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Bone defect is a prevalent and complex challenge in orthopedics and oral-maxillofacial surgery, severely compromising skeletal integrity and functional recovery. Autologous Guided Bone Regeneration (GBR) has emerged as a highly effective therapeutic strategy, demonstrating remarkable efficacy in treating long bone fractures, nonunions, post-tumor resection bone defects, and alveolar bone augmentation for dental implant procedures. This narrative review comprehensively synthesizes the latest research progress, core mechanisms, technical innovations, existing challenges, and future prospects of Autologous GBR through an extensive analysis of domestic and international literature. Its core mechanism relies on selective cell occlusion theory: barrier membranes construct a bone regeneration microenvironment, blocking non-osteoblastic invasion while promoting osteoblast migration and differentiation. Autologous components play key roles: autologous bone (gold standard for grafting) has osteogenic activity, osteoinductivity and osteoconductivity; autologous bone marrow provides mesenchymal stem cells (MSCs) for osteoblast differentiation and microenvironment regulation; autologous growth factors (e.g., Bone Morphogenetic Proteins [BMP], Transforming Growth Factor-β [TGF-β]) regulate bone regeneration via cell signaling pathways. Technical advances include site-specific autologous bone harvesting (ilium, mandible, etc.) and optimized barrier membranes (absorbable Poly Lactic-co-Glycolic Acid [PLGA]/collagen, non-absorbable expanded Polytetrafluoroethylene [ePTFE]). Cell-molecular studies (MSCs differentiation, Wnt pathway) offer theoretical basis. Challenges include surgical infection, potential immune rejection and poor osseointegration. Prospects involve 3D-printed scaffolds, gene therapy-tissue engineering combination, and application in complex diseases like osteogenesis imperfecta. This review provides references for researchers and clinicians.

Post-transplant relapse remains a major clinical challenge in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Real-time quantitative PCR (RQ-PCR) for BCR::ABL1 is the current standard for measurable residual disease (MRD) monitoring, whereas digital PCR (dPCR) offers substantially higher analytical sensitivity. Whether this increased sensitivity translates into additional prognostic value after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this prospective study (NCT06211166), 270 patients with Ph + ALL were longitudinally monitored after allo-HSCT. MRD was assessed in parallel using dPCR, RQ-PCR, and MFC. Based on the first post-transplant MRD detection pattern, patients were categorized into four groups: double-negative (n = 80), dPCR-single-positive (n = 158), RQ-PCR-single-positive (n = 3), and double-positive (n = 29). The dPCR-single-positive pattern was the most prevalent MRD status, accounting for 58.5% of patients. dPCR positivity independently predicted subsequent MFC-MRD conversion (HR 9.56, P = 0.029), with a median lead time of 77 days. In addition, dPCR detected BCR::ABL1 positivity earlier than RQ-PCR, preceding subsequent hematologic relapse by a median of 64.5 and 91.5 days, respectively. However, the cumulative incidence of hematologic relapse (CIR), the primary endpoint of this study, did not differ significantly among the four MRD-defined groups (P = 0.60). Consistently, isolated dPCR positivity was not associated with inferior 2-year leukemia-free survival (LFS; P = 0.30) or overall survival (OS; P = 0.60). Although dPCR detects molecular disease earlier and anticipates MFC-MRD by 2 months after allo-HSCT in Ph + ALL, isolated ultra-low-level BCR::ABL1 positivity does not impact relapse risk, LFS, or OS. Routine MRD monitoring with RQ-PCR plus MFC remains sufficient for prognostic stratification, while dPCR primarily provides an ultra-early signal to guide timely intervention rather than improving survival prediction.

