Twisted Intramolecular Charge Transfer-Based Viscosity-Responsive Probe Reveals Lysosomal Degradation Process of Endocytosed Foreign Bodies.

The optimization of nanomedicines requires a thorough understanding of nanocarrier attrition during lysosome-mediated biological processes. Real-time monitoring of endocytosis provides valuable insights into the lysosomal effects on nanocarriers and the release of nanodrugs. We report the development of a coresponsive probe that detects changes in the spatial viscosity of the intracellular domain caused by lysosomal degradation of foreign bodies. The probe, based on a benzofuro[2,3-d]pyrimidine structure, exhibits torsional intramolecular charge transfer (TICT) and responds to ambient viscosity changes with a sensitive fluorescence intensity. The antidiffused fluorescence transition of the probe in the spatially restricted domain serves as a key indicator for real-time monitoring. When encapsulated with diverse foreign bodies and emitted into macrophages by endocytosis, the probe forms nanoparticles. Lysosomes uptake these materials for intracellular digestion, causing alterations in the aggregation or depolymerization state of the nanoparticles, leading to viscosity changes manifested by the probe's fluorescence. By studying the spatial viscosity changes caused by lysosomal degradation of foreign bodies, our monitoring strategy contributes to understanding the digestion or escape capabilities of potential pharmaceutical-carrying nanocarriers, providing guidelines to design more effective nanocarriers that navigate lysosomal degradation to achieve precise drug payloads and release.

Novel functions of o-cymen-5-ol nanoemulsion in reversing colistin resistance in multidrug-resistant Klebsiella pneumoniae infections.

Multidrug resistance (MDR) Klebsiella pneumoniae (K. pneumoniae) is a major emerging threat to human health, and leads to very high mortality rate. The effectiveness of colistin, the last resort against MDR Gram-negative bacteria, is significantly compromised due to the widespread presence of plasmid- or chromosome-mediated resistance genes. In this study, o-cymen-5-ol has been found to greatly restore colistin sensitivity in MDR K. pneumoniae. Importantly, this compound does not impact bacterial viability, induce resistance, or cause any noticeable cell toxicity. Various routes disclosed the potential mechanism of o-cymen-5-ol potentiating colistin activity against MDR K. pneumoniae. These include inhibiting the activity of plasmid-mediated mobile colistin resistance gene (mcr-1), accelerating lipopolysaccharide (LPS) - mediated membrane damage, and promoting the ATP-binding cassette (ABC) transporter pathway. To enhance the administration and bioavailability of o-cymen-5-ol, a nanoemulsion has been designed, which significantly improves the loading efficiency and solubility of o-cymen-5-ol, resulting in antimicrobial potentiation of colistin against K. pneumoniae infection. This study has revealed a new understanding of the o-cymen-5-ol nanoemulsion as a means to enhance the effectiveness of colistin against resistant factors. The finding also suggests that o-cymen-5-ol nanoemulsion could be a promising approach in the development of potential treatments for multidrug-resistant Gram-negative bacterial infections.

Epigenetic therapy: Research progress of decitabine in the treatment of solid tumors.

Decitabine's early successful therapeutic outcomes in hematologic malignancies have led to regulatory approvals from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for addressing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These approvals have sparked keen interest in exploring the potential of decitabine for treating solid tumors. Continuous preclinical and clinical trials have proved that low doses of decitabine also bring benefits in treating solid tumors, and various proposed mechanisms attempt to explain the potential efficacy. It is important to note that the application of decitabine in solid tumors is still considered investigational. This article reviews the application mechanism and current status of decitabine in the treatment of solid tumors.

Coercive Parent-Adolescent Interactions Predict Substance use and Antisocial Behaviors Through Early Adulthood: A Dynamic Systems Perspective.

This study revisits the association between coercive parent-adolescent interactions and adolescent externalizing behaviors. Specifically, we investigate the moment-to-moment coercive exchanges between parents and adolescents and how these dynamic processes map to the long-term development of substance use and antisocial behavior from middle adolescence to early adulthood. We collected videotaped observations with 794 adolescents (ages 16-17 years) and their parents during interactions and coded their real-time behavioral exchanges. State Space Grid analyses were used to measure the proportion of time in which each parent-adolescent dyad engaged in the Dyadic Coercion region as an indicator of rigidity in dyadic coercion. We also measured adolescents' substance use and antisocial behavior at ages 16-17, ages 18-19, and ages 21-22. The enduring impact of parent-adolescent coercive interaction on substance use and antisocial behavior was tested using categorical latent growth curve models and path models. Adolescents with more coercive interactions with parents showed higher rates of increase in alcohol use and higher levels of antisocial behavior through early adulthood. The findings highlight the unique contribution of using intensive data to understand coercive interactions on a micro-timescale and how these dynamics influence long-term development in externalizing behaviors. Implications for intervention studies are discussed.

Linking observing and nonreactivity mindfulness to parenting: Moderated direct and indirect effects via inhibitory control.

To disentangle the effects of key dimensions of dispositional mindfulness on parenting, the present study tests the hypotheses that parental Nonreactivity moderates the association between Observing and effective parenting behaviors, and that parental inhibitory control mediates the relationship between Observing and parenting depending on levels of Nonreactivity. The sample consists of 294 fathers (95.9% deployed) and 313 mothers (81.5% nondeployed) from 336 military families with a child aged between 4 and 13 years at baseline. Parents reported Observing and Nonreactivity at baseline using the Five Facet Mindfulness Questionnaire and completed a computerized Go/No-Go task for assessing inhibitory control at baseline and 1-year follow-up. Families completed a series of in-home interaction tasks at baseline and 2-year follow-up, and effective parenting behaviors were observed and coded using a theory-driven, empirically validated coding system. Results showed that when fathers reported low Nonreactivity, the association between Observing and effective parenting behaviors 2 years later was negative, but this association became positive when fathers reported high Nonreactivity. Fathers' Observing was associated with decreased inhibitory control 1 year later when they reported low (vs. high) Nonreactivity, whereas mothers' Observing was associated with increased inhibitory control 1 year later when they reported high (vs. low) Nonreactivity. The hypothesized effect of inhibitory control as a mediator was not found. Understanding specificity in the effects of dispositional mindfulness dimensions on parenting behaviors will drive effective and efficient designs of mindful parenting interventions. Future research should use dismantling experimental designs to test the synergistic effects of Observing and Nonreactivity in parents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Dataset on the Dynamic Monitoring of Health and Family Planning of China's Internal Migrants: A Multi-Wave Large-Scale, National Cross-Sectional Survey from 2009 to 2018.

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.

Cerebral Neural Changes in Venous-Arterial Extracorporeal Membrane Oxygenation Survivors.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in patients with critical ailments, but very little is known about the functional cerebral changes in ECMO survivors. Degree centrality (DC), a graph-based assessment of network organization, was performed to explore the neural connectivity changes in ECMO survivors compared to controls and their correlation with cognitive and neurological measures. METHODS: This exploratory observational study was conducted from August 2020 to May 2022. ECMO survivors and controls underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were performed. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA). Blood serum neuron-specific enolase and the Glasgow Coma Scale (GCS) were assessed in ECMO survivors. RESULTS: DC values in the right insula and right precuneus gyrus were lower in ECMO survivors and higher in the right medial superior frontal gyrus compared to controls (all p < 0.001). Decreased connectivity in the right insular and right precuneus gyrus correlated with total MoCA scores, delayed recollection, and calculation (all p < 0.05). Increased serum NSE levels, GCS score, and GCS-motor response correlated with decreased connectivity in the right insular and right precuneus gyrus and increased connectivity in the right medial superior frontal gyrus (all p < 0.05). CONCLUSIONS: We showed that both functional impairment and adaptation were observed in survivors of ECMO, suggesting that neural connectivity changes may provide insights into the mechanisms that may potentially link ECMO survivors to neurological and cognitive disorders.

Telehealth delivery of modified attachment and biobehavioral catch-up: feasibility, acceptability, and lessons learned.

The COVID-19 pandemic necessitated dramatic shifts in the delivery and evaluation of attachment-based home-visiting services. The pandemic disrupted a pilot randomized clinical trial of modified Attachment and Biobehavioral Catch-Up (mABC), an attachment-based intervention adapted for pregnant and peripartum mothers with opioid use disorders. We transitioned from in-person to telehealth delivery of mABC and modified Developmental Education for Families, an active comparison intervention targeting healthy development. Of 40 mothers then enrolled in study interventions, 30 participated in telehealth, completing an average of 4.7 remote sessions each (SD = 3.0; range = 1-11). Following the transition to telehealth, 52.5% of randomized cases and 65.6% of mothers maintaining custody completed study interventions, comparable to pre-pandemic rates. Overall, telehealth delivery was feasible and acceptable, and mABC parents coaches' ability to observe and comment on attachment-relevant parenting behaviors was preserved. Two mABC case studies are presented and lessons learned for future telehealth implementation of attachment-based interventions are discussed. .

Intensity of Grandparent Caregiving, Health, and Well-Being in Cultural Context: A Systematic Review.

BACKGROUND AND OBJECTIVES: Grandparents are key resources in grandchildren care globally. However, mixed findings indicated that multiple role engagement may enhance well-being and bring demands on grandparent caregivers in different contexts. This systematic review examines the association between the intensity of grandparent caregiving and their health and well-being (i.e., physical, mental, cognitive, and life satisfaction) by continent and country/region. RESEARCH DESIGN AND METHODS: Systematic searches were conducted in 4 databases. Peer-reviewed articles with quantitative designs published between 1990 and November 2021 were identified. A rigorous selection process was followed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The studies were critically appraised, and their results were narratively synthesized. RESULTS: Sixty-five articles from 29 countries/regions were included. Findings suggested a concave curvilinear relationship between the intensity of grandparent caregiving and their health and well-being, with the optimal caregiving intensity varying across sociocultural contexts. In Europe, Oceania, the Middle East, and South America, providing supplementary or occasional care seems beneficial for grandparents' health and well-being, especially supporting dual-earner families. In East Asia, economic resources appear to buffer the adverse effect of primary care on grandparents' well-being. In the United States, findings vary across ethnicity/race. DISCUSSION AND IMPLICATIONS: Collectively, the intensity of grandparent caregiving, health, and well-being is complicated by grandparents' roles in the family and cultural differences. Acknowledging the bidirectional relationship between well-being and grandparents' capacity for providing care, the well-being as outcome is a limitation. Despite so, this systematic review calls for culturally-tailored family programs to support grandparent caregiving.

Emotion Regulation Difficulties in Military Fathers Magnify Their Benefit from a Parenting Program.

Military service members who were exposed to combat-related traumatic events may exhibit emotion regulation problems, which can compromise emotion-related parenting practices (ERPPs). After Deployment, Adaptive Parenting Tools (ADAPT) is a preventive intervention developed for military families to improve parenting behaviors, including ERPPs. Parental emotion regulation difficulties may affect parents' responses to this parenting program. Thus, this study aimed to use a baseline target moderated mediation design to examine the intent-to-treat (ITT) effect of the ADAPT program on deployed fathers' emotion-related parenting practices (ERPPs) at the 1-year follow-up as well as the moderation and mediation effect of fathers' emotion regulation difficulties. The sample consisted of 181 deployed fathers and their 4-13-year-old children. At both baseline and 1 year, fathers' ERPPs (i.e., positive engagement, withdrawal avoidance, reactivity-coercion, and distress avoidance) were observed during a series of structured parent-child interaction tasks. Results of path analyses showed no ITT effects on fathers' ERPPs, but emotion regulation difficulties significantly moderated ITT effects on distress avoidance. Fathers with higher levels of emotion regulation difficulties at baseline showed decreases in distress avoidance behaviors at 1 year if randomized to the intervention condition. Emotion regulation difficulties also significantly mediated the program's effect on reductions in reactivity coercion for fathers with high levels of emotion regulation difficulties at baseline. These findings highlight parental emotion regulation as a key baseline target of the ADAPT program and provide insight into how and for whom a parenting program improves parenting practices.

The correlation between serum Cyclophilin A level and severity, prognosis of craniocerebral injury.

Background: To investigate the value of serum Cyclophilin A(Cyp A) in evaluating the prognosis of patients with different severity of craniocerebral injury. Methods: The clinical data of patients with craniocerebral injury treated in the Department of Emergency from July 2014 to August 2017 were collected. The patients were divided into survival group and death group, good neurological function group and poor neurological function group with 28-day prognosis and were divided into mild (13-15) group, moderate (9-12) group, and severe (3-8) group with Glasgow Coma Scale (GCS) score. Clinical parameters such as Cyp A and mortality in groups and the relationship between Cyp A and GCS score were compared and its predictive value for prognosis was analyzed with Binary Logistics regression, Cox proportional hazards model and kaplan-meier survival curve. Results: In a single-center retrospective study, 503 patients were enrolled, including 365 males and 138 females; serum Cyp A in the survival group was significantly smaller than the death group [18.7 (10.1, 51.5) ng/mL vs. 149.8 (79.5, 194.4) ng/mL, P < 0.005]. There were significant differences in mortality and Cyp A levels between patients with different severity of craniocerebral injury (P < 0.001). Serum Cyp A levels were negatively correlated with GCS scores in all patients with craniocerebral injury, mild, moderate, or severe craniocerebral injury (r = -0.844, r = -0.256, r = -0.540, r = -0.531, P < 0.001). Predictive value of Serum Cyp A level for all patients with craniocerebral injury, mild, moderate, and severe craniocerebral injury is 0.890, 0.789, 0.806, and 0.833, respectively. Logistics regression analysis showed that lactate (OR = 1.260, 95%CI: 1.023-1.551) and Cyp A (OR = 1.021, 95%CI: 1.011-1.031) were positively correlated with death (P < 0.05), Lactic acid (HR 1.115; 95%CI:1.001-1.243; P = 0.048), GCS score (HR 0.888; 95% CI: 0.794-0.993; P = 0.038), Cyp A levels (HR 1.009; 95% CI: 1.004-1.013; P < 0.001) had a significant effect on short-term mortality. Similar results were seen when neurologic function was used as the outcome. Kaplan-meier survival curve analysis found survival rate of patients with Cyp A level below the cut-off value was significantly higher. Conclusion: Serum Cyp A has a certain predictive value for the prognosis of patients with different severity of craniocerebral injury. Among them, patients with severe craniocerebral injury have the highest predictive value and mild craniocerebral injury patients have the least.

