Mechanical energy triggered piezo-catalyzation of Bi2WO6 nanoplates on ferrate (Fe(VI)) oxidation in alkaline media: Performance and mechanism.

Piezo-electricity, as a unique physical phenomenon, demonstrates high effectiveness in capturing the environmental mechanical energy into polarization charges, offering the possibility to activate the advanced oxidation processes via the electron pathway. However, information regarding the intensification of Fe(VI) through piezo-catalysis is limited. Therefore, our study is the first to apply Bi2WO6 nanoplates for piezo-catalyzation of Fe(VI) to enhance bisphenol A (BPA) degradation. Compared to Fe(VI) alone, the Fe(VI)/piezo/Bi2WO6 system exhibited excellent BPA removal ability, with the degradation rate increased by 32.6% at pH 9.0. Based on the experimental and theoretical results, Fe(VI), Fe(V), Fe(IV) and •OH were confirmed as reaction active species in the reaction, and the increased BPA removal mainly resulted from the enhanced formation of Fe(IV)/Fe(V) species. Additionally, effects of coexisting anions (e.g., Cl-, NO3-, SO42- and HCO3-), humic acid and different water matrixes (e.g., deionized water, tap water and lake water) on BPA degradation were studied. Results showed the Fe(VI)/piezo/Bi2WO6 system still maintained satisfactory BPA degradation efficiencies under these conditions, guaranteeing future practical applications in surface water treatment. Furthermore, the results of intermediates identification, ECOSAR calculation and cytotoxicity demonstrated that BPA degradation by Fe(VI)/piezo/Bi2WO6 posed a diminishing ecological risk. Overall, these findings provide a novel mechanical energy-driven piezo-catalytic approach for Fe(VI) activation, enabling highly efficient pollutant removal under alkaline condition.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022. / 浙江省1200ä¸‡ä¾‹æ–°ç”Ÿå„¿å ˆå¤©æ€§ç”²çŠ¶è ºåŠŸèƒ½å‡é€€ç—‡ã€é«˜è‹¯ä¸™æ°¨é ¸è¡€ç—‡ç­›æŸ¥ç»“æžœåˆ†æž.

OBJECTIVES: To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. METHODS: A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 µIU/mL was considered positive for CH, while Phe>120 µmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. RESULTS: The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. CONCLUSIONS: The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

ATAD3A gene variations in a family with Harel-Yoon syndrome. / Harel-Yoon综合征一家系临床表型及ATAD3AåŸºå› å˜å¼‚åˆ†æž.

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.

Long-term follow-up of children with carbamoyl phosphate synthase 1 deficiency detected in newborn screening. / æ–°ç”Ÿå„¿ç­›æŸ¥å‘çŽ°çš„æ°¨ç”²é °ç£·é ¸åˆæˆé ¶1ç¼ºä¹ç—‡æ‚£å„¿é•¿æœŸéšè®¿ç ”ç©¶.

OBJECTIVES: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province. METHODS: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed. RESULTS: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 µmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight. CONCLUSIONS: Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.

Treatment and management for children with urea cycle disorder in chronic stage. / å°¿ç´ å¾ªçŽ¯éšœç¢æ‚£å„¿æ ¢æ€§æœŸæ²»ç–—å’Œç®¡ç†.

Urea cycle disorder (UCD) is a group of inherited metabolic diseases with high disability or fatality rate, which need long-term drug treatment and diet management. Except those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; supplementing essential amino acids and protein-free milk are also needed if necessary. The drugs for long-term use include nitrogen scavengers (sodium benzoate, sodium phenylbutyrate, glycerol phenylbutyrate), urea cycle activation/substrate supplementation agents (N-carbamylglutamate, arginine, citrulline), etc. Liver transplantation is recommended for pediatric patients not responding to standard diet and drug treatment, and those with severe progressive liver disease and/or recurrent metabolic decompensations. Gene therapy, stem cell therapy, enzyme therapy and other novel technologies may offer options for treatment in UCD patients. The regular biochemical assessments like blood ammonia, liver function and plasma amino acid profile are needed, and physical growth, intellectual development, nutritional intake should be also evaluated for adjusting treatment in time.