Salmonella is one of the leading causes of foodborne illnesses worldwide, with the ability to contaminate a wide range of sources. The identification of the frequently contaminated sources is vital for improving the management of Salmonella infections and outbreaks. As there is growing concern on bacterial resistance to antimicrobial agents globally, it is crucial to monitor the resistance of Salmonella to antimicrobial agents for effective treatment of salmonellosis and prudent use of antibiotics. The epidemiology of Salmonella, including outbreak patterns, serovars prevalence and antimicrobial resistance profiles, could differ by region. Therefore, assessing the local status of Salmonella is crucial for implementing targeted interventions. This review provides an overview of foodborne disease and Salmonella-related outbreaks in Malaysia, focusing on Salmonella's sources of isolation, serovars and antimicrobial resistance patterns. In Malaysia, food poisoning outbreaks remain a recurring public health issue, and Salmonella is one of the main causative agents with fatal cases. However, the true burden of salmonellosis is difficult to determine as data on non-typhoidal salmonellosis are lacking. Salmonella was detected in both human and non-human samples, with S. Typhimurium and S. Enteritidis being the most common serovars. Salmonella isolates in Malaysia exhibited a wide range of antimicrobial susceptibility patterns, with notably high resistance to erythromycin and penicillin. The review highlights the need for continuous surveillance of Salmonella infections, encompassing both typhoidal and non-typhoidal salmonellosis, as well as systematic monitoring of contamination sources and antimicrobial resistance patterns to improve understanding and ensure effective management of salmonellosis in Malaysia.

Hookworm disease is one of the tropical neglected diseases that significantly impacts human health to varying degrees. Hookworms produce various proteins to facilitate host invasion and immune evasion. Despite available treatments, reinfection is common, underscoring the need for effective vaccines. However, the complexity of the hookworm's life cycle poses a challenge in understanding the immune response in the vaccine candidates. Reverse vaccinology (RV) offers a powerful approach to understand the immune response by using various bioinformatics tools. This study begins by identifying hookworm antigens capable of inducing host immune responses, followed by docking analysis with different dendritic cell (DC) receptors to investigate the immunological response of antigenic peptides and further correlated to the immunogenicity findings in clinical trial. Necator americanus GlutathioneS-Transferase-1 (Na-GST-1), a known immunogenic protein from Necator americanus, was selected for docking due to its strong antigenic properties. Fifteen DC receptors were evaluated against Na-GST-1, of which seven receptors (TLR2, TLR3, TLR4, TLR7, DEC-205, CD206, and CD36) exhibited stronger predicted interactions, as indicated by stronger binding affinities with Na-GST-1 utilizing various immunoinformatic tools. These receptors are associated with the mediation of Th1/Th2 immune responses, suggesting a potential correlation between docking affinity and the predicted immunogenicity of Na-GST-1. Overall, this study provides valuable insights into DC receptor-antigen interactions and demonstrate a computational approach for assessing the potential of hookworm antigens to engage DC receptors, thereby supporting rational hookworm vaccine design. These findings support the application of early in silico strategies for advancing vaccine candidates against hookworm infection and strengthening control efforts for neglected tropical diseases.

Background and Study AimsTibial plateau fractures with articular depression are difficult to treat. The purpose of this paper is to present a novel technique for the effective and efficient use of crushed cancellous allograft for management of depressed tibial plateau fractures.Patients and MethodsA retrospective, single-surgeon study of sixteen cases of depressed tibial plateau fractures augmented with cancellous allograft via the following technique was conducted. The technique involved utilization of multiple 3 mL syringes for introduction of allograft into the identified tibial metaphyseal defects followed by bone tamping to create a packed bed of structural allograft. Patients were included only if presenting with traumatic, closed tibial plateau fractures who underwent indicated open reduction and internal fixation with the noted technique with at least 12 months of radiographic follow-up.ResultsAll sixteen cases went on to union as determined by radiographic evaluation with minimal subsidence of the articular surface.ConclusionThe described technique provides an effective, efficient, and novel method of filling the metaphyseal defect created after restoring articular depression in tibial plateau fractures.

Lymphatic filariasis (LF) remains a significant public health challenge in many tropical regions where the disease is endemic. In Malaysia, LF is found in small pockets across the country. Asymptomatic carriers play a critical role in transmission but are often undetected. This report details an investigation of an asymptomatic filariasis reported by local health authorities involving an 83-year-old female patient residing in the Bako area, Sarawak. Despite being immobile due to a stroke, routine screening identified an infection with Brugia malayi through microscopy and a rapid diagnostic test. Interestingly, the patient exhibited no acute or chronic symptoms typically associated with filariasis. Contact tracing among her family members revealed that her son was also infected. Both patients received treatment with diethylcarbamazine (DEC) at a dosage of 6 mg/kg, along with albendazole 400 mg and ivermectin 12 mg. Preventive measures included health education, entomological studies, and the implementation of a 'Test & Treat Filariasis' program in the village. By documenting both the index case and a secondary asymptomatic case within the same household, the study provides a strong example of how routine screening and contact tracing can identify hidden sources of infection. This adds significant value to LF elimination strategies and emphasizes the importance of community-level surveillance programs. Coordinated efforts by health authorities, including contact tracing, environmental assessments, and targeted treatment, are essential for controlling the spread of LF and safeguarding public health.

This JAMA Patient Page describes how chikungunya virus infection is acquired and provides information on the diagnosis, treatment, and prognosis for patients.

In the rapidly developing world, artificial intelligence (AI) is one of the emerging applications in the medical domain. Early detection of cancer is one of the most difficult processes, especially when it comes to the differentiation of cancer's structure, length, and size. AI methodology offers innovations and decision-making applicable to specific processes like data collecting, management, results, and conclusions. Due to the lack of particular indicators, the difficult location of the pancreas, and the absence of early symptoms, pancreatic cancer (PC) is difficult to identify with low and late analysis. However, the imaging approach is slightly improving analysis, but there is still potential for enhancement in systematizing guidelines. This comprehensive review will mainly focus on various applications of AI in pancreatic cancer diagnosis. Furthermore, this review presents various architectures based on machine learning (ML) and deep learning (DL) methods for applications such as early detection, classification, tumor staging, and pancreatic cancer survival prediction. In order to better comprehend challenging cases, clinical practitioners can benefit from the supplementary information and useful recommendations provided by various techniques. Finally, this review potentially analyzes the advantages and drawbacks present in pancreatic cancer. This review provides an overview of research based on AI methods and algorithms that provide superior performance from a variety of pancreatic cancer patients while also providing viable future perspectives with significant advancements to overcome drawbacks in previous research and provide enhanced performance, stating their effectiveness and robustness analysis.

Shoulder arthroscopy is associated with significant postoperative pain. Interscalene brachial plexus block (ISBPB) provides excellent analgesia but frequently causes hemidiaphragmatic paralysis (HDP) and respiratory impairment. Cervical erector spinae plane block (ESPB) has been proposed as a possible alternative approach, but its comparative efficacy, safety, and anatomical spread remain uncertain. In this randomized non-inferiority trial, 70 patients undergoing arthroscopic shoulder surgery received cervical ESPB or ISBPB with 20&#xa0;ml 0.375% ropivacaine. The primary endpoint was resting visual analog scale (VAS) pain at 6&#xa0;h. Secondary outcomes included static and dynamic VAS, diaphragm ultrasound, respiratory function, handgrip strength, opioid use, adverse events, and satisfaction. The median between-group difference in resting VAS at 6&#xa0;h was 0 (range 0-1), meeting the non-inferiority margin. VAS pain scores were lower with ISBPB at 1 and 3&#xa0;h at rest (p&#x2009;=&#x2009;0.008 and p&#x2009;=&#x2009;0.003) and at 3 and 6&#xa0;h during movement (p&#x2009;<&#x2009;0.001 and p&#x2009;=&#x2009;0.007); however, all 95% confidence intervals for median differences were&#x2009;<&#x2009;1, confirming non-inferiority of ESPB. Cumulative sufentanil use and rescue analgesia were similar. ESPB was associated with greater diaphragmatic excursion and thickening fraction and a lower HDP incidence (RR 0.2 post-block; 0.4 in the PACU; both p&#x2009;<&#x2009;0.001). Respiratory declines were smaller with ESPB for FVC (5.8% vs. 14.8%; p&#x2009;<&#x2009;0.001), FEV&#x2081; (4.9% vs. 18.8%; p&#x2009;<&#x2009;0.001), MIP and MEP (both p&#x2009;<&#x2009;0.001). Handgrip strength was better maintained and Horner syndrome was less frequent (8.6% vs. 34.3%; p&#x2009;=&#x2009;0.018). Other adverse events and patient satisfaction were similar between groups. In this low-risk study population, cervical ESPB met the predefined non-inferiority criterion for postoperative analgesia compared with ISBPB and was associated with less diaphragmatic and respiratory impairment. However, cervical ESPB should not be considered risk-free, and further anatomical, dose-finding, and clinical studies are needed before any broader clinical role can be defined. ClinicalTrials.gov identifier no. ChiCTR2200060019.

Dimethyl ether (DME) is widely used in calculations as a model ligand due to its structural simplicity. In contrast, its application in structural chemistry is limited. Here, we present the first crystal structures of standard lithiumorganics with this simplest gaseous ether to provide an experimental basis for calculated geometries. The aggregation sizes are comparable to those with tetrahydrofuran, showing that DME can replace this ligand without changing the geometrics drastically. The solid-state structure of tert-BuLi&#xb7;3DME is particularly interesting, representing the first lithiumorganic high-resolution structure with only etheric ligands. To put the compound into context, a high-resolution structure of monomeric LiI&#xb7;3DME was obtained, and experimental charge density studies for both compounds were carried out, raising new insights into bond situations. The density at the Li-C bond contains more shared density than Li-I, which is much more on the closed shell interaction side. The shorter Li-O distances in LiI&#xb7;3DME witness that the halide provides less density to the metal than the carbanion. This deficiency is counterbalanced by the more closely coordinated DME donors. These results establish DME as a unique rigid ligand, enabling access to high-quality crystal structures that provide experimental insights into the bonding properties of lithiumorganic compounds.

In recent years, the modification of gem-dinitro and trinitromethyl-based energetic materials has attracted considerable attention. This study summarizes recent strategies for improving material performance by introducing fluorine atoms into asymmetric gem-polynitro structures. It was found that the introduction of fluorine atoms effectively increases the thermal stability and density of these materials while maintaining their detonation performance. Frontier molecular orbital (FMO) analysis reveals that the incorporation of fluorine atoms enlarges the HOMO-LUMO gap, thereby enhancing molecular stability. Furthermore, atomic dipole moment corrected Hirshfeld (ADCH) atomic charge and electrostatic potential (ESP) analyses indicate that introducing fluorine into the parent asymmetric gem-dinitro/trinitromethyl energetic materials effectively enhances thermal stability by promoting a more uniform charge distribution across the system. Finally, based on the known experimental structure 5, a novel compound (5-F) was designed. Computational results demonstrate that both the detonation velocity and density of compound 5-F are significantly improved. This research strategy provides valuable guidance for the design and synthesis of next-generation gem-polynitro energetic materials. All calculations were performed using Gaussian 16 software and the Multiwfn program package, and the Grimme dispersion correction was employed in the present work. Specifically, the M06-2X functional combined with the def2-TZVP basis set was used for molecular structure (1-4) optimization and frequency calculation; the B3PW91 functional and 6-31G** basis set were adopted for density calculation (5-F); the B3LYP functional and 6-31G** basis set were utilized for structural optimization in enthalpy of formation calculation, while the single-point energy was calculated at the M06-2X/def2-TZVP level (5-F).

Selective synthesis of hydrogen peroxide (H2O2) by two-electron oxygen reduction reaction (2e- ORR) has emerged as an attractive alternative to the complex and energy-consuming anthraquinone method. Electrocatalysts play a crucial role in this process, as they determine catalytic activity and selectivity, which are strongly related to their geometric and electronic structures. However, the complexity of the composition and structure of the catalytically active site poses a significant challenge to understanding the relationship between the geometric/electronic structures and ORR activity/selectivity of the electrocatalyst. Herein, we systematically summarize and discuss the latest advances in the geometric and electronic modulations of electrocatalysts toward H2O2 synthesis. First, the basic principle of adsorption and reduction behaviors of oxygen species on the catalyst surface is introduced, and the influence of geometric and electronic structures is highlighted. Secondly, the recent advances in catalyst design via these two strategies are presented. Thirdly, the features of various electrocatalysts associated with their electrochemical performance are summarized and analyzed. Finally, the current challenges and future directions for the research and development of H2O2 production are discussed. This review provides insights that contribute to the development of next-generation catalysts for sustainable H2O2 production, addressing both environmental and energy challenges.

