Development Of Strategies Research Articles

Development and characterization of a double-fluorescent HIV-1 reporter cellular model to tackle the Rev-dependent export pathway.

The Rev-dependent nuclear export of unspliced and singly-spliced transcripts of human immunodeficiency virus type 1 (HIV-1) constitutes a critical yet poorly characterized post-transcriptional event essential for effective viral replication. In this study, we engineered a dual-fluorescent HIV-1-based cellular reporter system to elucidate the mechanisms underpinning Rev-dependent export. By generating multiple stably integrated inducible cellular clones, we ensured the expression of two distinct fluorescent proteins, mKO2, and ECFP, from unspliced (Rev dependent) and multiply spliced (Rev independent) HIV-1 transcripts, respectively. Utilizing flow cytometry, we performed quantitative analyses of dual-fluorescent cell populations. The developed tool enables precise assessment of the Rev-dependent export, and we validated it using known inhibitors of this pathway (leptomycin D), as well as targeted depletion of MATR3, an essential cofactor of Rev, and CRNKL1, a repressor of unspliced HIV-1 RNA export.IMPORTANCEThe developed dual-fluorescent reporter system represents a powerful and handy tool for the identification and characterization of novel molecular players involved in the Rev-dependent export pathway. This system not only holds promise for advancing our understanding of human immunodeficiency virus type 1 (HIV-1) biology but also serves as an invaluable platform for high-throughput drug screening aimed at targeting post-transcriptional HIV-1 RNA processes, particularly nuclear export. Consequently, this study offers significant implications for the development of novel therapeutic strategies to eradicate the virus.

Chimeric Antigen Receptor Cells Solid Tumor Immunotherapy Assisted by Biomaterials Tools.

Chimeric antigen receptor (CAR) immune cell therapies have revolutionized oncology, particularly in hematological malignancies, yet their efficacy against solid tumors remains limited due to challenges such as dense stromal barriers and immunosuppressive microenvironments. With advancements in nanobiotechnology, researchers have developed various strategies and methods to enhance the CAR cell efficacy in solid tumor treatment. In this Review, we first outline the structure and mechanism of CAR-T (T, T cell), CAR-NK (NK, natural killer), and CAR-M (M, macrophage) cell therapies and deeply analyze the potential of these cells in the treatment of solid tumors and the challenges they face. Next, we explore how biomaterials can optimize these treatments by improving the tumor microenvironment, controlling CAR cell release, promoting cell infiltration, and enhancing efficacy. Finally, we summarize the current challenges and potential solutions, emphasize the effective combination of biomaterials and CAR cell therapy, and look forward to its future clinical application and treatment strategies. This Review provides important theoretical perspectives and practical guidance for the future development of more effective solid tumor treatment strategies.

Systematic Review on 1,2,3-Oxadiazoles, 1,2,4-Oxadiazoles, and 1,2,5-Oxadiazoles in the Antimycobacterial Drug Discovery.

Tuberculosis remains a leading global health threat, exacerbated by the emergence of multi-drug-resistant strains. The search for novel therapeutic agents is critical in addressing this challenge. This review systematically summarizes the potential of oxadiazole derivatives as promising candidates in antimycobacterial drug discovery. We focus on various classes of oxadiazoles, especially 1,2,3-oxadiazoles, 1,2,4-oxadiazoles, and 1,2,5-s in structure-activity relationship studies are discussed, emphasizing the mechanisms of antimycobacterial action. Additionally, the synergistic potential of 1,2,4-oxadiazoles in enhancing the efficacy of existing tuberculosis treatment with ethionamide is also discussed. By integrating insights from recent research, this review aims to provide a comprehensive overview of the role of oxadiazoles in the fight against tuberculosis, paving the way for future investigations and the development of effective therapeutic strategies.

The Role of Muscle Architecture as a Determinant of Functional Performance in Women With Knee Osteoarthritis.

