Energy stress promotes P-bodies formation via lysine-63-linked polyubiquitination of HAX1.

Energy stress, characterized by the reduction of intracellular ATP, has been implicated in various diseases, including cancer. Here, we show that energy stress promotes the formation of P-bodies in a ubiquitin-dependent manner. Upon ATP depletion, the E3 ubiquitin ligase TRIM23 catalyzes lysine-63 (K63)-linked polyubiquitination of HCLS1-associated protein X-1 (HAX1). HAX1 ubiquitination triggers its liquid‒liquid phase separation (LLPS) and contributes to P-bodies assembly induced by energy stress. Ubiquitinated HAX1 also interacts with the essential P-body proteins, DDX6 and LSM14A, promoting their condensation. Moreover, we find that this TRIM23/HAX1 pathway is critical for the inhibition of global protein synthesis under energy stress conditions. Furthermore, high HAX1 ubiquitination, and increased cytoplasmic localization of TRIM23 along with elevated HAX1 levels, promotes colorectal cancer (CRC)-cell proliferation and correlates with poor prognosis in CRC patients. Our data not only elucidate a ubiquitination-dependent LLPS mechanism in RNP granules induced by energy stress but also propose a promising target for CRC therapy.

Catalytic Enantioselective Nucleophilic α-Chlorination of Ketones with NaCl.

Catalytic enantioselective α-chlorination of ketones is a highly desirable process. Different from the conventional approaches that employ corrosive electrophilic chlorination reagents, the process disclosed here employs nucleophilic chloride, aqueous NaCl solution, and even seawater, as green inexpensive chlorine sources. This mechanistically distinct and electronically opposite approach provides facile access to diverse highly enantioenriched acyclic α-chloro ketones that are less straightforward by conventional approaches. With a chiral thiourea catalyst, a range of racemic α-keto sulfonium salts underwent enantioconvergent carbon-chlorine bond formation with high efficiency and excellent enantioselectivity under mild conditions. The sulfonium motif plays a crucial triple role by permitting smooth dynamic kinetic resolution to take place via a chiral anion binding mechanism in a well-designed phase-transfer system. This protocol represents a new general platform for the asymmetric nucleophilic α-functionalization of carbonyl compounds.

Self-Oxygenated Hydrogel Enhances Immune Cell Response and Infiltration Via Triggering Dual DNA Damage to Activate cGAS-STING and Inhibiting CAFs.

Immune checkpoint inhibitors (ICIs) offer promise in breaking through the treatment and survival dilemma of triple-negative breast cancer (TNBC), yet only immunomodulatory subtype and ≈5% TNBC patients respond as monotherapy due to lack of effector immune cells (internal problem) and physical barrier (external limitation) formed by cancer-associated fibroblasts (CAFs). A hydrogel drug-delivery platform, ALG@TBP-2/Pt(0)/nintedanib (ALG@TPN), is designed to induce strong immune functions and the dual elimination of the internal and external tumor microenvironment (TME). Activated by white light, through type I and II photodynamic therapy (PDT), TBP-2 generates large amounts of reactive oxygen species (ROS) intracellularly, oxidizing mitochondrial DNA (mtDNA). The unique catalase activity of Pt(0) converts endogenous H2O2 to O2, reducing the anoxia-limiting PDT and enhancing ROS generation efficacy. Abundant ROS can oxidize Pt(0) to cytotoxic Pt(II), damaging the nuclear DNA (nDNA). Dual damage to mtDNA and nDNA might bi-directionally activate the cGAS/STING pathway and enhance the immune cell response. Besides, nintedanib demonstrates a significant inhibitory effect on CAFs, weakening the immune barrier and deepening immune cell infiltration. Overall, the study provides a self-oxygenating hydrogel with the "PDT/chemotherapy/anti-CAFs" effect, triggering the cGAS/STING pathway to reshape the TME. Both internal and external interventions increase anti-TNBC immune responses.

A molecularly imprinted electrochemical sensor MIP/Cu-MOF/rGO/AuNPs/GCE for highly sensitive detection of electroneutral organophosphorus pesticide residues.

