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The path-selectivity and stereoselectivity of gridization pathways into fluorene-based drawing hand grids (DHGs-F) are precisely modulated through tuning acid conditions and side-chain effects. BF3·OEt2 supports the realization of the gridization path (rac-DHG1-F, yield: 82%, meso-DHG1-F, yield: 11%). On the contrary, CF3SO3H will lead to the enhancements in polymerization pathways (about 85% yield). When the side chain is a methoxyl group, rac-DHG1-F and meso-DHG1-F will be obtained. However, when the side chain is a group without an oxygen atom, only rac-DHGs-F can be obtained (de = 100%). Moreover, through excitonic physical properties, rac-DHGs-F exhibits a more π-electronic delocalization, potentially serving as the intriguing tactic strategy to modulate the optoelectronic properties.

Two novel meso-CF3 BODIPY-based fluorescent rotors are rationally prepared and sensitively respond to cellular viscosity through restricted rotation of meso-CF3 group. The monostyryl one (2) exhibits good mitochondrial localization and AIE property.

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (

Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.

An efficient method was developed for synthesis of 2,3-diarylbenzofuran-4-carboxylic acids from m-hydroxybenzoic acids and alkynes via Ru-catalyzed C–H alkenylation and aerobic annulation, in which air was employed as a mild oxidant. This method is compatible for various substrates with high regioselectivity for the C–H bonds. The obtained products can be transformed to polycyclic compounds via intramolecular Friedel–Crafts acylation. This protocol was successfully applied for total synthesis of diptoindonesin G, a natural product with a benzofuran-containing tetracyclic scaffold and potent biological activities.

Alzheimer's disease (AD), known as a common incurable and elderly neurodegenerative disease, has been widely explored for accurate detection of its biomarker (Aβ oligomers) for early diagnosis. Although great efforts have been made, it is still of great importance to develop fluorescence probes for Aβ oligomers with good selectivity and low background. Herein, starting from BODIPY493/503 (a commercial dye for neutral lipid droplets), which exhibited a small Stokes shift and no response toward Aβ peptides, two fluorescence probes

Sodium-ion batteries (SIBs) are recognized as attractive alternatives for grid-scale electrochemical energy storage applications. Transition metal oxide cathodes represent one of the most dynamic materials for industrialization among the various cathodes for SIBs. Here, a cation-doped cathode Na

Conditioned place preference (CPP) is a learned behavior, in which animals learn to associate environmental contexts with rewarding effects. The formation of CPP is an integrated outcome of multiple learning processes. Although multiple anatomical substrates underlying this contextual learning have been proposed, it remains unknown whether a specific molecular signaling pathway within CA1 mediates context learning associated with morphine conditioning. Here, we showed that repeated context learning associated with morphine conditioning significantly increased CXCL12 levels in hippocampal CA1 neurons, and the inhibition of CXCL12 expression ameliorated the CPP behavior following context exposure with morphine conditioning. Additionally, repeated context exposure with morphine conditioning increased the phosphorylation of STAT3 and the acetylation of histone H4 in CXCL12-expressing neurons in CA1. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that repeated context exposure with morphine conditioning increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in the CXCL12 gene promoter. The inhibition of STAT3 by intrathecal injection of S3I-201 suppressed the acetylation of histone H4. These data demonstrated the epigenetic upregulation of CXCL12 following repeated context exposure with morphine conditioning, which potentially contributed to the spatial memory consolidation associated with conditioned place preference induced by morphine conditioning.

