Inflammatory bowel disease(IBD)is a chronic condition consisting of two main types:Crohn’s disease and ulcerative colitis.Conventional treatments for these diseases include aminosalicylates,corticosteroids,immunomodu...Inflammatory bowel disease(IBD)is a chronic condition consisting of two main types:Crohn’s disease and ulcerative colitis.Conventional treatments for these diseases include aminosalicylates,corticosteroids,immunomodulators,and biologics.However,these treatments have several drawbacks,including high costs for patients and numerous side effects.Recently,advanced treatments have been developed,such as small-molecule therapies,targeted biologics,innovative drug delivery systems,and microbiome-based interventions.Emerging therapies like anti-interleukin-23 monoclonal antibody inhibitors,sphingosine-1-phosphate receptor modulators,and Janus kinase inhibitors are more specialized in reducing immune activity.They enhance bioavailability,reduce side effects,and specifically target the gastrointestinal tract without affecting other systems.Innovative drug delivery systems for IBD,such as nanoparticles,hydrogels,and microgrippers,improve bioavailability and prolong drug release.The combination of conventional and advanced therapies may benefit from the synergistic effects of both.Furthermore,fecal microbiota transplantation and probiotics can help restore the balance of gastrointestinal microbiota,reducing disease flare-ups.Advances in artificial intelligence,endoscopic techniques,and stem cell therapies have shown great potential in treating IBD,although several significant challenges remain.Treating this disease requires multidisciplinary integration and the application of technology and telemedicine.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the mali...BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.展开更多
Lignocellulosic biomass is one of the viable solutions to alleviate the global warming. However, the limited utilization of biomass majorly focused on cellulose and hemicellulose restricts the economic and environment...Lignocellulosic biomass is one of the viable solutions to alleviate the global warming. However, the limited utilization of biomass majorly focused on cellulose and hemicellulose restricts the economic and environmental feasibilities. To cope with this issue, we proposed an integrated process of co-producing 1,6-hexanediol(1,6-HDO) with tetrahydrofuran and adipic acid from biomass, referred to as Strategy A. To compare the impacts of lignin upgrading and feedstock, Strategy B, which co-produces tetrahydrofuran alone, and Strategy C, which is the traditional route to produce 1,6-HDO from fossil fuels, were used. Heat networks are also designed to reduce operating costs and indirect carbon emissions due to energy consumption, saving 87% and 83% of the heat and cooling requirements, respectively, in Strategy A. The market competitiveness of Strategy A was evaluated by determining the minimum selling price through techno-economic analysis, and sustainability was thoroughly investigated by quantifying the environmental impacts through both midpoint and endpoint life-cycle assessments(LCAs).Strategy A was found to be the most favorable both economically(USRDSCHARDOLLAR3,402/ton) and environmentally(-26.9 kg CO_(2)eq.). This indicates that lignin valorization is not only economically but also environmentally preferred. Finally, changes in economic and environmental feasibilities depending on economic, process, and environmental parameters were investigated using sensitivity and uncertainty analyses. The results of these analyses provide valuable insight into bio-based chemical production.展开更多
Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adi...Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adipocytes and high-fat diet(HFD)-induced obese zebrafish larvae.Methods:GCSW210 was fractionated through solvent partitioning,ion-exchange chromatography,and silica gel medium-pressure liquid chromatography,followed by preparative high performance liquid chromatography.At each step,bioactivities were assessed in 3T3-L1 adipocytes by Oil Red O staining and 2-NBDG uptake assays.The most active fractions were further purified,and isolated compounds were tested in HFD-induced obese zebrafish larvae.Results:Liquid chromatography-hyphenated analysis with reference standards identified two major compounds in GCSW210:5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether.Both compounds significantly inhibited lipid accumulation in 3T3-L1 adipocytes and modulated gene expression associated with adipogenesis,glucose metabolism,and inflammation in zebrafish.They also enhanced glucose uptake,reduced circulating glucose levels,and improved insulin sensitivity.Notably,the effects were comparable to those of the crude GCSW210 extract.In silico docking studies confirmed stable interactions of both compounds with key metabolic and inflammatory targets,with bis(5-formylfurfuryl)ether showing stronger binding affinities.Conclusions:These findings suggest that 5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether are key contributors to the therapeutic activity of Gracilaria chorda,highlighting its potential as a functional food ingredient for the prevention or management of metabolic disorders.展开更多
