Viral metagenomics combined with non-targeted serum metabolomics reveals the role of enteroviruses in a mouse model of coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is a common cardiovascular disease that is associated with altered gut microbiota. Enteroviruses, an essential component of the gut microbiome, may play an important role in disease progression. However, the relationship between enteroviruses and CHD remains unclear. The development of high-throughput sequencing technologies has facilitated research on the interconnections between viruses and disease-related metabolites. METHODS AND RESULTS: Mice were fed a high-fat diet (CHD group) or chow diet (Sham group) for 12 weeks, and ligation of the left anterior descending coronary artery was performed at the end of week 8. After 4 weeks, all animals were euthanised. Subsequently, the animals were evaluated for basic haemato-biochemical parameters and cardiac function, and aorta staining was performed. Based on enteroviral metagenomics and serum UPLC-MS/MS metabolomics analyses, we evaluated the association between enteroviral groups and serum metabolites of CHD mouse model. A high-fat diet and coronary ligation enabled the establishment of the CHD mouse model. Notably, the enterovirus spectrum of the sham group was significantly different from that of the CHD group, with 24 viral communities of different family and species classification, such as Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus, exhibiting significant differences. In addition, 731 Differential metabolites were detected in the serum of both groups of mice. Correlation network analysis revealed a close relationship between various metabolites related to lipid metabolism and different viruses, including Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus. CONCLUSIONS: An animal model of CHD, characterised by lipid disturbance and myocardial ischaemia, was established using a high-fat diet and ligation of the left anterior descending branch of the coronary artery. Tsarbombavirus, Firehammervirus, Mingyongvirus, and Claudivirus were associated with metabolites in the lipid metabolism pathway. The results indicate that Tsarbombavirus may be the main genus interacting with CHD-related metabolites in mice. Conclusively, the findings of our study provide novel insights into the potential relationship enterovirus groups and metabolites associated with CHD.

Childhood maltreatment and substance use risk: A moderated mediation model of autonomic reactivity and distress tolerance.

BACKGROUND/AIMS: The link between child maltreatment (CM) and substance use (SU) in young adulthood is established. The sympathetic nervous system (SNS) division of the autonomic nervous system may mediate this link. However, less is known on the indirect link between CM and SU via SNS functioning. Due to individual variability in the link between SNS functioning and SU risk, we aimed to examine the moderating role of distress tolerance (DT). METHODS: A longitudinal sample of 118 young adults (YAs) from a low socioeconomic status background were assessed twice (between 9 and 12 months apart). CM, DT, and galvanic skin response (GSR) stress reactivity were measured during the initial study visit, while SU was assessed at both timepoints. Stress reactivity was assessed by measuring the GSR reactivity during a stress task. We tested the indirect associations between CM and changes in SU problems via GSR stress reactivity, and the moderation effects of DT on these indirect associations. A mediation model in the structural equation modeling (SEM) framework was then followed by a moderated mediation model to analyze these data. RESULTS: YA's stress reactivity mediated the association between CM and alcohol use problems, and this indirect effect was weaker among YAs who had higher levels of DT. This pattern did not emerge with drug use problems. CONCLUSIONS: Findings suggest that intervention and prevention efforts for SU outcomes should consider incorporating strategies that increase at-risk individuals' levels of DT. Providing strategies to help individuals stem their stress reactivity may reduce their risk for alcohol use.

Strengthening through adversity: The hormesis model in developmental psychopathology.

