Extended Residence Time Research Articles

Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies

Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, natural pH, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system based on modified chitosan, which enhances solubility at natural pH and is coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and evaluate their efficacy both in vitro and in streptozotocin-induced diabetic male rats. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. In vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells using an MTT assay and fluorescent microscopy, respectively. The in vivo blood glucose-lowering effect was assessed in diabetic male Sprague–Dawley rats, with in vivo toxicity evaluated in the liver, spleen, duodenum, pancreas, and kidney through histological studies (H&E staining). The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 %, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40. Furthermore, in vivo studies demonstrated a sustained reduction in blood glucose levels after oral administration, peaking after 8 h with a glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity. Overall, the developed colon-targeted oral insulin delivery system shows great potential as a candidate for oral insulin administration.

A new low NOx emission technique for NH3/H2 blends in a flameless combustor through offset injection

The application of ammonia (NH3) as a possible future fuel presents a plausible solution for green energy storage. It helps provide a carbon-neutral fuel alternative for industrial power generation and transportation. However, the combustion of NH3 presents a formidable challenge due to its low reactivity, inadequate flame stability, sluggish flame propagation, and high NOx emissions. Consequently, its integration into combustion systems necessitates substantial system and strategy modification to enable its deployment to industrial systems. The current study presents a novel fuel/air injection technique, which emphasizes the high recirculation of hot combustion products and the extended residence time of fuel/air mixtures. A comprehensive experimental and numerical investigation is conducted using a swirl air injection and offset fuel injection to achieve the flameless combustion mode for optimized NH3/H2 fuel blends. A range of mixture conditions (ϕ = 0.5–1.2) and NH3/H2 compositions (50/50–70/30) are experimentally examined. The investigations helped elucidate the effect of residence time and recirculation on NOx emissions through kinetic simulations using a reactor network model. Subsequently, 3-D numerical simulations helped identify regions of high recirculation, quantified through reactant dilution ratios and uniform temperature distribution. These aspects are determined using a new parameter, the temperature uniformity index along the axial direction of the combustor. The emissions of NOx, unburnt NH3, and unburnt H2 are quantified for different equivalence ratios and NH3 mole fractions in the fuel mixture. The investigations reveal that NOx emissions reached their minimum (450–654 ppm) and (344-211 ppm), when the burner operated at lean (ϕ = 0.5–0.8) and rich (ϕ = 1.0–1.2) conditions, respectively, for 70/30 NH3/H2 blend. The emissions of unburnt NH3 and H2 species remain minimal for lean conditions. Both lean and rich operational regimes demonstrated similar or superior emission characteristics in flameless combustion mode when compared to the conventional combustion mode.

Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time (> 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

Residence time effects on arsenate sorption on an allophanic Andosol

ABSTRACT The mobility and bioavailability of As in agricultural soils are controlled by sorption onto minerals. The effect of the residence time on the reaction between arsenate and allophanic Andosol, a typical agricultural soil in Japan, remains unclear. Therefore, we investigated the reaction between arsenate and allophanic Andosol and its components allophane and ferrihydrite over several months, based on the desorption experiment and X-ray diffraction (XRD) measurements in the long-term sorption experiment. The reaction between arsenate and three sorbents continued for approximately 150 d. The XRD patterns of allophane and ferrihydrite that reacted with arsenate did not change during the long-term sorption experiments under near-neutral pH conditions, suggesting negligible formation of surface precipitation. Furthermore, the irreversibility of arsenate sorption onto allophanic Andosol and allophane increased with extended residence time. These results suggested that the slow sorption of arsenate onto the materials could be ascribed to internal diffusion.

Production of high calorific value hydrogen-rich combustible gas by supercritical water gasification of straw assisted by machine learning

This article reveals the basic laws of straw supercritical water gasification (SCWG) and provides basic experimental data for the effective utilization of straw. The paper studied the impact of three operational conditions on the production of high-calorific value hydrogen-rich combustible gases through SCWG of straw within a quartz tube reactor. The findings reveal that elevated reaction temperatures, extended residence times, and reduced feedstock concentrations favor the SCWG of straw. When combustible gas contains carbon dioxide, the maximum low heating value (LHV) of the gas is 21 MJ/Nm3. Upon removing carbon dioxide, the LHV of the gas reached 38 MJ/Nm3. Subsequently, a machine learning (ML) model was developed to forecast gas yield and LHV during the SCWG process. The results demonstrate that the model exhibits robust generalization capabilities. ML can be extensively applied to forecast biomass SCWG processes across various operational conditions.

