A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Evaluating the influence of Nano-GO concrete pavement mechanical properties on road performance and traffic safety using ANN-GA and PSO techniques.

The burgeoning demand for durable and eco-friendly road infrastructure necessitates the exploration of innovative materials and methodologies. This study investigates the potential of Graphene Oxide (GO), a nano-material known for its exceptional dispersibility and mechanical reinforcement capabilities, to enhance the sustainability and durability of concrete pavements. Leveraging the synergy between advanced artificial intelligence techniques-Artificial Neural Networks (ANN), Genetic Algorithms (GA), and Particle Swarm Optimization (PSO)-it is aimed to delve into the intricate effects of Nano-GO on concrete's mechanical properties. The empirical analysis, underpinned by a comparative evaluation of ANN-GA and ANN-PSO models, reveals that the ANN-GA model excels with a minimal forecast error of 2.73%, underscoring its efficacy in capturing the nuanced interactions between GO and cementitious materials. An optimal concentration is identified through meticulous experimentation across varied Nano-GO dosages that amplify concrete's compressive, flexural, and tensile strengths without compromising workability. This optimal dosage enhances the initial strength significantly, and positions GO as a cornerstone for next-generation premium-grade pavement concretes. The findings advocate for the further exploration and eventual integration of GO in road construction projects, aiming to bolster ecological sustainability and propel the adoption of a circular economy in infrastructure development.

Concurrent abnormalities in galvanic cervical and ocular vestibular-evoked myogenic potentials as a predictive marker for prolonged dizziness in vestibular neuritis.

BACKGROUND: Despite the growing use of cervical (cVEMP) and ocular (oVEMP) VEMP tests, their effectiveness in predicting chronic dizziness in vestibular neuritis (VN) patients remains unclear. Our research examines the link between long-lasting dizziness and inner ear assessments, encompassing VEMPs induced by air-conducted sound (ACS), bone-conducted vibration (BCV), and galvanic vestibular stimulation (GVS). OBJECTIVES: This study explores prognostic markers by examining the relationship between the persistence of dizziness symptoms and various inner ear test findings in VN patients. MATERIAL AND METHODS: A retrospective cohort of 60 unilateral VN patients underwent comprehensive audiovestibular tests, including pure tone audiometry, cVEMP and oVEMP induced by ACS, BCV, GVS, and caloric tests. Patient subgroups were established based on dizziness duration: short-term (<3 months) and long-term (≥3 months). RESULTS: No substantial correlation existed between the dizziness duration and the outcomes of any particular single inner ear test. However, patients exhibiting concurrent abnormal GVS-cVEMP and GVS-oVEMP were more likely to experience prolonged dizziness, indicating more extensive vestibular system involvement. CONCLUSIONS: Concurrent abnormalities in GVS-cVEMP and GVS-oVEMP may indicate a higher chance of long-term dizziness in VN. SIGNIFICANCE: This study identifies concurrent abnormalities in GVS-cVEMP and GVS-VEMP as a potential prognostic marker for prolonged dizziness in VN.

Evaluation of the quality and readability of ChatGPT responses to frequently asked questions about myopia in traditional Chinese language.

Introduction: ChatGPT can serve as an adjunct informational tool for ophthalmologists and their patients. However, the reliability and readability of its responses to myopia-related queries in the Chinese language remain underexplored. Purpose: This study aimed to evaluate the ability of ChatGPT to address frequently asked questions (FAQs) about myopia by parents and caregivers. Method: Myopia-related FAQs were input three times into fresh ChatGPT sessions, and the responses were evaluated by 10 ophthalmologists using a Likert scale for appropriateness, usability, and clarity. The Chinese Readability Index Explorer (CRIE) was used to evaluate the readability of each response. Inter-rater reliability among the reviewers was examined using Cohen's kappa coefficient, and Spearman's rank correlation analysis and one-way analysis of variance were used to investigate the relationship between CRIE scores and each criterion. Results: Forty-five percent of the responses of ChatGPT in Chinese language were appropriate and usable and only 35% met all the set criteria. The CRIE scores for 20 ChatGPT responses ranged from 7.29 to 12.09, indicating that the readability level was equivalent to a middle-to-high school level. Responses about the treatment efficacy and side effects were deficient for all three criteria. Conclusions: The performance of ChatGPT in addressing pediatric myopia-related questions is currently suboptimal. As parents increasingly utilize digital resources to obtain health information, it has become crucial for eye care professionals to familiarize themselves with artificial intelligence-driven information on pediatric myopia.

Solitary Myofibroma of the oral and maxillofacial regions in pediatric patients: A clinicopathological analysis of ten patients and review of 75 cases.

BACKGROUND: The imaging manifestations of oral and maxillofacial myofibroma/myofibromatosis can vary among patients. Although many clinical cases have been reported, a consensus on the clinicopathological features of and treatment principles for this disease is lacking. PURPOSE: This study aimed to summarize the clinicopathological features of solitary myofibroma of the oral and maxillofacial regions in pediatric patients. METHODS: The clinical data, histological features, and immunohistochemical characteristics of ten pediatric patients who underwent surgical removal and subsequent pathological diagnosis of myofibroma were collected and retrospectively and cross-sectionally analyzed. RESULTS: Seven patients were male, and 3 were female, with ages ranging from 3 months to 6 years (mean: 2.6 years). The patients presented with solitary lesions involving the mandibular gingiva and adjacent mandible (4 patients), mandible (2 patients), oral floor and submandibular area and adjacent mandible (1 patient), gingiva (1 patient), maxilla (1 patient), and oropharynx (1 patient). Light microscopy revealed spindle-shaped tumor cells organized in bundles or vortex patterns, forming a hemangiopericytoma-like perivascular pattern, whereas immunohistochemical staining revealed diffuse smooth muscle actin (SMA) positivity. All patients underwent surgical resection, and none experienced recurrence over the 12- to 82-month follow-up. CONCLUSIONS: Solitary myofibroma in the oral and maxillofacial regions is predominantly observed in infants and young children, with a higher incidence among males. The prognosis is favorable following localized lesion resection or curettage of jawbone lesions. Accurate recognition of the clinical, radiological, and pathological features of the disease will reduce the misdiagnosis rate.

SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.

SPHK1 (sphingosine kinase type 1) is characterized as a rate-limiting enzyme in sphingolipid metabolism to phosphorylate sphingosine into sphingosine-1-phosphate (S1P) that can bind to S1P receptors (S1PRs) to initiate several signal transductions leading to cell proliferation and survival of normal cell. Many studies have indicated that SPHK1 is involved in several types of cancer development, however, a little is known in bladder cancer. The TCGA database analysis was utilized for analyzing the clinical relevance of SPHK1 in bladder cancer. Through CRISPR/Cas9 knockout (KO) and constitutive activation (CA) strategies on SPHK1 in the bladder cancer cells, we demonstrated the potential downstream target could be programmed cell death 1 ligand 2 (PD-L2). On the other hand, we demonstrated that FDA-approved SPHK1 inhibitor Gilenya® (FTY720) can successfully suppress bladder cancer metastasis by in vitro and in vivo approaches. This finding indicated that SPHK1 as a potent therapeutic target for metastatic bladder cancer by dissecting the mechanism of action, SPHK1/S1P-elicited Akt/ß-catenin activation promoted the induction of PD-L2 that is a downstream effector in facilitating bladder cancer invasion and migration. Notably, PD-L2 interacted with c-Src that further activates FAK. Here, we unveil the clinical relevance of SPHK1 in bladder cancer progression and the driver role in bladder cancer metastasis. Moreover, we demonstrated the inhibitory effect of FDA-approved SPHK1 inhibitor FTY720 on bladder cancer metastasis from both in vitro and in vivo models.

Recent Advances in Electrochemical Carboxylation with CO2.

ConspectusCarbon dioxide (CO2) is recognized as a greenhouse gas and a common waste product. Simultaneously, it serves as an advantageous and commercially available C1 building block to generate valuable chemicals. Particularly, carboxylation with CO2 is considered a significant method for the direct and sustainable production of important carboxylic acids. However, the utilization of CO2 is challenging owing to its thermodynamic stability and kinetic inertness. Recently, organic electrosynthesis has emerged as a promising approach that utilizes electrons or holes as environmentally friendly redox reagents to produce reactive intermediates in a controlled and selective manner. This technique holds great potential for the CO2 utilization.Since 2015, our group has been dedicated to exploring the utilization of CO2 in organic synthesis with a particular focus on electrochemical carboxylation. Despite the significant advancements made in this area, there are still many challenges, including the activation of inert substrates, regulation of selectivity, diversity in electrolysis modes, and activation strategies. Over the past 7 years, our team, with many great experts, has presented findings on electrochemical carboxylation with CO2 under mild conditions. In this context, we primarily highlight our contributions to selective electrocarboxylations, encompassing new reaction systems, selectivity control methods, and activation approaches.We commenced our research by establishing a Ni-catalyzed electrochemical carboxylation of unactivated aryl halides and alkyl bromides in conjunction with a useful paired anodic reaction. This approach eliminates the need for sacrificial anodes, rendering the carboxylation process sustainable. To further utilize the widely existing yet cost-effective alkyl chlorides, we have developed a deep electroreductive system to achieve carboxylation of unactivated alkyl chlorides and poly(vinyl chloride), allowing the direct modification and upgrading of waste polymers.Through precise adjustment of the electroreductive conditions, we successfully demonstrated the dicarboxylation of both strained carbocycles and acyclic polyarylethanes with CO2 via C-C bond cleavage. Furthermore, we have realized the dicarboxylative cyclization of unactivated skipped dienes to produce the valuable ring-tethered adipic acids through single-electron reduction of CO2 to the CO2 radical anion (CO2•-). In terms of the asymmetric carboxylation, Guo's and our groups have recently achieved the nickel-catalyzed enantioselective electroreductive carboxylation reaction using racemic propargylic carbonates and CO2, paving the way for the synthesis of enantioenriched propargylic carboxylic acids.In addition to the aforementioned advancements, Lin's and our groups have also developed new electrolysis modes to achieve regiodivergent C-H carboxylation of N-heteroarenes dictated by electrochemical reactors. The choice of reactors plays a crucial role in determining whether the hydrogen atom transfer (HAT) reagents are formed anodically, consequently influencing the carboxylation pathways of N-heteroarene radical anions in the distinct electrolyzed environments.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

