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It is of great significance to accurately predict the operation of the system economy, analyze the gains and losses of macrocontrol policies, evaluate the operation quality of the economic system, and correctly formulate the future development plan and strategy. This paper introduces the deep belief network, which has attracted much attention in the field of deep learning in recent years, into the research of system economic operation and management. This method solves the problems of slow training and learning speed, easy to fall into local minima and insufficient generalization of BP artificial neural network in the research of system economic operation and management. Taking the consumer price index and total import and export volume of F Province as the research object, the experiment proves that DBN has better application in system economic operation and management than BP neural network and vector autoregressive analysis. This paper analyzes and compares the modeling performance of DBN, BP neural network, and VaR method from many aspects, such as prediction accuracy, training convergence speed, and pretraining with or without samples. Relevant empirical results show that DBN has better economic prediction performance than BP neural network and ver. On the other hand, DBN can effectively use nonstandard samples to pretrain network weight parameters. Therefore, DBN is a better operation and management modeling means of economic system, with excellent practicability and application, and is expected to be popularized and applied in the field of economic forecasting.

Zhenzhu Zheng, Ying Lei, Yinna Wang, Chunli Lin, Jiansheng Lin Department of Laboratory Medicine, Quanzhou Women’s and Children’s Hospital, Quanzhou, People’s Republic of ChinaCorrespondence: Jiansheng LinDepartment of Laboratory Medicine, Quanzhou Women’s and Children’s Hospital, 700 Fengze Street, Fengze District, Quanzhou, Fujian Province, 350122, People’s Republic of ChinaTel +86 0595 22196131Email 63678462@qq.comBackground: The purpose of this study was to evaluate the prevalence of mobile colistin resistance genes (mcr) in Gram-negative bacteria and to analyze the molecular characteristics of mcr-1 positive Salmonella typhimurium strain 75 and Escherichia coli strain 107 from the Quanzhou Women’s and Children’s Hospital in China.Methods: The genes mcr-1 through mcr-9 were screened via multiplex PCR. Antibiotic susceptibility was detected using a GN11 card with the VITEK-2 compact automated system. Whole genomes were sequenced using PacBio’s single molecule real-time (SMRT) technology.Results: In this study, mcr-1 was detected in only four strains, with a positivity rate of 0.65% (4/616). All the four strains were resistant to more than three different kinds of antibiotics. The mcr-1 positive S. typhimurium strain 75 harbored IncHI2 plasmid, which carried mcr-1 gene, while the mcr-1 positive E. coli strain 107 contained four plasmids including one mcr-1 harboring IncHI2 plasmid, one IncFII plasmid and two IncI1-I (Alpha) plasmids. Mobile elements carrying mcr-1 in the 75_plasmid and 107_plasmid-1 were located in the IS1086(ISApl1)-IS30A(ISApl1)-mcr-1-hp and IS1086(ISApl1)-mcr-1-hp regions, respectively. Tn6010 carrying drug efflux pump genes was found in 75_plasmid, while cn_31611_IS26 carrying multi-drug resistance (MDR) genes were found in 107_plasmid-1.Conclusion: This study found that mcr-1 was prevalent at a low frequency in the Quanzhou Women’s and Children’s Hospital. A similar genetic pattern of mcr-1 transmission was found in both E. coli and S. typhimurium.Keywords: mcr-1, Salmonella typhimurium, Escherichia coli, molecular characteristics

Hyperphenylalaninemia (HPA) is the most common congenital amino acid metabolism-related defect, but its incidence differs substantially between northern and southern China. We aimed to elucidate the incidence, proportion, and genetic features of HPA in a southern Chinese population.We analyzed the HPA screening results for 580,460 newborns from 2014 to 2021.Of the 296 newborns who tested HPA positive, 56 were diagnosed with HPA, including 47 with phenylalanine hydroxylase deficiency and nine with tetrahydrobiopterin deficiency (BHNewborn screening is an effective method for early detection of HPA, but differential diagnosis of BH

