Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

Maternal Prenatal Inflammation Increases Brain Damage Susceptibility of Lipopolysaccharide in Adult Rat Offspring via COX-2/PGD-2/DPs Pathway Activation.

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aß, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aß, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.

Exploring the Molecular Mechanism and Biomarker of Recurrent Spontaneous Abortion Based on RNA Sequencing Analysis.

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation. It is a hot issue in contemporary obstetrics. The etiology of RSA is complicated. Exploring the molecular mechanisms of RSA will be helpful for the prevention and precise therapy at the molecular level. This study aimed to provide novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in RSA. METHODS: The data set GSE121950 was obtained from GEO data sets. We identified the DEGs using the affy pack-age in R programming software. Gene set enrichment analysis (GESA) and GenePattern tools were performed to examine the gene expression differences between RSA and control group. Protein-protein interaction (PPI) analysis was performed using STRING online tool (https://string-db.org/). qRT-PCR was carried out to validate the expression levels of DEGs in 16 villus tissue samples from patients with induced abortion and 16 villus tissue samples from RSA patients. RESULTS: A total of 628 DEGs with adjPval < 0.05 and |logFC| > 1 were obtained, including 155 up-regulated genes and 473 down-regulated genes. Ten gene ontology (GO) terms and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened out by comparing the genome-wide gene set expression patterns of normal and RSA tissues. Eight genes involved in RSA were identified from the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway. CONCLUSIONS: Present findings demonstrated that several cytokine regulation processes have a deep impact on RSA. A number of genes involved in the hippo signaling pathway, cytokine-cytokine receptor interaction pathway, and allograft rejection pathway may be critical mediators or participators in the pathogenesis of RSA. Although further in vivo and in vitro validations are required, our data may provide an important theoretical basis to elucidate the pathogenesis of RSA.

Copper nanoclusters@Al3+ complexes with strong and stable aggregation-induced emission for application in enzymatic determination of urea.

The aggregates of glutathione-capped CuNCs induced by Al3+ (named CuNCs@Al3+ complexes) show a stable aggregation-induced emission (AIE) for about 1 month. Their fluorescence maintains a high level in the pH range 4.0 to 7.0, while it quenches as pH increases from 7.0 to 7.7 or decreases from 4.0 to 3.0. Under urease-catalyzed hydrolysis, urea produces ammonia, which can be further hydrolyzed to yield OH-. This leads to a pH increase of the immediate environment. Hence, the CuNCs@Al3+ complexes are a suitable probe to determine urea. The fluorescence of CuNCs@Al3+ complexes quenches linearly at 585 nm with the excitation wavelength at 340 nm when the concentration of urea increases from 20 to 150 µM. The limit of detection (LOD) of urea is 5.86 µM. This sensitivity is superior to other reported works due to the narrow pH response range of CuNCs@Al3+ complexes. This method has been successfully applied for measuring urea in human urine samples with satisfactory recoveries. Graphic abstract Schematic representation of urea determination based on pH-responsive property of copper nanoclusters@Al3+ complexes. Ammonia is produced in the hydrolysis of urea by urease, and it is further hydrolyzed to yield OH-, leading to increasing pH of the environment.

High-mobility group box-1 inhibition stabilizes intestinal permeability through tight junctions in experimental acute necrotizing pancreatitis.