The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the cur...The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.展开更多
Effect of perturbations in Coriolis and centrifugal forces on the non-linear stability of the libration point L4 in the restricted three body problem is studied when both the primaries are axis symmetric bodies (triax...Effect of perturbations in Coriolis and centrifugal forces on the non-linear stability of the libration point L4 in the restricted three body problem is studied when both the primaries are axis symmetric bodies (triaxial rigid bodies) and the bigger primary is a source of radiation. Moser’s conditions are utilized in this study by employing the iterative scheme of Henrard for transforming the Hamiltonian to the Birkhoff’s normal form with the help of double D’Alembert’s series. It is found that L4 is stable for all mass ratios in the range of linear stability except for the three mass ratios μc1, μc2 and μc3, which depend upon the perturbations ε1 and ε1 in the Coriolis and centrifugal forces respectively and the parameters A1,A2,A3 and A4 which depend upon the semi-axes a1,b1,c1;a2,b2,c2 of the triaxial rigid bodies and p, the radiation parameter.展开更多
As environmental concerns from fossil fuel consumption intensify,large-scale energy storage becomes imperative for the integration of renewable sources like wind,hydro,and solar with the electrical grid.Redox flow bat...As environmental concerns from fossil fuel consumption intensify,large-scale energy storage becomes imperative for the integration of renewable sources like wind,hydro,and solar with the electrical grid.Redox flow batteries,particularly those employing organic molecules,are positioned as a key technology for this purpose.This review explores the growing field of symmetric organic redox flow batteries(ORFBs)within this context.Unlike traditional asymmetric designs based on unique active materials for each electrode,symmetric ORFBs involve a single bipolar species for both electrodes.This review highlights the benefits of a symmetric design,and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents.By providing a comprehensive overview of their cell cycling and performance characteristics,the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems,as are opportunities for future development.This should guide new research directions and advance the development of practical symmetric ORFBs.展开更多
A series of laboratory pull-out tests was conducted to study the effects of temperature on the performance and behaviours of fully grouted rock bolt specimens cured within a specific temperature range,as well as for d...A series of laboratory pull-out tests was conducted to study the effects of temperature on the performance and behaviours of fully grouted rock bolt specimens cured within a specific temperature range,as well as for different durations.Each specimen consisted of a 20M rebar bolt at 1300 mm embedment length grouted inside a Schedule 80 steel pipe using Portland cement grout at a 0.4 water-to-cement ratio.Two temperatures(20℃and 45℃)were explored to investigate the effects of geothermally active temperature conditions on fully grouted rock bolts.Distributed fiber optic sensors were employed to provide continuous strain profiles along the entire embedment length to observe micro-mechanisms and monitor internal specimen temperature change during testing.The specimens cured at 45℃generally resulted in higher grout UCS(in certain cases 25%e50%higher)compared to those at 20℃;the ultimate capacity was not significantly impacted as the specimens'embedment length allowed full development of the rock bolt's capacity.The resulting strain profile trends showed generally higher strains experienced by the shorter(i.e.3-d)curing duration specimens under both curing temperatures compared to long-term curing.The 45℃specimens generally experienced lower strains and faster strain profile attenuation compared to specimens cured at 20℃.Understanding these effects and further analysis of FGRB specimen behaviours over time provide insights for mobilized and critical embedment lengths,capacity development,and support system stabilization.This paper highlights the results of this study and aims to bridge selected gaps in existing literature with a view to aid practitioners.展开更多
BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often ci...BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often cited as a concern when initiating treatment.Hepatitis B treatment adherence in the context of the patient’s medical and life experiences remains underexplored.AIM To evaluate factors associated with adherence to hepatitis B oral antiviral treatment.METHODS A global online survey was administered anonymously to adults(aged 18 years or older)living with chronic hepatitis B.A subsample of 614 individuals who reported being on hepatitis B treatment was included in the analysis.Indices for treatment affordability,healthcare service acceptability,and individual physical,psychological,and emotional functioning were constructed(Cronbach’s alpha=0.71-0.83).Data analysis was conducted using Stata/BE 17.0.RESULTS Overall,81%of respondents reported high adherence to hepatitis B treatment.Lower adherence was observed among individuals who identified as African or African American(P=0.008).Among participants with low adherence,60%cited affordability as a challenge(P=0.068),53%identified healthcare service acceptability as a challenge(P=0.04),79%described physical functioning as a challenge(P=0.002),and 40.5%reported difficulties with psychological functioning(P=0.55).CONCLUSION Findings demonstrate high treatment adherence,although access to and acceptability of healthcare services,as well as an individual’s physical functioning challenges,appear to be related to low adherence.展开更多
This study investigates the complex heat transfer dynamics inmultilayer bifacial photovoltaic(bPV)solar modules under spectrally resolved solar irradiation.A novel numericalmodel is developed to incorporate internal h...This study investigates the complex heat transfer dynamics inmultilayer bifacial photovoltaic(bPV)solar modules under spectrally resolved solar irradiation.A novel numericalmodel is developed to incorporate internal heat generation resulting from optical absorption,grounded in the physical equations governing light-matter interactions within the module’smultilayer structure.The model accounts for reflection and transmission at each interface between adjacent layers,as well as absorption within individual layers,using the wavelength-dependent dielectric properties of constituent materials.These properties are used to calculate the spectral reflectance,transmittance,and absorption coefficients,enabling precise quantification of internal heat sources from irradiance incidents on both the front and rear surfaces of the module.The study further examines the influence of irradiance reflection on thermal behavior,evaluates the thermal impact of various supporting materials placed beneath the module,and analyzes the role of albedo in modifying heat distribution.By incorporating spectrally resolved heat generation across each layer often simplified or omitted in conventional models,the proposed approach enhances physical accuracy.The transient heat equation is solved using a one-dimensional finite difference(FD)method to produce detailed temperature profiles under multiple operating scenarios,including Standard Test Conditions(STC),Bifacial Standard Test Conditions(BSTC),Normal Operating Cell Temperature(NOCT),and Bifacial NOCT(BNOCT).The results offer valuable insights into the interplay between optical and thermal phenomena in bifacial systems,informing the design and optimization of more efficient photovoltaic technologies.展开更多
The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the reg...The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the regulatory mechanisms that control immune responses.This dysregulation varies widely among patients and can evolve over time,ranging from systemic inflammatory responses to immunosuppression,greatly contributing to the morbidity and mortality of individuals with SCI(Bao et al.,2011;Brennan et al.,2024).展开更多
We explored a distinct mechanism for matter creation via electron-positron pair production during bound-bound transitions in the deexcitation of muonic atoms.For ions with nuclear charges Z≥24,transitions from low-ly...We explored a distinct mechanism for matter creation via electron-positron pair production during bound-bound transitions in the deexcitation of muonic atoms.For ions with nuclear charges Z≥24,transitions from low-lying excited states to the 1s-muon state can lead to the production of electron-positron pairs.We show that the Breit interaction determines the transition probabilities for states with nonzero orbital momentum.We show that the pair production arises mainly from the decay of the 2p states.Thus,the Breit interaction governs electron-positron pair production in bound-bound muon transitions.This process offers a unique opportunity to explore quantum electrodynamics in strong fields,as well as a class of nonradiative transitions involving electron-positron pair production.展开更多
Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown rem...Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.展开更多
Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of...Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of turbulences in the very early universe in sustaining intense and persistent fluctuations in energy or mass density,which could provide a natural mechanism for PBH formation in the primordial universe. We analyze the mass range and abundance of PBHs produced in the magnetohydrodynamic turbulence induced by the electroweak phase transition. Remarkably, we find that the mass range of the produced PBHs falls within the most viable“asteroid mass” window from the present-day observations, and within natural parameter regions their abundance can be sufficiently large. These findings suggest that PBHs produced during magnetohydrodynamic turbulence in the very early universe may comprise a dominant part of dark matter.展开更多
A field study was conducted to investigate the effect of Aquasap, a commercially manufactured biostimulant from seaweed Kappapphycus alvarezii on some hills and foothills banana varieties namely Robusta （AAA）, Njali...A field study was conducted to investigate the effect of Aquasap, a commercially manufactured biostimulant from seaweed Kappapphycus alvarezii on some hills and foothills banana varieties namely Robusta （AAA）, Njali poovan （AB）, Red banana （AAA） and Nendran （AAB） by applying at 5% through foliar spray at the 3rd, 5th and 7th month of plantation. Both quantitative and quality data of fruits were analyzed along with vegetative growth of the plants. The seaweed biostimulant was found very effective on increasing the weight and nutritional contents of all four banana varieties tested. The highest yield was found in Robusta with 56.58% over control followed by Njali poovan, Red banana and Nendran with 19.08%, 39.35% and 11.46%, respectively. Yield of fruits per hectare of four varieties treated were 76.96, 19.23, 29.68 and 23.37 metric ton （mt）, respectively. Fruits of treated plants also showed less moisture level as compared to control with 240.61%, 62.30%, 61.68% and 37.18% more carbohydrate, 283.71%, 94.07%, 62.87% and 38.93% higher proteins and 153.02%, 47.37%, 58.73% and 31.48% higher minerals respectively as compare to control plants. Therefore, the simple practice of application of eco-friendly seaweed based biostimulant would benefit small and marginal farmers of banana.展开更多
Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a diffi...Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a difficult task to deal with because the presence of buildings,infrastructures,and human activities usually conceals the morphological signs of these landslide activities.So,in the last decades,numerous researchers have shown new methodologies to deepen the studies of similar instability phenomena.The present research is based on an integrated approach to investigate the landslide boundaries,type of movement,failure surface depth,and vulnerability state of buildings in Rota Greca Village(Calabria region,southern Italy) affected by a slowmoving landslide.For this purpose,multi-source data were acquired through geological and geomorphological surveys,recognition of landslide-induced damage on the built environment,subsurface investigations(e.g.,continuous drill boreholes,Standard Penetration Test,Rock Quality Designation index and inclinometer monitoring),laboratory tests(direct shear tests on undisturbed samples),geophysical survey,and InSAR-derived map of deformation rates.The complete integration of multi-source data allowed for the construction of reliable landslide modelling with relative geotechnical properties.In addition,the cross-comparison between surface deformation data by SAR images and severity damage level collected on the exposed buildings enabled to obtain the vulnerability map of the built area.In particular,the achieved goals highlighted two failure surfaces at about-13 and-25 m depth,causing a high vulnerability value for the buildings allocated in the central portion of the Rota Greca Village.The knowledge acquired by the multi-approach can be used to manage and implement appropriate landslide risk mitigation strategies,providing helpful advice and best practices to state-run organisations and stakeholders for landslide management in urban sites.展开更多
Wastewater treatment is a process that is vital to protecting both the environment and human health. At present, the most cost-effective way of treating wastewater is with biological treatment processes such as the ac...Wastewater treatment is a process that is vital to protecting both the environment and human health. At present, the most cost-effective way of treating wastewater is with biological treatment processes such as the activated sludge process, despite their long operating times. However, population increases have created a demand for more efficient means of wastewater treatment, Fluidization has been demonstrated to in- crease the efficiency of many processes in chemical and biochemical engineering, but it has not been widely used in large-scale wastewater treatment. At the University of Western Ontario, the circulating fluidized-bed bioreactor （CFBBR） was developed for treating wastewater. In this process, carrier particles develop a biofilm composed of bacteria and other microbes. The excellent mixing and mass transfer characteristics inherent to fluidization make this process very effective at treating both municipal and industrial wastewater. Studies of lab- and pilot-scale systems showed that the CFBBR can remove over 90% of the influent organic matter and 80% of the nitrogen, and produces less than one-third as much biological sludge as the activated sludge process. Due to its high efficiency, the CFBBR can also be used to treat wastewaters with high organic solid concentrations, which are more difficult to treat with conventional methods because they require longer residence times; the CFBBR can also be used to reduce the system size and footprint. In addition, it is much better at handling and recovering from dynamic loadings （i.e., varying influent volume and concentrations） than current systems. Overall, the CFBBR has been shown to be a very effective means of treating wastewa- ter, and to be capable of treating larger volumes of wastewater using a smaller reactor volume and a shorter residence time. In addition, its compact design holds potential for more geographically localized and isolat- ed wastewater treatment systems.展开更多
Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify...Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.展开更多
BACKGROUND The anterior talofibular ligament(ATFL)is the most commonly injured ligament in ankle sprains.While most individuals recover with conservative management,some patients develop persistent pain and instabilit...BACKGROUND The anterior talofibular ligament(ATFL)is the most commonly injured ligament in ankle sprains.While most individuals recover with conservative management,some patients develop persistent pain and instability from chronic ATFL tears.Surgical repair is often required,and minimally invasive techniques are gaining popularity.AIM To evaluate the clinical outcomes of a novel,totally percutaneous(TP)modified Broström repair(MBR)for chronic ATFL insufficiency in a cohort of patients who failed conservative treatment.METHODS This retrospective study analyzed 20 patients(14 males,6 females;mean age,28.7 years)who underwent TP-MBR between 2023 and 2024 at a tertiary trauma center.All patients had persistent pain and instability for at least 3 months despite conservative treatment.Diagnosis was confirmed by magnetic resonance imaging,arthroscopy,and stress testing.TP-MBR was performed using suture anchors and percutaneous ligament advancement.Functional outcomes were assessed using American Orthopaedic Foot and Ankle Society score and Karlsson score at a mean follow-up of 1.5 years.RESULTS All procedures were completed successfully with no intraoperative complications.At a mean follow-up of 1.5 years,patients showed significant improvements in American Orthopaedic Foot and Ankle Society score(from 39.85 to 84.4;P<0.001)and Karlsson scores(from 43.8 to 87.4;P<0.001).All patients returned to pre-injury activity levels with resolution of instability.The technique resulted in minimal tissue trauma,reduced operative time,accelerated recovery,and excellent cosmetic outcomes.No recurrences or major complications occurred.CONCLUSION TP-MBR is a safe and effective alternative to open Broström repair for chronic ATFL tears.It offers the benefits of a minimally invasive approach,including less trauma and faster rehabilitation,making it a valuable option for appropriately selected patients.展开更多
文摘Inflammatory bowel disease(IBD)is a chronic condition consisting of two main types:Crohn’s disease and ulcerative colitis.Conventional treatments for these diseases include aminosalicylates,corticosteroids,immunomodulators,and biologics.However,these treatments have several drawbacks,including high costs for patients and numerous side effects.Recently,advanced treatments have been developed,such as small-molecule therapies,targeted biologics,innovative drug delivery systems,and microbiome-based interventions.Emerging therapies like anti-interleukin-23 monoclonal antibody inhibitors,sphingosine-1-phosphate receptor modulators,and Janus kinase inhibitors are more specialized in reducing immune activity.They enhance bioavailability,reduce side effects,and specifically target the gastrointestinal tract without affecting other systems.Innovative drug delivery systems for IBD,such as nanoparticles,hydrogels,and microgrippers,improve bioavailability and prolong drug release.The combination of conventional and advanced therapies may benefit from the synergistic effects of both.Furthermore,fecal microbiota transplantation and probiotics can help restore the balance of gastrointestinal microbiota,reducing disease flare-ups.Advances in artificial intelligence,endoscopic techniques,and stem cell therapies have shown great potential in treating IBD,although several significant challenges remain.Treating this disease requires multidisciplinary integration and the application of technology and telemedicine.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
文摘BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.
