An inulin-type fructan CP-A from Codonopsis pilosula alleviates TNBS-induced ulcerative colitis based on serum-untargeted metabolomics.

Ulcerative colitis (UC) is an inflammatory disease with abdominal pain, diarrhea, and bloody stool as the main symptoms. Several studies have confirmed that polysaccharides are effective against UC. It is commonly accepted that the traditional benefits of Radix Codonopsis can be attributed to its polysaccharide contents, and inulin-type fructan CP-A is the main active monomer in the polysaccharide components. Herein, we established a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) to investigate the effect of CP-A on UC. Untargeted metabolomics studies were conducted to identify differential metabolites using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and enrich metabolic pathways in rat serum. The in vivo assays demonstrated that CP-A reduces colonic macroscopic injury, disease activity index (DAI), histopathological score, interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) levels, as well as the expression of intercellular adhesion molecules. On the other hand, CP-A increases IL-10 and transforming growth factor-ß (TGF-ß) levels. The in vitro experiments indicated that CP-A treatment could reduce nitric oxide (NO) and IL-1ß after LPS stimulation. The metabolomics results suggested that CP-A therapy for UC may be related to the mammalian target of rapamycin (mTOR) signaling pathway. The in vitro and in vivo validation of the pathway showed similar results, indicating that CP-A alleviates UC by preventing the activation of mTOR/p70S6K signaling pathway. These findings offer a fresh approach to treating UC and a theoretical foundation for the future advancement of CP-A.NEW & NOTEWORTHY We report that an inulin-type fructan from Codonopsis pilosula CP-A exhibits a therapeutic effect on experimental colitis. Its mechanism may be to alleviate intestinal inflammation by preventing the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. These findings offer a fresh approach to treating ulcerative colitis (UC) and a theoretical foundation for the future advancement of CP-A.

Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial.

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 × 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.

Switching Electrocatalytic Hydrogen Evolution Pathways through Electronic Tuning of Copper Porphyrins.

The electronic structure of metal complexes plays key roles in determining their catalytic features. However, controlling electronic structures to regulate reaction mechanisms is of fundamental interest but has been rarely presented. Herein, we report electronic tuning of Cu porphyrins to switch pathways of the hydrogen evolution reaction (HER). Through controllable and regioselective ß-oxidation of Cu porphyrin 1, we synthesized analogues 2-4 with one or two ß-lactone groups in either a cis or trans configuration. Complexes 1-4 have the same Cu-N4 core site but different electronic structures. Although ß-oxidation led to large anodic shifts of reductions, 1-4 displayed similar HER activities in terms of close overpotentials. With electrochemical, chemical and theoretical results, we show that the catalytically active species switches from a CuI species for 1 to a Cu0 species for 4. This work is thus significant to present mechanism-controllable HER via electronic tuning of catalysts.

Water-Ice Microstructures and Hydration States of Acridinium Iodide Studied by Phosphorescence Spectroscopy.

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5 M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

Sigma-Bond Metathesis as an Unusual Asymmetric Induction Step in Rhodium-Catalyzed Enantiodivergent Synthesis of C-N Axially Chiral Biaryls.

Mechanistic understanding of asymmetric induction plays a crucial role in designing new catalytic asymmetric reactions. Reported herein is atroposelective access to C-N axially chiral isoquinolones via rhodium-catalyzed C-H activation of N-alkoxy benzamides and annulation with imidoyl sulfoxonium ylides. The coupling system proceeded with excellent functional group tolerance, and different conditions were identified to afford one or the other enantiomeric product each in excellent enantioselectivity for a representative class of the sulfoxonium ylide reagent, thus making both enantiomers readily available using the same catalyst. Experimental and computational studies revealed a pathway of C-H alkylation and enantio-determining formal nucleophilic substitution-C-N cyclization that is mediated by the rhodium catalyst via σ-bond metathesis as the asymmetric induction mechanism. Computational studies indicated that the solvent-dependent enatiodivergence originated from different levels of σ-bond metathesis mediated by neutral versus cationic rhodium species.

Long-term outcomes of sirolimus treatment for kaposiform hemangioendothelioma: Continuing successes and ongoing challenges.

Treatment with sirolimus, an inhibitor of the mammalian target of rapamycin pathway, has improved the prognosis of patients with kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0 months. A total of 154 (92.2%) patients had a durable response to sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P = .002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P = .047) were associated with tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of sirolimus persisted over time and that long-term treatment with sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse, tumor relapse and long-term sequelae remained challenges despite intensified and prolonged sirolimus therapy.

Blockage of glycolysis by targeting PFKFB3 suppresses the development of infantile hemangioma.

BACKGROUND: Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. METHODS: Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. RESULTS: PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. CONCLUSIONS: Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.

Laparoscopic Ladd's procedure for intestinal malrotation in small infants with midterm follow-up.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of laparoscopic Ladd's procedure (LL) for intestinal malrotation (IM) in small infants. METHODS: All patients aged < 6 months with IM who underwent Ladd's procedures between January 2012 and December 2019 were enrolled. The perioperative demographics and midterm follow-up results were retrospectively reviewed and compared between patients who underwent LL and open Ladd's operation (OL). RESULTS: Fifty-five patients were enrolled for analysis. The baseline characteristics were well matched in the two groups. The rate of volvulus was similar in the two groups (76.2% vs. 73.5%, P = 0.81). Two cases in the LL group were converted to OL due to intraoperative bleeding and intestinal swelling. The operative time (ORT) was not significantly different between the two groups (73.8 ± 18.7 vs. 66.8 ± 11.6 min, P = 0.76). Compared to the OL group, the LL group had a shorter time full feed (TFF) (3.1 ± 1.2 vs. 7.3 ± 1.9 days, P = 0.03) and a shorter postoperative hospital stay (PHS) than the OL group (5.5 ± 1.6 vs. 11.3 ± 2.7 days, P = 0.02). The rate of postoperative complications was similar in the two groups (9.5% vs. 11.8%, P = 0.47). The LL group had a lower rate of adhesive obstruction than the OL group, but the difference was not significant (0.0% vs. 11.8%, P = 0.09). One patient suffered recurrence in the LL group, while 0 patients suffered recurrence in the OL group (4.8% vs. 0.0%, P = 0.07). The rate of reoperation in the two groups was similar (4.8% vs. 8.8%). CONCLUSIONS: The LL procedure for IM in small infants was a safe and reliable method that had a satisfactory cosmetic appearance and shorter TFF and PHS than OL.

The strategy of laparoscopic surgery for asymptomatic antenatally diagnosed choledochal cyst.

BACKGROUND: The aim was to investigate the characteristics, surgical management, and outcomes of asymptomatic patients with antenatally diagnosed choledochal cysts (ADCCs) and to justify the strategy of laparoscopic surgery (LS) for them in our hospital. METHODS: We developed our LS strategy for asymptomatic ADCCs. Patients with asymptomatic ADCCs who underwent LS or open surgery (OS) during January 2010 and January 2020 were included. Patients with recorded symptomatic ADCCs were exclude. All data of group LS and group OS were statistically compared and analyzed. RESULTS: Twenty-five patients received LS and 18 patients received OS were included. There was no significant difference in baseline characteristics between the groups. A total of 65.1% of biliary sludge formation was detected preoperatively by ultrasonography (US) (72.0% in group LS, 55.6% in group OS, P = 0.26). Compared to the OS group, the LS group had a longer operative time (313.4 ± 27.2 vs. 154.0 ± 11.9 min, P = 0.02), shorter postoperative fasting period (3.1 ± 1.2 vs. 6.2 ± 2.3 days, P = 0.03), and shorter postoperative hospital stay (5.1 ± 1.9 vs. 9.2 ± 1.1 days, P = 0.03). The incidence of late complications, such as reflux cholangitis, adhesive intestinal obstruction, and biliary enteric anastomotic stricture with stone formation, was not significantly different between the two groups. The liver function and liver stiffness of all patients in the two groups were normal. CONCLUSIONS: Based on the strategy for asymptomatic ADCCs in our hospital, the perioperative safety and midterm follow-up results after LS were satisfactory and comparable to those after OS.