BACKGROUND: In acute necrotizing pancreatitis (ANP), bacterial translocation (BT) from the gastrointestinal tract is the essential pathogenesis in the development of septic complications. Although high-mobility group box-1 (HMGB1) is associated with BT and organ dysfunction in ANP, the mechanism of HMGB1 in the intestinal barrier dysfunction and BT has not been well addressed. In this study, we intend to address the role of HMGB1 in ANP involving BT and intestinal barrier dysfunction. METHODS: Experimental ANP was achieved in male Sprague-Dawley rats through a retrograde injection of taurocholate into the common biliopancreatic duct following a laparotomy operation. HMGB1 blockade intervention was conducted with a subcutaneous injection of anti-HMGB1 antibody immediately before the laparotomy procedure. Twenty-four hours after ANP induction, pancreatic and intestinal tissues and blood samples were collected for a histopathological assessment and lipid peroxidation or glutathione (GSH) evaluation. AP-induced barrier dysfunction was determined by an intestinal permeability assessment. Tight junction proteins and autophagy regulators were investigated by western blotting, immunohistological analysis and confocal immunofluorescence imaging. RESULTS: ANP developed as indicated by microscopic parenchymal necrosis and fat necrosis, which were associated with intestinal mucosal barrier dysfunction. HMGB1 inhibition played a protective role in intestinal mucosal barrier dysfunction, protected against microbiome changes in ANP, and relieved intestinal oxidative stress. Additionally, HMGB1 inhibition attenuated intestinal permeability; preserved the expression of TJs, such as claudin-2 and occludin; and decreased autophagy. Furthermore, the autophagy regulator LC3 and TJ protein claudin-2 were both upregulated in ANP according to dual immunofluorescence analysis. CONCLUSION: HMGB1 inhibition ameliorated the severity of experimental ANP though beneficial effects on BT, mainly involving in TJ function.

Emissions of terbium metal-organic frameworks modulated by dispersive/agglomerated gold nanoparticles for the construction of prostate-specific antigen biosensor.

Herein, a universal and multifunctional fluorescence sensor platform is designed by the interaction of aggregation/dispersion gold nanoparticles (AuNPs) with Tb-metal-organic frameworks (Tb-MOFs). It is found that the dispersed AuNPs rather than the aggregated ones can quench effectively the fluorescence of Tb-MOFs, and the quenching process presumably involves the mechanism of inner filter effect (IFE), dynamic quenching effect (DQE), and fluorescence resonance energy transfer (FRET). The different affinities of aptamer and aptamer-target complex toward AuNPs are employed to modulate the fluorescence signal change of Tb-MOFs. As the proof of concept, prostate-specific antigen (PSA), an efficient tumor indicator for prostate cancer, is selected as the target. At first, the PSA aptamer can protect AuNPs against salt-induced aggregation, leading to the fluorescence of Tb-MOFs quenching. Subsequently, upon PSA introduction, the rigid aptamer-PSA complex is formed and cannot stabilize AuNPs in high salt conditions, so the AuNPs aggregate significantly and the fluorescence of Tb-MOFs is restored. The linear range of PSA is achieved from 1 to 100 ng/mL with a detection limit of 0.36 ng/mL. Finally, this method has been validated to be sensitive and specific for PSA in human urine samples. Graphical abstract.

Comparative Pharmacokinetic Study of Mangiferin in Normal and Alloxan-Induced Diabetic Rats after Oral and Intravenous Administration by UPLC-MS/MS.

BACKGROUNDS: Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. METHODS: Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (n = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard)  were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). RESULTS: Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in Cmax and AUC0-t, respectively, for mangiferin after oral administration, and 63.08% decreases in Cmax after intravenous administration. CONCLUSIONS: Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.

Determination of adenosine triphosphate based on the use of fluorescent terbium(III) organic frameworks and aptamer modified gold nanoparticles.

A thiol-labeled adenosine triphosphate (ATP) binding aptamer is covalently linked on the surface of gold nanoparticles (AuNPs). This warrants protection of the red AuNPs from aggregation in high salt condition. The dispersed AuNPs can quench the fluorescence of the Tb(III)-MOFs at 547 nm with the excitation wavelength of 290 nm. This is ascribed to the combined action of inner filter effect, dynamic quenching and fluorescence resonance energy transfer. If the aptamer binds ATP to form folded structures, the AuNPs aggregate in high salt medium and the green fluorescence of the Tb(III)-MOFs is recovered. This method shows good sensitivity and selectivity for ATP, and the linear range is from 0.5 to 10 µM of ATP with the detection limitat of 0.32 µM. It was applied to the determination of ATP in (spiked) human plasma with satisfactory recoveries (from 93.2% to 106.3%). Oppositely, when the unlabeled aptamer is used instead of thiol-labeled aptamer in this process, the ATP-aptamer complexes rather than unlabeled aptamer provide greater protection for AuNPs against salt-induced aggregation. It is found that when the aptamer covalently binds to AuNPs, the steric hindrance is dominant for the stabilization of AuNPs; for unlabeled aptamer, the electrostatic repulsion is responsible for their stability, irrespective of whether ATP is present or not. These two different forces lead to the aggregation or dispersion of AuNPs with addition of target in salt solution. Graphical abstractThe impact of two repulsive forces (electrostatic repulsion and steric repulsion) on the stabilization of gold nanoparticles, and its application in fluorescent terbium metal-organic frameworks as a nanoprobe for adenosine triphosphate.

