Generation of rat forebrain tissues in mice.

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation.

BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.

Psychometric validation of a patient-reported experience measure for older adults attending the emergency department: the PREM-ED 65 study.

INTRODUCTION: Optimising emergency department (ED) patient experience is vital to ensure care quality. However, there are few validated instruments to measure the experiences of specific patient groups, including older adults. We previously developed a draft 82-item Patient Reported Experience Measure (PREM-ED 65) for adults ≥65 attending the ED. This study aimed to derive a final item list and provide initial validation of the PREM-ED 65 survey. METHODS: A cross-sectional study involving patients in 18 EDs in England. Adults aged 65 years or over, deemed eligible for ED discharge, were recruited between May and August 2021 and asked to complete the 82-item PREM at the end of the ED visit and 7-10 days post discharge. Test-retest reliability was assessed 7-10 days following initial attendance. Analysis included descriptive statistics, including per-item proportions of responses, hierarchical item reduction, exploratory factor analysis (EFA), reliability testing and assessment of criterion validity. RESULTS: Five hundred and ten initial surveys and 52 retest surveys were completed. The median respondent age was 76. A similar gender mix (men 47.5% vs women 50.7%) and reason for attendance (40.3% injury vs 49.0% illness) was observed. Most participants self-reported their ethnicity as white (88.6%).Hierarchical item reduction identified 53/82 (64.6%) items for exclusion, due to inadequate engagement (n=33), ceiling effects (n=5), excessive inter-item correlation (n=12) or significant differential validity (n=3). Twenty-nine items were retained.EFA revealed 25 out of the 29 items demonstrating high factor loadings (>0.4) across four scales with an Eigenvalue >1. These scales were interpreted as measuring 'relational care', 'the ED environment', 'staying informed' and 'pain assessment'. Cronbach alpha for the scales ranged from 0.786 to 0.944, indicating good internal consistency. Test-retest reliability was adequate (intraclass correlation coefficient 0.67). Criterion validity was fair (r=0.397) when measured against the Friends and Families Test question. CONCLUSIONS: Psychometric testing demonstrates that the 25-item PREM-ED 65 is suitable for administration to adults ≥65 years old up to 10 days following ED discharge.

Using Information Available at the Time of Donor Offer to Predict Kidney Transplant Survival Outcomes: A Systematic Review of Prediction Models.

Statistical models that can predict graft and patient survival outcomes following kidney transplantation could be of great clinical utility. We sought to appraise existing clinical prediction models for kidney transplant survival outcomes that could guide kidney donor acceptance decision-making. We searched for clinical prediction models for survival outcomes in adult recipients with single kidney-only transplants. Models that require information anticipated to become available only after the time of transplantation were excluded as, by that time, the kidney donor acceptance decision would have already been made. The outcomes of interest were all-cause and death-censored graft failure, and death. We summarised the methodological characteristics of the prediction models, predictive performance and risk of bias. We retrieved 4,026 citations from which 23 articles describing 74 models met the inclusion criteria. Discrimination was moderate for all-cause graft failure (C-statistic: 0.570-0.652; Harrell's C: 0.580-0.660; AUC: 0.530-0.742), death-censored graft failure (C-statistic: 0.540-0.660; Harrell's C: 0.590-0.700; AUC: 0.450-0.810) and death (C-statistic: 0.637-0.770; Harrell's C: 0.570-0.735). Calibration was seldom reported. Risk of bias was high in 49 of the 74 models, primarily due to methods for handling missing data. The currently available prediction models using pre-transplantation information show moderate discrimination and varied calibration. Further model development is needed to improve predictions for the purpose of clinical decision-making. Systematic Review Registration: https://osf.io/c3ehp/l.

Estimating the correlation between semi-competing risk survival endpoints.

