Predictive Value of Amplitude-Integrated Electroencephalogram Combined with General Movements for Neurodevelopmental Outcomes in Neonates with Severe Hyperbilirubinemia.

Objective: To investigate the predictive value of amplitude-integrated electroencephalogram (aEEG) combined with general movements (GMs) for neurodevelopmental outcomes in neonates with severe hyperbilirubinemia. Methods: A total of 115 infants with severe hyperbilirubinemia admitted to our hospital from December 2021 to February 2024 were enrolled. All the subjects were tested using aEEG, GMs, cranial magnetic resonance imaging (MRI), or auditory brainstem response (ABR), and followed up for 12 months to evaluate the neurodevelopmental outcomes. Results: Among the 100 children who received follow-up, 19 had adverse neurodevelopmental outcomes. They had significantly higher levels of total serum bilirubin (P < .05) than those with positive neurodevelopmental outcomes. The examination results of abnormalities in aEEG, GMs, ABR, aEEG + GMs, aEEG + ABR, and MRI + ABR are all correlated with adverse neurodevelopmental outcomes (P < .05). Logistic regression analysis indicated that abnormal aEEG, GMs, and ABR were predictors of adverse neurodevelopmental outcomes. The aEEG + GMs method significantly outperformed the individual use of aEEG or GMs in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Conclusion: The aEEG + GMs technique can predict the neurodevelopmental outcomes of neonates with severe hyperbilirubinemia and outperforms the individual use of aEEG or GMs in terms of sensitivity, specificity, positive predictive value, and negative predictive value. As a result, the combined technique merits broader clinical use.

Integrated Transcriptomic and Metabolomics Analyses Reveal Molecular Responses to Cold Stress in Coconut (Cocos nucifera L.) Seedlings.

Coconut is an important tropical and subtropical fruit and oil crop severely affected by cold temperature, limiting its distribution and application. Thus, studying its low-temperature reaction mechanism is required to expand its cultivation range. We used growth morphology and physiological analyses to characterize the response of coconuts to 10, 20, and 30 d of low temperatures, combined with transcriptome and metabolome analysis. Low-temperature treatment significantly reduced the plant height and dry weight of coconut seedlings. The contents of soil and plant analyzer development (SPAD), soluble sugar (SS), soluble protein (SP), proline (Pro), and malondialdehyde (MDA) in leaves were significantly increased, along with the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the endogenous hormones abscisic acid (ABA), auxin (IAA), zeatin (ZR), and gibberellin (GA) contents. A large number of differentially expressed genes (DEGs) (9968) were detected under low-temperature conditions. Most DEGs were involved in mitogen-activated protein kinase (MAPK) signaling pathway-plant, plant hormone signal transduction, plant-pathogen interaction, biosynthesis of amino acids, amino sugar and nucleotide sugar metabolism, carbon metabolism, starch and sucrose metabolism, purine metabolism, and phenylpropanoid biosynthesis pathways. Transcription factors (TFs), including WRKY, AP2/ERF, HSF, bZIP, MYB, and bHLH families, were induced to significantly differentially express under cold stress. In addition, most genes associated with major cold-tolerance pathways, such as the ICE-CBF-COR, MAPK signaling, and endogenous hormones and their signaling pathways, were significantly up-regulated. Under low temperatures, a total of 205 differentially accumulated metabolites (DAMs) were enriched; 206 DAMs were in positive-ion mode and 97 in negative-ion mode, mainly including phenylpropanoids and polyketides, lipids and lipid-like molecules, benzenoids, organoheterocyclic compounds, organic oxygen compounds, organic acids and derivatives, nucleosides, nucleotides, and analogues. Comprehensive metabolome and transcriptome analysis revealed that the related genes and metabolites were mainly enriched in amino acid, flavonoid, carbohydrate, lipid, and nucleotide metabolism pathways under cold stress. Together, the results of this study provide important insights into the response of coconuts to cold stress, which will reveal the underlying molecular mechanisms and help in coconut screening and breeding.

Rhodium(III)-Catalyzed C-H/O2 Dual Activation and Macrocyclization: Synthesis and Evaluation of Pyrido[2,1-a]isoindole Grafted Macrocyclic Inhibitors for Influenza H1N1.