Knee osteoarthritis (KOA) is associated with early muscular alterations and muscle weakness, which contribute to disease progression. However, limited knowledge exists regarding the potential exacerbation of lower extremity muscle architecture and its impact on functional performance. This study aimed to investigate the relationship between knee extensor and ankle plantar flexor muscle architecture, femoral cartilage thickness, age, body mass index (BMI), pain severity, and functional performance in middle-aged women with KOA. A total of 87 patients diagnosed with KOA (mean age=51.48±4.89years, mean BMI=27.96±4.66kg/m2) were included in the study. Ultrasonography was used to assess muscle thickness, adipose tissue thickness, pennation angle, and the muscle/adipose tissue thickness ratio (MATR) of the Rectus Femoris (RF), Vastus Medialis (VM), Vastus Lateralis (VL), and Medial Gastrocnemius (MG) muscles. Physical performance was evaluated through the stair-climbing test and the 10-time sit to stand test. Pearson's correlation test and multiple linear regression analysis were used. The pennation angle of the VL and pain level predicted sit to stand test results; the pennation angle of RF, age, BMI and pain level predicted stair-climbing test results (p<0.001). Femoral cartilage thickness at the medial condyle, intercondylar area, and lateral condyle correlated with performance in both tests (p<0.001). Additionally, age, BMI, pain intensity, muscle thickness, pennation angle and MATR of RF, VL, and VM correlated with both functional tests (p<0.05). Muscle architecture alterations correlated with functional test results in patients with KOA. Understanding the influence of muscle architecture on functional parameters can facilitate the development of effective rehabilitation strategies to preserve and optimize patient function before it becomes compromised. Enrolled in clinical trials and awaiting approval.

Biology and Management of Acute Myeloid Leukemia With Mutated NPM1.

Mutations in nucleophosmin 1 (NPM1) are diseased-defining genetic alterations encountered in approximately one-third of cases of acute myeloid leukemia (AML). A mutation in NPM1 confers a more favorable prognosis; however, clinical outcomes of NPM1-mutated AML (NPM1mut AML) are diverse due to the heterogeneity of disease biology, patient characteristics, and treatment received. Research over the last two decades has dramatically expanded our understanding of the biology of NPM1mut AML and led to the development of new therapeutic approaches and strategies for monitoring measurable residual disease (MRD). Here, we review NPM1mut AML with a practical focus on the current treatment landscape, the role of MRD in guiding management, and emerging therapies, including menin inhibitors.

New Anti-Fibrotic Strategies for Keloids: Insights From Single-Cell Multi-Omics.

Keloids are complex pathological skin scars characterised by excessive growth of fibrous tissue and abnormal accumulation of extracellular matrix (ECM). Despite various treatment options available, the treatment of keloids remains a major clinical challenge due to high recurrence rates and inconsistent therapeutic outcomes. By collecting three keloid tissues and three normal skin samples and utilising single-cell RNA sequencing (scRNA-seq), we delved into the cellular heterogeneity and molecular mechanisms of keloids. Our study identified multiple fibroblast subpopulations within keloid tissue. Enrichment and cell-cell communication analyses revealed that POSTN-positive mesenchymal fibroblasts (POSTN+ mesenchymal fibs) are more prevalent in keloids and exhibit higher transforming growth factor β (TGF-β) signalling activity, potentially playing a central role in excessive fibrosis. In contrast, IGFBP2-positive fibroblasts (IGFBP2+ fibs) are more abundant in normal skin, insensitive to TGF-β and Periostin signalling, and possess anti-fibrotic potential, possibly related to limited tissue repair and regenerative capacity. Trajectory analysis inferred the differentiation states and patterns of different fibroblast subpopulations. Additionally, we explored the heterogeneity of endothelial cells, finding an endothelial cell subpopulation (EC10) exhibiting mesenchymal activation characteristics, which may work with specific fibroblasts to promote abnormal angiogenesis and endothelial-to-mesenchymal transition processes. Spatial transcriptomics analysis has shown that the proportion of IGFBP2+ fibroblasts relatively increases in acne keloidalis after hormonal treatment, further demonstrating their value as potential therapeutic targets. Ultimately, we separated these two subpopulations using flow cytometry, highlighting their opposing roles in the secretion of the ECM. These findings provide new insights into the pathogenesis of keloids and lay the theoretical foundation for the development of innovative anti-fibrotic treatment strategies.