Time-to-event, bivariate, semi-competing risk data occur when a terminal event can censor a non-terminal event, but not vice versa. There are potential correlations between these endpoints as they are measured on the same individual. However, traditional methods to estimate the correlations cannot be used directly due to the censoring of time-to-event endpoints. We develop methods using a copula-based approach to study the dependence structures between the two survival endpoints. We use a variety of copulas to estimate the correlation between endpoints and to acknowledge different dependence structures. The estimated association parameter in the copula function is transformed into Spearman's rank correlation coefficient. We conduct a simulation study to evaluate the estimation from the proposed models along with the effects of misspecification of the copula functions and survival distributions. The proposed methods are applied to two real-life data sets.

The Corticosterone-Glucocorticoid Receptor-AP1/CREB Axis Inhibits the Luteinizing Hormone Receptor Expression in Mouse Granulosa Cells.

Under stress conditions, luteinizing hormone (LH)-mediated ovulation is inhibited, resulting in insufficient oocyte production and excretion during follicular development. When the body is stressed, a large amount of corticosterone (CORT) is generated, which will lead to a disorder of the body's endocrine system and damage to the body. Our previous work showed that CORT can block follicular development in mice. Since LH acts through binding with the luteinizing hormone receptor (Lhcgr), the present study aimed to investigate whether and how corticosterone (CORT) influences Lhcgr expression in mouse ovarian granulosa cells (GCs). For this purpose, three-week-old ICR female mice were injected intraperitoneally with pregnant mare serum gonadotropin (PMSG). In addition, the treatment group was injected with CORT (1 mg/mouse) at intervals of 8 h and the control group was injected with the same volume of methyl sulfoxide (DMSO). GCs were collected at 24 h, 48 h, and 55 h after PMSG injection. For in vitro experiments, the mouse GCs obtained from healthy follicles were treated with CORT alone, or together with inhibitors against the glucocorticoid receptor (Nr3c1). The results showed that the CORT caused a downregulation of Lhcgr expression in GCs, which was accompanied by impaired cell viability. Moreover, the effect of the CORT was mediated by binding to its receptor (Nr3c1) in GCs. Further investigation revealed that Nr3c1 might regulate the transcription of Lhcgr through inhibiting the expression of Lhcgr transcription factors, including AP1 and Creb. Taken together, our findings suggested a possible mechanism of CORT-induced anovulation involving the inhibition of Lhcgr expression in GCs by the CORT-Nr3c1-AP1/Creb axis.

Albumin-Embellished Arsenic Trioxide-Loaded Polymeric Nanoparticles Enhance Tumor Accumulation and Anticancer Efficacy via Transcytosis for Hepatocellular Carcinoma Therapy.

Arsenic trioxide (ATO) has efficient anticancer effect on hepatocellular carcinoma (HCC) in clinical trials, but its off-target distribution and side effects have limited its use. Here, we demonstrate an albumin-embellished ATO-loaded polyethylene glycol-polycaprolactone-polyethyleneimine (PEG-PCL-PEI) nanoparticle (AATONP) to enhance the tumor distribution and intratumor drug release of ATO for HCC therapy. AATONP is prepared by surface embellishment with albumin on the cationic ATO-loaded PEG-PCL-PEI nanoparticles (CATONP). Albumin embellishment can reduce the cationic material's hemolytic toxicity in blood cells while maintaining the rapid internalization and lysosome escape abilities of the positively charged CATONP. AATONP provides sustained and low pH-responsive drug release, facilitating the targeted drug release in the intratumor acidic microenvironment. Moreover, AATONP can significantly improve the circulation time and tumor distribution of ATO via albumin-mediated transcytosis in HCC tumor-bearing mice. Compared with free ATO and the clinically used nanomedicine Genexol/PM, AATONP shows potent antitumor activity against a human HCC xenograft mouse model, leading to a higher tumor inhibition rate of 89.4% in HCC therapy. In conclusion, this work presents an efficient strategy to achieve tumor accumulation and the intratumor drug release of ATO for HCC therapy. An albumin-embellished arsenic trioxide (ATO)-loaded polyethylene glycol-polycaprolactone-polyethyleneimine nanoparticle (AATONP) is designed to enhance tumor distribution and intratumor drug release of ATO for hepatocellular carcinoma therapy. AATONP can achieve enhanced tumor distribution via albumin-mediated transcytosis and exhibit intratumor drug release of ATO via tumor acidic microenvironment-response, leading to potent antitumor activity.

Near-Infrared Fluorescent Probe for Imaging and Evaluating the Role of Vanin-1 in Chemotherapy.

Pantetheinase (also known as Vanin-1) is highly expressed in the liver, kidneys, and intestine and is closely associated with a number of diseases. Vanin-1 can hydrolyze pantetheine to pantothenic acid (vitamin B5) and cysteamine and participate in the synthesis of glutathione (GSH). GSH is highly expressed in tumor cells and plays a major role in the resistance of tumor cells to cisplatin. Therefore, we urgently need a method to monitor the activity level of Vanin-1 in tumor cells and tissues and elucidate the relationship between the role of Vanin-1 in GSH synthesis and tumor resistance. Herein, we report a Cy-Pa fluorescent probe for imaging Vanin-1 in cells and in vivo that can qualitatively and quantitatively detect the fluctuation of Vanin-1 concentrations in HepG2 and HepG2/DDP cells or tumor tissues of tumor-bearing mice. This probe shows excellent potential in in situ real-time monitoring of endogenous Vanin-1. Moreover, we proved that Vanin-1 can inhibit GSH synthesis using the probe. When the Vanin-1 inhibitor RR6 was used in combination with cisplatin, HepG2 and HepG2/DDP cells showed increased resistance to cisplatin, while the therapeutic efficiency of cisplatin was reduced in HepG2 and HepG2/DDP xenografts. In this study, Vanin-1 was shown to play an important role in the treatment of cancer, and the study of Vanin-1 may provide an idea for the treatment of cancer in the future.

Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy.

The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2-PEG-LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2-PEG-LP@CaAs was investigated both in vitro and in vivo. As a result, A2-PEG-LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2-PEG-LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.

Angiopep-2 modified lipid-coated mesoporous silica nanoparticles for glioma targeting therapy overcoming BBB.

Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

Integrative Proteomic and Phosphoproteomic Profiling of Testis from Wip1 Phosphatase-Knockout Mice: Insights into Mechanisms of Reduced Fertility.

Mice lacking wild-type p53-induced phosphatase 1 (Wip1) display male reproductive defects including smaller testes, subfertility and spermatogenesis defects at the round- and elongating-spermatid stages. However, the molecular mechanisms underlying these abnormalities remain unclear. Here we examined the proteome and phosphoproteome of testes from Wip1-knockout mice using a quantitative proteomic approach. From a total of 6872 proteins and 4280 phosphorylation sites identified, 58 proteins and 159 phosphorylation sites were found to be differentially regulated compared with wild type mice. Pathway enrichment analyses revealed that these regulated proteins and phosphosites were mainly involved in adherens/tight junctions, apoptosis, inflammatory response, spermatogenesis, sperm motility, and cytoskeletal assembly and depolymerization. Wip1-knockout mice showed decreased expression of junction-associated proteins (occludin, ZO-1, and N-cadherin) and impaired integrity of the blood-testis barrier. In addition, Wip1 deficiency was associated with elevated levels of cytokines and germ cell apoptosis in the testis. These results suggest that proinflammatory cytokines may impair the blood-testis barrier dynamics by decreasing the expression of junction-associated proteins, which could lead to subfertility and spermatogenesis defects. Collectively, these findings help to explain the low reproductive function caused by Wip1 deletion and provide novel insights into our understanding of causes of male infertility.

Insulin-like growth factor-I prevents hypoxia-inducible factor-1 alpha-dependent G1/S arrest by activating cyclin E/cyclin-dependent kinase2 via the phoshatidylinositol-3 kinase/AKT/forkhead box O1/Cdkn1b pathway in porcine granulosa cells†.

As the follicle develops, the thickening of the granulosa compartment leads to progressively deficient supply of oxygen in granulosa cells (GCs) due to the growing distances from the follicular vessels. These conditions are believed to cause hypoxia in GCs during folliculogenesis. Upon hypoxic conditions, several types of mammalian cells have been reported to undergo cell cycle arrest. However, it remains unclear whether hypoxia exerts any impact on cell cycle progression of GCs. On the other hand, although the GCs may live in a hypoxic environment, their mitotic capability appears to be unaffected in growing follicles. It thus raises the question whether there are certain intraovarian factors that might overcome the inhibitory effects of hypoxia. The present study provides the first evidence suggesting that cobalt chloride (CoCl2)-mimicked hypoxia prevented G1-to-S cell cycle progression in porcine GCs. In addition, we demonstrated that the inhibitory effects of CoCl2 on GCs cell cycle are mediated through hypoxia-inducible factor-1 alpha/FOXO1/Cdkn1b pathway. Moreover, we identified insulin-like growth factor-I (IGF-I) as an intrafollicular factor required for cell cycle recovery by binding to IGF-I receptor in GCs suffering CoCl2 stimulation. Further investigations confirmed a role of IGF-I in preserving G1/S progression of CoCl2-treated GCs via activating the cyclin E/cyclin-dependent kinase2 complex through the phoshatidylinositol-3 kinase/protein kinase B (AKT)/FOXO1/Cdkn1b axis. Although the present findings were based on a hypoxia mimicking model by using CoCl2, our study might shed new light on the regulatory mechanism of GCs cell cycle upon hypoxic stimulation.

Chronic Respiratory Symptoms and Lung Abnormalities Among People With a History of Tuberculosis in Uganda: A National Survey.

BACKGROUND: People with pulmonary tuberculosis are at risk of developing chronic respiratory disorders due to residual lung damage. To date, the scope of the problem in high-burden tuberculosis countries is relatively unknown. METHODS: Chronic respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung abnormalities were compared between adults with and without a history of tuberculosis among the general population of Uganda. Multivariable regression models were used to estimate odds ratios (ORs) with adjustment for age, gender, smoking, education, setting, and region. Random effects models accounted for village clustering effect. RESULTS: Of 45293 invited people from 70 villages, 41154 (90.9%) participated in the survey. A total of 798 had a history of tuberculosis and, among them, 16% had respiratory symptoms and 41% X-ray abnormalities. Adjusted ORs showed strong evidence for individuals with a history of tuberculosis having increased risk of respiratory symptoms (OR, 4.02; 95% confidence interval [CI], 3.25-4.96) and X-ray abnormalities (OR, 17.52; 95% CI, 14.76-20.79), attributing 6% and 24% of the respective population risks. CONCLUSIONS: In Uganda, a history of tuberculosis was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating tuberculosis disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.

Video feedback for parental sensitivity and attachment security in children under five years.

