Search

Represented herein is a new manner to form fluorenones via direct excitation of substrate instead of photocatalyst to activate sp2 C-H bond under redox-neutral condition. Our design relies on the photoexcited triplet state of aromatic aldehyde intermediates with higher reactivity that can be intercepted by cobaloxime catalyst through single electron transfer for following β-H elimination. The simple generation of acyl radical and successful interception by a metal catalyst cobaloxime avoid the use of both photocatalyst and stoichiometric external oxidants, affording a series of highly substituted fluorenones, even for six-membered ketones, such as xanthone and thioxanthone derivatives in good to excellent yields, and H2 is as the only byproduct. This catalytic system features the readily available metal catalyst, mild reaction conditions and broad substrate scope, in which sunlight reaction and scale-up experiment by the continuous-flow approach make the developed methodology sustainable and amenable for potentially operational procedures.

Laser beam offset welding of GH3128 and molybdenum (Mo) dissimilar joints was studied with an emphasis on the role of laser beam offset (LBO). It was found that the change of LBO significantly affected the properties of GH3128/Mo dissimilar joints. When the LBO increased from − 0.1 mm (i.e., laser spot was centered on Mo surface) to + 0.3 mm (i.e., laser spot was centered on GH3128 surface) at the step size of 0.1 mm, the amount of melted Mo gradually declined; the welding mode gradually changed from fusion welding to welding–brazing; macro-segregation of Mo-rich phases in fusion zone (FZ) gradually disappeared; the average microhardness of FZ significantly decreased, and therefore, microhardness distribution in FZ became more uniformly; the quantity of grain boundary liquation observed in heat-affected zone (HAZ) of GH3128 side gradually decreased; and recrystallization of grains in the HAZ of Mo was gradually suppressed. Joints with the optimal LBO of + 0.2 mm reached the maximum tensile strength of about 560 MPa. When using a small LBO, i.e., LBOs were + 0.1, 0, − 0.1 mm, the HAZ of Mo was greatly softened and embrittled. When adopting a large LBO, i.e., LBO was + 0.3 mm, the melt near Mo-FZ interface might fail to moisten Mo surface and spread on Mo surface, thus resulting in the reduction in tensile strength.

OBJECTIVE: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. METHODS: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter

Aims The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach. Methods Pharmacokinetic samples were collected from 99 Chinese newborns with premature apnoea. The median (range) of gestational age and postmenstrual age were 28.3 (25.0-33.4) weeks and 31.1 (26.4-38.0) weeks, respectively. Newborns were receiving caffeine citrate at a loading dose of 20 mg/kg/d and a maintenance dose of 5-10 mg/kg/d. Caffeine concentrations and CYP1A2 polymorphisms were investigated. Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population-wide scale was conducted using NONMEM. Results A 1-compartment model with first-order elimination was used to describe population pharmacokinetic. With current weight implemented using 0.75 allometric scaling, clearance (CL) was positively related to current weight and postmenstrual age, but a negative relationship was observed with serum creatinine concentration. Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters. Interindividual variability of CL and volume of distribution was 7.70 and 65.9%. The median (range) of 95% confidence intervals of CL were 0.0128 (0.0128-0.0131) L/h/kg. Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5-20 mg/L. Conclusion A population PK model of caffeine was developed in Chinese newborns. Body weight-implemented allometric scaling, postmenstrual age and serum creatinine concentration markedly affected caffeine clearance. The labelled dosing regimen is suitable for Chinese premature infants.

Purpose Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma. Methods Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS). Results The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53). Conclusions DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma.

Joining technology for zirconium (Zr) and molybdenum (Mo) dissimilar joints exerts significance on innovative design of nuclear power equipment. Fiber laser beam welding (LBW) of Zr-Mo dissimilar joints with and without Ti insert were welded in butt configuration with one centered pass. It was found that a transition layer containing brittle Mo2Zr phase with the thickness of about 2 μm formed at the interface of Mo and welded seam zone (FZ) after LBW. Transverse cracks and significant macro-segregation were observed in the FZ. Moreover, plenty of needle-like α' phases alternatively distributed in β phase matrix were found in FZ where the average microhardness was about 350 HV, which was significantly higher than those of base metals (BMs) of Mo (250 HV) and Zr (130 HV). The tensile strength of the welded joint was about 76 MPa and appeared the mixed of inter- and trans-granular fracture mode. Noting that titanium (Ti) exhibited a favorable metallurgical compatibility with both base metals (Zr and Mo), a pure Ti interlayer with width of 1 mm was inserted into the Zr/Mo interface to further conduct welding. It was found that, by adding Ti interlayer, macro-segregation in FZ was inhibited, needle-like microstructures in FZ greatly reduced and the average microhardness of FZ decreased to about 253 HV. During the tensile test, the joint with Ti addition was fractured in BM of Zr and showed the tensile strength of about 321 MPa.

OBJECT Peritumoral brain edema (PTBE) is a common phenomenon associated with high-grade gliomas (HGGs). In this study, the authors investigated the expression of Notch delta-like ligand 4 (DLL4) and its correlation with PTBE and prognosis in patients with an HGG. METHODS Tumors from 99 patients with HGG were analyzed for DLL4 expression using immunohistochemistry. PTBE on preoperative MR images and the relationship between PTBE and DLL4 expression were evaluated. The effect of DLL4 on patient prognosis was assessed by using Kaplan-Meier survival and Cox proportional hazard models. RESULTS Immunohistochemistry results revealed that the expression of DLL4 was distributed primarily within the cytoplasm of tumor vascular endothelial cells and seldom detected in tumor cells. DLL4 expression was correlated positively with the degree of edema (r = 0.845 and p < 0.001, Spearman’s test). In addition, DLL4 was an independent predictor of prognosis in patients with HGGs (p = 0.001). CONCLUSIONS DLL4 expression was correlated positively with the degree of PTBE and was an independent unfavorable prognostic indicator in patients with HGG.

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by increased medial and adventitial thickness of the lung vasculature. The underlying mechanisms that regulate the cell phenotype alteration during PPHN remodeling are largely unknown. We randomly selected newborn rats that were exposed to hypoxia (10-12%) or room air for 2 weeks and used a microarray to identify the lung tissue microRNAs (miRNAs) involved in PPHN progression. The role of a key miRNA that affects the endothelial-to-mesenchymal transition (EndMT) in primary cultured rat pulmonary microvascular endothelial cells (RPMECs) was investigated. The expression of miR-126a-5p was elevated in the PPHN model according to microarray analysis. The relative expression of miR-126a-5p in RPMECs increased when they were exposed to hypoxia (P0.05), consistent with the microarray results. Pecam1 expression decreased, whereas alpha-smooth muscle actin (α-SMA) increased in the hypoxic RPMECs. Knockdown of miR-126a-5p in RPMECs followed by treatment with hypoxia for 48 h resulted in a significant increase in the expression of Pecam1 and a reduction in α-SMA expression, with a simultaneous increase in PI3K (p85β) and phosphorylation of AKT at serine 473 compared with the negative control. Finally, the circulating miR-126a-5p concentration was upregulated in the PPHN model compared with healthy neonates. We concluded that hypoxia changed the cell homeostasis and that miR-126a-5p was upregulated in PPHN, which is partly responsible for hypoxia-induced EndMT. The mechanism underlying the upregulation of miR-126a-5p by hypoxia probably acts through the p85-β/p-AKT pathway.

Objective To investigate the factors influencing the prognosis of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants. Methods A total of 194 VLBW infants who were admitted from January 2012 to December 2014 were enrolled as study subjects. According to cardiac ultrasound findings and treatment outcome, these infants were divided into non-PDA group, spontaneous closure group, pharmaceutical closure group, and surgical closure group. Their clinical and echocardiographic characteristics were analyzed. Results The spontaneous closure rate of PDA was 58.7%. The spontaneous closure group showed significantly higher gestational age, birth weight, and proportion of small-for-gestational-age infants than the pharmaceutical and surgical closure groups (P < 0.05). The pharmaceutical and surgical closure groups had a significantly higher incidence rate of neonatal respiratory distress syndrome and a significantly higher proportion of infants who were given pulmonary surfactant (PS) than the spontaneous closure group (P < 0.05). During different periods of time, the spontaneous closure group had a significantly smaller ductus arteriosus diameter than the pharmaceutical and surgical closure groups (P < 0.05). The multivariate logistic regression analysis showed that gestational age, application of PS, and ductus arteriosus diameter at 48 hours were significantly associated with the prognosis of PDA. The major transductal flow pattern in the spontaneous closure group was closing pattern, while in the pharmaceutical and surgical closure groups, the main flow patterns were pulmonary hypertension and growing patterns within 48 hours and growing pattern on days 4 and 7. Conclusions The VLBW infants have a high spontaneous closure rate of PDA. A decreased closure rate of PDA is associated with the lower gestational age and the application of PS. PDA with a large ductus arteriosus diameter and a growing or pulsatile flow pattern cannot easily achieve spontaneous closure.