Preparation of chitosan/retinoic acid @ nanocapsules/TiO2 self-cleaning one-dimensional photonic crystals and the study of the visual detection of acute promyelocytic leukemia.

Sample exposure to air during optical detection leads to the widespread dispersal of microorganisms in the air, posing a health threat to patients and healthcare workers and potentially causing numerous nosocomial infections. In this study, a TiO2/CS-nanocapsules-Va visualization sensor was developed by alternatively spin-coating TiO2, CS and nanocapsules-Va. The uniformly distributed TiO2 can endow the visualization sensor with good photocatalytic performance, and the nanocapsules-Va can bind specifically to the antigen and change its volume. The research results showed that the visualization sensor cannot only detect acute promyelocytic leukemia conveniently, quickly and accurately, but also kill bacteria, decompose organic residues in blood samples under the influence of sunlight, and have an extensive application prospect in substance detection and disease diagnosis.

Tail-stiffness optimization for a flexible robotic fish.

Undulation regulation in a robotic fish propelled by a passive flexible tail is more similar to that of a natural fish than with a rigid tail, owing to the smooth curvature of the flexible tail. Moreover, it has been observed that fish change the stiffness of their bodies to adapt to various swimming states. Inspired by this, a stiffness optimization scheme is explored for a novel elastic tail, which can improve the performance of the robotic fish. Spring steels are used as passive flexible joints of the fishtail; these can be easily expanded into multi-joint structures and the joint stiffness can be altered by changing the joint size. In this study, the Lagrangian dynamic method is employed to establish a dynamic model of the robotic fish in which passive flexible joints are simplified by a pseudo-rigid-body model. In addition, the hydrodynamics of the head and tail are analyzed using the simplified Morison equation and quasi-steady wing theory, respectively. Furthermore, to determine unknown hydrodynamic parameters in the dynamic model, a parameter identification method is applied. The results show that the identified simulation speeds fit the experimental speeds well within a wide range of stiffness values. Finally, to improve performance, the influence of joint stiffness and frequency on swimming speed is investigated based on the identified dynamic model. At each frequency, the optimal joint stiffness distribution is one that reduces the stiffness from the front to the rear. At the maximum driving frequency of 2.5 Hz, the optimal swimming speed is 0.3 body lengths per second, higher than that when rigid joints are used.

The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute myocardial infarction.

AIM: In this study, we evaluated the utility of neutrophil percentage-to-albumin ratio (NPAR) in predicting in critically ill patients with acute myocardial infarction (AMI). METHODS: The information of patients were collected from Medical Information Mart for Intensive Care III database. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were 30-day, 90-day, 180-day, and 365-day all-cause mortality. Cox proportional hazards models and subgroup analyses were used to determine the relationship between admission NPAR and these endpoints. RESULTS: 798 critically ill patients with AMI were enrolled in. After adjustments for age, race and gender, higher admission NPAR was associated with increased risk of 30-day, 90-day, 180-day, and 365-day all-cause mortality in critically ill patients with AMI. And after adjusting for possible confounding variables, two different trends have emerged. Stratified by tertiles, high admission NPAR was independently associated with 180-day and 365-day all-cause mortality in critically ill patients with AMI (tertile 3 vs. tertile 1: adjusted HR, 95% CI 1.71, 1.10-2.66, p < 0.05; 1.66, 1.10-2.51, p < 0.05). In other hand, stratified by quartiles, highest admission NPAR levels were independently associated with 90-day, 180-day and 365-day all-cause mortality (quartile 4 vs. quartile 1: adjusted HR, 95% CI 2.36, 1.32-4.23, p < 0.05; 2.58, 1.49-4.47, p < 0.05; 2.61, 1.56-4.37, p < 0.05). ROC test showed that admission NPAR had a moderate ability to predict all-cause mortality of critically ill patients with AMI. No obvious interaction was found by subgroup analysis in most subgroups. CONCLUSIONS: Admission NPAR was an independent predictor for 180-day and 365-day all-cause mortality in critically ill patients with AMI.

Rapid screening of UPB1 gene variations by high resolution melting curve analysis.

The present study aimed to analyze gene mutations in patients with ß-ureidopropinoase deficiency and establish a rapid detection method for ß-ureidopropinoase (UPB1) pathogenic variations by high resolution melting (HRM) analysis. DNA samples with known UPB1 mutations in three patients with ß-ureidopropinoase deficiency were utilized to establish a rapid detection method for UPB1 pathogenic variations by HRM analysis. Further rapid screening was performed on two patients diagnosed with ß-ureidopropinoase deficiency and 50 healthy control individuals. The results showed that all known UPB1 gene mutations can be analyzed by a specially designed HRM assay. Each mutation has specific HRM profiles which could be used in rapid screening. The HRM method could correctly identify all genetic mutations in two children with ß-ureidopropinoase deficiency. In addition, the HRM assay also recognized four unknown mutations. To conclude, the results support future studies of applying HRM analysis as a diagnostic approach for ß-ureidopropinoase deficiency and a rapid screening method for UPB1 mutation carriers.