Lonicera caerulea Pomace Alleviates DSS-Induced Colitis via Intestinal Barrier Improvement and Gut Microbiota Modulation.

The objective of this investigation was to appraise the mitigative effects of Lonicera caerulea pomace (LCP)-supplemented diets on Dextran Sulfate Sodium (DSS)-induced colitis, and to discuss the potential mechanisms. LCP, a by-product of fruit juice processing, harbors a higher content of polyphenols and dietary fiber compared to the L. caerulea pulp. In a murine model of colitis, the LCP diet attenuated the symptoms of colitis, as evidenced by the reduction in the disease activity index (DAI), extension of colon length, and amelioration of histopathological damage. The anti-inflammatory attributes of LCP were substantiated by a decrease in myeloperoxidase (MPO) activity and suppression of inflammatory cytokine expressions within the colon. Meanwhile, LCP mediated the repair of the intestinal barrier, characterized by the upregulation of gene expressions of tight junction (TJ) proteins and Muc2. Furthermore, LCP altered the composition of the gut microbiota, manifested in increased alpha diversity, enhancement of the abundance of beneficial bacteria (Akkermansia, Coprococcus and Bifidobacterium), and diminishment in the abundance of pathogenic bacteria (Escherichia, Enterococcus, Mucispirillum and Clostridium). Dietary LCP also increased the concentrations of SCFAs within the intestinal luminal contents of colitis mice. Given the affirmative impact of LCP on colitis, LCP may possess great potential in promoting intestinal health.

Lonicera Caerulea Juice Alleviates Alcoholic Liver Disease by Regulating Intestinal Flora and the FXR-FGF15 Signaling Pathway.

Alcoholic liver disease (ALD) is a growing public health issue with high financial, social, and medical costs. Lonicera caerulea, which is rich in polyphenolic compounds, has been shown to exert anti-oxidative and anti-inflammatory effects. This study aimed to explore the effects and mechanisms of concentrated Lonicera caerulea juice (LCJ) on ALD in mice. ALD was established in mice via gradient alcohol feeding for 30 days. The mice in the experimental group were given LCJ by gavage. The reduction of aspartate transaminase (AST) and alanine transaminase (ALT) in the serum of mice indicated that LCJ has a liver-protective effect. LCJ improved the expression of AMPK, PPARα, and CPT1b in ALD mice to reduce the liver lipid content. Additionally, LCJ increased the expression of farnesoid X receptor (FXR), fibroblast growth factor 15 (FGF15), and fibroblast growth factor receptor 4 (FGFR4), which lowers the expression of cytochrome P450 7A1 (CYP7A1) and lessens bile acid deposition in the liver. In mice, LCJ improved the intestinal barrier by upregulating the expression of mucins and tight junction proteins in the small intestine. Moreover, it accelerated the restoration of microbial homeostasis in both the large and small intestines and increased short-chain fatty acids in the cecum. In conclusion, LCJ alleviates ALD by reducing liver and serum lipid accumulation and modulating the FXR-FGF15 signaling pathway mediated by gut microbes.

China nationwide landscape of 16 types inherited metabolic disorders: a retrospective analysis on 372,255 clinical cases.