BACKGROUND: Children who are securely attached to at least one parent are able to be comforted by that parent when they are distressed and explore the world confidently by using that parent as a 'secure base'. Research suggests that a secure attachment enables children to function better across all aspects of their development. Promoting secure attachment, therefore, is a goal of many early interventions. Attachment is mediated through parental sensitivity to signals of distress from the child. One means of improving parental sensitivity is through video feedback, which involves showing a parent brief moments of their interaction with their child, to strengthen their sensitivity and responsiveness to their child's signals. OBJECTIVES: To assess the effects of video feedback on parental sensitivity and attachment security in children aged under five years who are at risk for poor attachment outcomes. SEARCH METHODS: In November 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, nine other databases and two trials registers. We also handsearched the reference lists of included studies, relevant systematic reviews, and several relevant websites SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that assessed the effects of video feedback versus no treatment, inactive alternative intervention, or treatment as usual for parental sensitivity, parental reflective functioning, attachment security and adverse effects in children aged from birth to four years 11 months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 22 studies from seven countries in Europe and two countries in North America, with a total of 1889 randomised parent-child dyads or family units. Interventions targeted parents of children aged under five years, experiencing a wide range of difficulties (such as deafness or prematurity), or facing challenges that put them at risk of attachment issues (for example, parental depression). Nearly all studies reported some form of external funding, from a charitable organisation (n = 7) or public body, or both (n = 18). We considered most studies as being at low or unclear risk of bias across the majority of domains, with the exception of blinding of participants and personnel, where we assessed all studies as being at high risk of performance bias. For outcomes where self-report measures were used, such as parental stress and anxiety, we rated all studies at high risk of bias for blinding of outcome assessors. Parental sensitivity. A meta-analysis of 20 studies (1757 parent-child dyads) reported evidence of that video feedback improved parental sensitivity compared with a control or no intervention from postintervention to six months' follow-up (standardised mean difference (SMD) 0.34, 95% confidence interval (CI) 0.20 to 0.49, moderate-certainty evidence). The size of the observed impact compares favourably to other, similar interventions. Parental reflective functioning. No studies reported this outcome. Attachment security. A meta-analysis of two studies (166 parent-child dyads) indicated that video feedback increased the odds of being securely attached, measured using the Strange Situation Procedure, at postintervention (odds ratio 3.04, 95% CI 1.39 to 6.67, very low-certainty evidence). A second meta-analysis of two studies (131 parent-child dyads) that assessed attachment security using a different measure (Attachment Q-sort) found no effect of video feedback compared with the comparator groups (SMD 0.02, 95% CI -0.33 to 0.38, very low-certainty evidence). Adverse events. Eight studies (537 parent-child dyads) contributed data at postintervention or short-term follow-up to a meta-analysis of parental stress, and two studies (311 parent-child dyads) contributed short-term follow-up data to a meta-analysis of parental anxiety. There was no difference between intervention and comparator groups for either outcome. For parental stress the SMD between video feedback and control was -0.09 (95% CI -0.26 to 0.09, low-certainty evidence), while for parental anxiety the SMD was -0.28 (95% CI -0.87 to 0.31, very low-certainty evidence). Child behaviour. A meta-analysis of two studies (119 parent-child dyads) at long-term follow-up found no evidence of the effectiveness of video feedback on child behaviour (SMD 0.04, 95% CI -0.33 to 0.42, very low-certainty evidence). A moderator analysis found no evidence of an effect for the three prespecified variables (intervention type, number of feedback sessions and participating carer) when jointly tested. However, parent gender (both parents versus only mothers or only fathers) potentially has a statistically significant negative moderation effect, though only at α (alpha) = 0.1 AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that video feedback may improve sensitivity in parents of children who are at risk for poor attachment outcomes due to a range of difficulties. There is currently only little, very low-certainty evidence regarding the impact of video feedback on attachment security, compared with control: results differed based on the type of measure used, and follow-up was limited in duration. There is no evidence that video feedback has an impact on parental stress or anxiety (low- and very low-certainty evidence, respectively). Further evidence is needed regarding the longer-term impact of video feedback on attachment and more distal outcomes such as children's behaviour (very low-certainty evidence). Further research is needed on the impact of video-feedback on paternal sensitivity and parental reflective functioning, as no study measured these outcomes. This review is limited by the fact that the majority of included parents were mothers.

Synthesis of Mesoporous Co3O4/NiCo2O4 Nanorods and Their Electrochemical Study.

Mesoporous Co3O4/NiCo2O4 nanorods were obtained by a hydrothermal reaction with the assistance of Ni foam and subsequent annealing treatment. The characterization of this composition by X-ray diffraction, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, energy dispersive spectra and Brunauer-Emmett-Teller analysis revealed that the nanorods consisted of Co3O4 and NiCo2O4 phase, exhibiting high porosity and rich crystal defects. The electrochemical data showed a specific capacitance of 1173 mF cm-2 and 606 mF cm-2 at 2 mV s-1 and 1 mA cm-2, respectively. Its cycling performance was 83.9% at 3 mA cm-2 after 4000 cycles. Furthermore, the asymmetric supercapacitor Co3O4/NiCo2O4//AC delivered an energy density of 11.7 W h kg-1 and power density of 760 W kg-1.