Background and aims Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by functional defects in the carnitine transporter OCTN2 due to mutations in SLC22A5. Here, we aimed to understand the incidence, clinical, biochemical, and molecular features of PCD in Quanzhou, China. Materials and methods Newborn screening (NBS) was performed through tandem mass spectrometry (MS/MS) to detect genetic metabolic diseases. Next-generation sequencing was used to detect SLC22A5 mutations in patients with suspected PCD. Results From 364,545 newborns screened, 36 were diagnosed with PCD, in addition to five mothers. The incidence of PCD in children in the Quanzhou area was 1:10126. Eighteen SLC22A5 variants were found, with five novel ones. The most prevalent variant in neonatal and maternal patients was c.760C > T (p.R254*). Twenty-five neonatal patients received L-carnitine supplementation; however, one patient discontinued treatment and sudden death occurred. One sibling presented repeated fatigue, hypoglycemia, and coma, but the symptoms disappeared after treatment. Two mothers with PCD claimed to feel weak and easily fatigued. Conclusion The incidence of PCD is relatively high in the Quanzhou area. Five novel variants were found, broadening the mutation spectrum of SLC22A5. NBS is effective in identifying PCD, and sudden death may be prevented with timely treatment.

Background and aims Acyl-CoA dehydrogenase deficiencies are a group of mitochondrial fatty-acid oxidation disorders rarely reported in mainland China. We assessed the biochemical and genetic characteristics of patients with short- and very-long-chain-acyl-CoA dehydrogenase deficiencies (SCADD/VLCADD) discovered through newborn screening. Materials and methods We investigated the effects of genetic variations on protein function using in silico prediction and structural modelling. Results Of 364,545 screened newborns, four were diagnosed with SCADD and four with VLCADD. SCADD and VLCADD incidences in our population were 1:91,136. All patients exhibited elevated C4 or C14:1 levels. Three SCADD patients had increased urinary ethylmalonic acid concentrations. Six ACADS and eight ACADVL variants were identified, with no hotspot variants, and five were unreported, including four missense variants and one splice site variant. ACADVL c.1434 + 2 T > C is a splice site variant that could affect splicing, leading to exon 14 skipping. In silico tools predicted the missense variants as pathogenic. Structural modelling confirmed that the missense variants may affect quaternary structures, causing protein instability. Conclusions Our findings expanded the ACADS and ACADVL mutational spectra. The combination of in silico prediction and structural modelling can improve our understanding of the pathogenicity of unreported genetic variants, providing an explanation for variant assessment.

Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder affecting the carnitine cycle and resulting in defective fatty acid oxidation. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the main causes of inherited neonatal cholestasis. Both PCD and NICCD are included in the current expanded newborn screening (NBS) targets. Case presentation Targeted exome sequencing was performed on a Chinese proband, and Sanger sequencing was utilised to validate the detected mutations. The patient who was initially suspected to have PCD based on the NBS results presented with neonatal intrahepatic cholestasis and ventricular septal defect. Further investigations not only confirmed PCD but also revealed the presence of NICCD. Four distinct mutations were detected, including c.51C > G (p.F17L) and c.760C > T (p.R254X) in SLC22A5 as well as c.615 + 5G > A and IVS16ins3kb in SLC25A13. Conclusions This is the first reported case of PCD and NICCD occurring in the same patient. The dual disorders in a newborn broaden our understanding of inherited metabolic diseases. Thus, this study highlighted the importance of further genetic testing in patients presenting with unusual metabolic screening findings.

Background Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. Case presentation In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified. Conclusions The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.