Two novel

Hypochlorous acid/hypochlorite (HOCl/ClO

BACKGROUND: Effective cellulose hydrolysis has a huge potential for producing high value‐added biomass‐based platform chemicals, such as glucose, hydroxymethylfurfural, levulinic acid, and total reducing sugars (TRS). Particularly, a magnetic multifunctional solid acid catalyst (Fe₃O₄/Cl–MCMB–SO₃H) was synthesized by loading the active groups on the magnetic mesocarbon microbead (MCMB) derived from the co‐calcination of coal tar pitch and ferroferric oxide, which was applied as a catalyst in the conversion of cellulose into TRS. RESULTS: Given the superior properties of MCMB, a novel magnetic MCMB‐based solid acid with cellulose‐binding domain (–Cl group) and catalytic domain (–SO₃H group) was successfully prepared. Results indicated that this catalyst exhibited superior catalytic activity, recyclability and regenerability, and easy separation from the reactant. The acidic densities of –SO₃H and –Cl in Fe₃O₄/Cl–MCMB–SO₃H reached 1.77 and 1.32 mmol/g, respectively. The 68.6% TRS yield can be obtained from cellulose at 140 °C for 3 h in distilled water by using Fe₃O₄/Cl‐MCMB‐SO₃H as the catalyst. The TRS yield still reached 61.1% after the catalyst was used six times. Importantly, through catalyst regeneration, the –SO₃H density and TRS yield still reached 1.69 mmol/g and 67.3%, indicating that the catalyst exhibited excellent regenerability. CONCLUSION: Such multifunctional magnetic catalyst would be a promising catalyst in the conversion of cellulose into biofuels, which was attributed to the efficient catalytic performance, magnetism, and excellent recyclability and regenerability. © 2019 Society of Chemical Industry

Anion-doping strategy represents one efficient route to adjust the structure of electrode material for advanced reversible batteries. The work herein obtains an optimized F-doping sodium manganese oxide Na0.44MnO1.93F0.07 with a layer-tunnel hybrid structure, and the essential factors such as synthesis temperature and crystal structure which determine the electrochemical behavior for the F-doping cathode materials are systematically explored and investigated. The optimized cathode Na0.44MnO1.93F0.07 prepared at 900 °C for 3 h, among various Na0.44MnO2−xFx samples, delivers an extraordinary discharge capacity of 149 mA h g−1 and 138 mA h g−1 at 0.5 C and 1 C, respectively. In addition, the electrode displays an impressive cycling stability with a superb capacity retention rate of approximately 79% over 400 cycles at 5 C. And thus, it shows enhanced reversible capacity over the tunnel phase Na0.44MnO2. Therefore, this work provides a new avenue for designing and optimizing the advanced cathode materials with superior electrochemical performance for sodium-ion batteries by introducing halogen anions to modify the structure.

A novel H-shaped nonlinear optical chromophore B based on julolidinyl donors were designed and synthesized through Williamson ether reaction. The chromophore B is composed of two traditional rod-shaped chromophores A linked to each other through an isolation group, forcing chromophore separation through steric interaction. Chromophore B showed good thermal stability and film-forming ability. Besides, the reduction of intermolecular electrostatic interactions allows for increased active chromophore number density in the formulation of a host-guest doping material, thus enhancing electro-optic response. Polymers doped with 35 wt% chromophore B have been poled to afford large electro-optic coefficient (r33) of 180 pm/V at 1310 nm, which is nearly two times higher than that obtained from the chromophore A (92 pm/V) at the doping concentration of 25 wt%. These results indicated that the H-shaped chromophore B has the advantages over rod-shaped chromophore A in transforming the microscopic hyperpolarizability into a macroscopic electro-optic coefficient.

A near-infrared distyryl boron dipyrromethene-based sensor bearing one bis(1,2,3-triazole)amino receptor has been synthesized. This probe selectively and quickly binds to Hg2+ and Cu2+ ions in CH3CN/H2O (5:1 v/v) and exhibits remarkably blue-shifted absorption and fluorescence bands due to the inhibition of the intramolecular charge transfer process. The fluorescence changes of this probe upon binding to Hg2+ or Cu2+ ion are totally different, undergoing a ratiometric fluorescence enhancement (for Hg2+) or a fluorescence quenching (for Cu2+) mechanism. The corresponding vivid color changes can be easily seen by the naked eye. This probe was further introduced into Hela cells for living cell imaging and found to discriminate Hg2+ and Cu2+ ions through two near-infrared fluorescence emission channels. These overall results indicate that this Click-derived near-infrared BODIPY-based probe is potentially useful for ratiometric and discriminative detection of Hg2+ and Cu2+ ions in solutions and living cells.

