A hemin/rGO/MWCNT nanocomposite-based dual signal electrochemical aptasensor for sensitive detection of NSE.

Neuron-specific enolase (NSE), a tumor marker of small cell lung cancer (SCLC), has high application value in the early diagnosis of SCLC. In this study, a dual signal electrochemical aptasensor for NSE was constructed based on hemin/reduced graphene oxide/multi-walled carbon nanotube (H-rGO-MWCNT) nanocomposites. Hemin played a dual role, functioning not only as an in situ electrochemical probe but also exhibiting excellent peroxidase-like properties, effectively catalyzing the electroreduction of H2O2. Reduced graphene oxide and multi-walled carbon nanotubes exhibited excellent conductivity. Through their binding with hemin, the nanocomposites achieved a larger specific surface area, providing numerous active sites for capturing the NSE aptamer. In the presence of NSE, the specific adsorption between the antigen and the aptamer formed a stable antigen-aptamer structure, which inhibited the performance of hemin, resulting in the weakening of the electrochemical signals of hemin and H2O2. Leveraging these characteristics, the sensitive and cost-effective dual-signal electrochemical aptasensor has been fabricated for the detection of NSE. One signal corresponded to differential pulse voltammetry (DPV) of hemin, while the other signal was derived from chronoamperometry, capturing the catalytic reduction of H2O2. The linear ranges for NSE were 1 pg mL-1 to 1 µg mL-1 and 100 pg mL-1 to 100 ng mL-1 with the limit of detection (LOD) of 0.21 pg mL-1 and 11.22 pg mL-1 by DPV and chronoamperometry, respectively. In addition, this aptasensor exhibited good reproducibility, stability and specificity. The recovery of NSE in human blood serum samples was from 89% to 131%. It provided a promising strategy for the detection of NSE in clinical diagnostics.

SOLAMEN syndrome with cardiovascular damage.

SOLAMEN syndrome is a rare, recently recognized congenital syndrome that is characterized by progressive and hypertrophic diseases involving multiple systems, including segmental overgrowth, lipomatosis, arteriovenous malformation (AVM) and epidermal nevus. According to literatures, SOLAMEN syndrome is caused by heterozygous PTEN mutation. Phenotypic overlap complicates the clinical identification of diseases associated with PTEN heterozygous mutations, making the diagnosis of SOLAMEN more challenging. In addition, SOLAMEN often presents with segmental tissue overgrowth and vascular malformations, increasing the possibility of misdiagnosis as klipple-trenaunay syndrome or Parks-Weber syndrome. Here, we present a case of a child presenting with macrocephaly, patchy lymphatic malformation on the right chest, marked subcutaneous varicosities and capillaries involving the whole body, overgrowth of the left lower limb, a liner epidermal nevus on the middle of the right lower limb, and a large AVM on the right cranial thoracic entrance. Based on the typical phenotypes, the child was diagnosed as SOLAMEN syndrome. detailed clinical, imaging and genetic diagnoses of SOLAMEN syndrome was rendered. Next-generation sequencing (NGS) data revealed that except for a germline PTEN mutation, a PDGFRB variant was also identified. A subsequent echocardiographic examination detected potential cardiac defects. We suggested that given the progressive nature of AVM and the potential severity of cardiac damage, regular echocardiographic evaluation, imaging follow-up and appropriate interventional therapy for AVM are recommended.

WS2 nanosheets-based electrochemical biosensor for highly sensitive detection of tumor marker miRNA-4484.

In this paper, a few-layer WS2 nanosheets-based electrochemical biosensor was fabricated for the highly sensitive detection of breast cancer tumor marker miRNA-4484. Firstly, few-layer WS2 nanosheets were prepared by shear stripping and characterized by SEM, TEM, AFM and UV spectrophotometer. After modification of few-layer WS2 nanosheets on the electrode surface, the miRNA probe was fixed on the few-layer WS2 nanosheets by polycytosine (PolyC). Then short-chain miRNA containing PolyC was used as the blocking agent to close the excess active sites on the surface of WS2 nanosheets to complete the fabrication of the sensor biosensing interface. Finally, the current changes caused by the specific binding of miRNA-4484 to the probe were analyzed by differential pulse voltammetry (DPV). The results showed that the sensor had a good linear relationship for the detection of miRNA-4484 in the concentration range of 1 aM-100 fM, and the detection limit was as low as 1.61 aM. In addition, the electrochemical sensor had excellent selectivity, stability and reproducibility. The artificial sample tests indicated that the developed biosensors have the potential for clinical application in the future.

Multi-spectroscopies and molecular docking insights into the interaction mechanism and antioxidant activity of isoquercetin and zein nanoparticles.

The purpose of this study was to compare and characterize the theoretical properties and interaction mechanisms of zein and isoquercetin (ISO) from experimental and theoretical perspectives. Zein nanoparticles with different ISO concentrations (ZINPs) were prepared by the antisolvent precipitation method. The experimental results indicated all particles appeared spherical. When the mass ratio of zein to ISO was 10:1, the encapsulation efficiency of ZINPs reached 88.19 % with an average diameter of 126.67 nm. The multispectral method and molecular docking results confirmed that hydrogen bonding and van der Waals force played a dominant role for the binding of ISO to zein, and the primary fluorescence quenching mechanism for zein by ISO was static quenching. Furthermore, ZINPs had greater solubility and antioxidant activity, as well as inhibited the release of ISO during simulated gastrointestinal digestion processes. This research contributes to the understanding of the non-covalent binding mechanism between zein and ISO, providing a theoretical basis for the construction of ISO active carriers.

Hemp seed globulin-alginate nanoparticles for encapsulation of Cannabisin A with enhanced colloidal stability and antioxidant activity.

This study develops hemp seed globulin (GLB)-alginate (ALG) nanoparticles (GANPs) for Cannabisin A (CA) stabilization under environmental stress and during pepsin digestion. The optimal GLB: ALG mass ratio of 1: 1.5 was determined for GANPs formation at pH 3.5, resulting in a high yield of 95.13 ± 0.91 %, a ζ-potential of -35.73 ± 1.04 mV, a hydrodynamic diameter of 470.67 ± 11.36 nm, and a PDI of 0.298 ± 0.016. GANPs were employed to encapsulate CA, achieving a high loading capacity of 13.48 ± 0.04 µg mg-1. FTIR analysis demonstrated that the formation of CA-GLB-ALG nanoparticles (CGANPs) involves electrostatic interactions, hydrogen bonding, and hydrophobic interactions. XRD and DSC analyses revealed that CA is amorphous within the CGANPs. CGANPs demonstrated remarkable dispersion stability as well as resistance to high ionic strength and high-temperature treatments, indicating their potential as efficient hydrophobic drug-delivery vehicles. When compared to free CA, CA coated within CGANPs displayed greater DPPH/ABTS scavenging activity. Furthermore, the ALG-shelled nanoparticles protected GLB from pepsin digestion and slowed the release of CA throughout the release process, extending their stay on the intestinal wall mucosa. These findings imply that CGANPs is an ideal delivery vehicle for CA as they may expand the application of CA in food items.

Non-covalent interaction between hemp seed globulin and two hemp seed phenolic compounds: Mechanism and effects on protein structure, bioactivity, and in vitro simulated digestion.

This study focused on elucidating the non-covalent interactions between hemp seed globulin (GLB) and two hemp seed phenolic compounds, Cannabisin A (CA) and Cannabisin B (CB), and to explore these interactions on the protein's structure, conformation, and functionality. Fluorescence quenching and thermodynamic analysis revealed that static quenching governed non-covalent interaction processes, with hydrogen bonds and van der Waals forces functioning as major forces. This was further substantiated by molecular docking studies. The binding affinity order was CA > CB, indicating that the specific phenolic compound had a notable impact on the binding affinity. Furthermore, when complexed with CA, Tyr and Trp residues were exposed to a more hydrophilic environment than when complexed with CB. It was noted that the complexation with either CA or CB consistently affects GLB's secondary structure, particle size, and ζ-potential. GLB treated with the phenolic compounds exhibited enhanced ABTS and DPPH scavenging activities and improved digestibility compared to untreated GLB. Furthermore, the non-covalent interactions significantly increased CA's water solubility, highlighting GLB as a promising natural carrier for hydrophobic bioactive components. These findings hold potential implications for enhancing hemp seed protein applications within the food industry by positively influencing its functional properties and bioactivity.

Effect of hydrochloric acid and citric acid with ultrasound processing on characteristics of superfine-ground pectic polysaccharides from okra (Abelmoschus esculentus L.) peel.

The structural properties and biological activities of okra pectic polysaccharides (OPs) were impacted by various extraction methods. Based on commonly grinding (40, 100 meshes) and superfine grinding okra powders, two extraction solvents (hydrochloric acid, HA; citric acid, CA) were used firstly. Next, the extraction yield, physical and chemical properties, molecular structure and functional properties of OPs were analyzed by non-ultrasonic treatment and ultrasound-assisted superfine grinding method. The outcomes demonstrated that the extraction yield of OPs rose as the particle size of the powder decreased. HA-OPs had higher molecular weight (Mw), apparent viscosity and emulsification ability than CA-OPs. CA-OPs had higher esterification degree (DE), solubility and total sugar content, and higher amounts of rhamnogalacturonan-I (RG-I) segments. Compared with OPs without ultrasound-assisted extraction, ultrasound-assisted superfine grinding extraction exhibited higher sugar content, antioxidant capacity, emulsification ability, lower Mw, DE and apparent viscosity. Finally, the correlation between structure and function of OPs was further quantified. The antioxidant capacity was positively correlated with RG-I content, and negatively correlated with DE and Mw. The emulsification ability was mainly positively correlated with the GlcA of OPs. This study provides a theoretical basis for the development of OPs foods with clear structure-function relationship, which would be instructive for the application of OPs in food and cosmetics.

Application of Silicon Nanowire Field Effect Transistor (SiNW-FET) Biosensor with High Sensitivity.

As a new type of one-dimensional semiconductor nanometer material, silicon nanowires (SiNWs) possess good application prospects in the field of biomedical sensing. SiNWs have excellent electronic properties for improving the detection sensitivity of biosensors. The combination of SiNWs and field effect transistors (FETs) formed one special biosensor with high sensitivity and target selectivity in real-time and label-free. Recently, SiNW-FETs have received more attention in fields of biomedical detection. Here, we give a critical review of the progress of SiNW-FETs, in particular, about the reversible surface modification methods. Moreover, we summarized the applications of SiNW-FETs in DNA, protein, and microbial detection. We also discuss the related working principle and technical approaches. Our review provides an extensive discussion for studying the challenges in the future development of SiNW-FETs.

NRAS p.Q61R/K allele load is correlated to different phenotypes of congenital melanocytic naevi.

BACKGROUND: Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined. AIM: To determine the correlation of variants allele load and different phenotypes of CMN. METHODS: A panel of genes in the Ras/Raf/MAPK signalling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes, including anatomical localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, colour variation and hypertrichosis, were analysed. RESULTS: In addition to the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS (p.G13R and p.M72fs), BRAF (p.D22N) and MAP2K1 (p.I107fs, p.F209fs, p.Q354H and p.G91_L92insHDQARRLVGDLEHHKPSG). Furthermore, a higher allele load of NRAS p.Q61R/K was found in the trunk and limbs of CMN. It was also found in CMN with larger size, higher colour variation and more significant hypertrichosis, surface rugosity and asymmetry. CONCLUSION: We discovered more genetic variants of NRAS, BRAF and MAP2K1 and established a correlation between the allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitate a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics used in clinical practice.

A Review of Transition Metal Dichalcogenides-Based Biosensors.

Transition metal dichalcogenides (TMDCs) are widely used in biosensing applications due to their excellent physical and chemical properties. Due to the properties of biomaterial targets, the biggest challenge that biosensors face now is how to improve the sensitivity and stability. A lot of materials had been used to enhance the target signal. Among them, TMDCs show excellent performance in enhancing biosensing signals because of their metallic and semi-conducting electrical capabilities, tunable band gap, large specific surface area and so on. Here, we review different functionalization methods and research progress of TMDCs-based biosensors. The modification methods of TMDCs for biosensor fabrication mainly include two strategies: non-covalent and covalent interaction. The article summarizes the advantages and disadvantages of different modification strategies and their effects on biosensing performance. The authors present the challenges and issues that TMDCs need to be addressed in biosensor applications. Finally, the review expresses the positive application prospects of TMDCs-based biosensors in the future.

Leopard syndrome: the potential cardiac defect underlying skin phenotypes.

LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis.Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage.

Sirolimus treatment for neonate with blue rubber bleb nevus syndrome: A case report.

BACKGROUND: Blue rubber bleb naevus syndrome (BRBNS) is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract. Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia. The successful management of BRBNS with sirolimus had been reported in many institutions, due to its impact on signaling pathways of angiogenesis. However, the experience in treatment of neonates with BRBNS was limited. CASE SUMMARY: A 38-day-old premature female infant born with multiple skin lesions, presented to our center complaining of severe anemia and hematochezia. Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver. She was diagnosed as having BRBNS based on typical clinical and examination findings. The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate. A review of BRBNS case reports found that patients had been successfully treated with sirolimus. Then the patient was treated with sirolimus at an average dose of 0.95 mg/m2/d with a target drug level of 10-15 ng/mL. During 28 mo of treatment, the lesion was reduced, hemoglobin returned to normal, and there were no adverse drug reactions. CONCLUSION: This case highlights the dosing regimen and plasma concentration in neonates, for the current common empiric dose is high.

A supersensitive silicon nanowire array biosensor for quantitating tumor marker ctDNA.

Cancer has become one of the major diseases threatening human health and life. Circulating tumor DNA (ctDNA) testing, as a practical liquid biopsy technique, is a promising method for cancer diagnosis, targeted therapy and prognosis. Here, for the first time, a field effect transistor (FET) biosensor based on uniformly sized high-response silicon nanowire (SiNW) array was studied for real-time, label-free, super-sensitive detection of PIK3CA E542K ctDNA. High-response 120-SiNWs array was fabricated on a (111) silicon-on-insulator (SOI) by the complementary metal oxide semiconductor (CMOS)-compatible microfabrication technology. To detecting ctDNA, we modified the DNA probe on the SiNWs array through silanization. The experimental results demonstrated that the as-fabricated biosensor had significant superiority in ctDNA detection, which achieved ultralow detection limit of 10 aM and had a good linearity under the ctDNA concentration range from 0.1 fM to 100 pM. This biosensor can recognize complementary target ctDNA from one/two/full-base mismatched DNA with high selectivity. Furthermore, the fabricated SiNW-array FET biosensor successfully detected target ctDNA in human serum samples, indicating a good potential in clinical applications in the future.

Ultrasonic pretreatment enhanced the glycation of ovotransferrin and improved its antibacterial activity.

This study aims to evaluate the effect of ultrasonic pretreatment combined with glycation on the structural characteristics and antibacterial activity of ovotransferrin (OVT). Firstly, OVT (purity >90%) was isolated from egg white with a simple and efficient method. After the treatment of ultrasound and glycation, the browning degree of OVT increased with the rising power of ultrasound, while the number of free amino groups obviously decreased to 25.4%. Various spectrum detection showed that the structures of OVT have changed significantly, indicating the tertiary structure became more flexible and looser. The minimal inhibitory concentration of ultrasound glycated OVT were 25.0 and 32.1 µmol/L for E. coli and S. aureus, respectively. In summary, ultrasound-assisted glycation is an effective technique to improve the biological activity of OVT.

[Application of modified vermillion flap and orbicularoris oris bundle anastomosis in repair of transverse facial cleft].

OBJECTIVE: To improve the method of vermillion flap and orbicularis oris bundle anastomosis in repair of transverse facial cleft. METHODS: Based on the precise fixed point, the modified vermillion flap was designed slender at the new corner of the upper lip, and was inserted into the lower lip after removing part tissue. The orbicularis oris was divided into two bands and cross-stitched. RESULTS: Fifteen patients with unilateral transverse facial cleft form the Children's Hospital of Zhejiang University during September 2016 and December 2018 were operated, and the position and shape of the commissure were almost normal. CONCLUSIONS: The cosmetic effect and oral function are satisfactory when the modified vermillion flap and bundle anastomosis of orbicularis oris is used to repair transverse facial cleft.

Plasma gelsolin level predicts acute kidney injury after cardiopulmonary bypass in infants and young children.

BACKGROUND: Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is a common complication especially in pediatric population. Plasma gelsolin (pGSN) is an anti-inflammatory factor through binding with actin and pro-inflammatory cytokines in circulation. Decrease in pGSN has been reported in some pathologic conditions. The purpose of the study was to determine the alterations of pGSN level in infants and young children after CPB and the role of pGSN as a predictor for the morbidity and severity of post-CPB AKI. METHODS: Sixty-seven infants and young children at age ≤ 3 years old undergoing CPB were prospectively enrolled. PGSN levels were measured during peri-operative period with enzyme-linked immuno-sorbent assay and normalized with plasma total protein concentration. Other clinical characteristics of the patients were also recorded. RESULTS: In patients developing AKI, the normalized pGSN (pGSNN) levels significantly decreased at 6 h post-operation and remained low for 24 h post-operation as compared to the patients with non-AKI. PGSNN at 6 h post-operation combining with CPB time presents an excellent predictive value for AKI. CONCLUSIONS: Decreased pGSNN identifies post-CPB AKI in the patients ≤ 3 years old, and is associated with adverse clinical outcomes. The findings suggest that circulating GSN in post-CPB patients may have beneficial effects on diminishing inflammatory responses.

Episode of Kasabach-Merritt phenomenon following Japanese encephalitis vaccination: Case report.

Kasabach-Merritt phenomenon (KMP) is a rare potentially life-threatening consumptive coagulopathy characterized by thrombocytopenia and hypofibrinogenemia occurring associated with the vascular tumors kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). A 10-month old male infant, diagnosed with KHE on his left leg, underwent a rapid increase of the lesion and severe thrombocytopenia, one day after the first dose of inactivated Japanese encephalitis (JE) vaccination. The episode of KMP was treated successfully by steroid. KMP is a rare complication of vaccination that physicians should be aware of. Giving up the following vaccination to provide the recurrence of KMP is not recommended.

[Effects of histone H3 K4L and K36L mutations on the cell growth and the transcription of GAL1, SSA3 and PHO5 in Saccharomyces cerevisiae].

Post-translational modifications of histones, such as acetylation and methylation, have a pivotal role in regulating gene expression and cell growth. To elucidate the different roles and importance of H3K4 and H3K36 modifications in expression of inducible genes such as Cal1, SSA3, PHO5 and the growth of yeast cell, we constructed three different yeast mutant strains carrying mutations of lysine 4, 36, or both to leucine in the histone H3 tail. Real-time PCR and sensitive assay under the conditions of high temperature, NaCl, caffeine, 6-AU, or other conditions were carried out to characterize the effects of these mutations on cell growth and transcription levels of GAL1, SSA3 and PHO5. The results showed that three histone methylation mutants exhibited more severe growth defects and slower activation of GAL1, SSA3 and PHO5 than those of wild type; H3K4L/H3K36L double mutant strain D436 has the most severe phenotype. H3K4L mutants S4 exhibited more severe defects than those of H3K36L S36 mutants, especially at high temperature and high NaCl stresses. These results show that H3K4L and H3K36L are important for the growth and survival of yeast in unfavorable conditions, and that different mutations have different effects on the expression of single inducible gene, whereas the same mutation has different effects on the activation of different inducible genes in vivo. The post-translational modification of H3K4 is more important than H3K36 on the adaptation to harsh condition for yeast cell. The growth defects of histone mutant strains might arise from the slow activation of inducible gene essential for survival at harsh conditions.