Research Review: Grandparental care and child mental health - a systematic review and meta-analysis.

BACKGROUND: The number of children residing in grandfamilies is growing worldwide, leading to more research attention on grandparental care over the past decades. Grandparental care can influence child well-being in various forms and the effects vary across contexts. In this systematic review and meta-analysis, we synthesize the evidence on the relation between grandparental care and children's mental health status. METHODS: We identified 5,745 records from seven databases, among which 38 articles were included for review. Random effects meta-analyses were used to synthesize evidence from eligible studies. We also examined the variability across study and participant characteristics, including study design, recruitment method, child age, child gender, study region, family type, comparison group, and outcome rater. RESULTS: The meta-analysis consisted of 344,860 children from the included studies, whose average age was 10.29, and of which 51.39% were female. Compared with their counterparts, children being cared for by their grandparents had worse mental health status, including more internalizing problems (d = -0.20, 95% CI [-0.31, -0.09], p = .001), externalizing problems (d = -0.11, 95% CI [-0.21, -0.01], p = .03), overall mental problems (d = -0.37, 95% CI [-0.70, -0.04], p = .03), and poorer socioemotional well-being (d = -0.26, 95% CI [-0.49, -0.03], p = .03). The effects varied by study design and child gender. CONCLUSIONS: The findings highlight that grandparental care is negatively associated with child mental health outcomes with trivial-to-small effect sizes. More supportive programs and interventions should be delivered to grandfamilies, especially in disadvantaged communities.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

Nitrogen-rich Ce-N compounds under high pressure.

Four high-pressure N-rich compounds (Pmn21-CeN7, Amm2-CeN9, P1̄-CeN10, and P1̄-II-CeN10) are proposed using first-principles calculations. Novel polymeric units (a heart shaped layered structure, chain-like N8 rings, and two new banded structures) in four cerium nitrides are reported for the first time in this study. The analyses of electronic structures and bonding properties show that the charge transfer between Ce and N atoms promotes the formation of the Ce-N ionic bond and N-N covalent bond, which play an important role in stabilizing the nitrogen skeleton. Four new phases possess high energy densities (3.24-3.86 kJ g-1), indicating that they are favorable high-energy density materials. Moreover, P1̄-CeN10 possesses ultra-incompressibility along the [1 0 0] direction. Finally, infrared and Raman spectra are analyzed to provide guidance for experimental synthesis.

Glutamine-derived peptides: Current progress and future directions.

Glutamine, the most abundant amino acid in the body, plays a critical role in preserving immune function, nitrogen balance, intestinal integrity, and resistance to infection. However, its limited solubility and instability present challenges for its use a functional nutrient. Consequently, there is a preference for utilizing glutamine-derived peptides as an alternative to achieve enhanced functionality. This article aims to review the applications of glutamine monomers in clinical, sports, and enteral nutrition. It compares the functional effectiveness of monomers and glutamine-derived peptides and provides a comprehensive assessment of glutamine-derived peptides in terms of their classification, preparation, mechanism of absorption, and biological activity. Furthermore, this study explores the potential integration of artificial intelligence (AI)-based peptidomics and synthetic biology in the de novo design and large-scale production of these peptides. The findings reveal that glutamine-derived peptides possess significant structure-related bioactivities, with the smaller molecular weight fraction serving as the primary active ingredient. These peptides possess the ability to promote intestinal homeostasis, exert hypotensive and hypoglycemic effects, and display antioxidant properties. However, our understanding of the structure-function relationships of glutamine-derived peptides remains largely exploratory at current stage. The combination of AI based peptidomics and synthetic biology presents an opportunity to explore the untapped resources of glutamine-derived peptides as functional food ingredients. Additionally, the utilization and bioavailability of these peptides can be enhanced through the use of delivery systems in vivo. This review serves as a valuable reference for future investigations of and developments in the discovery, functional validation, and biomanufacturing of glutamine-derived peptides in food science.

KMT2D links TGF-ß signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity.