Oviposition Deterrents from Extracts of Eryngium foetidum Against Potato Tuber Moth Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae)

The potato tuber moth Phthorimaea operculella is a serious boring pest of potato. An integrated ecological approach to sustainable pest management is necessary for the control of this species. This study investigated the effects of minced leaves and plant extracts of Eryngium foetidum on the oviposition behavior of PTM females. The behavioral regulatory components of PTM females in response to the extracts were determined using chemical analyses and electrophysiological tests. Individual electroantennographic detection (EAD)-active compounds and mixtures were evaluated using oviposition choice bioassays. The results indicate that minced leaves had a deterrent effect on oviposition. The extracts at low dosages had an attraction effect, while high dosages had a repellent effect on the oviposition of PTM adult females. The dominant compounds of the extracts were trans-2-dodecenal and trans-2-tridecenal and showed EAD activity. trans-2-dodecenal, trans-2-tridecenal and their mixtures showed significant oviposition-repellent effects toward the PTM. The oviposition stimulation indices (OSIs) of trans-2-dodecenal and trans-2-tridecenal were −100% and −94.03% at 10 mg/mL, respectively. The OSIs of mixtures at natural ratios of 10 mg/mL and 5 mg/mL were −95.11% and −90.96%, respectively. The results can be used for the further development of ecological control strategies for this pest species.

5G Internet in Rural Areas: Impacts, Challenges and Sustainable Strategies for Development

Objective: This study aims to investigate the impacts, challenges, and strategies related to the implementation of 5G technology in rural areas, with the goal of promoting sustainable development and digital inclusion. The research also seeks to identify specific benefits of 5G for the agricultural sector and evaluate how its adoption can transform rural communities. Theoretical Framework: This study is based on concepts such as precision agriculture, agricultural automation, and digital inclusion, emphasizing the implications of high-speed connectivity in rural development. Theories related to the economic and social impacts of 5G technology provide a solid foundation for understanding the potential and barriers associated with its implementation. Method: The research adopted a systematic bibliographic review approach, including the selection of theoretical and empirical studies published in the last ten years. Data collection was conducted in recognized academic databases, such as Scopus, IEEE Xplore, and Web of Science, using keywords related to 5G and its application in rural areas. The analysis categorized the data into benefits, challenges, and strategies, allowing for a comparative discussion of the findings. Results and Discussion: The results revealed that, although the implementation of 5G faces significant challenges, such as insufficient infrastructure and high costs, the potential benefits are substantial. The technology can revolutionize precision agriculture through IoT sensors, drones, and artificial intelligence, increasing efficiency and sustainability in agricultural operations. Additionally, 5G's ability to drive economic development, expand digital inclusion, and improve access to essential services such as telemedicine and online education was highlighted. Research Implications: This study provides insights into how 5G technology can be applied to transform rural areas, benefiting sectors such as agriculture, healthcare, and education. The implications include strategies to overcome implementation barriers and the potential to reduce digital exclusion, promoting innovation and sustainability in rural communities. Originality/Value: The research contributes to the literature by offering a comprehensive analysis of the challenges and benefits of 5G in rural areas, highlighting its relevance for digital transformation in the agricultural sector and community development. Its originality lies in the integration of economic, social, and technological dimensions, providing practical recommendations for adopting 5G in remote regions.

أثر المرونة الاستراتيجية في تعزيز الثقافة التنظيمية في الجامعات الأهلية العراقية محافظة بغداد نموذجاً

The study conducted on a sample of 90 individuals from private universities in Baghdad, Iraq, shows that these universities possess a high level of strategic flexibility. This is reflected in their ability to adapt to environmental changes and competition in the educational sector. Innovation in academic programs and services is considered a key element that enhances the competitiveness of these universities. The study also demonstrates a clear positive impact of strategic flexibility on organizational culture. The results indicate that competitive flexibility plays a major role in strengthening organizational culture, while resource flexibility shows an important but less powerful effect. This underscores the importance of focusing on both aspects to improve the work environment in universities. The recommendations emphasize the need for private universities to develop programs that foster creative thinking and innovation. This can be achieved by establishing research and development centers that adopt and implement new ideas in line with market demands and student needs. Additionally, it is advised to implement comprehensive policies that focus on enhancing strategic flexibility in various aspects of university operations, whether in competitiveness or resource management. This will enable universities to adapt to future changes and achieve their goals effectively. Overall, the study highlights the significance of strategic flexibility as a fundamental factor in enhancing organizational culture in Iraqi private universities, necessitating the development of strategies that support continuous innovation and adaptation.

