Inflammatory markers predict survival in patients with postoperative urothelial carcinoma receiving tislelizumab (PD-1 inhibitor) adjuvant therapy.

BACKGROUND: In the management of urothelial carcinoma, patient selection for immunotherapy, particularly with immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1), is important for treatment efficacy. Inflammatory markers are useful for predicting treatment outcomes and immune-related adverse events (irAEs). This study aims to retrospectively explore the associations between inflammatory markers and outcomes in patients with postoperative urothelial carcinoma undergoing tislelizumab (PD-1 inhibitor) adjuvant therapy. METHODS: A retrospective analysis was conducted on 133 patients with postoperative urothelial carcinoma who received tislelizumab adjuvant therapy at the Affiliated Hospital of Xuzhou Medical University from April 2020 to August 2023. The prognostic effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) on disease-free survival (DFS) and overall survival (OS) were assessed using Cox regression models. The correlation between inflammatory markers and the onset of irAEs was analyzed using logistic regression models. RESULTS: NLR < 5 and MLR < 0.31 were significantly associated with better outcomes compared to NLR >5 and MLR >0.31, respectively. Multivariate analysis revealed that an NLR < 5 was independently associated with better DFS and OS. However, there was no significant effect on the DFS and OS between PLR < 135 and PLR >135. Patients who experienced irAEs had longer DFS and OS. Multivariate analysis demonstrated that irAEs were an independent prognostic risk factor for DFS and OS. There was no significant difference in the occurrence of irAEs among different NLR, PLR, and MLR groups. CONCLUSION: In patients with postoperative urothelial carcinoma receiving tislelizumab adjuvant therapy, the assessment of NLR and MLR before treatment may serve as valuable predictive markers of clinical outcome.

Exposure to parental depression in adolescence and proinflammatory phenotypes 20 years later.

Although the biological embedding model of adversity proposes that stressful experiences in childhood create a durable proinflammatory phenotype in immune cells, research to date has relied on study designs that limit our ability to make conclusions about whether the phenotype is long-lasting. The present study leverages an ongoing 20-year investigation of African American youth to test research questions about the extent to which stressors measured in childhood forecast a proinflammatory phenotype in adulthood, as indicated by exaggerated cytokine responses to bacterial stimuli, monocyte insensitivity to inhibitory signals from hydrocortisone, and low-grade inflammation. Parents reported on their depressive symptoms and unsupportive parenting tendencies across youths' adolescence. At age 31, youth participants (now adults) completed a fasting blood draw. Samples were incubated with lipopolysaccharide and doses of hydrocortisone to evaluate proinflammatory processes. Additionally, blood samples were tested for indicators of low-grade inflammation, including IL-6, IL-8, IL-10, and TNF-α, and soluble urokinase plasminogen activator receptor. Analyses revealed that parental depression across youths' adolescence prospectively predicted indicators of proinflammatory phenotypes at age 31. Follow-up analyses suggested that unsupportive parenting mediated these associations. These findings suggest that exposure to parental depression in adolescence leaves an imprint on inflammatory activity that can be observed 20 years later.

Higher substance use is associated with low executive control neural activity and higher inflammation.

Individuals with substance use problems show lower executive control and alterations in prefrontal brain systems supporting emotion regulation and impulse control. A separate literature suggests that heightened inflammation also increases risk for substance use, in part, through targeting brain systems involved in executive control. Research on neural and inflammatory signaling in substance use, however, has occurred in parallel. Drawing on recent neuroimmune network models, we used fMRI to examine the relationships between executive control-related brain activity (as elicited by an n-back working memory task), peripheral inflammation, as quantified by inflammatory cytokines and C-reactive protein (CRP), and substance use for the past month in 93 participants [mean age = 24.4 (SD = 0.6)]. We operationalized low executive control as a neural inefficiency during the n-back task to achieve normative performance, as reflected in higher working memory-related brain activity and lower activity in the default mode network (DMN). Consistent with prediction, individuals with low executive control and high inflammation reported more substance use over the past month, controlling for behavioral performance on the n-back, sex, time between assessments, body-mass-index (BMI), and personal socioeconomic status (SES) (interaction between inflammation and working memory-related brain activity, b = 0.210, p = 0.005; interaction between inflammation and DMN, b = -0.219, p < 0.001). Findings suggest that low executive control and high inflammation may be associated with higher substance use. This has implications for understanding psychological, neural, and immunological risk for substance use problems and the development of interventions to target each of these components.