Coordination Tuning of Metal Porphyrins for Improved Oxygen Evolution Reaction.

The nucleophilic attack of water or hydroxide on metal-oxo units forms an O-O bond in the oxygen evolution reaction (OER). Coordination tuning to improve this attack is intriguing but has been rarely realized. We herein report on improved OER catalysis by metal porphyrin 1-M (M=Co, Fe) with a coordinatively unsaturated metal ion. We designed and synthesized 1-M by sterically blocking one porphyrin side with a tethered tetraazacyclododecane unit. With this protection, the metal-oxo species generated in OER can maintain an unoccupied trans axial site. Importantly, 1-M displays a higher OER activity in alkaline solutions than analogues lacking such an axial protection by decreasing up to 150-mV overpotential to achieve 10 mA/cm2 current density. Theoretical studies suggest that with an unoccupied trans axial site, the metal-oxo unit becomes more positively charged and thus is more favoured for the hydroxide nucleophilic attack as compared to metal-oxo units bearing trans axial ligands.

Functional Roles of Polymers in Room-Temperature Phosphorescent Materials: Modulation of Intersystem Crossing, Air Sensitivity and Biological Activity.

Organic room-temperature phosphorescent (RTP) materials routinely incorporate polymeric components, which usually act as non-functional or "inert" media to protect excited-state phosphors from thermal and collisional quenching, but are lesser explored for other influences. Here, we report some exemplary "active roles" of polymer matrices played in organic RTP materials, including: 1) color modulation of total delayed emissions via balancing the population ratio between thermally-activated delayed fluorescence (TADF) and RTP due to dielectric-dependent intersystem crossing; 2) altered air sensitivity of RTP materials by generating various surface morphologies such as nano-sized granules; 3) enhanced bacterial elimination for enhanced electrostatic interactions with negatively charged bio-membranes. These active roles demonstrated that the vast library of polymeric structures and functionalities can be married to organic phosphors to broaden new application horizons for RTP materials.

Disorder-Enhanced Charge-Transfer-Mediated Room-Temperature Phosphorescence in Polymer Media.

Room-temperature phosphorescence (RTP) polymers have important applications for biological imaging, oxygen sensing, data encryption, and photodynamic therapy. Despite the many advantages polymeric materials offer such as great control over gas permeability and processing flexibility, disorder is traditionally considered as an intrinsic negative impact on the efficiency for embedded RTP luminophores, as various allowed thermal motions could quench the emitting states. However, we propose that such disorder-enabled freedoms of microscopic motions can be beneficial for charge-transfer-mediated RTP, which is facilitated by molecular conformational changes among different electronic transition states. Using the "classic" pyrene-aniline exciplex as an example, we demonstrate the mutual enhancement of red/near-infrared and green RTP emissions from the pyrene and aniline moieties, respectively, upon doping the aniline polymer with trace pyrene derivatives. In comparison, a pyrene-doped crystal formed with the same aniline structure exhibits only charge-transfer fluorescence with no red or green RTP observed, suggesting that order suppresses the RTP channels. The proposed polymerization strategy may be used as a unified method to generate multi-emissive polymeric RTP materials from a vast pool of known and unknown exciplexes and charge-transfer complexes.

Transition metal-mediated O-O bond formation and activation in chemistry and biology.

Oxygen evolution and reduction reactions are fundamental processes in biological energy conversion schemes, which represent an attractive method for artificial energy conversion for a world still largely depending on fossil fuels. A range of metalloenzymes achieve these challenging tasks in biology by activating water and dioxygen using cheap and abundant transition metals, such as iron, copper, and manganese. High-valent metal-oxo/oxyl, metal-superoxo, and/or metal-(hydro)peroxo species are common reactive intermediates that are found in the O-O bond formation and activation reactions. The transient nature of the metal-oxygen intermediates has, however, prevented their isolation and characterization in most cases. As a consequence, unambiguous mechanistic assignments in the O-O bond formation and cleavage processes in biological and chemical entries remain elusive, especially for the intermediates and mechanisms involved in the O-O bond formation reactions. This viewpoint article aims at summarizing the information obtained to date in enzymatic and biomimetic systems that fuels the debate regarding the nature of the active oxidants and the mechanistic uncertainties associated with the transition metal-mediated O-O bond formation and cleavage reactions.

