An urchin-like titanium nitride hollow sphere (TNHS) composite is designed and synthesized as the catalyst for bromine redox. The large difference in Br- and Br3 - adsorption capability of TNHS promotes rapid desorption of generated Br3 - during the oxidation process, liberating active sites timely to enable smooth ongoing reactions. Besides, the urchin-like microporous/mesoporous structure of TNHS provides abundant active surface for bromine redox reactions, and ample cavities for the bromine accommodation. The inherently high conductivity of TNHS enables facile electron transfer through multiple channels. Consequently, zinc-bromide flow batteries with TNHS catalyst exhibit significantly enhanced kinetics, stably operating at 80 mA cm-2 with 82.78% energy efficiency. Overall, this study offers a solving strategy and catalyst design approach to the sluggish kinetics that has plagued bromine-based flow batteries.

Gut Microbiota Improves Prognostic Prediction in Critically Ill COVID-19 Patients Alongside Immunological and Hematological Indicators.

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

A Self-supervised Learning-Based Fine-Grained Classification Model for Distinguishing Malignant From Benign Subcentimeter Solid Pulmonary Nodules.

RATIONALE AND OBJECTIVES: Diagnosing subcentimeter solid pulmonary nodules (SSPNs) remains challenging in clinical practice. Deep learning may perform better than conventional methods in differentiating benign and malignant pulmonary nodules. This study aimed to develop and validate a model for differentiating malignant and benign SSPNs using CT images. MATERIALS AND METHODS: This retrospective study included consecutive patients with SSPNs detected between January 2015 and October 2021 as an internal dataset. Malignancy was confirmed pathologically; benignity was confirmed pathologically or via follow-up evaluations. The SSPNs were segmented manually. A self-supervision pre-training-based fine-grained network was developed for predicting SSPN malignancy. The pre-trained model was established using data from the National Lung Screening Trial, Lung Nodule Analysis 2016, and a database of 5478 pulmonary nodules from the previous study, with subsequent fine-tuning using the internal dataset. The model's efficacy was investigated using an external cohort from another center, and its accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Overall, 1276 patients (mean age, 56 ± 10 years; 497 males) with 1389 SSPNs (mean diameter, 7.5 ± 2.0 mm; 625 benign) were enrolled. The internal dataset was specifically enriched for malignancy. The model's performance in the internal testing set (316 SSPNs) was: AUC, 0.964 (95% confidence interval (95%CI): 0.942-0.986); accuracy, 0.934; sensitivity, 0.965; and specificity, 0.908. The model's performance in the external test set (202 SSPNs) was: AUC, 0.945 (95% CI: 0.910-0.979); accuracy, 0.911; sensitivity, 0.977; and specificity, 0.860. CONCLUSION: This deep learning model was robust and exhibited good performance in predicting the malignancy of SSPNs, which could help optimize patient management.

A programmable topological photonic chip.

Controlling topological phases of light allows the observation of abundant topological phenomena and the development of robust photonic devices. The prospect of more sophisticated control with topological photonic devices for practical implementations requires high-level programmability. Here we demonstrate a fully programmable topological photonic chip with large-scale integration of silicon photonic nanocircuits and microresonators. Photonic artificial atoms and their interactions in our compound system can be individually addressed and controlled, allowing the arbitrary adjustment of structural parameters and geometrical configurations for the observation of dynamic topological phase transitions and diverse photonic topological insulators. Individual programming of artificial atoms on the generic chip enables the comprehensive statistical characterization of topological robustness against relatively weak disorders, and counterintuitive topological Anderson phase transitions induced by strong disorders. This generic topological photonic chip can be rapidly reprogrammed to implement multifunctionalities, providing a flexible and versatile platform for applications across fundamental science and topological technologies.

CDK5RAP3 is a novel super-enhancer-driven gene activated by master TFs and regulates ER-Phagy in neuroblastoma.

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.

p-Smad3 differentially regulates the cytological behavior of osteoclasts before and after osteoblasts maturation.

BACKGROUND: A series of previous investigations have revealed that p-Smad3 plays a facilitative role in the differentiation and maturation of osteoblasts, while also regulating the expression of certain intercellular communication factors. However, the effects of p-Smad3 in osteoblasts before and after maturation on the proliferation, migration, differentiation, apoptosis and other cellular behaviors of osteoclasts have not been reported. METHODS: MC3T3-E1 cells were cultured in osteogenic induction medium for varying durations, After that, the corresponding conditioned medium was collected and the osteoclast lineage cells were treated. To elucidate the regulatory role of p-Smad3 within osteoblasts, we applied the activator TGF-ß1 and inhibitor SIS3 to immature and mature osteoblasts and collected corresponding conditioned media for osteoclast intervention. RESULTS: We observed an elevation of p-Smad3 and Smad3 during the early stage of osteoblast differentiation, followed by a decline in the later stage. we discovered that as osteoblasts mature, their conditioned media inhibit osteoclasts differentiation and the osteoclast-coupled osteogenic effect. However, it promotes apoptosis in osteoclasts and the angiogenesis coupled with osteoclasts. p-Smad3 in immature osteoblasts, through paracrine effects, promotes the migration, differentiation, and osteoclast-coupled osteogenic effects of osteoclast lineage cells. For mature osteoblasts, p-Smad3 facilitates osteoclast apoptosis and the angiogenesis coupled with osteoclasts. CONCLUSIONS: As pre-osteoblasts undergo maturation, p-Smad3 mediated a paracrine effect that transitions osteoclast cellular behaviors from inducing differentiation and stimulating bone formation to promoting apoptosis and coupling angiogenesis.

Aging-induced MCPH1 translocation activates necroptosis and impairs hematopoietic stem cell function.

DNA damage contributes to the aging of hematopoietic stem cells (HSCs), yet the underlying molecular mechanisms are not fully understood. In this study, we identified a heterogeneous functional role of microcephalin (MCPH1) in the nucleus and cytoplasm of mouse HSCs. In the nucleus, MCPH1 maintains genomic stability, whereas in the cytoplasm, it prevents necroptosis by binding with p-RIPK3. Aging triggers MCPH1 translocation from cytosol to nucleus, reducing its cytoplasmic retention and leading to the activation of necroptosis and deterioration of HSC function. Mechanistically, we found that KAT7-mediated lysine acetylation within the NLS motif of MCPH1 in response to DNA damage facilitates its nuclear translocation. Targeted mutation of these lysines inhibits MCPH1 translocation and, consequently, compromises necroptosis. The dysfunction of necroptosis signaling, in turn, improves the function of aged HSCs. In summary, our findings demonstrate that DNA damage-induced redistribution of MCPH1 promotes HSC aging and could have broader implications for aging and aging-related diseases.

The association between leptin and diabetes: A meta-analysis.

PURPOSE: The study object was to determine the relationship between leptin and diabetes. METHODS: We searched for the literature on the relationship between leptin and diabetes from PubMed, EMBASE, Cochrane Library, and CNKI databases. We carried out the meta-analysis by calculating the Std. Mean Difference (SMD) and 95% confidence intervals (CIs) to study the relationship between leptin and diabetes. We performed the Chi-square-based Q test and I2 statistics to evaluate the potential heterogeneity, and the sensitivity analysis was performed to evaluate the stability of our results. Moreover, Begg's test was performed to evaluate the publication bias. RESULTS: There are 10 studies in this study for meta-analysis, which include 1879 patients (diabetic (n = 1024); and nondiabetic patients (n = 855)). The results indicated that the levels of serum leptin were significantly increased in patients with diabetes (SMD = 1.78, 95% CI [0.81, 2.76]), especially those with gestational diabetes mellitus compared with controls (SMD = 3.03, 95% CI [1.21, 4.86]). However, the results showed that there was no difference in serum leptin levels between type 2 diabetes and controls (SMD = 0.34, 95% CI [-1.06, 1.74]). CONCLUSIONS: Our analysis indicated that the levels of serum leptin were significantly elevated in patients with diabetes especially those with gestational diabetes mellitus compared with controls.

Secondary metabolites from Penicillium sp. HS-11, a fungal endophyte of Huperzia serrata.

Three new sorbicillinoids sorbicatechols E-G (1-3), along with seven known compounds 4-10, were obtained from the ethanol extract of Penicillium sp. HS-11, a fungal endophyte of the medicinal plant Huperzia serrata. The structures of 1-3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the ECD spectra. Sorbicatechol G (3) represented the first hybrid sorbicillinoid bearing a tetralone skeleton. In the in-vitro bioassay, trichodimerol (5) exhibited moderate inhibitory activity against the Escherichia coli ß-glucuronidase (EcGUS) with an IC50 value of 92.0 ± 9.4 µM.

METTL14 promotes neuroblastoma formation by inhibiting YWHAH via an m6A-YTHDF1-dependent mechanism.

Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5' UTR, were specifically recognized by the m6A "reader" protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

Ginsenoside Rc alleviates osteoporosis by the TGF-ß/Smad signaling pathway.

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.

Predicting epidermal growth factor receptor mutations in non-small cell lung cancer through dual-layer spectral CT: a prospective study.

OBJECTIVE: To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion. RESULTS: Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]). CONCLUSION: Quantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC. CRITICAL RELEVANCE STATEMENT: Quantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them. KEY POINTS: Determining EGFR mutation status in patients with NSCLC before starting therapy is essential. Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients. NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.

Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

Immune Responses in Discharged COVID-19 Patients With and Without Long COVID Symptoms.

The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)-immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities.

Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer.

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.