Relationship of mTORC1 and ferroptosis in tumors.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization. It highlights the dual role of neutrophils in tissue damage and repair, and the critical involvement of the blood-brain barrier (BBB) in stroke outcomes. Special emphasis is placed on ischemia-reperfusion injury, characterized by oxidative stress, inflammation, and endothelial dysfunction, which paradoxically exacerbates cerebral damage post-revascularization. The review also explores the potential of targeting molecular pathways involved in BBB integrity and inflammation to enhance the efficacy of recanalization therapies. By synthesizing current research, this paper aims to provide insights into optimizing treatment protocols and developing adjuvant neuroprotective strategies, thereby advancing stroke therapy and improving patient outcomes.

A wide landscape of morbidity and mortality risk associated with marital status in 0.5 million Chinese men and women: a prospective cohort study.

Background: A comprehensive depiction of long-term health impacts of marital status is lacking. Methods: Sex-stratified phenome-wide association analyses (PheWAS) of marital status (living with vs. without a spouse) were performed using baseline (2004-2008) and follow-up information (ICD10-coded events till Dec 31, 2017) from the China Kadoorie Biobank (CKB). We estimated adjusted hazard ratios (aHRs) to evaluate the associations of marital status with morbidity risks of phenome-wide significant diseases or sex-specific top-10 death causes in China documented in 2017. Additionally, the association between marital status and mortality risks among participants with major chronic diseases at baseline was assessed. Findings: During up to 11.1 years of the median follow-up period, 1,946,380 incident health events were recorded among 210,202 men and 302,521 women aged 30-79. Marital status was found to have phenome-wide significant associations with thirteen diseases among men (p < 9.92 × 10-5) and nine diseases among women (p < 9.33 × 10-5), respectively. After adjusting for all disease-specific covariates in the final model, participants living without a spouse showed increased risks of schizophrenia, schizotypal and delusional disorders (aHR [95% CI]: 2.55, [1.83-3.56] for men; 1.49, [1.13-1.97] for women) compared with their counterparts. Additional higher risks in overall mental and behavioural disorder (1.31, 1.13-1.53), cardiovascular disease (1.07, 1.04-1.10) and cancer (1.06, 1.00-1.12) were only observed among men without a spouse, whereas women living without a spouse were at lower risks of developing genitourinary diseases (0.89, 0.85-0.93) and injury & poisoning (0.93, 0.88-0.97). Among 282,810 participants with major chronic diseases at baseline, 39,166 deaths were recorded. Increased mortality risks for those without a spouse were observed in 12 of 21 diseases among male patients and one of 23 among female patients. For patients with any self-reported disease at baseline, compared with those living with a spouse, the aHRs (95% CIs) of mortality risk were 1.29 (1.24-1.34) and 1.04 (1.00-1.07) among men and women without a spouse (pinteraction<0.0001), respectively. Interpretation: Long-term associations of marital status with morbidity and mortality risks are diverse among middle-aged Chinese adults, and the adverse impacts due to living without a spouse are more profound among men. Marital status may be an influential factor for health needs. Funding: The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, and the UK Wellcome Trust.

Bimetal-bridging Nitrogen Coordination in Carbon-based Electrocatalysts for pH-universal Oxygen Reduction.

Electrocatalysts with atomically dispersed metal sites (e.g., metal-nitrogen-carbon) have been deemed as promising alternatives for noble-metal catalysts in couples of electrocatalytic reactions. However, the modulation of such atomic sites and the understanding of their interactions are still highly challenging. Herein, we propose a unique supermolecule assembly-profile coating strategy to prepare a series of diatomic electrocatalysts by profile coating of eight Prussian blue analogues (PBAs) on supramolecular supports respectively as bimetallic sources. The detailed microstructure analysis revealed that the metal-nitrogen-carbon sites with four- (Zn-N4 ) and five-coordination (Fe-N5 ) via the nitrogen coordination are similar to the cytochrome c oxidases. For promising electrocatalysis, such unique microstructure is able to activate oxygen molecules due to nitrogen-bonding coordination with bimetal sites, thus leading to efficient four-electron oxygen reduction in alkaline, neutral, and acid electrolytes. Especially, zinc group elements (e.g., Zn and Cd) with d10 electron configuration would significantly boost the nitrogen-bonding coordination with bimetal sites to enhance electrocatalytic activity. The proof-of-concept for the general synthesis of advanced electrocatalysts with controllable bimetal active sites and the mechanistic understanding will promote the promising electrocatalysis by applying the similar principles.