[Niche and interspecific association of main woody plants in Cunninghamia lanceolata plantation community in Jianfengling, China]. / 尖峰岭杉木人工林群落主要木本植物的生态位和种间联结.

Studies on niche and interspecific association can reveal plant interspecific relationship in the community, and provide theoretical support for promoting the transformation and development of plantation to natural forest. Based on Cunninghamia lanceolata investigation data of permanent plots of plantation in Jianfengling area of Hainan Tropical Rainforest National Park, we analyzed niche and interspecific association of the top 20 woody species in the community according to their importance values. The results showed that there were 163 species of woody species belonging to 101 genera and 55 families in the C. lanceolata plantation community, with complex species composition. As a constructive species, C. lanceolata had the highest importance value and niche breadth, and thus was the absolute dominant species in the community. It had a large niche overlap and niche similarity with many other species, among which the highest was observed in Adinandra hainanensis. The average niche overlap and niche similarity of the community were 0.54 and 0.49, respectively. The change trends of those two niche indicators were basically the same, indicating that some species were similar in resource demands. The overall association of main woody species was significantly positive. The χ2 test, association coefficient, Pearson correlation coefficient, and Spearman rank correlation coefficient suggested that the amounts of pairs with positive association were more than that with negative ones. The proportion of significant association species pairs was relatively low, indicating that the community stability was strong, species could coexist stably, and most species did not form close ties. On the whole, C. lanceolata had inhibited the regeneration of original tree species, and A. hainanensis, Garcinia oblongifolia, and Heptapleurum heptaphyllum could be used in natural transformation and restoration of C. lanceolata plantation in the Hainan Tropical Rainforest National Park.

Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to Helicobacter pylori in an acidic environment.

Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.

The radiation protection behavior of medical workers: A scoping review protocol.

INTRODUCTION: Radiation exposure in medical settings stands as the primary source of artificial radiation, compounded by the yearly rise in healthcare worker numbers. Ensuring radiation protection is crucial for safeguarding their occupational health. Nevertheless, existing studies on radiation protection behavior exhibit considerable heterogeneity due to various factors. OBJECTIVE: This scoping review aims to explore the current status of research on radiation protection behavior and identify research gaps, intending to guide future research directions. METHODS AND ANALYSIS: The scoping review will follow the Arksey and O'Malley framework and the Joanna Briggs Institute methodology. A systematic search will be conducted across English databases including PubMed, Web of Science, Embase, and Medline, as well as Chinese databases such as CNKI, Wanfang, VIP, and China Biomedical Literature Database. Two independent reviewers will screen the studies based on predefined eligibility criteria and extract the data. Any disagreements will be resolved through discussion by a third reviewer. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. STRENGTHS AND LIMITATIONS OF THIS STUDY: A stakeholder consultation will provide an opportunity to validate the findings and address any potential gaps in the article. In this scoping review, all types of studies will be considered. The effectiveness of the methodological quality of the included studies will not be reported, which may lead to some studies of poor quality being included. Only studies published in English or Chinese after 2010 will be considered in this review, potentially leading to the omission of relevant papers.

Shared decision-making, treatment decision regret, and vision-related quality of life among parents of children with myopia: An online survey in Taiwan.

OBJECTIVES: To investigate the relationships among myopia treatment, decision regret, shared decision-making, and vision-related quality of life among parents of 6-12-year-old children with myopia. METHODS: An online Google Forms questionnaire was developed using a cross-sectional design and distributed between January 16 and August 22, 2023. Parents of 6-12-year-old children with myopia were recruited through school nurses working in Taiwan. The children's and parents' demographic data were collected. Study instruments included the Decisional Regret Scale, Shared Decision-Making, and Vision-Related Quality of Life questionnaires. Multivariable linear regression analysis was used to identify factors influencing vision-related quality of life. RESULTS: Of 350 parents contacted, 314 questionnaires were analyzed. Among the respondents, 77.39 % (n = 243) were mothers, and most were aged >40 years. The mean age of children at myopia diagnosis was 7.12 ± 1.24 years; 46.50 % had < - 1.0 diopters of refractive error. Atropine eye drops were the primary treatment; 17.71 % of children were prescribed orthokeratology for myopia control. Parents reported low levels of decision regret and moderate levels of shared decision-making and vision-related quality of life. Children's age, use of orthokeratology lenses, decision regret, and shared decision-making significantly influenced the vision-related quality of life reported by the parents, accounting for 22.5 % of the variance. CONCLUSION: The study's findings emphasize the importance of addressing decision regret and promoting shared decision-making in myopia treatment. Eye care professionals should discuss treatment options thoroughly before making decisions. Through shared decision-making, parents can make informed choices about treatments based on a comprehensive understanding of the benefits and drawbacks, ultimately benefitting children's vision health.

Machine Learning on Ultrasound Texture Analysis Data for Characterizing of Salivary Glandular Tumors: A Feasibility Study.

BACKGROUND: Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors. MATERIAL AND METHODS: 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. Representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use a t-test to test the significance and use the receiver operating characteristic curve method to find the optimal cut-point for these significant features. After splitting 80% of the data into a training set and 20% data into a testing set, we use five machine learning models, k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANNs) and supportive vector machine (SVM), to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors. RESULTS: This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign and malignant tumors (p < 0.05). In ML, the overall accuracy rates are 74.3% (95%CI: 59.8-88.8%), 94.3% (86.6-100%), 72% (54-89%), 84% (69.5-97.3%) and 73.5% (58.7-88.4%) for kNN, Naïve Bayes, Logistic regression, a one-node ANN and SVM, respectively. CONCLUSIONS: US texture analysis with ML has potential as an objective and valuable tool to make a differential diagnosis between benign and malignant salivary gland tumors.

Analyzing three pedigrees in X-linked Alport syndrome with the presentation of nephrotic syndrome.

Background: Alport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations. Methods: Three Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals' peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members. Results: Both probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A's mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C>T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects. Conclusion: The novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C>T may present NS as their primary clinical manifestation.

Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.

BACKGROUND: Lytic Epstein-Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs. METHODS: By culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs. RESULTS: When IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs. CONCLUSION: We established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.

In vitro study of ATP1A3 p.Ala275Pro mutant causing alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism.

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

Research progress of nano delivery systems for intraocular pressure lowering drugs.

Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, ß-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.

How the root bacterial community of Ficus tikoua responds to nematode infection: enrichments of nitrogen-fixing and nematode-antagonistic bacteria in the parasitized organs.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant-nematode-microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant-nematode-bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

Attitude and utilization of ChatGPT among registered nurses: A cross-sectional study.

AIM: This study explores the influencing factors of attitudes and behaviors toward use of ChatGPT based on the Technology Acceptance Model among registered nurses in Taiwan. BACKGROUND: The complexity of medical services and nursing shortages increases workloads. ChatGPT swiftly answers medical questions, provides clinical guidelines, and assists with patient information management, thereby improving nursing efficiency. INTRODUCTION: To facilitate the development of effective ChatGPT training programs, it is essential to examine registered nurses' attitudes toward and utilization of ChatGPT across diverse workplace settings. METHODS: An anonymous online survey was used to collect data from over 1000 registered nurses recruited through social media platforms between November 2023 and January 2024. Descriptive statistics and multiple linear regression analyses were conducted for data analysis. RESULTS: Among respondents, some were unfamiliar with ChatGPT, while others had used it before, with higher usage among males, higher-educated individuals, experienced nurses, and supervisors. Gender and work settings influenced perceived risks, and those familiar with ChatGPT recognized its social impact. Perceived risk and usefulness significantly influenced its adoption. DISCUSSION: Nurse attitudes to ChatGPT vary based on gender, education, experience, and role. Positive perceptions emphasize its usefulness, while risk concerns affect adoption. The insignificant role of perceived ease of use highlights ChatGPT's user-friendly nature. CONCLUSION: Over half of the surveyed nurses had used or were familiar with ChatGPT and showed positive attitudes toward its use. Establishing rigorous guidelines to enhance their interaction with ChatGPT is crucial for future training. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers should understand registered nurses' attitudes toward ChatGPT and integrate it into in-service education with tailored support and training, including appropriate prompt formulation and advanced decision-making, to prevent misuse.

A novel splicing mutation DNAH5 c.13,338 + 5G > C is involved in the pathogenesis of primary ciliary dyskinesia in a family with primary familial brain calcification.

BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.