Genome-edited powdery mildew resistance in wheat without growth penalties.

Disruption of susceptibility (S) genes in crops is an attractive breeding strategy for conferring disease resistance1,2. However, S genes are implicated in many essential biological functions and deletion of these genes typically results in undesired pleiotropic effects1. Loss-of-function mutations in one such S gene, Mildew resistance locus O (MLO), confers durable and broad-spectrum resistance to powdery mildew in various plant species2,3. However, mlo-associated resistance is also accompanied by growth penalties and yield losses3,4, thereby limiting its widespread use in agriculture. Here we describe Tamlo-R32, a mutant with a 304-kilobase pair targeted deletion in the MLO-B1 locus of wheat that retains crop growth and yields while conferring robust powdery mildew resistance. We show that this deletion results in an altered local chromatin landscape, leading to the ectopic activation of Tonoplast monosaccharide transporter 3 (TaTMT3B), and that this activation alleviates growth and yield penalties associated with MLO disruption. Notably, the function of TMT3 is conserved in other plant species such as Arabidopsis thaliana. Moreover, precision genome editing facilitates the rapid introduction of this mlo resistance allele (Tamlo-R32) into elite wheat varieties. This work demonstrates the ability to stack genetic changes to rescue growth defects caused by recessive alleles, which is critical for developing high-yielding crop varieties with robust and durable disease resistance.

A crowdsourcing open platform for literature curation in UniProt.

The UniProt knowledgebase is a public database for protein sequence and function, covering the tree of life and over 220 million protein entries. Now, the whole community can use a new crowdsourcing annotation system to help scale up UniProt curation and receive proper attribution for their biocuration work.

Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases.

BACKGROUND: Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut-type MMA in Chinese patients. METHODS: We recruited 365 patients with mut-type MMA; investigated their disease onset, newborn screening (NBS) status, biochemical metabolite levels, gene variations and prognosis; and explored the relationship between phenotype and genotype. RESULTS: There were 152 patients diagnosed by tandem mass spectrometry (MS/MS) expanded NBS, 209 patients diagnosed because of disease onset without NBS and 4 cases diagnosed because of sibling diagnosis. The median age of onset was 15 days old, with a variety of symptoms without specificity. Urinary levels of methylmalonic acid and methylcitric acid (MCA) decreased after treatment. Regarding the prognosis, among the 152 patients with NBS, 50.6% were healthy, 30.3% had neurocognitive impairment and/or movement disorders and 13.8% died. Among the 209 patients without NBS, 15.3% were healthy, 45.9% had neurocognitive impairment and/or movement disorders and 33.0% died. In total, 179 variants were detected in the MMUT gene, including 52 novel variations. c.729_730insTT, c.1106G>A, c.323G>A, c.914T>C and c.1663G>A were the five most frequent variations. The c.1663G>A variation led to a milder phenotype and better prognosis. CONCLUSION: There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

[Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency].

OBJECTIVE: To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD). METHODS: Two children with HMGCLD diagnosed at Henan Provincial Children's Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively. RESULTS: Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutaconic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c.722C>T variants of the HMGCL gene, which was rated as uncertain significance (PM2_Supporting+PP3). Child 2 was found to harbor homozygous c.121C>T variants of the HMGCL gene, which was rated as pathogenic variant (PVS1+PM2_Supporting+PP4). CONCLUSION: Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

[Clinical features and genetic analysis of three children with ß-ketothiolase deficiency].

OBJECTIVE: To explore the clinical features and genetic variants in three children suspected for ß-ketothiolase deficiency (BKTD). METHODS: Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children's Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed. RESULTS: The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c.1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c.121-3C>G and c.826+5_826+9delGTGTT in child 2, and c.928G>C and c.1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c.1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+PP3+PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. CONCLUSION: The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

[Analysis of clinical features and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency].

OBJECTIVE: To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ). METHODS: Clinical data of three children diagnosed with late-onset MADD at the Children's Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years. RESULTS: The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. CONCLUSION: The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Interfered chromosome pairing at high temperature promotes meiotic instability in autotetraploid Arabidopsis.

