Shorter Lag Time Research Articles

Exercise and hypoxia-induced hypercoagulability is counterbalanced in women in part by decreased platelet reactivity

Hypoxia plays an important role in several pathologies, e.g. chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, and is linked to an increased thrombosis risk. Furthermore, oxygen deprivation is associated with hypercoagulability.In this study, we investigated the effect of gender and exercise on the coagulation potential under hypoxic conditions at high altitude by assessing thrombin generation (TG) and platelet activation. Hereto, ten healthy volunteers were included (50 % male, median age of 27.5 years). The measurements were conducted first at sea level and then twice at high altitude (3883 m), first after a passive ascent by cable car and second after an active ascent by a mountain hike.As expected, both the passive and active ascent resulted in a decreased oxygen saturation and an increased heart rate at high altitude. Acute mountain sickness symptoms were observed independently of the ascent method. After the active ascent, platelet, white blood cell and granulocyte count were increased, and lymphocytes were decreased, without a gender-related difference. FVIII and von Willebrand factor were significantly increased after the active ascent for both men and women. Platelet activation was reduced and delayed under hypobaric conditions, especially in women. TG analysis showed a prothrombotic trend at high altitude, especially after the active ascent. Women had a hypercoagulable phenotype, compared to men at all 3 timepoints, indicated by a higher peak height and endogenous thrombin potential (ETP), and shorter lag time and time-to-peak. In addition, ETP and peak inhibition by thrombomodulin was lower in women after the active ascent, compared to men. Interestingly, data normalisation for subject baseline values indicated an opposing effect of altitude-induced hypoxia on α2-macroglobulin levels and TG lag time between men and women, decreasing in men and increasing in women.We conclude that hypoxia increases TG, as well as FVIII and VWF levels in combination with exercise. In contrast, platelets lose their responsiveness at high altitude, which is most pronounced after heavy exercise. Women had a more pronounced prothrombotic phenotype compared to men, which we theorize is counterbalanced under hypobaric conditions by decreased platelet activation.

Bridging the new drug access gap between China and the United States and its related policies.

Introduction: The access gap for novel pharmaceuticals between China and the developed countries is a major public health issue in China. It is crucial to understand the determinants of this gap to ensure timely access to new drugs and enhance patient health. Methods: We included all new drugs approved by the US Food and Drug Administration (FDA) between 2012 and 2019, and collected their approval timings in China. Major factors of interest comprised orphan designation and expedited review pathways granted by the FDA, along with the proportion of Asian subjects in the pivotal trial supporting the FDA approval and whether the trial included study sites in China. The elapsed time from the FDA approval to the market authorization in China constituted the time-to-event outcome, and Cox proportional-hazards regression was used for multivariate analysis. Results: A total of 327 new drugs were approved by the FDA between 2012 and 2019, among which 41.3% were found to be authorized in China as of 1 November 2023. The median lag time for the mutually approved drugs was 3.5years. The Cox model found that orphan drugs had lower likelihood of being approved in China (HR = 0.59, 95% CI 0.39-0.89; p = 0.011), while the FDA's Breakthrough-Therapy drugs (HR = 2.33, 95% CI 1.39-3.89; p = 0.001) and Fast-Track drugs (HR = 1.58, 95% CI 1.05-2.38; p = 0.028) had shorter lag times. In the pivotal trials that supported the FDA approvals, a higher proportion of Asian subjects was associated with faster drug entry into the Chinese market (HR = 1.02, 95% CI 1.01-1.03; p < 0.001), and the inclusion of study sites in China mainland was likewise conducive to reducing the drug lag (HR = 5.30, 95% CI 3.20-8.77; p < 0.001). After the trials with China-based sites supported the FDA approvals, 77.8% of the trials also supported the subsequent approvals in China. Discussion: China's involvement in global drug co-development can streamline clinical development, by reducing repeated trials solely in the Chinese population. This is primarily due to the openness of the Chinese drug agency towards overseas clinical data and is a positive sign that encourages global drug developers to include Chinese patients in their development plans as early as possible.

Squamous Cell Carcinoma Arising in Chronic Inflammatory Dermatoses.