Incidence of Ventriculomegaly in Patients With Craniosynostosis.

Hydrocephalus is variously associated with syndromic craniosynostosis (CS), while it is randomly encountered in nonsyndromic CS. But actually, the ventriculomegaly in CS is less described. In this study, the authors aim to establish whether ventriculomegaly is common in patients with CS, in both syndromic and nonsyndromic. Retrospective measurements of Evans index (EI) were taken from thin-section computed tomography scans of 169 preoperative CS patients to assess cerebral ventricular volume. EI >0.3 indicates ventricular enlargement. A total of 169 CS patients who underwent computed tomography scan from February 2018 to December 2021 were retrospectively evaluated, including 114 males and 55 females. The average age at diagnosis was 16 months (range: 1-103 mo). Among them, 37 with syndromic CS, including 17 ventricular megaly patients, had an EI >0.3 (46.0%), and 4 of them had intracranial hypertension and needed ventriculoperitoneal shunt treatment before cranial vault remolding. One hundred and thirty-two had nonsyndromic CS (100 single-suture CS, 32 multisuture CS), and 26 of them had an EI of 0.3 or greater (19.7%). Ventrocular megaly is common among patients with CS. Early craniotomy may stabilize ventricular dilation.

Understanding Gaps in the Hypertension and Diabetes Care Cascade: Systematic Scoping Review.

BACKGROUND: Hypertension and diabetes are global health challenges requiring effective management to mitigate their considerable burden. The successful management of hypertension and diabetes requires the completion of a sequence of stages, which are collectively termed the care cascade. OBJECTIVE: This scoping review aimed to describe the characteristics of studies on the hypertension and diabetes care cascade and identify potential interventions as well as factors that impact each stage of the care cascade. METHODS: The method of this scoping review has been guided by the framework by Arksey and O'Malley. We systematically searched MEDLINE, Embase, and Web of Science using terms pertinent to hypertension, diabetes, and specific stages of the care cascade. Articles published after 2011 were considered, and we included all studies that described the completion of at least one stage of the care cascade of hypertension and diabetes. Study selection was independently performed by 2 paired authors. Descriptive statistics were used to elucidate key patterns and trends. Inductive content analysis was performed to generate themes regarding the barriers and facilitators for improving the care cascade in hypertension and diabetes management. RESULTS: A total of 128 studies were included, with 42.2% (54/128) conducted in high-income countries. Of them, 47 (36.7%) focused on hypertension care, 63 (49.2%) focused on diabetes care, and only 18 (14.1%) reported on the care of both diseases. The majority (96/128, 75.0%) were observational in design. Cascade stages documented in the literature were awareness, screening, diagnosis, linkage to care, treatment, adherence to medication, and control. Most studies focused on the stages of treatment and control, while a relative paucity of studies examined the stages before treatment initiation (76/128, 59.4% vs 52/128, 40.6%). There was a wide spectrum of interventions aimed at enhancing the hypertension and diabetes care cascade. The analysis unveiled a multitude of individual-level and system-level factors influencing the successful completion of cascade sequences in both high-income and low- and middle-income settings. CONCLUSIONS: This review offers a comprehensive understanding of hypertension and diabetes management, emphasizing the pivotal factors that impact each stage of care. Future research should focus on upstream cascade stages and context-specific interventions to optimize patient retention and care outcomes.

Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3.

PURPOSE: Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. PATIENTS AND METHODS: We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. RESULTS: The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. CONCLUSION: Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.

Bionic Mineralization toward Scalable MOF Films for Ampere-Level Biomass Upgrading.