A novel electrochemical sensor, MIP/Cu-MOF/rGO/AuNPs/GCE, was developed by depositing gold nanoparticles, coating Cu-MOF/GO on the surface of glassy carbon electrode (GCE) before electroreducing graphene oxide (GO) to rGO and covering molecularly imprinted membrane by electropolymerization for highly sensitive detection of electroneutral organophosphorus pesticide residues in agricultural product. Cyclic voltammetry, differential pulse voltametry, scanning electron microscopy, energy-dispersive spectroscopy, and atomic force microscopy were used to characterize the imprinted sensor. Several key factors such as chitosan concentration, suspension volume, pH of polymerization solution, and polymerization scanning rate during preparation of the imprinted sensor were optimized in detail. When electroneutral phosmet was used as a template, the linear range of MIP/Cu-MOF/rGO/AuNPs/GCE for detecting phosmet was 1.00 × 10-14-5.00 × 10-7 mol/L with the limit of detection of 7.20 × 10-15 mol/L at working potentials of - 0.2 to 0.6 V. The selectivity, reproducibility, and repeatability of MIP/Cu-MOF/rGO/AuNPs/GCE were all acceptable. The recoveries of this method for determining phosmet in real samples ranged from 94.2 to 106.5%. The MIP/Cu-MOF/rGO/AuNPs/GCE sensor could be applied to detect electroneutral pesticide residues in organisms and agricultural products.

The effects of scar in psychological disorder: A bibliometric analysis from 2003 to 2022.

Scars are fibrous tissues that replace normal tissue during the wound healing process. Scarring can lead to low self-esteem, social impairment, depression, anxiety, and other psychiatric and psychological distress, necessitating a comprehensive understanding of the latest perspectives, topical research, and directions in scarring-mental health. This is a biblioshiny and VOSviewer based bibliometric analysis study. All data were obtained from the Web of Science, and a total of 664 articles from 2003 to 2022 met the criteria. The last 7 years have been a period of rapid growth in the field, with 2022 having the highest number of articles. The United States is the core country with the highest production and citation rate. The most cited literature was written in 2003 by Van Loey NE et al. Van Loey NE is the most prolific and influential author in this field. The top five popular keywords include "quality of life", "depression", "management", "anxiety", and "prevalence". The paper concludes that the current focus of scholars in the field is on the treatment of scars and that multidisciplinary treatment of such patients is worth exploring. These findings provide relevant researchers with the current state of research and possible future directions in this field.

DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming.

BACKGROUND: DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia (AML) with Arg882His (R882H) as the hotspot mutation. It has been reported that DNMT3A mutation plays a key role in leukemogenesis through hypomethylation of some target genes associated with cell growth and differentiation. In this study, we investigated the function of DNMT3A R882H in the malignant progression of AML by regulating metabolic reprogramming. METHODS: Ultra-High Performance Liquid Chromatography-High Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS) was used to detect metabolites in the serum of mice harboring Dnmt3a R878H mutation and the wild-type Dnmt3a. Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) were used to analyze the levels of DNA methylation and mRNA expression of genes in mouse Gr1+ bone marrow cells respectively. The TCGA and GO databases were used to analyze the differential genes between human samples carrying the DNMT3A R882 mutation and the wild-type DNMT3A. Co-immunoprecipitation and immunoblotting were used to illustrate the binding levels of Cyclins-CDKs and CDK inhibitors including CDKN1A and CDKN1B. Flow cytometry was used to analyze the cell differentiation, division, apoptosis and cell cycle. The effect of NAMPT inhibition on leukemia was evaluated by using in vivo fluorescence imaging in NOG mouse model bearing OCI-AML3 cells. RESULTS: DNMT3A mutation caused high expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the nicotinamide adenine dinucleotide (NAD) salvage synthetic pathway, through DNA hypomethylation, and finally led to abnormal nicotinamide (NAM) metabolism and NAD synthesis. The NAM-NAD metabolic abnormalities caused accelerated cell cycle progression. Inhibition of NAMPT can reduce the binding degree between Cyclins-CDKs, and increase the binding interaction of the CDK inhibitors with Cyclins-CDKs complexes. Moreover, cells with high expression of NAMPT were more sensitive to the NAMPT inhibitor FK866 with a lower IC50. The inhibition of NAMPT can remarkably extend the survival time of tumor-bearing mice and reduce the infiltration of tumor cells. CONCLUSIONS: Taken together, our data showed that DNMT3A mutation caused NAMPT overexpression to induce the reprogramming of NAM-NAD metabolism and contribute to abnormal proliferation, which provided a potential direction for targeted therapy at the metabolic level in AML with DNMT3A mutation.

A simple and available measurement of onco-sEV dsDNA to protein ratio as a potential tumor marker.

BACKGROUND: Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies. RESULTS: In this study, CEA+ sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ sEVs was determined. It was found that the NPr of CEA+ sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer. CONCLUSIONS: This study demonstrates that the dsDPr of CEA+ sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.

Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). METHODS: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. RESULTS: Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. CONCLUSIONS: Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies.

High Circulating FGF-23 and Its Relationship with Severity of Spinal Involvement in Diffuse Idiopathic Skeletal Hyperostosis.

The primary objective of this study was to determine the role of fibroblast growth factor 23 (FGF-23) in the pathogenesis of diffuse idiopathic skeletal hyperostosis (DISH). A total of 61 patients with DISH and 61 age- and sex-matched control patients without DISH were included in this study. The serum FGF-23, creatinine, inorganic phosphate, calcium, albumin, albumin-adjusted calcium and alkaline phosphatase, and C-reactive protein were assessed in both groups. Based on the extent of ossification, DISH group was further divided into T-DISH and L-DISH subgroups. Data were comparatively analyzed between DISH and Non-DISH groups and among T-DISH, L-DISH, and Non-DISH groups, respectively. Besides, the number of ossification segments of all DISH patients was quantified and the correlation between the number of ossification segments and the serum concentration of FGF-23 was analyzed. The results revealed that serum FGF-23 was significantly higher in DISH group than in Non-DISH group, regardless of gender. Interestingly, serum Pi was significantly lower in DISH group than in Non-DISH group. Moreover, a significant difference in serum FGF-23 among T-DISH, L-DISH, and Non-DISH groups was also observed. In contrast to Non-DISH group, both T-DISH and L-DISH subgroups displayed significantly higher serum FGF-23 level. Although the mean value was relatively higher in L-DISH subgroup, no statistically significant difference was found between T-DISH and L-DISH subgroups. In addition, a moderately positive correlation was identified between the number of ossification segments and the serum level of FGF-23. It can be concluded that serum FGF-23 could serve as a positive biomarker for DISH and may play a significant role in ectopic ossification in DISH.

Access to Amides and Lactams via Pyridotriazole as a Transformable Directing Group.

Amide and lactam frameworks were synthesized via an efficient two-step strategy. In this protocol, pyridotriazoles were first treated with isocyanates to form the corresponding amides, which were found to be sufficiently reactive to undergo subsequent intramolecular N-H insertion in the absence of any additional reagents or catalysts.

NiFe Nanoparticle-Encapsulated Ultrahigh-Oxygen-Doped Carbon Layers as Bifunctional Electrocatalysts for Rechargeable Zn-Air Batteries.

There is an urgent demand for developing highly efficient bifunctional electrocatalysts with excellent stability toward the oxygen evolution and reduction reactions (OER and ORR, respectively) for rechargeable Zn-air batteries (ZABs). In this work, NiFe nanoparticles encapsulated within ultrahigh-oxygen-doped carbon quantum dots (C-NiFe) as bifunctional electrocatalysts are successfully obtained. The accumulation of carbon layers formed by carbon quantum dots results in abundant pore structures and a large specific surface area, which is favorable for improving catalytic active site exposure, ensuring high electronic conductivity and stability simultaneously. The synergistic effect of NiFe nanoparticles enriched the number of active centers and naturally increased the inherent electrocatalytic performance. Benefiting from the above optimization, C-NiFe shows excellent electrochemical activity for both OER and ORR processes (the OER overpotential is only 291 mV to achieve 10 mA cm-2). Furthermore, the C-FeNi catalyst as an air cathode displays an impressive peak power density of 110 mW cm-2, an open-circuit voltage of 1.47 V, and long-term durability over 58 h. The preparation of this bifunctional electrocatalyst provides a design idea for the construction of bimetallic NiFe composites for high-performance Zn-air batteries.

Safety and feasibility of a modularized procedure for trans-subxiphoid robotic extended thymectomy.

BACKGROUND: The purpose of this study was to introduce an "eight-step modularized procedure (M-RET)" for trans-subxiphoid robotic extended thymectomy for patients with myasthenia gravis (MG). Its safety and feasibility were further verified in this study. MATERIALS AND METHODS: This retrospective study included 87 consecutive MG patients who underwent trans-subxiphoid robotic extended thymectomy at our institution between September 2016 and August 2021. According to different resection models, patients were divided into two groups: traditional trans-subxiphoid robotic extended thymectomy group (T-RET group) and eight-step modularized technique group (M-RET group). Baseline demographic characteristics and operation-related parameters were collected and compared between the two groups. RESULTS: There were 41 (47.1%) patients in the M-RET group and 46 (52.9%) patients in the T-RET group. The M-RET group resected a greater amount of mediastinal adipose tissues and required more dissection time (median and interquartile range: 135.0, 125.0 to 164.0 v. 120.0, 105.0 to 153.8, P = 0.006) compared with the T-RET group. There were no statistically significant differences in terms of the intraoperative blood loss, duration of chest drainage, length of hospital stay, and postoperative complications between the two groups. There was no mortality or conversion in each of the two groups and all patients recovered well upon discharge. CONCLUSION: The eight-step modularized technique of trans-subxiphoid robotic extended thymectomy was verified to be a safe, effective, radical procedure, which offers unique superiority over ectopic thymic tissue resection.