BACKGROUND: Employing a developmental psychopathology framework, we tested the utility of the hormesis model in examining the strengthening of children and youth through limited levels of adversity in relation to internalizing and externalizing outcomes within a brain-by-development context. METHODS: Analyzing data from the Adolescent Brain and Cognitive Development study (N = 11,878), we formed latent factors of threat, deprivation, and unpredictability. We examined linear and nonlinear associations between adversity dimensions and youth psychopathology symptoms and how change of resting-state functional connectivity (rsFC) in the default mode network (DMN) from Time 1 to Time 5 moderates these associations. RESULTS: A cubic association was found between threat and youth internalizing problems; low-to-moderate family conflict levels reduced these problems. Deprivation also displayed a cubic relation with youth externalizing problems, with moderate deprivation levels associated with fewer problems. Unpredictability linearly increased both problem types. Change in DMN rsFC significantly moderated the cubic link between threat levels and internalizing problems, with declining DMN rsFC levels from Time 1 to Time 5 facilitating hormesis. Hormetic effects peaked earlier, emphasizing the importance of sensitive periods and developmental timing of outcomes related to earlier experiences. CONCLUSIONS: Strengthening through limited environmental adversity is crucial for developing human resilience. Understanding this process requires considering both linear and nonlinear adversity-psychopathology associations. Testing individual differences by brain and developmental context will inform preventive intervention programming.

Fludarabine Enhances Radiosensitivity by Promoting Ferroptosis in B-Cell Lymphoma.

The objective of this study is to investigate the impact of fludarabine, a signal transducer and activator of transcription-1 (STAT1) inhibitor, on the radiosensitivity of B-cell lymphoma (BCL) and to explore the underlying mechanisms. Radiotherapy is one of the primary treatments for BCL, and STAT1 plays a critical role in the transcription of cell proliferation-related genes, which are associated with radiotherapy and ferroptosis. This study aims to determine whether fludarabine can enhance the radiosensitivity of BCL and to elucidate the molecular pathways involved. Various in vitro methodologies, including CCK-8 assays, clonogenic formation assays, immunohistochemistry, immunofluorescence, flow cytometry, qRT-PCR, and Western blot analyses, were employed in B-cell lymphoma cell models to thoroughly investigate the effects of fludarabine on radiosensitivity. Subsequently, the obtained results were further validated through in vivo animal models and by examining human diffuse large B-cell lymphoma (DLBCL) cancer samples. Our findings demonstrate that the combination of fludarabine and irradiation synergistically inhibits cell viability and colony formation, while inducing apoptosis and ferroptosis in B-cell lymphoma cell lines Raji and Su-DHL-10. Moreover, fludarabine was found to enhance the ferroptosis induced by radiation, thereby synergistically impeding the growth of BCL. In vivo experiments confirmed these findings, revealing that the intraperitoneal injection of fludarabine significantly enhanced the inhibitory effects of radiation on Raji cell xenograft models, leading to an increased percentage of ferroptosis compared to models without fludarabine. Additionally, the administration of liproxstatin-1, a ferroptosis inhibitor, attenuated the inhibition of xenograft growth caused by the combination of fludarabine and irradiation. Furthermore, our analysis of clinical data revealed that increased co-expression of STAT1 and GPX4 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. These results highlight the potential of fludarabine to enhance radiosensitivity and ferroptosis induction as a promising therapeutic strategy for BCL. Our results demonstrated that fludarabine promoted radiation-induced BCL death through the ferroptosis pathway. We have identified a previously unrecognized mechanism in the fludarabine and radiation combination, indicating that it is necessary to conduct prospective clinical trials to verify this new treatment regimen in BCL.

The longitudinal role of family conflict and neural reward sensitivity in youth's internalizing symptoms.

Adolescence is often associated with an increase in psychopathology. Although previous studies have examined how family environments and neural reward sensitivity separately play a role in youth's emotional development, it remains unknown how they interact with each other in predicting youth's internalizing symptoms. Therefore, the current research took a biopsychosocial approach to examine this question using two-wave longitudinal data of 9353 preadolescents (mean age = 9.93 years at T1; 51% boys) from the Adolescent Brain Cognitive Development study. Using mixed-effects models, results showed that higher family conflict predicted youth's increased internalizing symptoms 1 year later, whereas greater ventral striatum (VS) activity during reward receipt predicted reduced internalizing symptoms over time. Importantly, there was an interaction effect between family conflict and VS activity. For youth who showed greater VS activation during reward receipt, high family conflict was more likely to predict increased internalizing symptoms. In contrast, youth with low VS activation during reward receipt showed high levels of internalizing symptoms regardless of family conflict. The findings suggest that youth's neural reward sensitivity is a marker of susceptibility to adverse family environments and highlight the importance of cultivating supportive family environments where youth experience less general conflict within the family.