Socioeconomic disadvantage and high-effort coping in childhood: evidence of skin-deep resilience.

BACKGROUND: Low socioeconomic status (SES) is a risk factor for poor outcomes across development. Recent evidence suggests that, although psychosocial resilience among youth living in low-SES households is common, such expressions of resilience may not extend to physical health. Questions remain about when these diverging mental and physical health trajectories emerge. The current study hypothesized that skin-deep resilience - a pattern wherein socioeconomic disadvantage is linked to better mental health but worse physical health for individuals with John Henryism high-effort coping - is already present in childhood. METHODS: Analyses focus on 165 Black and Latinx children (Mage = 11.5) who were free of chronic disease and able to complete study procedures. Guardians provided information about their SES. Children reported on their John Henryism high-effort coping behaviors. They also provided reports of their depressed and anxious mood, which were combined into a composite of internalizing symptoms. Children's cardiometabolic risk was captured as a composite reflecting high levels of systolic or diastolic blood pressure, waist circumference, HbA1c, triglycerides, and low high-density lipoprotein cholesterol. RESULTS: Among youth who reported using John Henryism high-effort coping, SES risk was unrelated to internalizing symptoms and was positively associated with cardiometabolic risk. In contrast, for youth who did not engage in high-effort coping, SES risk was positively associated with internalizing symptoms and was unrelated to cardiometabolic risk. CONCLUSIONS: For youth with high-effort coping tendencies, socioeconomic disadvantage is linked to cardiometabolic risk. Public health efforts to support at-risk youth must consider both mental and physical health consequences associated with striving in challenging contexts.

Evaluating Cryo-TEM Reconstruction Accuracy of Self-Assembled Polymer Nanostructures.

Cryogenic transmission electron microscopy (cryo-TEM) combined with single particle analysis (SPA) is an emerging imaging approach for soft materials. However, the accuracy of SPA-reconstructed nanostructures, particularly those formed by synthetic polymers, remains uncertain due to potential packing heterogeneity of the nanostructures. In this study, the combination of molecular dynamics (MD) simulations and image simulations is utilized to validate the accuracy of cryo-TEM 3D reconstructions of self-assembled polypeptoid fibril nanostructures. Using CryoSPARC software, image simulations, 2D classifications, ab initio reconstructions, and homogenous refinements are performed. By comparing the results with atomic models, the recovery of molecular details is assessed, heterogeneous structures are identified, and the influence of extraction location on the reconstructions is evaluated. These findings confirm the fidelity of single particle analysis in accurately resolving complex structural characteristics and heterogeneous structures, exhibiting its potential as a valuable tool for detailed structural analysis of synthetic polymers and soft materials.

CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer.

Circular RNAs (circRNAs) have emerged as key regulators of human cancers, yet their modes of action in gastric cancer (GC) remain largely unknown. Here, we identified circURI1 back-spliced from exons 3 and 4 of unconventional prefoldin RPB5 interactor 1 (URI1) from circRNA profiling of five-paired human gastric and the corresponding nontumor adjacent specimens (paraGC). CircURI1 exhibits the significantly higher expression in GC compared with paraGC and inhibitory effects on cell migration and invasion in vitro and GC metastasis in vivo. Mechanistically, circURI1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to modulate alternative splicing of genes, involved in the process of cell migration, thus suppressing GC metastasis. Collectively, our study expands the current knowledge regarding the molecular mechanism of circRNA-mediated cancer metastasis via modulating alternative splicing.

Skin-deep Resilience and Early Adolescence: Neighborhood Disadvantage, Executive Functioning, and Pubertal Development in Minority Youth.