The development of environment-friendly, step economic couplings to generate structurally diverse macrocyclic compounds is highly desirable but poses a marked challenge. Inspired by the C-H oxidation mechanism of cytochromes P450, an unprecedented and practical RhIII -catalyzed acylmethylation macrocyclization via C-H/O2 dual activation has been developed by us. The process of macrocyclization is facilitated by a synergic coordination from pyridine and ester group. Interestingly, the reaction mode derives from a three-component coupling which differs from established olefination and alkylation paths. Density functional theory (DFT) calculations and control experiments revealed the mechanism of this unique C-H/O2 dual activation. The newly achieved acylmethylation macrocyclic products and their derivatives showed a potent anti-H1N1 bioactivity, which may provide an opportunity for the discovery of novel anti-H1N1 macrocyclic leading compounds.

CFD-Based Flow Channel Optimization and Performance Prediction for a Conical Axial Maglev Blood Pump.

Ventricular assist devices or total artificial hearts can be used to save patients with heart failure when there are no donors available for heart transplantation. Blood pumps are integral parts of such devices, but traditional axial flow blood pumps have several shortcomings. In particular, they cause hemolysis and thrombosis due to the mechanical contact and wear of the bearings, and they cause blood stagnation due to the separation of the front and rear guide wheel hubs and the impeller hub. By contrast, the implantable axial flow, maglev blood pump has the characteristics of no mechanical contact, no lubrication, low temperature rise, low hemolysis, and less thrombosis. Extensive studies of axial flow, maglev blood pumps have shown that these pumps can function in laminar flow, transitional flow, and turbulent flow, and the working state and performance of such pumps are determined by their support mechanisms and flow channel. Computational fluid dynamics (CFD) is an effective tool for understanding the physical and mechanical characteristics of the blood pump by accurately and effectively revealing the internal flow field, pressure-flow curve, and shear force distribution of the blood pump. In this study, magnetic levitation supports were used to reduce damages to the blood and increase the service life of the blood pump, and a conical impeller hub was used to reduce the speed, volume, and power consumption of the blood pump, thereby facilitating implantation. CFD numerical simulation was then carried out to optimize the structural parameters of the conical axial maglev blood pump, predict the hemolysis performance of the blood pump, and match the flow channel and impeller structure. An extracorporeal circulation simulation platform was designed to test whether the hydraulic characteristics of the blood pump met the physiological requirements. The results showed that the total pressure distribution in the blood pump was reasonable after optimization, with a uniform pressure gradient, and the hemolysis performance was improved.

Rh-Catalyzed C-H alkylation enabling modular synthesis of CF3-substituted benzannulated macrocyclic inhibitors of B cell responses.

Inspired by aspirin and chalcone, herein, we describe a modular biomimetic strategy to achieve a new class of CF3-bearing benzannulated macrolactams. The key to the success of macrolactams was the utilization of a highly chemoselective Rh(iii)-catalyzed native carboxylic acid-directed C-H alkylation. Moreover, the unique CF3-containing benzannulated macrocycles showed decent immunosuppressive effects on B cells in vitro, including proliferation, activation, and antibody production upon specific stimulation implicating TLR and BCR signaling.

Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors.

The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.

Manipulating the Click Reactivity of Dibenzoazacyclooctynes: From Azide Click Component to Caged Acylation Reagent by Silver Catalysis.

Strain-promoted azide-alkyne cycloaddition using dibenzoazacyclooctyne (DBCO) is widely applied in copper-free bioorthogonal reactions. Reported here is the efficient acid-promoted rearrangement and silver-catalyzed amidation of DBCO, which alters its click reactivity robustly. In the switched click reaction, DBCO, as a caged acylation reagent, enables rapid peptide/protein modification after decaging facilitated by silver catalysts, rendering site-specific conjugation of an IgG antibody by a Fc-targeting peptide.

Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study.

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 µg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.

Lamb Wave-Minimum Sampling Variance Particle Filter-Based Fatigue Crack Prognosis.