By using a copper-promoted alkyne-azide cycloaddition reaction, two boron dipyrromethene (BODIPY) derivatives bearing a bis(1,2,3-triazole)amino receptor at the meso position were prepared and characterized. For the analogue with two terminal triethylene glycol chains, the fluorescence emission at 509 nm responded selectively toward Hg2+ ions, which greatly increased the fluorescence quantum yield from 0.003 to 0.25 as a result of inhibition of the photoinduced electron transfer (PET) process. By introducing two additional rhodamine moieties at the termini, the resulting conjugate could also detect Hg2+ ions in a highly selective manner. Upon excitation at the BODIPY core, the fluorescence emission of rhodamine at 580 nm was observed and the intensity increased substantially upon addition of Hg2+ ions due to inhibition of the PET process followed by highly efficient fluorescence resonance energy transfer (FRET) from the BODIPY core to the rhodamine moieties. The Hg2+ -responsive fluorescence change of these two probes could be easily seen with the naked eye. The binding stoichiometry between the probes and Hg2+ ions in CH3 CN was determined to be 1:2 by Job's plot analysis and 1 H NMR titration, and the binding constants were found to be (1.2±0.1)×1011 m-2 and (1.3±0.3)×1010 m-2 , respectively. The overall results suggest that these two BODIPY derivatives can serve as highly selective fluorescent probes for Hg2+ ions. The rhodamine derivative makes use of a combined PET-FRET sensing mechanism which can greatly increase the sensitivity of detection.

Four nonlinear optical chromophores A–D based on the thiolated-isophorone-derived bridge have been synthesized and systematically investigated. In particular, both the donor and bridge sections of the chromophores were functionalized with different isolation groups including tert-butyltrimethylsilane, tert-butyl(methyl)diphenylsilane, benzene ring and 1,2,3,4,5-pentafluorobenzene ring, respectively. All these four chromophores showed high thermal stabilities with decomposition temperatures above 220 °C. Most importantly, the rigid steric hindrance groups can effectively reduce the intermolecular electrostatic interactions to transform their hyperpolarizabilities into large electro-optic (EO) coefficients (r33). Polymeric thin films doped with 30 wt% chromophores A–D have been poled to afford large r33 values of 96, 143, 115, and 109 pm V−1 at 1.31 μm, respectively. Electro-optic performance together with density functional theory (DFT) calculations suggests that the isolation groups show different effects on the hyperpolarizability and poling efficiency of chromophores. The normalized r33 value of chromophore B increased to 8.36 × 10−19 pm cc per (V molecules) indicating the largest steric hindrance group and the highest polarization efficiency. All these results provide valuable insight into the understanding of the impact of isolation groups on macroscopic EO activities of materials.

In this work, a novel Cu(I) coordination polymer, Cu2LBr2 (1) based on a pyridyl-functionalized resorcin[4]arene [L = (2,8,14,20-tetraethyl-4,10,16,22-tetra kis((2-pyridylmethylene)oxy)-6,12,18,24-tetramethoxy-resorcin[4]arene)] has been synthesized under solvothermal condition. 1 was characterized by various physicochemical analyses and it shows a ribbon structure. Notably, 1 exhibits an outstanding thermal stability. 1 possesses strong luminescent property, and can selectively probe Cr2O72−, MnO4− and nitrobenzene via luminescent quenching. In addition, 1 is an efficient catalyst for azide–alkyne cycloaddition reaction.

In order to reveal the nature of intercalative binding of drug to DNA, the cooperativity effect of the π⋯π interaction was investigated in the curcumin⋯adenine⋯H2O model system by applying a combined QM and QTAIM computational approach. The H-bonds between the electron-donating group of curcumin and adenine induce the formation of the π⋯π stacking. The introduction of H2O weakens the H-bonding and π⋯π interactions, leading to an anti-cooperativity effect, as is confirmed by the AIM (atoms in molecules) and RDG (reduced density gradient) analysis. Thus, it can be inferred that the anti-cooperative effect is the main driving force for the intercalative binding of drug to DNA bases, which is in agreement with many experimental phenomena. Therefore, the designed DNA-targeted intercalating drugs should possess not only hydrophobic moieties, but also strong electron-donating groups bound to the DNA bases with H-bonds, which can slow the variation rates of the strengths of the H-bonding and π⋯π interactions between drug and DNA bases in the anti-cooperative process, leading to the intercalation formation. The enthalpy change is the major factor driving the positive thermodynamic cooperativity.

