Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction.

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.

Characterization of near-field temporal and spatial variations of pesticide residues using honeybee specimens as bio-sensing matrices.

This study was prompted by recent reports of the ubiquity of neonicotinoids (neonics) in environment and the likelihood of exposures and health hazards to non-target organisms. We aimed to quantify neonics levels in time- and location-match pollen and nectar samples foraged by honeybees (Apis mellifera) and characterized the temporal and spatial variations using a relative potency factor method to determine the total neonic levels, expressed as the imidacloprid-adjusted total neonics, IMIRPF (ng/g). Six pairs of pollen and nectar samples, a total of twelve samples, were collected from each of the thirty-two experimental hives during the active foraging months of March, April, and June and analyzed for eight neonics. We found 59% and 64% of pollen and nectar contained at least one neonic, respectively. Among those neonic-detected pollen and nectar samples, 45% and 77% of them contained more than one neonic, respectively. Imidacloprid and acetamiprid in pollen and clothianidin and thiamethoxam in nectar accounted for 60% and 83% detection, respectively. The highest 3-month average of IMIRPF in pollen (6.56 ng/g) and nectar (11.19 ng/g) were detected in a location with the predominant production of citrus fruit. The temporal and spatial variations of IMIRPF levels demonstrated the robustness of using paired pollen and nectar data as the bio-sensing matrices to facilitate the assessment of near-field exposure to total neonics and the delineation of risks.

Identification and expression analysis of the KNOX genes during organogenesis and stress responseness in Camellia sinensis (L.) O. Kuntze.

Tea plant (Camellia sinensis L.), whose leaves are the major reproductive organs, has been cultivated and consumed widely for its economic and health benefits. The Knotted1-like Homeobox (KNOX) proteins play significant roles in leaf morphology formation and development. However, the functions of KNOX proteins in tea plants are still unknown. Here, 11 CsKNOX genes from the tea plants were cloned and divided into Class I, II, and KNATM clades based on their protein sequences. These 11 CsKNOX genes were mapped on 8 out of 15 tea plant chromosomes, all localized in the nucleus. Specific spatiotemporal expression patterns of CsKNOX genes were found in various tissues and different development periods of buds, flowers, and roots of tea plants. Meanwhile, transcript levels of CsKNOX in tea leaves were strongly correlated with the accumulation of flavan-3-ols and proanthocyanidins. It was found that most of the CsKNOX genes could respond to drought, salt, cold, and exogenous MeJA and GA3 by analysis of transcriptomics data and promoter elements. The protein interaction analysis showed that CsKNOX could cooperate with CsAS1 and other critical functional proteins. In conclusion, this research provided the basic information for the functions of the CsKNOX family during organogenesis and stress response in tea plants, which was necessary for further functional characterization verification.

Toddlers at Elevated Likelihood for Autism: Exploring Sensory and Language Treatment Predictors.

Baseline child characteristics may predict treatment outcomes in children with or at elevated likelihood of developing autism (EL-ASD). Little is known about the role of child sensory and language features on treatment outcome. Participants were randomly assigned to a parent-mediated intervention or control condition. Analyses explored the relationship between baseline child sensory and language characteristics and changes in ASD symptoms over approximately 9 months. Higher baseline sensory hyporeactivity was significantly related to less improvement in social communication (SC) for the treatment group only. More baseline atypical vocalizations were significantly related to less improvement on SC across treatment and control groups. This work provides an initial framework to encourage the tailoring of interventions for EL-ASD children, suggesting sensory reactivity and atypical vocalizations may be useful behaviors to consider in treatment planning.

An fgf21-like gene from swamp eel (Monopterus albus): Recombinant expression and its potential roles in glucose and lipid homeostasis.

Fibroblast growth factor 21 (FGF21) plays important roles in the regulation of glucose and lipid metabolism and energy balance in mammals. In this study, the full-length cDNA of swamp eel fgf21 was cloned. Sequence analysis showed that swamp eel FGF21 displayed high similarity with FGF21 of other vertebrates. Subsequently, a prokaryotic expression vector for swamp eel fgf21 was constructed, and recombinant FGF21 (rFGF21) was successfully induced and purified. To investigate the potential roles of swamp eel FGF21 in glucose and lipid metabolism, we examined the effects of rFGF21 on regulation of glucose and lipid homeostasis in type 1 diabetes mellitus (T1DM) mice as well as swamp eels under glucose stress. In T1DM mice, the levels of blood glucose, serum triglyceride (TG), liver TG, serum total cholesterol (TC), and liver TC were significantly downregulated after repeated daily injection of rFGF21 for 15 days. In addition, liver pathological section analysis indicated that rFGF21 alleviated the degree of damage to liver cells in T1DM mice. Furthermore, rFGF21 significantly upregulated the mRNA expression levels of peroxisome proliferators-activated receptor alpha (Pparα), ß-Klotho, fibroblast growth factor receptor 1 (Fgfr1), phosphoenolpyruvate carboxykinase (Pepck), glucose transporter 1 (Glut1), and glucose transporter 4 (Glut4) in T1DM mouse livers. Moreover, in swamp eels, rFGF21 significantly decreased blood glucose and liver TC levels under glucose stress and upregulated the mRNA expression levels of fgf21, pparα, ß-klotho, and fgfr1 in liver tissue. These results suggested that FGF21 plays important roles in the regulation of glucose and lipid homeostasis in swamp eel.

Characterization, expression, and function analysis of AKR1A1 gene from yellow catfish (Tachysurus fulvidraco).

Aldehyde reductase (AKR1A1) is a carbonyl detoxification protein in toxic aldehyde removal. In the present study, the full-length cDNA of yellow catfish AKR1A1 (TfAKR1A1) was cloned. As expected, yellow catfish AKR1A1 showed similarities with that of other species. Subsequently, prokaryotic expression vector was constructed and recombinant TfAKR1A1 (rTfAKR1A1) was successfully induced and purified. rTfAKR1A1 exhibited reductive activity to many aldehydes and ketones. To determine whether TfAKR1A1 could confer stress tolerance in vitro, the viability of control and TfAKR1A1 expression E. coli under abiotic stress was compared by spot assay. Results showed that the recombinant strain had better stress resistance under cadmium, hydrogen peroxide, and DL-glyceraldehyde stress. Then, effects of an intraperitoneal injection of rTfAKR1A1 protein on cadmium-induced oxidative stress were evaluated. Results displayed that TfAKR1A1 and Nrf2 expression levels were significantly decreased, CAT and SOD expression levels were significantly increased, BCL-2 and IL-10 expression levels were significantly increased, and caspase3a, NF-κB, and IL-1ß expression levels were significantly decreased in protein-injection group. Furthermore, oxidative stress indexes in livers under different protein injection doses were examined by ELISA. Results showed that CAT, SOD, and GSH-Px activities were upregulated, ROS and T-AOC contents were also improved, while MDA content was significantly decreased both in lower and middle dose injection groups. Finally, liver pathological section analysis was performed. Results displayed that liver injury degree in protein-injected groups was lower than that of PBS group under cadmium stress. These results suggested that TfAKR1A1 played important roles in response to cadmium stress in yellow catfish.

[Effects of Immune Cells on Luteal Development and Regression in the Mammalian Ovary].

Corpus luteum,an important endocrine tissue in mammalian ovary,plays a role in the regulation of reproductive cycle and the establishment of early pregnancy.While studying the luteal development and its molecular regulation,we have discovered a variety of immune cells,such as T lymphocytes,macrophages,neutrophils,and eosinophils,in the corpus luteum.These immune cells accumulate and support luteal angiogenesis and progesterone production during the luteal development,thus participating in the regulation of luteal functions.In luteal regression,prostaglandin F2 can stimulate the production of inflammatory cytokines and chemokines,which help immune cells enter the corpus luteum and enhance the decomposition of corpus luteum through inflammatory reactions.According to our research achievements,we reviewed the roles of different types of immune cells in the development and degradation of mammalian luteal functions,aiming to further understand the biology of corpus luteum and provide a reference for the clinical manipulation of luteal functions.

Adsorption-Free Growth of Ultra-Thin Molybdenum Membranes with a Low-Symmetry Rectangular Lattice Structure.

Although low-symmetry lattice structure of 2D transition metals is highly anticipated for both fundamental research and potentially distinctive application, it still has not been experimentally realized, which greatly hinders the exploration of the unique properties. Here, ultra-thin body-centered-cubic (bcc) phase molybdenum (Mo) membranes are successfully synthesized with a low-symmetry rectangular (110) crystal face via an adsorption-free reaction. Through experimental and density functional theory studies, no foreign atoms being adsorbed is shown to be a key factor for the successful preparation of the bcc phase 2D transition metal with (110) faces. The realization of 2D Mo(110) with a low-symmetric rectangular lattice structure extends the scope of 2D structures and is also beneficial for the exploration and development of low-symmetry rectangular lattice-structured materials with unique properties.

Heme oxygenase 1 plays a crucial role in swamp eel response to oxidative stress induced by cadmium exposure or Aeromonas hydrophila infection.

