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.

Combined effects of polystyrene nanoplastics and lipopolysaccharide on testosterone biosynthesis and inflammation in mouse testis.

Microplastics (MPs)/nanoplastics (NPs), as a source and vector of pathogenic bacteria, are widely distributed in the natural environments. Here, we investigated the combined effects of polystyrene NPs (PS-NPs) and lipopolysaccharides (LPS) on testicular function in mice for the first time. 24 male mice were randomly assigned into 4 groups, control, PS-NPs, LPS, and PS-NPs + LPS, respectively. Histological alterations of the testes were observed in mice exposed to PS-NPs, LPS or PS-NPs + LPS. Total sperm count, the levels of testosterone in plasma and testes, the expression levels of steroidogenic acute regulatory (StAR) decreased more remarkable in testes of mice treated with PS-NPs and LPS than the treatment with LPS or PS-NPs alone. Compared with PS-NPs treatment, LPS treatment induced more sever inflammatory response in testes of mice. Moreover, PS-NPs combined with LPS treatment increased the expression of these inflammatory factors more significantly than LPS treatment alone. In addition, PS-NPs or LPS treatment induced oxidative stress in testes of mice, but their combined effect is not significantly different from LPS treatment alone. These results suggest that PS-NPs exacerbate LPS-induced testicular dysfunction. Our results provide new evidence for the threats to male reproductive function induced by both NPs and bacterial infection in human health.

[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.

Hysteretic Spin Crossover with High Transition Temperatures in Two Cobalt(II) Complexes.

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

Syntheses, Structures, and Magnetic Properties of Three Cyano-Bridged FeII-MoIII Single-Molecule Magnets.

Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.

Emotional problems mediate the association between attention deficit/hyperactivity disorder and obesity in adolescents.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) has been identified as a risk factor for obesity in both children and adolescents. However, the mechanisms underlying the relationship between ADHD and obesity are still unclear. This study aimed to test a theoretical model of whether anxiety/depression is an intermediary factor in the ADHD-obesity relationship. METHODS: Data were derived from the National Health Interview Survey (NHIS), a principal source of information on the health of the civilian noninstitutionalized population of the United States. A total of 35,108 adolescents aged 12-17 years old from 2010-2015 NHIS and 2016-2018 NHIS representing 46,550,729 individuals in the weighted population, had a parent-reported previous ADHD diagnosis, emotional problems, and height and weight data. Mediation analyses were used to explore whether anxiety/depression is an intermediary factor in the relationship between ever having ADHD and obesity. Mediation analyses were performed using multiple logistic regressions. RESULTS: The findings showed that ADHD was a predictor of obesity. This relationship was partially mediated by depression(2010-2015: ß=0.28, 95%CI:0.13-0.43; 2016-2018: ß=0.26, 95%CI:0.03-0.49), as well as anxiety (2010-2015: ß=0.28, 95%CI:0.18-0.38). CONCLUSIONS: Our study suggests the hypothetical role of depression and anxiety as underlying mechanisms in the association between ever having ADHD and obesity in adolescents. When treating children with ADHD, clinicians need to be particularly attentive to whether they show emotional problems and use interventions to eliminate anxiety/depression to protect against obesity.

Status and related factors of anxiety of primary caregivers of children with type 1 diabetes: a prospective study.

Primary caregivers of children with type 1 diabetes mellitus (T1DM) are prone to negative emotions. This study explored the anxiety status of the caregivers and analyzed the related factors. In this prospective study, 245 primary caregivers of T1DM children who were reexamined in the outpatient clinic of Children's Hospital affiliated to Zhengzhou University between April 2020 and Sep 2022 were surveyed with a questionnaire and the Hamilton Anxiety Rating Scale (HAMA). The detection rate of anxiety symptoms in T1DM primary caregivers was 21.2%, with a total score of HAMA score of 11.74 ± 2.50. There were significant differences between the anxiety and non-anxiety groups in treatment method, HbA1C to standard (≤7.0%), severe hypoglycemia in the last 1 year and the number of adolescent cases (χ2 = 15.798, p = 0.000; χ2 = 4.197, p = 0.040; χ2 = 5.291, p = 0.021; χ2 = 14.279, p = 0.000). Multivariable logistic regression analysis showed that insulin pump treatment, HbA1C to standard (≤7.0%) and adolescence were associated with anxiety in primary caregivers (OR = 4.040, 95%CI 1.969-8.289, p = 0.000; OR = 0.472, 95%CI 0.237-0.955, p = 0.037; OR = 2.952, 95%CI 1.495-5.831, p = 0.002). Pediatric endocrine care should pay more attention to the anxiety of the caregivers of adolescent T1DM children treated with insulin pumps while helping the children manage their disease.