Although KMT2D, also known as MLL2, is known to play an essential role in development, differentiation, and tumor suppression, its role in pancreatic cancer development is not well understood. Here, we discovered a novel signaling axis mediated by KMT2D, which links TGF-ß to the activin A pathway. We found that TGF-ß upregulates a microRNA, miR-147b, which in turn leads to post-transcriptional silencing of KMT2D. Loss of KMT2D induces the expression and secretion of activin A, which activates a noncanonical p38 MAPK-mediated pathway to modulate cancer cell plasticity, promote a mesenchymal phenotype, and enhance tumor invasion and metastasis in mice. We observed a decreased KMT2D expression in human primary and metastatic pancreatic cancer. Furthermore, inhibition or knockdown of activin A reversed the protumoral role of KMT2D loss. These findings support a tumor-suppressive role of KMT2D in pancreatic cancer and identify miR-147b and activin A as novel therapeutic targets.

m6A methyltransferase METTL3 programs CD4+ T-cell activation and effector T-cell differentiation in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder in which excessive CD4+ T-cell activation and imbalanced effector T-cell differentiation play critical roles. Recent studies have implied a potential association between posttranscriptional N6-methyladenosine (m6A) modification and CD4+ T-cell-mediated humoral immunity. However, how this biological process contributes to lupus is not well understood. In this work, we investigated the role of the m6A methyltransferase like 3 (METTL3) in CD4+ T-cell activation, differentiation, and SLE pathogenesis both in vitro and in vivo. METHODS: The expression of METTL3 was knocked down and METTL3 enzyme activity was inhibited using siRNA and catalytic inhibitor, respectively. In vivo evaluation of METTL3 inhibition on CD4+ T-cell activation, effector T-cell differentiation, and SLE pathogenesis was achieved using a sheep red blood cell (SRBC)-immunized mouse model and a chronic graft versus host disease (cGVHD) mouse model. RNA-seq was performed to identify pathways and gene signatures targeted by METTL3. m6A RNA-immunoprecipitation qPCR was applied to confirm the m6A modification of METTL3 targets. RESULTS: METTL3 was defective in the CD4+ T cells of SLE patients. METTL3 expression varied following CD4+ T-cell activation and effector T-cell differentiation in vitro. Pharmacological inhibition of METTL3 promoted the activation of CD4+ T cells and influenced the differentiation of effector T cells, predominantly Treg cells, in vivo. Moreover, METTL3 inhibition increased antibody production and aggravated the lupus-like phenotype in cGVHD mice. Further investigation revealed that catalytic inhibition of METTL3 reduced Foxp3 expression by enhancing Foxp3 mRNA decay in a m6A-dependent manner, hence suppressing Treg cell differentiation. CONCLUSION: In summary, our findings demonstrated that METTL3 was required for stabilizing Foxp3 mRNA via m6A modification to maintain the Treg differentiation program. METTL3 inhibition contributed to the pathogenesis of SLE by participating in the activation of CD4+ T cells and imbalance of effector T-cell differentiation, which could serve as a potential target for therapeutic intervention in SLE.

Targeting Ibrutinib to Tumor-Infiltrating T Cells with a Sialic Acid Conjugate-Modified Phospholipid Complex for Improved Tumor Immunotherapy.

Immune checkpoint blockade (ICB) treatment for the clinical therapy of numerous malignancies has attracted widespread attention in recent years. Despite being a promising treatment option, developing complementary strategies to enhance the proportion of patients benefiting from ICB therapy remains a formidable challenge because of the complexity of the tumor microenvironment. Ibrutinib (IBR), a covalent inhibitor of Bruton's tyrosine kinase (BTK), has been approved as a clinical therapy for numerous B-cell malignancies. IBR also irreversibly inhibits interleukin-2 inducible T cell kinase (ITK), an essential enzyme in Th2-polarized T cells that participates in tumor immunosuppression. Ablation of ITK by IBR can elicit Th1-dominant antitumor immune responses and potentially enhance the efficacy of ICB therapy in solid tumors. However, its poor solubility and rapid clearance in vivo restrict T cell targetability and tumor accumulation by IBR. A sialic acid derivative-modified nanocomplex (SA-GA-OCT@PC) has been reported to improve the efficacy of IBR-mediated combination immunotherapy in solid tumors. In vitro and in vivo experiments showed that SA-GA-OCT@PC effectively accumulated in tumor-infiltrating T cells mediated by Siglec-E and induced Th1-dominant antitumor immune responses. SA-GA-OCT@PC-mediated combination therapy with PD-L1 blockade agents dramatically suppressed tumor growth and inhibited tumor relapse in B16F10 melanoma mouse models. Overall, the combination of the SA-modified nanocomplex platform and PD-L1 blockade offers a treatment opportunity for IBR in solid tumors, providing novel insights for tumor immunotherapy.