Pseudostellaria heterophylla is a very popular traditional Chinese medicine herb, also called "Taizishen." Discrimination of P. heterophylla from different regions is critical for ensuring the effectiveness of drug use, because the drug effects of P. heterophylla from different regions are diversity of each other. To discriminate P. heterophylla from different regions rapidly and effectively, a model extracted by competitive adaptive reweighted sampling (CARS) was established. Original spectra of P. heterophylla in wave number range of 10,000 to 4,000 cm-1 were acquired. Orthogonal partial least squares discriminant analysis (OPLS-DA) was also used to establish a suitable model. CARS was performed for extracting key wave number variables. We found that the near-infrared spectrum of a series of samples analyzed by Row-center-SG, CARS, and OPLS-DA can effectively distinguish the P. heterophylla from different regions, and the accuracy of OPLS-DA model is also satisfactory in terms of good discrimination rate. These results show that the Row-center-SG, CARS, and OPLS-DA model can be used to identify the P. heterophylla from different regions. PRACTICAL APPLICATION: According to our research results, we can draw a conclusion that our research results may be used to distinguish the traditional Chinese medicine from those from different places of origin and the powder with similar appearance.

Background Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 identified through NBS. Results From January 2014 to September 2020, 517,484 newborns were screened by tandem mass spectrometry, 102 newborns with elevated glutarylcarnitine (C5DC) levels were called back. Thirteen patients were diagnosed with GA1, including 11 neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated at 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderate to markedly increased C5DC levels. Notably, one neonatal patient with low free carnitine (C0) level suggest primary carnitine deficiency (PCD) but was ultimately diagnosed as GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA and 3HGA levels, and one was reported to be within the normal range. Ten distinct GCDH variants were identified. Eight were previously reported, and two were newly identified. In silico prediction tools and protein modeling analyses suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2 A>C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G>A (p.Ala421Thr) at 9.09% (2/22). Conclusions Neonatal GA1 patients with increased C5DC levels can be identified through NBS. Maternal GA1 patients can also be detected using NBS due to the low C0 levels in their infants. Few neonatal GA1 patients may have atypical acylcarnitine profiles that are easy to miss during NBS; therefore, multigene panel testing should be performed in newborns with low C0 levels. This study indicates that the GCDH variant spectra were heterogeneous in this southern Chinese cohort.

A feasible manufacturing & forming integration technology for production of TiB-TiAl composite sheets was successfully explored by employing reaction annealing of sandwich-structured (TiB/Ti)–Al laminates. Phase transformation, microstructure evolution of (TiB/Ti)–Al laminates during different reaction annealing processes were systematically investigated by means of optical microscope, scanning electron microscopy, transmission electron microscope and X-ray diffraction. The results showed that the resulting TiB-TiAl composites displayed a unique micro-laminated structure, composing of alternating fully lamellar (α2-Ti3Al/γ-TiAl) layers, equiaxed γ-TiAl layers and TiB-rich layers. Actually, TiB whiskers exhibited a layered distribution in fully lamellar α2/γ layers, which was in favor of α2/γ lamellae refinement. Moreover, formation mechanism of the micro-laminated structure was illustrated. It is noteworthy that the micro-laminated TiB-TiAl composites showed a significant increase in ductility while maintaining or even improving high-temperature tensile strength, in comparison with monolithic TiAl. In addition, fracture behavior of the novel TiB-TiAl composites was characterized by three-dimensional X-ray microscope (3D-XRM) and finally strengthening-toughening mechanism were clarified.