Injectable Nanocomposite Hydrogels Improve Intraperitoneal Co-delivery of Chemotherapeutics and Immune Checkpoint Inhibitors for Enhanced Peritoneal Metastasis Therapy.

Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.

Effect of Biomass Torrefaction on the Syngas Quality Produced by Chemical Looping Gasification at 20 kWth Scale.

The innovative Biomass Chemical Looping Gasification (BCLG) process uses two reactors (fuel and air reactors) to generate nitrogen-free syngas with low tar content under autothermal conditions. A solid oxygen carrier supplies the oxygen for partial oxidation of the fuel. This study investigated the BCLG process, conducted over 25 h of continuous operation at 20 kWth scale, using ilmenite as the oxygen carrier and wheat straw pellets as fuel (WSP). The effect of using torrefied wheat straw pellets (T-WSP) on the syngas quality was assessed. In addition, the impact of several operational variables on the overall process performance and syngas yield was analyzed. The primary factors influencing the syngas yield were the char conversion through gasification and the oxygen-to-fuel ratio. Higher temperatures, extended residence times of solids in the fuel reactor, and using a secondary gasifier led to increased char conversion, enhancing H2 and CO production. Optimizing the air reactor design could enhance the CO2 capture potential by inhibiting the combustion of bypassed char. While char conversion and syngas yield with T-WSP were lower than those with WSP at temperatures below 900 °C, T-WSP achieved a higher syngas yield under conditions favoring high char conversion. The presence of CH4 and light hydrocarbons showed minimal sensitivity to operating conditions variation, limiting the theoretical syngas yield. Overall, the CLG unit operated smoothly without any agglomeration issues.

Partial upgrading of bitumen with supercritical water— liquid products characteristics, gas composition and coke morphology

The study aimed to investigate the partial upgrading of bitumen in the absence of water (non-water) and the presence of supercritical water (SCW). Partial upgrading experiments were conducted at the target temperature of 420 °C, with the reaction time varying from zero to 60 min in a batch reactor. The liquid products were analyzed for density, viscosity, composition, total acid number (TAN), olefin content, and elemental analysis. The gas composition and morphology of solid products were also studied. The experimental results revealed that while partial upgrading of bitumen with SCW could accelerate improvement in oil quality, particularly in terms of API and viscosity, it concurrently led to elevated gas and coke formation levels. Moreover, the difference in the distribution of oil fractions between the two environments (absence and presence of SCW) tends to diminish with an extended residence time. Additionally, as the residence time increases, the efficiency of TAN reduction under SCW conditions is less pronounced compared to the non-water conditions. Liquid products obtained in an SCW environment exhibited higher olefin content (between 3 and 4 wt %) compared to non-water conditions (between 1.8 and 2.7 wt %). In both environments, the olefin content was initially increased up to a residence time of 20 min and then decreased. Regarding heteroatoms, the sulphur (S) and nitrogen (N) contents decreased up to 36 % and 72 %, respectively, while a greater reduction was observed in the presence of SCW. More non-hydrocarbon gases (H2S, CO2 and CO) were produced in the presence of SCW. SEM images showed that an extended residence time led to a shift in coke morphology towards a more uniform and compact structure, regardless of the upgrading environment. However, the porous structures of coke samples obtained under SCW are distinguished from those formed without water, which is attributed to the phase inversion of precursors. The findings of this study confirm that SCW plays a beneficial role as a solvent in the partial upgrading of bitumen, expediting the process. However, the increased level of coke formation and olefin contents suggest that it may not function effectively as a hydrogen donor in the process.

Formulation and evaluation of hydrocortisone micro beads

The current study aimed to develop hydrocortisone mucoadhesive microbeads to prolong the drug's action in the gastrointestinal system, targeting Crohn's disease treatment. Hydrocortisone, known for its anti-inflammatory and anti-rheumatic effects, was utilized in bead form to enhance therapeutic efficacy, extend residence time, and reduce dosage frequency. Using sodium alginate, HPMC, and Eudragit L-100 as adhesive polymers, and calcium chloride and aluminium chloride as cross-linking agents, the study crafted microbeads with an entrapment efficiency between 57.23% and 91.69%. Evaluations focused on in vitro drug release, particle size, surface characteristics, entrapment efficiency, and the role of cross-linking ions. Of the formulations, HCS-8 (with sodium alginate and Eudragit L-100 using aluminium chloride as the gelling solution) and HCS-2 showed optimal drug release profiles. Notably, HCS-8 achieved a 12-hour drug release delay, attributed to aluminium chloride's cross-linking action. Drug release kinetics revealed a zero-order linearity (R2=0.99), suggesting super case 2 transport as the primary release mechanism.