Fatigue cracks are one of the common failure types of key aircraft components, and they are the focus of prognostics and health management (PHM) systems. Monitoring and prediction of fatigue cracks show great application potential and economic benefit in shortening aircraft downtime, prolonging service life, and enhancing maintenance. However, the fatigue crack growth process is a non-linear non-Gaussian dynamic stochastic process, which involves a variety of uncertainties. Actual crack initiation and growth sometimes deviate from the results of fracture mechanics analysis. The Lamb wave-particle filter (LW-PF) fatigue-crack-life prediction based on piezoelectric transducer (PZT) sensors has the advantages of simple modeling and on-line prediction, making it suitable for engineering applications. Although the resampling algorithm of the standard particle filter (PF) can solve the degradation problem, the discretization error still exists. To alleviate the accuracy decrease caused by the discretization error, a Lamb wave-minimum sampling variance particle filter (LW-MSVPF)-based fatigue crack life prediction method is proposed and validated by fatigue test of the attachment lug in this paper. Sampling variance (SV) is used as a quantitative index to analyze the difference of particle distribution before and after resampling. Compared with the LW-PF method, LW-MSVPF can increase the prediction accuracy with the same computational cost. By using the minimum sampling variance (MSV) resampling method, the original particle distribution is retained to a maximum degree, and the discretization error is significantly reduced. Furthermore, LW-MSVPF maintains the characteristic of dimensional freedom, which means a broader application in on-line prognosis for more complex structures.

Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C-N/C-S Bond Formation in Allylic Surrogates.

Switchable catalytic transformation of reactants can be a powerful approach towards diversity-orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand-controlled, Pd-catalyzed allylic substitution allowing for either selective C-N or C-S bond formation using vinylethylene carbonates (VECs) and N-sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo- and stereoselective synthesis of functional allylic sulfones or sulfonohydrazides. The newly developed protocol features wide substrate scope (nearly 80 examples), broad functional group tolerance, and potential for the late-stage functionalization of bioactive compounds. The isolation and crystallographic analysis of a catalytically competent π-allyl Pd complex suggests that the pathway leading to the allylic products proceeds through a different manifold as previously proposed for the functionalization of VECs with nucleophiles.

The development of the social health scale for the elderly.

BACKGROUND: With the elderly population comprising an increasing large proportion of society, a valid and reliable measure of social health in the elderly is indispensable for a comprehensive health assessment. The objective of this study is to develop a Social Health Scale for the Elderly (SHSE). METHODS: A draft scale was generated based on a literature review and expert surveys. Pilot testing was conducted from December 14, 2015, to January 8, 2016. Some items were removed after assessment with five statistical analysis methods. Field testing began on November 6, 2016, and ended on January 20, 2017. After field testing, the reliability and validity of the scale were assessed and the norms in Hangzhou were calculated. RESULTS: In the two tests, 430 and 2404 subjects were included in the statistical analyses. The long form of the SHSE (SHSE-L) contained 25 items, 14 of which were also in the short form (SHSE-S). The internal consistency of the SHSE-L was acceptable. The test-rest reliability and inter-rater reliability were moderate, but the concurrent validity, construct validity, and convergent and discriminant validity were desirable in both versions. The standard and percentile rank norms in Hangzhou, China were developed based on the field testing data. CONCLUSIONS: The population-based social health of the Chinese elderly can be validly and reliably assessed with the SHSE.

Real-world treatment patterns and clinical outcomes of HCV treatment-naive patients in China: an interim analysis from the CCgenos study.

BACKGROUND AND AIM: In China, chronic hepatitis C virus (HCV) infection represents a considerable healthcare burden. Although interferon-based therapy has been the standard-of-care for many years, few long-term, real-life studies have assessed interferon-based treatment in China. The objective of CCgenos follow-up study was to analyze long-term treatment patterns and outcomes in a cohort of treatment-naïve, Han ethnic, patients with chronic HCV infection. METHODS: Patients who had participated in the CCgenos cross-sectional study were invited to enter this 5-year follow up. Clinical information and centralized HCV-RNA measures were collected at scheduled study visits every 6 months for untreated patients and every 3 months for treated patients. RESULTS: Among 512 patients enrolled, 334 (65.2%) received interferon-based treatment and 178 (34.8%) remained untreated over a median of 4.1 (1.2-4.3) years. A total of 82.8% (424/512) of patients had an IL28B CC genotype (GT); 60.7% (311/512) had HCV GT1b infection, including 121 (38.9%) untreated. Most patients with baseline cirrhosis were untreated (26/46, 56.5%). Among patients who completed treatment and 24 weeks of post-treatment follow up, the duration of interferon-based therapy was frequently longer than recommended (52.9% [92/174] of GT1b-infected were treated for > 1 year). Rates of sustained virologic response (SVR24) were 71.1% (226/318) overall; 62.4% (111/178) among patients with HCV GT1b infection; and 42.9% (15/35) among patients with cirrhosis. CONCLUSIONS: There remains a high unmet need for effective HCV treatment in China, evidenced by a high proportion of patients remaining untreated by the current standard-of-care and relatively low SVR24 rates for patients with both GT1b infection and cirrhosis.