Background and aims Glutaric acidemia type 1 (GA1) is a treatable disorder of cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. There is scarcity of reports of GA1 diagnoses following newborn screening (NBS) in the Chinese population. We assessed the acylcarnitine profiles and genetic characteristics of patients with GA1 identified via NBS.Materials and methods From January 2014 to September 2020, a total of 517,484 newborns screened by tandem mass spectrometry were recruited for this study. Newborns with elevated isovalerylcarnitine (C5DC) levels were recalled, those who tested positive on second screen were referred for confirmatory tests.Results Of 517,484 screened newborns, thirteen patients were diagnosed with GA1, including eleven neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated to be 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderately or markedly increased C5DC levels. The neonatal GA1 patient with low free carnitine (C0) level suggestive of primary carnitine deficiency (PCD) while just the contrary to a typical GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA levels and one was reported in the normal range. Ten distinct GCDH variants were identified, eight were previously reported and two were newly identified. In silico prediction tools and protein modelling analysis suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2A > C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G > A (p.Ala421Thr) (9.09%, 2/22). Conclusions GA1 patients may show only with low C0 levels at the initial screening and recall stages that may be overlooked. Maternal GA1 patients can also be detected during NBS duo to the low C0 levels in their infants. Therefore, PCD should be included in the differential diagnosis for GA1, and multigene panel testing should be performed in newborns with low C0 levels.

Background The urea cycle plays a key role in preventing the accumulation of toxic nitrogenous waste products, including two essential enzymes: ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL). Ornithine transcarbamylase deficiency (OTCD) results from mutations in the OTC. Meanwhile, argininosuccinate lyase deficiency (ASLD) is caused by mutations in the ASL. Methods Blood tandem mass spectrometric analysis and urea organic acidemia screening were performed on five Chinese cases, including three OTCD and two ASLD patients. Next‐generation sequencing was then used to make a definite diagnosis, and the related variants were validated by Sanger sequencing. Results The five patients exhibited severe clinical symptoms, with abnormal biochemical analysis and amino acids profile. Genetic analysis revealed two variants [c.77G>A (p.Arg26Gln); c.116G>T (p.Gly39Val)] in the OTC, as well as two variants [c.1311T>G (p.Tyr437*); c.961T>A (p.Tyr321Asn)] in the ASL. Conservation analysis showed that the amino acids of the two novel mutations were highly conserved in different species and were predicted to be possibly damaging with several in silico prediction programs. 3D‐modeling analysis indicated that the two novel missense variants might result in modest distortions of the OTC and ASL protein structures, respectively. Conclusions Two novel variants expand the mutational spectrums of the OTC and ASL. All the results may contribute to a better understanding of the clinical course and genetic characteristics of patients with urea cycle disorders., Firstly, we have demonstrated five Chinese urea cycle disorder cases in detail, including three ornithine transcarbamylase deficiency patients and two argininosuccinate lyase deficiency patients. Secondly, two novel missense variants including c.116G>T in OTC and c.961T>A in ASL are found and discussed fully.

Background Isovaleric acidemia (IVA) is a rare autosomal recessive disorder of leucine metabolism caused by a defective isovaleryl-CoA dehydrogenase (IVD) gene. Reports of IVA diagnoses following newborn screening (NBS) in the Chinese population are few. Methods We investigated the biochemical, clinical, and molecular profiles of 5 patients with IVA in China. The estimated incidence of IVA in Quanzhou, China is 1 in 1:84,469. Results Initial NBS revealed mild to markedly increased isovalerylcarnitine (C5) concentrations in all 5 patients, and differential diagnosis revealed increased urinary isovaleryglycine concentrations in 2 patients. One patient presented with acute neonatal symptoms, whereas the other 4 remained asymptomatic. Eight distinct IVD gene variants were identified. The most common variant was c.1208A > G (p.Y403C), with an allele frequency of 30%. Five variants were previously unreported, namely, c.499A > G (p.M167V), c.640A > G (p.T214A), c.740G > A (p.G247E), c.832G > C (p.V278L), and c.1195G > C (p.D399H). Different in silico prediction analyses suggested that these previously unreported missense variants are pathogenic. Protein modelling analyses also showed that these missense variants may cause structural damage and dysfunction in IVD. Conclusions Patients with IVA may have C5 concentrations approaching the cut-off values, highlighting the need for stringent recall criteria and second-tier tests to improve screening performance.

Additional file 1: Figure S1. A The BAEP study during an acute episode in the patient. (B) The BAEP study after biotin therapy for 43 days.

Additional file 1: Table S1. The list of targeted genes

The quality of Pseudostellaria heterophylla depends on the growing area of the plants greatly. Compared with near infrared spectroscopy employed to discriminate the geographic regions before, the Raman signal is more obvious. So far, discrimination of P. heterophylla from different regions by Raman spectroscopy has not yet been realized. Hence, Raman spectroscopy coupled with chemometric methods to rapidly and effectively discriminate P. heterophylla from different regions was studied. Original spectra of P. heterophylla in wavenumber range of 4000–100 cm−1 were acquired. Then, a steady and exact model, partial least squares discriminant analysis (PLS-DA), was constructed. And competitive adaptive reweighted sampling (CARS) was further used to extract effective wavelength spectral characteristic variables. Results show that CARS-PLS-DA model is an appropriate model to discriminate the P. heterophylla, with determination coefficient of calibration (R2C), root mean square error of cross validation (RMSECV), determination coefficient of prediction (R2P), and root mean squared error of prediction (RMSEP) are 0.9468, 0.1979, 0.9665, and 0.1120, respectively. These results demonstrated that the built method is useful and effective to discriminate P. heterophylla from different regions, which provide a new idea in the application of rapid field test.

Hot extrusion is used to improve the distribution of whiskers and refine the whisker sizes of 2024Al/Al18B4O33w composite. The grain size and the ultimate tensile strength of the extruded 2024Al/Al18B4O33w composite are analyzed. The results show that the average length of whiskers decreases due to the whisker breakage. The nonuniform distributions of stress and velocity along the whisker lead to whisker breakage. The microcrack between the broken whiskers can propagate into the interface or the matrix, related to the wedge angle of the broken whisker. The extrusion is beneficial to the whisker staggered and makes it easy for the microcracks filled with matrix. The whisker breakage and the whisker staggered result in the decreasing distance between the neighboring whiskers. Due to the dislocation motion constrained by matrix and the overlap of the deformation areas, the decreasing distance between the neighboring whiskers promoting the recrystallization results in the smaller grain size. During tensile tests, due to the smaller resistance with the smaller distance between the neighboring whiskers, the cracks between the progressive broken whiskers are easy to coalesce resulting in the lower ultimate tensile strength of the extruded composite.

Background Non-ketotic hyperglycinemia (NKH) is a rare, devastating autosomal recessive disorder of glycine metabolism with a very poor prognosis. Currently, few studies have reported genetic profiling of Chinese NKH patients. This study aimed to identify the genetic mutations in a Chinese family with NKH. Methods A Chinese family of Han ethnicity, with three siblings with NKH was studied. Sanger sequencing and multiplex ligation-dependent probe amplification combined with SYBR green real-time quantitative PCR was used to identify potential mutations in the GLDC, AMT and GCSH genes. The potential pathogenicity of the identified missense mutation was analyzed using SIFT, PolyPhen-2, PROVEAN and MutationTaster software. Results All patients exhibited severe and progressive clinical symptoms, including lethargy, hypotonia and seizures, and had greatly elevated glycine levels in their plasma and CSF. Molecular genetic analysis identified compound heterozygous variants in the GLDC gene in these three siblings, including a novel missense variant c.2680A > G (p.Thr894Ala) in exon 23 and a heterozygous deletion of exon 3, which were inherited respectively from their parents. In silico analysis, using several different types of bioinformatic software, predicted that the novel variant c.2680A > G in the GLDC gene was pathogenic. Moreover, the deletion of exon 3 was identified for the first time in a Chinese population. Conclusions A novel missense variant and a previously reported deletion in GLDC gene were identified. The two variants of GLDC gene identified probably underlie the pathogenesis of non-ketotic hyperglycinemia in this family, and also enrich the mutational spectrum of GLDC gene. Electronic supplementary material The online version of this article (10.1186/s12881-017-0517-1) contains supplementary material, which is available to authorized users.

The aim of the present study is to reveal the most critical underlying factor influencing the mechanical properties of metal matrix composites (MMCs). It is shown that the mechanical properties of MMCs are essentially governed by the degree of strain localisation during plastic deformation. In other words, the MMCs exhibit superior mechanical performance only if the strain localisation is obviously inhibited and the accumulated stresses can be effectively transferred out. The work provides a new perspective in guiding the design of next-generation high-performance MMCs by suppressing the strain localisation as far as possible.

Short/branched chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of impaired isoleucine catabolism caused by mutations in the ACADSB gene. There are limited SBCADD cases worldwide and to date no Chinese patients with SBCADD have been reported. The aim of this study was to investigate the biochemical, clinical information, and genotypes of twelve patients with SBCADD in China for the first time. The estimated incidence of SBCADD was 1 in 30,379 in Quanzhou, China. The initial newborn screening (NBS) results revealed that all patients showed slightly or moderately elevated C5 concentrations with C5/C2 and C5/C3 ratios in the reference range, which has the highest risk of being missed. All patients who underwent urinary organic acid analysis showed elevation of 2-methylburtyrylglycine in urine. All patients were asymptomatic at diagnosis, and had normal growth and development during follow-up. Eight different variants in the ACADSB gene, including five previously unreported variants were identified, namely c.596A > G (p.Tyr199Cys), c.653T > C (p.Leu218Pro), c.746del (p.Pro249Leufs*15), c.886G > T (p.Gly296*) and c.923G > A (p.Cys308Tyr). The most common variant was c.1165A > G (33.3%), followed by c.275C > G (20.8%). All previously unreported variants may cause structural damage and dysfunction of SBCAD, as predicted by bioinformatics analysis. Thus, our findings indicate that SBCADD may be more frequent in the Chinese population than previously thought and newborn screening, combined with genetic testing is important for timely diagnosis. Although the clinical course of Chinese patients with SBCADD is likely benign, longitudinal follow-up may be helpful to better understand the natural history of SBCADD.

To evaluate the incidence, disease spectrum, and genetic characteristics of inherited metabolic disorders (IMDs) of newborns in Quanzhou area, China. We analyze the expanded newborn screening results of IMDs detected by tandem mass spectrometry (MS/MS) during 5 years. Suspected positive patients were diagnosed through next-generation sequencing and validated by Sanger sequencing. In addition, multiplex ligation-dependent probe amplification technology has also been applied to assist in diagnosis of diseases with deletion or duplication mutations. A total of 364,545 newborns were screened, 130 IMDs were identified yielding an incidence of 1:2804. In addition, 9 cases of maternal disorders were also identified by our MS/MS newborn screening program. There were 42 newborns with amino acid disorders (1:8680), 39 with organic acid disorders (1:9347), and 49 with fatty acid oxidation disorders (1:7440). Unlike other studies, our study indicated that fatty acid oxidation disorder has the highest proportion (37.7%), particularly primary carnitine deficiency (PCD) with incidence up to 1:10,126 was the most common disorder in the region. The recurrent mutations of relatively common diseases like PCD, phenylalanine hydroxylase deficiency, short-chain acyl-CoA dehydrogenase deficiency, citrin deficiency, glutaric acidemia type I, isobutyryl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency in this region were also clearly elucidated. Therefore, our data indicated that IMDs are never uncommon in Quanzhou, the disease spectrum and genetic backgrounds were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in this region.

The hot extrusion is used to align the whiskers and improve the strength of the 2024Al/Al 18 B 4 O 33 w composite. The effects of extrusion and T6 treatment on the microstructure, matrix hardening and tensile properties of 2024Al/Al 18 B 4 O 33 w composite are investigated. The results show that the nano-hardness of matrix in the extruded composite increases. The yield strength increases and then reduces with increasing extrusion ratio. The alignment of whiskers along the extrusion direction and matrix hardening result in the increase in yield strength of the extruded composite. Compared with the continuous decrease in effective average aspect ratio of whiskers, matrix hardening has the obvious effect on the strengthening efficiency and the increase in σ U T S − σ Y S of the extruded composite. The T6 treatment leads to the improvement in strength of the extruded composite. The extruded-T6 composite with the higher yield strength of the matrix has the lower hardening capacity.