Aorta and tracheobronchial invasion in esophageal cancer: comparing diagnostic performance of 3.0-T MRI and CT.

OBJECTIVES: To compare between the diagnostic performance of 3.0-T MRI and CT for aorta and tracheobronchial invasion in patients with esophageal cancer (EC). METHODS: We prospectively included patients with pathologically confirmed EC from November 2018 to June 2021, who had baseline stage of T3-4N0-2M0 and restaging after neoadjuvant chemotherapy. All patients underwent contrast-enhanced CT and MRI of the thorax. Two independent blinded radiologists scored image quality and the presence of invasion. Agreements between the two readers were calculated using kappa test. The sensitivity, specificity, accuracy, positive predict value (PPV), and negative predict value (NPV) of MRI and CT in evaluating invasion were calculated. The net reclassification index (NRI) was used to evaluate the change in the number of patients correctly classified by MRI and CT. RESULTS: A total of 70 patients (64.8 ± 9.0 years; 53 men) were enrolled. Inter-reader agreements of image quality scores and presence of invasion by MRI and CT between the two readers were almost perfect (kappa > 0.80). The accuracy of MRI in evaluating thoracic aorta invasion was significantly higher than that of CT (reader 1: 90.0% vs. 71.4%; reader 2: 92.9% vs. 70.0%, respectively), and the accuracy of MRI in evaluating tracheobronchial invasion also was significantly higher than that of CT (reader 1: 92.9% vs. 72.9%; reader 2: 95.7% vs. 70.0%, respectively). NRI values were positive in both the evaluation of aorta and tracheobronchial invasion. CONCLUSIONS: The accuracy of 3-T MRI in determining thoracic aorta and tracheobronchial invasion is significantly higher than that of CT. KEY POINTS: • 3.0-T MRI was significantly more accurate than CT in assessing invasion of the thoracic aorta in patients with esophageal cancer. • 3.0-T MRI was also significantly more accurate than CT in assessing tracheobronchial invasion in patients with esophageal cancer. • 3.0-T MRI has a higher diagnostic performance than CT in evaluating patients with suspected aortic or tracheobronchial invasion in esophageal cancer.

MR imaging characteristics of different pathologic subtypes of esophageal carcinoma.

