Development of trivalent DNA vaccine encapsulated in chitosan TPP nanoparticles against EV-A71 and CV-A16

Hand foot and mouth disease (HFMD) is a prevalent global disease commonly occurring in young children under 6 years of age. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) have been isolated as the major causative agents for most HFMD outbreaks in the Asia Pacific region. Severe HFMD could lead to cardiopulmonary and neurological failure or death. Currently, there are no US-FDA approved HFMD vaccines or antiviral treatments available in the market. The current China FDA approved vaccine for HFMD is a monovalent inactivated vaccine targeting EV-A71 without providing protection against CV-A16. In this study, we attempt to design a trivalent DNA vaccine candidate that could be administered to confer cross protection against EV-A71 and CV-A16. Chitosan-TPP Nanoparticles encapsulation of plasmid vaccine candidate was carried out to enhance immune response and prevent degradation. The VP1, VP2 genes of EV-A71 and VP1 gene of CV-A16 were cloned into the pIRES2-AcGFP1vector to form the recombinant plasmid pIRES-VP121. Chitosan TPP nanoparticles (NPs) encapsulating the trivalent pDNA were synthesized through ionic gelation followed by in vitro characterization. In vivo immunization of 4 weeks old ICR mice was carried out to evaluate the immunologic enhancement of Chitosan Nanoparticles. The formulated chitosan TPP (CS-TPP-NPs (pIRES-VP121)) were highly monodispersed with an average size of ~200nm. Chitosan TPP NPs encapsulating the pDNA showed >70% encapsulation efficiency and good cellular uptake in mice macrophage cells were observed. The plasmid DNA vaccine was protected from DNase I digestion by chitosan TPP NPs. In vivo immunization studies demonstrated enhanced immunogenic responses by CS-TPP-NPs (pIRES-VP121) due to self adjuvanting properties of chitosan nanoparticles. Mice administered with CS-TPP NPs (pIRES-VP121) intramuscularly were observed to have the highest IFN-γ response (~15-fold increment). Sera from mice immunized with the naked pDNA and CS-TPP-NPs (pIRES-VP121) demonstrated good viral clearance against wild-type EV-A71 and CV-A16 in RD cells. Unfortunately, murine sera administered with naked pDNA and CS-TPP-NPs (pIRES-VP121) showed reduced ability to neutralize mouse adapted virus (MAV) strains of EV-A71 and CV-A16. CS-TPP-NPs (pIRES-VP121) could serve as a prototype for future development of multivalent HFMD DNA vaccine candidates

Improved Manta Ray Foraging Optimizer-based SVM for Feature Selection Problems: A Medical Case Study

Support Vector Machine (SVM) has become one of the traditional machine learning algorithms the most used in prediction and classification tasks. However, its behavior strongly depends on some parameters, making tuning these parameters a sensitive step to maintain a good performance. On the other hand, and as any other classifier, the performance of SVM is also affected by the input set of features used to build the learning model, which makes the selection of relevant features an important task not only to preserve a good classification accuracy but also to reduce the dimensionality of datasets. In this paper, the MRFO + SVM algorithm is introduced by investigating the recent manta ray foraging optimizer to fine-tune the SVM parameters and identify the optimal feature subset simultaneously. The proposed approach is validated and compared with four SVM-based algorithms over eight benchmarking datasets. Additionally, it is applied to a disease Covid-19 dataset. The experimental results show the high ability of the proposed algorithm to find the appropriate SVM’s parameters, and its acceptable performance to deal with feature selection problem

Malaysian Carrageenophyte Kappapphycus species inhibit Lipopolysaccharides-Induced Neuroinflammation by suppressing the AKT/NFxB and ERK signaling pathways in BV2 Microglia AKT/NFkB and ERK signaling pathways in BV2 Microglia.