Tobacco waste, rich in nicotine, is both an environmental burden and a potential feedstock for high-value chemicals. Here, we developed a proximity-enhanced co-immobilized multi-enzyme cascade that efficiently converts the nicotine into a pharmaceutical intermediate 3-succinoylpyridine (SP). The cascade system comprises the nicotine oxidoreductase NicA2 V321 (NicAm), pseudooxynicotine amine oxidase (Pnao), and 3-succinoylsemialdehyde-pyridine dehydrogenase (Sapd) for sequential nicotine conversion, coupled with an aldehyde-ketone reductase (AKR) module for in situ NADP+ regeneration. To improve nicotine-to-SP conversion and facilitate multi-enzyme recycling, a SpyCatcher/SpyTag self-assembled cofactor regeneration enzyme scaffold was adopted, in conjunction with AviTag-BirA-mediated biotinylation for cascade enzyme site-specific co-immobilization on streptavidin-coated supports. This proximity-enhanced design promoted efficient cofactor cycling and boosted the nicotine-to-SP conversion to approximately 63%, much higher than the 42.7% achieved by free enzymes. The co-immobilized system also showed improved pH and thermal stability, retaining over 60% of its initial activity after eight reuse cycles. This modular biocatalytic strategy provides a green and promising route for the valorization of nicotine-rich tobacco waste.

Fluorescent sensors have emerged as indispensable tools for detecting various fields, including visualising biological processes in molecular biology, clinical diagnostics, biotechnology, and environmental monitoring, due to their high sensitivity, selectivity, excellent biocompatibility, ease of use, and low cost. However, conventional fluorophores, which exhibit diminished fluorescence upon aggregation/detection, that is, in the aggregated state, predominantly suffer from aggregation-caused quenching (ACQ); thus, limit their potential in sensing technologies. To overcome, the new aggregation-induced emission (AIE)-luminogens have been extensively applied in biomedical imaging, optoelectronics, stimuli-responsive systems, drug delivery, and chemical sensing, as AIEgens display greater fluorescence upon aggregation, offering a powerful solution. This review provides a comprehensive, systematic overview of the latest advancements in organic AIE-based fluorescent luminogens. It begins with the fundamentals of AIE and their use in ion sensing, followed by a discussion of the detection of explosives and bioactive molecules. We then summarized by highlighting the diverse range of approaches to establishing an association between the structures of AIEgens and their sensing performance, and finally discussed the current challenges and future opportunities in this rapidly growing research area. We hope this review will spark new ideas and inspire new endeavors in this emerging research area, thereby further promoting state-of-the-art progress in sensing.

To evaluate the dissemination and real-world implementation of recommendations from the 5th Edition of the Japanese Esophageal Cancer Practice Guidelines and to inform development of the upcoming 6th Edition, the Guideline Committee of the Japanese Esophageal Society conducted a nationwide Quality Indicator (QI) survey in Japan. A nationwide, cross-sectional, web-based questionnaire survey was distributed to 381 certified institutions participating in the 2023 National Registry of Esophageal Cancer in Japan. Conducted in November 2024, the survey covered six domains-epidemiology, surgery, endoscopy, chemotherapy, radiation therapy, and pathology-reflecting key recommendations of the 5th Edition. Responses were summarized descriptively at the institutional level. Valid responses were obtained from 190 institutions (49.9%). Smoking cessation guidance was implemented in more than 90% of institutions, and over 90% also provided guidance on alcohol abstinence or moderation, although complete alcohol abstinence was less uniformly recommended. Minimally invasive, including robot-assisted, esophagectomy was adopted by over 90% of institutions. The proportion of institutions performing prophylactic cervical lymph node dissection varied by tumor location and stage, reflecting contemporary staging concepts. The DCF regimen was the predominant neoadjuvant therapy for stage II/III disease (94.7%), and immune checkpoint inhibitor-based chemotherapy was widely used for unresectable or recurrent disease. Advanced endoscopic diagnostic modalities, including magnifying and image-enhanced endoscopy, were widely adopted. This nationwide QI survey demonstrates broad adherence to guideline-based multidisciplinary management of esophageal cancer in Japan and provides an evidence base for refining recommendations in the 6th Edition of the Japanese Esophageal Cancer Practice Guidelines.