A resonance Rayleigh scattering sensor for sensitive differentiation of telomere DNA length and monitoring special motifs (G-quadruplex and i-motif) based on the Ag nanoclusters and NAND logic gate responding to chemical input signals.

BACKGROUND: Differentiation of telomere length is of vital importance because telomere length is closely related with several deadly diseases such as cancer. Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown to act as a negative regulator of telomere elongation by telomerase in vivo and are considered as an attractive drug target for cancer chemotherapy. RESULTS: In this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI-Ag NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for sensitive differentiation of telomere length and monitoring special motifs (G-quadruplex and i-motif). In this assay, free PEI-Ag NC probe or DNA sequence alone emits low intensities of RRS, while the formation of PEI-Ag NCs/DNA complexes yields greatly enhanced RRS signals; however, when PEI-Ag NCs react with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At the same concentration, the enhancement of RRS signal is directly proportional to the length of telomere, and the sensitivity of 64 bases is the highest with the linear range of 0.3-50 nM (limit of detection 0.12 nM). On the other hand, due to the conversion of telomere DNA molecules among multiple surrounding conditions, a DNA logic gate is developed on the basis of two chemical input signals (K+ and H+) and a change in RRS intensity as the output signal. CONCLUSION: Our results indicate that PEI-Ag NCs can serve as a novel RRS probe to identify DNA length and monitor G-quadruplex/i-motif through the different increasing degrees of RRS intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to those involving dyes or labeled DNA because of no chemical modification, low cost, green, and high efficiency.

Simultaneous Detection of Adenosine Triphosphate and Glucose Based on the Cu-Fenton Reaction.

Both adenosine triphosphate (ATP) and glucose are important to human health, and their abnormal levels are closely related to angiocardiopathy and hypoglycaemia. Therefore, the simultaneous determination of ATP and glucose with a single test mode is highly desirable for disease diagnostics and early recognition. Herein, a new fluorescence on/off switch sensing platform is developed by carbon nanodots (CNDs) to detect ATP and glucose simultaneously. The fluorescence of CNDs can be quenched by Cu2+ and hydrogen peroxide (H2O2), due to the formation of hydroxyl radicals (·OH) produced in the Cu-Fenton reaction. Based on the high affinity of Cu2+ with ATP, the fluorescence of CNDs will recover effectively after adding ATP. Additionally, glucose can be efficiently catalyzed by glucose oxidase (GOx) to generate H2O2, so the platform can also be utilized to analyze glucose. Under optimum conditions, this sensing platform displays excellent sensitivity and the linear ranges are from 0.1 to 7 μM for ATP with a limit of detection (LOD) of 30.2 nM, and from 0.1 to 7 mM for glucose with a LOD 39.8 μM, respectively. Benefiting from the high sensitivity and selectivity, this sensing platform is successfully applied for simultaneous detection of ATP and glucose in human serum samples with satisfactory recoveries.

Extent of compassion satisfaction, compassion fatigue and burnout in nursing: A meta-analysis.

