Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

[Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond].

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

[Clinical characteristics and risk factors for early-onset necrotizing enterocolitis in preterm infants with very/extremely low birth weight]. / 极/è¶ ä½Žå‡ºç”Ÿä½“é‡æ—©äº§å„¿æ—©å‘åž‹åæ­»æ€§å°è‚ ç»“è‚ ç‚Žä¸´åºŠç‰¹å¾å’Œå±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). METHODS: A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. RESULTS: Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). CONCLUSIONS: VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.

Artificial microbial consortium producing oxidases enhanced the biotransformation efficiencies of multi-antibiotics.

Antibiotic mixtures in the environment result in the development of bacterial strains with resistance against multiple antibiotics. Oxidases are versatile that can bio-remove antibiotics. Various laccases (LACs), manganese peroxidases (MNPs), and versatile peroxidase (VP) were reconstructed in Pichia pastoris. For the single antibiotics, over 95.0% sulfamethoxazole within 48 h, tetracycline, oxytetracycline, and norfloxacin within 96 h were bio-removed by recombinant VP with α-signal peptide, respectively. In a mixture of the four antibiotics, 80.2% tetracycline and 95.6% oxytetracycline were bio-removed by recombinant MNP2 with native signal peptide (NSP) within 8 h, whereas < 80.0% sulfamethoxazole was bio-removed within 72 h, indicating that signal peptides significantly impacted removal efficiencies of antibiotic mixtures. Regarding mediators for LACs, 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) resulted in better removal efficiencies of multi-antibiotic mixtures than 1-hydroxybenzotriazole or syringaldehyde. Furthermore, artificial microbial consortia (AMC) producing LAC2 and MNP2 with NSP significantly improved bio-removal efficiency of sulfamethoxazole (95.5%) in four-antibiotic mixtures within 48 h. Tetracycline and oxytetracycline were completely bio-removed by AMC within 48 and 72 h, respectively, indicating that AMC accelerated sulfamethoxazole, tetracycline, and oxytetracycline bio-removals. Additionally, transformation pathways of each antibiotic by recombinant oxidases were proposed. Taken together, this work provides a new strategy to simultaneously remove antibiotic mixtures by AMC.

Co-culture of Bacillus amyloliquefaciens and recombinant Pichia pastoris for utilizing kitchen waste to produce fengycins.

Kitchen waste (KW) is a vast potential source of fermentable substrates. To bio-convert the KW into high-value chemicals, we used KW as substrate for the production of fengycin by an artificial consortium containing Bacillus amyloliquefaciens HM618 producing fengycin and the engineering Pichia pastoris producing amylase, glucosidase, or lipases. The maximal amylase activity of the constructed amylase-producing engineering strain (recombinant P. pastoris GS115-amy98) reached 385.4 U‧mL-1. The engineering strain GS115-α-glu53 producing glucosidase reached an enzyme activity titer of 247.3 U‧mL-1, while the lipase activities of the engineering strains GS115-lip2, GS115-α-lip2, and GS115-lip7 were around 90.0 U‧mL-1, with no significant differences among them. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the components of fengycin synthesized by B. amyloliquefaciens HM618 were complex, including C14-C18 fengycins A, C13-C14 fengycins B, C16-C18 fengycins B, C16 fengycin B2 and some fengycin homologues with unsaturated fatty acid chains. The levels of fengycin were 15.9 mg‧L-1 and 4.6 mg‧L-1 under the co-culture with strain HM618 and the recombinant strains producing amylase and lipase, respectively. The maximal titer of fengycin was 21.2 mg‧L-1 in the artificial consortia consisting of HM618 and the engineering strains producing glucosidase, amylase and lipase. Taken together, these results show that the co-culture of B. amyloliquefaciens HM618 and engineering strains producing amylase and lipase can promote the conversion of KW into fengycin. The work provides a new strategy for boosting the resource utilization of KW.

Improved the lipopeptide production of Bacillus amyloliquefaciens HM618 under co-culture with the recombinant Corynebacterium glutamicum producing high-level proline.

The application of antibacterial lipopeptides is limited by high cost and low yield. Herein, the exogenous L-proline significantly improved lipopeptide production by Bacillus amyloliquefaciens HM618. A recombinant Corynebacterium glutamicum producing high levels of proline using genetically modifying proB and putA was used to establish consortium, to improve lipopeptide production of strain HM618. Compared to a pure culture, the levels of iturin A, fengycin, and surfactin in consortium reached 67.75, 39.32, and 37.25 mg L-1, respectively, an increase of 3.19-, 2.05-, and 1.63-fold over that produced by co-cultures of B. amyloliquefaciens and recombinant C. glutamicum with normal medium. Commercial amylase and recombinant Pichia pastoris with a heterologous amylase gene were used to hydrolyze kitchen waste. A three-strain consortium with recombinant P. pastoris and C. glutamicum increased the lipopeptide production of strain HM618 in medium containing KW. This work provides new strategies to improve lipopeptide production by B. amyloliquefaciens.