With significant advances in metal-organic framework (MOF) nanostructure preparation, however, the facile synthesis of large-scale MOF films with precise control of the interface structure and surface chemistry is still challenging to achieve with satisfactory performance. Herein, we introduce a universal strategy bridging metal corrosion chemistry and bionic mineralization to synthesize 16 MOF films on 7 metal supports under ambient conditions. The robustness to explore unlimited libraries of MOF films (e.g., carboxylate-, N-heterocycle-, phenolic-, and phosphonate-MOFs) on supports is evoked by independently regulating the metal redox behavior, electrolyte properties, and organic ligands along with hydrogen evolution or oxygen reduction, which offers the basic guidelines for regulating the microstructure and composition of MOFs on the Pourbaix diagram. In conjunction with multiple manufacturing methods, we demonstrated proof of concept for "printing" a large variety of MOF patterns from micrometer to meter scales. Furthermore, a large-area electrolyzer (64 cm2) devised enables 5-hydroxymethylfurfural oxidation to achieve a record-breaking current of 3.0 A at 1.63 V with 2,5-furandicarboxylic acid production, leading to the simultaneous production of H2 gas and valuable feedstocks. The improved electrocatalytic activity for significantly boosting the 5-hydroxymethylfurfural oxidation exemplifies one of the functional MOF films for given applications beyond biomass upgrading.

Associations of residential greenness and ambient air pollution with overweight and obesity in older adults.

OBJECTIVE: This study aimed to examine the impact of greenness and fine particulate matter <2.5 µm (PM2.5 ) on overweight/obesity among older adults in China. METHODS: A total of 21,355 participants aged ≥65 years were included from the Chinese Longitudinal Healthy Longevity Survey between 2000 and 2018. Normalized difference vegetation index (NDVI) with a radius of 250 m and PM2.5 in a 1 × 1-km grid resolution were calculated around each participant's residence. Cox proportional hazards models were used to estimate the effects of NDVI and PM2.5 on overweight/obesity. Interaction and mediation analyses were conducted to explore combined effects. RESULTS: The study observed 1895 incident cases of overweight/obesity over 109,566 person-years. For every 0.1-unit increase in NDVI the hazard ratio of overweight/obesity was 0.91 (95% CI: 0.88-0.95), and for every 10-µg/m3 increase in PM2.5 the hazard ratio was 1.11 (95% CI: 1.07-1.14). The effect of NDVI on overweight/obesity was partially mediated by PM2.5 , with a relative mediation proportion of 20.10% (95% CI: 1.63%-38.57%). CONCLUSIONS: Greenness exposure appears to lower the risk of overweight/obesity in older adults in China, whereas PM2.5 , acting as a mediator, partly mediated this protective effect.

The role of TGF-ß in the tumor microenvironment of pancreatic cancer.

Pancreatic cancer (PC) is an aggressive malignant tumor with low rate of surgical resection and poor prognosis. Transforming growth factor-ß (TGF-ß) is a cytokine that has both protumor and antitumor activities, depending on tumor microenvironment. The interaction between TGF-ß signaling and the tumor microenvironment in PC is complex. Here, we reviewed the role of TGF-ß in the tumor microenvironment of PC, highlighting producers of TGF-ß and TGF-ß responders in the tumor microenvironment of PC.

Atomic bismuth induced ensemble sites with indium towards highly efficient and stable electrocatalytic reduction of carbon dioxide.

Structural reconstruction is commonly observed during electrocatalytic CO2 reduction (CO2RR) process. However, the proper modulation of interface and defect sites remains challenging with the mechanism understanding to realize the favorable electrocatalysis. Herein, the atomic bridging of bismuth with indium atoms is elaborately designed for improving electrocatalysis of CO2RR via electrochemical reduction and in situ anchoring strategy. As revealed by in situ structure analysis and theoretical studies, the ensemble sites supported on carbon matrix enable the charge density gradient to significantly promote the adsorption of *OCHO intermediate by the regulation of σ bonding and π* back-donation. Consequently, such unique electrocatalyst achieves the high formate faradaic efficiency of 95.1% over the entire potential range tested and the long-lived stability for 9 d. With coupling of CO2RR, the solar-driven full cell demonstrates the spontaneous production of formate and 2,5-furandicarboxylic acid via the efficient oxidation of 5-hydroxymethylfurfural with an outstanding yield of 88.2%, highlighting the impressive solar-to-fuel conversion selectivity. Monitoring and understanding the intrinsic active sites of biatomic bridge are crucial to elucidate the synergic electrocatalysis for rationally designing high-performance electrocatalysts.

Metal coordinating-induced self-assembly of cyclic lipopeptides into high-performance antimicrobial supramolecules.

This study designed a green hydrothermally-chelating approach to generate robust antimicrobial complexes via metal-coordinated supramolecular self-assembly of cyclic lipopeptides (CLs). The metal ion (Ca2+ and Zn2+)-coordinated CL (Ca/CL or Zn/CL complex; 1 mg/mL) demonstrated potent antibacterial activity against fungi (A. niger) and bacteria (E. coli and S. aureus) respectively, and in particular, completely suppressed the microbial resistance. Further physicochemical and spectal analysis showed that this coordination approach led to CL with enhanced hydrophobic and intermolecular electrostatic interactions, forming ß-sheet-rich secondary structures allowing the complexes easily contact with and destroy the membrane of microorganisms. Practical application experiments validated that the Ca/CL and Zn/CL complexes strongly avoided table grape and fresh tomato from the contamination of pathogen. The findings of this study laid foundation for the utilization of metal ions to improve the biological activity of natural antimicrobial peptides.

Depolymerization of plastics by means of electrified spatiotemporal heating.

Depolymerization is a promising strategy for recycling waste plastic into constituent monomers for subsequent repolymerization1. However, many commodity plastics cannot be selectively depolymerized using conventional thermochemical approaches, as it is difficult to control the reaction progress and pathway. Although catalysts can improve the selectivity, they are susceptible to performance degradation2. Here we present a catalyst-free, far-from-equilibrium thermochemical depolymerization method that can generate monomers from commodity plastics (polypropylene (PP) and poly(ethylene terephthalate) (PET)) by means of pyrolysis. This selective depolymerization process is realized by two features: (1) a spatial temperature gradient and (2) a temporal heating profile. The spatial temperature gradient is achieved using a bilayer structure of porous carbon felt, in which the top electrically heated layer generates and conducts heat down to the underlying reactor layer and plastic. The resulting temperature gradient promotes continuous melting, wicking, vaporization and reaction of the plastic as it encounters the increasing temperature traversing the bilayer, enabling a high degree of depolymerization. Meanwhile, pulsing the electrical current through the top heater layer generates a temporal heating profile that features periodic high peak temperatures (for example, about 600 °C) to enable depolymerization, yet the transient heating duration (for example, 0.11 s) can suppress unwanted side reactions. Using this approach, we depolymerized PP and PET to their monomers with yields of about 36% and about 43%, respectively. Overall, this electrified spatiotemporal heating (STH) approach potentially offers a solution to the global plastic waste problem.

Efficient O-demethylation of lignin-derived aromatic compounds under moderate conditions.

Lignin is a potential feedstock to produce renewable aromatic chemicals. However, lignin-derived aromatics are heavily methoxylated, which affects their reactivity in some downstream valorization attempts. Herein, we report an efficient method for the demethylation of the aromatics derived from lignin depolymerization using acidic concentrated lithium bromide (ACLB) under moderate conditions (e.g., 1.5 M HCl, 110 °C, and 2 h). Aromatics with one or two methoxy groups (G-type and S-type), alkyl hydroxyl and carbonyl groups, and electron-donating and electron-withdrawing substituents were used to investigate the demethylation mechanisms. S-type aromatics were demethylated faster than their G-type analogs. Alkyl hydroxyl groups were brominated under the conditions. Carbonyl groups (aldehydes and ketones) promoted unwelcome condensation. Electron-donating substituents promoted demethylation, whereas electron-withdrawing substituents retarded the demethylation. An ortho-carboxylic group enhanced the demethylation because of the formation of a stable intermediate.

Uncovering potential diagnostic biomarkers of acute myocardial infarction based on machine learning and analyzing its relationship with immune cells.