BACKGROUND: Inherited metabolic disorders (IMDs) usually occurs at young age and hence it severely threatening the health and life of young people. While so far there lacks a comprehensive study which can reveals China's nationwide landscape of IMDs. This study aimed to evaluate IMDs incidence and regional distributions in China at a national and province level to guide clinicians and policy makers. METHODS: The retrospective study conducted from January 2012 to March 2021, we analyzed and characterized 372255 cases' clinical test information and diagnostic data from KingMed Diagnostics Laboratory. The samples were from 32 provincial regions of China, the urine organic acids were detected by gas chromatography-mass spectrometry (GC-MS), amino acids and acylcarnitines in dried blood spots were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We did a statistical analysis of the distribution of the 16 most common IMDs in amino acid disorders and organic acidemias, and then paid special attention to analyze the age and regional distributions of different IMDs. The statistical analyses and visualization analysis were performed with the programming language R (version 4.2.1). RESULTS: There were 4911 positive cases diagnosed, which was 1.32% of the total sample during the ten-year study period. Most diseases tended to occur at ages younger than 18 year-old. The Ornithine Transcarbamylase Deficiency tended to progress on male infants who were less than 28 days old. While the peak of the positive case number of Citrin Deficiency disease (CD) was at 1-6 months. Different IMDs' had different distribution patterns in China's provinces. Methylmalonic Acidemias and Hyperphenylalaninemia had an imbalanced distribution pattern in China and its positive rate was significantly higher in North China than South China. Conversely, the positive rate of CD was significantly higher in South China than North China. CONCLUSIONS: Results of this work, such as the differences in distribution pattern of different diseases in terms of age, region, etc. provide important insights and references for clinicians, researchers and healthcare policy makers. The policy makers could optimize the better health screening programs for covering children and infants in specific ages and regions based on our findings.

[Preliminary study of glyceryl phenylbutyrate therapy for Ornithine transcarbamylase deficiency and a literature review].

OBJECTIVE: To evaluate the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy for patients with Ornithine transcarbamylase deficiency (OTCD). METHODS: Two children with OTCD were selected as the study subjects, and their clinical manifestations, blood ammonia, liver enzymes, growth and development information following the treatment with GPB were retrospectively analyzed. A literature review was also carried out by searching the PubMed database for studies on the GPB treatment for urea cycle disorders. RESULTS: With the GPB treatment, the blood ammonia and liver enzyme level in both patients have decreased to the normal range within 3 months. Motor development in child 2 has improved. No adverse reaction was noted, except for transient palmar greasy smell and loss of appetite in child 1. Analysis of the literature showed that patients had lower ammonia exposure, lower annual incidence of hyperammonemic crisis, more actual protein intake and fewer adverse events during GPB treatment. CONCLUSION: GPB is safe and effective for the treatment of OTCD.

Fe(VI) activation system mediated by a solar-driven TiO2 nanotubes electrode for CLQ degradation: Performances, mechanisms and pathways.

Ferrate (Fe(VI), FeO42-) has been widely used in the degradation of micropollutants with the advantages of high redox potential, no secondary pollution and inhibition of disinfection byproducts. However, the low transformation of Fe(V) and/or Fe(IV) by Fe(VI) and incomplete mineralization of pollutants limit their application. In this work, we designed a photo electric cell with TiO2 nanotubes (TNTs) and Pt serving as the anode and cathode to enhance the utilization of Fe(VI) (Fe(VI)-TNTs system). TNTs accelerated the generation of •OH via hVB+ oxidation of OH- and photogenerated electrons at Pt boosted the transformation of Fe(VI) to Fe(V) and/or Fe(IV), resulting in a 22.2 % enhancement of chloroquine (CLQ) removal compared to Fe(VI) alone. The results from EPR and quenching tests showed that Fe(VI), Fe(V), Fe(IV), •OH, O2•- and hVB+ coexisted in the Fe(VI)-TNTs system, among which Fe(V) and Fe(IV) were testified as the primary reactive substances accounting for 59 % of CLQ removal. The performance tests and recycling tests demonstrated that the Fe(VI)-TNTs system maintained excellent performance in an authentic water environment. The plausible degradation pathway of CLQ oxidized in the Fe(VI)-TNTs system was proposed with nine identified oxidation products via N-C cleavage, electrophilic addition and carboxylation processes. Based on the ECOSAR calculation, the constructed reaction system allowed a decrease in acute and chronic toxicity. Our findings provide a highly efficient and cost-effective strategy to enhance Fe(VI) application for micropollutant degradation in the future.

Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency in Zhejiang province, China.

BACKGROUND: 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an autosomal recessive inborn defect of leucine catabolism caused by MCCC1 or MCCC2 variants. 3-MCCD is considered to be a relatively benign disorder with favorable outcome. We report the biochemical, clinical, and molecular features of patients with 3-MCCD. METHODS: From January 2009 to August 2022, 4,402,587 newborns were screened by tandem mass spectrometry. Newborns with increased C5OH concentrations were recalled for repeated testing, urine organic acid analysis and molecular genetic analysis were performed if the second test was still positive. RESULTS: A total of 53 patients were diagnosed with 3-MCCD. The estimated incidence of 3-MCCD in Zhejiang Province was 1 in 83,068 newborns. All these 53 patients exhibited increased C5OH concentrations in blood. 94 % (50/53) of the patients had markedly increased urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. All these 53 patients did not present any clinical symptom. Twenty-three of 53 patients had secondary carnitine deficiency. Twenty-eight patients had variants in MCCC1 and 25 had variants in MCCC2. Eleven novel variants were found in MCCC1 and MCCC2. The c.639 + 2 T > A and c.1144-1147delinsTTTT were the most common variant in MCCC1 and MCCC2 gene, respectively. CONCLUSION: We elucidated the incidence of 3-MCCD in Zhejiang province, China. All patients showed asymptomatic and present normal growth and development during follow-up. Eleven novel MCCC1 and MCCC2 variants were identified, which expanded the variant spectrum.

[Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening].

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION: SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.

Effect of hot water extracts of Arthrospira maxima (spirulina) against respiratory syncytial virus.

BACKGROUND: Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV). PURPOSE: There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action. METHODS: Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis. RESULTS: The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC50) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry. CONCLUSION: SHD1 serves as an effective candidate for novel drug development against RSV infection.

Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency.

Introduction: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood. Methods: A total of 169 patients with NICCD who have biallelic pathogenic SLC25A13 variants detected by targeted next-generation sequencing were collected. They were divided into the "Newborn-screen Group" and "Clinical diagnosed Group" depending on the newborn screening results. Amino acid and acylcarnitine profiles were measured by MS/MS. The total bile acids, blood amino acids and acylcarnitines, general biochemistry, blood count, and coagulation parameters were monitored every 2-3 months. We compared the differences in metabolic indices and their dynamic changes between these two groups. The Mann-Whitney test and orthogonal partial least squares discrimination analysis (OPLS-DA) were used for statistical analysis. Results: At the onset of NICCD, we found that the "Clinical diagnosed Group" had higher levels of intermediate products of the urea cycle, free carnitine, and short-chain and long-chain acylcarnitines than those in the "Newborn-screen Group," but the levels of ketogenic/glucogenic amino acids and several medium-chain acylcarnitines were lower. Furthermore, concentrations of direct bilirubin, total bile acid, lactate, prothrombin time, and several liver enzymes were significantly higher while total protein, amylase, and hemoglobin were lower in the "Clinical diagnosed Group" than in the "Newborn-screen Group." Dynamic change analysis showed that direct bilirubin, albumin, arginine, and citrulline were the earliest metabolic derangements to reach peak levels in NICCD groups, followed by acylcarnitine profiles, and finally with the elevation of liver enzymes. All abnormal characteristic metabolic indicators in the "Newborn-screen Group" came back to normal levels at earlier ages than the "Clinical diagnosed Group." c.852_855del (41.2%), IVS16ins3kb (17.6%), c.615 + 5G>A (9.6%), 1638_1660dup (4.4%), and c.1177 + 1G>A (3.7%) accounted for 76.5% of all the mutated SLC25A13 alleles in our population. Conclusion: Argininosuccinate synthesis, gluconeogenesis, ketogenesis, fatty acid oxidation, liver function, and cholestasis were more severely affected in the "Clinical diagnosed Group." The "Newborn-screen Group" had a better prognosis which highlighted the importance of newborn screening of NICCD.

