A study protocol for investigating the sonographic characteristics of neonates with critical illness: an observational cohort study.

BACKGROUND: Haemodynamic instability and hypoxaemia are common and serious threats to the survival of neonates. A growing body of literature indicates that critical care ultrasound has become the optimal evaluation tool for sick neonates. However, few studies have described sonographic characteristics of haemodynamics systematically in the neonates with critical illness. This protocol describes a prospective observational cohort study aimed at (1) characterising the sonographic characteristics of the neonates with critical diseases; and (2) assessing the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation, duration of ventilation, etc. METHODS AND ANALYSIS: This is a single-centre, prospective and observational study conducted in Chengdu Women's and Children's Central Hospital from 1 December 2022 to 31 December 2027. Neonates admitted to the neonatal intensive care unit will be recruited. After inclusion, the neonates will undergo the neonatal critical care ultrasound. The data collected via case report forms include clinical variables and sonographic measures. The primary outcome is to identify the sonographic characteristics of sick neonates with different diseases, and the secondary outcome is to describe the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation and duration of ventilation. DISCUSSION: Our study provided an organised neonatal critical care ultrasound workflow, which can be applied in practice. Accordingly, this study will first set up large data on the sonographic description of the neonates with critical illness, which can help to understand the pathophysiology of the critical illness, potentially titrating the treatment. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200065581; https://www.chictr.org.cn/com/25/showproj.aspx?proj=184095).

Novel pyrimidin-4-one derivatives as potential T3SS inhibitors against Xanthomonas campestris pv. campestris.

BACKGROUND: Cruciferous black rot is caused by Xanthomonas campestris pv. campestris (Xcc) infection and is a widespread disease worldwide. Excessive and repeated use of bactericide is an important cause of the development of bacterial resistance. It is imperative to take new approaches to screening compounds that target virulence factors rather than kill bacterial pathogens. The type III secretion system (T3SS) invades a variety of cells by transporting virulence effector factors into the cytoplasm and is an attractive antitoxic target. Toward the search of new T3SS inhibitors, an alternative series of novel pyrimidin-4-one derivatives were designed and synthesized and assessed for their effect in blocking the virulence. RESULTS: All of the target compounds were characterized by proton (1 H) nuclear magnetic resonance (NMR), carbon-13 (13 C) NMR, fluorine-19 (19 F) NMR and high-resolution mass spectrometry (HRMS). All compounds were evaluated using high-throughput screening systems against Xcc. The results of the biological activity test revealed that the compound SPF-9 could highly inhibit the activity of xopN gene promoter and the hypersensitivity (HR) of tobacco without affecting bacterial growth. Moreover, messenger RNA (mRNA) level measurements showed that compound SPF-9 inhibited the expression of some representative genes (hrp/hrc genes). Compound SPF-9 weakened the pathogenicity of Xcc to Raphanus sativus L. CONCLUSION: Compound SPF-9 has good potential for further development as a novel T3SS inhibitor against Xcc. © 2023 Society of Chemical Industry.

Deep Learning-Based Road Traffic Noise Annoyance Assessment.

With the development of urban road traffic, road noise pollution is becoming a public concern. Controlling and reducing the harm caused by traffic noise pollution have been the hot spots of traffic noise management research. The subjective annoyance level of traffic noise has become one of the most important measurements for evaluating road traffic pollution. There are subjective experimental methods and objective prediction methods to assess the annoyance level of traffic noise: the subjective experimental method usually uses social surveys or listening experiments in laboratories to directly assess the subjective annoyance level, which is highly reliable, but often requires a lot of time and effort. The objective method extracts acoustic features and predicts the annoyance level through model mapping. Combining the above two methods, this paper proposes a deep learning model-based objective annoyance evaluation method, which directly constructs the mapping between the noise and annoyance level based on the listening experimental results and realizes the rapid evaluation of the noise annoyance level. The experimental results show that this method has reduced the mean absolute error by 30% more than the regression algorithm and neural network, while its performance is insufficient in the annoyance interval where samples are lacking. To solve this problem, the algorithm adopts transfer learning to further improve the robustness with a 30% mean absolute error reduction and a 5% improvement in the correlation coefficient between the true results and predicted results. Although the model trained on college students' data has some limitations, it is still a useful attempt to apply deep learning to noise assessment.

Stereoselective Iron-Catalyzed Alkylation of Enamides with Cyclopropanols via Oxidative C(sp2)-H Functionalization.

Established herein is a radical-mediated C-H alkylation of enamides with cyclopropanols. An environmentally benign catalytic system with iron salt and air is used to permit the oxidative coupling process. The protocol demonstrates a broad substrate scope, allowing the stereoselective synthesis of alkylated enamides. The value of this strategy is further reflected by late-stage diversification of complex cyclopropanol-containing molecules and downstream transformations. Mechanistic studies reveal the dual role of iron salt in the reaction.

Therapeutic Effect of Renifolin F on Airway Allergy in an Ovalbumin-Induced Asthma Mouse Model In Vivo.

