Efficient Delivery Research Articles

Delivery of a STING Agonist Using Lipid Nanoparticles Inhibits Pancreatic Cancer Growth.

The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive and characterized by a large number of cancer-associated fibroblasts, myeloid-derived suppressor cells, and regulatory T cells. Stimulator of interferon genes (STING) is an endoplasmic reticulum receptor that plays a critical role in immunity. STING agonists have demonstrated the ability to inflame the TME, reduce tumor burden, and confer anti-tumor activity in mouse models. 2'3' cyclic guanosine monophosphate adenosine monophosphate (2'3'-cGAMP) is a high-affinity endogenous ligand of STING. However, delivering cGAMP to antigen-presenting cells and tumor cells within the cytosol remains challenging due to membrane impermeability and poor stability. In this study, we encapsulated 2'3'-cGAMP in a lipid nanoparticle (cGAMP-LNP) designed for efficient cellular delivery. We assessed the properties of the nanoparticles using a series of in-vitro studies designed to evaluate their cellular uptake, cytosolic release, and minimal cytotoxicity. Furthermore, we examined the nanoparticle's anti-tumor effect in a syngeneic mouse model of pancreatic cancer. The lipid platform significantly increased the cellular uptake of 2'3'-cGAMP. cGAMP-LNP exhibited promising antitumor activity in the syngeneic mouse model of pancreatic cancer. The LNP platform shows promise for delivering exogenous 2'3'-cGAMP or its derivatives in cancer therapy.

Soil moisture-based irrigation interval and irrigation performance evaluation: In the case of lower kulfo catchment, Ethiopia

The lack of soil moisture-based irrigation intervals, poor distribution of irrigation water among users, and the time-based and spatial variability of water supply have been challenges for the productivity of irrigation schemes in the Lower Kulfo catchment, Southern Ethiopia. This study was conducted to develop soil moisture-based irrigation intervals and to evaluate irrigation water delivery and field level irrigation efficiencies. Soil water content, and flow along the canal and in the field were measured directly, and irrigation duty was estimated by using CropWat 8 model. To minimize water stress or excess problems, irrigation needs to be applied when soil water content drops to 35.7 % for onion and pepper, 34.4 %% for watermelon, and 32.5 % for wheat and maize from field capacity. However, irrigation was applied at 36.2 % for onion, 35.4 % for watermelon, 36.4 % for pepper, 36.2 % for maize, and 35 % for wheat in the existing irrigation scheme that increased irrigation amount in the field. The average percentage of soil moisture depletion (p) at time of irrigation was 27.4 %, which was below the recommended value. The average adopted irrigation and design irrigation interval were 4 & 6 days for onion and pepper, 5 & 7 days for watermelon and wheat, and 6 & 7 days for maize, respectively. The mean irrigation adequacy and dependability of the irrigation scheme in the lower Kulfo catchment were 1 & 0 for Arba Minch irrigation scheme, 0.5 & 0.2 for Arba Minch University farmland, 0.4 & 0.25 for private farmland and 0.1 & 0.43 for Kollashara farmland, respectively. The value of irrigation equity was 0.7 in January, 0.6 in February, and 0.8 in March which indicates the highly temporary variation of irrigation adequacy. The mean value of canal conveyance was 82.7 % and the average on-farm irrigation efficiency also was 56.6 %. The average value crop yield in the present study were 0.5ton/ha for wheat, 4.9ton/ha for onion, 6.2ton/ha for pepper, 0.6ton/ha for watermelon, 4.2ton/ha for maize that was very low compared with other control irrigation in the study area. Inadequate soil moisture-based intervals, inequitable water distribution, and variable supply hinder irrigation in the Lower Kulfo catchment; adopting optimized practices and robust management can enhance efficiency, equity, and crop productivity.

Efficient control of root-knot nematode by expressing Bt nematicidal protein in root leucoplast

Root-knot nematodes (RKNs) are plant pest that infect the roots of host plants. Bacillus thuringiensis (Bt) nematicidal proteins showed toxicity to nematodes. However, the application of nematicidal proteins in plant protection is hampered by the lack of effective delivery system in transgenic plants. In this study, we discovered the accumulation of leucoplasts (root plastids) in galls and RKN-induced giant cells. RKN infection caused the degradation of leucoplasts into small vesicle-like structures, and are responsible for delivering proteins to RKNs, as seen through confocal microscopy and immunoelectron microscopy. We further showed that different sized proteins from leucoplasts could be taken up by female of Meloidogyne incognita by western blot analysis. To further explore the potential applications of leucoplasts, we introduced the Bt crystal protein Cry5Ba2 into tobacco and tomato leucoplasts by fusing it with a transit peptide. The resulting transgenic plants showed significant resistance to RKNs. Intriguingly, RKN females preferentially uptake Cry5Ba2 protein when it was delivered through plastids rather than the cytosol. The decrease in progeny production was positively correlated with the delivery efficiency of the nematicidal protein. In conclusion, this study provides new insights into the feeding behavior of RKNs and their ability to ingest leucoplast proteins. Furthermore, it demonstrates the potential use of leucoplasts as an efficient delivery system for nematicidal proteins, offering a promising approach for controlling nematodes.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

Can Operating Room Design Make Orthopedic Surgeries Shorter, Safer, and More Efficient?: A Quasi-Experimental Study.

The study aimed to fill the knowledge gap about how operating room (OR) design could reduce orthopedic surgery duration and contribute to surgical care safety and efficiency. Long surgery duration may lead to delays and cancellations of surgeries, deteriorated patient experiences, postoperative complications, and waste of healthcare resources. The OR physical environment may contribute to the reduction of surgery duration by minimizing workflow disruptions and personnel movements during surgeries. Unobtrusive observations were conducted of 70 unilateral total knee or hip replacement surgeries in two differently designed ORs at a community hospital in the United States. A set of computer-based forms adapted from recent research was used to measure the surgery duration, environment-related disruptions, and ambulatory movements involving circulators. Potential confounding factors like surgery type were controlled in statistical analyses. Significantly shorter surgery durations were recorded in the larger OR with more clearances on both sides of the operating table, a wider door located on the sidewall, more cabinets, and more clearance between the circulator workstation and the sterile field (p =.019). The better-designed OR was also associated with less frequent disruptions and fewer movements per case (p < .001). Significant correlations existed between surgery duration, the number of disruptions, and the number of movements (rs = .576-.700, ps < .001). The study demonstrated the important role of OR physical environment in supporting the safe and efficient delivery of surgical care, which should be further enhanced through research and design innovations.

Efficient delivery of curcumin by functional solid lipid nanoparticles with promoting endosomal escape and liver targeting properties

In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of ∼228 nm, with impressive encapsulation efficiencies (EE) of 87.5 % ± 2.3 % for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2 %. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.

Biological Fate Tracking of Nitric Oxide-Propelled Microneedle Delivery System Using an Aggregation-Caused Quenching Probe.

Nanoparticle-loaded dissolving microneedles (DMNs) have attracted increasing attention due to their ability to provide high drug loading, adjustable drug release behavior, and enhanced therapeutic efficiency. However, such delivery systems still face unsatisfied drug delivery efficiency due to insufficient driving force to promote nanoparticle penetration and the lack of in vivo fate studies to guide formulation design. Herein, an aggregation-caused quenching (ACQ) probe (P4) was encapsulated in l-arginine (l-Arg)-based nanomicelles, which was further formulated into nitric oxide (NO)-propelled nanomicelle-integrated DMNs (P4/l-Arg NMs@DMNs) to investigate their biological fate. The P4 probe could emit intense fluorescence signals in intact nanomicelles, while quenching with the dissociation of nanomicelles, providing a "distinguishable" method for tracking the fate of nanomicelles at a different status. l-Arg was demonstrated to self-generate NO under the tumor microenvironment with excessive reactive oxygen species (ROS), providing a pneumatic force to promote the penetration of nanomicelles in both three-dimensional (3D)-cultured tumor cells and melanoma-bearing mice. Compared with passive microneedles (P4 NMs@DMNs) without a NO propellant, the P4/l-Arg NMs@DMNs possessed a good NO production performance and higher nanoparticle penetration capacity. In conclusion, this study offered an ACQ probe-based biological fate tracking approach to demonstrate the potential of NO-propelled nanoparticle-loaded DMNs in penetration enhancement for topical tumor therapy.

Magnetized electroosmotic drug delivery of Au-SiO2 nanocarriers through blood-based jeffrey hybrid nanofluid in a microchannel: Caputo Fabrizio derivative modeling

Fractional calculus is emerging as a promising field to overcome the intricacies inherent in biological systems that prevent conventional techniques from producing optimal results. The present research emphasizes the impact of thermal radiation, chemical reactions, and radiation absorption on an electroosmotic magnetohydrodynamic (MHD) blood-based Jeffrey hybrid nanofluid flow in a microchannel, employing the novel Caputo-Fabrizio fractional calculus approach. This study is carried out on two models: ramped and constant boundary conditions with distinct zeta potentials. The graphs are drawn with the help of MATLAB software. Our results demonstrate that the fractional order significantly influences the drug dispersion, and for α=0.9 (fractional parameter), the blood flow becomes wavy. The presence of nanoparticles improves drug transport, hence enhancing the drug concentration in proximity to the target site. For α=0.1, the Jeffrey nanofluid with ramped conditions shows the highest velocity enhancement in the case of pressure-driven, natural convective flow. Electroosmotic force facilitates fluid flow and enhances drug transport efficiency. For Ha < 4, the blood velocity decreases in the vicinity of the plate y = 0, and reverse behavior is observed as it passes y = 0.5, which can aid in effective drug delivery. At y = 0, the heat transfer rate increases by a maximum of 199.18 % while skin friction decreases to 3.07 %, aiding in maintaining medications at the desired temperature and improving drug delivery efficiency. The temperature and velocity of the blood hybrid nanofluid are maximized under ramping wall settings compared to constant wall conditions.

Biomodulatory Effects of Molecular Delivery in Human T Cells Using 3D-Printed Acoustofluidic Devices

ObjectiveCell-based therapies have shown significant promise for treating many diseases, including cancer. Current cell therapy manufacturing processes primarily utilize viral transduction to insert genomic material into cells, which has limitations, including variable transduction efficiency and extended processing times. Non-viral transfection techniques are also limited by high variability or reduced molecular delivery efficiency. Novel 3D-printed acoustofluidic devices are in development to address these challenges by delivering biomolecules into cells within seconds via sonoporation. MethodsIn this study, we assessed biological parameters that influence the ultrasound-mediated delivery of fluorescent molecules (i.e., calcein and 150 kDa FITC-Dextran) to human T cells using flow cytometry and confocal imaging. ResultsLow cell plating densities (100,000 cells/mL) enhanced molecular delivery compared to higher cell plating densities (p < 0.001), even though cells were resuspended at equal concentrations for acoustofluidic processing. Additionally, cells in the S phase of the cell cycle had enhanced intracellular delivery compared to cells in the G2/M phase (p < 0.001) and G0/G1 phase (p < 0.01), while also maintaining higher viability compared to G0/G1 phase (p < 0.001). Furthermore, the calcium chelator (EGTA) decreased overall molecular delivery levels. Confocal imaging indicated that the actin cytoskeleton had important implications on plasma membrane recovery dynamics after sonoporation. In addition, confocal imaging indicates that acoustofluidic treatment can permeabilize the nuclear membrane, which could enable rapid intranuclear delivery of nucleic acids. ConclusionsThe results of this study demonstrate that a 3D-printed acoustofluidic device can enhance molecular delivery to human T cells, which may enable improved techniques for non-viral processing of cell therapies.

A novel pH-responsive multi-component nanodelivery system with siRNA for plant disease management

At the present time, the control of plant viral diseases is primarily achieved through the use of traditional pesticides. However, the tendency of RNA viruses to mutate and develop resistance to pesticides represents a significant challenge. The development of nanoscale strategies based on RNA interference (RNAi) represents a rapidly evolving approach to sustainable plant disease control. In this study, an siRNA was screened that effectively targets the 70-kDa heat shock protein (HSP70), which is closely associated with plant virus infection and replication. Additionally, a novel nanosystem for hierarchical delivery of siRNA was developed. This consisted of the cellular shuttle peptide (CPP)-modified tetrahedral DNA nanoparticles (TDN) as the core and polydopamine-hybridized mesoporous silica nanoparticles (PDA-MSN) as the shell. This was named TDN-siR099@CPP@PDA-MSNs. The results demonstrated that upon entering the leaf tissue through the stomata, TDN-siR099@CPP@PDA-MSNs encountered a weak acidic environment, prompting the PDA-MSN to release TDN-siR099@CPP. This resulted in the intercellular shuttling of TDN-siR099@CPP. The nanoscale dimensions of TDN-siR099@CPP facilitate facile displacement, while the intrinsic properties of CPP enhance the efficacy of long-distance siR099 intercellular shuttling. In this nanosystem, we also demonstrated that PDA-MSN retarded the susceptible degradation of siRNA in vitro and responded to the acidic release of the drug, which improve the utilization efficiency of siRNA in terms of both improving the delivery efficiency and delaying the degradation. It effectively down-regulated 56.2% of HSP70 protein and inhibited the infection of tobacco mosaic virus (TMV) and potato Y virus (PVY) by 70.2% and 41.0%, respectively. By skillfully constructing a framework for siRNA inhibition of target genes, this technology broadens the application of RNA silencing in plant disease management.

Delivering DNA Aptamers Across the Blood-Brain Barrier Reveals Heterogeneous Decreased ATP in Different Brain Regions of Alzheimer's Disease Mouse Models.

DNA aptamers have been developed as sensors to detect metabolites with high sensitivity, selectivity, and biocompatibility. While they are effective in sensing important targets in the brain, the lack of methods for their efficient delivery across the blood-brain barrier (BBB) has significantly hindered their applications in brain research. To address this issue, we herein report the development of brain cell-derived exosomes as endogenous BBB delivery vehicles to deliver an ATP-responsive aptamer across the BBB of live mice for noninvasive live brain imaging. We found that the system uses endosome recycling to transfer the sensors between the delivered exosomes and native recycling endosomes, resulting in high delivery efficiencies. Using this system, we observed unique signal distributions for ATP across different brain regions, with significant accumulation in the subiculum and cortex in healthy mice. In an Alzheimer's disease transgenic mouse model, ATP levels decreased in the subiculum and cortex, demonstrating this method's capability to determine metabolite location and relative abundance with high spatial resolution in vivo. Since DNA aptamers have been obtained for many other targets, the method developed in this work can be applied to deliver sensors across the BBB to image a wide range of other brain-related metabolites.

Trust Evaluation Techniques for 6G Networks: A Comprehensive Survey with Fuzzy Algorithm Approach

Sixth-generation (6G) networks are poised to support an array of advanced technologies and promising high-quality and secure services. However, ensuring robust security, privacy protection, operational efficiency, and superior service delivery poses significant challenges. In this context, trust emerges as a foundational element that is critical for addressing the multifaceted challenges inherent in 6G networks. This review article comprehensively examines trust concepts, methodologies, and techniques that are vital for establishing and maintaining a secure and reliable 6G ecosystem. Beginning with an overview of the trust problem in 6G networks, this study underscores their pivotal role in navigating the network’s complexities. It proceeds to explore the conceptual frameworks underpinning trust and discuss various trust models tailored to the unique demands of 6G networks. Moreover, this article surveys a range of scholarly works presenting diverse techniques for evaluating trust by using the fuzzy logic algorithm, which is essential for ensuring the integrity and resilience of 6G networks. Through a meticulous analysis of these techniques, this study elucidates their technical nuances, advantages, and limitations. By offering a comprehensive assessment of trust evaluation methodologies, this review facilitates informed decision making in the design and implementation of secure and trustworthy 6G networks.

Increased Superoxide Dismuatase (SOD) In Mice Infected by Plasmodium Berghei ANKA Treated with Nanoparticle Extract of Beetroot (Beta Vulgaris L)

BACKGROUND: Malaria infection causes increased free radicals which leads to severity and decreases antioxidant activity, thus increasing the risk of severe malaria complications. Beetroot extract has active compounds that function as anti-inflammatory and antioxidants. Nanoparticles are a technology that can be used to improve drug delivery efficiency in smaller doses. AIMS: to prove the effectiveness of beetroot extract nanoparticles on SOD levels in mice infected with malaria and treated with artemisinin METHOD: An experimental study using a post-test-only randomized control group design. The research sample used 30 male Balb/c mice divided into 6 groups. Group 1 was the healthy group, group 2 was the infected group without treatment, group 3 was the infected group with artemisinin treatment, group 4 was the infected group with artemisinin treatment and 50 mg/kgBW/day beetroot extract nanoparticles, group 5 was the infected group with artemisinin treatment and 100 mg/kg BW/day beetroot extract nanoparticles, and group 6 was the infected group with artemisinin treatment and 200 mg/kg BW/day beetroot extract nanoparticles. Beetroot extract and artemisinin supplementation were given after parasitemia index &gt; 1% and given for 4 days. On the 5th day after therapy, serum SOD levels were measured using ELISA. RESULT: The measurement of SOD levels in the artemisinin group supplemented with nanoparticle extracts of beetroot at doses 100-200 mg/KgBW were 21,48-21,59 ng/ml. Kruskal Wallis and Mann Whitney test showed that they are significantly higher serum SOD levels compared to the infected mice group (p&lt;0.05). CONCLUSION: Supplementation of beetroot extract nanoparticles has an antioxidant effect by increasing SOD levels in mice infected with malaria and receiving artemisinin therapy.

Improvement of Therapeutic Effect via Inducing Non-Apoptotic Cell Death Using mRNA-Protection Nanocage.

Necroptosis, a cell death mechanism with the characteristics of both apoptosis and necrosis, is proposed as a promising therapeutic approach for cancer therapy. Induction of necroptosis for cancer therapy may be possible through the regulation of the expression of a key factor gene receptor-interacting protein kinase-3 (RIPK3) via in vitro transcription (IVT) mRNA delivery. However, mRNA is susceptible to degradation and has a low delivery efficiency, which highlights the requirement of a proper delivery vehicle for intracellular delivery. Therefore, a new mRNA delivery system based on the nanostructured silica nanoparticles, termed mRNA-protective nanocage (mPN) has been developed. High-efficiency expression of RIPK3 and induction of necroptosis is achieved through delivery of RIPK3 IVT mRNA with mPN in vitro and in vivo models. Importantly, the mPN carrying RIPK3 mRNA distributed locally in tumors upon intravascular injection, and successfully induced necroptosis and immune cell infiltration, a hallmark of necroptosis. the suppression of tumor growth in a murine cancer model, demonstrating the synergistic effect of RIPK3 mRNA- and immune cell-mediated therapy is also observed. These findings suggest the potential for anticancer therapy through necroptosis induction and provide a strategy for the development of mRNA-based nanomedicine.

In Vitro Comparison of Aerosol Delivery in High-Frequency Assisted Airway Clearance Devices With Integrated Nebulizers.

High-frequency assisted airway clearance systems combine positive expiratory pressure or oscillatory positive airway pressure with integrated nebulizers to improve the delivery of aerosols and assist with airway clearance. This aerosol study evaluated lung delivery efficiency during positive expiratory pressure and oscillatory positive airway pressure therapy of 2 high-frequency assisted airway clearance/nebulizer systems. Aerosol delivery was evaluated during positive expiratory pressure therapy of 10 cm H2O and oscillatory positive airway pressure therapy of 20 cm H2O with the BiWaze Clear and the Volara high-frequency assisted airway clearance/nebulizer systems. The handset and nebulizer were attached to an anatomic upper-airway model via a mouthpiece and placed into a plethysmograph. A tracheal filter was placed to capture the inhaled aerosol. A vacuum filter entrained fugitive aerosols from the plethysmograph. After nebulization of technetium in 3.0 mL normal saline solution, the components were scanned by using scintigraphy and the decay-corrected radiation counts were referenced to the initial nebulizer technetium charges. Aerosol delivery during positive expiratory pressure therapy of 10 cm H2O resulted in higher lung deposition with the BiWaze Clear versus the Volara (28 vs 6.2%; P < .001; 95% CI 16.5-27.7), and higher fugitive losses (23.7 vs 2.8%; P = .004) and nebulizer losses (55 vs 3.3%; P < .001) with the Volara than with the BiWaze Clear. Aerosol delivery during oscillatory positive airway pressure of 20 cm H2O resulted in a higher lung deposition with the BiWaze Clear versus the Volara (16.3 vs 7.3%; P = .005; 95% CI 3.3-15) and higher fugitive (22.3 vs 3.8%; P = .02) and nebulizer (58.8 vs 7.2%; P = .004) losses with the Volara. There were no differences at the other locations during testing. The BiWaze Clear system showed greater delivery efficiency than did the Volara during positive expiratory pressure and oscillatory positive airway pressure. The high residual nebulizer dose and fugitive aerosol losses through the handset leak valve contributed to the lower delivery efficiency observed with the Volara. The nebulizer type, circuit design, and handset are important factors when targeting effective aerosol delivery to the lungs with high-frequency assisted airway clearance therapy.

Enhancing service delivery via Work-Integrated Learning (WIL) at uMzimkhulu Local Municipality, South Africa

Municipalities in South Africa face numerous challenges that hinder efficient service delivery. One of these challenges is the lack of implementation of required services, leading to citizen dissatisfaction and protest actions. This study aims to investigate methods for improving service delivery in public institutions in South Africa through the implementation of work-integrated learning (WIL) programmes. Data for this study was collected from the uMzimkhulu local municipality in KwaZulu-Natal, specifically from the Harry Gwala District. A total of 56 participants took part in the study, including 28 WIL students and 28 mentors. This ensured representation from all departments within the municipality. Two separate sets of questionnaires were used to collect data from these two groups. Data analysis was performed using the Statistics Packaging for Social Sciences (SPSS) version 27. The study identified several challenges that currently hinder the effective implementation of WIL programmes within the municipality. As a result, it is recommended that the municipality provide training for WIL students and establish efficient monitoring and evaluation processes for the WIL programmes. Additionally, the municipality should involve students in WIL programmes in matters related to progressive initiatives and provide further support to enhance their ability to handle client services. It is also advised that the municipality prioritise the development of facilities and resources for WIL students to fully engage them in their work.

Secure and efficient device‐to‐device communication in IoT: The DMBSOA‐enhanced MQTT protocol

AbstractThe Internet of Things (IoT) plays a crucial role in enhancing technology by facilitating data transfer, storage, control, and management across networks. Secure communication within IoT environments remains a significant challenge. This research aims to enhance IoT security by integrating Message Queuing Telemetry Transport (MQTT) and MQTT‐Sensor Network (MQTT‐SN) protocols with the Dual Mutation‐Based Seagull Optimization Algorithm (DMBSOA). MQTT, known for its lightweight and dependable messaging, is widely used in the IoT community but is vulnerable to cyber‐attacks, particularly concerning privacy and authentication. DMBSOA, inspired by seagulls' foraging behavior, optimizes MQTT settings to enhance security, reliability, and performance. The proposed model dynamically adjusts key parameters such as transmission frequency, Quality of service (QoS) levels, and message size to improve energy consumption, throughput, end‐to‐end delay, and packet delivery ratio. A comprehensive system model is presented, comprising publisher, subscriber, and broker nodes, with security mechanisms integrated into the broker to ensure data integrity, authentication, and encryption. MQTT operates over Transmission Control Protocol/Internet Protocol (TCP/IP), while MQTT‐SN uses User Datagram Protocol (UDP), catering to resource‐constrained devices and low‐power modes. The proposed technique attained throughput (68 kB), energy consumption (120 mJ), security level (96%), energy efficiency (98.80%), path loss (22 dB), end‐to‐end delay (35 ms), processing time (230 s) and packet delivery ratio (0.98). The DMBSOA‐optimized MQTT protocol demonstrates superior performance compared to these models, highlighting its potential to meet the evolving demands of IoT security. This research underscores the effectiveness of DMBSOA in enhancing MQTT protocol security and efficiency, providing a promising solution for secure IoT communication.

LEGAL FRAMEWORK FOR E-SYARIAH AND I-SYARIAH IN JUDICIAL SERVICE DELIVERY IN MALAYSIA: ITS DEVELOPMENT AND CHALLENGES

The electronic technology transformation within the Syariah Court management system in Malaysia has created a new dimension which is geared towards a more efficient, comprehensive, and allinclusive Syariah Court service delivery process. This research aims to analyse the challenges in developing this Syariah Court management system, namely the e-Syariah system implemented at the Federal level and the i-Syariah system which is applicable in Sarawak. An in-depth investigation was conducted on the modules developed in the e-Syariah and i-Syariah systems to obtain inclusive research information on the areas of concerned. A qualitative research method was employed to explore the progressive challenges in developing the e-Syariah and i-Syariah systems, and this was followed by a comparison of the systems applied by the Civil Courts and the contents of the system applied by the Syariah judiciary institutions in Malaysia. The findings revealed several challenges in developing the Syariah Court management system in Malaysia from the perspective of legal provisions, as well as information and communications technology (ICT). This matter has been viewed positively by the Department of Syariah Judiciary Sarawak (JKSS) and the Department of Syariah Judiciary Malaysia (JKSM), leading to the close cooperation with the Sarawak Information System Sdn. Bhd. (SAINS) in developing i-Syariah and e-Syariah to be applied in the Civil Courts. An upgrade of the e-Syariah system was carried out by the JKSM to respond to the challenges of digital technology applications in Malaysia, hence enabling the delivery of Syariah judiciary service that can be implemented successfully, systematically, and dynamically.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke: a special outlook on mitochondrial delivery.

Ischemic stroke is a secondary cause of mortality worldwide, imposing considerable medical and economic burdens on society. Extracellular vesicles, serving as natural nano-carriers for drug delivery, exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke. However, the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency. By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles, their delivery efficacy may be greatly improved. Furthermore, previous studies have indicated that microvesicles, a subset of large-sized extracellular vesicles, can transport mitochondria to neighboring cells, thereby aiding in the restoration of mitochondrial function post-ischemic stroke. Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components, such as proteins or deoxyribonucleic acid, or their sub-components, for extracellular vesicle-based ischemic stroke therapy. In this review, we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies. Given the complex facets of treating ischemic stroke, we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process. Moreover, given the burgeoning interest in mitochondrial delivery, we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Quality-by-Design (QbD) Assisted Synthesis of Nanoparticle for Efficient Loading, Stabilization, and Intracellular Delivery of Bioactive for the Treatment of Arthritis

Quality-by-Design (QbD) Assisted Synthesis of Nanoparticle for Efficient Loading, Stabilization, and Intracellular Delivery of Bioactive for the Treatment of Arthritis