Pullulan-Based Spray-Dried Mucoadhesive Microparticles for Sustained Oromucosal Drug Delivery.

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 μm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.

Distinct differences of vertical phytoplankton community structure in mainstream and a tributary bay of the Three Gorges Reservoir, China.

The vertical distribution of phytoplankton plays a crucial role in shaping the dynamics and structure of aquatic communities. In highly dynamic reservoir systems, water level fluctuations significantly affect the physiochemical conditions and the phytoplankton community. However, the specific effects on the vertical characteristics of phytoplankton between the mainstream and the tributary bay of the reservoir remain unstudied. This study investigated the vertical aspects of phytoplankton density, biomass, α and β diversity through monthly sampling over two years in the mainstream (Chang Jiang, CJ) and a tributary bay (Xiang Xi, XX) of the Three Gorges Reservoir in China. Phytoplankton density and biomass were significantly higher in XX, indicating an increased risk of algal blooms in the tributary. The phytoplankton community in CJ showed more stable species-environment relationships, a lower Shannon index and a higher evenness index, suggesting a relatively simple structure and a more uniform distribution of phytoplankton among different water layers. Conversely, XX showed greater differences between water layers (higher β diversity), with significant negative correlations with water level and positive correlations with DO difference, dissolved silica (DSi) difference, and stratification. Peak phytoplankton density and biomass, as well as high β diversity in XX, occurred during periods of decreased water levels with strong stratification in spring and summer. A structural equation model complemented by path analysis revealed that a decrease in water level could increase β diversity either directly through internal processes with extended residence time or indirectly by modifying stratification and the vertical distribution of DSi in XX. Therefore, a proposed water quality management strategy for XX was to increase the water level or reduce β diversity by implementing artificial mixing during stratification periods. Overall, this study lies in its comprehensive investigation of the vertical characteristics of the phytoplankton community in both the mainstream and the tributary bay of the Three Gorges Reservoir, elucidating the significant impact of water level fluctuations and providing insights for targeted water quality management strategies in the tributary bay to mitigate potential ecological impacts.

Long-Residence Time Peptide Antagonist for the Vasopressin V2 Receptor to Treat Autosomal Dominant Polycystic Kidney Disease.

The dysregulated intracellular cAMP in the kidneys drives cystogenesis and progression in autosomal dominant polycystic kidney disease (ADPKD). Mounting evidence supports that vasopressin V2 receptor (V2R) antagonism effectively reduces cAMP levels, validating this receptor as a therapeutic target. Tolvaptan, an FDA-approved V2R antagonist, shows limitations in its clinical efficacy for ADPKD treatment. Therefore, the pursuit of better-in-class V2R antagonists with an improved efficacy remains pressing. Herein, we synthesized a set of peptide V2R antagonists. Peptide 33 exhibited a high binding affinity for the V2R (Ki = 6.1 ± 1.5 nM) and an extended residence time of 20 ± 1 min, 2-fold that of tolvaptan. This prolonged interaction translated into sustained suppression of cAMP production in washout experiments. Furthermore, peptide 33 exhibited improved efficacies over tolvaptan in both ex vivo and in vivo models of ADPKD, underscoring its potential as a promising lead compound for the treatment of ADPKD.

Systematic experiments and multiscale simulation calculations reveal chemical stability differences in dry/wet nanofiltration membranes

This study investigated the chemical stability differences between dry and wet nanofiltration membranes when immersed in strong acid and base environments. Systematic experimental studies were conducted on both types of nanofiltration (NF) membranes, supplemented by Molecular Dynamics (MD) simulations and Density Functional Theory (DFT) calculations. The results indicate that wet NF membranes, soaked in deionized water for a week, exhibit higher chemical stability compared to dry membranes treated only with air. Traditional air heating causes membrane pore contraction and excessive crosslinking. However, after a week of immersion in water, the polyamide (PA) layer gradually becomes a loose and well-extendable PA layer. MD simulations revealed that H+ and OH− ions possess lower diffusion coefficients and extended residence times in dry NF membranes, making them more prone to damage. Additionally, DFT calculations disclosed that the Gibbs free energy (ΔG) for amide bond hydrolysis in wet NF membranes, in the presence of water molecules, is elevated, significantly delaying their hydrolysis rate under extreme conditions. This study highlights the pivotal role of membrane wetness in the chemical durability of NF membranes and offers a novel perspective for improving membrane lifespan and efficiency.

Investigation of decomposition and partial oxidation of mixed acid gas and methane for syngas production

Reaction processes of decomposition and partial oxidation of a mixture of acid gas (H2S and CO2) and methane (CH4) could enable the efficient production of valuable syngas resource (H2 and CO). In this work, the decomposition and partial oxidation of H2S–CH4–CO2 system was experimentally studied in a tube furnace. Effects of temperature, CH4 and CO2 addition, equivalence ratio and residence time were studied for syngas production and H2/CO variation. Extended temperature and pressure were then studied by equilibrium calculation for thermodynamic analysis in Aspen Plus software. The results showed the increasing temperature favored reactant conversion and syngas production. H2S decomposition was the dominant reaction at temperature below 1050 °C while threshold temperature for CH4 conversion over H2S was about 1100 °C. H2 was formed mainly via H2S decomposition at low temperatures. CH4 addition promoted H2 formation and conversely restrained H2S conversion. The introduction of O2 brought partial oxidation, favored the reaction rate, balanced H2/CO but reduced syngas production. H2/CO ratio also remained at an appropriate level at high CO2 addition since CO2 evidently adjusted the ratio via CO2+H2↔CO + H2O. However, this CO2 reactivity was only adequately expressed under high temperature and extended residence time. Equilibrium calculation confirmed experimental variation trends and revealed reducing pressure favored the syngas production. It could be inferred that extended residence time, higher temperature, suitable equivalence ratio, CH4 and CO2 addition and low pressure could enable improvement in both syngas production and H2/CO. This study revealed high syngas production and adjustment of H2/CO could be realized in H2S–CH4–CO2 system and this might be of great practical in industry.

Understanding the effect of heating rate on hydrothermal liquefaction: A comprehensive investigation from model compounds to a real food waste

Hydrothermal liquefaction (HTL) emerges as an efficient technology for converting food waste into biocrude. Among HTL parameters, the impact of heating rate is understudied. This study systematically explores its variation (5–115 K/min) on HTL performance using actual food waste and model compounds representing its constituents. Results revealed that an increase in heating rates significantly impacts HTL performances (+63 % biocrude and −34 % solid with food waste) with short residence times, as slower heating rates imply a longer overall time and a higher kinetic advancement of the reaction. Conversely, with longer residence times, the influence of heating rates becomes negligible, as kinetics during heating times are overshadowed by those at operating temperatures. A subtle effect of heating variation at extended residence time was observed only with carbohydrates. This research emphasizes the utility of a kinetic severity factor (KSF) as a valuable tool for simultaneously considering heating rates, operating times, and temperatures.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss.

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27days) compared to the saline + D group (1.1 ± 0.3days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.

Hyaluronan nanoplatelets exhibit extended residence time compared to spherical and ellipsoidal nanomaterials with equivalent surface potentials and volumes after oral delivery in rats.

The physicochemical properties of colloidal particles-such as size, surface properties, and morphology-play a crucial role in determining their behaviors and transit through the gastrointestinal (GI) tract. While some data exist for nonspherical nanomaterials (NMs) composed of silica or polystyrene, there is limited understanding of NMs composed of polysaccharides and polymers. This study explores the fate and GI tract residence time of hyaluronan-based NMs with distinctive hexagonal morphology and flat surfaces (nanoplatelets) following administration to rats. The behavior of these nanoplatelets was compared to NMs with spherical and ellipsoidal morphologies. The three types of NMs were labeled with a near-infrared dye (Cy5.5) and administered in single doses to healthy rats, followed by real-time in vivo imaging over 24 hours. The results revealed that altering NM morphology from spherical to ellipsoidal did not significantly affect GI tract residence time or toxicity profiles in vitro and in vivo. However, nanoplatelets exhibited a stronger Cy5.5 fluorescence signal in the abdominal region and demonstrated slower gastric emptying than spherical and ellipsoidal NMs. Ex vivo analysis of excised GI tracts rinsed with saline indicated that nanoplatelets adhered more effectively to the tightly bound mucus layer. Furthermore, histological examination of colon sections showed that nanoplatelets induced a minimal global inflammation score comparable to that of healthy rats. This study underscores the potential of hyaluronan-based nanoplatelets for oral administration, offering promising directions for both fundamental research and practical applications in nanomedicine.

Changes of C, H, and N Elements of Corn Straw during the Microwave Heating Process

Due to the rapid growth of the global economy, energy consumption has been steadily increasing, leading to increasing issues such as energy shortages and environmental concerns. Biomass energy, a critical renewable energy source, plays a vital role in advancing low-carbon energy development and resource sustainability. In this study, experiments were conducted to study the migration of C, H, and N elements of corn straw during the microwave heating process, and the effects of residence time, heating temperature, and microwave power were also investigated. The results showed that when the temperature rose, both the proportion of C and H elements fluctuated slightly. Specifically, when the temperature rose from 75 °C to 275 °C, there was a 1.02% increase in the proportion of the C element and a 0.25% decrease in the proportion of the H element. Residence time appeared to be a significant factor influencing the changes in C, H, and N elements. For a 40 min residence time, the proportion of the C element increased from 31.77% to 35.36%, while the proportion of the H element decreased from 4.50% to 3.83%. When there was an increase in the microwave power between 160 W and 200 W, higher temperatures were reached in the samples, leading to the carbonization process of corn straw being more complete. Consequently, the proportion of the C element rose with extended residence time, whereas the proportion of the H element decreased as the residence time increased.

Evaluating the role of operating temperature and residence time in the torrefaction of betel nutshells for solid fuel production

This research addresses the urgent need for sustainable bioenergy alternatives, specifically evaluating betel nutshells as potential replacements for conventional biomass materials like coconut and palm fibers. The objective of the study was to gauge the inherent bioenergy potential of betel nutshells through an investigation of torrefaction under varying conditions, specifically temperatures ranging from 200-300 °C and residence times between 20-60 minutes in an inert environment. In this study, proximate analyses were utilized to investigate essential characteristics including moisture content, volatile matter, ash content, and fixed carbon, while a bomb calorimeter was used to determine their higher heating values. Initial results indicated that untreated betel nutshells had higher heating values and compositional similarities to coconut and palm fibers, highlighting their potential as a bioenergy source. Advanced torrefaction processes, involving increased temperatures and extended residence times, raised the fixed carbon content and reduced moisture in betel nutshells, thereby optimizing their higher heating value. This improvement is attributed to the decomposition of covalent bonds in the biomass structures, leading to the release of volatile compounds and consequent reductions in both oxygen-to-carbon and hydrogen-to-carbon ratios. Remarkably, at an operating temperature of 300 °C and a residence time of 60 minutes, torrefied betel nutshells reached a higher heating value of 25.20 MJ/kg, marking a substantial 31.39 % increase compared to untreated specimens. This study conclusively positions betel nutshells, typically considered agricultural waste, as competitive alternatives to traditional biomass resources in the biofuel industry.

Unraveling the Mechanism of Epichaperome Modulation by Zelavespib: Biochemical Insights on Target Occupancy and Extended Residence Time at the Site of Action.

Drugs with a long residence time at their target sites are often more efficacious in disease treatment. The mechanism, however, behind prolonged retention at the site of action is often difficult to understand for non-covalent agents. In this context, we focus on epichaperome agents, such as zelavespib and icapamespib, which maintain target binding for days despite rapid plasma clearance, minimal retention in non-diseased tissues, and rapid metabolism. They have shown significant therapeutic value in cancer and neurodegenerative diseases by disassembling epichaperomes, which are assemblies of tightly bound chaperones and other factors that serve as scaffolding platforms to pathologically rewire protein-protein interactions. To investigate their impact on epichaperomes in vivo, we conducted pharmacokinetic and target occupancy measurements for zelavespib and monitored epichaperome assemblies biochemically in a mouse model. Our findings provide evidence of the intricate mechanism through which zelavespib modulates epichaperomes in vivo. Initially, zelavespib becomes trapped when epichaperomes bound, a mechanism that results in epichaperome disassembly, with no change in the expression level of epichaperome constituents. We propose that the initial trapping stage of epichaperomes is a main contributing factor to the extended on-target residence time observed for this agent in clinical settings. Zelavespib's residence time in tumors seems to be dictated by target disassembly kinetics rather than by frank drug-target unbinding kinetics. The off-rate of zelavespib from epichaperomes is, therefore, much slower than anticipated from the recorded tumor pharmacokinetic profile or as determined in vitro using diluted systems. This research sheds light on the underlying processes that make epichaperome agents effective in the treatment of certain diseases.