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Squalene plays a crucial role in plant growth, development, and stress tolerance. To select the best reference genes (RGs) for expression profile analysis of genes involved in squalene biosynthesis in olives under stress tolerance, the expression stability of 22 candidate RGs across four tissues (root, stem, leaf, and fruit) and five representative cultivars under drought stress was assessed using six methods. Our study showed that, ubiquitin-conjugating enzyme1 (UBC1) and 60S ribosomal protein L18-2-like (60S) were the most stable RGs across five different cultivars and various tissues. Additionally, elongation factor 1-alpha-like (EF1-α2) and UBC1 were the most stable RG in olives under drought stress. UBC1 was the appropriate RG for further study, qPCR analysis showed that five certain genes involved in the squalene biosynthesis exhibited significant differential expression under varying conditions. Specially, the expression level of squalene synthase (SQS) in the leaves was highest, and HPLC analysis showed that squalene content was the highest in leaves. Likewise, the expression levels of SQS and farnesyl diphosphate synthase (FPPS) in the leaves of the cultivar Arbosana and Chelmsford Lal were significantly higher than those of the other cultivars, respectively, and HPLC analysis also showed that squalene content was highest in the two cultivars. Interestingly, the amount of squalene increased dramatically in olive under drought stress, as lupeol synthase (LUPS) was significantly up-regulated. To date, this study firstly provided the comprehensive analysis of RGs related to squalene biosynthesis in various cultivars and tissues of olives under drought stress.

Background This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy.Methods Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10−4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period.Results Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I.Conclusion The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.

Abstract Background The COVID-19 pandemic have impacts on the prevalence of other pathogens and people’s social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. Methods Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. Results Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P

Abstract Background To study whether the four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of the Kazak children in Xinjiang, China. Methods Four single nucleotide polymorphisms about the 4 genes were genotyped in asthma group and control group of Han children and Kazak children respectively. The frequencies of different genotypes and alleles were compared between the asthma group and the control group in the two nationalities. Different risk genotypes for asthma were evaluated in the two nationalities. Results The differences about frequencies of genotypes in ADRB2 rs1042713 and IL4 rs2243250 and IL13 rs20541 between asthma group and control group were statistically significant in Han children, as were the frequencies of alleles in the 3 single nucleotide polymorphisms, but there were no statistical differences in FCER1B rs569108(P > 0.05). For the Kazak children, no differences were existed among all the genotypes and alleles in asthma group and control group. For the Han children, more children were asthma high risk genotype in the asthma group than those in the control group and no difference was found in the Kazak children. Conclusions The four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of Han children but not for the Kazak children in Xinjiang, which illustrating that the difference of asthma prevalence between different races is closely related to the genetic background.

Abstract Background Social connection and loneliness in adolescence are increasingly understood as critical influences on adult mental and physical health. The unique impact of the social isolation imposed by the COVID-19 lockdown on emerging adults is therefore expected to be especially profound. We sought to investigate the feasibility of using ecological momentary assessment (EMA) and wearable accelerometers to characterize the effects of social isolation and/or loneliness experienced by adolescents during the COVID-19 pandemic. Methods We recruited 19 participants aged 13–18 from an Adolescent Medicine practice in Atlanta, GA. Participants completed surveys at baseline and throughout a 2-week study period using EMA regarding their degree of social isolation, loneliness, family functioning, school climate, social media use, and COVID-19 experiences surrounding their physical, mental, and social domains. Six participants agreed to wear an activity tracker and heart rate measurement device for 14 days to monitor their emotional state and physical health. Participant feedback was collected via open-ended exit interviews. Feasibility of recruitment/retention, adherence, and outcome measures were investigated. Implementation was also assessed by evaluating the barriers and facilitators to study delivery. Associations between the social isolation and loneliness variables and all other variables were performed with univariate linear regression analysis with significance set at p 30% and a retention rate of > 80%. Results Progression criteria were met for recruitment (76%) of participants, but not retention (38%). Adherence to EMA survey completion was highly variable with only 54% completing ≥ 1 survey a day, and accelerometry use was not feasible. Social isolation was significantly correlated with lower school climate, higher COVID-19 experiences, higher depression scores, and lower sleep quality. Loneliness also showed a significant correlation with all these factors except COVID-19 experiences. Conclusions EMA and wearable accelerometer use was not feasible in this longitudinal study of adolescents during the COVID-19 pandemic. Future research should further investigate barriers to conducting long-term research with adolescents and the potential effects of the pandemic on subject recruitment and retention.

Background: Early life stress (ELS) is a major risk factor for depression in adolescents. The nucleus accumbens (NAc) is a key center of the reward system, and spine remodeling in the NAc contributes to the development of depression. The Si-Ni-San formula (SNS) is a fundamental prescription for treating depression in traditional Chinese medicine. However, little is known about the effects of SNS on behavioral abnormalities and spine plasticity in the NAc induced by ELS.Purpose: This study aimed to investigate the therapeutic effect and the modulatory mechanism of SNS on abnormal behaviors and spine plasticity in the NAc caused by ELS.Methods: We utilized a model of ELS that involved maternal separation with early weaning to explore the protective effects of SNS on adolescent depression. Depressive-like behaviors were evaluated by the sucrose preference test, the tail suspension test, and the forced swimming test; anxiety-like behaviors were monitored by the open field test and the elevated plus maze. A laser scanning confocal microscope was used to analyze dendritic spine remodeling in the NAc. The activity of Rac1 was detected by pull-down and Western blot tests. Viral-mediated gene transfer of Rac1 was used to investigate its role in ELS-induced depression-like behaviors in adolescence.Results: ELS induced depression-like behaviors but not anxiety-like behaviors in adolescent mice, accompanied by an increase in stubby spine density, a decrease in mushroom spine density, and decreased Rac1 activity in the NAc. Overexpression of constitutively active Rac1 in the NAc reversed depression-related behaviors, leading to a decrease in stubby spine density and an increase in mushroom spine density. Moreover, SNS attenuated depression-like behavior in adolescent mice and counteracted the spine abnormalities in the NAc induced by ELS. Additionally, SNS increased NAc Rac1 activity, and the inhibition of Rac1 activity weakened the antidepressant effect of SNS.Conclusion: These results suggest that SNS may exert its antidepressant effects by modulating Rac1 activity and associated spine plasticity in the NAc.

It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death. Tanshinone IIA (Tan IIA), an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza, provides a new direction to develop a new strategy for the treatment. It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis. Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9, decreased B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio in human non-small cell lung cancer (NSCLC) cell lines, which was promoted by an autophagy activator Rapamycin, and weaken by autophagy inhibitor 3-methyladenine (3-MA). In addition, Tan IIA induced more autophagosomes, up-regulated light chain 3β (LC-3B) I and LC-3B II conversion and less sequestosome 1 (SQSTM1/p62) expression, which cannot be weakened by the caspase 3 antagonist. Moreover, overexpression of LC-3B gene (LC3B) and downregulation of autophagic gene 5 (ATG5) further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines. Beclin-1 gene (BECN1) overexpression and silence attenuated the effects of Tan IIA, suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1. Overall, our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.

Milk protein is an important component in milk and dairy products, and its content and composition are important factors influencing the functionality of milk such as nutrition and immunity. Protein components in milk are complex, and the content of different components varies greatly. With the development of functional properties of milk protein, it is of great significance and value to determine the content of milk protein components in a faster and more accurate way. Currently, enzyme-linked immunosorbent assay (ELISA), capillary electrophoresis (CE), high performance liquid chromatography (HPLC) and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) are the main methods used to determine protein components in milk. In this article, the measurement principle, applicability, and the characteristics of these methods are reviewed, which could provide reliable technical reference for accurate measurement and establishment of a novel method in milk protein evaluation, while this could also be a theoretical support for dairy nutrition research, development of dairy products and infant formula optimization.

Introduction Young, minority women are less likely to follow recommendations to prevent infant sleep-related deaths putting their children at risk. This study extended the past pre/post study designs to an RCT design and included both parent report and objective observation of the sleep environment. Objective This study focused on this population in a quantitative, randomized controlled trial using a low-cost, brief educational intervention, a Safety Baby Shower (SBS). Methods Pregnant teens aged 13–19 (N = 147) were recruited as a dyad with a senior female caregiver and randomized to intervention or control groups. Results Comparing self-report, safe sleep knowledge, attitudes, beliefs, and intent (KABI) to act scores across the two groups found intervention dyads to have more positive views on all four constructs than controls. Specifically, intervention dyad young mothers were significantly more likely to have positive beliefs about safe sleep and were more likely to report intent to practice infant safe sleep than control young mothers. Intervention dyad young mothers also had higher self-efficacy related to infant safety and more positive attitudes about safe sleep practices than control young mothers. Observations at a home visit conducted after delivery found no differences in the safe sleep practices by intervention status. Participant report of behaviors at the home visit also showed no differences in the use of safe position between the intervention and control groups. Conclusion It appears that even when young mothers gain knowledge and self-efficacy, they have difficulty implementing this knowledge. In practice, this suggests that exploring barriers prenatally with this population and offering suggestions to overcome them may be indicated.

Abstract Background Sanziguben polysaccharides (SZP) are large amounts of classical Chinese medicines from Sanziguben (SZGB). Moreover, SZGB is a widely applied compound prescription for diabetic nephropathy (DN) treatment, but the role is still unclear. This study initially explores the mechanism of SZP in the treatment of DN. Methods The high-fat diet plus streptozotocin injections were used to replicate the DN models in male C57BL/6 mice. DN mice were divided into five groups: DN mice, DN mice treated with SZP(1.01 or 2.02 g/kg), DN mice treated with SZGB decoction(4.7 g/kg), and DN mice treated with metformin (300 mg/kg). HG and LPS plus TNFα stimulated human tubule epithelial (HK-2) cells to establish an in vitro model and treated with SZP (100 or 200 μg/mL). Results SZP was found to comprise sugar, protein, and uronic acid. Furthermore, SZP alleviated the progression of inflammation in vivo and in vitro by inhibiting the expression of NF-κB. Conclusions NF-κB plays a critical role in the development of DN induced by STZ and HG. Furthermore, SZP can attenuate the NF-κB‐mediated progression of diabetic nephropathy, improve DN through anti-inflammation.

BackgroundThe American Academy of Pediatrics and Pediatric Endocrine Society neonatal hypoglycemia guidelines based their glucose concentration treatment thresholds on studies that predominantly used Beckman and Yellow Springs Glucose Oxidase Analyzers. Currently, a majority (76%) of U.S. hospital laboratories utilizing glucose oxidase methodology use Vitros® Glucose Analyzers. However, a bias of ~+5% between glucose concentrations from Beckman vs. Vitros Glucose Analyzers has been reported; this could have a clinically significant effect when using published guideline treatment thresholds.MethodsTo determine if there is similar instrument bias between Beckman and Vitros Analyzers in reported glucose concentrations from term newborns, we compared plasma glucose concentrations measured within the first 3 h after birth by Beckman vs. Vitros Analyzers in a total of 1,987 newborns (Beckman n = 904, Vitros n = 1,083). Data were fit using nonlinear cubic spline models between collection time and glucose concentration.ResultsThe non-linear patterns of initial glucose concentrations (during the first 3 h after birth) as measured by Beckman and Vitros Analyzers paralleled each other with no overlap of the fit spline curve 95% confidence intervals, with an approximate +5 mg/dL constant bias. Additionally, in method comparison studies performed in the Chemistry Laboratory on adult samples, there was a +4.2-7.4 mg/dL measured glucose bias for the Beckman vs. Vitros Analyzer.ConclusionGlucose concentrations from term, appropriate size for gestational age newborns were about 5 mg/dL higher when measured by Beckman vs. Vitros Analyzers. Perhaps, concentrations of 45 mg/dL reported from Beckman Analyzers may be equivalent to 40 mg/dL from Vitros Analyzers. When managing neonatal hypoglycemia, it is important to know which analyzer was used and whether adjusting for potential instrument bias is necessary when following published guidelines.

Red blood cell transfusions are common in patients with sickle cell disease who are at increased risk of stroke. Unfortunately, transfusion thresholds needed to sufficiently dilute sickle red blood cells and adequately restore oxygen delivery to the brain are not well defined. Previous work has shown that transfusion is associated with a reduction in oxygen extraction fraction and cerebral blood flow, both of which are abnormally increased in sickle patients. These reductions are thought to alleviate hemometabolic stress by improving the brain's ability to respond to increased metabolic demand, thereby reducing susceptibility to ischemic injury. Monitoring the cerebral hemometabolic response to transfusion may enable individualized management of transfusion thresholds. Diffuse optical spectroscopies may present a low-cost, non-invasive means to monitor this response. In this study, children with SCD undergoing chronic transfusion therapy were recruited. Diffuse optical spectroscopies (namely, diffuse correlation spectroscopy combined with frequency domain near-infrared spectroscopy) were used to quantify oxygen extraction fraction (OEF), cerebral blood volume (CBV), an index of cerebral blood flow (CBFi), and an index of cerebral oxygen metabolism (CMRO2i) in the frontal cortex immediately before and after transfusion. A subset of patients receiving regular monthly transfusions were measured during a subsequent transfusion. Data was captured from 35 transfusions in 23 patients. Transfusion increased median blood hemoglobin levels (Hb) from 9.1 to 11.7 g/dL (p < 0.001) and decreased median sickle hemoglobin (HbS) from 30.9 to 21.7% (p < 0.001). Transfusion decreased OEF by median 5.9% (p < 0.001), CBFi by median 21.2% (p = 0.020), and CBV by median 18.2% (p < 0.001). CMRO2i did not statistically change from pre-transfusion levels (p > 0.05). Multivariable analysis revealed varying degrees of associations between outcomes (i.e., OEF, CBFi, CBV, and CMRO2i), Hb, and demographics. OEF, CBFi, and CBV were all negatively associated with Hb, while CMRO2i was only associated with age. These results demonstrate that diffuse optical spectroscopies are sensitive to the expected decreases of oxygen extraction, blood flow, and blood volume after transfusion. Diffuse optical spectroscopies may be a promising bedside tool for real-time monitoring and goal-directed therapy to reduce stroke risk for sickle cell disease.

BackgroundLactopontin (LPN) in breast milk, also known as milk osteopontin is thought to play a myriad of important roles in infants when they are immature. The purpose of the present study was to examine the longitudinal changes in LPN concentrations in term and preterm milk, and elucidate the links between maternal characteristics, LPN levels, and child growth in a birth cohort.Methods131 mothers who delivered term, moderate-late preterm (MPT), very preterm (VPT), and extremely preterm (EPT) infants were included, milk samples were collected at 7, 14, 28, and 120 days postpartum. LPN concentration was determined by multiple reaction monitoring (MRM) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).ResultsOur results indicated that LPN change over time of VPT (P = 0.024) and EPT (P = 0.003) were significantly different from term milk, although they all gradually decreased with lactation. In terms of LPN-related factors, maternal age was a significant contributor in late mature milk and pre-pregnancy BMI a significant contributor to colostrum and transitional milk. We further investigated relationships between LPN levels and infant weight and our results suggested that high levels of LPN in breast milk might be useful for the catch-up growth of infants.ConclusionLPN levels in breast milk are related to maternal factors, and differences in LPN levels may affect the growth of infants. As milk is a critical part in the mother–breastmilk–infant “triad,” the association between maternal-infant factors and milk LPN levels warrants further study.

The dorsal raphe nucleus (DRN) is a major source of serotonin in the central nervous system, which is closely related to depression-like behaviors and is modulated by local GABAergic interneurons. Although serotonin neurons are known to be activated by struggling behavior in tail suspension test (TST), the exact electrophysiological characteristics are still unclear. Here, we combined in vivo electrode recording and behavioral test to explore the mice neuron electrophysiology in DRN during TST and observed that gamma oscillation was related to despair-like behaviors whereas burst fraction was crucial for survival-like behaviors. We reported the identification of a subpopulation of DRN neurons which change their firing rates when mice get into and during TST immobile states. Both increase (putative despair units, D units for short) and decrease (putative survival units, S units for short) in firing rate were observed. Furthermore, using optogenetics to identify parvalbumin-positive (PV+) and serotonin transporter-positive (SERT+) neurons, we found that SERT+ neurons were almost S units. Interestingly, those that have been identified PV+ neurons include ~20% of D units and ~50% of S units. These results suggest that electrophysiological characteristics incorporated in despair-like behavior studies can provide new insight into the study of anti-depression targets, and GABAergic interneuron is a complex key hub to the coding and regulation of local neural network.