BACKGROUND: Acute myocardial infarction (AMI) is a common cardiovascular disease. This study aimed to mine biomarkers associated with AMI to aid in clinical diagnosis and management. METHODS: All mRNA and miRNA data were downloaded from public database. Differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were identified using the metaMA and limma packages, respectively. Functional analysis of the DEmRNAs was performed. In order to explore the relationship between miRNA and mRNA, we construct miRNA-mRNA negative regulatory network. Potential biomarkers were identified based on machine learning. Subsequently, ROC and immune correlation analysis were performed on the identified key DEmRNA biomarkers. RESULTS: According to the false discovery rate < 0.05, 92 DEmRNAs and 272 DEmiRNAs were identified. GSEA analysis found that kegg_peroxisome was up-regulated in AMI and kegg_steroid_hormone_biosynthesis was down-regulated in AMI compared to normal controls. 5 key DEmRNA biomarkers were identified based on machine learning, and classification diagnostic models were constructed. The random forests (RF) model has the highest accuracy. This indicates that RF model has high diagnostic value and may contribute to the early diagnosis of AMI. ROC analysis found that the area under curve of 5 key DEmRNA biomarkers were all greater than 0.7. Pearson correlation analysis showed that 5 key DEmRNA biomarkers were correlated with most of the differential infiltrating immune cells. CONCLUSION: The identification of new molecular biomarkers provides potential research directions for exploring the molecular mechanism of AMI. Furthermore, it is important to explore new diagnostic genetic biomarkers for the diagnosis and treatment of AMI.

An Intelligent Method for Predicting the Pressure Coefficient Curve of Airfoil-Based Conditional Generative Adversarial Networks.

Recently, extensive studies have focused on analyzing aerodynamic performance due to its important impact on aircraft design. Most of these works compute the aerodynamic coefficient of the airfoil through computational fluid dynamics (CFD) simulation, which is too time-consuming. To reduce the computational time required, some intelligence-based methods have been presented. However, these methods also suffer from certain issues. First, most of them directly implement existing machine learning methods used to predict the aerodynamic coefficient without adding any improvements. Second, some methods convert the airfoil shape and aerodynamic curves into images, which may lead to curve distortion and the introduction of noise. Third, some methods learn the relationship between the airfoil shape and aerodynamic coefficients but ignore the influence of initial inflow conditions. Accordingly, to address these issues, we propose an intelligent method for predicting the pressure coefficients (Cp) of airfoil based on a conditional generative adversarial network (cGAN). More specifically, we first present a two-step data augmentation strategy designed to expand the original airfoil dataset. Subsequently, we design a novel cGAN-based neural network to predict the Cp curve. To the best of our knowledge, this is the first work to apply generative adversarial network (GAN) to aerodynamic coefficient prediction. Moreover, we design a new loss function to train our network. Extensive experimental results demonstrate that the Cp curve predicted by our method is very close to that generated via CFD simulation. More importantly, our method achieves a speedup close to 1000x compared with CFD simulation.

Cysteine Metabolism in Tumor Redox Homeostasis.

Cysteine (Cys) is a semi-essential nutrient amino acid that plays an important role in cells through endogenous production and various transport systems. Intracellular Cys can be used as a precursor of protein synthesis to maintain cell homeostasis and to generate sulfur-containing substances, including glutathione (GSH), hydrogen sulfide (H2S), and taurine. There have been quite a few reports that Cys is related to tumor occurrence and development, and its level is closely related to tumor proliferation, invasion, and metastasis. Moreover, it helps in maintaining the tumor redox balance and increasing drug resistance. This review aims to summarize the production and metabolism of Cys and its role in tumors, with special emphasis on the potential therapeutic value of Cys in tumors to improve the quality of life of cancer patients.

High mobility group box 1 derived mainly from platelet microparticles exacerbates microvascular obstruction in no reflow.

INTRODUCTION: No reflow manifests coronary microvascular injury caused by continuous severe myocardial ischemia and reperfusion. Microvascular obstruction (MVO) has emerged as one fundamental mechanism of no reflow. However, the underlying pathophysiology remains incompletely defined. Herein, we explore the contribution of high mobility group box 1 (HMGB1), derived mainly from platelet microparticles exacerbating MVO in no reflow. MATERIALS AND METHODS: 44 STEMI patients undergoing successful primary percutaneous coronary intervention (PCI) were included in our study. Plasma HMGB1 levels in both the peripheral artery (PA) and infarct-related coronary artery (IRA) were measured by ELISA. Flow cytometry and confocal microscopy assessed the level of HMGB1+ platelet derived microparticles (PMPs) and platelet activation. Flow cytometry and western blot evaluated the procoagulant activity (PCA) and the release of inflammatory factors of human microvascular endothelial cells (HCEMCs). RESULTS: HMGB1 levels were significantly higher in the IRA in no-reflow patients. The levels of HMGB1+ PMPs were considerably higher in the IRA of patients with no reflow and were strongly associated with platelet activation. Moreover, our results show that HMGB1 interacts with human microvascular endothelial cells primarily through TLR4, inducing HCMEC proinflammatory, procoagulant phenotype, and monocyte recruitment, accelerating microvascular obstruction and facilitating the development of no reflow. CONCLUSION: Our results illustrate a novel mechanism by which HMGB1, derived mainly from PMPs, plays a crucial role in the pathogenesis of no-reflow, revealing a novel therapeutic target.