Squamous cell carcinoma (SCC) is a known sequela of chronic inflammatory conditions of the skin. Labial discoid lupus erythema-tosus (DLE), oral lichen planus (OLP), and lichen sclerosus have a relatively short lag time from dermatosis onset to manifestation of malignancy; cutaneous DLE, hypertrophic lichen planus, chronic wounds, hidradenitis suppurativa (HS), and necrobiosis lipoidica can be present for decades before an associated malignancy is observed. Vigilant monitoring is essential for orolabial DLE, chronic HS, and chronic wounds because malignancies in these settings are particularly aggressive and often fatal. We summarize what is known about the nature and demographics of SCC arising within chronic inflammatory dermatoses, emphasizing lag time from dermatosis diagnosis to malignancy onset of common inflammatory conditions.

Design of Ionic Liquid Formulations with Azone-Mimic Structures for Enhanced Drug Skin Permeation

Although laurocapram (Azone) significantly enhances the skin permeation of drugs, its development was hindered by its skin irritation. We then developed an Azone-mimic ionic liquid (IL-Azone), composed of less irritating cationic ε-caprolactam and anionic myristic acid. IL-Azone dissociates to the original cation and anion in the presence of water in the formulation. We tried to select a formulation suitable for IL-Azone in the present study. Each formulation contained 5% of either Azone or IL-Azone along with the model drug antipyrine, and skin permeation experiments of the drug were conducted. The results revealed that IL-Azone did not enhance skin permeation when combined with most formulations tested. However, a notable and rapid enhancement in skin permeation was observed when combined with white petrolatum. This effect could be attributed to the minimal water content in white petrolatum, which prevented IL-Azone degradation. Furthermore, its permeation-enhancing effects from IL-Azone in white petrolatum were more pronounced and rapid than Azone. The rapid onset observed with IL-Azone can be attributed to its degradation into its original components at the interface between the stratum corneum and the living epidermis, which results in a shorter lag time before achieving a steady-state concentration in the SC compared to Azone.

An innovative method for measuring the hysteresis effects of soil moisture on meteorological variables at various time scales and climate conditions

ABSTRACTUnderstanding the feedback and reactions of soil moisture to meteorological factors in meteorological-hydrological processes is essential due to the growing importance of soil moisture in energy and water cycles in critical zones. Using soil moisture and meteorological data from 1984 to 2018, based on Mann-Kendall and Sen slope trend, two possible patterns of land–atmosphere interaction were discovered in the Yangtze River Basin (YRB), low soil moisture model with less precipitation and higher evapotranspiration, and high-temperature mode with less soil moisture and less evapotranspiration. To measure the hysteresis between soil moisture and precipitation, temperature, and evapotranspiration, a novel method named Three-Step Method was put out. The lag times were measured at ground stations spread across various climatic zones and timescales. The findings demonstrated that the lag times are generally controlled by the regional climate, with shorter lag times in drier regions. Both long-term and short-term responses were seen in soil moisture to meteorological variables. On a monthly scale, soil moisture correlated positively with precipitation but negatively with temperature and evapotranspiration. On an annual scale, precipitation (temperature, evapotranspiration) lagged by roughly 0 to 2 months in the upper and middle regions and by －2 to －6 months in the lower region of the YRB. The contribution rates of meteorological elements on soil moisture were enhanced by taking lag time into account. This study provides a unique perspective for better understanding climate process forecasts and related drought management by considering the hysteresis of soil moisture on the feedback and responses of climate variables.

Impact of broiler breeder hens’ age and egg storage on egg quality, embryonic development, and hatching traits of FUNAAB-alpha chickens

This study aimed to determine the impact of the age of breeder hens and egg storage on egg quality, embryonic development, hatching events and chick quality in FUNAAB-alpha chickens. The study involved the use of 500 hatching eggs each collected from 32-wk and 60-wk-old of FUNAAB-alpha broiler breeder hens at the Animal Breeding and Genetic Unit of the Federal University of Agriculture, Abeokuta, Nigeria and subjected to 5 storage periods (0, 3, 7, 11, and 15 d). The quality traits of the eggs were recorded and incubated using the conventional protocol. Data were collected on the internal and external egg characteristics, embryonic development, hatching events, and chick quality. The data collected were laid out in 2 by 5 factorial design. The results showed that eggs from 32-wk-old breeder hens had higher albumen height and Haugh unit (HU) value than those from 60-wk-old breeders. The albumen height and HU decreased progressively with storage length in the 2 age groups. Extended storage duration linearly increased (P < 0.01) egg weight loss and decreased (P < 0.01) yolk height. The eggs from both breeder ages had increasing blastodermal diameters at oviposition up until d 11 of storage but decreased on d 15 of storage in eggs from 32 wk breeders. Eggs of 32-wk-old FUNAAB-alpha breeder hens had larger diameters at oviposition compared with 60-wk-old breeders. The chicks from 60-wk breeder had late internal pipping (469.06 h), early external pipping (474.46 h) and a shorter time lag between both pips (9.00 h) compared to chicks from 32 wk breeder. The highest fertility was recorded in eggs stored for 3 d (80.7% and 79.6%), while the lowest fertility was in eggs stored for 15 d (53.4% and 47.7%) in both 32-wk and 60-wk-old breeders, respectively. Chicks from young breeder hens stored for 3 d had better quality scores (100%) compared to 0, 7, 11, and 15-d storage duration and in 60-wk-old breeders across all storage duration. It was concluded that both egg storage duration and age of breeder affected egg quality, hatching events and hatchling quality of FUNAAB-alpha chickens and the interaction effects of both factors was recorded for some of these traits. However, extended storage beyond 7 d had a larger negative impact on egg quality and hatchability of eggs from an old breeder (60 wk) than on eggs of a young breeder (32 wk).

Enhanced transdermal delivery of apremilast loaded ethosomes: Optimization, characterization and in vivo evaluation

The low aqueous solubility and permeability of apremilast restricted its clinical efficiency in oral therapy for psoriasis arthritis. This research aimed to develop nanosized lipid carrier with high payload and can provide greater transdermal flux in an attempt to enhance the clinical efficiency of apremilast. Apremilast loaded ethosomes were efficiently formulated by a single-step injection technique. A 33 statistical Box-Behnken experimental design was employed to identify the optimum desirability of ethosomes by assessing the effect of three formulation components (soy lecithin, ethanol and apremilast) on responses such as vesicle size, drug entrapment and transdermal flux. The optimized ethosomes were formulated into a gel and evaluated for in vitro and in vivo characteristics including drug release, permeation and pharmacokinetics in rats. The optimization results indicated a significant effect (p < 0.05) of all three formulation variables on the responses evaluated. Optimized ethosomes exhibited spherical shape, nano-size with good payload and greater transdermal flux. The developed ethosomal gel had good physicochemical and rheological properties suitable for topical application and exhibited prolonged drug release by Weibull diffusion. A short lag time and higher transdermal flux (∼4 folds higher than control, p < 0.0001) noticed with ethosomes indicates rapid and greater diffusion through the skin barriers. Pharmacokinetic results demonstrated the potential of ethosomes in the transdermal therapy of apremilast as evidenced by the extent of absorption (AUC0-24, p < 0.0001) when compared with the oral counterpart. In nutshell, the data presented here establish the practical feasibility of ethosomal transdermal delivery and can be an alternative option for oral therapy in treating psoriasis arthritis.

Thrombosis Caused By a Novel Coagulation Factor IX Mutation (FIX Shanghai II)

Most thrombophilia patients are caused by insufficient suppression of coagulation reactions, which could be either mediated by deficiencies of protein C, protein S,antithrombin, or inhibition-resistant coagulation factor mutants, such as Factor V Leiden and prothrombin Yukuhashi. The thrombosis caused by coagulation factor mutants with increased procoagulant activity is very rare and so far only two Factor IX (FIX) variants involving residue Arg384, FIX Padua (p.Arg384Leu) and Shanghai (p.Arg384Gln), which increased FIX activity by up to 8 folds, had been reported to be associated with the incidence of thrombosis. In a young male venous thrombosis patient we had identified a novel F9 gene missense mutation c.1018G&amp;gt;A, resulting in p. Glu340Lys substitution (designated as FIX Shanghai II). The patient's APTT time was 28.9 seconds (normal reference 22.3~38.7s), and his PT was also within the normal reference range (11.5 seconds, normal reference 10.0~16.0s). Although the patient had the FIX: Ag comparable to the normal reference, 128.20±6.07%, the his FIX:C was around 201.69±10.38% of normal control (normal reference 50~150%). Thrombin generation assay (TGA) showed that compared with normal control, the patient had a shorter Lag time (2.67 vs 3.33 min), elevated ETP (1649.43 vs 1311.62 nM*min), and higher Peak value (387.34 vs 200.86 nM), indicating increased global coagulation activity of the patient. The activity of protein C, protein S, and antithrombin were all within the normal reference ranges and the patient was negative for antiphospholipid antibodies. Consistent with the patient's coagulation laboratory manifestations, the purified recombinant FIX Glu340Lys mutant showed 1.82 folds higher procoagulant activity than wild type FIX as determined by FIX:C/FIX:Ag ratio. The recombinant FIX Shanghai II mutant can be converted into FIXa by activated factor XI (FXIa) in a similar fashion as FIX WT. The kinetic study of FIXa-catalyzed FX activation showed that p. Glu340Lys mutation led to accelerated FX activation by FIXa. The p.Glu340Lys mutation also enhanced the procoagulant activity of previously reported thrombosis-causing FIX mutants, FIX Shanghai and Padua, in a similar fashion as it did on FIX WT. The FIX:C/FIX:Ag ratio of double mutants containing Glu340Lys and Arg384Gln (FIX Shanghai) or Arg384Leu (FIX Padua) was about twice of FIX Shanghai or Padua alone, 11.48- and 22.53-folds vs 6.16- and 8.13- folds higher than FIX WT respectively.

Measuring Thrombin Generation in Platelet Rich Plasma with the ST Genesia

Background: Thrombin generation (TG) is nowadays used more and more for diagnosing and monitoring of patients. The ST Genesia is a fully automated device for measuring TG in platelet poor plasma (PPP). As the samples are not being inverted prior to the measurement once loaded in the device, it was not known whether it was possible to measure TG in platelet rich plasma (PRP). Platelets can sediment in time possibly affecting TG results. The goal of this study was to evaluate the use of the ST Genesia for measuring TG in PRP in time and to investigate whether the assay is sensitive to platelet antagonists. Methods: Blood was taken from 6 healthy donors and PRP was immediately prepared by centrifuging the blood once for 15 minutes at 220g. The PRP was divided into 14 tubes: 11 tubes for measuring TG in time; i.e. after 0, 15, 30, 45, 60, 75, 90, 105, 120, 180, 240 minutes after the samples were loaded on board; 1 tube for platelet count measurement, 1 tube for TG with the Calibrated Automated Thrombogram (CAT) assay and 1 tube for freezing the PRP. The PRP reagent of the CAT assay was used for triggering TG that contains a low tissue factor concentration. Tukey's multiple comparisons test was used for statistical analysis. Results: The platelet count remained stable in time even without inverting the vial prior to the measurement up to 3 hours. After 4 hours, platelet count was significantly lower (p&amp;lt;0.01). TG in PRP remained stable in time up to 3 hours, after that lagtime and time-to-peak were extended by an average of 48% and 16%, respectively (p-values &amp;lt;0.0001 and 0.0121, respectively), while ETP and peak height remained stable (with low CV's of &amp;lt;6.0% and &amp;lt;7.3%, respectively). The ST Genesia proved to be sensitive to platelet antagonists aspirin (100µM) and Cangrelor (500nM) as peak height decreased with 22% and 24%, respectively. TG measured with the CAT and the ST Genesia was comparable. Measuring TG in PRP after being frozen at -80°C resulted TG kinetics similar to TG in PPP, with a shorter lagtime (-67%) and time-to-peak (-64%), with an increased peak height (+82%), and velocity index (+383%), and an unaffected ETP. Conclusion: The ST Genesia can be used for the reproducible measurement of TG in PRP up to two hours after loading the samples in the device.

Development of a Novel Self-Dissolving Microneedle-Assisted Percutaneous Delivery System of Diacerein through Solid Dispersion Gel: Solubility Enhancement, Proof of Anti-inflammatory Activity and Safety.

Diacerein, an osteoarthiritis drug, experiences slow topical permeation due to limited solubility. Additionally, it shows a laxative effect due to acid/base hydrolysis of the drug in the colon. Diacerein solubility was improved to increase percutaneous drug delivery. To improve saturation solubility of the drug, Diacerein was pre-treated with Polysorbate 80 aqueous solution (1% v/v) to obtain lyophilized powder after wet milling or formulated as solid dispersion using PEG 4000 by fusion method. The lyophilized Diacerein in hydroxypropyl methylcellulose (HPMC 8% w/w) and polyvinyl pyrrolidone (PVP 30% w/w) matrix, with PEG 400 as co-solvent, provided an optimized array. The solid dispersion was loaded in the CMC based gel for subsequent administration on dissolving microneedle-treated skin. The addition of PEG 400 increased Diacerein loading in microneedles to 390.35±4.28 μg per array. The lyophilized drug displayed amorphous characteristics in the dissolving microneedles as per XRD analysis. SEM photographs showed uniformity in the surface topology of microneedles. The needles showed rapid polymer dissolution within 5 minutes, whereas methylene-blue distribution confirmed the formation of microcavities in excised rat skin. The drug-loaded arrays showed better permeation (74.39%) and skin deposition (15.75%) after 24 hours, however, ⁓12% of Diacerein remained in the baseplate. This led to the tailoring of CMC-based gel (3% w/v) containing 0.4% solid dispersion of Diacerein. When compared to untreated skin, the gel improved permeation rate by 2.43 folds through aqueous microchannels generated by dissolving microneedle pre-treatment and allowed 98% drug permeation. The quasi-Fickian diffusion mechanism was found to drive ex vivo release kinetics, with a shorter lag time (0.88 h) and higher flux (26.65 μg/sq.cm.h). Microneedle-assisted Diacerein gel showed a positive anti-inflammatory effect in the paw edema model and reduced diarrheal episodes in comparison to the marketed oral formulation. The gel showed desired characteristics at 5°C±2°C when tested under accelerated stability conditions. The present study reports for the first time the verification of efficacy and safety to advocate the suitability of Diacerein for percutaneous delivery through dissolving microneedle-treated skin.

Effects of Zn2+ and Mn2+ on the photo-fermentative performance of HY01 in biohydrogen production from xylose fermentation

ABSTRACT The addition of specific ions has a significant effect on the characteristics and kinetics of hydrogen production by photofermentation (PFHP). In this article, a new basic research investigated by us find that adjusting the addition ratio of Zn2+ and Mn2+ ions in the R. sphaeroides HY01 system can effectively improve their biohydrogen production from xylose. The largest biohydrogen yield can be obtained as high as 219.2 mL/g xylose at concentration levels of 12 mg/L Zn2+ and 8 mg/L Mn2+. The shortest lag time is 5.76 h, along with most of the organic energy in the substrate transferred to H2. To evaluate the effect of Zn2+ and Mn2+, the Gompertz model with appropriately modification is applied on the photosynthetic bacteria R. sphaeroides HY01, and the corresponding constants are obtained by fitting the model, which is of great guiding significance for the optimization of fermentation conditions.

Effect of anode material and dispersal limitation on the performance and biofilm community in microbial electrolysis cells

In a microbial electrolysis cell (MEC), the oxidization of organic compounds is facilitated by an electrogenic biofilm on the anode surface. The biofilm community composition determines the function of the system. Both deterministic and stochastic factors affect the community, but the relative importance of different factors is poorly understood. Anode material is a deterministic factor as materials with different properties may select for different microorganisms. Ecological drift is a stochastic factor, which is amplified by dispersal limitation between communities. Here, we compared the effects of three anode materials (graphene, carbon cloth, and nickel) with the effect of dispersal limitation on the function and biofilm community assembly. Twelve MECs were operated for 56 days in four hydraulically connected loops and shotgun metagenomic sequencing was used to analyse the microbial community composition on the anode surfaces at the end of the experiment. The anode material was the most important factor affecting the performance of the MECs, explaining 54–80 % of the variance observed in peak current density, total electric charge generation, and start-up lag time, while dispersal limitation explained 10–16 % of the variance. Carbon cloth anodes had the highest current generation and shortest lag time. However, dispersal limitation was the most important factor affecting microbial community structure, explaining 61–98 % of the variance in community diversity, evenness, and the relative abundance of the most abundant taxa, while anode material explained 0–20 % of the variance. The biofilms contained nine Desulfobacterota metagenome-assembled genomes (MAGs), which made up 64–89 % of the communities and were likely responsible for electricity generation in the MECs. Different MAGs dominated in different MECs. Particularly two different genotypes related to Geobacter benzoatilyticus competed for dominance on the anodes and reached relative abundances up to 83 %. The winning genotype was the same in all MECs that were hydraulically connected irrespective of anode material used.

Formulation of Gel Containing Phenylbutenoid Extract for Pain Relief

Objective: A phenylbutenoid extract (PE) was obtained from Zingiber cassumunar rhizomes. Phenylbutenoids; namely DMPBD, compound D, and compound D acetate, have been identified as major anti-inflammatory and analgesic constituents. This present study aimed to formulate a gel containing PE that could be used as an alternative ultrasound gel for acute or chronic inflammatory treatment. Material and Methods: Gel formulations containing 0.5, 1, and 2% w/w PE were prepared using Carbopol 934 and hydroxyethylcellulose (HEC 4,000) as gelling agents. The contents of phenylbutenoids were quantified by a high-performance liquid chromatography (HPLC). PE gels were studied on physicochemical properties and accelerated stability tests. The PE gels, F2 and F5, were used to evaluate the release of phenylbutenoids using a modified Franz diffusion cell. In the skin permeation study, the 2% PE gels were applied either with or without a 0.8 W/cm2 intensity ultrasound for 2, 5, and 10 min. Results: Based on physicochemical properties and accelerated stability tests, F2 and F5 formulations showed good stability. The release kinetics of 0.5% and 1% and 2% w/w PE of both formulations were best fit to Higuchi’s model and zero-order model, respectively. In the skin permeation study, PE gel combined with ultrasound application for 2 min exhibited higher phenylbutenoids in the skin and also a shorter lag time than PE gel application alone. Conclusion: The gel containing 2% w/w phenylbutenoid extract was suggested as an alternative ultrasound gel containing an anti-inflammatory agent for the treatment of musculoskeletal disorders in phonophoresis.

Oxygen isotope variability in precipitation, dripwater, and modern calcite responding to ENSO based on 11 years’ monitoring in Yuhua Cave, Southeast China

The scientific explanation of cave δ18O in the East Asian Summer Monsoon (EASM) region is a crucial issue restricting stalagmite-inferred paleoclimate research. The connection between El Niño Southern Oscillation (ENSO) and monsoonal precipitation/cave δ18O and the mechanism involved also remain contentious. Long-term cave monitoring is an effective solution to deal with these issues. Here, we present 11-year-long precipitation, dripwater, and modern calcite δ18O data from Yuhua Cave in Southeast China, located in the frontal zone affected by the EASM. The upstream convection and rainout processes mainly regulate seasonal and interannual variations in precipitation δ18O (δ18Op). The δ18Op series shows a strong response to EASM activities associated with the Intertropical Convergence Zone migrations and the activities of the West Pacific Subtropical High affected by ENSO activities. Due to the influence of the epikarst reservoir mixing effect, the seasonal variation of dripwater δ18O (δ18Od) is irregular, and its amplitude is much smaller than that of δ18Op. The δ18Od can reflect integrated δ18Op changes within the residence time of rainwater in the karst reservoir and can inherit the ENSO signal in δ18Op. The inferred recharge models for the Yuhua drip sites reveal differences in the response to ENSO in terms of both timing and amplitude, which can be attributed to variations in the residence time of rainwater and the mixing ratio of new and old water within the karst aquifer. Higher rainfall would lead to a more sensitive response of δ18Od to ENSO activities, with a shorter time lag and greater amplitude. The modern calcite δ18O (δ18Oc) series show significant seasonal variations controlled by the fractionation coefficient varied with cave temperature. On the inter-annul time scale, the change of δ18Oc is mainly controlled by δ18Od and can record the ENSO-related variations. Our findings imply that high-resolution stalagmite δ18O reconstructions from Yuhua Cave may be able to identify historical ENSO-related variability in the EASM on annual to decade time scales.

Synergistic effect of pH-shift and controlled heating on improving foaming properties of pea vicilin and its adsorption behavior at the air-water interface

In this study, the impact of pH-shift (PV-pH), controlled heating (PV–H), high intensity ultrasound (PV–U), and their combinations (PV-pH-H, PV-pH-U, PV-H-U) on the structural, foaming, and surface behavior at the air-water interface of the modified pea vicilin (PV) protein fraction were comprehensively evaluated. Results showed that the foaming capacity (FC) of samples treated by either PV-pH or PV-H was significantly increased (105.26%, 105.64%) as compared to the control (73.53%). This synergistic effect was observed with the combination of pH-shift and controlled heating (PV-pH-H), which drastically improved the FC of the modified PV (153.97%). Interestingly, ultrasound treatment exhibited the least effect on the FC of PV, no matter whether it was applied individually or combined with other treatments. The improved FC of PV was mainly attributed to newly formed soluble aggregates, the transition of β-sheet to α-helix, and increased surface hydrophobicity (H0), allowing PV to exist in a more flexible structure. The dynamic adsorption behaviors of the modified PV at the air-water interface indicated that its improvement in FC was also associated with the high surface pressure with short lag time. In addition, the modified PVs formed a strong elastic interfacial film through densely packed protein molecule as evidenced by E-π slop (>1). This study demonstrated that a simple pH shift combined with controlled heating technique could be applied to improve the foaming properties of PV.

Research on the Logical Mechanism of China's State-Owned Economy Exerting the Value of Macro Policy

The state economy is the material foundation and political foundation of Chinese socialism, has unique macro-policy value function, is our system advantage. Based on the typical characteristics of state-owned economy, such as wide layout, leading industry, leadership by the Party and solid foundation of development, this paper proposes three advantages of state-owned economy, such as wide range of strategic landing, short time lag of strategic landing and precise and powerful strategic landing, and then analyzes the logical mechanism of its macro policy value and puts forward relevant policy suggestions.

Near real-time monitoring of tropical forest disturbance by fusion of Landsat, Sentinel-2, and Sentinel-1 data

The ability to detect forest disturbance rapidly relies heavily on the frequency of usable satellite observations. Combining optical and SAR data can provide the most usable observations in the tropics and hence has the potential to achieve more timely detection of forest disturbance than using any individual sensor system. A new algorithm (Fusion Near Real-Time, or FNRT) for near real-time monitoring of tropical forest disturbance by fusion of Landsat, Sentinel-2, and Sentinel-1 data fits a time series model to the data of each individual sensor system and produces a change score for each clear observation during the monitoring period. The change scores from the three different kinds of sensors are then combined for disturbance monitoring. Applying FNRT using all three data sources in eight selected sites in the Amazon Basin detected 69.8 ± 5% and 84.6 ± 4.1% of the forest disturbances within the first 30 and 60 days, respectively. FNRT using all three sensors reached a peak producer's accuracy of 91.6 ± 3.2% at approximately a 100-day lag time, compared to 86.4 ± 3.8% using the two optical sensors combined, and 71.7 ± 4.7% using Landsat only (the best-performing single-sensor). The user's accuracy of FNRT using all three sensors increased to 90.9 ± 3.3% when excluding false detections in non-forest areas. Overall, the model result using all three data sources had the highest detection rate with shorter lag times. Although modest, including Sentinel-1 data in the multi-sensor fusion approach improved the detection speed of some disturbance events. Given the abundance of optical data during the dry season in our study region, Sentinel-1 data would be more valuable during the wet season or in persistently cloudy regions such as Madagascar or coastal West Africa.

The vicious cycle of psychopathology and stressful life events: A meta-analytic review testing the stress generation model.

Stress generation theory initially posited that depression elevates risk for some stressful events (i.e., dependent events) but not others (i.e., independent events). This preregistered meta-analytic review examined whether stress generation occurs transdiagnostically by examining 95 longitudinal studies with 38,228 participants (537 total effect sizes) from over 30 years of research. Our multilevel meta-analyses found evidence of stress generation across a broad range of psychopathology, as evidenced by significantly larger prospective effects for dependent (overall psychopathology: r = .23) than independent (overall psychopathology: r = .10) stress. We also identified unique patterns of effects across specific types of psychopathology. For example, effects were larger for depression than anxiety. Furthermore, effects were sometimes larger in studies with younger participants, shorter time lags between assessments, checklist measures of stress, and for interpersonal stressors. Finally, a multilevel meta-analytic structural equation model suggested that dependent stress exacerbates psychopathology symptoms over time (β = .04), possibly contributing to chronicity. Interventions targeting the prevention of stress generation may mitigate chronic psychopathology. Conclusions of this study are limited by the predominance of depression effect sizes in the literature and our review of only English language articles. On the other hand, the findings are strengthened by rigorous inclusion criteria, lack of publication bias, and absence of moderating effects by publication year. The latter underscores the replicability of the stress generation effect over the last 30 years. Taken together, the review provides robust evidence that stress generation is a cross-diagnostic phenomenon that contributes to a vicious cycle of increasing stress and psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Abstract 263: Prothrombotic State Exists In Long-COVID Even After Mild Acute Infection

Long-term consequences of COVID-19 (long-COVID) are becoming a significant burden to health care. Many people remain symptomatic for months or years after recovery from COVID-19, including some who had only mild symptoms during acute infection. Sustained increases in pro-thrombotic markers have been reported in patients who were initially hospitalized with acute COVID-19. However, whether patients with less severe acute infection develop a prothrombotic-state during long-COVID is unclear. Our objective was to measure prothrombotic factors in long-COVID patients with mild disease (non-hospitalization) during acute infection. We recruited 47 consecutive adult patients with long-COVID symptoms seen in the Post-COVID clinic. All patients had a confirmed COVID-19 diagnosis by RT-PCR or antibody test during acute infection and had at least one of the symptoms of long-COVID per WHO criteria. Twenty asymptomatic healthy subjects not previously diagnosed with COVID-19 were recruited as controls. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole blood flow cytometry. Serum levels of cell-free DNA (cfDNA) and citrullinated histones (H3Cit) and thrombin generation potential in plasma was measured. At the time of recruitment (6 weeks to 2 years after acute infection), the most common post-COVID symptoms included fatigue, chest pain, shortness of breath, headache, and dizziness. In whole blood, activation with TRAP caused increased surface expression of P-selectin without inducing activation of integrin αII b β 3 on platelets (P&lt;0.001 and P=0.5 respectively vs control). Concurrently, there was increased PNA in the long-COVID cohort (P&lt;0.01 vs. control). H3Cit and cfDNA were elevated in long-COVID (P&lt;0.01 and P&lt;0.05 respectively vs. control) and thrombin generation potential was increased, reflected by shorter lag-time, higher peak thrombin and increased velocity index (P&lt;0.01, P&lt;0.05 and P&lt;0.0001 respectively vs control). Within the long-COVID cohort, these markers were not different for age, sex, BMI or time since infection. We conclude that a prothrombotic state persists for months to years in long-COVID patients who exhibited mild disease at the time of initial infection.

In Vitro and In Vivo Characterization of the Transdermal Gel Formulation of Desloratadine for Prevention of Obesity and Metabolic Syndrome.

Chronic use of antihistamines can induce abnormalities in lipid absorption with potential excessive accumulation of lipids in the mesentery that can lead to the development of obesity and a metabolic syndrome. The focus of the present work was to develop a transdermal gel formulation of desloratadine (DES) to prevent/reduce obesity and metabolic syndromes. Nine formulations were prepared to contain hydroxypropyl methylcellulose (2-3%), DES (2.5-5.0%), and Transcutol® (15-20%). The formulations were evaluated for cohesive and adhesive properties, viscosity, drug diffusion through synthetic and pig ear skin, and pharmacokinetics in New Zealand white rabbits. Drug permeation was faster through the skin compared to synthetic membranes. The drug had good permeation, as indicated by very short lag time (0.08-0.47 h) and high flux (59.3-230.7 μg/cm2.h). The maximum plasma concentration (Cmax) and area under the curve (AUC) of transdermal gel formulations were 2.4 and 3.2 fold that of the Clarinex tablet formulation. In conclusion, as indicated by the higher bioavailability, transdermal gel formulation of DES may decrease the dose of the drug, compared to commercial formulation. It has the potential to reduce or eliminate metabolic syndromes associated with oral antihistamine therapy.