[Rapid screening of a hotspot variant c.609G>A in MMACHC gene by using PCR-high-resolution melting curve analysis].

OBJECTIVE: To carry out genetic testing for two families affected with cobalamin C (cblC) and establish a rapid method for the detection of a hotspot pathogenic variant c.609G>A of the MMACHC gene by using a PCR-high-resolution melting curve (PCR-HRM) method. METHODS: Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Potential variants of the MMACHC gene was analyzed by Sanger sequencing. The c.609G>A variant of the MMACHC gene was screened among 100 healthy children with the PCR-HRM method. RESULTS: Sanger sequencing revealed that proband 1 carried compound heterozygous variants c.394C>T and c.609G>A of the MMACHC gene, while proband 2 carried compound heterozygous variants c.482G>A and c.609G>A of the same gene. PCR-HRM analysis of the two probands and the 100 healthy children were consistent with the Sanger sequencing. CONCLUSION: c.609G>A is a hotspot pathogenic variant of the MMACHC gene. The diagnosis of cblC may be rapidly attained through detection by PCR-HRM.

Rapid screening of MMACHC gene mutations by high-resolution melting curve analysis.

BACKGROUND: Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the MMACHC gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations. METHODS: A PCR followed by high-resolution melting curve analysis (PCR-HRM) method covering all coding exons of MMACHC gene was designed to verify 14 pathogenic MMACHC gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC. RESULT: By PCR-HRM analysis, 14 pathogenic variants of MMACHC showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G > A (p.Trp203Ter) can also be analyzed by specially designed PCR-HRM. CONCLUSION: The established PCR-HRM method for screening common pathogenic MMACHC variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large-sample screening of suspected children with methylmalonic acidemia and carriers in population.

An antibacterial and biocompatible multilayer biomedical coating capable of healing damages.

Besides the excellent biocompatibility and high antibacterial property, multifunctional biomedical coatings with a long service time is highly desirable for extended applications, which is still an ongoing challenge. The self-healing property enables new directions for effectively prolonging their service life and significantly improving their reliability. Herein, an efficient and simple method is used to facilely prepare antibacterial, biocompatibile multilayer polyelectrolyte coatings, which are capable of healing damages. The synthetic strategy involves the alternate deposition of Chitosan (CS) and sodium carboxymethyl cellulose (CMC) via the layer-by-layer (LBL) self-assembly technique. The CS/CMC multilayer polyelectrolyte coating features high antibacterial property, fast and efficient self-healing property, and excellent biocompatibility. These features allow the CS/CMC polyelectrolyte coating to have extended lifespan and to be highly promising for novel functional stent coating applications.

A novel missense in GLI3 possibly affecting one of the zinc finger domains may lead to postaxial synpolydactyly: case report.

BACKGROUND: Polydactyly is one of the most common congenital hand/foot malformations in humans. Mutations in GLI3 have been reported to cause syndromic and non-syndromic forms of preaxial and postaxial polydactylies. CASE PRESENTATION: The patient was a 2-year-old boy who underwent surgery in our hospital. The right hand and left foot of the patient were labelled as postaxial polydactyly type B, and there was cutaneous webbing between the 3rd and 4th fingers of the left hand. We identified a novel c. 1622C > T variant in GLI3 leading to an isolated postaxial synpolydactyly. CONCLUSIONS: The patient carries a novel autosomal dominant heterozygous missense mutation. This mutation c.1622C > T;p.(Thr541Met) in the GLI3 gene may affect the normal function of the zinc finger domain (ZFD) in a different way. However, it seems that more research is needed to determine the exact effects of this mutation.

A case of intellectual disability reveals a novel mutation in IQSEC2 gene by whole exome sequencing.

Intellectual disability refers to significantly subaverage intellectual function (intelligence quotient < 70) with impairment of adaptive function. The IQSEC2 gene is one of the pathogenic genes located on chromosome Xp11.22. IQSEC2 is an X-linked gene correlated with intellectual disability and epilepsy. In this study, we reported a 2-year-old male patient presented with reacting sluggishly with people and surroungdings. Active electroencephalogram showed the background of epileptic activity. Brain MRI revealed patchy hyperintensity of bilateral parietal lobe white matter on fluid-attenuated inversion recovery image and widened ventricle, cistern and sulci on T2-weighted image. Delayed myelination was considered. The diagnosis of intellectual disability and epilepsy was made. Whole exome-sequencing was conducted and identified a novel frameshift mutation in exon 15 of IQSEC2 (NM_001111125.2: c.4164dupC: p.Ile1389 Hisfs*218). The variant resulted in the deletion of termination codon, and the protein was extended to termination after stretch of 218 amino acids.This study expands the mutation spectrum of IQSEC2. It supports the published data suggesting that IQSEC2 plays a significant part in patients with intellectual disability and epilepsy. IQSEC2 should be detected in patients with intellectual disability and epilepsy.