Markhor-derived Introgression of a Genomic Region Encompassing PAPSS2 Confers High-altitude Adaptability in Tibetan Goats.

Understanding the genetic mechanism of how animals adapt to extreme conditions is fundamental to determine the relationship between molecular evolution and changing environments. Goat is one of the first domesticated species and has evolved rapidly to adapt to diverse environments, including harsh high-altitude conditions with low temperature and poor oxygen supply but strong ultraviolet radiation. Here, we analyzed 331 genomes of domestic goats and wild caprid species living at varying altitudes (high > 3000 m above sea level and low < 1200 m), along with a reference-guided chromosome-scale assembly (contig-N50: 90.4 Mb) of a female Tibetan goat genome based on PacBio HiFi long reads, to dissect the genetic determinants underlying their adaptation to harsh conditions on the Qinghai-Tibetan Plateau (QTP). Population genomic analyses combined with genome-wide association studies (GWAS) revealed a genomic region harboring the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene showing strong association with high-altitude adaptability (PGWAS = 3.62 × 10-25) in Tibetan goats. Transcriptomic data from 13 tissues revealed that PAPSS2 was implicated in hypoxia-related pathways in Tibetan goats. We further verified potential functional role of PAPSS2 in response to hypoxia in PAPSS2-deficient cells. Introgression analyses suggested that the PAPSS2 haplotype conferring the high-altitude adaptability in Tibetan goats originated from a recent hybridization between goats and a wild caprid species, the markhor (Capra falconeri). In conclusion, our results uncover a hitherto unknown contribution of PAPSS2 to high-altitude adaptability in Tibetan goats on QTP, following interspecific introgression and natural selection.

Neural Dysconnectivity in the Hippocampus Correlates With White Matter Lesions and Cognitive Measures in Patients With Coronary Artery Disease.

Purpose: Recent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures. Methods: Thirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE). Results: Our data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R. Conclusion: These findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.

Characterization of Necroptosis-Related Molecular Subtypes and Therapeutic Response in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with high morbidity and mortality and is usually associated with therapeutic resistance and poor prognosis because of individual biological heterogeneity. There is an unmet need to screen for reliable parameters, especially immunotherapy-related biomarkers to predict the patient's outcomes. Necroptosis is a special caspase-independent form of necrotic cell death associated with the pathogenesis, progression, and prognosis of multiple tumors but the potential connection between necroptosis-related genes (NRGs) and LUAD still remains unclear. In this study, we expounded mutational and transcriptional alterations of 67 NRGs in 522 LUAD samples and proposed a consensus-clustering subtype of these patients into two cohorts with distinct immunological and clinical prognosis characteristics. Cluster B patients were associated with a better prognosis and characterized by relatively lower expression of NRGs, higher immune scores in the tumor microenvironment (TME), more mild clinical stages, and downregulated expression of immunotherapy checkpoints. Subsequently, the NRG score was further established to predict the overall survival (OS) of LUAD patients using univariate Cox, LASSO, and multivariate Cox regression analyses. The immunological characteristics and potential predictive capability of NRG scores were further validated by 583 LUAD patients in external datasets. In addition to better survival and immune-activated conditions, low-NRG-score cohorts exhibited a significant positive correlation with the mRNA stem index (mRNAsi) and tumor mutation burden (TMB) levels. Combined with classical clinical characteristics and NRG scores, we successfully defined a novel necroptosis-related nomogram to accurately predict the 1/3/5-year survival rate of individual LUAD patients, and the potential predictive capability was further estimated and validated in multiple test datasets with high AUC values. Integrated transcriptomic analysis helps us seek vital NRGs and supplements a novel clinical application of NRG scores in predicting the overall survival and therapeutic benefits for LUAD patients.