Changes in environmental temperature affect multiple meiotic processes in flowering plants. Polyploid plants derived from whole-genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress but face challenges in organizing and segregating doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis (Arabidopsis thaliana). Under low to mildly increased temperatures (5°C-28°C), irregular chromosome segregation universally occurred in synthetic autotetraploid Columbia-0 (Col-0). Similar meiotic lesions occurred in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv Westar), but not in evolutionarily derived hexaploid wheat (Triticum aestivum). At extremely high temperatures, chromosome separation and tetrad formation became severely disordered due to univalent formation caused by the suppression of crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which were negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over predominantly by impacting homolog pairing. We also showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of the syn1 mutant and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects the lateral region of synaptonemal complex (SC) by impacting the stability of the chromosome axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than those in diploid Arabidopsis. Taken together, our data provide evidence suggesting that WGD negatively affects the stability and thermal tolerance of meiotic recombination in newly synthetic autotetraploid Arabidopsis.

Efficient removal and recovery of phosphorus from industrial wastewater in the form of vivianite.

With the shortage of phosphorus resources, the concept of phosphorus recovery from wastewater is generally proposed. Recently, phosphorus recovery from wastewater in the form of vivianite has been widely reported, which could be used as a slow-release fertilizer as well as the production of lithium iron phosphate for Li-ion batteries. In this study, chemical precipitation thermodynamic modeling was applied to evaluate the effect of solution factors on vivianite crystallization with actual phosphorus containing industrial wastewater. The modeling results showed that the solution pH influences the concentration of diverse ions, and the initial Fe2+ concentration affects the formation area of vivianite. The saturation index (SI) of vivianite increased with the initial Fe2+ concentration and Fe:P molar ratio. pH 7.0, initial Fe2+ concentration 500 mg/L and Fe:P molar ratio 1.50 were the optimal conditions for phosphorus recovery. Mineral Liberation Analyzer (MLA) accurately determined the purity of vivianite was 24.13%, indicating the feasibility of recovering vivianite from industrial wastewater. In addition, the cost analysis showed that the cost of recovering phosphorus by the vivianite process was 0.925 USD/kg P, which can produce high-value vivianite products and realize "turn waste into treasure".

Valorization of sewage sludge for facile and green wood bio-adhesives production.

A method is presented herein for the design of wood bio-adhesives using sewage sludge extracts (SSE). SSE was extracted from SS using deep eutectic solvents and processed with glycerol triglycidyl ether (GTE) to disrupt the secondary structure of proteins. An additive was also used to improve mechanical performance. The resulting bio-adhesive (SSE/GTE@TA) had a wet shear strength of 0.93 MPa, meeting the Chinese national standard GB/T 9846-2015 (≥0.7 MPa). However, the high polysaccharide content in SSE would weaken the mechanical properties of wood bio-adhesives. The key to improve bio-adhesive quality was the formation of a strong chemical bond via Maillard reaction as well as higher temperatures (140 °C) to reduce polysaccharide content via dehydration. This approach has lower environmental impact and higher economic efficiency compared to incineration and anaerobic digestion of sewage sludge. This work provides a new perspective on the high-value utilization of SS and offers a novel approach to developing bio-adhesives for the wood industry.

CircDENND2D Inhibits PD-L1-Mediated Non-Small Cell Lung Cancer Metastasis and Immune Escape by Regulating miR-130b-3p/STK11 Axis.

Local recurrence and distant metastasis of non-small cell lung cancer (NSCLC) caused by immune escape is one of the root causes of treatment difficulties. We aim to investigate the mechanism of immune escape in NSCLC. NSCLC tissues were collected. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion ability was measured by Transwell assay. The expressions of E-cadherin, N-cadherin and PD-L1 were detected by Western blot. NSCLC cells were co-cultured with CD8+ T cells to simulate tumor microenvironment in vitro. The proportion of CD8+ T cells and apoptosis were detected by flow cytometry. Dual-luciferase reporter gene assay confirmed the targeting relationship of circDENND2D and STK11. The expressions of circDENND2D and STK1 were down-regulated, while miR-130b-3p expression was up-regulated in NSCLC tissues. Overexpression of circDENND2D or STK11 inhibited NSCLC cells proliferation, migration and invasion, and attenuated the immune escape of NSCLC cells. CircDENND2D targeted miR-130b-3p to competitively promote STK11 expression. STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.

Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer.