Clinical diagnosis and mutation analysis of four Chinese families with succinic semialdehyde dehydrogenase deficiency.

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessively-inherited defect of γ-aminobutyric acid (GABA) metabolism. The absence of SSADH, which is encoded by aldehyde dehydrogenase family 5 member A1 (ALDH5A1) gene, leads to the accumulation of GABA and γ-hydroxybutyric acid (GHB). Few cases with SSADH deficiency were reported in China. CASE PRESENTATION: In this study, four Chinese patients were diagnosed with SSADH deficiency in Tianjin Children's Hospital. We conducted a multidimensional analysis with magnetic resonance imaging (MRI) of the head, semi quantitative detection of urine organic acid using gas chromatography-mass spectrometry, and analysis of ALDH5A1 gene mutations. Two of the patients were admitted to the hospital due to convulsions, and all patients were associated with developmental delay. Cerebral MRI showed symmetrical hyperintense signal of bilateral globus pallidus and basal ganglia in patient 1; hyperintensity of bilateral frontal-parietal lobe, widened ventricle and sulci in patient 2; and widened ventricle and sulci in patient 4. Electroencephalogram (EEG) revealed the background activity of epilepsy in patient 1 and the disappearance of sleep spindle in patient 2. Urine organic acid analysis revealed elevated GHB in all the patients. Mutational analysis, which was performed by sequencing the 10 exons and flanking the intronic regions of ALDH5A1 gene for all the patients, revealed mutations at five sites. Two cases had homozygous mutations with c.1529C > T and c.800 T > G respectively, whereas the remaining two had different compound heterozygous mutations including c.527G > A/c.691G > A and c.1344-2delA/c.1529C > T. Although these four mutations have been described previously, the homozygous mutation of c.800 T > G in ALDH5A1 gene is a novel discovery. CONCLUSION: SSADH deficiency is diagnosed based on the elevated GHB and 4, 5DHHA by urinary organic acid analysis. We describe a novel mutation p.V267G (c.800 T > G) located in the NAD binding domain, which is possibly crucial for this disease's severity. Our study expands the mutation spectrum of ALDH5A1 and highlights the importance of molecular genetic evaluation in patients with SSADH deficiency.

[Inhibitory effect of magnesium cantharidate on human hepatoma SMMC-7721 cell proliferation by blocking MAPK signaling pathway].

Objective To investigate the anticancer mechanism of magnesium cantharidate by observing its effect on the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma SMMC-7721 cells. Methods The protein phosphatase 2A (PP2A) activity detection kit was used to detect the effects of magnesium cantharidate and okadaic acid (OA) on PP2A activity. After the treatment of SMMC-7721 cells with magnesium cantharidate and/or OA, mRNA levels of extracellular signal-regulated kinase 1 (ERK1), ERK2, p38MAPK, c-Jun N-terminal kinase 1 (JNK1) and JNK2 were detected by real-time quantitative PCR, and the protein expression levels and protein phosphorylation of ERK1, ERK2, p38 MAPK and JNK were determined by Western blotting. Results The effect of magnesium cantharidate on the activity of PP2A in SMMC-7721 cells was not evident at the concentration of 0.283 µmol/L, but the activity of PP2A was declined significantly at 0.567 µmol/L or higher concencentrations in a concentration-dependent manner. Likewise, OA also displayed apparent inhibitory effect on the activity of PP2A at 0.059 nmol/L. Compared with the control group, mRNA levels of ERK1 and ERK2 were not changed by magnesium cantharidate at 0.283 µmol/L, but they significantly declined at the concentrations greater than 0.567 µmol/L. In contrast, mRNA levels of ERK1 and ERK2 were significantly elevated by 0.059 nmol/L OA. mRNA levels of p38MAPK, JNK1 and JNK2 significantly increased after the treatment of 0.059 nmol/L OA or magnesium cantharidate at varying concentrations. Compared with the control group, phosphorylation levels of ERK1 and ERK2 were not changed by 0.283 µmol/L magnesium cantharidate, but decreased significantly when the concentration was 0.567 µmol/L or above. In contrast, the phosphorylation levels of ERK1 and ERK2 showed a significant increase in 0.059 nmol/L OA treated group. The phosphorylation levels of p38 MAPK, JNK1 and JNK2 were also significantly increased by 0.059 nmol/L OA or magnesium cantharidate in a concentration-dependent manner. Conclusion Magnesium cantharidate may inhibit the proliferation of SMMC-7721 cells by inhibiting the activity of PP2A and ERK1/2 signaling pathway.