Search Results (725)

As one of the key vectors for the transmission of Dengue fever, Aedes albopictus is highly ecologically adaptable. The development of environmentally compatible biological defence and control technologies has therefore become an urgent need for vector biological control worldwide. This study constructed and used double-stranded RNA (dsRNA) expression vectors targeting the cyp314a1 and cyp315a1 genes of Ae. albopictus to transform Chlamydomonas reinhardtii and Chlorella vulgaris, achieving RNA interference (RNAi)-mediated gene silencing. The efficacy of the RNAi recombinant algal strain biocide against Ae. albopictus was evaluated by administering it to Ae. albopictus larvae. The results showed that the oral administration of the cyp314a1 and cyp315a1 RNAi recombinant C. reinhardtii/C. vulgaris strains was lethal to Ae. albopictus larvae and severely affected their pupation and emergence. The recombinant algal strains triggered a burst of ROS (Reactive Oxygen Species) in the mosquitoes’ bodies, resulting in significant increases in the activities of the superoxide dismutase (SOD), peroxiredoxin (POD) and catalase (CAT), as well as significant upregulation of the mRNA levels of the CME pathway genes in larvae. In the simulated field experiment, the number of Ae. albopictus was reduced from 1000 to 0 in 16 weeks by the RNAi recombinant Chlorella, which effectively controlled the population of mosquitoes. Meanwhile, the levels of nitrogen (N), phosphorus (P), nitrate, nitrite, ammonia and COD (Chemical Oxygen Demand) in the test water decreased significantly. High-throughput sequencing analyses of 18S rDNA and 16S rDNA showed that, with the release of RNAi recombinant Chlorella into the test water, the biotic community restructuring dominated by resource competition caused by algal bloom, as well as the proliferation of anaerobic bacteria and the decline of aerobic bacteria triggered by anaerobic conditions, are the main trends in the changes in the test water. This study is an important addition to the use of RNAi recombinant microalgae as a biocide. Full article

This study introduces a single-step method to synthesize guar gum-based interpenetrating polymer network (IPN) hydrogels, achieving simultaneous Diels–Alder crosslinking and amoxicillin (AMOX) encapsulation under mild conditions. To evaluate the influence of porogen addition on IPN structure, drug loading and release, twenty-one formulations were developed, including AMOX loading (25% or 40% w/w relative to the polymer) and biocompatible porogens incorporation [polyethylene glycol (PEG) or sucrose at 5%, 10%, or 50% w/w]. All crosslinked IPN hydrogels formed robust gels, unlike non-crosslinked controls. Porogen choice strongly influenced hydrogel performance: PEG quadrupled the swelling index while enhancing storage modulus (up to 10,054 Pa) and complex viscosity (up to 1302 Pa·s), whereas high sucrose concentrations produced soft, ductile networks with critical strains above 20% and swelling indices up to 1895%. All hydrogels released AMOX at levels above MIC₅₀ for H. pylori. PEG-based IPN provided superior drug delivery profiles, with extended AMOX release (t₅₀ up to 15.5 h at pH 5.0), while sucrose-rich matrices exhibited faster burst release and disintegration. Single-step (pre-loading) AMOX during synthesis improved release control compared to post-loading. These findings highlight the potential of one-pot IPN synthesis with porogen modulation offering a promising gastroretentive platforms for sustained AMOX delivery against H. pylori. Full article

Nuclear fuel cladding serves as the primary barrier to the release of radioactive fission products and is subjected to high-temperature and high-pressure environments during both normal reactor operation and accident scenarios such as loss of coolant accidents (LOCAs). Predicting the burst behavior of cladding is essential for ensuring structural integrity, especially under varying heating rates—an aspect inadequately addressed in existing empirical models. In this study, a finite element-based damage model is developed to simulate the ballooning and burst behavior of Zircaloy-4 cladding. The model incorporates creep deformation, stress triaxiality, and time-dependent damage accumulation. Material behavior is characterized using experimentally determined creep constants and the model is calibrated against burst test data from the literature. A new heating-rate-dependent burst correlation is proposed based on model outputs. The results indicate that increasing the heating rate raises the burst temperature due to reduced exposure time in the temperature regime where creep damage accumulates significantly. The model accurately reproduces burst behavior across a wide range of internal pressures (1–10 MPa) and heating rates (5–100 °C/s). The newly developed correlation improves predictive capability in accident analysis tools and can be directly implemented into safety analysis codes for Indian pressurized heavy water reactors (PHWRs), contributing to enhanced reactor safety evaluations. Full article

