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Gene-editing technology shows great potential in glioblastoma (GBM) therapy. Due to the complexity of GBM pathogenesis, a single gene-editing-based therapy is unlikely to be successful; therefore, a multi-gene knockout strategy is preferred for effective GBM inhibition. Here, a non-invasive, biodegradable brain-targeted CRISPR/Cas12a nanocapsule is used that simultaneously targeted dual oncogenes, EGFR and PLK1, for effective GBM therapy. This cargo nanoencapsulation technology enables the CRISPR/Cas12a system to achieve extended blood half-life, efficient blood-brain barrier (BBB) penetration, active tumor targeting, and selective release. In U87MG cells, the combinatorial gene editing system resulted in 61% and 33% knockout of EGFR and PLK1, respectively. Following systemic administration, the CRISPR/Cas12a system demonstrated promising brain tumor accumulation that led to extensive EGFR and PLK1 gene editing in both U87MG and patient-derived GSC xenograft mouse models with negligible off-target gene editing detected through NGS. Additionally, CRISPR/Cas12a nanocapsules that concurrently targeted the EGFR and PLK1 oncogenes showed superior tumor growth suppression and significantly improved the median survival time relative to nanocapsules containing single oncogene knockouts, signifying the potency of the multi-oncogene targeting strategy. The findings indicate that utilization of the CRISPR/Cas12a combinatorial gene editing technique presents a practical option for gene therapy in GBM.

Abstract Purpose This study aims to establish reference values for the normal bone axis in children to assess the effectiveness of corrective osteotomy procedures and guide the treatment of congenital hand malformations and post-operative axis deviations. Methods A retrospective study was carried out between January 1, 2022, and October 9, 2024. A total of 192 individuals were included. In both abnormal and normal individuals, we measured the angles within the zone of provisional calcification and the bone axis. The metacarpal, proximal, and distal phalanx of the thumb were measured in both males and females. We calculated the average and standard deviations for both groups. These normal reference values were then compared with the abnormal reference values of patients who had types II and IV polydactyly. Results Our work effectively established thorough reference values for the thumb's normal axis. Considering the success of corrective osteotomies in children with congenital deformities depends mostly on these values. In polydactyly type IV, we observed a change in the angle on the side with the axis deviation. Our results highlight the need for an exact preoperative design for thumb reconstruction. It also implies the possibility of choosing the side with little or no axis deviation during operation. This strategic selection can help prevent the need for additional osteotomies or subsequent surgeries. Conclusion Evaluating and preparing corrective osteotomy treatments benefits significantly from the reference values for the proper alignment of the thumb's bones. These results enable surgeons to predict the degree of corrective osteotomy needed, thereby improving postoperative surgical results and patient satisfaction.

The extracellular matrix of bacterial biofilms consists of diverse components including polysaccharides, proteins and DNA. Extracellular RNA (eRNA) can also be present, contributing to the structural integrity of biofilms. However, technical difficulties related to the low stability of RNA make it difficult to understand the precise roles of eRNA in biofilms. Here, we show that eRNA associates with extracellular DNA (eDNA) to form matrix fibres in Pseudomonas aeruginosa biofilms, and the eRNA is enriched in certain bacterial RNA transcripts. Degradation of eRNA associated with eDNA led to a loss of eDNA fibres and biofilm viscoelasticity. Compared with planktonic and biofilm cells, the biofilm matrix was enriched in specific mRNA transcripts, including lasB (encoding elastase). The mRNA transcripts colocalised with eDNA fibres in the biofilm matrix, as shown by single molecule inexpensive FISH microscopy (smiFISH). The lasB mRNA was also observed in eDNA fibres in a clinical sputum sample positive for P. aeruginosa. Thus, our results indicate that the interaction of specific mRNAs with eDNA facilitates the formation of viscoelastic networks in the matrix of Pseudomonas aeruginosa biofilms.

Objectives: Stroke is a major cause of disability in adults, necessitating consistent patient-therapist interactions and diligent adherence to home-based rehabilitation programs to achieve substantial functional recovery. This study assessed audio-based telerehabilitation's (TR) preliminary effect and feasibility in promoting home-based upper extremity exercises among stroke survivors. Methods: A 4-week parallel two-arm pilot study design was employed. Fourteen stroke survivors (seven each in the experimental and control groups) were recruited. Individuals in the control group received standard care consisting of visits to physiotherapy outpatient clinics, while the intervention group received standard care in addition to audio-based TR. The independent t-test and chi-square test were used to analyze differences in the clinical and sociodemographic data. The independent t-test was used to measure the treatment effect on the upper limb motor function (Fugl-Meyer upper extremity [FMA-UE] and Wolf motor function test [WMFT]), quality of life (QOL) (the World Health Organization (WHO) QOL brief, [WHOQOL-BREF]), and activities of daily living (Barthel index [BI]). Results: The overall Mean±SD age of the participants is 50±8.2 years. The FMA-UE and WMFT scores changed from 17.57 to 25.86 (P=0.02) and 28.14 to 43.71 (P=0.03). No significant improvements in physical health, psychological, and social relationships domains of WHOQOL-BREF were recorded after the intervention. However, the environmental domain showed significant improvement (P=0.001). Scores of BI did not change significantly (P=0.49). Discussion: The findings of this study provided preliminary evidence to support the feasibility and benefits of audio-based TR in promoting functional regain after the stroke. However, further studies with a robust design are needed to validate the reported effectiveness.