LncRNA SATB2-AS1 promotes tumor growth and metastasis and affects the tumor immune microenvironment in osteosarcoma by regulating SATB2.

Our previous report has identified a lncRNA SATB2-AS1, which was significantly up-regulated in osteosarcoma tissue and promotes the proliferation of osteosarcoma cells in vitro. However, the mechanisms of SATB2-AS1 regulating the growth and metastasis of osteosarcoma cells in vivo and its role in the prognosis of osteosarcoma patients are still unclear. In this study, the transcriptome sequencing data of 87 patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and 7 patients from our clinical center (GZFPH) was used to evaluate the importance of SATB2-AS1 and SATB2 on the prognosis. The effect of SATB2-AS1 on the growth and metastasis of osteosarcoma cells in vivo was verified by a mouse tumor model. The potential mechanisms of SATB2-AS1 regulating SATB2 were further explored by dual-luciferase reporter gene assay, RNA pull-down assay, and bioinformatics analysis. The results suggested that increased co-expression of SATB2-AS1 and SATB2 was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), and was a biomarker for risk stratification in patients with osteosarcoma. Mechanistically, SATB2-AS1 promotes tumor growth and lung metastasis by regulating SATB2 in vivo. SATB2-AS1 directly binds to POU3F1 for mediating SATB2 expression in MNNG/HOS cells. In addition, SATB2-AS1 and SATB2 might be potential immunomodulators for negatively affecting immune cell infiltration by the IL-17 signaling pathway. In summary, SATB2-AS1 promoted tumor cell growth and lung metastasis by activating SATB2, thereby associated with poor prognosis in patients with osteosarcoma, which indicated that SATB2-AS1 and SATB2 might be novel biomarkers for risk stratification and promising therapeutic targets for osteosarcoma.

Transcriptomic analysis reveals the role of Glycolysis pathway in Litopenaeus vannamei during DIV1 infection.

In recent years, shrimp farming has experienced significant losses due to the emergence of DIV1 (Decapod iridescent virus 1), an infectious virus with a high fatality rate among shrimp. In this study, we conducted transcriptomic analyses on shrimp Litopenaeus vannamei hemocytes following DIV1 infection and focused on the function of genes in the Glycolysis pathway during DIV1 infection. A total of 2197 differentially expressed genes (DEGs) were identified, comprising 1506 up-regulated genes and 691 down-regulated genes. These genes were primarily associated with Phagosome, ECM-Receptor Interaction, Drug Metabolism-Other Enzymes, and the AGE-RAGE signaling pathway in diabetic complications. KEGG pathway enrichment analysis of the DEGs revealed a noteworthy correlation with metabolic pathways, with a specific focus on glucose metabolism. Specifically, the Glycolysis/Gluconeogenesis pathway exhibited significant upregulation following DIV1 infection. In line with this, we observed an augmented accumulation of glycolytic-related metabolites in the hemolymph following DIV1 challenge along with upregulation of the relative mRNA expression of several glycolytic-related genes. Moreover, we found that the inhibition of lactate dehydrogenase (LDH) activity through RNAi or the use of an inhibitor resulted in reduced lactate production, effectively safeguarding shrimp from DIV1 infection. These findings not only provide a comprehensive dataset for further investigation into DIV1 pathogenesis but also offer valuable insights into the immunometabolism mechanisms that govern shrimp responses to DIV1 infection.

Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis.