Perihematomal edema after minimally invasive surgery: a matter of concern to neurosurgeons.

The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.

Microvascular decompression using a fully transcranial neuroendoscopic approach.

OBJECTIVE: To evaluate the effectiveness and safety of microvascular decompression (MVD) using a fully transcranial neuroendoscopic approach. METHODS: Thirty-one patients who underwent MVD using a fully transcranial neuroendoscopic approach in our department between May 2016 and September 2019 were retrospectively reviewed. RESULTS: All patients successfully underwent MVD, and immediate pain relief was achieved in all 17 cases of trigeminal neuralgia (TGH) and 3 cases of glossopharyngeal neuralgia (GPN). Hemifacial spasm (HFS) was completely resolved in all 11 patients. No mortality or permanent complication was seen. CONCLUSIONS: The endoscope is a useful tool for confirming vascular conflict identified by the microscope and is helpful in detecting the vessel responsible for neuralgia without retracting the brain and nerves. MVD using a fully transcranial neuroendoscopic approach is an effective and safe alternative to endoscopic-assisted MVD and traditional MVD.

Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway.

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1ß, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.

Research progress of severe acute respiratory syndrome coronavirus 2 on aerosol collection and detection.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 has negatively affected people's lives and productivity. Because the mode of transmission of SARS-CoV-2 is of great concern, this review discusses the sources of virus aerosols and possible transmission routes. First, we discuss virus aerosol collection methods, including natural sedimentation, solid impact, liquid impact, centrifugal, cyclone and electrostatic adsorption methods. Then, we review common virus aerosol detection methods, including virus culture, metabolic detection, nucleic acid-based detection and immunology-based detection methods. Finally, possible solutions for the detection of SARS-CoV-2 aerosols are introduced. Point-of-care testing has long been a focus of attention. In the near future, the development of an instrument that integrates sampling and output results will enable the real-time, automatic monitoring of patients.

Ru-Catalyzed Hydroboration of Ynones Leads to a Nontraditional Mode of Reactivity.

Although hydroboration of simple ketones and alkynes have been well-established, little is known about the unique hydroboration reactivity for ynones, a family of important building blocks. Herein we report a new reaction mode of ynones leading to structurally novel and synthetically useful but previously inaccessible products, vinyl α-hydroxylboronates, under mild ruthenium-catalyzed hydroboration conditions. This reaction features high efficiency, a broad scope, and complete chemo-, regio-, and stereoselectivity, in spite of many possible competitive pathways. Both control experiments and detailed DFT studies suggested a two-step mechanism, involving initial rate-determining conjugate addition of hydroborane to form the key boryl allenolate intermediate followed by a fast second hydroboration of the enolate motif of the allenolate. Notably, direct 1,4-addition of hydroborane to carbonyl-conjugated alkynes also represents a new mode of reactivity. Despite the overwhelming complexity of this process, which involves selectivity control in almost every step, a thorough and detailed computation on a large set of possible transition states explained the unusual reactivity and intrinsic origin of selectivity.

Identification of a 5-gene-risk score model for predicting luminal A-invasive lobular breast cancer survival.

Breast cancer is a devastating malignancy, among which the luminal A (LumA) breast cancer is the most common subtype. In the present study, we used a comprehensive bioinformatics approach in the hope of identifying novel prognostic biomarkers for LumA breast cancer patients. Transcriptomic profiling of 611 LumA breast cancer patients was downloaded from TCGA database. Differentially expressed genes (DEGs) between tumor samples and controls were first identified by differential expression analysis, before being used for the weighted gene co-expression network analysis. The subsequent univariate Cox regression and LASSO algorithm were used to uncover key prognostic genes for constructing multivariate Cox regression model. Patients were stratified into high-risk and low-risk groups according to the risk score, and subjected to multiple downstream analyses including survival analysis, gene set enrichment analysis (GSEA), inference on immune cell infiltration and analysis of mutation burden. Receiving operator curve analysis was also performed. A total of 7071 DEGs were first identified by edgeR package, pink module was found significantly associated with invasive lobular carcinoma (ILC). 105 prognostic genes and 9 predictors were identified, allowing the identification of a 5-key prognostic genes (LRRC77P, CA3, BAMBI, CABP1, ATP8A2) after intersection. These 5 genes, and the resulting Cox model, displayed good prognostic performance. Furthermore, distinct differences existed between two risk-score stratified groups at various levels. The identified 5-gene prognostic model will help deepen the understanding of the molecular and immunological mechanisms that affect the survival of LumA-ILC patients and guide and proper monitoring of these patients.