Nipah virus (NiV), a pathogen with pandemic potential, lacks approved treatments or vaccines, highlighting the urgent need for research on immune-targeted antigenic determinants. A significant gap persists in NiV research, as studies on the fusion (F) protein critical for viral entry as well as the B cells epitopes, have primarily focused on computational prediction rather than experimental validation of immunogenic epitopes obtained through immunoinformatics approach. This study focused on the conserved F protein across NiV human isolates and employed an immunoinformatics approach to predict linear B-cell epitopes capable of direct immune activation. Predicted epitopes were screened for antigenicity, toxicity, and allergenicity. Molecular docking analysis was performed to evaluate its binding affinity with B-cell receptors (BCRs). To validate its immunogenicity, the LF6 peptide was synthesized and used in an indirect ELISA to test sera from cohort previously infected with NiV as well as with negative cohort. Epitope LF6 (LISNIEIGFCL) was identified as a strong candidate based on its immunogenic properties. Molecular docking showed favorable binding of LF6 with BCR. ELISA results revealed that one sera from the survival cohort showed positive response which is an IgG antibody response 2-fold higher (0.343) than the cut-off value (0.0171). This study provides the first reported evidence linking computational predictions with functional immune reactivity for a B-cell epitope of NiV. The findings suggest that LF6 has the potential to elicit specific immune responses. However, given the small sample size, further validation in larger cohorts is essential to confirm LF6's vaccine relevance.

Cardiorespiratory fitness (CRF) is a strong predictor of cardiovascular morbidity and mortality. This study aimed to describe age- and sex-specific reference values for CRF in healthy adults in Kazakhstan and to examine age-related changes in key physiological parameters, including peak heart rate and body mass index. The research included 3271 nonsmoking adults aged 20 to 59&#x2009;years, free of health issues, who performed symptom-limited incremental cardiopulmonary exercise testing on a cycle ergometer between 2018 and 2025. The highest 30-s average value from exercise testing defined peak oxygen uptake (VO2 peak). VO2 peak were lower in older age groups in both sexes. In men, VO2 peak values was 43.4&#x2009;&#xb1;&#x2009;7.41&#x2009;mL/kg/min during ages 20-29 and 38.3&#x2009;&#xb1;&#x2009;6.32&#x2009;mL/kg/min during ages 50-59. In women, corresponding VO2 peak values were 39.2&#x2009;&#xb1;&#x2009;6.49 and 30.8&#x2009;&#xb1;&#x2009;5.78&#x2009;mL/kg/min. Peak heart rate also was lower in older ages (men: 174&#x2009;&#xb1;&#x2009;11 to 142&#x2009;&#xb1;&#x2009;8 bpm; women: 179&#x2009;&#xb1;&#x2009;10 to 143&#x2009;&#xb1;&#x2009;11 bpm). Simple linear regression results showed that age was a significant predictor of VO2 peak, BMI, and peak heart rate in both men and women (p&#x2009;<&#x2009;.001). This study provides the first nationally relevant descriptive data on CRF reference values for Kazakh adults. Cardiorespiratory fitness describes how well the heart and lungs supply oxygen to the body during physical activity. It is an important indicator of overall health and is strongly linked to the risk of heart disease and early death. However, until now, there has been little information about typical fitness levels in adults living in Kazakhstan. This study included over 3200 healthy, nonsmoking adults aged 20 to 59&#x2009;years. Participants completed a controlled exercise test on a stationary bicycle to measure their maximum oxygen use (a key marker of fitness). The study also examined heart rate and body weight changes with age. The results showed that fitness levels decrease as people get older in both men and women. Younger adults had higher fitness levels and higher maximum heart rates during exercise, while older adults showed lower values. Body weight tended to increase with age. When compared with other countries, fitness levels in Kazakhstan were lower than in some Western populations (such as the United States and Norway), but higher than in others (such as Korea and Lithuania). These findings provide the first reference values for cardiorespiratory fitness in Kazakh adults. This information can help doctors better assess patient health and support the development of targeted prevention programs. Improving fitness through regular physical activity may play an important role in reducing the risk of heart disease and improving long-term health outcomes.