Skin-deep resilience, in which youth overcome adversity and achieve success in psychological and academic domains but at a cost to their physiological well-being, has been documented in late adolescence and adulthood. However, its potential to emerge at earlier developmental stages is unknown. To address this gap, secondary data analyses were executed using waves 1 and 2 of the Adolescent Brain Cognitive Development study (n = 7712; ages 9-10 years at baseline [mean: 9.92; SD = 0.63]; 47.1% female; 66.1% White, 13.4% Black, and 20.6% Hispanic). The results indicated high levels of executive functioning were associated with improved psychological and behavioral outcomes at one-year follow-up. However, for racial and ethnic minority (i.e., Black or Hispanic) youth from disadvantaged neighborhoods, high levels of executive functioning were also associated with accelerated pubertal development. No significant interaction was observed among White youth. The findings suggest the skin-deep resilience pattern may be evident in early adolescence.

Uncovering the Optimal Molecular Characteristics of Hydrophobe-Containing Polypeptoids to Induce Liposome or Cell Membrane Fragmentation.

Cellular functions of membrane proteins are strongly coupled to their structures and aggregation states in the cellular membrane. Molecular agents that can induce the fragmentation of lipid membranes are highly sought after as they are potentially useful for extracting membrane proteins in their native lipid environment. Toward this goal, we investigated the fragmentation of synthetic liposome using hydrophobe-containing polypeptoids (HCPs), a class of facially amphiphilic pseudo-peptidic polymers. A series of HCPs with varying chain lengths and hydrophobicities have been designed and synthesized. The effects of polymer molecular characteristics on liposome fragmentation are systemically investigated by a combination of light scattering (SLS/DLS) and transmission electron microscopy (cryo-TEM and negative stained TEM) methods. We demonstrate that HCPs with a sufficient chain length (DPn ≈ 100) and intermediate hydrophobicity (PNDG mol % = 27%) can most effectively induce the fragmentation of liposomes into colloidally stable nanoscale HCP-lipid complexes owing to the high density of local hydrophobic contact between the HCP polymers and lipid membranes. The HCPs can also effectively induce the fragmentation of bacterial lipid-derived liposomes and erythrocyte ghost cells (i.e., empty erythrocytes) to form nanostructures, highlighting the potential of HCPs as novel macromolecular surfactants toward the application of membrane protein extraction.

Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization.

Besides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-degrading enzyme led to insufficient insulin levels in diabetic skin during wound healing, which ultimately reduced the recovery rate of diabetic wounds. We confirmed that topical insulin application could reverse the impaired inflammation reaction in the diabetic wound environment and promote healing of diabetic wounds. Our study revealed that insulin promoted apoptosis of neutrophils and subsequently triggered polarization of macrophages. Both in vivo and in vitro studies verified that insulin re-established phagocytosis function and promoted the process of phagocytosis-induced apoptosis in neutrophils. Furthermore, we found that insulin treatment also promoted efferocytosis of the apoptosed neutrophils by macrophages, and thus induced macrophages to change their polarization state from M1 to M2. In conclusion, our studies proved that the exogenous application of insulin could improve diabetic wound healing via the restoration of the inflammatory response.

Childhood poverty, immune cell aging, and African Americans' insulin resistance: A prospective study.

The present study investigated developmental pathways that can contribute to chronic disease among rural African Americans. With a sample of 342 African American youth (59% female) from the southeastern United States followed for nearly two decades (2001-2019), we examined the prospective association between family poverty during adolescence (ages 11-18) and insulin resistance (IR) in young adulthood (ages 25-29) as well as underlying biological and psychosocial mechanisms. Results indicated family poverty during adolescence forecast higher levels of IR in young adulthood, with accelerated immune cell aging at age 20 partially mediating this association. Serial mediational models confirmed the hypothesized pathway linking family poverty, perceived life chances, cellular aging, and IR. Findings provide empirical support for theorized developmental precursors of chronic disease.

Contextual risks and psychosocial outcomes among rural African American emerging adults: A latent profile analysis.

African American emerging adults face unique contextual risks that place them at heightened risk for poor psychosocial outcomes. The purpose of this study was to identify profiles of contextual risks among rural African American emerging adults and determine how risk profiles relate to psychosocial outcomes. Our representative sample included 667 fifth graders who live in the rural South and were followed from preadolescence into emerging adulthood. Contextual risks were assessed at ages 19-21 years via six indicators: perceived stress, daily stress, community disadvantage, parent-child conflict, racial discrimination, and childhood trauma. Four psychosocial variables were also assessed at ages 19-21 years: self-regulation, racial identity, parent support, and friend support. Psychosocial outcomes were assessed at age 25 years: education, substance use, future orientation, depressive symptoms, and externalizing behaviors. Latent profile analysis results indicated that the sample could be characterized by three patterns of contextual risk: low contextual risk, high contextual risk, and high contextual risk-childhood trauma. Risk profiles were associated with psychosocial outcomes, with the childhood trauma and high-risk profiles faring worse than the low-risk profile. Further, childhood trauma was particularly predictive of worse outcomes for emerging adults. Findings highlight the need for research and prevention programs that mitigate the effects of contextual risks on psychosocial outcomes for African American emerging adults in rural areas.

Construction of Glucose-6-Phosphate Dehydrogenase Overexpression Strain of Schizochytrium sp. H016 to Improve Docosahexaenoic Acid Production.

Docosahexaenoic acid (DHA) is an important omega-3 polyunsaturated fatty acid (PUFA) that plays a critical physiological role in human health. Schizochytrium sp. is considered an excellent strain for DHA production, but the synthesis of DHA is limited by the availability of nicotinamide adenine dinucleotide phosphate (NADPH). In this study, the endogenous glucose-6-phosphate dehydrogenase (G6PD) gene was overexpressed in Schizochytrium sp. H016. Results demonstrated that G6PD overexpression increased the availability of NADPH, which ultimately altered the fatty acid profile, resulting in a 1.91-fold increase in DHA yield (8.81 g/L) and increased carbon flux by shifting it from carbohydrate and protein synthesis to lipid production. Thus, G6PD played a vital role in primary metabolism. In addition, G6PD significantly increased DHA content and lipid accumulation by 31.47% and 40.29%, respectively. The fed-batch fermentation experiment results showed that DHA production reached 17.01 g/L in the overexpressing G6PD strain. These results elucidated the beneficial effects of NADPH on the synthesis of PUFA in Schizochytrium sp. H016, which may be a potential target for metabolic engineering. Furthermore, this study provides a promising regulatory strategy for the large-scale production of DHA in Schizochytrium sp.

Neighborhood poverty, allostatic load, and changes in cellular aging in African American young adults: the moderating role of attachment.

Attachment experiences are thought to contribute to physical health across the lifespan. Evidence suggests that attachment style may serve as a protective factor for individuals' physical health by mitigating the negative effects of social and environmental risk factors. In the present study, we evaluated how attachment styles may moderate the link between African American adolescents' exposure to neighborhood poverty and accelerated cellular aging in young adulthood. Analyses revealed that allostatic load at age 19 mediated the association between neighborhood poverty in adolescence and changes in cellular aging from age 20 to 27. Notably, attachment avoidance (but not attachment anxiety) moderated this association, such that allostatic load was only associated with faster cellular aging for individuals who were high in avoidance. These findings suggest that allostatic load may give rise to faster cellular aging, but these detrimental effects of allostatic load can be offset by young adults' effective use of attachment figures.

Modulating the Molecular Geometry and Solution Self-Assembly of Amphiphilic Polypeptoid Block Copolymers by Side Chain Branching Pattern.

Solution self-assembly of coil-crystalline diblock copolypeptoids has attracted increasing attention due to its capability to form hierarchical nanostructures with tailorable morphologies and functionalities. While the N-substituent (or side chain) structures are known to affect the crystallization of polypeptoids, their roles in dictating the hierarchical solution self-assembly of diblock copolypeptoids are not fully understood. Herein, we designed and synthesized two types of diblock copolypeptoids, i.e., poly(N-methylglycine)-b-poly(N-octylglycine) (PNMG-b-PNOG) and poly(N-methylglycine)-b-poly(N-2-ethyl-1-hexylglycine) (PNMG-b-PNEHG), to investigate the influence of N-substituent structure on the crystalline packing and hierarchical self-assembly of diblock copolypeptoids in methanol. With a linear aliphatic N-substituent, the PNOG blocks pack into a highly ordered crystalline structure with a board-like molecular geometry, resulting in the self-assembly of PNMG-b-PNOG molecules into a hierarchical microflower morphology composed of radially arranged nanoribbon subunits. By contrast, the PNEHG blocks bearing bulky branched aliphatic N-substituents are rod-like and prefer to stack into a columnar hexagonal liquid crystalline mesophase, which drives PNMG-b-PNEHG molecules to self-assemble into symmetrical hexagonal nanosheets in solution. A combination of time-dependent small/wide-angle X-ray scattering and microscopic imaging analysis further revealed the self-assembly mechanisms for the formation of these microflowers and hexagonal nanosheets. These results highlight the significant impact of the N-substituent architecture (i.e., linear versus branched) on the supramolecular self-assembly of diblock copolypeptoids in solution, which can serve as an effective strategy to tune the geometry and hierarchical structure of polypeptoid-based nanomaterials.

Disproportionate School Punishment and Significant Life Outcomes: A Prospective Analysis of Black Youths.

This study tested relationships between racial inequalities in the school system-specifically, the disproportionate punishment of Black students-and life outcomes for Black youths, along with moderating psychological factors. In an 18-year longitudinal study of 261 Black youths (ages 11-29), we investigated whether adult life outcomes varied as a function of adolescent self-control and academic achievement. We tested whether relationships were moderated by the racial climates of the high schools that youths attended, using administrative data on relative punishment rates of Black and White students. Among Black youths who attended schools that disproportionately punished Black students, high self-control in early adolescence presaged higher academic orientation in late adolescence, which in turn predicted higher educational attainment, higher income, and better mental health in adulthood. However, among these same youths, higher academic orientation forecasted higher adult insulin resistance, a key process in cardiometabolic disease. These findings suggest that achieving successes in life in the face of racial inequalities may come at a physical health cost for Black youths.

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1.

Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients' exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.

Evidence for skin-deep resilience using a co-twin control design: Effects on low-grade inflammation in a longitudinal study of youth.

This study tested the skin-deep resilience hypothesis - that low socioeconomic status (SES) youth who are working hard to succeed in life experience good psychological and educational outcomes but at a cost to their physical health - in a sample of monozygotic (MZ) twins. The National Longitudinal Study of Adolescent Health (Add Health) contained a sample of 226 MZ twin pairs at Wave 1 (M age = 16 years), of whom 141 pairs completed the Wave 4 assessment 13 years later (M age = 29 years). Family SES was measured at Wave 1 via income, education, and occupation. Conscientiousness was measured at Wave 4 as an indicator of those who were working hard to succeed in life. Outcomes measured at Wave 4 included low-grade inflammation (C-reactive protein, CRP), mental health (depression, problematic alcohol use), and academic success (educational attainment). A co-twin control design was utilized which directly compared within-twin differences in the association between conscientiousness and life outcomes. Main effects of between-twin conscientiousness were found such that higher levels of conscientiousness were associated with higher educational attainment, fewer symptoms of depression, and less problematic alcohol use, across all SES groups. An interaction between family SES and within-twin difference in conscientiousness was found for CRP, such that, among twins growing up in lower SES households, the twin with higher levels of conscientiousness had higher levels of CRP. These patterns provide support for the phenomenon of skin-deep resilience using a twin methodology that reduces the possibility of confounding by shared genetic and environmental factors.

A family-centered prevention ameliorates the associations of low self-control during childhood with employment income and poverty status in young African American adults.