Triple branched RGD modification on liposomes: A prospective strategy to enhance the glioma targeting efficiency.

Glioma, as one of the most common primary intracranial tumors, is in an urgent need for specific targeting agents. Multi-branched RGD ligand is a promising alternative for liposome functionalization which combines the benefits of high affinity with αvß3 receptors and proper branching structure in response to the receptor clustering. Herein, we designed and synthesized single branched, double branched and triple branched RGD ligand (1RGD-Chol, 2RGD-Chol and 3RGD-Chol) respectively, which were then modified on the liposomes to prepare six different kinds of liposomes (including 1RGD-Lip, 2RGD-Lip, 3RGD-Lip, 2 × 1RGD-Lip, 3 × 1RGD-Lip and unmodified Lip). Subsequently, a series of assays were conducted. The results exhibited that the liposome decorated with 3RGD-Chol ligand possessed superior cellular internalization ability in C6 cells and bEnd.3 cells, suggesting the strongest ability of 3RGD-Lip to target the blood-brain barrier (BBB) and glioma cells. Besides, both the cytotoxicity and pro-apoptotic assays revealed that PTX-3RGD-Lip had the strongest ability to inhibit the survival of C6 cells. Moreover, the enrichment of liposomes at tumor site was 3RGD-Lip > 3 × 1RGD-Lip ≈ 2RGD-Lip ≈ 2 × 1RGD-Lip > 1RGD-Lip > Lip according to the in vivo imaging of C6-bearing mice, which was consistent with the result of in vitro targeting experiments. To sum up, the targeting efficiency of liposomes can be strongly promoted by improving the amount of targeting molecules, whereas the branching structure and spatial distance of RGD residues also accounted for the affinity between liposomes and αvß3 receptors. Collectively, PTX-3RGD-Lip would be a prospective strategy in glioma treatment.

Comparison of epicardial adipose tissue volume quantification between ECG-gated cardiac and non-ECG-gated chest computed tomography scans.

BACKGROUND: This study investigated accuracy and consistency of epicardial adipose tissue (EAT) quantification in non-ECG-gated chest computed tomography (CT) scans. METHODS: EAT volume was semi-automatically quantified using a standard Hounsfield unit threshold (- 190, - 30) in three independent cohorts: (1) Cohort 1 (N = 49): paired 120 kVp ECG-gated cardiac non-contrast CT (NCCT) and 120 kVp non-ECG-gated chest NCCT; (2) Cohort 2 (N = 34): paired 120 kVp cardiac NCCT and 100 kVp non-ECG-gated chest NCCT; (3) Cohort 3 (N = 32): paired non-ECG-gated chest NCCT and chest contrast-enhanced CT (CECT) datasets (including arterial phase and venous phase). Images were reconstructed with the slice thicknesses of 1.25 mm and 5 mm in the chest CT datasets, and 3 mm in the cardiac NCCT datasets. RESULTS: In Cohort 1, the chest NCCT-1.25 mm EAT volume was similar to the cardiac NCCT EAT volume, while chest NCCT-5 mm underestimated the EAT volume by 7.5%. In Cohort 2, 100 kVp chest NCCT-1.25 mm were 13.2% larger than 120 kVp cardiac NCCT EAT volumes. In Cohort 3, the chest arterial CECT and venous CECT dataset underestimated EAT volumes by ~ 28% and ~ 18%, relative to chest NCCT datasets. All chest CT-derived EAT volumes were similarly associated with significant coronary atherosclerosis with cardiac CT counterparts. CONCLUSION: The 120 kVp non-ECG-gated chest NCCT-1.25 mm images produced EAT volumes comparable to cardiac NCCT. Chest CT EAT volumes derived from consistent imaging settings are excellent alternatives to the cardiac NCCT to investigate their association with coronary artery disease.