Oxidative stress contributes a lot to initiation and progression of pathological conditions. Heme oxygenase 1 (HO1), a cytoprotective enzyme, is usually upregulated to alleviate oxidative stress in vivo. The function of teleost HO1 in the response to oxidative stress induced by heavy metal exposure and in pathogenic bacterial infection remains uncertain. In the present study, both complementary DNA and genomic sequence of a HO1-like gene cloned from the liver of swamp eel (Monopterus albus) are reported. Sequence analysis showed that the putative amino acid sequence contained a conserved heme oxygenase signature and displayed higher similarity to HO1 genes of other teleosts. Expression profile of swamp eel HO1 was investigated in healthy tissues and in tissues following stimulation with pathogenic bacteria (Aeromonas hydrophila) or cadmium chloride (CdCl2) exposure. Results demonstrated that HO1 messenger RNA (mRNA) was highly expressed in the liver and relatively less in other tissues. Bacterial infection with A. hydrophila significantly changed HO1 mRNA expression in the liver, spleen, and kidney, and the mRNA expression of HO1 and Nrf2 in the liver was elevated after the fish were exposed to CdCl2. Subsequently, the swamp eel HO1 was subcloned into a pET28a expression vector and transformed into Escherichia coli BL21 (DE3). Recombinant HO1 (rHO1) was successfully induced by 0.1 mmol/l IPTG and purified by Ni-NTA His Bind Resin purification system. To determine whether the rHO1 could confer stress tolerance in vitro, the viability of control and HO1-expressing E. coli under CdCl2 stress was compared by spot assay. The rHO1 protein significantly increased survival rates of the bacterial hosts. To evaluate whether intraperitoneal injection with rHO1 protected the liver of swamp eel against A. hydrophila-induced oxidative stress, mRNA expression of HO1, Nrf2, hepcidin, and IL-1ß as well as the oxidative stress-related parameters (ROS and total antioxidant capacity (T-AOC)) in the liver were examined. The results showed that exogenous rHO1 could significantly upgrade the mRNA expression of HO1 and hepcidin, coupled with increased ROS and T-AOC levels. However, Nrf2 and IL-1ß expression levels were significantly downregulated and upregulated, respectively. These results suggested that HO1 should not only play a protective role in oxidative stress response and its adverse effects deserved further investigation.

Hypovolaemia was associated with clustering of major cardiovascular risk factors in general population.

BACKGROUND: Previous studies indicated that the clustering of major cardiovascular disease (CVD) risk factors is common, and multiple unhealthy lifestyles are responsible for the clustering of CVD risk factors. However, little is known about the direct association between the volume load and the clustering of CVD risk factors in general population. METHODS: We investigated the association of the clustering of CVD risk factors (defined as two or more of the following factors: hypertension, diabetes, dyslipidemia and overweight) with volume load, which was evaluated by bioelectrical impedance analysis. Hypovolaemia was defined as extracellular water/total body water (ECW/TBW) at and under the 10th percentile for the normal population. RESULTS: Among the 7900 adults, only 29.3% were free of any pre-defined CVD risk factors and 40.8% had clustering of CVD risk factors. Hypovolaemia in clustering group was statistically higher than that either in the single or in the none risk factor group, which was 23.7% vs. 17.0% and 10.0%, respectively (P <0.001). As a categorical outcome, the percentage of the lowest quartiles of ECW/TBW and TBW/TBWwatson in clustering group were statistically higher than either those in the single or in the none risk factor group, which were 44.9% vs. 36.9% and 25.1% (P <0.001), 36.2% vs. 32.2% and 25.0%, respectively (P <0.001). After adjusting of potential confounders, hypovolaemia was significantly associated with clustering of CVD risk factors, with an OR of 1.66 (95% CI, 1.45-1.90). CONCLUSIONS: Hypovolaemia was associated with clustering of major CVD risk factors, which further confirms the importance of lifestyle for the development of CVD.

Special considerations for assessing and caring for autism in girls and women.

PURPOSE OF REVIEW: As the specificities of autistic women are increasingly recognized, this review aims to highlight emerging areas of research. These areas primarily focus on measurement bias of diagnostic tools, the physical and mental health of autistic women, and the unique aspects of the lives of autistic women, both personally and professionally across all life stages. RECENT FINDINGS: Conventional diagnostic tools struggle to capture the specificities of autism in females, but more sensitive instruments like the GQ-ASC (Girls' Questionnaire for Autism Spectrum Conditions), later also referred to as Q-ASC (Questionnaire for Autism Spectrum Conditions) in the scientific literature, show better performances. Autistic women face particular challenges, including an increased risk of physical and mental health problems throughout their lives as women (puberty, motherhood, menopause). Autistic women also encounter specific difficulties in their employment that require greater consideration. SUMMARY: The findings of this review identify research areas that need to be developed to better understand and support autistic girls and women and to enhance clinical practice for them.

Perspectives on Employer-Initiated Terminations Among Young Adults on the Autism Spectrum.

Job instability is high among autistic adults, with employer-initiated terminations a common reason for job loss. The current study used qualitative methods to code reasons that autistic adults identified for their employer-initiated termination. From 315 autistic individuals ages 18-35 who completed an online survey, 93 (29.5%) reported having been terminated from a job. These individuals were asked about the reasons for their termination and responses were coded into thematic categories. Common reasons included work performance, social difficulties, attendance, and mental health challenges. Adults were more likely to attribute terminations to internal causes (related to the individual) than to external causes (environment-related). A good fit between workplace, individual preferences, skills, and abilities is likely key to promoting job continuity for autistic adults.

Associations between social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder: Testing the indirect effects of loneliness.

LAY ABSTRACT: Previous studies have found that social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder are related. To better understand the relationship between these issues, this study examined the frequency of various types of social activities as well as if the participants felt that the frequency of time spent in the activity met their personal needs. In addition, the role of loneliness was tested as a possible way to understand the relationship between activities and depressive symptoms. To test these ideas, 321 participants who were recruited from the Simons Foundation Powering Autism Research for Knowledge (SPARK) research match registry and completed online measures of social activities, depressive symptoms, and loneliness. While the specific pattern was different for individual activities, it was found that those who felt that their current frequency of activities did not meet their needs had higher rates of depressive symptoms than those who felt they did meet their needs. Also, loneliness helps to understand relationship between social activities and depressive symptoms. The findings were discussed in light of previous study findings, interpersonal theories of depression, and clinical implications.

Evaluation of Chongqing Tuo Tea at Different Grades: An Integrated Approach by Artificial and Intelligent Sensory, Non-Volatile, and Volatile Compounds Analysis.

This study aims to investigate the relationship between the grades of Tuo tea and the quality of compounds. A combination of artificial sensory evaluation, intelligent sensory technologies (electronic nose and electronic tongue), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), chemical-physical analysis, and multivariate statistical analysis were employed to examine the differences among three grades of Tuo tea (SG, 1G, and 2G). The results of artificial sensory evaluation, electronic tongue, and electronic nose revealed that the aroma and taste of different grades of Tuo tea varied greatly. A total of 112 volatile compounds and 44 non-volatile compounds were identified. In order to elucidate the key components that cause differences in the quality of Tuo tea, 2 partial least squares discriminant analysis (PLS-DA) models with excellent parameters (volatile, R2Y = 0.999 and Q2 = 0.996; non-volatile, R2Y = 0.992 and Q2 = 0.972) were established. A total of 80 key differential volatile compounds were identified with the double selection criterion of variable importance in projection (VIP) greater than 1 and p < 0.05. Among these, 43 compounds with OAV > 1 were further identified as the odor-active compounds in all three grades of Tuo. Moreover, 22 key non-volatile compounds that contribute to the quality differences have been screened out. This investigation implied that the volatile and non-volatile compounds of Tuo tea could serve as indicators of its quality. The results provided a new approach to distinguish the grades of Tuo tea.

Associations between Social Experiences and Psychological Health for Autistic Youth with Low IQ.

PURPOSE: Social experiences are consistently associated with psychological health among autistic individuals. However, most extant studies on this topic exclude individuals with autism who have lower IQ or are otherwise unable to self-report. The current study addresses this gap by examining associations of negative peer experiences and social participation with psychological health among autistic youth with low IQ. METHODS: An online survey was collected from 268 parents of autistic adolescents and adults ages 15-25. Negative peer experiences included measures of peer victimization and being ignored. Social participation was assessed by the amount of participation and parents' perceptions of whether their youth felt the amount of participation was meeting their needs. Psychological health was assessed by parents' report of their youth's psychological quality of life, as well as whether they felt their son/daughter was currently depressed. RESULTS: Results suggested low rates of social participation in this sample, with relatively high rates of being ignored. Regression analysis found that lower rates of peer victimization and more activities in which parents perceived that the amount of time was meeting their youth's needs was associated with higher psychological quality of life and lower likelihood that parents felt their son/daughter was depressed. CONCLUSION: Though youth with autism and low IQ are often excluded from interventions aimed at improving social experiences, these findings suggest that promoting positive social experiences and ameliorating negative ones might be an avenue to improving psychological health in this group.