Mechanism of One-Step Hydrothermally Synthesized Titanate Catalysts for Ozonation.

A titanate nanotube catalyst for ozonation was synthesized with a simple one-step NaOH hydrothermal treatment without energy-consuming calcination. The synthesized titania catalysts were characterized by X-ray diffraction (XRD), Raman, porosimetry analysis, high-resolution transmission electron microscopy (HR-TEM), Fourier transformed infrared (FTIR), and electron paramagnetic resonance (EPR) analysis. The catalyst treated with a higher concentration of NaOH was found to be more catalytically active for phenol removal due to its higher titanate content that would facilitate more OH groups on its surface. Furthermore, the main active oxidizing species of the catalytic ozonation process were recognized as singlet oxygen and superoxide radical, while the hydroxyl radical may only play a minor role. This work provides further support for the correlation between the properties of titania and catalytic performance, which is significant for understanding the mechanism of catalytic ozonation with titania-based materials.

Newborn Screening for Mitochondrial Carnitine-Acylcarnitine Cycle Disorders in Zhejiang Province, China.

Background: Disorders of mitochondrial carnitine-acylcarnitine cycle is a heterogeneous group of hereditary diseases of mitochondrial ß-oxidation of fatty acids tested in NBS program in Zhejiang province, China. Large-scale studies reporting disorders of mitochondrial carnitine-acylcarnitine cycle among Chinese population in NBS are limited. The aim of this study was to explain the incidence and biochemical, clinical, and genetic characteristics of disorders of mitochondrial carnitine-acylcarnitine cycle in NBS. Methods: From January 2009 to June 2021, 4,070,375 newborns were screened by tandem mass spectrometry. Newborns with elevated C0 levels and/or C0/(C16 + C18) ratios were identified as having CPT1D, whereas those with decreased C0 levels and/or C0/(C16 + C18) ratios and/or elevated C12-C18:1 level were identified as having CPT2D or CACTD. Suspected positive patients were further subjected to genetic analysis. All confirmed patients received biochemical and nutritional treatment, as well as follow-up sessions. Results: Overall, 20 patients (12 with CPT1D, 4 with CPT2D, and 4 with CACTD) with disorders of mitochondrial carnitine-acylcarnitine cycle were diagnosed by NBS. The overall incidence of these disorders was one in 203,518 newborns. In toal, 11 patients with CPT1D exhibited increased C0 levels and C0/(C16 + C18) ratios. In all patients of CPT2D, all long chain acyl-carnitines levels were elevated except for case 14 having normal C12 levels. In all patients with CACTD, all long chain acyl-carnitines levels were elevated except for case 17 having normal C12, C18, and C18:1 levels. Most patients with CPT1D were asymptomatic. Overall, two of 4 patients with CPT2D did not present any clinical symptom, but other two patients died. In 4 cases with CACTD, the disease was onset after birth, and 75% patients died. In total, 14 distinct mutations were identified in CPT1A gene, of which 11 were novel and c.1910C > A (p.S637T), c.740C > T (p.P247L), and c.1328T > C (p.L443P) were the most common mutations. Overall, 3 novel mutations were identified in CPT2 gene, and the most frequent mutation was c.1711C > A (p.P571T). The most common variant in SLC25A20 gene was c.199-10T > G. Conclusion: Disorders of mitochondrial carnitine-acylcarnitine cycle can be detected by NBS, and the combined incidence of these disorders in newborns was rare in Zhejiang province, China. Most patients presented typical acylcarnitine profiles. Most patients with CPT1D presented normal growth and development, whereas those with CPT2D/CACTD exhibited a high mortality rate. Several novel CPT1A and CPT2 variants were identified, which expanded the variant spectrum.

Biochemical, molecular, and clinical features of patients with glutaric acidemia type 1 identified through large-scale newborn screening in Zhejiang Province, China.