Isobutyryl-CoA dehydrogenase deficiency (IBDHD) is a rare autosomal recessive metabolic disorder related to valine catabolism and results from variants in ACAD8. Here, we present the clinical, biochemical, and genotypes of seven patients with IBDHD in China for the first time. Five patients remained asymptomatic during follow-up, whereas one juvenile had speech delay and one newborn exhibited clinical symptoms. All patients showed remarkably increased concentrations of C4-aclycarnitine with elevated C4/C2 and C4/C3 ratios. In urine organic acid tests, only one patient presented with an increased concentration of isobutyrylglycine excretion. Genetic testing was performed to detect the causative variants. Five previously unreported variants, c.235C > G, c.286G > A, c.444G > T c.1092 + 1G > A, and c.1176G > T, and one known variant, c.1000C > T, in ACAD8 were identified. These previously unreported variants in ACAD8 were predicted to be disease-causing and the c.1092 + 1G > A variant was confirmed to cause skipping of exon 9 by reverse transcription PCR. The most common variant was c.286G > A, which showed an allelic frequency of 50% (7/14), and thus may be a prevalent variant among Chinese patients. Our results broaden the mutational spectrum of ACAD8 and improve the understanding of the clinical phenotype of IBDHD.

OBJECTIVE To detect potential mutations of GCDH gene in five patients with glutaric acidemia type I (GA-I). METHODS Genomic DNA was extracted from peripheral blood samples from the patients. The 11 exons and their flanking sequences of the GCDH gene were amplified with PCR and subjected to direct sequencing. RESULTS Four mutations of the GCDH gene were identified among the patients, which included c.532GA (p.G178R), c.533GA (p.G178E), c.106_107delAC (p.Q37fs*5) and c.1244-2AC. Among these, c.1244-2AC was the most common, while c.106_107delAC was a novel mutation, which was predicted to be pathogenic by MutationTaster software. CONCLUSION The diagnosis of GA-I has been confirmed in all of the five patients. Identification of the novel GCDH mutations has enriched the mutational spectrum of the GCDH gene.

Pathogenicity prediction analysis of GLDC c.2680Aâ >â G alteration (DOC 29Â kb)

List of the primers used for Sanger sequencing and Q-PCR (DOCX 13Â kb)

Table S1. Summary of targeted gene sequencing data in the proband. (DOC 29 kb)

Table S2. Shortlist of seven variants identified in MMA-related genes by targeted NGS. (DOC 35 kb)

The 2024Al/Al 18 B 4 O 33 w composite fabricated by the squeeze casting technique is forged with different deformation levels to improve tensile properties. The work hardening rates of 2024Al/Al 18 B 4 O 33 w composite with different forging deformation levels are studied. The results show that the forging process plays a very important role in work hardening rate due to the reduction in the aspect ratios of whiskers and the increase in the dislocation density and the angle between whisker axis and forging direction with increasing deformation level. The variations of work hardening rates in the microscopic yield stage, yield stage and macro plastic stage are correlated with the variation of the aspect ratio of whisker. The initial work hardening rate is higher then rapidly decreases due to the more favorable for annihilation than multiplication of the initial stored dislocations. The work hardening rate of the forged 2024Al/Al 18 B 4 O 33 w composite at the deformation level of 70% with the highest initial stored dislocation density is the highest in the microscopic yield stage and macro plastic stage, but is the lowest in the yield stage due to the interaction of dislocations. The work hardening exponent increases with decreasing the aspect ratio of whiskers. The cracked and progressive cracking whiskers have an impact on work hardening capacity.