AIMS: A meta-analysis was conducted of the prevalence rates of compassion satisfaction, compassion fatigue and burnout to identify the factors influencing these rates. BACKGROUND: The extents of compassion fatigue and burnout adversely affect nursing efficiency. However, the reported prevalence rates vary considerably. METHODS: Data were acquired from electronic databases. Random effects meta-analyses were performed to obtain pooled estimates of the prevalence rates of compassion satisfaction, compassion fatigue and burnout and their respective instrumental scores. Meta-regression analyses were performed to identify factors influencing these rates. RESULTS: Data from 21 studies were used for the meta-analysis. The prevalence rates of compassion satisfaction, compassion fatigue and burnout were 47.55%, 52.55% and 51.98%, respectively. The possession of Bachelor's or Master's degrees by the nurses was significantly inversely associated with the percent prevalence of compassion fatigue (coefficient: -1.187) and burnout (coefficient: -0.810). The compassion fatigue score was also significantly inversely associated with nursing status as registered or licensed practical nurse (coefficient: -0.135). CONCLUSION: In nursing, the prevalence rates of compassion fatigue and burnout are high. Better education and training may have a moderating effect on compassion fatigue and burnout and could improve the quality of life of nurses.

Interleukin-1ß Promotes Epithelial-Derived Alveolar Elastogenesis via αvß6 Integrin-Dependent TGF-ß Activation.

BACKGROUND/AIMS: IL-1ß creates persistent pulmonary inflammation accompanied by elevated transforming growth factor ß (TGF-ß levels and is associated with abnormal elastogenesis, which is observed in bronchopulmonary dysplasia (BPD). Although progress has been made in this field, the mechanisms underlying this process remain only partially understood. METHODS: We assessed aberrant elastin localization-associated signaling in mouse pups exposed to 85% O2 treated with either IL-1Ra or 1D11, using morphometric analyses, quantitative RT-PCR, immunostaining, and ELISA. We also evaluated the derivation of elastin-producing cells using dual marker tracking. The regulatory mechanisms of IL-1ß were investigated in vitro in lung epithelial and mesenchymal cells. RESULTS: Elevated levels of IL-1ß, αvß6 and TGF-ß1 were each associated with aberrant elastin production in O2-exposed lungs. IL-1Ra abolished TGF-ß1 activation and αvß6 upregulation, which occurred as a result of exposure to hyperoxia, whereas 1D11 had no discernible effect on the expression of either αvß6 or IL-1ß even following O2-exposure, suggesting that IL-1ß was initially induced. Additionally, double staining revealed the presence of epithelium-derived elastin-producing cells, which was confirmed via in vitro IL-1ß stress-induced epithelial-mesenchymal transformation (EMT) morphological and molecular marker changes, which may explain the altered lung elastin deposition and defective septation observed in BPD. CONCLUSIONS: These data support the hypothesis that IL-1ß was initially induced by hyperoxia; αvß6 subsequently interacted with and activated TGF-ß1, acting as an epithelial/mesenchymal signaling molecule that contributed to excessive alveolar elastogenesis, the primary pathological feature of BPD.

Aberrant elastin remodeling in the lungs of O2-exposed newborn mice; primarily results from perturbed interaction between integrins and elastin.

Excessive localization of elastin from septal tips to alveolar walls is a key feature of bronchopulmonary dysplasia (BPD). The abnormal accumulation of lung elastin, involving the structural and functional interaction of a series of proteins, remains poorly understood. To further investigate the mechanisms accounting for the abnormal accumulation of elastin in the lungs of newborn mice with BPD, we evaluate elastin distribution and its interaction with proteins involved in its aberrant localization, such as integrin αv, fibulin-5 and transforming growth factor ß1 (TGF-ß1), in lungs of newborn mice exposed to 60% O2 for 21 days. Lung histology revealed aberrant elastin production and impaired lung septation in O2-exposed lungs, while tropoelastin, integrin αv, fibulin-1, fibulin-2 and fibulin-4 gene expression were elevated. Dual staining image analysis of lung sections revealed that co-localization of integrin αv and elastin increased following O2 exposure with elastin distributed throughout the walls of air spaces rather than at septal tips. Furthermore, integrin αv appeared to be induced initially. Concurrently, increased fibulin-5 and TGF-ß1 (which may regulate elastic fiber assembly) expression was detected, which may explain the altered lung elastin deposition and defective septation that are observed during BPD. These data support the hypothesis that excessive and aberrant αv integrin expression was initially induced by hyperoxia; αv integrin then interacted with and recruited elastin. These alterations were accompanied by fibulin-5 deposition and TGF-ß1 activation, which may impede normal matrix remodeling, thereby contributing to the pathological pulmonary features of BPD.