基金Material Parts Technology Development Program (20017461, Development and Performance Improvement of Air Operated Valve for 105 MPa Hydrogen Charging Station) funded by the Ministry of Trade,Industry and Energy(MOTIE, Republic of Korea)Korea Evaluation Institute of Industrial Technology (KEIT, Republic of Korea)+1 种基金financial support from the Korea Institute of Energy Technology Evaluation and Planning (KETEP)Ministry of Trade,Industry&Energy (MOTIE) of the Republic of Korea(RS-2024-00419764)。
文摘Lignocellulosic biomass is one of the viable solutions to alleviate the global warming. However, the limited utilization of biomass majorly focused on cellulose and hemicellulose restricts the economic and environmental feasibilities. To cope with this issue, we proposed an integrated process of co-producing 1,6-hexanediol(1,6-HDO) with tetrahydrofuran and adipic acid from biomass, referred to as Strategy A. To compare the impacts of lignin upgrading and feedstock, Strategy B, which co-produces tetrahydrofuran alone, and Strategy C, which is the traditional route to produce 1,6-HDO from fossil fuels, were used. Heat networks are also designed to reduce operating costs and indirect carbon emissions due to energy consumption, saving 87% and 83% of the heat and cooling requirements, respectively, in Strategy A. The market competitiveness of Strategy A was evaluated by determining the minimum selling price through techno-economic analysis, and sustainability was thoroughly investigated by quantifying the environmental impacts through both midpoint and endpoint life-cycle assessments(LCAs).Strategy A was found to be the most favorable both economically(USRDSCHARDOLLAR3,402/ton) and environmentally(-26.9 kg CO_(2)eq.). This indicates that lignin valorization is not only economically but also environmentally preferred. Finally, changes in economic and environmental feasibilities depending on economic, process, and environmental parameters were investigated using sensitivity and uncertainty analyses. The results of these analyses provide valuable insight into bio-based chemical production.
文摘Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adipocytes and high-fat diet(HFD)-induced obese zebrafish larvae.Methods:GCSW210 was fractionated through solvent partitioning,ion-exchange chromatography,and silica gel medium-pressure liquid chromatography,followed by preparative high performance liquid chromatography.At each step,bioactivities were assessed in 3T3-L1 adipocytes by Oil Red O staining and 2-NBDG uptake assays.The most active fractions were further purified,and isolated compounds were tested in HFD-induced obese zebrafish larvae.Results:Liquid chromatography-hyphenated analysis with reference standards identified two major compounds in GCSW210:5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether.Both compounds significantly inhibited lipid accumulation in 3T3-L1 adipocytes and modulated gene expression associated with adipogenesis,glucose metabolism,and inflammation in zebrafish.They also enhanced glucose uptake,reduced circulating glucose levels,and improved insulin sensitivity.Notably,the effects were comparable to those of the crude GCSW210 extract.In silico docking studies confirmed stable interactions of both compounds with key metabolic and inflammatory targets,with bis(5-formylfurfuryl)ether showing stronger binding affinities.Conclusions:These findings suggest that 5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether are key contributors to the therapeutic activity of Gracilaria chorda,highlighting its potential as a functional food ingredient for the prevention or management of metabolic disorders.
文摘The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.
文摘Effect of perturbations in Coriolis and centrifugal forces on the non-linear stability of the libration point L4 in the restricted three body problem is studied when both the primaries are axis symmetric bodies (triaxial rigid bodies) and the bigger primary is a source of radiation. Moser’s conditions are utilized in this study by employing the iterative scheme of Henrard for transforming the Hamiltonian to the Birkhoff’s normal form with the help of double D’Alembert’s series. It is found that L4 is stable for all mass ratios in the range of linear stability except for the three mass ratios μc1, μc2 and μc3, which depend upon the perturbations ε1 and ε1 in the Coriolis and centrifugal forces respectively and the parameters A1,A2,A3 and A4 which depend upon the semi-axes a1,b1,c1;a2,b2,c2 of the triaxial rigid bodies and p, the radiation parameter.
基金Natural Sciences and Engineering Research Council(NSERC)of Canada(RGPIN-2022-03488)New Brunswick Innovation Foundation(NBIF)。
文摘As environmental concerns from fossil fuel consumption intensify,large-scale energy storage becomes imperative for the integration of renewable sources like wind,hydro,and solar with the electrical grid.Redox flow batteries,particularly those employing organic molecules,are positioned as a key technology for this purpose.This review explores the growing field of symmetric organic redox flow batteries(ORFBs)within this context.Unlike traditional asymmetric designs based on unique active materials for each electrode,symmetric ORFBs involve a single bipolar species for both electrodes.This review highlights the benefits of a symmetric design,and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents.By providing a comprehensive overview of their cell cycling and performance characteristics,the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems,as are opportunities for future development.This should guide new research directions and advance the development of practical symmetric ORFBs.