Cancer immune escape is associated with the metabolic reprogramming of the various infiltrating cells in the tumor microenvironment (TME), and combining metabolic targets with immunotherapy shows great promise for improving clinical outcomes. Among all metabolic processes, lipid metabolism, especially fatty acid metabolism (FAM), plays a major role in cancer cell survival, migration, and proliferation. However, the mechanisms and functions of FAM in the tumor immune microenvironment remain poorly understood. We screened 309 fatty acid metabolism-related genes (FMGs) for differential expression, identifying 121 differentially expressed genes. Univariate Cox regression models in The Cancer Genome Atlas (TCGA) database were then utilized to identify the 15 FMGs associated with overall survival. We systematically evaluated the correlation between FMGs' modification patterns and the TME, prognosis, and immunotherapy. The FMGsScore was constructed to quantify the FMG modification patterns using principal component analysis. Three clusters based on FMGs were demonstrated in breast cancer, with three patterns of distinct immune cell infiltration and biological behavior. An FMGsScore signature was constructed to reveal that patients with a low FMGsScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, better survival advantage, and were more sensitive to immunotherapy than those with a high FMGsScore. Finally, the expression and function of the signature key gene NDUFAB1 were examined by in vitro experiments. This study significantly demonstrates the substantial impact of FMGs on the immune microenvironment of breast cancer, and that FMGsScores can be used to guide the prediction of immunotherapy efficacy in breast cancer patients. In vitro experiments, knockdown of the NDUFAB1 gene resulted in reduced proliferation and migration of MCF-7 and MDA-MB-231 cell lines.

Large-scale (500 kg N/day) two-stage partial nitritation/anammox (PN/A) process for liquid-ammonia mercerization wastewater treatment: Rapid start-up and long-term operational performance.

The nitrogen pollution control of liquid-ammonia mercerization wastewater (LMWW) is one of the typical obstacle restricting the sustainability of textile industry. In this study, a 500 kg N/day two-stage partial nitritation/anammox (PN/A) process containing PN reactor filled with zeolite and biofilm anammox reactors was successfully started up in 45 days and operated stably with high shock resistance over one year for LMWW treatment. The large-scale process achieved an average ammonium removal efficiency (94.3 ± 2.3%), total nitrogen removal efficiency (89.4 ± 2.7%) and nitrogen removal rate (1.003 ± 0.386 kg N/m3/day) during one year engineering operation. Simultaneous denitrification was revealed by the contribution of 5.2% total nitrogen removed. High-throughput sequencing results showed that Nitrosomonas was the most dominant genus in PN reactor, and Ca. Anammoxoglobus and Ca. Kuenenia were the functional bacteria for nitrogen removal in anammox reactors. Compared to traditional nitrification-denitrification process, the large-scale process reduced a total operational cost of 46.03 CNY/kg N for LMWW. This study revealed the proposed process was quite reliable with fast start-up and high impact resistance to overcome the obstacle of nitrogen pollution control for LMWW economically and conducive to the sustainable development for textile industry.

[Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene].

OBJECTIVE: To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. METHODS: Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. RESULTS: Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. CONCLUSION: FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.

The CC-NB-LRR protein BSR1 from Brachypodium confers resistance to Barley stripe mosaic virus in gramineous plants by recognising TGB1 movement protein.

Although some nucleotide binding, leucine-rich repeat immune receptor (NLR) proteins conferring resistance to specific viruses have been identified in dicot plants, NLR proteins involved in viral resistance have not been described in monocots. We have used map-based cloning to isolate the CC-NB-LRR (CNL) Barley stripe mosaic virus (BSMV) resistance gene barley stripe resistance 1 (BSR1) from Brachypodium distachyon Bd3-1 inbred line. Stable BSR1 transgenic Brachypodium line Bd21-3, barley (Golden Promise) and wheat (Kenong 199) plants developed resistance against BSMV ND18 strain. Allelic variation analyses indicated that BSR1 is present in several Brachypodium accessions collected from countries in the Middle East. Protein domain swaps revealed that the intact LRR domain and the C-terminus of BSR1 are required for resistance. BSR1 interacts with the BSMV ND18 TGB1 protein in planta and shows temperature-sensitive antiviral resistance. The R390 and T392 residues of TGB1ND (ND18 strain) and the G196 and K197 residues within the BSR1 P-loop motif are key amino acids required for immune activation. BSR1 is the first cloned virus resistance gene encoding a typical CNL protein in monocots, highlighting the utility of the Brachypodium model for isolation and analysis of agronomically important genes for crop improvement.

Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster.

KEY MESSAGE: Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.

Application of the FreeStyle®Libre Glucose Monitoring System in type 1 diabetes mellitus patients aged 1-4 years.

BACKGROUND: To investigate the analytical accuracy, safety performance, and user satisfaction (guardians of study participants) of the FreeStyle®Libre Glucose Monitoring System in the treatment of type 1 diabetes mellitus (T1DM), in children aged <4 years. METHODS: Sixteen hospitalized children with new onset T1DM, aged 4 months to 4 years, were enrolled in this study. Patients wore the sensor for 14 days; sensor scans were performed immediately and at 5, 10, and 15 min after capillary blood glucose (BG) measurements to evaluate the effectiveness of the device and the lag effect. RESULTS: The consensus error grid showed that 96.40% of values fell within zone A (no clinical impact) and 3.60% within zone B (little/no clinical impact). Overall, the mean absolute relative difference (MARD) was 9.34%, and was higher in the capillary BG <4.0 mmol/L group (15.18%) than in the 4-10 mmol/L (9.63%) and >10 mmol/L (7.17%) groups. The MARD increased gradually with scanning time extension, indicating a short lag effect. Regression analysis showed that a higher BG level was associated with a greater difference in FreeStyle®Libre System measurements. CONCLUSIONS: The use of the FreeStyle®Libre System in children aged 1-4 years is accurate and safe, and may be accurate down to 4 months, independent of patient characteristics.

Sulfammox forwarding thiosulfate-driven denitrification and anammox process for nitrogen removal.

The coupled process of thiosulfate-driven denitrification (NO3-→NO2-) and Anammox (TDDA) was a promising process for the treatment of wastewater containing NH4+-N and NO3--N. However, the high concentration of SO42- production limited its application, which needs to be alleviated by an economical and effective way to promote the application of TDDA process. In this study, TDDA process was started in a relatively short time by stepwise replacing nitrite with nitrate and operated continuously for 146 days. Results presented that the average total nitrogen removal efficiency of 82.18% can be acquired at a high loading rate of 1.98 kg N/(m3·d) with maximum nitrogen removal efficiency up to 87.04%. It was observed that the increase of S/N ratio improved the denitrification efficiency and slightly inhibit the Anammox process. Batch tests showed that Sulfammox process appeared in TDDA process under certain conditions, further contributing 2.59% nitrogen removal and 10.46% sulfur removal (14.42 mg/L NH4+-N and 37.68 mg/L SO42--S were removed). This finding was mainly attributed to the reduction of sulfate in TDDA system to elemental S0 or HS-, which subsequently was used as an electron donor to realize the recycling of sulfate (SO42--S) pollutants and promote the sulfur-nitrogen (S-N) cycle. High-throughput analysis displayed that Anammox bacteria (Candidatus_Kuenenia), Sulfur-oxidizing bacteria (Thiobacillus) with relatively high abundance of 5.37%, 7.74%, respectively, guaranteeing the excellent nitrogen and sulfate removal performance in the reactor. The enrichment of phyla Chloroflexi (31.79%), Proteobacteria (31.82%), class Ignavibacteriales (10.55%), genus Planctomycetes (13.57%) further verified the exitence of Sulfammox process in the TDDA reactor. This study provides a new perspective for the practical application of TDDA in terms of reducing the production of high concentration SO42- and saving operational cost and strengthening deeply nitrogen removal.

[Factors affecting phenotypes in the patients with MMACHC gene c.609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria].

OBJECTIVE: To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c.609G>A homologous variant. METHODS: A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164 patients of cblC type with MMACHC c.609G>A homologous variant was conducted. The patients were diagnosed by biochemical and genetic analysis from January 1998 to December 2020. RESULTS: Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated from the age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance (P<0.05). CONCLUSION: Most of the patients with MMACHC c.609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Progranulin and Activin A Concentrations are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study. METHODS: Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups. RESULTS: Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p < 0.001). PGRN and activin A levels were significantly negatively correlated with carbon monoxide diffusion capacity r = - 0.857 (p < 0.001) and r = - 0.757 (p < 0.001). CONCLUSION: Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF.