Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.

BACKGROUND: KCNQ is a voltage-gated K + channel that controls neuronal excitability and is mutated in epilepsy and autism spectrum disorder (ASD). We focus on the KV7.2 voltage-gated potassium channel gene (KCNQ2), which is known for its association with developmental delay and various seizures (including self-limited benign familial neonatal epilepsy and epileptic encephalopathy). But the pathogenicity of many variants remains unproven, potentially leading to misinterpretation of their functional consequences. METHODS: In this study, we studied a patient who visited Nanhua Hospital. Targeted next-generation sequencing and Sanger sequencing were used to identify the pathogenic variants. Meanwhile, computational models, including hydrogen bonding and docking analyses, suggest that variants cause functional impairment. In addition, functional validation was performed in the drosophila to further evaluate the missense variant in the KCNQ2 gene as the cause of this patient. RESULTS: A new missense variant in the KCNQ2 gene was identified: NM_172107.4:c.1007C > A(p.ALa336Glu), which resulted in the change from alanine to glutamate at amino acid position 336 in the KCNQ2 gene. After computational modeling, including hydrogen bond analysis and docking analysis, it is indicated that the variants cause functional impairment. Furthermore, RNAi-mediated KCNQ knockout in flies led to the onset of epileptic behavior, lifespan and climbing capacity were affected, expression of the normal human KCNQ2 rescues the in flies RNAi-mediated KCNQ knockout behavioral abnormalities. CONCLUSION: Our findings expands the genetic profile of KCNQ2 and enhances the genotype - phenotype link.

Hydrogel Coatings of Implants for Pathological Bone Repair.

Hydrogels are well-suited for biomedical applications due to their numerous advantages, such as excellent bioactivity, versatile physical and chemical properties, and effective drug delivery capabilities. Recently, hydrogel coatings have developed to functionalize bone implants which are biologically inert and cannot withstand the complex bone tissue repair microenvironment. These coatings have shown promise in addressing unique and pressing medical needs. This review begins with the major functionalized performance and interfacial bonding strategy of hydrogel coatings, with a focus on the novel external field response properties of the hydrogel. Recent advances in the fabrication strategies of hydrogel coatings and their use in the treatment of pathologic bone regeneration are highlighted. Finally, challenges and emerging trends in the evolution and application of physiological environment-responsive and external electric field-responsive hydrogel coatings for bone implants are discussed.

Comparison of the impact of team-based learning and lecture-based learning on nursing students' core competencies: A systematic review and meta-analysis.

AIM: This study aims to evaluate the effect of team-based learning on the core competence of nursing students compared with traditional teaching methods. BACKGROUND: In recent years, team-based learning has been widely used as a learning and teaching method in the world. Not only the necessary knowledge, skills and attitudes, but also the core competence is necessary to cope with various clinical situations for nursing students. However, the effect of this new teaching method on core competence of nursing students is not consistent. DESIGN: The study was designed according to the preferred reporting entries guidelines statement for systematic reviews and meta-analyses and population, intervention, comparison, outcome and study. METHODS: Data were collected from PubMed, Embase, Web of Science, ScienceDirect and Scopus. The quality of studies was assessed using "The Newcastle Ottawa scale". A random-effect model of meta-analyses was conducted to generate pooled standardized mean differences (SMD) for core competence using Rev Man 5.4.1 software and STATASE 15. Moreover, subgroup, heterogeneity, sensitivity and publication bias analyses were conducted. RESULTS: A total of 14 articles with 1942 participants were included in the meta-analysis. Compared with the traditional pedagogy among nursing students, team-based learning pedagogy significantly increased theoretical performance, professional effects (self-directed learning ability and communication ability) but did not affect practice skills. In addition, one study found that learning attitudes were not improved in students with high or low academic performance. This might mean that the teaching model should be implemented for a long time, which essentially changed students' learning attitudes to improve students' self-directed learning ability and core competence, especially for students with low scores. CONCLUSIONS: In summary, findings indicated that team-based learning pedagogical approaches might be beneficial to improve teaching quality in nursing education. However, practice skills might not be sensitive to team-based learning because of the seriation of the original course. Nursing educators need to explore teaching strategies to cultivate high-quality nursing talents to cultivate nursing students with core competence and ensure that they are successfully qualified for new employment.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

NIR-responsive micropatterned nanocomposite functionalized implant for sequential antibacterial and osteogenesis.

The long-term durability of the implant is influenced by two significant clinical challenges, namely bacterial infection and fixation loosening. Conventional implant materials have failed to meet the demands of the dynamic process of infectious bone repair, which necessitates early-stage bacterial sterilization and a conducive environment for late-stage osteogenesis. Consequently, there is an urgent requirement for an implant material that can sequentially regulate antibacterial properties and promote osteogenesis. The study aimed to develop a micropatterned graphene oxide nanocomposite on titanium implant (M-NTO/GO) for the sequential management of bacterial infection and osteogenic promotion. M-NTO/GO exhibited a micropattern nanostructure surface and demonstrated responsiveness to near-infrared (NIR) light. Upon NIR light irradiation, M-NTO/GO exhibited effective antibacterial properties, achieving antibacterial rates of 96.9% and 98.6% against E. coli and S. aureus, respectively. Under no-light condition, the micropatterned topography of M-NTO/GO exhibited the ability to induce directed cell growth, enhance cell adhesion and spreading, and facilitate osteogenic differentiation. These findings suggest the successful development of a functionalized micropatterned nanocomposite implant capable of sequentially regulating antibacterial and osteogenesis activity. Consequently, this highly effective strategy holds promise for expanding the potential applications of orthopedic implants.

Research progress on the relationship between epilepsy and circRNA.

OBJECTIVE: This review aims to provide a comprehensive summary of the latest research progress regarding the relationship between epilepsy and circular RNA (circRNA). METHODS: Relevant literature from the PubMed database was meticulously searched and reviewed. The selected articles focused on investigating the association between epilepsy and circRNA, including studies on expression patterns, diagnostic markers, therapeutic targets, and functional mechanisms. RESULTS: Epilepsy, characterized by recurrent seizures, is a neurological disorder. Numerous studies have demonstrated significant alterations in the expression profiles of circRNA in epileptic brain tissues, animal models, and peripheral blood samples. These differential expressions of circRNA are believed to be closely linked with the occurrence and development of epilepsy. Moreover, circRNA has shown promising potential as diagnostic markers for epilepsy, as well as prognostic indicators for predicting disease outcomes. Furthermore, circRNA has emerged as a potential therapeutic target for epilepsy treatment, offering prospects for gene therapy interventions. CONCLUSION: The dysregulation of circRNA expression in epilepsy suggests its potential involvement in the pathogenesis and progression of this disorder. Identifying specific circRNA molecules associated with epilepsy may pave the way for novel diagnostic approaches and therapeutic strategies. However, further investigations are imperative to elucidate the precise functional mechanisms of circRNA in epilepsy and validate its clinical utility.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Critical thinking disposition of medical students in Anhui Province, China: a cross-sectional investigation.

OBJECTIVE: To investigate the critical thinking disposition of medical undergraduates. METHODS: This cross-sectional study was performed on 426 students from four majors, including preventive medicine, maternal and children's health care medicine, health inspection and quarantine, and food quality and safety. The survey was completed in May 2019 using the California Critical Thinking Dispositions Inventory-Chinese version (CTDI-CV). RESULTS: A total of 435 questionnaires were distributed and 426 valid questionnaires were collected, with an effective rate of 97.93%. The CTDI-CV overall average score was 262.02 ± 34.74 points indicating an ambivalent disposition in medical undergraduate students. Only one of the subscales (maturity in judgment) had mean scores of 43.35 ± 8.23 indicating the positive disposition of students. Among them, males scored 257.42 ± 35.06 lower than females' 264.82 ± 34.32, the difference was statistically significant. The target scores of preventive medicine, maternal and children's health medicine, health inspection and quarantine, and food quality and safety were 265.17 ± 30.10, 260.26 ± 37.05, 271.73 ± 33.55, and 252.11 ± 39.87, respectively. The difference was statistically significant. Among the three dimensions of seeking truth, open mind, and cognitive maturity, the scores of males were 38.26 ± 7.48, 38.78 ± 6.46 and 41.03 ± 8.69, which were lower than females' 39.97 ± 7.11, 40.48 ± 6.48 and 44.91 ± 7.60, respectively. The scores of food quality and safety students were 37.23 ± 7.08, 36.61 ± 7.41 and 40.57 ± 8.60, respectively, which were lower than the preventive medicine (39.98 ± 7.07, 40.60 ± 5.96 and 44.44 ± 6.97, respectively). CONCLUSION: Most medical students were found to have an ambivalent disposition which meant they were not disposed toward critical thinking. These findings suggested that more effective teaching methods should be taken to facilitate critical thinking disposition and problem-solving ability.

Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

Electro-mechanical coupling directs endothelial activities through intracellular calcium ion deployment.

Conversion between mechanical and electrical cues is usually considered unidirectional in cells with cardiomyocytes being an exception. Here, we discover a material-induced external electric field (Eex) triggers an electro-mechanical coupling feedback loop in cells other than cardiomyocytes, human umbilical vein endothelial cells (HUVECs), by opening their mechanosensitive Piezo1 channels. When HUVECs are cultured on patterned piezoelectric materials, the materials generate Eex (confined at the cellular scale) to polarize intracellular calcium ions ([Ca2+]i), forming a built-in electric field (Ein) opposing Eex. Furthermore, the [Ca2+]i polarization stimulates HUVECs to shrink their cytoskeletons, activating Piezo1 channels to induce influx of extracellular Ca2+ that gradually increases Ein to balance Eex. Such an electro-mechanical coupling feedback loop directs pre-angiogenic activities such as alignment, elongation, and migration of HUVECs. Activated calcium dynamics during the coupling further modulate the downstream angiogenesis-inducing eNOS/NO pathway. These findings lay a foundation for developing new ways of electrical stimulation-based disease treatment.