Renifolin F is a prenylated chalcone isolated from Shuteria involucrata, a traditional minority ethnic medicine used to treat the respiratory diseases and asthma. Based on the effects of the original medicine plant, we established an in vivo mouse model of allergic asthma using ovalbumin (OVA) as an inducer to evaluate the therapeutic effects of Renifolin F. In the research, mice were sensitized and challenged with OVA to establish an allergic asthma model to evaluate the effects of Renifolin F on allergic asthma. The airway hyper-reactivity (AHR) to methacholine, cytokine levels, ILC2s quantity and mircoRNA-155 expression were assessed. We discovered that Renifolin F attenuated AHR and airway inflammation in the OVA-induced asthmatic mouse model by inhibiting the regulation of ILC2s in the lung, thereby, reducing the upstream inflammatory cytokines IL-25, IL-33 and TSLP; the downstream inflammatory cytokines IL-4, IL-5, IL-9 and IL-13 of ILC2s; and the co-stimulatory factors IL-2 and IL-7; as well as the expression of microRNA-155 in the lung. The findings suggest a therapeutic potential of Renifolin F on OVA-induced airway inflammation.

Evaluation of the clinical effect of an artificial intelligence-assisted diagnosis and treatment system for neonatal seizures in the real world: a multicenter clinical study protocol. / æ–°ç”Ÿå„¿æƒŠåŽ¥æ™ºèƒ½è¯Šç–—ç³»ç»ŸçœŸå®žåœºæ™¯ä¸´åºŠå®žæ–½æ•ˆæžœç»¼åˆè¯„ä»·çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.

Copper-Catalyzed Cross-Nucleophile Coupling of ß-Allenyl Silanes with Tertiary C-H Bonds: A Radical Approach to Branched 1,3-Dienes.

Described herein is a distinctive approach to branched 1,3-dienes through oxidative coupling of two nucleophilic substrates, ß-allenyl silanes, and hydrocarbons appending latent functionality by copper catalysis. Notably, C(sp3)-H dienylation proceeded in a regiospecific manner, even in the presence of competitive C-H bonds that are capable of occurring hydrogen atom transfer process, such as those located at benzylic and other tertiary sites, or adjacent to an oxygen atom. Control experiments support the intermediacy of functionalized alkyl radicals.

A 3-armed multicenter randomized controlled trial: Placental Transfusion in Very Preterm Infants (PT-VPI).

Preterm infants constitute an important proportion of neonatal deaths and various complications, and very preterm infants (VPI) are more likely to develop severe complications, such as intraventricular hemorrhage (IVH), anemia, and sepsis. It has been confirmed that placental transfusion can supplement blood volume in infants and reduce preterm-associated complications, which is further conducive to the development of the nervous system and a better long-term prognosis. Based on these advantages, placental transfusion has been widely used in VPI. There are three main types of placental transfusion: delayed cord clamping (DCC), intact umbilical cord milking (I-UCM), and cut umbilical cord milking (C-UCM). However, the optimal method for PT-VPI remains controversial, and it is urgent to identify the best method of placental transfusion. We plan to fully evaluate the safety and effectiveness of these three placental transfusion methods in VPI in a 3-arm multicenter randomized controlled trial: Placental Transfusion in Very Preterm Infants (PT-VPI). Trial registration: chictr.org.cn, number ChiCTR2000030953.

Iron-Catalyzed Tertiary Alkylation of Terminal Alkynes with 1,3-Diesters via a Functionalized Alkyl Radical.

Direct oxidative C(sp)-H/C(sp3 )-H cross-coupling offers an ideal and environmentally benign protocol for C(sp)-C(sp3 ) bond formations. As such, reactivity and site-selectivity with respect to C(sp3 )-H bond cleavage have remained a persistent challenge. Herein is reported a simple method for iron-catalyzed/silver-mediated tertiary alkylation of terminal alkynes with readily available and versatile 1,3-dicarbonyl compounds. The reaction is suitable for an array of substrates and proceeds in a highly selective manner even employing alkanes containing other tertiary, benzylic, and C(sp3 )-H bonds alpha to heteroatoms. Elaboration of the products enables the synthesis of a series of versatile building blocks. Control experiments implicate the in situ generation of a tertiary carbon-centered radical species.

Merging alkenyl C-H activation with the ring-opening of 1,2-oxazetidines: ruthenium-catalyzed aminomethylation of enamides.

1,2-Oxazetidines have been utilized as formaldimine precursors for the direct aminomethylation of enamides under a Ru(ii) species. By merging alkenyl C-H activation with ring-opening of 1,2-oxazetidines, this efficient protocol provides a facile and novel approach to synthesize Z-selective aminomethyl substituted enamides. Furthermore, two exemplified synthetic elaborations highlight the potential of this transformation.

Selective Dehydrogenative Acylation of Enamides with Aldehydes Leading to Valuable ß-Ketoenamides.

We have presented a unique example of dehydrogenative acylation of enamides with aldehydes enabled by an earth-abundant iron catalyst. The protocol provides the straightforward access to valuable ß-ketoenamides with ample substrate scope and excellent functional group tolerance. Notably, distinct C-H acylation of enamide rather than at N-H moiety site occurs with absolute Z-selectivity was observed. Late-stage modifications of complex molecules and versatile synthetic utility of ß-ketoenamides further highlight the practicability of this transformation.