Background:. Spirituality is an important, yet often overlooked, component of personal well-being. The purpose of this study was to assess whether spirituality plays an important role in the well-being of US plastic surgeons and residents, and whether spirituality is viewed as an important component of patient care. Methods:. An anonymous and voluntary email survey was distributed to 3375 members of ASPS during the months of April through June of 2020. The survey distribution included 2230 active members of ASPS and 1149 resident members, all who practice or train within the United States. The survey consisted of 18 multiple-choice questions with answer choices based on a descriptive five-point Likert scale and ranking by priority. Statistical analysis of the results was performed using StataCorp 2019 software. Results:. A total of 431 completed surveys were received for a response rate of 12.7%. The majority of participants (70%) reported that personal spiritual beliefs and faith contribute positively to emotional well-being. In total, 65% agreed or strongly agreed that their spiritual beliefs provide a healthy framework for handling conflict, suffering, and loss. More than half (51%) reported that as a result of the COVID-19 global pandemic, their spiritual beliefs and practices have provided increased support and guidance. Conclusions:. Spirituality is an important component of maintaining wellness for plastic surgeons, and spirituality is recognized by plastic surgeons as an important aspect of the healing process for patients. Efforts should be made to promote spiritual health among the surgical community both during training and in practice.

OBJECTIVES/GOALS: To compare rates and types of neurological symptoms in children hospitalized with seizures and respiratory infections, including SARS-CoV-2, influenza, and endemic coronaviruses. METHODS/STUDY POPULATION: Retrospective cohort study of children between 0-21 years of age admitted to a single pediatric free-standing quaternary referral center from January 1, 2014 to June 1, 2021 for seizures who had positive respiratory infection PCR for SARS-CoV-2, other coronaviruses (Coronavirus NL63 and Coronavirus OC34), influenza (A and B), adenovirus, Mycoplasma pneumoniae, and parainfluenza 3 or 4 infections. Patient characteristics including age, race, sex, ethnicity, hospital length of stay, intensive care unit admission, intubation, chest x-ray, and MRI results were included. The primary outcomes were rates of neurological diagnoses and mortality. RESULTS/ANTICIPATED RESULTS: A total of 883 children were included: 68 SARS-CoV-2, 232 influenza, and 187 with other coronaviruses (OC), 214 adenovirus, 20 M. pneumoniae, 121 parainfluenza 3, and 41 parainfluenza 4. Mortality rates were 0% M pneumoniae to 4.9% in parainfluenza 4, with 2.9% in SARS-CoV-2. Encephalopathy was noted in 5-15.6% and strokes were seen in all infections except for coronavirus OC43 and M. pneumoniae, with 4.9% in parainfluenza 4 and 5.9% in SARS-CoV-2. The most common brain MRI abnormality was diffusion restriction. Differences between SARS-CoV-2 and OC were observed in stroke (5.9% vs. 0.5%, p-value=0.019), ICU admission (50% vs. 69%, p-value=0.008), and intubation (19.1% vs. 34.8%, p-value=0.021, respectively). However, the rates of neurological symptoms were similar between SARS-CoV-2 and influenza. DISCUSSION/SIGNIFICANCE: We found higher rates of stroke, but lower rates of ICU admission and intubation in SARS-CoV-2 versus OC. Strokes were observed in many infections. Rates of neurological symptoms were similar in SARS-CoV-2 versus influenza patients. Vigilance should be undertaken in treatment of children presenting with all respiratory illnesses.