Pharmacokinetics of single- and multiple-dose emtricitabine in healthy male Chinese volunteers.

Emtricitabine (FTC) is used for the treatment of HIV infection and pre-exposure chemoprophylaxis. It is often used in combination with tenofovir disoproxil fumarate (TDF). This study was designed to evaluate FTC pharmacokinetics in healthy male Chinese volunteers. Sixty subjects were recruited into this single-centre, randomised, open-label study and randomly received single (groups A, B and C) or multiple oral doses (once daily for 6 days; groups D, E and F) of 200-mg FTC capsules alone (A and D), or combined with 300-mg TDF tablets (B and E), or 200 mg of FTC plus 300 mg of TDF with a high-fat diet (C and F), respectively. FTC was well-tolerated in all groups. After a single dose, there were no differences in the mean AUC0-∞ values; however, there were significant differences in the mean Tmax values (1.05, 1.40 and 2.10 h for groups A, B and C, respectively; p < 0.05). In the multiple-dose study, our results were significantly different from published t1/2 values following single-dose FTC.

The safety of maxillary sinus floor elevation and the accuracy of implant placement using dynamic navigation.

OBJECTIVE: To date, it remains a challenge to conduct maxillary sinus floor elevation (MSFE) owing to heterogeneity of anatomical structures and limited operative visibility of the maxillary sinus. The aim of this study is to investigate the safety of MSFE and the accuracy of implant placement using dynamic navigation. METHODS: Forty-two implants were placed in thirty-five patients requiring implantation in posterior maxilla with dynamic navigation. They were assigned to either lateral window sinus floor elevation (LWSFE) group (n = 22) or transcrestal sinus floor elevation (TSFE) group (n = 20) according to the residual alveolar bone height (RBH). Platform deviation, apex deviation and angular deviation between actual and planned implant placement were measured in precision evaluation software. Three deviations of two groups were compared via SPSS 22.0 software. RESULTS: Neither accidental bleeding nor perforation of Schneiderian membrane occurred in any patients. The actual window position of LWSFE was consistent with the preoperative design. There were no significant differences in platform, apex and angular deviations between the two groups (P > 0.05). CONCLUSION: In this study the dynamic navigation harvested clinically acceptable safety of MSFE and accuracy for implant placement in posterior maxillary region. The dynamic navigation would provide the clinician with assistance in achieving precise preoperative planning and reducing complications in surgical procedures. The granular bone grafts used in the LWSFE did not significantly affection on the accuracy of the simultaneous implant placement under the guidance of dynamic navigation.

Hydrogel-Transformable Antioxidant Poly-γ-Glutamic Acid/Polyethyleneimine Hemostatic Powder for Efficient Wound Hemostasis.

Hemostatic powder, which can absorb large amounts of water and tends to produce repeated hydration with tissue, has been clinically proven as an ideal engineering material for treating wounds and tissues. We herein designed a polypeptide-based hemostatic powder. A water-soluble polypeptide, γ-polyglutamic acid (γ-PGA), was mixed with the polyethyleneimine (PEI), N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide. The solution of these polymers was lyophilized to harvest the γ-PGA/PEI powder (PP hemostatic powder). When deposited on a bleeding wound, the PP hemostatic powder can quickly absorb a large amount of blood and interstitial fluid, concentrate coagulation factors, coagulate blood cells, and eventually form a stable mechanical hydrogel. The wound bleeding time of the PP hemostatic powder group was 1.8 ± 0.4 min, significantly lower than that of the commercial chitosan hemostatic powder group (2.8 ± 0.4 min). The PP hemostatic powder was endowed with antioxidant capacity by introducing protocatechuic aldehyde, which can effectively inhibit inflammation and promote wound healing. Therefore, via preparation through a facile lyophilization method, the PP hemostatic powder is expected to find a wide application prospect as a qualified hemostatic powder.

The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing.

BACKGROUND: Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified. METHODS: In our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups. RESULTS: Our results showed that totally 20 gut microbes were significantly different between two groups (p<0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p<0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p<0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p<0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p<0•05). CONCLUSION: In this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.