OBJECTIVE: The comorbidities of coronary artery disease (CAD) and rheumatoid arthritis (RA) are mutual risk factors, which lead to higher mortality, but the biological mechanisms connecting the two remain unclear. Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases. METHOD: The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms. RESULT: Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc. CONCLUSION: Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.

TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

Biological sensitivity to context as a dyadic construct: An investigation of child-parent RSA synchrony among low-SES youth.

Parenting behaviors are significantly linked to youths' behavioral adjustment, an association that is moderated by youths' and parents' self-regulation. The biological sensitivity to context theory suggests that respiratory sinus arrhythmia (RSA) indexes youths' varying susceptibility to rearing contexts. However, self-regulation in the family context is increasingly viewed as a process of "coregulation" that is biologically embedded and involves dynamic Parent×Child interactions. No research thus far has examined physiological synchrony as a dyadic biological context that may moderate associations between parenting behaviors and preadolescent adjustment. Using a two-wave sample of 101 low-socioeconomic status (SES) families (children and caretakers; mean age 10.28 years), we employed multilevel modeling to examine dyadic coregulation during a conflict task, indicated by RSA synchrony, as a moderator of the linkages between observed parenting behaviors and preadolescents' internalizing and externalizing problems. Results showed that high dyadic RSA synchrony resulted in a multiplicative association between parenting and youth adjustment. High dyadic synchrony intensified the relations between parenting behaviors and youth behavior problems, such that in the context of high dyadic synchrony, positive and negative parenting behaviors were associated with decreased and increased behavioral problems, respectively. Parent-child dyadic RSA synchrony is discussed as a potential biomarker of biological sensitivity in youth.

Mental-Health Trajectories of U.S. Parents With Young Children During the COVID-19 Pandemic: A Universal Introduction of Risk.

Parents of young children were a subgroup of the population identified early in the pandemic as experiencing significant mental-health symptoms. Using a longitudinal sample of 3,085 parents from across the United States who had a child or children age 0 to 5, in the present study, we identified parental mental-health trajectories from April to November 2020 predicted by pre-COVID-19 cumulative risk and COVID-19-specific risk factors. Both growth-mixture modeling and latent-growth-curve modeling were used to test the relationship between risk factors and parent mental health. Pre-COVID-19 cumulative risk and COVID-19-specific risks of financial strain, decreased employment, and increased family conflict were salient risk factors predicting poor mental-health trajectories across both modeling approaches. These finding have public-health implications because prolonged exposure to mental-health symptoms in parents constitutes a risk factor for child development.

Improving Children's Expressive Language and Auditory Comprehension Through Responsive Caregiving: Evidence from a Randomized Controlled Trial of a Strength-Based Video-Coaching Intervention.

Young children from low-SES backgrounds are at higher risk for delayed language development, likely due to differences in their home language environment and decreased opportunities for back and forth communicative exchange. Intervention strategies that encourage reciprocal caregiver-child interactions may effectively promote young children's language development and enhance optimal language outcomes. The Filming Interactions to Nurture Development (FIND) program is a brief strength-based video-coaching intervention designed to promote increased back and forth ("serve and return") interactions between caregivers and their children. The current study used data from a randomized controlled trial (RCT) to examine the effectiveness of the FIND program in improving auditory comprehension and expressive communication skills among children from low-SES backgrounds. The current study used a pretest-posttest design to evaluate intervention effects from an RCT with 91 low-SES families. Families with children aged 4 to 36 months old (41.8% female) were randomly assigned to an active control or FIND intervention group. Children's auditory comprehension and expressive communication were assessed using the Preschool Language Scales, Fifth Edition (PLS-5) during both pre- and post-intervention sessions. Children in the FIND intervention group showed significantly increased expressive communication skills and a non-significant increase in auditory comprehension skills across the intervention period. In contrast, children in the active control group showed non-significant changes in expressive communication and a statistically significant decline in auditory comprehension abilities between pre- and post-intervention assessments. All analyses controlled for sex, age, and home language. This study provides preliminary evidence that the FIND intervention promotes the development of expressive and receptive language skills among young children in high-stress, low-SES environments.

The promotive and protective effects of parents' perceived changes during the COVID-19 pandemic on emotional well-being among U.S. households with young children: an investigation of family resilience processes.

Introduction: The COVID-19 pandemic may constitute a traumatic event for families with young children due to its acute onset, the unpredictable and ubiquitous nature, and the highly distressing disruptions it caused in family lives. Despite the prevalent challenges such as material hardships, child care disruptions, and social isolation, some families evinced remarkable resilience in the face of this potentially traumatic event. This study examined domains of changes perceived by parents of young children that were consistent with the post-traumatic growth (PTG) model as factors that facilitate family resilience processes. Methods: This study drew data from the RAPID project, a large ongoing national study that used frequent online surveys to examine the pandemic impact on U.S. households with young children. A subsample of 669 families was leveraged for the current investigation, including 8.07% Black, 9.57% Latino(a), 74.44% non-Latino(a) White families, and 7.92% households of other racial/ethnic backgrounds. In this subsample, 26.36% were below 200% federal poverty level. Results: Approximately half of the parents reported moderate-to-large degrees of changes during the pandemic, and the most prevalent domain of change was appreciation of life, followed by personal strengths, new possibilities, improved relationships, and spiritual growth. Black and Latino(a) parents reported more changes in all five domains than White parents and more spiritual growth than parents of the other racial/ethnic groups. Moreover, parent-reported improved relationships were found to indirectly reduce young children's overall fussiness/defiance and fear/anxiety symptoms through reducing parents' emotional distress. Perceived changes in the new possibilities, personal strengths, and appreciation of life domains were found to serve as protective factors that buffered the indirect impacts of material hardship mean levels on child behavioral symptoms via mitigating parents' emotional distress. Discussion: These findings shed light on resilience processes of a family system in a large-scale, disruptive, and stressful socio-historical event such as the COVID-19 pandemic. The five PTG domains could inform therapeutic and intervention practices in the face of future similar events. Importantly, these findings and the evinced family resilience should not negate the urgent needs of policy and program efforts to address material hardships, financial instabilities, and race/ethnicity-based structural inequalities for families of young children.

Distribution of Trace Metals in Ice and Water of Liaodong Bay, China.

Trace metal pollution in coastal seas has been of great concern because of its persistence, toxicity, and biological accumulation through the food chain. The role of sea ice in trace metal transport and distribution in Liaodong Bay is still unknown. Sea ice and water samples were collected in Liaodong Bay in February 2021 to assess the distributions of Cu, Pb, Cd, Zn, Cr and Hg during the frozen season. Total dissolved (<0.45 µm) and particulate (>0.45 µm) heavy metal concentrations were measured by atomic absorption spectrophotometry (Cu, Pb, Cd, Zn and Cr) and atomic fluorescence spectrophotometer (Hg). The ice held significantly higher levels of total Cr when compared to water. There were no significant differences in total concentrations of Cu, Pb, Cd, Zn and Hg between water and ice samples. An analysis of dissolved-to-total metal ratios shows that all studied metals in the dissolved phase, except Hg, are found exclusively in Liaodong Bay nearshore ice as a result of desalination. Concentrations of particulate metals are higher in sea ice than in seawater due to suspended/bed sediment entrainment and atmospheric deposition. The partitioning coefficients of six trace metals are not increased with the increase in the concentration of particulate matter in sea ice due to sediment accumulation. The redistribution of trace metals between seawater and ice was a result of comprehensive effects of physico-chemical processes and environmental factors, such as chemical oxygen demand, salinity, and suspended particulate material.

Anticancer mechanism studies of iridium(III) complexes inhibiting osteosarcoma HOS cells proliferation.

Three iridium (III) polypyridine complexes [Ir(bzq)2(maip)](PF6) (Ir1，bzq = benzo[h]quinoline, maip = 3-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(bzq)2(apip)](PF6) (Ir2, apip = 2-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(bzq)2(paip)](PF6) (Ir3, paip = 4-aminophenyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The cytotoxic activities of the three complexes against human osteosarcoma HOS, U2OS, MG63 and normal LO2 cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that Ir1-3 exhibited moderate antitumor activity against HOS with IC50 of 21.8 ± 0. 4 µM,10.5 ± 1.8 µM and 7.4 ± 0.4 µM, respectively. We found that Ir1-3 can effectively inhibit HOS cells growth and blocked the cell cycle at the G0/G1 phase. Further studies revealed that complexes can increase intracellular reactive oxygen species (ROS) and Ca2+, which accompanied by mitochondria-mediated intrinsic apoptosis pathway. In addition, autophagy was also investigated. Taken together, the complexes induce HOS apoptosis through a ROS-mediated mitochondrial dysfunction pathway and inhibition of the PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway. This study provides useful help for understanding the anticancer mechanism of iridium (III) complexes toward osteosarcoma treatment.

[Historical evolution of Xuanfu Daizhe Decoction].

Xuanfu Daizhe Decoction, first seen in Zhang Zhongjing's Treatise on Cold Damage Diseases, was composed of seven medicinal materials: Inulae Flos, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma Recens, Haematitum, Pinelliae Rhizoma and Jujubae Fructus. It was used to treat gastric fullness and hardness and belching due to the wrong treatment of typhoid fever and sweating. With detailed records and description in ancient medical books, Xuanfu Daizhe Decoction was widely adopted in clinical practice by physicians of later generations, which expanded its main therapeutic functions. By comprehensive collation of ancient and modern literature on Xuanfu Daizhe Decoction, this paper systematically explored the historical evolution of the prescription from the source, composition, dosage, processing, clinical application, function interpretation and decocting method. It was found that the composition and processing method of the prescription in the past dynasties were relatively consistent, and there was a gradual decrease in dosage in clinical application. In ancient times, Xuanfu Daizhe Decoction was mainly used to treat nausea, vomiting, hiccups, constipation, etc., while modern clinicians mainly used it for digestive diseases such as reflux esophagitis and gastritis. Through the analysis and textual research, the composition, dosage, processing, function evolution and decocting method of this prescription were determined, which provided reference for the research and development of compound preparations of Xuanfu Daizhe Decoction.

EID3 Promotes Cancer Stem Cell-Like Phenotypes in Osteosarcoma through the Activation of PI3K-AKT Signaling Pathway.

The aim of this study is to elucidate molecular mechanism by which E1A-like inhibitor of differentiation 3 (EID3) promotes cancer stem cell-like phenotypes in osteosarcoma. Overexpression of EID3 in osteosarcoma cells generated more spherical clones, enhanced the expression of stemness-associated genes, and promoted chemoresistance, invasion, and metastasis. Furthermore, osteosarcoma cells overexpressing EID3 had increased ability to grow in suspension as osteospheres with high expression of Sox2 and stem cell marker CD133. In addition, knockdown of EID3 reduced sphere formation and inhibited osteosarcoma cell migration and invasion. RNA sequencing and bioinformatics analysis revealed that PI3K-Akt signaling pathway and MAPK pathway-related genes were enriched in osteosarcoma cells with high expression of EID3. Taken together, EID3 promotes osteosarcoma, and EID3-PI3K-Akt axis is a potential therapeutic target for osteosarcoma treatment.

