Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China

Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This study aimed to analyze the biochemical, clinical, and genetic characteristics of PCD patients identified by newborn screening (NBS) in Shanghai.Methods: Dried blood spot (DBS) samples of newborns were analyzed through tandem mass spectrometry (MS/MS) from January 2003 to December 2021. Newborns with low free carnitine (C0) levels were recalled. Mutation in the SLC22A5 gene was analyzed on suspected positive newborns with low C0 levels after recall.Results: 1,247,274 newborns were screened by MS/MS and 40 newborns were diagnosed with PCD, therefore the incidence of PCD in Shanghai was approximately 1:31,200. The mean C0 level in newborns with PCD was 5.37 ± 1.79 μmol/L before treatment and increased to 24.45 ± 10.87 μmol/L after treatment with L-carnitine. Twenty-three different variants were identified in the SLC22A5 gene, including 8 novel variants, of which c.51C>G (p.F17L) was the most frequent (27.27%, 18/66), followed by c.1400C>G (p.S467C) (25.76%, 17/66). Almost all the screened PCD patients were asymptomatic.Conclusion: NBS via MS/MS was a quick and efficient method for the early diagnosis of PCD. The incidence of PCD in Shanghai was 1:31,200. Eight novel variants were identified, which greatly expanded the variant spectrum of SLC22A5. MS/MS combined with genetic testing could effectively improve the diagnostic accuracy of PCD

Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1

AbstractType I interferons (IFN-α/β) are the major components of the innate immune response of hosts, and in turn many viruses have evolved to modulate the host response during infection. We found that the IFN-β production was significantly suppressed during PEDV infection in cells. To identify viral IFN antagonists and to study their suppressive function, viral coding sequences for the entire structural and nonstructural proteins were cloned and expressed. Of 16 PEDV nonstructural proteins (nsps), nsp1, nsp3, nsp7, nsp14, nsp15 and nsp16 were found to inhibit the IFN-β and IRF3 promoter activities. The sole accessory protein ORF3, structure protein envelope (E), membrane (M), and nucleocapsid (N) protein were also shown to inhibit such activities. PEDV nsp1 did not interfere the IRF3 phosphorylation and nuclear translocation but interrupted the enhanceosome assembly of IRF3 and CREB-binding protein (CBP) by degrading CBP. A further study showed that the CBP degradation by nsp1 was proteasome-dependent. Our data demonstrate that PEDV modulates the host innate immune responses by degrading CBP and suppressing ISGs expression

Effects of Cerium Doping on the Mechanical Properties and Energy-Releasing Behavior of High-Entropy Alloys

Energetic structural materials play an important role in improving the damage performance of future weapons. To improve the energy-releasing behavior, Al0.5NbZrTi1.5Ta0.8Cex high-entropy alloys were prepared by vacuum-arc melting. The results showed the presence of BCC and FCC phases in the alloy with dendritic-morphology-element segregation and there were significant dislocations in the alloys. The current study focused on the effects of cerium content on the dynamic compressive mechanical and energetic characteristics. Cerium doping enhanced the energy-releasing characteristics of high-entropy alloys. The severity of the reaction increased with the increase in the cerium content, while the dynamic compressive strength generally decreased with the increase in cerium content. The Al0.5NbZrTi1.5Ta0.8Ce0.25 showed excellent mechanical and energy-releasing characteristics. The ballistic experiments indicated that Al0.5NbZrTi1.5Ta0.8Ce0.25 can penetrate 6-millimeter A3 plates and ignite the cotton behind the target at a velocity of 729 m/s, making it an ideal energetic structural material

Mechanical properties and impact energy release characteristics of Al0.5NbZrTi1.5Ta0.8Ce0.85 high-entropy alloy

To explore the potential of high-entropy alloys (HEAs) as energetic structural materials (ESMs), Al _0.5 NbZrTi _1.5 Ta _0.8 Ce _0.85 high-entropy alloys were prepared by vacuum arc melting. XRD and TEM indicated the coexistence of BCC and FCC structures. SEM images illustrated element segregation in HEA. HEA exhibited excellent mechanical properties and impact energy release characteristics. When the strain rate increased from 10 ^–3 s ^−1 to 4500 s ^−1 , the yield strength increased by 56.2% from 909 MPa to 1420 MPa. Under impact, the threshold of strain rate of HEA was about 1200 s ^−1 . Ballistic gun tests were performed to investigate the penetration behaviour and energy release characteristics. Al _0.5 NbZrTi _1.5 Ta _0.8 Ce _0.85 could penetrate 6 mm A _3 plate at the speed of 712 m s ^−1 and ignite the cotton behind the target, combining excellent mechanical properties and impact energy release characteristics