BACKGROUND: Glutaric acidemia type 1 (GA1) is a treatable neurometabolic disorder caused by biallelic variants in the glutaryl-CoA dehydrogenase (GCDH) gene. There are few large-scale reports describing newborn screening (NBS) for GA1 in China. We report the NBS results, genotypes, and clinical features of patients diagnosed through NBS. METHODS: From January 2009 to August 2021, 4,202,587 newborns were screened by tandem mass spectrometry. Newborns with increased glutarylcarnitine (C5DC) concentrations were recalled for repeated test, and confirmatory examinations were performed if the second test was still positive. The pathogenicity of novel variants was predicted using computational programs. RESULTS: A total of 693 had increased C5DC concentrations, and 19 patients were diagnosed with GA1. Thus, the estimated incidence of GA1 in Zhejiang Province was 1 in 221,053 newborns. All the 19 patients had markedly increased C5DC concentrations and C5DC/octanoylcarnitine (C8) ratios; one had a slightly low free carnitine concentration. Seventeen (17/18, 94.4%) patients had increased GA concentrations, 15 were of high excretor phenotype and 3 were of low excretor phenotype. Twenty-three distinct GCDH variants were detected, of which 2were novel. Novel variants were predicted to be potentially pathogenic by computational programs. c.1244-2A > C was the most common variant, with an allelic frequency of 14.7%, followed by c.914C > T (p.S305L) (8.8%). The most common clinical symptom was movement disorder, followed by seizure, macrocephaly, and failure to thrive. Sylvian fissures widening was the most common MRI finding. CONCLUSIONS: Nineteen GA1 patients were diagnosed through the large-scale NBS in Zhejiang Province, with an estimated incidence of 1 in 221,053 newborns. The GCDH mutational spectrum is heterogenous, with the c.1244-2A > C variant being the most frequent variant in this population. NBS for GA1 should be promoted to achieve timely diagnosis and treatment.

Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates.

BACKGROUND: Newborn screening (NBS) has been implemented for neonatal inborn disorders using various technology platforms, but false-positive and false-negative results are still common. In addition, target diseases of NBS are limited by suitable biomarkers. Here we sought to assess the feasibility of further improving the screening using next-generation sequencing technology. METHODS: We designed a newborn genetic sequencing (NBGS) panel based on multiplex PCR and next generation sequencing to analyze 134 genes of 74 inborn disorders, that were validated in 287 samples with previously known mutations. A retrospective cohort of 4986 newborns was analyzed and compared with the biochemical results to evaluate the performance of this panel. RESULTS: The accuracy of the panel was 99.65% with all samples, and 154 mutations from 287 samples were 100% detected. In 4986 newborns, a total of 113 newborns were detected with biallelic or hemizygous mutations, of which 36 newborns were positive for the same disorder by both NBGS and conventional NBS (C-NBS) and 77 individuals were NBGS positive/C-NBS negative. Importantly, 4 of the 77 newborns were diagnosed currently including 1 newborn with methylmalonic acidemia, 1 newborn with primary systemic carnitine deficiency and 2 newborns with Wilson's disease. A total of 1326 newborns were found to be carriers with an overall carrier rate of 26.6%. CONCLUSION: Analysis based on next generation sequencing could effectively identify neonates affected with more congenital disorders. Combined with C-NBS, this approach may improve the early and accurate identification of neonates with inborn disorders. Our study lays the foundation for prospective studies and for implementing NGS-based analysis in NBS.

Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: Outcome and cost-utility analysis.

OBJECTIVES: Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit-cost ratio (BCR), cost-utility ratio (CUR) and incremental cost-utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. METHODS: The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009-2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost-benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. RESULTS: Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders (n = 276), then fatty acid oxidation disorders (n = 248), followed by organic acidaemias (n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ -768,428.76/QALY, and the BCR was 6.09. CONCLUSIONS: NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.