Material hardship level and unpredictability in relation to U.S. households' family interactions and emotional well-being: Insights from the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has been recognized to provide rare insight to advance the scientific understanding of early life adversity, such as material hardship. During the COVID-19 pandemic, material hardship (i.e., difficulty paying for basic needs) in families of young children has had detrimental effects on caregivers' and children's well-being. In addition to the degree of material hardship, the week-to-week and month-to-month unpredictability of hardship status may add to families' stress and worsen well-being. This study examined the magnitude of and mechanisms underlying the effects of material hardship level and unpredictability on the well-being of U.S. households with young children during the pandemic. METHODS: Data were drawn from the RAPID project, a large ongoing national study that used weekly/biweekly online surveys to investigate the pandemic impact on U.S. households with young children. The current study leveraged data from 4621 families who provided at least three responses between April 2020 and October 2021. RESULTS: Findings indicated that racial/ethnic minorities and lower-income households experienced higher levels of material hardship and unpredictability during the pandemic, compared to their White or higher-income counterparts. Levels of pandemic-related material hardship and hardship unpredictability were both significantly associated with worsened well-being among caregivers and children. Finally, the effects of hardship level and unpredictability on well-being outcomes were partially mediated through disrupted family routines. CONCLUSIONS: The findings from this study highlight that ensuring equal and adequate access to financial resources, as well as promoting financial stability for households with young children are both critical for maintaining functional family dynamics and promoting caregivers' and children's optimal well-being.

Is perceived stress linked to enhanced cognitive functioning and reduced risk for psychopathology? Testing the hormesis hypothesis.

Extensive research documents the impact of psychosocial stress on risk for the development of psychiatric symptoms across one's lifespan. Further, evidence exists that cognitive functioning mediates this link. However, a growing body of research suggests that limited stress can result in cognitive benefits that may contribute to resilience. The hypothesis that low-to-moderate levels of stress are linked to more adaptive outcomes has been referred to as hormesis. Using a sample of young adults from the Human Connectome Project (N = 1,206, 54.4% female, Mage = 28.84), the present study aims to test the hormetic effect between low-to-moderate perceived stress and psychopathological symptoms (internalizing and externalizing symptoms), as well as to cross-sectionally explore the intermediate role of cognitive functioning in this effect. Results showed cognitive functioning as a potential intermediating mechanism underlying the curvilinear associations between perceived stress and externalizing, but not internalizing, behaviors. This study provides preliminary support for the benefits of limited stress to the process of human resilience.

Combined effects of S-metolachlor and benoxacor on embryo development in zebrafish (Danio rerio).

It is necessary to study the combined toxicity of an herbicide and its safener because the two are often used in combination. S-metolachlor and its safener benoxacor have been detected in aquatic environments and can individually damage the oxidative stress system in zebrafish embryos (Danio rerio). However, only their separate toxicity in zebrafish (Danio rerio) embryo development has been reported. This study assessed the combined toxicity of benoxacor and S-metolachlor in zebrafish embryo development, including acute toxicity, developmental toxicity, oxidative damage, and cell apoptosis. The 96-h LC50 values were higher in mixtures of benoxacor and S-metolachlor than in benoxacor alone. The treatments included S-metolachlor, Mix-1 (0.1 mg/L benoxacor + 0.1 mg/L S-metolachlor), Mix-2 (0.1 mg/L benoxacor + 0.3 mg/L S-metolachlor) and benoxacor alone. Embryos exposed to Mix-1 and Mix-2 had lower developmental toxicities, superoxide dismutase (SOD) activity, osx and cat expression levels than those exposed to benoxacor alone. Moreover, glutathione S-transferase (GST), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) activities, and the expressions of tbx16, nrf2, bcl2, and caspase9 were higher in the mixtures than in the benoxacor group. High-throughput RNA sequencing revealed that benoxacor had a greater effect on gene regulation than Mix-1 and Mix-2. The malformation rate, different enrichment gene numbers, and gene expression levels of hatched embryos were higher in Mix-1 than in Mix-2. The results indicate that a mixture of S-metolachlor and benoxacor has antagonistic effects in the early stage of embryo development. The mixtures can break the reactive oxygen species balance, causing abnormal cell apoptosis and developmental malformation in embryos. Besides investigating the combined toxicity of benoxacor and S-metolachlor in zebrafish embryo development, this study provides a risk assessment basis for a herbicide combined with its safener.