Role-Specialized Division of Labor in CO2 Reduction with Doubly-Functionalized Iron Porphyrin Atropisomers.

In enzymes, the active site residues function differently to promote chemical reactions. Such a role-specialized division of labor has been rarely realized by synthetic catalysts. We report herein on catalytic CO2 reduction with Fe porphyrins decorated with two cationic N,N,N-trimethylbenzylamine groups in cis- or trans-arrangement. The cis-isomer outperforms the trans-isomer and reaches a TOFmax of 4.4×105  s-1 in acetonitrile using phenol proton source. Theoretical studies revealed that the two cationic units in the cis-isomer are more effective than a single cationic unit to improve the CO2 binding, and more importantly, they function differently but cooperatively to promote the C-O bond cleavage: one interacts with the CO2 -adduct, while the other one interacts with the phenol molecule through electrostatic interactions. This work therefore presents a significant example of synthetic catalysts, which boost chemical reactions using a role-specialized strategy for substrate activation.

Introducing Water-Network-Assisted Proton Transfer for Boosted Electrocatalytic Hydrogen Evolution with Cobalt Corrole.

Proton transfer is vital for many biological and chemical reactions. Hydrogen-bonded water-containing networks are often found in enzymes to assist proton transfer, but similar strategy has been rarely presented by synthetic catalysts. We herein report the Co corrole 1 with an appended crown ether unit and its boosted activity for the hydrogen evolution reaction (HER). Crystallographic and 1 H NMR studies proved that the crown ether of 1 can grab water via hydrogen bonds. By using protic acids as proton sources, the HER activity of 1 was largely boosted with added water, while the activity of crown-ether-free analogues showed very small enhancement. Inhibition studies by adding 1) external 18-crown-6-ether to extract water molecules and 2) potassium ion or N-benzyl-n-butylamine to block the crown ether of 1 further confirmed its critical role in assisting proton transfer via grabbed water molecules. This work presents a synthetic example to boost HER through water-containing networks.

Identifying Intermediates in Electrocatalytic Water Oxidation with a Manganese Corrole Complex.

Water nucleophilic attack (WNA) on high-valent terminal Mn-oxo species is proposed for O-O bond formation in natural and artificial water oxidation. Herein, we report an electrocatalytic water oxidation reaction with MnIII tris(pentafluorophenyl)corrole (1) in propylene carbonate (PC). O2 was generated at the MnV/IV potential with hydroxide, but a more anodic potential was required to evolve O2 with only water. With a synthetic MnV(O) complex of 1, a second-order rate constant, k2(OH-), of 7.4 × 103 M-1 s-1 was determined in the reaction of the MnV(O) complex of 1 with hydroxide, whereas its reaction with water occurred much more slowly with a k2(H2O) value of 4.4 × 10-3 M-1 s-1. This large reactivity difference of MnV(O) with hydroxide and water is consistent with different electrocatalytic behaviors of 1 with these two substrates. Significantly, during the electrolysis of 1 with water, a MnIV-peroxo species was identified with various spectroscopic methods, including UV-vis, electron paramagnetic resonance, and infrared spectroscopy. Isotope-labeling experiments confirmed that both O atoms of this peroxo species are derived from water, suggesting the involvement of the WNA mechanism in water oxidation by a Mn complex. Density functional theory calculations suggested that the nucleophilic attack of hydroxide on MnV(O) and also WNA to 1e--oxidized MnV(O) are feasibly involved in the catalytic cycles but that direct WNA to MnV(O) is not likely to be the main O-O bond formation pathway in the electrocatalytic water oxidation by 1.

A prospective multicenter study of sirolimus for complicated vascular anomalies.

OBJECTIVE: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs. METHODS: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months. The primary endpoint was the response, which was measured using sequential volumetric magnetic resonance imaging. The secondary endpoints were the disease severity score and quality of life. RESULTS: Of 126 patients enrolled on an intention-to-treat basis, 98 (77.8%) had had an objective response to sirolimus, with a ≥20% decrease in lesion volume. Compared with those with arteriovenous malformations, the response rates were higher (>80%) for patients with common lymphatic malformations, venous malformations, kaposiform hemangioendothelioma, and combined malformations with a prominent venous and/or lymphatic component (P < .05). Improvements in the disease severity score and quality of life were obtained in 83.3% and 79.4% of patients, respectively. The most common adverse event was mucositis in 47 patients. More serious adverse events included reversible grade 4 pneumonitis in 3 patients and grade 4 upper respiratory infection in 1 patient. All these adverse events were considered at least possibly related to the treatment. CONCLUSIONS: Sirolimus is an apparently effective option for pediatric patients with various types of complicated VAs. Close monitoring of possible adverse events is required. The results from the present trial are the basis for future prospective studies using new therapeutic approaches.

Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis.

BACKGROUND: Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS: Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS: Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17-0.88, P = 0.02] and full enteral feeding days (mean difference = -2.66, 95% CI: -4.51 to -0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26-0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34-1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40-1.01, P = 0.06). CONCLUSIONS: OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT: OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP.

Selective Gram-Scale C-H Carbenoid Functionalization of N-Sulfonylarylamides with a Rhodium Catalyst.

This work describes an effective Cp*RhIII-catalyzed C-H carbenoid functionalization of N-sulfonylarylamides. Compared to the previous late-stage C-H modification methods of N-sulfonylarylamide analogues, this method efficiently achieves the gram-scale transformation with 2.5 mol % Rh-catalyst loading at 0 °C or with a 0.1 mol % Rh-catalyst loading at room temperature. The reaction medium has a great influence on the reaction rate. Methanol is optimal, and adding a nonpolar solvent (such as toluene or 1,2-dichloroethane) causes the rate to decrease. Experiments and density functional theory calculations were performed to rationalize the mechanism of rate control by a polar medium.

Discrepancy between Proline and Homoproline in Chiral Recognition and Diastereomeric Photoreactivity with Iridium(III) Complexes.

The chiral-recognition processes of homoproline (hpro) and [Ir(pq)2(MeCN)2](PF6) (pq is 2-phenylquinoline; MeCN is acetonitrile) are investigated, in favor of formation of the thermodynamically stable diastereomers Λ-[Ir(pq)2(d-hpro)] and Δ-[Ir(pq)2(l-hpro)]. Moreover, the diastereoselective photoreactions of Δ-[Ir(pq)2(d-hpro)] and Δ-[Ir(pq)2(l-hpro)] are reported in the presence of O2 at room temperature. Diastereomer Δ-[Ir(pq)2(l-hpro)] is dehydrogenatively oxidized into imino acid complex Δ-[Ir(pq)2(hpro-2H2)] (hpro-2H2 is 3,4,5,6-tetrahydropicalinate), while diastereomer Δ-[Ir(pq)2(d-hpro)] occurs by interligand C-N cross-coupling and dehydrogenative oxidation reactions, affording three products: Δ-[Ir(pq)(d-pqh)] [pqh is N-(2-phenylquinolin-8-yl)homoproline], Δ-[Ir(pq)2(hpro-2H2)], and Δ-[Ir(pq)2(d-hpro-2H6)] [hpro-2H6 is 2,3,4,5-tetrahydropicalinate]. The C-N cross-coupling and dehydrogenative oxidation reactions are competitive, and the dehydrogenative oxidation reactions are regioselective. By optimization of the photoreaction parameters such as the diastereomeric substrate, solvent, and temperature as well as base, each possible competitive product is selectively controlled. In addition, density functional theory calculations are performed to elucidate the distinctly chiral recognition between proline and hpro with an iridium(III) complex.