A Metal-Sulfur-Carbon Catalyst Mimicking the Two-Component Architecture of Nitrogenase.

The production of ammonia (NH3) from nitrogen sources involves competitive adsorption of different intermediates and multiple electron and proton transfers, presenting grand challenges in catalyst design. In nature nitrogenases reduce dinitrogen to NH3 using two component proteins, in which electrons and protons are delivered from Fe protein to the active site in MoFe protein for transfer to the bound N2. We draw inspiration from this structural enzymology, and design a two-component metal-sulfur-carbon (M-S-C) catalyst composed of sulfur-doped carbon-supported ruthenium (Ru) single atoms (SAs) and nanoparticles (NPs) for the electrochemical reduction of nitrate (NO3-) to NH3. The catalyst demonstrates a remarkable NH3 yield rate of ~37 mg L-1 h-1 and a Faradaic efficiency of ~97% for over 200 hours, outperforming those consisting solely of SAs or NPs, and even surpassing most reported electrocatalysts. Our experimental and theoretical investigations reveal the critical role of Ru SAs with the coordination of S in promoting the formation of the HONO intermediate and the subsequent reduction reaction over the NP-surface nearby. This study proves a better understanding of how M-S-Cs act as a synthetic nitrogenase mimic during ammonia synthesis, and contributes to the future mechanism-based catalyst design.

Transient diabetes mellitus with ABCC8 variant successfully treated with sulfonylurea: Two case reports and review of literature.

BACKGROUND: Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that usually presents within the first 6 mo of life. Patients often enter remission within several months, although relapse can occur later in life. Mutations in the ABCC8 gene, which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells, are associated with TNDM and permanent neonatal diabetes. This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulf-onylurea therapy. CASE SUMMARY: We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed, treated, or referred for follow-up between September 2017 and September 2023. The patients were tested for mutations using targeted next-generation sequencing. Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before. Both children had an onset of post-infectious diabetic ketoacidosis, which is worth noting. At a follow-up visit after discontinuing insulin injection, oral glyburide was found to be effective with no adverse reactions. CONCLUSION: Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.

[Phenotypic and molecular characterizations of 46,XY disorders of sex development due to variants of NR5A1 gene].

OBJECTIVE: The clinical and molecular genetic characteristics of 46,XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. METHODS: The clinical data of children with NR5A1 gene variants diagnosed at the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. RESULTS: At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1 ~ 9), including micropenis (100.0%), hypospadias (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~ Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomal karyotypes were 46,XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. CONCLUSION: The clinical phenotype of 46,XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.

[Clinical and genetic analysis of three children with Legius syndrome due to variants of SPRED1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of three children with Leguis syndrome. METHODS: Three children suspected as Legius syndrome at the Henan Children's Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c.751C>T (p.Arg251Ter194) in child 1, c.229A>T (p.Lys77Ter368) in child 2, and c.1044_1046delinsC (p.R349fs*11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. CONCLUSION: All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

LncRNA HILPDA promotes contrast-induced acute kidney injury by recruiting eIF4B to upregulate XPO1 expression.

Background: Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication following the use of iodinated contrast media, with a 20% fatality rate. The function of long non-coding RNA HILPDA (lnc-HILPDA) in CI-AKI development was investigated in this study. Methods: CI-AKI models were constructed by iopromide treatment. Kidney pathological changes were analyzed by HE staining. TUNEL labeling and flow cytometry were used to examine cell apoptosis. CCK-8 assay was used to determine cell viability. The interactions between lnc-HILPDA, eIF4B, and XPO1 were verified by RIP or Co-IP assay. Results: Lnc-HILPDA was upregulated in CI-AKI, and its knockdown decreased contrast-trigged oxidative stress and apoptosis in HK-2 cells. Mechanically, lnc-HILPDA activated the NF-κB pathway by upregulating XPO1 through interacting with eIF4B. Moreover, the inhibitory effect of lnc-HILPDA downregulation on contrast-induced oxidative stress and apoptosis in HK-2 cells was weakened by XPO1 overexpression. Conclusion: Lnc-HILPDA accelerated CI-AKI progression by elevating XPO1 expression through eIF4B to activate NF-κB pathway.