Aedes aegypti and Aedes albopictus mosquitoes are the primary vectors of tropical diseases, including dengue fever (DHF), chikungunya, and Zika, particularly in tropical regions such as Malaysia. Vector control efforts are now increasingly focused on biological and environmentally friendly approaches, one of which is using insect growth regulator (IGR)-based insecticides such as pyriproxyfen. Pyriproxyfen works by disrupting the metamorphosis process of mosquito larvae into adults without causing direct death, but it is effective in inhibiting the emergence of adult mosquitoes by more than 90%, depending on the dose and environmental conditions. This study evaluated the concentration-dependent effects of pyriproxyfen on laboratory and field populations of Aedes spp. Laboratory strains exhibited 100% adult mortality at 1.04 ppm (Ae. aegypti) and 1.08 ppm (Ae. albopictus), whereas field populations required 1.15 - 1.71 ppm depending on locality. LC50 values were lowest in laboratory strains (0.267 ppm for Ae. aegypti and 0.236 ppm for Ae. albopictus), while field strains ranged from 0.326 to 0.571 ppm. LC95 values followed a similar trend, with 1.026 ppm (Ae. aegypti) and 1.107 ppm (Ae. albopictus) in laboratory strains. Inhibition of emergence (IE%) was high in laboratory strains, reaching 97.89% at 0.50 ppm in Ae. aegypti and 63.54% at 0.50 ppm in Ae. albopictus. Field populations required higher concentrations for similar suppression, with IE% ranging from 17.68 - 98.23% in Ae. aegypti and 13.14- 98.24% in Ae. albopictus, peaking at 1.50 ppm. From this finding, it is suggested that pyriproxyfen effectively inhibits adult emergence in both laboratory and field populations, with laboratory strains more sensitive at lower concentrations and field strains responding at higher doses. These results provide strong evidence for pyriproxyfen as an effective, adaptive, and sustainable component of integrated vector management in Malaysia.

Hepatocellular carcinoma (HCC) is one of the most metastatic and aggressive malignancies. Circular RNAs (circRNAs) are associated with the pathogenesis and prognosis of HCC. This study aimed to explore the role of circ_0020236 in HCC progression. Expression levels of circ_0020236, miR-1825, and IKBKB were assessed in HCC clinical samples and cell lines using quantitative real-time PCR. Bioinformatics predictions combined with dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays validated molecular interactions. Functional assays, including CCK-8, colony formation, and Transwell migration, were employed to evaluate cell proliferation and migration. The results indicated that circ_0020236 and IKBKB were significantly downregulated, whereas miR-1825 was upregulated in HCC. Ectopic expression of circ_0020236 suppressed HCC cell proliferation, migration, and tumor growth in vivo. Mechanistically, circ_0020236 functioned as a molecular sponge for miR-1825, which directly targeted IKBKB. Rescue experiments showed that miR-1825 overexpression reversed the tumor-suppressive effects of circ_0020236, while IKBKB knockdown abrogated the inhibitory phenotype induced by miR-1825 silencing. Furthermore, the RNA-binding protein ESRP2 was identified as a positive regulator of circ_0020236 biogenesis. In conclusion, our findings reveal that the ESRP2/circ_0020236/miR-1825/IKBKB axis plays a critical role in inhibiting HCC progression, positioning circ_0020236 as a promising therapeutic target for HCC intervention.