Optimizing Urban Ventilation in Heritage Settings: A Computational Fluid Dynamics and Field Study in Zhao’an Old Town, Fujian

This study investigates the optimization of urban ventilation in Zhao’an Old Town, Fujian, through the integration of Computational Fluid Dynamics (CFD) simulations and field measurements. The findings underscore the critical roles of spatial layout indicators, such as the Frontal Area Index (FAI), Opening-to-Facade Ratio (OFR), and Building Volume Density (BVD), in influencing wind flow and thermal performance. The FAI was identified as the most influential factor in shaping airflow, while the OFR and BVD highlighted the importance of open spaces and balanced building density for natural ventilation and thermal comfort. Practical strategies, such as optimizing building orientations, increasing facade permeability, and leveraging natural cooling elements like the Dongxi River, are proposed to address ventilation challenges while preserving the town’s cultural and historical integrity. Unlike previous studies, this research combines CFD simulations with summer field measurements to provide a highly accurate and contextually relevant evaluation of wind flow dynamics in compact urban environments. By systematically analyzing the interplay between urban morphology and ventilation efficiency, this study offers actionable recommendations for improving outdoor comfort in heritage settings. The outcomes serve as a valuable reference for sustainable urban planning, contributing to the development of strategies that balance environmental performance with the preservation of Zhao’an Old Town’s unique cultural heritage.

Type IV PilD mutant stimulates the formation of persister cells in Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolates that lack motility do not express type IV pilin, yet the biological roles of this absence in the infection process remain poorly understood. We asked whether the absence of motility in these bacteria is associated with increased antibiotic persistence. In this study, we analysed type IV PilD protein sequences in the database and conducted antibiotic-tolerant persister cell assays. We found that PilD variants were common in P. aeruginosa clinical isolates. Our results revealed that inactivation of PilD resulted in a significantly higher level of surviving persister cells following ciprofloxacin treatment. This PilD-mediated persistence did not involve previously described mechanisms, such as phenazine pyocyanin, biofilm or stringent response. Our findings connect the non-motility of clinical P. aeruginosa isolates with the survival of persister cells, highlighting the clinical significance for the development of strategies to eradicate P. aeruginosa infections.

Level of Innovation as a Product Development Strategy for MSME Es Dawet Ayu: A Case Study in Ambarawa

This research explores the role of innovation in the product development strategy of MSME Es Dawet Ayu in Ambarawa. Using a qualitative descriptive approach, the study involved six key informants, including the business owner, suppliers, producers, distributors, employees, and consumers. Data were gathered through interviews, observations, and documentation. The findings suggest that product innovation in Es Dawet Ayu has been successfully implemented by introducing new flavor variations, utilizing natural ingredients, and improving packaging design. The shift from standard plastic cups to modern bottles and premium packaging has enhanced the product’s hygiene and exclusivity. Additionally, marketing strategies such as social media promotion and special discounts have significantly contributed to expanding the MSME’s market reach and customer base.

Developing Cultural Tourism in Vietnam

Vietnam is recognized with more than 40000 historical and cultural relics, including more than 3600 national relics. This is a potential factor, creating an advantage for Vietnam to develop cultural tourism. In the current development process, Vietnam is focusing on developing cultural tourism as an important content of the tourism development strategy. Localities in Vietnam all evaluate heritage values ​​and implement programs and plans to exploit and promote cultural heritage values ​​in a suitable manner for socio-economic development. Many localities have been successful in exploiting diverse cultural tourism products, becoming a competitive advantage for development, especially some localities with many famous landscapes, capitals, ancient capitals, etc. In this study, the author focuses on analyzing the practical development of cultural tourism in Vietnam based on a practical survey in the ancient capital of Ninh Binh - a place with many famous landscapes and cultural heritages, with a history of development as the capital of Vietnam in the 10th century; the uniqueness and cultural diversity of Ninh Binh province plays a major role and influence on the economic and social development of the locality and of Vietnam. The research results also assess the factors affecting the development of cultural tourism in Ninh Binh province, thereby discussing and researching related policy issues.