Reactive oxygen species (ROS) are among the most effective tools of the innate immune response against pathogenic microbes. The respiratory burst (RB) of polymorphonuclear leukocytes (PMNs) generates an electron current that reduces molecular oxygen to superoxide. Superoxide reacts to form hydrogen peroxide as a precursor to the highly bactericidal hypochlorous acid. Here, we investigated whether alterations in extracellular potassium concentration impact H₂O₂ production. Such changes may occur, for example, during massive cell death due to necrosis or due to trauma injuries when potassium diffuses out of the cells. We recorded H₂O₂ release over a 2 h period of RB under varying potassium concentrations. Except for 100 mM potassium chloride, which increased the time delay before detectable H₂O₂ production, none of the potassium concentrations had a substantial effect on RB. We further examined whether this effect depended on the specific monovalent ion species. When sodium or methanesulfonate was used instead of potassium or chloride, respectively, no changes in H₂O₂ production were observed. Cell volume measurements under different potassium concentrations showed that only 100 mM potassium chloride significantly shrank the cells. We propose that hypertonic stress is crucial for delaying RB in human granulocytes, whereas the RB itself is independent of the tested ionic species. Additionally, the conducted hypertonic stress experiments revealed an unexpected time-dependence during the course of the RB, showing that the first 6 min were almost inert to hyperosmotic stress. Full article

Background/Objectives Conventional eye drops are the primary therapeutic option for ocular diseases; however, their clinical utility is hindered by several drawbacks, including limited bioavailability and suboptimal patient compliance. To overcome these challenges, we designed a sustained-release contact lens (CL) device loaded with tranilast (TRA) and determined whether the TRA-laden CL could provide sustained drug delivery to the lacrimal fluid and aqueous humor. Methods TRA nanocrystals were prepared using the bead-milling approach. Using three types of CLs (nonionic, anionic, and cationic), we prepared TRA-laden CLs by employing a combination of solid TRA nanocrystals and soaking methods under high-temperature and high-pressure conditions in an autoclave (the hThP method). Male Japanese albino rabbits (2–3 kg) were used to evaluate the CLs. Results Bead milling reduced the size of the solid TRA nanoparticles (STNs) to approximately 35–180 nm. The TRA-laden cationic CLs prepared using STNs and the hThP method contained a higher amount of TRA than those prepared using the corresponding conventional soaking method. The CLs prepared using the hThP method remained transparent after drug loading. Compared with nonionic and anionic CLs, cationic CLs had the highest drug-loading capacity and allowed for sustained drug release. Moreover, STNs were observed in the released TRA, with no corneal damage or light scattering detected in the rabbits’ eyes. TRA-laden cationic CLs prepared using the hThP method achieved sustained and higher drug delivery into the lacrimal fluid and aqueous humor than those prepared using the conventional soaking method. Conclusions Our findings suggest that TRA-laden cationic CLs prepared using STNs and the hThP method can overcome the challenges associated with the conventional soaking method, including low drug uptake and high burst release. Full article