Validation of an AI-Powered Automated X-ray Bone Age Analyzer in Chinese Children and Adolescents: A Comparison with the Tanner-Whitehouse 3 Method.

INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.

Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established Tanner­Whitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.

Clinical outcomes of patients with mut-type methylmalonic acidemia identified through expanded newborn screening in China.

BACKGROUND: Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. DESIGN & METHODS: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. RESULTS: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality. CONCLUSIONS: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.

Optimum seeding density and seedling age for the outstanding yield performance of Japonica rice using crop straw boards for seedling cultivation.

Crop straw boards, a novel nursery material, has proven effective for cultivating dense, young rice seedlings suitable for mechanized transplanting, thereby saving labor. However, under high-density nursery conditions, the biomass accumulation and yield formation in rice vary with different seedling ages, necessitating exploration of optimal seeding densities and seedling ages to achieve high yields. This study aims to determine the appropriate seeding densities and seedling ages using crop straw boards to maximize rice yield. Over two years, field studies were conducted using crop straw boards for rice cultivation at seeding densities of 150, 200, 250, 300, and 350 g/tray (labeled as D1, D2, D3, D4, and D5) and seedling ages of 10, 15, 20, and 25 days (labeled as A1, A2, A3, and A4).The results indicated that D4A2 significantly enhanced tiller number, dry matter accumulation, and photosynthetic capacity, resulting in a yield increase of 2.89% compared to the conventional method of D1A3. High-density and short-aged seedlings cultivated with crop straw boards can enhance rice yield by improving photosynthetic capacity and crop quality. This study emphasizes the importance of using crop straw boards for rice nursery practices, as well as selecting the appropriate seeding densities and seedling ages for optimizing rice production.

The profile of blood microbiome in new-onset type 1 diabetes children.

Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

[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.

iProps: A comprehensive software tool for protein classification and analysis with automatic machine learning capabilities and model interpretation capabilities.

Protein classification is a crucial field in bioinformatics. The development of a comprehensive tool that can perform feature evaluation, visualization, automated machine learning, and model interpretation would significantly advance research in protein classification. However, there is a significant gap in the literature regarding tools that integrate all these essential functionalities. This paper presents iProps, a novel Python-based software package, meticulously crafted to fulfill these multifaceted requirements. iProps is distinguished by its proficiency in feature extraction, evaluation, automated machine learning, and interpretation of classification models. Firstly, iProps fully leverages evolutionary information and amino acid reduction information to propose or extend several numerical protein features that are independent of sequence length, including SC-PSSM, ORDip, TRC, CTDC-E, CKSAAGP-E, and so forth; at the same time, it also implements the calculation of 17 other numerical features within the software. iProps also provides feature combination operations for the aforementioned features to generate more hybrid features, and has added data balancing sampling processing as well as built-in classifier settings, among other functionalities. Thus, It can discern the most effective protein class recognition feature from a multitude of candidates, utilizing three automated machine learning algorithms to identify the most optimal classifiers and parameter settings. Furthermore, iProps generates a detailed explanatory report that includes 23 informative graphs derived from three interpretable models. To assess the performance of iProps, a series of numerical experiments were conducted using two well-established datasets. The results demonstrated that our software achieved superior recognition performance in every case. Beyond its contributions to bioinformatics, iProps broadens its applicability by offering robust data analysis tools that are beneficial across various disciplines, capitalizing on its automated machine learning and model interpretation capabilities. As an open-source platform, iProps is readily accessible and features an intuitive user interface, ensuring ease of use for individuals, even those without a background in programming. The source code of the software is available for download at the following website: https://github.com/LigosQ/iProps and https://gitee.com/LigosQ/iProps.

Elucidating Facet-Dependent Photocatalytic Activities of Metastable CdS and Au@CdS Core-Shell Nanocrystals.

Controlling the crystal facets of semiconductor nanocrystals (NCs) has been proven as an effective approach to tune their physicochemical properties. However, the study on facet-engineering of metastable zinc blende CdS (zb-CdS) and its heterostructures is still not fully explored. In this study, the zb-CdS and Au@zb-CdS core-shell NCs with tunable terminating facets are controllably synthesized, and their photocatalytic performance for water splitting are evaluated. It is found that the {111} facets of the zb-CdS NCs display higher intrinsic activity than the {100} counterparts, which originates from these surfaces being much more efficient, facilitating electron transition to enhance the adsorption ability and the dissociation of the adsorbed water, as revealed by theoretical calculations. Moreover, the Au@zb-CdS core-shell NCs exhibit better photocatalytic performance than the zb-CdS NCs terminated with the same facets under visible light irradiation (≥400 nm), which is mainly ascribed to the accelerated electron separation at the interface, as demonstrated by femtosecond transient absorption (fs-TA) spectroscopy. Importantly, the quantum yield of plasmon-induced hot electron transfer quantified by fs-TA in the Au@zb-CdS core-shell octahedrons can be reached as high as 1.2% under 615 nm excitation, which is higher than that of the Au@zb-CdS core-shell cubes. This work unravels the face-dependent photocatalytic performance of the metastable semiconductor NCs via a combination of experiments and theoretical calculations, providing the understanding of the underlying mechanism of these photocatalysts.

A SERS-based point-of-care testing approach for efficient determination of diquat and paraquat residues using a flexible silver flower-coated melamine sponge.

Diquat (DQ) and paraquat (PQ) residues in food are potential hazards to consumers' health. Point-of-care testing (POCT) of them remains challenging. Based on surface-enhanced Raman spectroscopy (SERS) technology, we developed a POCT strategy for DQ and PQ on apple surface and in apple juice. A point-of-use composite was fabricated using a piece of porous melamine sponge (MS) modified with silver nanoflowers (AgNFs), combining the specificity of the SERS fingerprint and the excellent adsorption capacity of MS. Using this dual-functional AgNFs@MS, the on-site determination of the DQ and PQ residues was completed within 3 min without pretreatment. Clear trends were observed between SERS intensity and logarithmic concentrations, with r values from 0.962 to 0.984. The limit of detection of DQ and PQ were 0.14-0.70 ppb in apple juice and on apple surface. This study provides a new point-of-use alternative for rapidly detecting DQ and PQ residues in nonlaboratory settings.

Evolutionary Diversity of Coxsackievirus A6 Causing Severe Hand, Foot, and Mouth Disease - China, 2012-2023.

Introduction: Coxsackievirus A6 (CVA6) has emerged as a significant pathogen responsible for severe cases of hand, foot, and mouth disease (HFMD). This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6, thereby assisting in its surveillance and management. Methods: In this investigation, 74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and 2023. The VP1 gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST, DnaSP6, and PopART. Results: A significant portion (94.4%) of severe CVA6-associated HFMD cases (51 out of 54, with 20 lacking age information) were children under 5 years old. Among the 74 CVA6 strains analyzed, 72 belonged to the D3a sub-genotype, while only two strains were D2 sub-genotype. The average genetic distance between VP1 sequences prior to 2015 was 0.027, which increased to 0.051 when compared to sequences post-2015. Historical population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2012-2013, 2013-2014, and 2019-2020, resulting in the formation of 65 distinct haplotypes. Consistent with the MCC tree findings, transitioning between regional haplotypes required multiple base substitutions, showcasing an increase in population diversity during the evolutionary process (from 14 haplotypes in 2013 to 55 haplotypes over the subsequent decade). Conclusions: CVA6, associated with severe HFMD, is evolving and presents a risk of outbreak occurrence. Thus, enhanced surveillance of severe HFMD is imperative.

A stacking-based algorithm for antifreeze protein identification using combined physicochemical, pseudo amino acid composition, and reduction property features.

Antifreeze proteins have wide applications in the medical and food industries. In this study, we propose a stacking-based classifier that can effectively identify antifreeze proteins. Initially, feature extraction was performed in three aspects: reduction properties, scalable pseudo amino acid composition, and physicochemical properties. A hybrid feature set comprised of the combined information from these three categories was obtained. Subsequently, we trained the training set based on LightGBM, XGBoost, and RandomForest algorithms, and the training outcomes were passed to the Logistic algorithm for matching, thereby establishing a stacking algorithm. The proposed algorithm was tested on the test set and an independent validation set. Experimental data indicates that the algorithm achieved a recognition accuracy of 98.3 %, and an accuracy of 98.5 % on the validation set. Lastly, we analyzed the reasons why numerical features achieved high recognition capabilities from multiple aspects. Data dimensionality reduction and the analysis from two-dimensional and three-dimensional views revealed separability between positive and negative samples, and the protein three-dimensional structure further demonstrated significant differences in related features between the two samples. Analysis of the classifier revealed that Hr*Hr, HrHr, and Sc-PseAAC_1, 188D(152,116,57,183) were among the seven most important numerical features affecting algorithm recognition. For Hr*Hr and HrHr, supportive sequence level evidence for the reduction dictionary was found in terms of conservation area analysis, multiple sequence alignment, and amino acid conservative substitution. Moreover, the importance of the reduction dictionary was recognized through a comparative analysis of importance before and after the reduction, realizing the effectiveness of the dictionary in improving feature importance. A decision tree model has been utilized to discern the distinctions between dipeptides associated with the physical and chemical properties of His(H), Iso(I), Leu(L), and Lys(K) and other dipeptides. We finally analyzed the other seven features of importance, and data analysis confirmed that hydrophobicity, secondary structure, charge properties, van der Waals forces, and solvent accessibility are also factors affecting the antifreeze capability of proteins.

Evolution, recombination and geographic spreading of global Coxsackievirus A6.

BACKGROUND: The increasing incidence of hand, foot, and mouth disease (HFMD) associated with Coxsackievirus A6 (CVA6) has become a very significant public health problem. The aim of this study is to investigate the recombination, geographic transmission, and evolutionary characteristics of the global CVA6. METHODS: From 2019 to 2022, 73 full-length CVA6 sequences were obtained from HFMD patients in China and analyzed in combination with 1032 published whole genome sequences. Based on this dataset, the phylogenetic features, recombinant diversity, Bayesian phylodynamic characteristics, and key amino acid variations in CVA6 were analyzed. RESULTS: The four genotypes of CVA6, A, D, E, and F, are divided into 24 recombinant forms (RFs, RF-A - RF-X) based on differences in the P3 coding region. The eastern China region plays a key role in the dissemination of CVA6 in China. VP1-137 and VP1-138 are located in the DE loop on the surface of the CVA6 VP1 protein, with the former being a highly variable site and the latter having more non-synonymous substitutions. CONCLUSIONS: Based on whole genome sequences, this study contributes to the CVA6 monitoring, early warning, and the pathogenic mechanism by studying recombination diversity, geographical transmission characteristics, and the variation of important amino acid sites.

Combining WO3@AuNPs with Poly(amidoamine) Allows Sensitive Electrochemical Detection of DR1 Based on Dual Signal Amplification.

Down-regulator of transcription 1 (DR1) is considered as a biomarker of hashimoto's thyroiditis (HT), which is a risk factor for thyroid cancer. Here, a label-free electrochemical biosensor for DR1 detection was constructed based on polyamidoamine (PAMAM) polymer and the nanocomposite (WO3@AuNPs) composed of tungsten trioxide (WO3) and gold nanoparticles (AuNPs). WO3@AuNPs was obtained by combining monolayer WO3 nanosheets, which has high conductivity, and AuNPs. The modification of WO3@AuNPs can not only increase the conductivity of the electrode but also provide more active sites for signaling units, thus greatly improve the sensitivity of the sensor. The polymer PAMAM is biocompatible and non-immunogenic, and its end functional group can bind to the target molecules, providing them with more binding sites and thus improving the sensitivity of the sensor. Under optimal conditions, the label-free biosensor showed a good linear relationship between the logarithm of DR1 concentration and the impedance in the range of 10 fg ⋅ mL-1 to 100 ng ⋅ mL-1, with a detection limit as low as 0.3 fg ⋅ mL-1. Besides, this label-free electrochemical platform exhibited satisfactory selectivity and anti-interference capability in human serum samples. Therefore, this method has considerable potential in clinical detection of DR1.

Evaluating the relationship between the proportion of X-chromosome deletions and clinical manifestations in children with turner syndrome.

Purpose: Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS). Methods: X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed. Results: A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis (r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease (p = 0.26), central nervous system, thyroid, or liver disease. Conclusion: The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics.

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.