Clinical characteristics of 683 children and adolescents, aged 0-18 years, newly diagnosed with type 1 diabetes mellitus in Henan Province: a single-center study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a common chronic systemic disease that threatens the health of children worldwide. Diabetic ketoacidosis (DKA) is the most severe acute complication of diabetes and can lead to death. This study aimed to explore the epidemiological features, clinical manifestations, and risk factors for DKA in children and adolescents newly diagnosed with T1DM in the Department of Endocrinology of the Children's Hospital of Henan Province. METHODS: Medical records of 683 children and adolescents newly diagnosed with T1DM in our center from March 2014 to November 2021 were retrospectively analyzed. The data included the general condition, laboratory indexes, and clinical symptoms. The patients were divided into three groups according to age: Group I, 0-3 years; Group II, 4-9 years; and Group III, 10-18 years. RESULTS: The incidence of DKA was 62.96% and was highest in Group I. Group I had the lowest C-peptide and hemoglobin A1c, but the highest blood glucose at first diagnosis, and 25-hydroxyvitamin D3 levels, hospitalization lengths, and medical costs. 25.5% of the children were delayed in diagnosis. Logistic regression analysis showed that elevated HbA1c levels and hyperglycemia were independent risk factors for DKA. On the other hand, C-peptide and 25- hydroxyvitamin D were protective factors for DKA. CONCLUSIONS: The incidence of DKA among children and adolescents in the Henan Province is very high. Moreover, DKA can be easily delayed in diagnosis. Newly diagnosed infants with T1DM are more likely to present with DKA, suffer more severe metabolic disorders, endure longer hospital stays, and accrue higher medical costs.

Ticlopidine induces embryonic development toxicity and hepatotoxicity in zebrafish by upregulating the oxidative stress signaling pathway.

Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 µg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 µg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.

Effects of biochar on rice yield, grain quality and starch viscosity attributes.

BACKGROUND: Biochar can play a key role in improving paddy soil and productivity. However, there is limited information on the effects of biochar on rice quality and starch gelatinization. In this study, four rice straw biochar dosage treatments (0, 20, 40 and 60 g kg-1 ; CK, C20, C40 and C60, respectively) were set up to investigate rice yield components, rice processing, appearance and cooking quality, and starch gelatinization. RESULTS: Addition of biochar increased the effective panicle, grain number per panicle and seed setting rate. However, it decreased the 1000-grain weight, resulting in an increase in yield. In 2019, all the biochar treatments improved the head rice rate (9.13-11.42%), whereas in 2020 only the C20 treatment improved. Low biochar dosage had little effect on grain appearance. High biochar dosage significantly decreased the chalky rice rate by 21.47% and chalkiness by 19.44% in 2019. However, it significantly increased the chalky rice rate and chalkiness by 118.95% and 85.45% in 2020, respectively. Biochar significantly lowered the amylose content except for the C20 and C40 treatments in 2020, and the gel consistency. The C40 and C60 treatments significantly increased the peak and breakdown viscosities and decreased the setback viscosity compared with CK. Correlation analysis showed that starch gelatinization characteristics were significantly correlated with the head rice rate, chalky rate and amylose content. CONCLUSION: A lower biochar dosage can improve the yield and milled rice rate and maintain a higher quality of appearance, whereas a higher biochar dosage can significantly improve starch gelatinization. © 2023 Society of Chemical Industry.

[Genetic analysis of a case with 11ß hydroxylase deficiency caused by CYP11B2/CYP11B1 chimeric gene].

OBJECTIVE: To analyze a child with 11ß hydroxylase deficiency (11ß-OHD) due to CYP11B2/CYP11B1 chimeric gene. METHODS: Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene. RESULTS: The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11ß-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis. CONCLUSION: 11ß-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.

[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.

Role of Key Infectivity Parameters in the Transmission of Ebola Virus Makona in Macaques.

Many characteristics associated with Ebola virus disease remain to be fully understood. It is known that direct contact with infected bodily fluids is an associated risk factor, but few studies have investigated parameters associated with transmission between individuals, such as the dose of virus required to facilitate spread and route of infection. Therefore, we sought to characterize the impact by route of infection, viremia, and viral shedding through various mucosae, with regards to intraspecies transmission of Ebola virus in a nonhuman primate model. Here, challenge via the esophagus or aerosol to the face did not result in clinical disease, although seroconversion of both challenged and contact animals was observed in the latter. Subsequent intramuscular or intratracheal challenges suggest that viral loads determine transmission likelihood to naive animals in an intramuscular-challenge model, which is greatly facilitated in an intratracheal-challenge model where transmission from challenged to direct contact animal was observed consistently.

Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study.

Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.

An effective preselection criterion for MODY with an increasingly positive genetic testing rate by NGS: results from two cohorts of Chinese children.

The purpose of this study was to determine the frequency of maturity-onset diabetes of the young (MODY) in two selected cohorts of Chinese children with diabetes and clinically suspected MODY, using next-generation sequencing (NGS). Ninety-three children who met the comprehensive criteria of suspected MODY were enrolled in two cohorts. A custom NGS panel or a whole exon group was used for sequencing. We identified 55/93 (59.1%) children with pathogenic and likely pathogenic MODY variants. Forty-two (76.3%) were confirmed to have the GCK (MODY2) mutation. Additionally, five had the HNF1A (MODY3), two the HNF1B (MODY5), one the 17q12 microdeletion (MODY5), two the HNF4A (MODY1), two the ABCC8 (MODY12), and one the PDX1 mutation (MODY4). Of these, 13 novel variants were detected in different genes. By comparing the gene-positive with gene-negative children, we found that discriminatory factors for MODY at diagnosis included lower HbA1c [7.4% vs. 10.2% (53 vs. 86 mmol/mol); P = 0.002], lower body mass index z score (0.2 vs. 1.0; P = 0.01), lower onset age (8.1 vs. 11.2 years; P = 0.001), and lower C-peptide (1.4 vs. 2.5 ng/mL; P = 0.02). In conclusion, the criteria used in this study for screening MODY are effective, and MODY2 is the most common subtype (76%), followed by MODY3 and MODY5. Some rare MODY subtypes have been reported in Chinese children.NEW & NOTEWORTHY We proved the clinical suspicion of maturity-onset diabetes of the young (MODY) according to the comprehensive criterion for next-generation sequencing testing, which helps to identify both common and rare MODYs, leading to accurate diagnosis and personalized treatment.

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.

Single boron modulated graphdiyne nanosheets for efficient electrochemical nitrogen fixation: a first-principles study.

The electroreduction of dinitrogen (N2) is a promising alternative approach for ammonia synthesis under mild conditions. In this work, metal-free electrocatalysts using a single boron atom doped into a graphdiyne (GDY) monolayer are fabricated for N2 fixation and conversion to NH3. The NRR electrochemical mechanism has been examined by density functional theory (DFT) calculations. Our calculations revealed that configuration B(S3)@GDY fabricated using a single boron substituting the diacetylene carbon atom exhibits superior catalytic activity in the nitrogen reduction reaction. The preferred distal pathway of the NRR has an extremely low limiting potential of only 0.27 V. In addition, boron atom doping in GDY results in a small band gap (0.24 eV for B(S3)@GDY) and redistribution of the electron density. The electron deficient boron atom is largely positively charged, and thus plays a crucial role in the activation of the NN bond. Moreover, the competing HER is effectively suppressed. This work provides an efficient metal-free single atom electrocatalyst for the NRR based on a 2D graphdiyne monolayer.

Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Arabinogalactan protein-rare earth element complexes activate plant endocytosis.

Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate endocytosis. Here, we report a mechanism for clathrin-mediated endocytosis (CME) of extracellular lanthanum [La(III)] cargoes, which requires extracellular arabinogalactan proteins (AGPs) that are anchored on the outer face of the plasma membrane. AGPs were colocalized with La(III) on the cell surface and in La(III)-induced endocytic vesicles in Arabidopsis leaf cells. Superresolution imaging showed that La(III) triggered AGP movement across the plasma membrane. AGPs were then colocalized and physically associated with the µ subunit of the intracellular adaptor protein 2 (AP2) complexes. The AGP-AP2 interaction was independent of CME, whereas AGP's internalization required CME and AP2. Moreover, we show that AGP-dependent endocytosis in the presence of La(III) also occurred in human cells. These findings indicate that extracellular AGPs act as conserved CME cargo receptors, thus challenging the current paradigm about endocytosis of extracellular cargoes.