Applying therapeutic elements to prevent injury from potential infections is a promising avenue in the development of novel bone substitutes; however, achieving controllable delivery of therapeutic ions is crucial to realizing their expected functions. In this study, a Ag nanoparticle core wrapped in an MSN shell was successfully synthesized using a one-pot sol–gel process. Subsequently, the produced Ag@MSN was functionalized with amino and carboxylic groups. The experimental results indicated that these core–shell-structured Ag@MSN spheres had a uniform size of ~60 nm and a specific area of 904.6 m²/g. Their release profiles, influenced by different surface charges, were investigated, with the aim of achieving sustainable release of Ag ions. The concentration-dependent biological effects of Ag@MSNs, including their anti-infection properties and biocompatibility, were comprehensively characterized in vitro, considering their potential for use as bioactive bone substitutes. Functionalized mesoporous silica nanoparticles significantly enhanced the sustained release profile of silver ions, achieving a cumulative release efficiency greater than 50% within 24 h. These nanoparticles also demonstrated exceptional antibacterial efficacy, with an inhibition rate surpassing 98% at a concentration of 30 μg/mL, while concurrently maintaining cell viability above 88%, indicating high biocompatibility. We achieved our goal of effectively decreasing the burst release of Ag to satisfy the intrinsic need for long-term resistance to bacteria in bone substitutes and stimulate osteoblast proliferation. Full article

Bone tissue restoration requires biomaterials, which combine osteoinductivity and the capability to prevent surgical site infections. Magnesium-substituted biphasic calcium phosphate (Mg-BCP) represents a promising solution, as magnesium substitution increases the biodegradation rate of calcium phosphate ceramics and provides inherent antibacterial properties. This study aimed to achieve wet precipitation synthesis of magnesium-substituted (1–10 mol%) biphasic calcium phosphate and to evaluate its drug delivery potential and antibacterial performance. Porous Mg-BCP granules were fabricated via the gelation of Mg-BCP suspension in sodium alginate followed by polymer removal. Drug delivery potential was evaluated using methylene blue as a model compound, with methylcellulose encapsulation implemented to ensure prolonged release. Magnesium content directly ruled the phase composition: low concentrations (1%) favored hydroxyapatite phase prevalence, while higher concentrations led to the β-tricalcium phosphate formation. Further assessment of drug delivery potential revealed that direct drug loading resulted in burst release, whereas methylcellulose encapsulation successfully enabled prolonged drug delivery. Mg-5BCP formulation demonstrated significant antimicrobial activity with growth inhibition of 17.7 ± 4.1% against C. albicans, 20.8 ± 7.0% against E. faecalis, and 12.9 ± 7.5% against E. coli. Therefore, Mg-5BCP–methylcellulose composite granules present a versatile platform for antibacterial drug delivery for bone tissue engineering applications. Full article

Background/Objectives: Oral delivery of biologics offers advantages for patient access and adherence compared to injection, but suffers from low bioavailability due to mucosal barriers and drug degradation in the gastrointestinal tract. We previously developed an oral self-pressurized aerosol (OSPRAE) capsule that uses effervescent excipients to generate CO₂ gas, building internal pressure to eject powdered drug at high velocity across intestinal mucosa. Methods: Here, we developed two key design improvements: (i) an enteric covering to protect the capsule delivery orifice in gastric fluids and (ii) reduced humidity content of capsules to extend shelf-life. Results: Enteric-covered capsules prevented drug release in simulated gastric fluid and then enabled rapid release upon transfer to simulated intestinal fluid. Burst pressure for enteric-covered capsules was ~3–4 times higher than non-covered capsules. After storage for up to three days, the capsules’ effervescent excipients pre-reacted, making them unable to achieve high pressure during subsequent use. To address this limitation, we prepared capsules under reduced humidity conditions, which inhibited pre-reaction of effervescent excipients during storage, and a polyurethane coating to improve water uptake into the capsule to drive the effervescence reaction in intestinal fluid. Conclusions: These design improvements enable improved functionality of OSPRAE capsules for continued translation in pre-clinical and future clinical development. Full article