The ruthenium-catalyzed C-H functionalization of enamides with isocyanates: easy entry to pyrimidin-4-ones.

Ruthenium-catalyzed heteroannulation between enamides and isocyanates has been realized as a complementary approach to conventional strategies for the synthesis of pyrimidin-4-ones. High step- and atom-economy was achieved for the rapid construction of such privileged scaffolds, which are found in a multitude of pharmaceutical compounds. The generality and practicability of this transformation were reflected by the broad scope of substrates with diverse functional groups, large-scale synthesis, and late-stage diversification.

Site-selective C(sp3)-H amination of thioamide with anthranils under Cp*CoIII catalysis.

Synthetically versatile anthranils as a bifunctional amino source have been employed for the first time to enable direct amination on unactivated C(sp3)-H bonds of thioamides under Cp*CoIII catalysis. The excellent site-selectivity on primary C(sp3)-H bonds is observed for a diverse array of thioamides with high functional group tolerance. Further applicability of the products is also highlighted through a series of interesting synthetic elaborations.

Divergent C-H Oxidative Radical Functionalization of Olefins to Install Tertiary Alkyl Motifs Enabled by Copper Catalysis.

An efficient tertiary alkylation reaction of olefins with 1,3-dicarbonyl compounds was developed by virtue of copper catalyst without the use of expensive ligands or additives. In contrast to alkyl Heck-type reaction, alkyl halide is not required. Notably, by varying the nitrogen and air atmosphere, the reaction selectively produces alkylation and alkylation-oxygenation products, respectively. Initial investigations revealed that an α-carbonyl alkyl radical species might be involved in the process.

Cobalt-Catalyzed N-O and C-C Bond Cleavage in 1,2-Oxazetidines: Solvent-Controlled C-H Aminomethylation and Hydroxymethylation of Heteroarenes.

An efficient cobalt-catalyzed ring-opening reaction of bench-stable 1,2-oxazetidines with heteroarenes was unprecedentedly developed. The sustainable Cp *Co(III) catalyst enables a distinctive merger of C-H activation with concomitant N-O and C-C cleavages of 1,2-oxazetidine, leading to site-selective C-H aminomethylation and hydroxymethylation of heteroaromatic compounds containing a broad range of functional groups. Preliminary control experiments unravel some essential mechanistic features of this one-pot transformation.

Regioselective Copper-Catalyzed Oxidative Coupling of α-Alkylated Styrenes with Tertiary Alkyl Radicals.

A radical-mediated oxidative cross-coupling of readily accessible α-alkylated styrenes with 1,3-dicarbonyl compounds utilizing a combination of Cu(OAc)2 and air as a catalytic system is described. Rather than requiring α-halocarbonyl compounds, this efficient approach enables direct installation of tertiary functionalized alkyl motifs to olefins with simple carbonyl derivatives. The novel protocol is characterized with high allylic selectivities via a competing ß-H elimination. Both radical-clock and -trapping experiments provided clear-cut evidence for the intermediacy of an α-keto carbon-centered radical.

Iron-catalyzed peroxidation-carbamoylation of alkenes with hydroperoxides and formamides via formyl C(sp2)-H functionalization.

A reaction protocol in which FeCl3 and tert-butyl hydroperoxide facilitated a selective radical coupling reaction of aryl alkenes or 1,3-enynes with tert-butyl hydroperoxide and formamides to prepare an array of ß-peroxy amides has been achieved. The ß-peroxy amide could serve as a synthetic precursor which was facilely converted to ß-hydroxy amide, ß-keto amide and ß-lactam following subsequent chemical transformation.

Selective Alkenylation and Hydroalkenylation of Enol Phosphates through Direct C-H Functionalization.

An efficient and selective Rh-catalyzed direct CH functionalization reaction of enol phosphates was developed. The method is applicable to a variety of coupling partners, including activated alkenes, alkynes, and allenes, and leads to the formation of various valuable alkenylated and hydroalkenylated enol phosphates through the action of the phosphate directing group. The versatility and utility of the coupling products were demonstrated through further transformations into synthetically useful building blocks.

Expedient synthesis of pyrroloquinolinones by Rh-catalyzed annulation of N-carbamoyl indolines with alkynes through a directed C-H functionalization/C-N cleavage sequence.

A Rh-catalyzed redox-neutral C-H functionalization of N-carbamoyl indolines with various internal alkynes has been developed. The reaction, which involves the sequential cleavage of the C-H bond of the indoline at the C7-position and the C-N bond of the urea motif, provides a divergent protocol to rapidly assemble fused-ring pyrroloquinolinone analogues by using a direct alkenylation/annulation strategy with high efficiency and selectivity.

Rhodium(III)-catalyzed C7-position C-H alkenylation and alkynylation of indolines.

A Rh(III)-catalyzed regioselective C-H alkenylation and alkynylation of indolines is described. This protocol relies on the use of a removable pyridinyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance.