A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

SBC的Media-release功能在IMS网络中的部署探讨

文章先简要介绍SBC启用Media-release带来的益处,再通过分别对ASBC和ISBC的Media-release应用场景进行详细分析,得出结论:Media-release功能在ASBC的场景下使用有诸多网络限制,实际部署较困难,而在ISBC场景下具备较好的可实施性。

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.

Effects of the kinetic pattern of dietary glucose release on nitrogen utilization, the portal amino acid profile, and nutrient transporter expression in intestinal enterocytes in piglets

Background Promoting the synchronization of glucose and amino acid release in the digestive tract of pigs could effectively improve dietary nitrogen utilization.The rational allocation of dietary starch sources and the exploration of appropriate dietary glucose release kinetics may promote the dynamic balance of dietary glucose and amino acid supplies.However,research on the effects of diets with different glucose release kinetic profiles on amino acid absorption and portal amino acid appearance in piglets is limited.This study aimed to investigate the effects of the kinetic pattern of dietary glucose release on nitrogen utilization,the portal amino acid profile,and nutrient transporter expression in intestinal enterocytes in piglets.Methods Sixty-four barrows(15.00±1.12 kg)were randomly allotted to 4 groups and fed diets formulated with starch from corn,corn/barley,corn/sorghum,or corn/cassava combinations(diets were coded A,B,C,or D respectively).Protein retention,the concentrations of portal amino acid and glucose,and the relative expression of amino acid and glucose transporter m RNAs were investigated.In vitro digestion was used to compare the dietary glucose release profiles.Results Four piglet diets with different glucose release kinetics were constructed by adjusting starch sources.The in vivo appearance dynamics of portal glucose were consistent with those of in vitro dietary glucose release kinetics.Total nitrogen excretion was reduced in the piglets in group B,while apparent nitrogen digestibility and nitrogen retention increased(P<0.05).Regardless of the time(2 h or 4 h after morning feeding),the portal total free amino acids content and contents of some individual amino acids(Thr,Glu,Gly,Ala,and Ile)of the piglets in group B were significantly higher than those in groups A,C,and D(P<0.05).Cluster analysis showed that different glucose release kinetic patterns resulted in different portal amino acid patterns in piglets,which decreased gradually with the extension of feeding time.The portal His/Phe,Pro/Glu,Leu/Val,Lys/Met,Tyr/Ile and Ala/Gly appeared higher similarity among the diet treatments.In the anterior jejunum,the glucose transporter SGLT1 was significantly positively correlated with the amino acid transporters B0AT1,EAAC1,and CAT1.Conclusions Rational allocation of starch resources could regulate dietary glucose release kinetics.In the present study,group B(corn/barley)diet exhibited a better glucose release kinetic pattern than the other groups,which could affect the portal amino acid contents and patterns by regulating the expression of amino acid transporters in the small intestine,thereby promoting nitrogen deposition in the body,and improving the utilization efficiency of dietary nitrogen.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Experimental and theoretical study of coupled influence of flow velocity increment and particle size on particle retention and release in porous media

Experimental and theoretical studies were carried out to investigate the coupled influence of flow velocity increment and particle size on the retention and release of particles in porous media. Particle release was examined through measurement of changes in effluent particle concentrations, and particle retention was assessed through measurement of the final spatial distribution of particles remaining in the soil columns after the experiments. Particle release curves were simulated using a convection-dispersion model that includes the instantaneous release of the line source. Fitted model parameters were used to gain insights into the mechanisms that control particle retention and release. When the flow velocity increment was 0.0435 cm/s, the peak concentration of particles decreased with increasing flow velocity until the latter approached a critical level, beyond which the particle concentration increased. Particle wedging and fouling were considered the primary mechanisms that controlled particle retention and release beyond the critical particle velocity. In experiments with large flow velocity increments, small particles exhibited lower particle mass fraction than large particles as particle wedging and fouling increased with particle size. The range of longitudinal dispersivity decreased with an increasing particle size and flow velocity increment. Moreover, the mean particle velocity increased with the mean interstitial fluid velocity. The mean particle velocity profile was highly sensitive to the particle size at low velocity increments. In general,particle release rates increased with both flow velocity and velocity increment. The mass of the released particles provides further evidence that particle wedging and fouling are the major factors that control particle release in sand columns.

Effect of nonionic surfactants in release media on accelerated in-vitro release profile of sirolimus eluting stents with biodegradable polymeric coating

It is a well-known fact that sirolimus(SRL) undergoes degradation process via hydrolysis in aqueous media, leading to incorrect assessment of drug amount and thus release characteristics of formulations.The main objective of the present study was to evaluate the effect of nonionic surfactants in media on invitro release profiles for sirolimus eluting stents(SES) coated with biodegradable polymeric matrix.Phosphate buffer and acetate buffer incorporating nonionic surfactants with varying concentrations were examined for adequate solubility and stability(by RP-HPLC). Good sink condition was achieved in phosphate buffer(at pH 4.0) with 1.0% Tween 20, 1.0% Brij 35% and 0.5% Brij 58. Hydrodynamic size(by DLS) and the micelle-water partition coefficient(P) with standard free energy of solubilization(ΔGs°) of drug were evaluated to get some understanding about the solubilization phenomena. About 80% of drug release during the period of 48 h was achieved in optimized drug release media which was 1.0% Tween20 in phosphate buffer pH 4.0. The obtained accelerated SRL release profile in optimized medium correlated well with the real time in-vitro release in phosphate buffer(pH 7.4). Surface morphology changes(by SEM), changes in gravimetric weights and molecular weight change(by GPC) were examined before and after drug release to understand the drug release mechanism which explains that the polymer did not undergo degradation during the drug release.

Use of an immunocapture device to detect cytokine release in discrete brain regions

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

Colorectal mucosal histamine release by mucosa oxygenation in comparison with other established clinical tests in patients with gastrointestinally mediated allergy

AIM： This study evaluated colorectal mucosal histamine release in response to blinded food challenge-positive and-negative food antigens as a new diagnostic procedure. METHODS： 19 patients suffering from gastrointestinally mediated allergy confirmed by blinded oral provocation were investigated on grounds of their case history, skin prick tests, serum IgE detection and colorectal mucosal histamine release by ex vivo mucosa oxygenation. Intact tissue particles were incubated/stimulated in an oxygenated culture with different food antigens for 30 min. Specimens challenged with anti-human immunoglobulin E and without any stimulus served as positive and negative controls, respectively. Mucosal histamine release （% of total biopsy histamine content） was considered successful （positive）, when the rate of histamine release from biopsies in response to antigens reached more than twice that of the spontaneous release. Histamine measurement was performed by radioimmunoassay. RESULTS： The median （range） of spontaneous histamine release from colorectal mucosa was found to be 3.2 （0.1%-25.8%） of the total biopsy histamine content. Food antigens tolerated by oral provocation did not elicit mast cell degranulation 3.4 （0.4%-20.7%, P=0.4）, while anti-IgE and causative food allergens induced a significant histamine release of 5.4 （1.1%-25.6%, P = 0.04） and 8.1 （1.5%-57.9%, P = 0.008）, respectively. 12 of 19 patients （63.1%） showed positive colorectal mucosal histamine release in accordance with the blinded oral challenge responding to the same antigen （s）, while the specificity of the functional histamine release to accurately recognise tolerated foodstuffs was found to be 78.6%. In comparison with the outcome of blinded food challenge tests, sensitivity and specificity of history （30.8% and 57.1%）, skin tests （47.4% and 78.6%） or antigen-specific serum IgE determinations （57.9% and 50%） were found to be of lower diagnostic accuracy in gastrointestinally mediated allergy. CONCLUSION： Functional testing of the reactivity of colorectal mucosa upon antigenic stimulation in patients with gastrointestinally mediated allergy is of higher diagnostic efficacy.