Neuroinflammation is normally caused by the stimulation of microglia and astrocytes with the production of proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO) and cyclooxygenase-2 (COX-2), as well as the generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Unregulated activities and overproduction of proinflammatory mediators and cytokines will cause neuronal death, which will trigger the development of neurodegenerative diseases. Kappaphycus alvarezii and Kappaphycus malesianus are red algae cultivated in Semporna, Sabah, East Malaysia. They are remarkable with their k-carrageenans which have been widely used as a thickening agent in food, cosmetics, and nutraceutical industry. Kappaphycus spp. have been reported with several pharmacological effects, including antioxidant, anti-viral and anti-cancer effects. However, limited research was focusing on their neurological effects. Therefore, it is our interest to explore and compare the bioactivity of K. alvarezii and K. malesianus from the neuroprotective aspect. This study aimed to investigate the anti-neuroinflammatory activity in K. alvarezii and K. malesianus crude extracts (ethyl acetate, ethanol, and methanol extracts) on lipopolysaccharides (LPS)-induced BV2 microglial cell line and their underlying mechanisms. Cell viability assay (MTT assay) was used to examine the percentage of viable BV2 microglial cell line after treating with respective K. alvarezii and K. malesianus crude extracts. Nitric oxide inhibition assay (Griess assay) was used to investigate the nitric oxide inhibitory activity of all crude extracts, while the crude extract with the highest nitric oxide inhibitory activity was used for western blot and ELISA analyses to investigate the proinflammatory mediators (iNOS and COX-2) and cytokines (TNF-⍺, IL-6 and IL-1β) expression in LPS-induced BV2 microglial cell line. The potential compound(s) in the extract with the highest promising anti-neuroinflammatory effect were identified using the liquid chromatography-mass spectrometry (LC-MS) analysis. Our results indicated that all extracts of both seaweeds had maintained cell viability above 80% at the concentration of 2.5 mg/mL, except for K.malesianus ethanol extract (69.7% ± 0.31 mg/mL). K. alvarezii ethyl acetate extract and K. malesianus methanol extract indicated the highest nitric oxide inhibitory activity without showing significant cytotoxicity towards BV2 microglial cell line. Thus, K. alvarezii ethyl acetate and K. malesianus methanol extract was selected to further evaluate their proinflammatory mediators and proinflammatory cytokines expressions and signaling pathways. The results disclosed that K. malesianus methanol extract demonstrated higher inhibitory activity in the formation of proinflammatory mediators and cytokines via AKT/NF-kB and ERK pathways. According to the LC-MS analysis for K. malesianus methanol extract, three known bioactive compounds were identified with anti-neuroinflammatory activities, namely, 2,6-nonadien-1-ol, prosopinine and eplerenone. In conclusion, all K. alvarezii and K. malesianus extracts showed inhibitory activity on nitric oxide and proinflammatory cytokines production, which may contribute to the anti-neuroinflammatory activity. Moreover, western blot results explained that K. alvarezii and K. malesianus extracts had contributed to anti-neuroinflammatory activity through inhibiting iNOS and COX-2 production via AKT/NF-kB, and ERK pathways. K. malesianus methanol extract is the most potent extract and may acts as a potent anti-neuroinflammatory therapy in the prevention of neurodegenerative disorders

Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients

Background: Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients. Methods: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted. Results: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046). Conclusions: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study

Debunking The Myth: Malaysia’s Universities Thrive In Regional Rankings

The article “Malaysia Fails In Southeast Asia Best Universities Ranking; So, What Went Wrong?” paints a grim picture of Malaysian universities’ rankings, suggesting that they have completely “failed” compared to other Southeast Asian nations. However, this is utterly misleading. As per the QS World University Rankings 2025, 8 out of the top 15 universities in Southeast Asia are Malaysian universities

Mutual fund performance and the validity of fund manager's outperformance claims in G7 economies: an empirical investigation

Mutual funds are prominent in the global capital market, offering diversification and professional management to individual investors. In view of their crucial role in the global financial landscape, this study aims to assess mutual funds' ability to outperform market benchmarks, evaluate fund managers' stock selection skills, and investigate market timing across G7 countries The dataset includes 50 mutual funds (25 equity-based and 25 bond-based) from each G7 nation between 2015 and 2022. Various performance metrics such as Sharpe Ratio, Treynor Ratio, Jensen’s Alpha, and market timing models are employed. Our findings generally support the efficient market hypothesis (EMH), as most G7 mutual funds fail to outperform market benchmarks. Negative Sharpe and Treynor ratios across the sample suggest insufficient risk-adjusted returns. Additionally, the lack of positive Jensen’s Alpha and weak performance under the Fama-French three-factor model indicate that most fund managers lack stock-picking skill. However, a few funds from the US and UK do exhibit positive Jensen’s Alpha, suggesting that skilled management may be present in some cases. In terms of market timing, only Italian fund managers demonstrate statistically significant positive abilities, while fund managers in other countries show limited or negative timing skills. These findings suggest that, contrary to the hopes of active management, most G7 mutual funds do not consistently outperform the market, aligning with the core prediction of EMH. Similarly, actively managed exchange-traded funds (ETFs) show limited success in outperforming passive benchmarks. These findings emphasize the importance of carefully evaluating fund performance before making investment decisions and tempering expectations regarding the potential for abnormal returns from actively managed funds. Investors should consider focusing on low-cost passive investment strategies, particularly in light of the limited evidence for consistent outperformance in active management

Nanoparticle enchanced salt hydrate eutectic phase change material for thermal energy regulation in buildings

Global energy storage trends are emerging as the energy market shifts from fossil fuels to renewable energy for electrification. Meanwhile, the indoor thermal conditions of buildings and offices are inversely proportional to the quantity of energy consumed and CO2 emitted. To reduce the energy consumption in thermal conditioning of buildings, phase change materials (PCM)s are predominant owing to their energy storage capability and passive operation. Inorganic salt hydrate PCMs are recognized as high energy storage materials with less toxicity, non-flammable nature and economically viable than organic PCMs. However, inherent thermal characteristics, low energy storage potential of PCM with low temperature, and degree of supercooling associated with salt hydrate are of utmost concern, which is resolved via tailored eutectic PCM. This encourages investigation and development of new type of inorganic-inorganic eutectic phase change material (EPCM). Nanoparticles are dispersed to enhance the thermal features and thermal reliability. Subsequently, substantial research is underway to investigate the performance of unique dimensioned nanoparticles in conjunction with PCM. Herein, the main objective of this research was to develop and evaluate the potential of an inorganic salt hydrate nanocomposite EPCM, intended for passive thermal regulation of buildings towards sustainable future. To achieve this objective, four inorganic salt hydrate with low melting temperature were selected to formulate 21 different combinations of EPCM adopting the Schrader equation. Among them, binary combination of 62% of sodium sulphate decahydrate (SSD) and 38% of sodium phosphate dibasic dodecahydrate (SPDD) displayed eutectic melting temperature of 27.6°C, eutectic melting enthalpy of 216 J/g and thermal conductivity of 0.464 W/m⋅K. Subsequently, 1D multi-walled carbon nanotube (MWCNT) and 2D graphene nanoplatelets (GNP); lab synthesised 2D nanomaterial MXene, 3D nano-sized tetrapods (thin-arms and thick-arms), and 3D ecofriendly coconut shell biochar were dispersed with EPCM individually to identify the suitable nanocomposite. Phase transition temperature, thermal conductivity, energy storage, degree of supercooling, chemical stability, optical absorbance & transmittance and corrosion analysis of the developed nanocomposite EPCMs are experimentally characterised. Nanocomposites EPCM improved thermal conductivity by 106.1% (0.956 W/m⋅K with 1.2 wt.% of GNP), optical absorbance by 746.15% (1.1 wt.% of MXene), reduction in degree of supercooling by 91.1% (0.9 wt.% of MWCNT). Thermal properties of superior nanocomposites EPCMs are used as input parameter via Type1270 PCM layer in TRNSYS simulation studio to analyse the variation in heating and cooling load of building integrated with PCM. On integrating 2 cm thickness of SSD/SPDD+GNP EPCM layer within the ceiling/roof of study space, cooling load for climatic condition of Kuala Lumpur and New Delhi decreases by 38.8% and 30.5%. Integration of nanocomposite EPCM with building structures assists passive thermal regulation with better thermal conditions for occupants. Furthermore, real-time experimental investigation on nanocomposite EPCM integrated constructions is needed to assess the real-time performance of building thermal comfort. Research presented in this thesis significantly contributes towards the sustainable development goal of SDG-07 (Affordable and Clean energy) in specific to target SDG-7.3 by facilitating improved energy efficiency; and SDG11 (Sustainable Cities and Communities) in specific to target 11.c by constructing sustainable and resilient building

Evaluating the impact of technological innovation and energy efficiency on load capacity factor: empirical analysis of India

The determinants of environmental degradation have been investigated many times by utilizing carbon dioxide emissions and/or ecological footprint. However, these traditional environmental degradation indicators do not consider the supply side of environmental problems. Therefore, this study focuses on the dynamic influence of financial development, energy efficiency, economic growth, and technological innovation on environmental degradation in India through the load capacity factor, including both the supply and demand sides of environmental problems. For that purpose, the recently developed dynamically simulated autoregressive distributed lag (ARDL) method is employed using the annual time-series data extending from 1980–2020. The dynamically simulated ARDL results demonstrate that financial development, economic growth, and technological innovation have a dynamic adverse impact on the load capacity factor, whereas energy efficiency has a positive dynamic influence on environmental quality. In addition, the results support the validity of the environmental Kuznets curve hypothesis as the negative effect of economic growth on environmental quality decreases over time. Based on the study findings, policy recommendations are provided for India. Finally, this study utilizing load capacity factor as an indicator for environmental quality will provide new topics in exploring the determinants of environmental degradation

The interaction between remittance, FDI, renewable energy, and environmental quality: a panel data analysis for the top remittance-receiving countries

A country’s financing system is essential in addressing sustainable development requirements. National sources and international financial flows contribute to economic growth and environmental quality in many ways, and their impact can be critical. This paper applied panel data analysis using a comparative approach of Pooled Mean Group Auto Regressive Distribute Lags (PMG-ARDL) and Cross Sectionally ARDL (CS-ARDL) to estimate the effects of FDI, renewable energy, and remittance on environmental quality in the top remittance-receiving countries, during 2000–2021. The study emphasized the positive relationship between FDI and carbon emissions. Moreover, renewable energy and remittances revealed an inverted U-shaped relationship with carbon emissions. In the case of developing countries from the panel, remittance improves environmental quality after reaching the threshold. Moreover, for some of the developing countries included in the panel, we found that they do not achieve the desired carbon mitigation effect in their early stages of renewable energy implementation. However, renewable energy becomes a key factor for tackling environmental pollution after a certain threshold. The mixed results determined diverse policy recommendations for various stakeholders

Accessibility to plasma-derived medicinal products in Malaysia: The challenges faced by patients with inborn errors of immunity

Inborn errors of immunity (IEI) (also known as primary immunodeficiencies) is an umbrella term for a growing group of over 450 different disorders that are characterized by defects in some of the components of the immune system. IEI are chronic diseases of genetic origin that render individuals suffering from them susceptible to infections. The mainstay of treatments for most patients with IEI, that is, predominantly antibody deficiencies is immunoglobulin replacement therapy (IRT), which is commonly delivered intravenously. Immunoglobulin (IG) therapy contains antibodies to compensate for the defective immune system’s inability to produce them. Individuals with IEI need IRT regularly throughout their lives to help combat infections and prevent organ damage. Without IRT, they are in danger of suffering from morbidity, poor quality of life, and reduced life expectancy. In the last 20 years, the use of IG preparation has tripled and this is partly attributed to the growing awareness and improved diagnoses of IEI cases. IG preparations are also used for the treatment of other medical conditions including secondary immunodeficiencies and autoimmune diseases. As IG is derived from human plasma, there are concerns about the availability of supply, particularly to treat life-threatening conditions that cannot be improved with other medications. It is estimated that 75% to 80% of IEI patients do not have access to adequate IG therapy throughout the world. This concern of supply and other challenges faced by patients with IEI in Malaysia are described from the patients’ perspective