OBJECTIVES: To describe the specific MRI characteristics of different pathologic subtypes of esophageal carcinoma (EC) METHODS: This prospective study included EC patients who underwent esophageal MRI and esophagectomy between April 2015 and October 2021. Pathomorphological characteristics of EC such as localized type (LT), ulcerative type (UT), protruding type (PT), and infiltrative type (IT) were assessed by two radiologists relying on the imaging characteristics of tumor, especially the specific imaging findings on the continuity of the mucosa overlying the tumor, the opposing mucosa, mucosa linear thickening, and transmural growth pattern. Intraclass correlation coefficients (ICC) were calculated for the consistency between two readers. The associations of imaging characteristics with different pathologic subtypes were assessed using multilogistic regression model (MLR). RESULTS: A total of 201 patients were identified on histopathology with a high inter-reader agreement (ICC = 0.991). LT showed intact mucosa overlying the tumor. IT showed transmural growth pattern extending from the mucosa to the adventitia and a "sandwich" appearance. The remaining normal mucosa on the opposing side was linear and nodular in UT. PT showed correlation with T1 staging and grade 1; IT showed correlation with T3 staging and grades 2-3. Four MLR models showed high predictive performance on the test set with AUCs of 0.94 (LT), 0.87 (PT), 0.96 (IT), and 0.97 (UT), respectively, and the predictors that contributed most to the models matched the four specific characteristics. CONCLUSIONS: Different pathologic subtypes of EC displayed specific MR imaging characteristics, which could help predict T staging and the degree of pathological differentiation. CLINICAL RELEVANCE STATEMENT: Different pathologic subtypes of esophageal carcinoma displayed specific MR imaging characteristics, which correspond to differences in the degree of differentiation, T staging, and sensitivity to radiotherapy, and could also be one of the predictive factors of cause-specific survival and local progression-free rates. KEY POINTS: Different types of EC had different characteristics on MR images. A total of 91/95 (96%) LTEC showed intact mucosa over the tumor, while masses or nodules are specific to PTEC; 21/27 (78%) ITEC showed a "sandwich" sign; and 33/35 (60%) UTEC showed linear and nodular opposing mucosa. In the association of tumor type with degree of differentiation and T staging, PTEC was predominantly associated with T1 and grade 1, and ITEC was associated with T3 and grades 2-3, while LTEC and UECT were likewise primarily linked with T2-3 and grades 2-3.

Complex role of strain engineering of lattice thermal conductivity in hydrogenated graphene-like borophene induced by high-order phonon anharmonicity.

Strain engineering has been used as a versatile tool for regulating the thermal transport in various materials as a result of the phonon frequency shift. On the other hand, the phononic bandgap can be simultaneously tuned by the strain, which can play a critical role in wide phononic bandgap materials due to the high-order phonon anharmonicity. In this work, we investigate the complex role of uniaxial tensile strain on the lattice thermal conductivity of hydrogenated graphene-like borophene, by using molecular dynamics simulations with a machine learning potential. Our findings highlight a novel and intriguing phenomenon that the thermal conductivity in the armchair direction is non-monotonically dependent on the uniaxial armchair strain. Specifically, we uncover that the increase of phonon group velocity and the decrease of three-phonon scattering compete with the enhancement of four-phonon scattering under armchair strain, leading to the non-monotonic dependence. The enhanced four-phonon scattering originates from the unique bridged B-H bond that can sensitively control the phononic bandgap under armchair strain. This anomalous non-monotonic strain-dependence highlights the complex interplay between different mechanisms governing thermal transport in 2D materials with large phononic bandgaps. Our study offers valuable insights for designing innovative thermal management strategies based on strain.

Polymerization State of Vanadyl Species Affects the Catalytic Activity and Arsenic Resistance of the V2O5-WO3/TiO2 Catalyst in Multipollutant Control of NOx and Chlorinated Aromatics.

The conventional V2O5-WO3/TiO2 catalyst suffers severely from arsenic poisoning, leading to a significant loss of catalytic activity. The doping of Al or Mo plays an important role in promoting the arsenic resistance on NH3 selective catalytic reduction (NH3-SCR), but their promotion mechanism remains in debate and has yet to be explored in multipollutant control (MPC) of NOx and chlorinated organics. Herein, our experimental characterizations and density functional theory (DFT) calculations confirmed that arsenic species preferentially adsorb on both Al and Mo to form arsenate, thereby avoiding bonding to the catalytically active V sites. More importantly, Al doping partially converted the polymeric vanadyl species into monomeric ones, thereby inhibiting the near-surface and bulk lattice oxygen mobility of the V2O5-WO3/TiO2 catalyst, while Mo doping resulted in vanadyl polymerization with an enriched V5+ chemical state and exhibited superior MPC activity and COx selectivity. Our work shows that antipoisoning catalysts can be designed with the combination of site protection and occurrence state modification of the active species.

Association of total body fat and fat distribution with bone mineral density among children and adolescents aged 6-17 years from Guangzhou, China.

This study aimed to assess the associations of total body fat and fat distribution with bone mineral density (BMD) among children and adolescents in this cross-sectional study. A total of 1032 boys and 897 girls aged 6-17 years were enrolled between May 2019 and June 2019 in Guangzhou, China. BMD, total body fat (fat mass index [FMI] and body fat percentage [BF%]), and fat distribution (trunk-to-limb and android-to-gynoid ratios) were measured by dual-energy X-ray absorptiometry. Inverse probability of treatment weighting regression was used to explore the association between fat and BMD. Traditional regression of covariate adjustment was applied as sensitivity analysis. Regression with inverse probability weighting suggested BF% and android-to-gynoid ratio were negatively associated with BMD in boys (ß = - 0.12 and - 0.16, respectively; P < 0.05). Android-to-gynoid ratio was also inversely associated with BMD in girls (ß = - 0.08, P < 0.05). When stratified by age, the negative associations were retained in boys aged 12-17 years (ß = - 0.23 and - 0.25, respectively; P < 0.001). But for girls, it showed a positive association of FMI with BMD in the 6-9 years group (ß = 0.33, P < 0.001) and a negative association between the android-to-gynoid ratio and BMD in the 10-17 years group (ß = - 0.10, P < 0.05). Traditional regression supported the robustness of the results.  Conclusion: Total body fat is positively associated with BMD in younger girls but inversely associated in older boys. As for abdominal adipose, it is associated with lower BMD in both older boys and girls. What is Known: • The lean mass has been consistently positively associated with bone mineral density (BMD) among children and adolescents. However, the impact of fat mass on BMD remained controversial. • Beyond total body fat, site-specific fat mass, especially abdominal adiposity, might impede bone formation. What is New: • The associations of total body fat and fat distribution with BMD in children and adolescents were gender- and age-specific. • More attention should be paid to the abdominal fat accumulation to promote bone health in older children.

A ratiometric fluorescence sensor for tetracycline detection based on two fluorophores derived from Partridge tea.

Blue fluorescent carbon dots (PCDs) were prepared by hydrothermal method with Partridge tea. The ethanol extract of Partridge tea (PEE) was found to emit red fluorescence. Thus, a novel ratiometric sensor was constructed by simply mixing the two fluorophores derived from Partridge tea. The presence of tetracycline (TET) at lower concentrations enhanced the emission peak at 508 nm of PCDs and had a negligible effect on the emission peak at 680 nm of PEE. TET at higher concentrations led to  quenching  both the fluorescence of PCDs and PEE via inner filter effect and fluorescence resonance energy transfer, separately. Good linearities for the detection of TET were obtained in the ranges 0.67 to 15.00 µM and 33.33 to 266.67 µM, with limit of detection of 0.095 µM. The sensor was successfully applied to detect TET in lake water and milk samples with good recoveries ranging from 93.27 ± 4.04% to 107.30 ± 6.16%. This study provided a simple, selective, sensitive, rapid, and environmentally friendly method of monitoring TET residues in the environment and food.

Stachydrine Hydrochloride Regulates the NOX2-ROS-Signaling Axis in Pressure-Overload-Induced Heart Failure.

Our previous studies revealed the protection of stachydrine hydrochloride (STA) against cardiopathological remodeling. One of the underlying mechanisms involves the calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII). However, the way STA influences CaMKII needs to be further investigated. The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-coupled reactive oxygen species (ROS) overproduction putatively induces the oxidative activation of CaMKII, resulting in the occurrence of pathological cardiac remodeling and dysfunction in experimental models of mice. Thus, in this study, we assessed the role of the NOX2-ROS signal axis in STA cardioprotection. The transverse aortic constriction (TAC)-induced heart failure model of mice, the phenylephrine-induced hypertrophic model of neonatal rat primary cardiomyocytes, and the H2O2-induced oxidative stress models of adult mouse primary cardiomyocytes and H9c2 cells were employed. The echocardiography and histological staining were applied to assess the cardiac effect of STA (6 mg/kg/d or 12 mg/kg/d), which was given by gavage. NOX2, ROS, and excitation-contraction (EC) coupling were detected by Western blotting, immunofluorescence, and calcium transient-contraction synchronous recordings. ROS and ROS-dependent cardiac fibrosis were alleviated in STA-treated TAC mice, demonstrating improved left ventricular ejection fraction and hypertrophy. In the heart failure model of mice and the hypertrophic model of cardiomyocytes, STA depressed NOX2 protein expression and activation, as shown by inhibited translocation of its phosphorylation, p67phox and p47phox, from the cytoplasm to the cell membrane. Furthermore, in cardiomyocytes under oxidative stress, STA suppressed NOX2-related cytosolic Ca2+ overload, enhanced cell contractility, and decreased Ca2+-dependent regulatory protein expression, including CaMKⅡ and Ryanodine receptor calcium release channels. Cardioprotection of STA against pressure overload-induced pathological cardiac remodeling correlates with the NOX2-coupled ROS signaling cascade.

Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis.

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.

Enhancing intergroup relationship between local and mainland college students in Hong Kong - an intensive contact-based intervention.

This study examined the efficacy of an intensive one-day intergroup contact intervention for two groups under tension: local and mainland Chinese college students in Hong Kong. The differential effects of contact intimacy at cognitive, interpersonal, and emotional levels in fostering changes in knowledge, attitude, and behavior were evaluated. Adopting a two-arm Randomized Controlled Trial (RCT) design, participants (N = 72) were randomly assigned to the intervention group that facilitated progressively higher levels of contact intimacy, or the control group that had limited level of contact intimacy. The results support the short-term intervention efficacy in enhancing outgroup knowledge, attitude, and behavior, with Cohen's d of 0.97, 0.60 and 0.30, respectively. Specifically, cognitive-level intergroup contact enhanced outgroup knowledge only. Adding interpersonal-level intergroup contact further enhanced outgroup attitude. Notably, adding emotional-level intergroup contact enhanced changes in all three domains: knowledge, attitude, and behavior. One-month maintenance effect was found in outgroup knowledge, with Cohen's d increased to 1.33.

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OBJECTIVES: To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls. METHODS: The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing. RESULTS: A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing. CONCLUSIONS: High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Integration of metabolomics and lipidomics reveals serum biomarkers for systemic lupus erythematosus with different organs involvement.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects various organs or systems. We performed metabolomic and lipidomic profiles analyses of 133 SLE patients and 30 HCs. Differential metabolites and lipids were integrated, and then the biomarker panel was identified using binary logistic regression. We found that a combination of four metabolites or lipids could distinguish SLE from HC with an AUC of 0.998. Three lipids were combined to differentiate inactive SLE and active SLE. The AUC was 0.767. In addition, we also identified the biomarkers for different organ phenotypes of SLE. The AUCs for diagnosing SLE patients with only kidney involvement, skin involvement, blood system involvement, and multisystem involvement were 0.766, 0.718, 0.951, and 0.909, respectively. Our study succeeded in identifying biomarkers associated with different clinical phenotypes in SLE patients, which could facilitate a more precise diagnosis and assessment of disease progression in SLE.

Biocompatible Inorganic Nanoagent for Efficient Synergistic Tumor Treatment with Augmented Antitumor Immunity.

Synergistic therapy for malignant tumors has been developed in the past. However, several disadvantages that are associated with the applied inorganic nanoagents cannot be avoided, including intrinsic systemic toxicity, immunosuppression, and low therapeutic efficiency. Herein, a biocompatible, multifunctional, inorganic nanoagent that simultaneously integrates chemodynamic, starvation, and photothermal therapies is developed. This nanoagent effectively converts endogenous H2 O2 into highly toxic hydroxyl radicals via the Fenton reaction. Self-reinforced cancer therapy is achieved via the scavenging of intracellular glutathione and glucose. The encapsulation of nanoagent by erythrocytes drastically reduces its immune recognition by macrophages. Thus, an augmented anti-tumor immune response is realized. Moreover, in contrast to traditional inorganic chemodynamic nanomaterials, the nanoagent has outstanding photothermal efficiency. Therefore, the present system exhibits an effective tumor therapeutic outcome. This work may facilitate a new pathway for the development of highly efficacious synergetic therapies.