Tailoring Iron-Ion Release of Cellulose-Based Aerogel-Coated Iron Foam for Long-Term High-Power Microbial Fuel Cells

The presence of iron(Fe) has been found to favor power generation in microbial fuel cells(MFCs). To achieve long-term power production in MFCs, it is crucial to effectively tailor the release of Fe ions over extended operating periods. In this study, we developed a composite anode(A/IF) by coating iron foam with cellulose-based aerogel. The concentration of Fe ions in the anode solution of A/IF anode reaches 0.280 μg/mL(Fe^(2+) vs. Fe^(3+) = 61%:39%) after 720 h of aseptic primary cell operation. This value was significantly higher than that(0.198 μg/mL, Fe^(2+) vs. Fe^(3+) = 92%:8%) on uncoated iron foam(IF), indicating a continuous release of Fe ions over long-term operation. Notably, the resulting MFCs hybrid cell exhibited a 23% reduction in Fe ion concentration(compared to a 47% reduction for the IF anode) during the sixth testing cycle(600-720 h). It achieved a high-power density of 301 ± 55 mW/m^(2) at 720 h, which was 2.62 times higher than that of the IF anode during the same period. Furthermore, a sedimentary microbial fuel cell(SMFCs) was constructed in a marine environment, and the A/IF anode demonstrated a power density of 103 ± 3 mW/m^(2) at 3240 h, representing a 75% improvement over the IF anode. These findings elucidate the significant enhancement in long-term power production performance of MFCs achieved through effective tailoring of Fe ions release during operation.

Assessing the energy release characteristics during the middle detonation reaction stage of aluminized explosives

Afterburning behind the detonation front of an aluminized explosive releases energy on the millisecond timescale,which prolong the release of detonation energy and the energy release at different stages also shows significant differences.However,at present,there are few effective methods for evaluating the energy release characteristics of the middle reaction stage of such explosives,which can have a duration of tens to hundreds of microseconds.The present work demonstrates an approach to assessing the midstage of an aluminized explosive detonation based on a water push test employing a high degree of confinement.In this method,the explosive is contained in a steel cylinder having one end closed that is installed at the bottom of a transparent water tank.Upon detonation,the gaseous products expand in one direction while forcing water ahead of them.The resulting underwater shock wave and the interface between the gas phase products and the water are tracked using an ultra-high-speed framing and streak camera.The shock wave velocity in water and the expansion work performed by the gaseous detonation products were calculated to assess the energy release characteristics of aluminized explosives such as CL-20 and RDX in the middle stage of the detonation reaction.During the middle stage of the detonation process of these aluminized explosives,the aluminum reaction reduced the attenuation of shock waves and increased the work performed by gas phase products.A higher aluminum content increased the energy output while the presence of oxidants slowed the energy release rate.This work demonstrates an effective means of evaluating the performance of aluminized explosives.

The effect of Ti and Zr content on the structure,mechanics and energy-release characteristics of Ti—Zr—Ta alloys

Energetic structural materials(ESMs)are a new type of structural materials with bearing and damage characteristics.In this work the microstructure,mechanical properties and energy release characteristics of multi-element Ti-Zr-Ta alloys with good casting performance were studied.The microstructure of the Ti_(x)ZrTa alloys gradually change from BCC+HCP to single BCC structure with the increase of Ti.While the Ti_(2)Zr_(y)Ta alloys was still uniform and single BCC structure with the increase of Zr.The evolution of microstructure and composition then greatly affect the mechanical properties and energy-release characteristics of Ti-Zr-Ta alloys.The synergistic effect of dual phase structure increases the fracture strain of Ti_(x)ZrTa(x=0.2,0.5)with the Ti content decreases,while the fracture strain of Ti_(x)ZrTa(x=2.0,3.0,4.0)gradually increase with the Ti content increases caused by the annihilation of the obstacles for dislocation movement.And as Zr content increases,the fracture strain of Ti_(2)Zr_(y)Ta alloys decrease,then the oxidation reaction rate and fragmentation degree gradually increase.The higher oxidation rate and the lager exposed oxidation area jointly leads the higher releasing energy efficiency of Ti_(x)ZrTa alloys with low Ti content and Ti_(2)Zr_(y)Ta alloys with high Zr content.

Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

Release characteristics and stabilization of heavy metals in antimony tailings in Yunnan Province,China

The pollution caused by the mining and smelting of heavy metals is becoming an increasingly severe environmental problem.In this study,the environmental risks of mine tailings were explored using typical antimony tailings(the depth of the sample taken from the ground to the deepest position of 120 cm)from the Zuoxiguo mine in Yunnan Province,Southwest China.The tailings were examined to explore the geological background,distribution characteristics,and release characteristics of heavy metals.Additionally,stabilizer treatments for heavy metals were investigated in consideration of waste treatment.The results showed that the contents of Sb and As(8.93×103 and 425 mg/kg,respectively)in the tailings were considerably higher than the local soil background values,suggesting that these metals pose a considerable threat to the surrounding environment.The geological background values of Cr,Cd,Pb,Cu,and Zn were relatively low.The results of static release showed that Sb,As,Cd,and Cr leached from the tailings more easily than Cu,Zn,and Pb under acidic conditions(pH=2.98).Geo-accumulation indices and potential ecological risk indices showed that Sb,As,Cd,and Pb were highly enriched in the tailings,whereas Cu,Cr,and Zn contents were relatively low.The single factor ecological risk index of the mining area showed that Sb and As are high ecological risk factors,whereas Cr,Cu,Zn,Cd,and Pb are not.The results of the orthogonal test results showed that by adding 15.0%(m/m)fly ash and 15.0%(m/m)zeolite powder to the quicklime and curing for 28 d,a significant stabilization effect was observed for Sb,As,and Pb.This study helps determine the priority control components for characteristic heavy metals in antimony tailings,and provides valuable insights regarding the formulation of appropriate mitigation strategies.

Parent-offspring relationship recognition based on SSR and mtDNA confirmed resource supplement effect of Fenneropenaeus chinensis release

The resource of Fenneropenaeus chinensis has declined sharply due to excessive fishing intensity,ecological changes and diseases.In order to supplement the fishing yield and restore resources of F.chinensis,the relevant authorities have carried out the activities of stock enhancement and releasing.It can increase biomass and recover resources.However,compared with increasing biomass,there were still few reports on its effect on the recovery of resources.Resource recovery is a process related to whether the released individuals can form a reproductive population.Up to now,there has been a lack of evidence whether the released F.chinensis can complete the entire life history,and form reproduction population.In this study,gravid female shrimp after spawning migration were captured from coastal waters of Haiyang,Qingdao,and Yellow Sea.After identifying parentage relationships using simple sequence repeat(SSR)and mtDNA haplotype,it was finally confirmed that there were eight released individuals in the recapture samples.It was confirmed for the first time that at least part of the released F.chinensis can complete overwintering and reproductive migration,and maintain the migration habits as their wild counterparts.Therefore,we infered that the released shrimp can reproduce under natural conditions,these F.chinensis can form reproductive populations theoretically if without human intervention.These results indicated that enhancenment and release activities have a positive effect on resource recovery.

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.

Ceremony for Launch of the Center for Global Security Initiative Studies and Release of the GSI Implementation Progress Report Held in Beijing

Under the auspices of the Foreign Ministry,CIIS held a ceremony for the establishment of the Center for Global Security Initiative Studies and the release of the Report on the Implementation Progress of the Global Security Initiative in Beijing on July 18.

2024 Report on the Development of China’s Import Released

The Ch ina Chamber of Commerce to the E.U.(CCCEU),in partnership with global consultancy Roland Berger,has published its annual flagship report on the state of Chinese enterprises in the E.U.recently in Brussels.The findings paint a sobering picture of strained ties and growing unease among Chinese businesses operating in the bloc.

ISO releases a standard for a Chinese medicinal material

Rehmannia glutinosa root is one of the most commonly used herbs in traditional Chinese medicine. It has a long history in East and Southeast Asian countries for relieving heat and cooling the blood, nourishing yin and body fluid.