Background: Although electrohydrodynamic atomization (EHDA) consistently provides drug-encapsulation efficiencies (DEE) far above those of conventional bottom-up nanotechnologies, the question of how to systematically push that efficiency even higher remains largely unexplored. Methods: This study introduces a modified triaxial electrospinning protocol tailored to the application and benchmarks it against two conventional techniques: single-fluid blending and coaxial electrospinning. Ethylcellulose (EC) served as the polymeric matrix, while curcumin (Cur) was chosen as the model drug. In the triaxial setup, an electrospinnable, drug-free EC solution was introduced as an intermediate sheath to act as a molecular barrier, preventing Cur diffusion from the core fluid. Ethanol alone was used as the outermost fluid to guarantee a stable and continuous jet. Results: This strategy provided a DEE value of 98.74 ± 6.45%, significantly higher than the 93.74 ± 5.39% achieved by coaxial electrospinning and the 88.63 ± 7.36% obtained with simple blending. Sustained-release testing revealed the same rank order: triaxial fibers released Cur the most slowly and exhibited the smallest initial burst release effect, followed by coaxial and then blended fibers. Mechanistic models for both fiber production and drug release are proposed to clarify how the tri-layer core–shell structure translates into superior performance. Conclusions: The modified triaxial electrospinning was able to open a new practical route to produce core-sheath nanofibers. These nanofibers could provide a higher DEE and a better sustained drug release profile than those from the coaxial and blending processes. Full article

This study presents the development of a degradable and biocompatible calcium phosphate cement (CPC) co-loaded with gentamicin (1.25 wt%) and vancomycin (4.25 wt%) for the local treatment of polymicrobial bone infections. The antibiotics were incorporated—individually or in combination—into the solid phase of Graftys^® Quickset (GQS), an injectable CPC. Antibiotic loading modifies some of the intrinsic properties of the GQS cement. Porosity exceeded 53%, compressive strength reduced around 5 MPa, which is comparable to calcium sulphates cements, and the setting time, although extended, remained within the clinically acceptable threshold (<20 min), ensuring suitable handling. A burst release of both antibiotics was observed within the first 24 h, with sustained release over time and no cytotoxic effects on human osteoblasts. The dual-loaded cement exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative strains, including methicillin-resistant isolates, in both planktonic and biofilm forms. Notably, the combination of both antibiotics demonstrated superior efficacy compared to either antibiotic alone. These findings suggest that this dual-antibiotic-loaded CPC offers a promising strategy for localised treatment of complex bone infections such as osteomyelitis, where polymicrobial involvement and antibiotic resistance pose significant therapeutic challenges. Full article

Sim, a potent HMG-CoA reductase inhibitor, exhibits notable anabolic effects on bone and can upregulate osteogenic genes such as BMP-2, thereby promoting bone formation. An ideal drug delivery system for Sim involves its controlled and sustained release at the defect site to minimize adverse side effects. In this study, Sim was first modified via HP-γ-CD to form a hydrophilic Sim/HP-γ-CD inclusion complex, thereby improving drug solubility and dispersion in aqueous systems. A gelatin–sodium alginate (Gel/SA) hydrogel was then employed as the drug delivery matrix to construct a Gel-SA-Sim/HP-γ-CD hydrogel sustained release system. This hydrogel system exhibited a high water content (82%), along with enhanced mechanical properties, including a compressive strength of 0.284 MPa and a compressive modulus of 0.277 MPa, suggesting strong load-bearing capacity and favorable stiffness. Importantly, Sim was released in a controlled and sustained manner over 7 days, without exhibiting burst release behavior. In vitro osteogenic differentiation assays demonstrated that optimal concentrations of Sim effectively enhanced cellular bioactivity and osteoinductive performance, offering a promising approach to enhance the bioactivity, osteogenesis, and osseointegration of orthopedic implants. Full article

In order to reveal the failure characteristics and burst tendency of coal after microwave irradiation, the microstructure damage effect of microwave irradiation on coal was explored. The microstructure damage, burst tendency and acoustic emission energy characteristics of coal samples before and after microwave irradiation were quantitatively evaluated, and the mechanisms behind porosity growth and the weakening effect of microwave irradiation were revealed. The results show that the damage amount D_E of coal samples after microwave irradiation is 0.018, the crack damage amount D_P is 0.015, and the crack damage amount accounts for 83.3% of the damage of coal samples. It is determined that the damage-weakening effect of microwave-irradiated coal is affected by the increase in cracks. The monitoring data show that the acoustic emission signals generated by its development are concentrated in the crack compaction stage and elastic stage, the energy dissipated by crack failure is proportional to the number of cracks, and the ability of coal samples to accumulate energy is inversely proportional to the number of cracks. After microwave irradiation, the mechanical properties of coal samples are weakened, the uniaxial compressive strength index is reduced by 67.66%, and the burst energy index is reduced by 66.67%, indicating that microwave irradiation can effectively reduce the bursting tendency of coal. Full article

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

Background: Dopamine (DA) is a critical neurotransmitter that regulates many physiological and behavioral processes. The central dopaminergic system plays a pivotal role in modulating general anesthesia (GA). DA release in the brain is mainly concentrated in the nucleus accumbens (NAc), prefrontal cortex, hypothalamus, and dorsal striatum. Several NAc neuron subtypes are essential for modulating states of consciousness during GA. However, whether NAc DA signal dynamics correlate with different states of consciousness under sevoflurane anesthesia remains to be elucidated. In this study, we measured the dynamic fluctuations of NAc DA levels throughout sevoflurane anesthesia to verify its role. Methods: An intensity-based genetically encoded DA indicator, dLight1.1, was employed to track DA release in the NAc. Fiber photometry combined with electroencephalogram/electromyogram recordings was employed to synchronously track NAc DA signal dynamics across different states of consciousness under sevoflurane anesthesia. Results: Under 2.5% sevoflurane exposure, DA release in the NAc significantly increased during the initial 100 s of sevoflurane induction, which was designated as sevo on-1 (mean ± standard error of the mean [SEM]; baseline vs. sevo on-1, p = 0.0261), and continued to decrease in the subsequent anesthesia maintenance phases (sevo on-1 vs. sevo on-4, p = 0.0070). Following the cessation of sevoflurane administration (with intervals denoted as sevooff), NAc DA gradually returned to baseline levels (sevo on-1 vs. sevo off-1, p = 0.0096; sevo on-1 vs. sevo off-3, p = 0.0490; sevo on-1 vs. sevo off-4, p = 0.0059; sevo on-4 vs. sevo off-4, p = 0.0340; sevo off-1 vs. sevo off-4, p = 0.0451). During the induction phase, NAc DA signal dynamics markedly increased during the pre-loss of consciousness (LOC) period (pre-anesthesia baseline vs. pre-LOC, p = 0.0329) and significantly declined after LOC (pre-LOC vs. post-LOC, p = 0.0094). For the emergence period, NAc DA release exhibited a noticeable increase during the initial period after recovery of consciousness (ROC) (anesthesia baseline vs. post-ROC, p = 0.0103; pre-ROC vs. post-ROC, p = 0.0086). Furthermore, the DA signals peaked rapidly upon the initiation of the burst wave and then gradually attenuated, indicating a positive correlation with the burst wave onset during burst suppression events. Conclusions: Our findings revealed that NAc DA neurotransmitter signal dynamics correlate with different states of consciousness throughout sevoflurane anesthesia. Full article

If untreated, skin wounds can lead to severe complications. Depending on the type of injury, long-term antibiotic administration is often required, and this decreases patient compliance. This limitation could be addressed by applying dressings capable of preventing infections by controlling drug release to the wound site. In this research, biodegradable wound dressings were investigated, based on natural polymers chitosan and alginate and incorporating the broad-spectrum gentamicin as antibiotic. Specifically, gentamicin was loaded into alginate nanoparticles, which were then loaded into chitosan-based films. This approach aimed at obtaining a system capable of modulating antibiotic release. The obtained nanoparticles had an average diameter of 86 nm and polydispersity index of 0.15. Antibiotic loading was around 600 µg/mg, with loading efficiency close to 100%. Films incorporating nanoparticles were compared to control films, which contained only gentamicin. Results showed that nanoparticles incorporation decreased film’s swelling in phosphate buffer saline, thus leading to a decrease in burst release while cytocompatibility for human dermal fibroblasts was maintained. Antibacterial activity was confirmed against both gram-positive and gram-negative bacteria. Moreover, the antibiotic was released as a function of pH, with distinct behavior at pHs ranging from 7.4 to 5.5. This indicates that alginate nanoparticles dispersed in chitosan films effectively release gentamicin on demand. Full article