OBJECTIVE: Children with low self-control who grow up in poverty are at elevated risk for living in poverty when they are adults. The purpose of this study was to further understanding of the intergenerational continuity of poverty by (a) examining the likelihood that children with low levels of self-control at age 11 earn less employment income and are more likely to live in poverty 14 years later, at age 25; and (b) determining, via a preventive intervention, whether enhancing supportive parenting during childhood will ameliorate these associations. METHODS: Parents and their 11-year-old children from 381 families participated in the Strong African American Families (SAAF) program or a control condition. Teachers assessed children's self-control at 11 years; parents reported their use of supportive parenting when children were 11 and 13 years; emerging adults provided data on cognitive and emotional self-control at 19, 20, and 21 years; and young adults indicated their employment income at 25 years. RESULTS: Significant two-way interactions were detected between children's self-control and prevention condition for employment income (b = -183.18, 95% CI [-363.82, -2.53], p < .05) and poverty status (b = 0.257, 95% CI [0.018, 0.497], p < .05). Low self-control at age 11 forecast less employment income and a greater likelihood of living in poverty among children in the control condition, but not among low self-control SAAF participants. Mediated moderation analyses confirmed that enhanced supportive parenting accounted for SAAF's effects on employment income (indirect effect = 63.057, 95% BCA [19.385, 124.748]) and poverty status (indirect effect = -0.071, 95% BCA [-0.165, -0.016]). CONCLUSIONS: This study is unique in using a randomized controlled trial to show that preventive interventions designed to enhance parenting and strengthen families can buffer the long-term economic consequences of low self-control.

Sublytic C5b-9 Induces IL-23 and IL-36a Production by Glomerular Mesangial Cells via PCAF-Mediated KLF4 Acetylation in Rat Thy-1 Nephritis.

Sublytic C5b-9 formation on glomerular mesangial cells in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by the production of proinflammatory cytokines, but the relationship between sublytic C5b-9 and cytokine synthesis and the underlying mechanism remains unclear. To explore the problems mentioned above, in this study, we first examined the levels of proinflammatory ILs (e.g., IL-23 and IL-36a) as well as transcription factor (KLF4) and coactivator (PCAF) in the renal tissues of Thy-1N rats and in the glomerular mesangial cell line (HBZY-1) stimulated by sublytic C5b-9. Then, we further determined the role of KLF4 and PCAF in sublytic C5b-9-induced IL-23 and IL-36a production as well as the related mechanism. Our results showed that the levels of KLF4, PCAF, IL-23, and IL-36a were obviously elevated. Mechanistic investigation revealed that sublytic C5b-9 stimulation could increase IL-23 and IL-36a synthesis through KLF4 and PCAF upregulation, and KLF4 and PCAF could form a complex, binding to the IL-23 or IL-36a promoter in a KLF4-dependent manner, causing gene transcription. Importantly, KLF4 acetylation by PCAF contributed to sublytic C5b-9-induced IL-23 and IL-36a transcription. Besides, the KLF4 binding regions on IL-23 or IL-36a promoters and the KLF4 lysine site acetylated by PCAF were identified. Furthermore, silencing renal KLF4 or PCAF gene could significantly inhibit IL-23 or IL-36a secretion and tissue damage of Thy-1N rats. Collectively, these findings implicate that the KLF4/PCAF interaction and KLF4 acetylation by PCAF play a pivotal role in the sublytic C5b-9-mediated IL-23 and IL-36a production of Thy-1N rats.

Why now? Examining antecedents for substance use initiation among African American adolescents.

Current adolescent substance use risk models have inadequately predicted use for African Americans, offering limited knowledge about differential predictability as a function of developmental period. Among a sample of 500 African American youth (ages 11-21), four risk indices (i.e., social risk, attitudinal risk, intrapersonal risk, and racial discrimination risk) were examined in the prediction of alcohol, marijuana, and cigarette initiation during early (ages 11-13), mid (ages 16-18), and late (ages 19-21) adolescence. Results showed that when developmental periods were combined, racial discrimination was the only index that predicted initiation for all three substances. However, when risk models were stratified based on developmental period, variation was found within and across substance types. Results highlight the importance of racial discrimination in understanding substance use initiation among African American youth and the need for tailored interventions based on developmental stage.