Hydroxyapatite (HA) Modified Nanocoating Enhancement on AZ31 Mg Alloy by Combined Surface Mechanical Attrition Treatment and Electrochemical Deposition Approach.

Hydroxyapatite (HA) nanocoating was electrodeposited on the surface mechanical attrition treated (SMATed) AZ31 magnesium alloy. Phases, morphologies and the adhesion of coating were characterized by X-ray diffraction, scanning electron microscopy (SEM) and 3D optical profiler. The corrosion resistance of the HA coating was tested by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The results showed that the HA coating on SMATed sample had a better crystallization than that on original one. The thickness of HA coating increased from 25 to 40 µm. The bonding strength between HA coating and SMATed substrate was higher than that between the coating and untreated counterpart. Potentiodynamic polarization and EIS demonstrated that the corrosion current density of HA coating on SMATed substrate decreased by 30.84% than that on original. The corrosion potential shifted 80.3 mV to the positive direction. The corrosion resistance of coatings on SMATed sample was significantly enhanced. The immersion experiments showed that the HA coatings on SMATed sample exhibited a better biological activity.

Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis, characterization, and pharmacokinetics.

OBJECTIVE: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability. SIGNIFICANCE: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability. METHODS: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35 mg/kg for pharmacokinetic studies in Sprague Dawley rats. RESULTS: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73 mg/mL, which exhibited a sustained release pattern over 72 h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T1/2 and AUC0-∞, respectively, as compared to RH suspension. CONCLUSION: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.

[Effect of emodin on gut microbiota of rats with acute kidney failure].

The aim of this paper was to investigate the effect of emodin on gut microbiota in acute kidney injury rats( AKI). Rats were randomly divided into several groups: normal group,model group,low-dose of emodin group( 10 mg·kg~(-1)),medium-dose of emodin group( 25 mg·kg~(-1)),high-dose of emodin group( 50 mg·kg~(-1)) and control group( 5 mg·kg~(-1) of benazepril hydrochloride).The AKI model rats were established by intraperitoneal injection of small dose of gentamicin sulfate for 7 days. Two hours after intraperitoneal injection,except for the normal group and the model group,the other groups were given corresponding doses of drugs for 15 days. The serum levels of serum creatinine( SCr),urea nitrogen( BUN),plasma endotoxin level,24 h urinary protein and D-lactate in the plasma were determined by sarcosine oxidase,urease method,tal reagent method,bromo cresol chloroform method and double antibody sandwich enzyme-linked immunoadsorbent assay,respectively. Gut microbial communities were assayed by fluorescent quantitative PCR methods. HE staining was used to detect the pathological changes of the kidneys. Compared with the normal group,there were significant differences in body weight,urinary protein( UTP),bacterial endotoxin,urea nitrogen,creatinine,D-lactate in the plasma and four bacterial contents in the model group( P<0. 05). The urinary protein,urea nitrogen,D-lactate,creatinine and plasma bacterial endotoxin in control group and each emodin group were lower than those in model group,especially for high-dose of emodin( P<0. 01). Moreover,pathology resolution in high-dose emodin was better than other groups. Except for low-dose of emodin group,qRT-PCR data suggested that the amounts of Escherichia coli and Enterococcus in medication administration group were increased,while the amounts of Lactobacilli and Bifidobacterium were reduced compared with model group( P<0. 05),especially for high-dose of emodin( P<0. 01). There is a clear imbalance of gut microbiota in rats with AKI. Emodin could regulate the imbalance of gut microbiota,which might be one of the mechanisms of its effects on AKI rats.