A novel near-infrared-emitting aza-BODIPY-based fluorescent probe with two tellurium atoms at two upper benzyl rings has been prepared and explored for its fluorescent sensing properties towards hypochlorous acid/hypochorite (HClO/ClO−), which showed high selectivity and absolutely fluorescent “turn-on” phenomenon at 738 nm. The fluorescence of this probe was sufficiently quenched due to photoindued electron transfer by two tellurium atoms. Upon exposure to HClO/ClO−, a strong near-infrared emission at 738 nm appeared with fluorescence quantum yields changing from 0 to 0.11. This remarkable fluorescence change was ascribed to the oxidation of both electron-rich tellurium atoms. The detection limit of this probe towards HClO/ClO− was calculated to 0.09 μM in acetonitrile aqueous solution by the linear fluorescence change at 738 nm in the HClO/ClO−-concentration range of 0–30 μM. Interestingly, this probe was found to be applicable in a broad pH range (2–10). Meanwhile, the oxidized probe could be further responsive to biothiols with substantial fluorescence disappearance. The bioimaging experiments in RAW264.7 cells showed the appearance of intracellular near-infrared fluorescence after addition of HClO/ClO− and PMA, and the fluorescence could also be reversed to be silenced by further introduction of GSH, confirming its potential application for exogenous and endogenous detection of HClO/ClO− in living cells.

Controlling the selectivity of detonation initiation reaction to reduce the explosive sensitivity has been a Holy Grail in the field of energetic materials. The effects of the external electric fields on the homolysis of the N−NO2 bond and initiation reaction dynamics of NH2NO2∙∙∙H2O (i.e., intermolecular and 1,3-intramolecular hydrogen transfers) were investigated at the MP2/6-311++G(2d,p) and CCSD/6-311++G(2d,p)//MP2/6-311++G(2d,p) levels. The results show that the N−NO2 bond is not the “trigger linkage.” The notable transiliences of the activation energy of the intermolecular hydrogen transfer are found with the field strength of − 0.012 a.u. along the −x-direction, leading to the conversion of the main reaction between the intermolecular and 1,3-intramolecular hydrogen transference. The activation energies of two kinds of the hydrogen transferences are increased under the external electric fields along the −y-direction. In particular, due to the conversion of the main reaction, the activation energies of the overall reaction are increased significantly along the −x-direction, leading to the significant reduced explosive sensitivities. Therefore, by controlling the field strengths and orientations between the “reaction axis” and external electric field along the y- and x-directions, the selectivity of the initiation reaction could be controlled and the explosive sensitivity could be reduced. Employing AIM (atoms in molecules) and surface electrostatic potentials, the origin of the control of reaction selectivity and the reduction of sensitivity is revealed. This work is of great significance to the improvement of the technology that the external electric fields are added safely into the energetic material system to enhance the explosive performance.

A new near-infrared (NIR)-emitting aza-boron-dipyrromethene dye with two electron-donating amino groups at 1- and 7-positions has been prepared via several steps of reactions. This probe showed a NIR absorption at 748 nm with an obvious shoulder peak at 634 nm in CH

Controlling the selectivity of detonation initiation reaction to reduce the explosive sensitivity has been a Holy Grail in the field of energetic materials. The effects of the external electric fields on the homolysis of the N-NO

External electric field has been regarded as an effective tool to induce the variation of melting points of molecular crystals. The melting point of 2,4,6-trinitrotoluene (TNT) was calculated by molecular dynamics simulations under external electric field, and the electric field effects on the cooperativity effects of the ternary (TNT)3 were investigated at the M06-2X/6-311+G(d) and ωB97X-D/6-311++G(2d,p) levels. The results show that the melting points are decreased while the intermolecular interactions are strengthened under the external electric fields, suggesting that the intermolecular interactions cannot be used to explain the decreased melting points. A deduction based on the cooperativity effect is put forward: the enhanced cooperativity effects create the more serious defects in the melting process of the molecular crystal under the external electric fields, and simultaneously the local order parameters are decreased, leading to the decreased melting point. Thus, the cooperativity effect stemmed from the intermolecular C-H∙∙∙O H-bonding interactions controls the change of TNT melting point under the external electric field. Employing the information-theoretic approach (ITA), the origin of the cooperativity effects on the melting points of molecular crystal is revealed. This study opens a new way to challenge the problems involving the melting points for the molecular crystal under the external electric fields. However, note that above deduction needs to be improved; after all, the simple (TNT)3 model cannot replace the crystal structure.

Recent studies have indicated the crucial regulator roles of a long non-coding RNA (lncRNA) LINC00673 in cancer pathogenesis and development. However, the clinical significance and functional effects of LINC00673 in cervical cancer remains unknown.LINC00673 mRNA expression in cervical cancer tissues was measured by quantitative Real-time PCR (qRT-PCR), and the association between LINC00673 expression and the overall survival (OS) time of patients was analyzed by Kaplan-Meier survival plot. Cell proliferation was assessed using CCK8 assay, Flow cytometry analysis and cell colony formation assay. The association between miR-126-5p and LINC00673 was clarified by Luciferase activity assay. Furthermore, xenografts model in mice in vivo were used to evaluate the effects of LINC00673 expression on tumor growth of cervical cancer.It was confirmed that the relative mRNA expression of LINC00673 was promoted in cervical cancer tissues and cancer cell lines compared with its corresponding normal tissues and cells (P 0.05). Higher LINC00673 expression was associated with tumor size, lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stage (P 0.05). Survival analysis showed higher LINC00673 expression predicted poor OS of cervical cancer patients, and Multivariate Cox analysis demonstrated that higher LINC00673 expression was identified as an independent risk factor for OS. LINC00673 overexpression promoted cell proliferation and cell cycle progression, but LINC00673 knockdown inhibited cell proliferation and cell cycle progression significantly (P 0.05). Besides, overexpression of LINC00673 was negatively correlated with lower miR-126-5p expression in cervical cancer tissues. In vivo xenograft tumor assay indicated that LINC00673 silencing reduced the tumor volume and weight. Bioinformatics analysis revealed that miR-126-5p targeted 3'-UTR of LINC00673, and LINC00673 promoted cell proliferation by sponging to miR-126-5p in cervical cancer cells. Additionally, it was demonstrated that LINC00673 significantly activated the PTEN/PI3K/AKT signaling pathway in cervical cancer cells.These results provide the evidence that LINC00673 overexpression promotes cervical cancer cells progression through regulating miR-126-5p and activating the PTEN/PI3K/AKT signaling pathway, indicating that LINC00673 may be a potential therapeutic target for cervical cancer treatment.

A series of novel near-infrared-absorbing aza boron dipyrromethenes (aza-BODIPYs) substituted with two electron-donating 4-(dimethylamino)phenylethynyl or 4-(diphenylamino)phenylethynyl groups at the 2- and 6-positions have been synthesized by palladium-catalyzed Sonogashira cross-coupling reactions. It has been found that the introduction of two dodecyloxy chains to the aza-BODIPY skeleton results in improved yield of the coupled products. These compounds have been fully characterized with various spectroscopic methods and elemental analysis. They display a strong Q-band absorption in the near-infrared region (up to 830 nm) and negligible fluorescence emission in toluene. Spectroscopic titration has also been performed for a dimethylamino derivative in chloroform. Upon addition of trifluoroacetic acid, which protonates the amino moieties, the compound shows remarkable ratiometric spectral changes. The Q-band absorption is blue-shifted from 830 to 736 nm and a new fluorescence emission at 756 nm appears, which can be attributed to inhibition of intramolecular charge transfer arising from the amino moieties. The color change from sky-blue to purple can be easily observed by direct visualization.

Sodium-ion batteries (SIBs) have drawn more attention to serve as one of the promising energy storage devices owing to the abundance of sodium resources and similar characters with lithium element. Hard carbon materials derived from biomass or biomass waste have been considered to act as candidate anode materials for SIBs. In this paper, we have successfully prepared curly hard carbon materials using pistachio shells as biomass template via a two-step approach including hydrothermal treatment and following a pyrolysis process at various temperatures. Physical properties of pistachio shell-derived hard carbons (PSHCs) including microstructure, morphology and pore size distribution are evaluated by X-ray diffraction, Raman spectrum and N2 sorption analysis. The PSHCs carbonized at 1000 °C (PSHC-1000) with average micropores of 0.7398 nm and larger interlayer space of the (002) crystal plane deliver the highest reversible capacity of 317 mAh g−1 at 0.1C, also show the excellent long-term cycling and rate performances. Electrochemical impedance spectroscopy technology is introduced to study the kinetics parameters during the first sodiation process of PSHC-1000 electrode, and also to compare the resistance of the charge transfer process for all the PSHCs. Results exhibit PSHC-1000 electrode with the symmetry factor of 0.1352 has the smallest charge transfer resistance, leading to more easily transportation of electrons and ions. This work can provide a simple and green route for preparation of hard carbon materials derived from biomass waste with unique morphology and microstructure which can exhibit an excellent electrochemical performance.

To determine the trend and causes of neonatal mortality in a large level III neonatal intensive care unit in Shanghai during a 15-year period. This is a retrospective, single-centered study. All neonates who died during the period from January 1, 1999 to December 31, 2013 at Children’s Hospital of Fudan University were included. We extracted relevant clinical information from their medical records, analyzed neonatal mortality rate and the characteristics of these patients, and compared neonatal deaths between different periods and populations. Among a total of 50,957 admissions during the study period, there were 929 neonatal deaths. The neonatal mortality rate was 1.82%. Trends in neonatal mortality rate showed an increase in the period from 1.0% in 2003 to 2.2% in 2013. The main causes of neonatal mortality were complications of preterm birth (33.6%), congenital anomalies (21.3%), infections (12.6%), and birth asphyxia (9.1%). The proportions of complications of preterm birth (P

Na0.44MnO2 has aroused global interest as a promising cathode material for sodium ion batteries due to its unique tunnel structure. Rod-like Na0.44MnO2 is synthesized here via a simple, fast and environment-friendly oxalate precursor-based process, and the electrochemical performances, as well as the structural evolution within the electrode redox process and the chemical mechanism for material synthesis, are systematically investigated. The Na0.44MnO2 material prepared at 900 °C for 3 h (denoted as NMO-9003) possesses the highest reversible capacity of 120 mAh g−1 at 0.2 C and an optimal rate capacity of 106 mAh g−1 at 1 C, while its long-term capacity retention is 86% after 500 cycles at 20 C, indicating superior structural reversibility. In addition, the NMO-9003 sample shows the fastest cationic diffusion rate at approximately 1.2 × 10−13 cm2 s−1. The density functional theory (DFT)-based calculation is adopted to explore the lattice variation of Na0.44MnO2 upon the electrode process, which confirms that the host structure bears a minor volume change approximately 7% from 2.0 to 3.8 V, well demonstrating the origin of excellent reversibility.

Several studies have clearly demonstrated a significantly higher incidence of persistent pulmonary hypertension of the newborn (PPHN) in neonates delivered by caesarean section (CS) compared to those delivered vaginally. The pathophysiological factors underlying the link between CS and PPHN are still poorly understood. In this review, we describe the mechanisms that could explain the association between CS delivery and subsequent PPHN, as well as potential preventive measures. A literature search was conducted by electronic scanning of databases such as PubMed and Web of Science using the key words “persistent pulmonary hypertension of the newborn”, “caesarean section”, “iatrogenic prematurity”, “oxidative stress”, “late preterm”, “labor” and “vasoactive agents”. Iatrogenic prematurity, higher rates of late preterm delivery and lack of physiological changes of labor play an important role in the association between CS and PPHN. CS delivery also results in limited endogenous pulmonary vasodilator synthesis and lower levels of protective anti-oxidants in the neonates. In addition, CS delivery exposes infants to a higher risk of respiratory distress syndrome and its concomitant increase in endothelin-1 levels, which might indirectly lead to a higher risk of developing PPHN. We believe that neonates delivered by CS are exposed to a combination of these pathophysiological events, culminating in an endpoint of respiratory distress, hypoxia, acidosis, and delayed transition and thereby increased risks of PPHN. The use of antenatal corticosteroids prior to elective CS in late preterm deliveries, promoting accurate informedconsent process, delaying elective CS to 39 weeks of gestation or beyond and antenatal maternal anti-oxidant supplementation could potentially mitigate the effects of CS delivery and minimize CS-related PPHN. The link between CS delivery and PPHN is complex. In view of the rising rates of CS worldwide, there is an urgent need to further explore the mechanisms linking CS to PPHN and experimentally test therapeutic options in order to allow effective targeted interventions.