Background: There is a pressing need for effective and non-invasive biomarkers to track intrahepatic triglyceride (IHTG) in children at-risk for non-alcoholic fatty liver disease (NAFLD), as standard-of-care reference tools, liver biopsy and magnetic resonance imaging (MRI), are impractical to monitor the course disease.Objective: We aimed to examine the association between serum fibroblast growth factor (FGF)-21 to adiponectin ratio (FAR) and IHTG as assessed by MRI in children with obesity.Methods: Serum FGF21 and adiponectin levels and IHTG were measured at two time points (baseline, 6 months) in obese children enrolled in a clinical weight loss program. The association between percent change in FAR and IHTG at final visit was examined using a multiple linear regression model.Results: At baseline, FAR was higher in the subjects with NAFLD (n = 23, 35.8 ± 41.9 pg/ng) than without NAFLD (n = 35, 19.8 ± 13.7 pg/ng; p = 0.042). Forty-eight subjects completed both visits and were divided into IHTG loss (≥1% reduction than baseline), no change (within ±1% change), and gain (≥1% increase than baseline) groups. At 6 months, the percent change in FAR was different among the three groups (p = 0.005). Multiple linear regression showed a positive relationship between percent change in FAR and the final liver fat percent in sex and pubertal stage-similar subjects with NAFLD at baseline (slope coefficient 6.18, 95% CI 1.90–10.47, P = 0.007), but not in those without NAFLD.Conclusions: Higher value in percent increase in FAR is positively associated with higher level of IHTG percent value at 6 months in children with baseline NAFLD. FAR could be a potential biomarker to monitor the changes in IHTG in children with NAFLD.

More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC–MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.

Isoorientin has anti-inflammatory effects; however, the mechanism remains unclear. We previously found isoorientin is an inhibitor of glycogen synthase kinase 3β (GSK3β) in vitro. Overactivation of GSK3β is associated with inflammatory responses. GSK3β is inactivated by phosphorylation at Ser9 (i.e., p-GSK3β). Lithium chloride (LiCl) inhibits GSK3β and also increases p-GSK3β (Ser9). The present study investigated the anti-inflammatory effect and mechanism of isoorientin via GSK3β regulation in lipopolysaccharide- (LPS-) induced RAW264.7 murine macrophage-like cells and endotoxemia mice. LiCl was used as a control. While AKT phosphorylates GSK3β, MK-2206, a selective AKT inhibitor, was used to activate GSK3β via AKT inhibition (i.e., not phosphorylate GSK3β at Ser9). The proinflammatory cytokines TNF-α, IL-6, and IL-1β were detected by ELISA or quantitative real-time PCR, while COX-2 by Western blotting. The p-GSK3β and GSK3β downstream signal molecules, including NF-κB, ERK, Nrf2, and HO-1, as well as the tight junction proteins ZO-1 and occludin were measured by Western blotting. The results showed that isoorientin decreased the production of TNF-α, IL-6, and IL-1β and increased the expression of p-GSK3β in vitro and in vivo, similar to LiCl. Coadministration of isoorientin and LiCl showed antagonistic effects. Isoorientin decreased the expression of COX-2, inhibited the activation of ERK and NF-κB, and increased the activation of Nrf2/HO-1 in LPS-induced RAW264.7 cells. Isoorientin increased the expressions of occludin and ZO-1 in the brain of endotoxemia mice. In summary, isoorientin can inhibit GSK3β by increasing p-GSK3β and regulate the downstream signal molecules to inhibit inflammation and protect the integrity of the blood-brain barrier and the homeostasis in the brain.

Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS).Method: Male neonatal Wistar rats were divided into six groups including control + ddH2O, MS + ddH2O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC.Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats.Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway.

The usage of prophylactic oral antibiotics following distal hypospadias repair with stenting has been recently challenged. This study evaluated the incidence of symptomatic urinary tract infections (UTIs) following stented, distal hypospadias repair and the impact of prophylactic antibiotic therapy. Subjects 0 to 5 years of age with distal hypospadias were randomized to either Group 1 (antibiotics) or Group 2 (no prophylactic therapy). Urinalysis/urine culture was obtained intraoperatively with no preoperative antibiotics given. Phone interviews at 1 month and 3 months after surgery were done. Forty-eight patients were successfully randomized to either Group 1 (24) or Group 2 (24). The incidence of symptomatic UTI in this pilot study is low, and prophylactic antibiotic therapy does not appear to lower the incidence of symptomatic UTI. A larger, randomized, multicenter trial is needed to determine whether antibiotic prophylaxis reduces the risk of symptomatic UTIs following stented, distal hypospadias repair.

BACKGROUND:The relative influence of prematurity vs. maternal social factors (socioeconomic status and education level) on academic performance has rarely been examined. OBJECTIVE:To examine the impact of prematurity and maternal social factors on academic performance from 3rd through 8th grade. METHODS:We conducted a retrospective cohort study of infants born in 1998 at the University of Arkansas for Medical Sciences. The study sample included 58 extremely low gestational age newborns (ELGANs, 23‒