Effects of gradient porosity in the metal foam flow field on the performance of a proton exchange membrane fuel cell

© 2024 Elsevier Ltd. All rights are reserved, This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1016/j.applthermaleng.2024.123638Proton exchange membrane fuel cells have become promising electrochemical energy conversion devices because of their high reliability, rapid response, and low pollutant emissions. As a place for transporting reactants and removing products, the structure of a bipolar plate flow field has an important effect on gas transportation and water management in fuel cells. A well-designed flow field can effectively and quickly remove the liquid water produced in a fuel cell and improve the overall output performance of the fuel cell. This study investigated the effect of three different cathode metal foam flow field structures on cell performance by constructing a three-dimensional computational fluid dynamics model. During the process, the polarization curve, oxygen distribution, liquid saturation, temperature distribution, and pressure drop of the aforementioned three flow field structures were systematically analyzed. The performance of the metal foam flow field was compared with that of the parallel flow field. The results indicated that the heat and mass transfer ability of the metal foam flow field was better than that of the traditional parallel flow field. The metal foam flow field in the cross-streamwise direction with decreasing porosity possessed the optimum performance. A better water management ability and a more uniform distribution of the reaction gas were achieved when the porosity of the metal foam flow field decreased cross-streamwise. The output current density of the metal foam flow field at 0.5 V with decreased cross-streamwise porosity was 2.15% higher than that of the metal foam flow field with uniform porosity. This study highlights the potential for optimizing fuel cell design by manipulating cathode flow field gradients, offering insight for enhancing performance.Peer reviewe

Preparation and characterization of small-diameter decellularized scaffolds for vascular tissue engineering in an animal model

Abstract Background The development of a suitable extracellular matrix (ECM) scaffold is the first step in vascular tissue engineering (VTE). Synthetic vascular grafts are available as an alternative to autologous vessels in large-diameter arteries (>8 mm) and medium-diameter arteries (6–8 mm). In small-diameter vessels (<6 mm), synthetic vascular grafts are of limited use due to poor patency rates. Compared with a vascular prosthesis, natural tissue ECM has valuable advantages. Despite considerable progress in recent years, identifying an optimal protocol to create a scaffold for use in small-diameter (<6 mm) fully natural tissue-engineered vascular grafts (TEVG), remains elusive. Although reports on different decellularization techniques have been numerous, combination of and comparison between these methods are scarce; therefore, we have compared five different decellularization protocols for making small-diameter (<6 mm) ECM scaffolds and evaluated their characteristics relative to those of fresh vascular controls. Results The protocols differed in the choice of enzymatic digestion solvent, the use of non-ionic detergent, the durations of the individual steps, and UV crosslinking. Due to their small diameter and ready availability, rabbit arteria carotis were used as the source of the ECM scaffolds. The scaffolds were subcutaneously implanted in rats and the results were evaluated using various microscopy and immunostaining techniques. Conclusions Our findings showed that a 2 h digestion time with 1× EDTA, replacing non-ionic detergent with double-distilled water for rinsing and the application of UV crosslinking gave rise to an ECM scaffold with the highest biocompatibility, lowest cytotoxicity and best mechanical properties for use in vivo or in situ pre-clinical research in VTE in comparison

Ectopic Overexpression of Pineapple Transcription Factor AcWRKY31 Reduces Drought and Salt Tolerance in Rice and <i>Arabidopsis</i>

Pineapple (Ananas comosus (L.) Merr.) is an important tropical fruit with high economic value, and its growth and development are affected by the external environment. Drought and salt stresses are common adverse conditions that can affect crop quality and yield. WRKY transcription factors (TFs) have been demonstrated to play critical roles in plant stress response, but the function of pineapple WRKY TFs in drought and salt stress tolerance is largely unknown. In this study, a pineapple AcWRKY31 gene was cloned and characterized. AcWRKY31 is a nucleus-localized protein that has transcriptional activation activity. We observed that the panicle length and seed number of AcWRKY31 overexpression transgenic rice plants were significantly reduced compared with that in wild-type plant ZH11. RNA-seq technology was used to identify the differentially expressed genes (DEGs) between wild-type ZH11 and AcWRKY31 overexpression transgenic rice plants. In addition, ectopic overexpression of AcWRKY31 in rice and Arabidopsis resulted in plant oversensitivity to drought and salt stress. qRT-PCR analysis showed that the expression levels of abiotic stress-responsive genes were significantly decreased in the transgenic plants compared with those in the wild-type plants under drought and salt stress conditions. In summary, these results showed that ectopic overexpression of AcWRKY31 reduced drought and salt tolerance in rice and Arabidopsis and provided a candidate gene for crop variety improvement