Moral value is one of the crucial elements in human development, where moral or civic education formed a substantial part of the focus on personal development. This study examined the inculcation of universal moral values (UMVs) using language in teaching and learning as a vehicle to instil the UMVs. It has been ascertained through previous research findings that there is a dearth of systemic review approaches used in examining the universality of moral values, and how they can be inculcated via language teaching and learning. Hence, the use of the systemic review approach in this study contributes significantly to the field of the research area, as it employed this type of approach to fill the gap in the field discipline. In this study, the relevant literature on UMVs in language pedagogy (teaching and learning) are analysed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement review method. Through the systematic review of Scopus, Web of Science, EBSCOhost, Google Scholar, ProQuest, and Research Gate databases, it was identified that there were 29 related studies. The result revealed four main themes related to the inculcation of UMVs in students through language teaching and learning (LTL). The four main themes comprised: the role of a language teacher, the language curriculum content, language activities, and interactive language multimedia. The researchers forwarded several findings-based recommendations from this study that for future studies there should be an emphasis on UMV-related language analysis, and a parallel research technique be conducted such as contacting experts in the field and citation tracking.

This study systematically investigates analog switching and neuromorphic characteristics in a ZnO-based memristor by varying the anodic top electrode (TE) materials [indium tin oxide (ITO), Ti, and Ta]. Compared with the TE materials (Ti and Ta), memristive devices with TEs made of ITO exhibit dual volatile and nonvolatile switching behavior and multistate switching characteristics assessed based on reset-stop voltage and current compliance (ICC) responses. The polycrystalline structure of the ZnO functional layer sandwiched between ITO electrodes was confirmed by high-resolution transmission electron microscopy analysis. The current transport mechanism in the ZnO-based memristor was dominated by Schottky emission, with the Schottky barrier height modulated from 0.26 to 0.4 V by varying the reset-stop voltage under different ICC conditions. The long-term potentiation and long-term depression synaptic characteristics were successfully mimicked by modulating the pulse amplitudes. Furthermore, a 90.84% accuracy was achieved using a convolutional neural network architecture for Modified National Institute of Standards and Technology pattern categorization, as demonstrated by the confusion matrix. The results demonstrated that the ITO/ZnO/ITO/Si memristor device holds promise for high-performance electronic applications and effective ITO electrode modeling. [ABSTRACT FROM AUTHOR]

Onchocerciasis is one of the tropical neglected diseases that is still prevalent in Nigeria. The disease is of considerable socio-economic and public health importance with a lot of implications. Therefore, this study aimed to determine the prevalence of human onchocerciasis in five communities of the Northern Senatorial District of Adamawa State, Nigeria. A total of 629 study subjects were randomly selected and enrolled for the study. Skin snip and venous blood were collected from 196 and 433 study subjects respectively and examined for microfilaria of Onchocerca volvulus. Results obtained showed an overall of 3.4% infection while different Local Government Areas had different distribution patterns vis-a-viz percentages. Mubi had the highest percentage of 32.4% infection followed by Michika at 2.5% and the least was Madagali with Zero prevalence. Among different occupational groups, students had 7.8% infection, farmers had 3.4%, and other groups had zero prevalence. As per the age bracket, 10-19 years had 9.1% infection followed by 50-59 years (5.0%), and the least was 60-70 years with 1.9%. The Northern Senatorial District population needs to be educated on the disease onchocerciasis as the infection rate is rather increasing or near status with modern-day technology. The government and Non-Governmental Organizations may come in to assist in lowering the infection rate by providing or identifying specific clinics for the treatment or providing preventive drugs free.

This research aimed to evaluate the larvicidal activity of the lower doses of commercially synthetic Bacillus thuringiensis israelensis (Vectobac 12 Aqueous Solution (12AS)) against the fourth instar larva. One hundred and fifty blood-fed female anopheles mosquitoes were collected from different resting sites from Abuja Quarters in June 2022 using an aspirator and allowed to breed until the first instar larva appeared. The larvae were monitored and fed with 10% yeast until the third instar emerged. 240 healthy third instar larvae were selected and grouped into three treatments containing sixty (60) larvae each and replicated three times. The first, second and third treatments were respectively treated with 0.84, 0.42 and 0.21ml/l of Vectobac 12AS. Each treatment has a control containing twenty (20) larvae. Larval mortality was determined using a glass rod at an interval of 15 minutes for 24 hours. ANOVA was used to statistically analysed differences in the larval mortality between the treatment and probit analysis was used to determine the lethal concentration (LC) and the lethal time (LT). Mortality of 1(6.7%) and 3(5.0%) were observed in the first treatment (0.84ml/l) after 15 and 30minute of exposure respectively. The highest mortality of 60(100%) was observed in all the treatments after 24 hours of exposure. Statistically, there was no significant difference (F=0.081, P> 0.05). 2.35 ml/l, 5.54 ml/l and 8.15 ml/l was determined to be LC50, LC90 and LC99 respectively and LT50, LT90 and LT99 were found to be, 1809.29min and 2451.34min respectively. Conclusively vectobac 12AS has demonstrated a high level of efficacy as it revealed 100% larval mortality even at a lower recommended dose. Further research should be carried out to study the impact of other biological and environmental factors on the efficacy of vectobac 12AS.