Influence of spin-off decision on financing risk: Empirical insight from Indonesian Islamic banks

Background Spin-offs play a significant role in organizational development strategies, particularly in Islamic banking, by fostering entrepreneurship, innovation, and Shariah-compliant management practices. Indonesia stands as a pioneer in implementing the dual banking system and has established a spin-off policy to foster the growth of Islamic banking. This study investigates whether the spin-off decision has a significant impact on financing risk in Indonesian Islamic banks. Methods Financing risk is measured by the non-performing financing ratio, while the spin-off decision is represented by a dummy variable equal to 1 for the post-spin-off period and 0 for the pre-spin-off period. This study utilizes data from semi-annual reports of 35 Indonesian Islamic banks and analyzes it using a dynamic panel model with the Generalized Method of Moments (GMM). Results The findings reveal that spin-offs significantly reduce financing risk, thereby enhancing the financial resilience and boosting investor appeal. Notably, this implies that Islamic banks operating as Islamic windows exhibit a higher level of financing risk compared to fully-fledged Islamic banks. Furthermore, a noteworthy pattern emerges that spin-off Islamic banks with substantial assets demonstrate greater risk in comparison to their counterparts with more modest assets. System GMM also confirmed the result. Conclusions Islamic banks can significantly reduce their financing risks by establishing independent Islamic banks, or spin-offs. Unlike Islamic windows, which are typically integrated within conventional banks and face higher risk levels, standalone Islamic banks offer greater flexibility and control over their operations.

Comparison of Methods for Determining the Oil Content in Medium-Mature Shale—A Case Study from the Fourth Member of the Shahejie Formation in the Dongying Depression

The oil content of shale oil reservoirs is a key parameter for reserve evaluation and “sweet spot” selection. However, discrepancies in the oil contents obtained by different methods have led to considerable disparities in the selection of exploration well locations and development strategies for shale oil. This study focuses on low to moderately mature sealed coring samples from the Dongying Depression in the Bohai Bay Basin. Three methods—NMR, Dean–Stark, and Rock-Eval—were employed to measure the oil content of shale. The results indicate that the oil content obtained by NMR is the highest, followed by the Dean–Stark distillation extraction method, while the pyrolysis method yields the lowest value. The study found that (1) the efficiency of the solvent extraction effect on moderately to low-mature shale is low since the occurrence of numerous closed pores leads to a lower yield when using the Dean–Stark method. (2) The exposure of shale samples to the air, sample crushing, and lag time for temperature increase cause a significant loss of light hydrocarbon components, resulting in the lowest oil content when measured by the Rock-Eval method. The NMR method, with its advantages of a short analysis time and non-destructive nature, appears to be the most advantageous method for shale oil content evaluation.

Evolving Research and Development Landscape for Rare Diseases: Growing Concerns Over Orphan Drug Lag in Japan.

Patients with rare diseases worldwide face substantial unmet therapeutic needs. In Japan, drug lag-delays in drug approval compared to other countries-has resurfaced as a pressing public health issue. This study analyzes orphan drugs (ODs) approved in the United States (US) from 2005 to 2021, examining OD lag trends, and research and development (R&D) models to streamline OD development in Japan. Despite increased OD approval in the United States since 2018, the number of unapproved ODs in Japan has substantially increased. Although OD lag decreased, it has resurged since 2017. This is largely due to changes in the R&D strategies of pharmaceutical companies, which are driven by the growing presence of US- and Europe-based small- to mid-sized enterprises (SMEs) and the evolving industry landscape. Large foreign pharmaceutical companies have shifted toward a global development strategy for Japan, aiming for more efficient development and competitive advantage. This has been propelled by a move toward in-licensing earlier-stage drug candidates with global exclusivity from SMEs. Japanese pharmaceutical companies have focused on in-licensing late-stage drug candidates for the Japanese market from SMEs without a business presence in Japan, which have not been developed locally, thereby employing a bridging strategy for Japan. With the increase in ODs developed in the United States by these SMEs, this practice has substantially exacerbated the OD lag. As these SMEs are unlikely to enter the Japanese market, it is crucial for Japanese pharmaceutical companies to proactively pursue earlier, more proactive global partnerships with SMEs.