How Parenting and Family Characteristics Predict the Use of Feeding Practices among Parents of Preschoolers: A Cross-Sectional Study in Beijing, China.

Parental coercive and structured feeding practices are linked with children's weight gain. Thus, identifying their predictors will assist in childhood obesity prevention. We explored how parents' concerns and perceptions of children's weight, parenting stress, parenting competence, parents' family roles, and only child status (of both parent and child) predict the use of restriction, pressure to eat, and monitoring practices among parents of preschoolers. Parent-child dyads (n = 2990) were recruited in Beijing in 2019. Parenting competence, parents' weight perceptions and feeding practices were assessed using the Chinese version of Parenting Sense of Competence Scale and Child Feeding Questionnaire (CFQ), respectively. Parenting stress and other variables were collected through self-administered questionnaires. Multivariate linear associations between parents' weight perceptions and feeding practices were significant among normal-weight children. Parents' concerns about children being overweight were positively associated with restriction and monitoring, and negatively associated with pressure to eat. Higher levels of parenting stress and parenting competence significantly improved the adoption of restriction and pressure to eat. Parents' only child status and that of children had an impact on parents' feeding practices. The fathers' feeding preferences were substantially different from what mothers preferred. In conclusion, such parenting and family characteristics significantly influenced feeding practices of preschoolers' parents. These were long neglected in China.

Prolonged blood circulation outperforms active targeting for nanocarriers-mediated enhanced hepatocellular carcinoma therapy in vivo.

Successful hepatocellular carcinoma (HCC) therapy in vivo remains a significant challenge due to the down-regulated expression of the receptors on the surface of tumor cells for compromised active targeting efficiency and cellular uptake of nanoparticles (NPs)-based drug delivery systems (DDSs) and "accelerated blood clearance" and premature unpackaging of NPs in vivo induced by the poly(ethylene glycol)ylation (PEGylation). Inspired by the repeatedly highlighted prolonged blood circulation property of RBCm-camouflaged NPs, we hypothesis that the prolonged blood circulation property resulting from RBCm coating outperforms the active targeting mechanisms of various targeting ligands for enhanced HCC therapy in vivo. Clarification of this hypothesis is therefore of great significance and urgency to break the afore mentioned bottlenecks that hamper the efficient HCC treatment in vivo. For this purpose, we reported in this study the first identification of a determining factor of nanocarriers for enhanced HCC therapy in vivo by the use of the previously fabricated pectin-doxorubicin nanoparticles (PDC-NPs) as a typical example, i.e., the natural RBCm was used as a stealth coating of PDC-NPs for the fabrication of biomimetic DDSs, PDC@RBC-NPs via hypotonic dialysis and mechanical co-extrusion methods. Comprehensive in vitro and in vivo evaluation and comparison of the properties and performance of PDC@RBC-NPs and PDC-NPs were performed in terms of colloidal stability, biosafety, drug release profiles, macrophage escape, anti-HCC effect. The resulting PDC@RBC-NPs outperformed PDC-NPs for HCC therapy in vitro and in vivo. Notably, PDC@RBC-NPs-treated BALB/c nude mice showed a significantly smaller final average tumor volume of 613 mm3 after 16 days than the PDC-NPs-treated group with an average value of 957 mm3. Therefore, the PDC@RBC-NPs developed herein showed great potential for clinical transformations due to the facile preparation and superior therapeutic efficiency against HCC. Most importantly, prolonged blood circulation was identified as a determining factor of nanocarriers instead of active targeting for enhanced HCC therapy in vivo, which could be used to direct the future design and development of advanced DDSs with greater therapeutic efficiency for HCC.