Advances in Hemostatic Hydrogels That Can Adhere to Wet Surfaces.

Currently, uncontrolled bleeding remains a serious problem in emergency, surgical and battlefield environments. Despite the specific properties of available hemostatic agents, sealants, and adhesives, effective hemostasis under wet and dynamic conditions remains a challenge. In recent years, polymeric hydrogels with excellent hemostatic properties have received much attention because of their adjustable mechanical properties, high porosity, and biocompatibility. In this review, to investigate the role of hydrogels in hemostasis, the mechanisms of hydrogel hemostasis and adhesion are firstly elucidated, the adhesion design strategies of hemostatic hydrogels in wet environments are briefly introduced, and then, based on a comprehensive literature review, the studies and in vivo applications of wet-adhesive hemostatic hydrogels in different environments are summarized, and the improvement directions of such hydrogels in future studies are proposed.

[Comparison of shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals].

PRUPOSE: To compare the shaping ability of 4 nickel-titanium rotary instruments in preparation of curved root canals. METHODS: Forty extracted human maxillary first or second molars with mesiobuccal root canal curvature ranging from 20°-40° were selected. The teeth were randomly equally divided into 4 groups(n=10). Mesial root canals were separately prepared using Protaper Universal, Protaper Next, TF, and S3 nickel-titanium instruments. A series of preoperative and postoperative images were taken by Micro-CT． Mimics 17.0 software was used to analyze the following parameters: canal transportation, centering ratio values, root canal volume, volume of removed dentin, and canal/root width ratio. Data analysis was performed by using SPSS 20.0 software package. RESULTS: In terms of canal transportation after preparation at 1, 3 and 5 mm from the apex, Protaper Universal was more than the other three groups(P＜0.05). The centering ratio value of Protaper Universal was significantly smaller than that of the other three groups at 1 mm from the apex(P＜0.05). The amount of dentin removal was significantly different after instrumentation with the four test systems(P＜0.05). Protaper Universal had the highest mean volume of removed dentin. After preparation, all root canals had a diameter that was not larger than 39% of the root diameter at the coronal and middle segments. CONCLUSIONS: Under the conditions of this study, Protaper Next, TF, S3 systems seem to be better choices than Protaper Universal system in preparing curved root canals.

Maternal Inflammation Exaggerates Offspring Susceptibility to Cerebral Ischemia-Reperfusion Injury via the COX-2/PGD2/DP2 Pathway Activation.

The pathogenesis of cerebral ischemia-reperfusion (I/R) injury is complex and does not exhibit an effective strategy. Maternal inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We aimed to investigate the effect of maternal inflammation on offspring susceptibility to cerebral I/R injury and the mechanisms by which it exerts its effects. Pregnant SD rats were intraperitoneally injected with LPS (300 µg/kg/day) at gestational days 11, 14, and 18. Pups were subjected to MCAO/R on postnatal day 60. Primary neurons were obtained from postnatal day 0 SD rats and subjected to OGD/R. Neurological deficits, brain injury, neuronal viability, neuronal damage, and neuronal apoptosis were assessed. Oxidative stress and inflammation were evaluated, and the expression levels of COX-2/PGD2/DP pathway-related proteins and apoptotic proteins were detected. Maternal LPS exposure significantly increased the levels of oxidative stress and inflammation, significantly activated the COX-2/PGD2/DP2 pathway, and increased proapoptotic protein expression. However, maternal LPS exposure significantly decreased the antiapoptotic protein expression, which subsequently increased neurological deficits and cerebral I/R injury in offspring rats. The corresponding results were observed in primary neurons. Moreover, these effects of maternal LPS exposure were reversed by a COX-2 inhibitor and DP1 agonist but exacerbated by a DP2 agonist. In conclusion, maternal inflammatory exposure may increase offspring susceptibility to cerebral I/R injury. Moreover, the underlying mechanism might be related to the activation of the COX-2/PGD2/DP2 pathway. These findings provide a theoretical foundation for the development of therapeutic drugs for cerebral I/R injury.