A Study on Consumer-Centric Health Information Provision Strategy Using SWOT-AHP -Focusing on the National Health Information Portal.

Approximately 70% of Koreans access health and medical information online. Health information providers play a crucial role in enhancing public health by ensuring that individuals can effectively consume and utilize this information according to their information-seeking behaviors. However, existing tools for evaluating health information websites have significant limitations. These tools are often one-size-fits-all and lack strategic recommendations for delivering consumer-centered health information. There is a clear need for alternative approaches beyond merely identifying the quality factors that satisfy consumers. A Strengths, Weaknesses, Opportunities, and Threats-Analytic Hierarchy Process (SWOT-AHP) evaluates both internal and external environmental factors of a health information website, which provides strategies based on the prioritization and weighting of quality factors. Specifically, the 'National Health Information Portal,' a platform provided by the Korea Disease Control and Prevention Agency, was assessed through a comprehensive review of prior research and a SWOT analysis, followed by an AHP survey involving 15 experts specializing in health information websites. The findings of the analysis indicate that the most effective development strategy is the SO (Strengths-Opportunities) strategy. This study highlights the need to move beyond uniform evaluation tools and consider the dynamic and complex nature of the Internet, emphasizing the importance of developing prioritized strategies based on evaluations from both consumers and providers.

An Improved Sporulation Method for Producing Asexual Zoospores of Pythium aphanidermatum on Culture Medium

An improved sporulation method for Pythium aphanidermatum on 10% V8-juice agar was developed to generate substantial quantities of zoospores. We conducted experiments using a 4 × 4 factorial design to evaluate the effects of temperature (20, 25, 30, and 35 °C) and incubation time (2, 3, 4, and 5 days) on zoospore production from isolates HSv05 and KACC 48066. The results indicated that a temperature of 30 °C consistently yielded the highest numbers of zoospores across all incubation periods. Applying the same temperature (30 °C) and all incubation periods to other isolates (CCp03, CCp04, CCp05, HSv10, and KACC 40156) also resulted in higher numbers of zoospores regardless of incubation times compared with that under the control condition (25 °C and 2 days). Further virulence tests of isolate HSv05 revealed that high concentrations of zoospores (5 × 102 − 105 zoospores/ml) induced severe rot symptoms; however, a low concentration of 102 zoospores/ml produced only considerably weak symptoms on inoculated potato tubers. No symptoms appeared in tubers inoculated with 0 (uninoculated control) or 101 zoospores/ml. These findings suggest that our sporulation method can help obtain adequate zoospores for various basic and applied studies, including pathogen identification, virulence assessment, resistance resource screening, and control strategy development.

Write to teach: reducing entrance barriers for special education teacher applicants through SRSD writing

ABSTRACT To help diversify the special education teacher workforce, support needs to be provided to help racially and ethnically diverse students pass required entrance exams to get into special education teacher preparation programs. Many universities and states require special education teacher candidates to pass the Praxis Core: Writing exam. Special education teachers need to be competent writers. This pretest posttest design study included special education teacher applicants from diverse backgrounds across the Hawaiian Islands. Participants were taught planning and composing strategies using the Self-Regulated Strategy Development model. The writing intervention statistically enhanced applicants’ writing knowledge, argumentative writing abilities, and informative source-based writing abilities. Furthermore, the majority of participants who took the official Praxis Core: Writing exam earned passing scores. Findings support the use of systematic writing instruction as an effective strategy in reducing entrance exam barriers, thereby providing more equitable recruitment and preparation of racially and ethnically diverse special education teachers.

Promoting international acceptance of clinical studies about traditional Chinese medicine interventions

Abstract Promoting the international acceptance of clinical studies about traditional Chinese medicine (TCM) interventions is a key strategy for internationalization of TCM. However, the complexities of TCM interventions—in terms of the theories, practice patterns, and components—pose challenges to the design and implementation of clinical studies that are well accepted by the international community. This article summarized the current status of clinical studies about TCM interventions that were published in international journals, explored underlying barriers hindering the international acceptance, and discussed potential strategies for future development.