Epidemiology of metabolic syndrome and its components in Chinese patients with a range of thyroid-stimulating hormone concentrations.

OBJECTIVE: To investigate the relationship between thyroid stimulating hormone (TSH) concentration and the risks of developing metabolic syndrome and its components. METHODS: A total of 10,140 residents of the Yunyan district of Guiyang (Guizhou, China) who were ≥40 years old were selected by cluster random sampling between May and August 2011, of whom 5692 were eligible. TSH concentration and indices of metabolic syndrome were documented at baseline and 3 years later. Participants were allocated to a euthyroid (TSH 0.55-4.78 mIU/L) or high TSH concentration (TSH >4.78 mIU/L) group. Patients with overt hypothyroidism or were undergoing treatment for hypothyroidism were excluded. RESULTS: The crude and adjusted prevalences of metabolic syndrome were 39.9% and 33.9% in the euthyroid group and 44.3% and 37.5% in the high TSH group, respectively. Binary logistic regression analysis revealed a positive correlation between a high TSH concentration at baseline and the cumulative incidence of metabolic syndrome during follow up. CONCLUSIONS: High TSH is associated with a higher risk of developing metabolic syndrome or one of its components; therefore, people with a high TSH concentration should be screened regularly to permit the early identification of metabolic syndrome and followed up thoroughly.

[Magnetic Responses of Heavy Metals in Street Dust of Typical Mine-Based City, Northwest China].

Magnetic characteristics and heavy metal properties of 43 street dust samples collected from Baiyin City, northwest of China were systematically analyzed. The results revealed that the main magnetic minerals were low-coercivity magnetite and maghemite with coarse pseudo single domain (PSD) and multi-domain (MD) in magnetic grain size. Compared with the domestic comprehensive cities, low frequency magnetic susceptibility(χlf) value of street dust samples in Binyin varied from 43. 75 x 10(-8) m3.kg-1 to 1 340. 08 x 10(-8) m3.kg-1 with the average value of 245. 98 x 10(-8) m3.kg-1, the magnetic mineral content in street dust samples of Binyin was low relatively, hut it varied among distinct districts with industrial district was the highest and the stripe traffic area was more higher than those of other regions(commercial district, new district). Different functional zones of Baiyin had a single pollution source relatively. Additionally, the contribution to strong magnetic minerals was predominated by industrial pollution and the distribution of pollution degrees in Bainyin showed a significant spatial difference. Concentrations of heavy metals(Cu, Pb, Zn) were generally high in Baiyin street dust. The significantly positive correlation between magnetic parameters(χlf, χARM, SIRM, SOFT) and pollution load index(PLI) and their consistent spatial characteristics confirm that magnetic concentration parameters can effectively monitor urban heavy metals pollution and determine the bounds and areas of pollution, providing a valuable tool for further urban pollution control.

Event-related potentials in response to emotional words in patients with major depressive disorder and healthy controls.

BACKGROUND: Dysfunctional cognitive processing and abnormal brain activation in response to emotional stimuli have long been recognized as core features of the major depressive disorder (MDD). The aim of this study was to examine how Chinese patients with MDD process Chinese emotional words presented to either the left (LH) or right hemisphere (RH). METHODS: Reaction time (RT) and the late positive component of the event-related potential were measured while subjects judged the valence (positive or negative) of emotional words written in Chinese. RESULTS: Compared to healthy controls, patients with MDD exhibited slower RTs in response to negative words. In all subjects, the RTs in response to negative words were significantly faster than RTs in response to positive words presented to the LH, as well as significantly faster than responses to negative words presented to the RH. Compared to healthy controls, MDD patients exhibited reduced activation of the central and left regions of the brain in response to both negative and positive words. In healthy controls, the posterior brain areas were more active than the anterior brain areas when responding to negative words. CONCLUSION: All individuals showed faster RTs in response to negative words compared to positive words. In addition, MDD patients showed lateralization of brain activity in response to emotional words, whereas healthy individuals did not show this lateralization. Posterior brain areas appear to play an especially important role in discriminating and experiencing negative emotional words. This study provides further evidence in support of the negative bias hypothesis and the emotional processing theory.

[Magnetic properties of topsoils in typical industrial belt along the Yellow River in arid regions in northwest China and their environmental significance].

We have carried out environmental magnetic investigation on topsoil samples of two industrial cities Wuhai and Shizuishan along the Yellow River in the arid regions in northwest China. The concentration, type, magnetic grain sizes of the magnetic minerals and the environmental significance were discussed. The results showed that the main magnetic grain sizes were multi-domain (MD) and pseudo single domain (PSD). The concentration and grain sizes of magnetic minerals showed differences in different functional zones. In industrial zone, the concentration was higher and the grain size was coarser, while there were obviously fewer and finer magnetic minerals in agricultural zone and raw coal zone. Environmental magnetic measurements were efficient to monitor pollution caused by burned fossil fuel, but were not sensitive to unburned fuel. X,, SIRM and SOFT were effective indicators to reflect urban soil pollution. Environmental magnetism method was found to be an important way to monitor and evaluate soil pollution in a city.

[An epidemiological survey of the prevalence of thyroid diseases in mild iodine deficiency city after salt iodization].

OBJECTIVE: To investigate the current status of iodine nutrition and the prevalence of thyroid diseases in Guiyang, a mild iodine deficiency city practiced salt iodization for 25 years. METHODS: A representative sample of 1509 adults aged 20 years old or above in Guiyang, selected by a multistage stratified sampling method, participated in the study. After an overnight fasting, serum thyroid hormones, serum thyroid autoantibodies, and urine iodine were measured. B-mode ultrasonography of the thyroid was performed in the population. Meanwhile, urine iodine of 80 children aged 8 - 10 years old in the same community were measured after an overnight fasting. RESULTS: The median of 8-10 years old children's urinary iodine was 228.7 µg/L. The prevalence of overt hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism and subclinical hyperthyroidism was 1.79%, 14.12%, 1.52% and 1.06% respectively. The prevalence of subclinical hypothyroidism was significantly higher than overt hypothyroidism (P < 0.05) and was significantly higher in female than that in male (P < 0.05). The prevalence of positive thyroid peroxidase antibody, positive thyroglobulin antibody and autoimmune thyroiditis was 14.38%, 13.59% and 4.44% respectively, which were significantly higher in female than that in male (all P values < 0.05). The prevalence of diffuse goiter and nodular goiter was 0.86% and 0.20% respectively, with a significant difference (P < 0.05). CONCLUSION: After 25 years of salt iodization, the iodine nutrition in Guiyang is more than adequate with high prevalence of overt hypothyroidism, subclinical hypothyroidism and autoimmune thyroiditis.

[Effect of UGTIA6 A541G genetic polymorphism on the metabolism of valproic acid in Han epileptic children from Henan].

OBJECTIVE: To investigate the distribution and frequency of UGTIA6 A541G genetic polymorphism in Han epileptic children from Henan and to evaluate the effect of UGTIA6 A541G genetic polymorphism on serum concentrations of valproic acid. METHODS: The method of gas chromatography was used to assay serum concentrations of valproic acid. UGTIA6 A541G genetic polymorphism was screened by PCR-RFLP. Direct sequencing was used to confirm the expected sequences of each genotype. RESULTS: The genotypic frequencies of UGTIA6 A541G were as follows: AA in 76 cases, AG in 65 cases and GG in 6 cases. The mean values of serum concentrations of valproic acid in patients with A541G AA, AG and GG were 3.91+/-1.57, 3.59+/-1.39 and 3.73+/-1.28 microg/mL, respectively (dose-adjusted trough concentration on a mg/kg basis). There were no significant differences in serum concentrations of valproic acid among the three groups. CONCLUSIONS: UGT1A6 A541G gene polymorphism does not influence serum concentrations of valproic acid in Han epileptic children. Individual differences in serum concentrations of valproic acid may be attributed to many factors.

[Identification and expression a D-amino acid dehydrogenase gene from Pseudomonas fluorescens TM5-2].

In the previous study we have isolated DNA fragment containing an alanine racemase gene (dadX) from Pseudomonas fluorescens TM5-2. Adjacent to dadX one ORF similar to a putative glycine/D-amino acid oxidase gene have been found. The same gene organization is found in several Pseudomonas species. Here, author would characterize this ORF to determine what kind of enzyme this gene encodes. DNA fragment containing gene encoding putative glycine/D-amino acid oxidase was cloned into the expression vector. Firstly oxidase activity in cell lysates prepared from the recombinant cells was measured, however, neither glycine nor D-alanine were oxidized judging from hydrogen peroxide formation. Secondly when the amino acid sequence deduced from the oxidase gene was compared to dye-linked D-amino acid dehydrogenases, all the important residues including FAD-binding motif were conserved. This gene was transformed and checked on TFC plate, it showed some activities of D-amino acid dehydrogenase. D-amino acid dehydrogenase activity was also detected when D-alanine and DCIP were used. The best substrate of this enzyme is D-histdine, which is different from some reports. Author will be in progress to purify the dehydrogenase and determine enzyme characteristics.