Ligand-Promoted C(sp(3) )-H Olefination en Route to Multi-functionalized Pyrazoles.

A Pd-catalyzed/N-heterocycle-directed C(sp(3) )-H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd-catalyzed C(sp(3) )-H olefination for the first time. Cu(OAc)2 instead of Ag(+) salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.

N-Heterocyclic Carbene Ligand-Enabled C(sp(3))-H Arylation of Piperidine and Tetrahydropyran Derivatives.

Pd(II)-catalyzed C(sp(3))-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp(3))-H insertion step by the Pd(II)/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd(0)/Pd(II) catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems.

Research on a Lamb Wave and Particle Filter-Based On-Line Crack Propagation Prognosis Method.

Prognostics and health management techniques have drawn widespread attention due to their ability to facilitate maintenance activities based on need. On-line prognosis of fatigue crack propagation can offer information for optimizing operation and maintenance strategies in real-time. This paper proposes a Lamb wave-particle filter (LW-PF)-based method for on-line prognosis of fatigue crack propagation which takes advantages of the possibility of on-line monitoring to evaluate the actual crack length and uses a particle filter to deal with the crack evolution and monitoring uncertainties. The piezoelectric transducers (PZTs)-based active Lamb wave method is adopted for on-line crack monitoring. The state space model relating to crack propagation is established by the data-driven and finite element methods. Fatigue experiments performed on hole-edge crack specimens have validated the advantages of the proposed method.

Mechanistic insights into the gold chemistry of allenes.

Although most mechanistic studies on gold-catalysed reactions focused on alkynes as substrates, some knowledge about gold-catalysed conversions of allenic substrates has been obtained. This contribution summarises these insights into the reaction mechanisms of gold-catalysed transformations of allenes which are based on computational studies, labelling studies, the detection of intermediates, chirality transfer and diastereoselective product formation.

Orchestrated triple C-H activation reactions using two directing groups: rapid assembly of complex pyrazoles.

A sequential triple C-H activation reaction directed by a pyrazole and an amide group leads to the well-controlled construction of sterically congested dihydrobenzo[e]indazole derivatives. This cascade reaction demonstrates that the often problematic competing C-H activation pathways in the presence of multiple directing groups can be harvested by design to improve step economy in synthesis. Pyrazole as a relatively weak coordinating group is shown to direct Csp3-H activation for the first time.

Highly diastereoselective and regioselective copper-catalyzed nitrosoformate dearomatization reaction under aerobic-oxidation conditions.

An unprecedented copper-catalyzed acylnitroso dearomatization reaction, which expands the traditional acylnitroso ene reaction and acylnitroso Diels-Alder reaction to a new type of transformation, has been developed under aerobic oxidation. Intermolecular and intra-/intermolecular reaction modes demonstrate an entirely different N- or O-acylnitroso selectivity. Hence, we can utilize this reaction as a highly diastereoselective access to a series of new pyrroloindoline derivatives, which are important structural motifs for natural-product synthesis.

Dehydrogenative Meyer-Schuster-like rearrangement: a gold-catalyzed reaction generating an alkyne.

Easily accessible propargylic esters are converted to the inverted alkynyl ketones in an oxidative gold-catalyzed reaction. Gagosz's catalyst in combination with PhI(OAc)2 is the best system for this conversion and 18 examples with yields up to 80 % are reported. The results indicate that the triple bond in the product is formed by elimination from a vinylgold intermediate. In a formal sense the new conversion overall is a dehydrogenative Meyer-Schuster rearrangement.

Small Molecule Targeting PPM1A Activates Autophagy for Mycobacterium tuberculosis Host-Directed Therapy.

Mycobacterium tuberculosis (Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify SMIP-30, targeting PPM1A (IC50 = 1.19 µM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. SMIP-30 restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned SMIP-30 to create SMIP-031, which is a more potent inhibitor for PPM1A (IC50 = 180 nM). SMIP-031 efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. SMIP-031 possesses a good pharmacokinetic profile and oral bioavailability (F = 74%). In vivo, SMIP-031 is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.