Self-reported Everyday Sources of Happiness and Unhappiness in Autistic Adults.

PURPOSE: Daily mood can be influenced by a range of experiences. Identifying everyday life experiences that make autistic adults happy and unhappy holds potential to foster positive mood and tackle mental health problems amongst this group. METHODS: A total of 293 autistic adults between the ages of 18 to 35 years old (mean age of 26.51 years old (SD = 4.62); 43.3% female gender, 4.8% nonbinary) provided open-text responses regarding everyday sources of happiness and unhappiness. Using an iterative process of inductive coding, 14 happy themes and 22 unhappy themes of mood-changing life experiences were identified based on self-report qualitative data. RESULTS: Common themes across the happy and unhappy domain involved social partners, social interactions, and engagement in recreational and employment activities, with additional distinct themes specific to happy or unhappy mood. Top themes identified in the happy domain emphasizes encouraging quality relationships and positive interactions with others and cultivating supportive work/societal environments to build a sense of achievement and value. Meanwhile, emotional tolls accompanied negative relationships and interactions, underscoring the necessity to provide autistic adults with conflict resolution and coping skills to increase feelings of happiness. CONCLUSION: Overall, the wide range of sources of happy and unhappy everyday experiences highlights the importance of considering personal preferences in engagement with others and activities in treatment.

Efficacy of Community-Delivered PEERS® for Adolescents: Increases in Social Skills and Decreases in Social Anxiety and Loneliness.

PURPOSE: PEERS® for Adolescents is an evidence-based social skills training program developed for individuals with autism spectrum disorder (ASD), which is now widely implemented by community providers in clinics and schools. However, majority of past efficacy studies on PEERS® were conducted in controlled research settings, with limited information about its effectiveness when delivered in the community. We sought to examine the effects of PEERS® on social functioning and mental health outcomes when delivered in an outpatient autism specialty clinic. METHODS: Clinical data from 45 adolescents with social challenges (age range: 11-18 years old; 31.1% female assigned at birth) were extracted for secondary analyses. Paired t-tests were performed to examine the pre- to post-intervention changes in social and mental health outcomes. Correlations between pre- and post-change scores of outcome measures were examined. RESULTS: Self-reported social skills knowledge, caregiver-reported social skills (measured by the Social Skills Improvement Systems) and the number of get-togethers hosted, increased significantly from pre- to post-intervention. Additionally, caregiver-reported anxiety and self-reported loneliness significantly decreased from pre- to post-intervention. Exploratory analyses showed that increases in caregiver-reported social skills were associated with decreases in self-reported loneliness. CONCLUSIONS: Our findings provide evidence supporting the efficacy of PEERS® for improving social knowledge and skills of adolescents with social challenges when delivered in the community. The current study also showed the potential benefit of PEERS® for improving adolescent mental health.

Cancer Radiosensitization Nanoagent to Activate cGAS-STING Pathway for Molecular Imaging Guided Synergistic Radio/Chemo/Immunotherapy.

Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, this work integrates hafnium oxide (HfO2) nanoparticles (radiosensitizer) and 7-Ethyl-10-hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)-coated core-shell nanoplatform (HfO2@PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co-delivery of HfO2/SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8+ T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor-bearing mice is efficiently inhibited. Moreover, the HfO2@PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation.

Measurement matters: A commentary on the state of the science on patient reported outcome measures (PROMs) in autism research.

High quality science relies upon psychometrically valid and reliable measurement, yet very few Patient Reported Outcome Measures (PROMs) have been developed or thoroughly validated for use with autistic individuals. The present commentary summarizes the current state of autism PROM science, based on discussion at the Special Interest Group (SIG) at the 2022 International Society for Autism Research (INSAR) Annual Meeting and collective expertise of the authors. First, we identify current issues in autism PROM research including content and construct operationalization, informant-structure, measure accessibility, and measure validation and generalization. We then enumerate barriers to conducting and disseminating this research, such as a lack of guidance, concerns regarding funding and time, lack of accessible training and professionals with psychometric skills, difficulties collecting large representative samples, and challenges with dissemination. Lastly, we offer future priorities and resources to improve PROMs in autism research including a need to continue to evaluate and develop PROMs for autistic people using robust methods, to prioritize diverse and representative samples, to expand the breadth of psychometric properties and techniques, and to consider developing field specific guidelines. We remain extremely optimistic about the future directions of this area of autism research. This work is well positioned to have an immense, positive impact on our scientific understanding of autism and the everyday lives of autistic people and their families.

Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample.

Background: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Methods: Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Results: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. Conclusions: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.