Irregular Baseline Brain Activity in Coronary Artery Disease Patients with Cognitive Impairment: A Resting-state Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Cognitive impairment has been suggested to be associated with coronary artery disease [CAD]; however, the underlying mechanism is not fully understood. Our current study aimed to explore the brain activity in CAD patients compared to healthy controls [HCs]. METHODS: Twenty-two CAD patients and 23 HCs were enrolled in our study. A low-frequency oscillation at the voxel level in all participants based on the amplitude of low-frequency fluctuations [ALFF] was measured using resting-state functional magnetic resonance imaging. All participants underwent neuropsychological examinations [Mini-Mental State Examination, MMSE and Montreal Cognitive Assessment, MoCA] and visual acuity examination. RESULTS: CAD patients showed significantly lower ALFF values [P < 0.05] in the right precuneus gyrus [Precuneus_R], left supramarginal gyrus [Supramarginal_L], left angular gyrus [Angular_L], and left middle cingulum gyrus [Cingulum_Mid_L] than healthy controls. Lower MoCA scores in CAD patients significantly correlated with lower Supramarginal_L [P = 0.001] and Cingulate_ Mid_L [P = 0.004] ALFF values. Reduced visual acuity significantly correlated with lower Precuneus_R [P = 0.019] and Cingulate_Mid_L [P = 0.011] ALFF values in CAD patients. CONCLUSION: These findings may provide further insight into the underlying neuropathophysiology of CAD with cognitive impairment.

Exploring the Effect of Enbrel Softgels on PWI Indicators in VCIND Patients.

Objective: To investigate the effect of Enbrel softgels on the head nuclear magnetic (PWI) indices in patients with vascular cognitive impairment-no dementia (vascular cognitive impairment-no dementia, VCIND). Methods: Patients with confirmed VCIND hospitalized in the Department of Neurology of the Affiliated Hospital of Hebei University from April 2017 to April 2019 were included in the study, and they were divided into experimental and control groups (30 patients in each group) according to the difference of interventions. The PWI examination and neuropsychological assessment were performed at the beginning of the experiment, 12 w after treatment, and 48 w after treatment in the two groups. Score differences between the two groups and the preliminary demonstration of the clinical value of the MMSE and ADAS-Cog in the diagnosis of VCIND. Results: (1) The difference in PWI positivity rate between the two groups at the beginning of the experiment was not statistically significant (P > 0.05); the PWI positivity rate in the experimental group at 12 W was significantly lower than that in the control group (P < 0.05); the difference in PWI positivity rate between the two groups at 48 W was not statistically significant (P < 0.05); (2) the MMSE scores of patients in the experimental group at 12 W and 48 W were higher than those in the control group, and the ADAS-Cog scores were lower than those in the control group (P < 0.05). (3) The diagnostic AUCs of MMSE and ADAS-Cog for VCIND were 0.7960 (95% CI = 0.6411-0.9508, P=0.0037) and 0.9291 (95% CI = 0.8390), respectively (95% CI = 0.8390-1.000, P < 0.0001). Conclusion: The addition of Enbrel softgels to concomitant therapy in VCIND patients can lead to changes in their PWI imaging indicators, which in turn can have a significant impact on their neuropsychological indicators, and quantitative analysis scales such as the MMSE and ADAS-Cog can be considered for the diagnostic treatment of VCIND.

Parent and Child Risk Profiles as Predictors of Response to a Conduct Problem Preventive Intervention.

Current evidence-based prevention programming targeting child externalizing problems demonstrates modest overall effect sizes and is largely ineffective for a sizable proportion of youth who participate. However, our understanding of the youth and family characteristics associated with response to specific programming is quite limited. The current study used child and family risk profiles as predictors of response trajectories to the Early Risers conduct problem preventive intervention. A sample of 240 kindergarten-aged youth displaying elevated school-based aggression were randomized by school to either the Early Risers intervention or a control condition. Using a number of child and family risk variables, a latent profile analysis produced a solution consisting of five unique risk profiles. Three low and mixed risk profiles were associated with a limited response to the intervention. One high-risk profile characterized by maladaptive parenting and elevated child externalizing demonstrated notably improved trajectories of externalizing behavior over a 3-year period relative to the control condition. Another high-risk profile characterized by inconsistent discipline, high parental distress, and elevated child internalizing and externalizing symptoms seemed to have positive developmental trends disrupted by the intervention relative to the control condition, potentially consistent with an iatrogenic effect relative to the control condition. The study results support continued efforts to use broader risk profiles to examine heterogeneity in response to preventive interventions and, with replication, will have implications for intervention tailoring.

Roles of Plasmacytoid Dendritic Cells in Gastric Cancer.

Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies.

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives.

Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.