基金funded by the Canadian Department of National Defence(DND),the RMC Green Team Military GeoWorks Lab,and the National Sciences and Engineering Research Council(NSERC)of Canada.
文摘A series of laboratory pull-out tests was conducted to study the effects of temperature on the performance and behaviours of fully grouted rock bolt specimens cured within a specific temperature range,as well as for different durations.Each specimen consisted of a 20M rebar bolt at 1300 mm embedment length grouted inside a Schedule 80 steel pipe using Portland cement grout at a 0.4 water-to-cement ratio.Two temperatures(20℃and 45℃)were explored to investigate the effects of geothermally active temperature conditions on fully grouted rock bolts.Distributed fiber optic sensors were employed to provide continuous strain profiles along the entire embedment length to observe micro-mechanisms and monitor internal specimen temperature change during testing.The specimens cured at 45℃generally resulted in higher grout UCS(in certain cases 25%e50%higher)compared to those at 20℃;the ultimate capacity was not significantly impacted as the specimens'embedment length allowed full development of the rock bolt's capacity.The resulting strain profile trends showed generally higher strains experienced by the shorter(i.e.3-d)curing duration specimens under both curing temperatures compared to long-term curing.The 45℃specimens generally experienced lower strains and faster strain profile attenuation compared to specimens cured at 20℃.Understanding these effects and further analysis of FGRB specimen behaviours over time provide insights for mobilized and critical embedment lengths,capacity development,and support system stabilization.This paper highlights the results of this study and aims to bridge selected gaps in existing literature with a view to aid practitioners.
文摘BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often cited as a concern when initiating treatment.Hepatitis B treatment adherence in the context of the patient’s medical and life experiences remains underexplored.AIM To evaluate factors associated with adherence to hepatitis B oral antiviral treatment.METHODS A global online survey was administered anonymously to adults(aged 18 years or older)living with chronic hepatitis B.A subsample of 614 individuals who reported being on hepatitis B treatment was included in the analysis.Indices for treatment affordability,healthcare service acceptability,and individual physical,psychological,and emotional functioning were constructed(Cronbach’s alpha=0.71-0.83).Data analysis was conducted using Stata/BE 17.0.RESULTS Overall,81%of respondents reported high adherence to hepatitis B treatment.Lower adherence was observed among individuals who identified as African or African American(P=0.008).Among participants with low adherence,60%cited affordability as a challenge(P=0.068),53%identified healthcare service acceptability as a challenge(P=0.04),79%described physical functioning as a challenge(P=0.002),and 40.5%reported difficulties with psychological functioning(P=0.55).CONCLUSION Findings demonstrate high treatment adherence,although access to and acceptability of healthcare services,as well as an individual’s physical functioning challenges,appear to be related to low adherence.
文摘This study investigates the complex heat transfer dynamics inmultilayer bifacial photovoltaic(bPV)solar modules under spectrally resolved solar irradiation.A novel numericalmodel is developed to incorporate internal heat generation resulting from optical absorption,grounded in the physical equations governing light-matter interactions within the module’smultilayer structure.The model accounts for reflection and transmission at each interface between adjacent layers,as well as absorption within individual layers,using the wavelength-dependent dielectric properties of constituent materials.These properties are used to calculate the spectral reflectance,transmittance,and absorption coefficients,enabling precise quantification of internal heat sources from irradiance incidents on both the front and rear surfaces of the module.The study further examines the influence of irradiance reflection on thermal behavior,evaluates the thermal impact of various supporting materials placed beneath the module,and analyzes the role of albedo in modifying heat distribution.By incorporating spectrally resolved heat generation across each layer often simplified or omitted in conventional models,the proposed approach enhances physical accuracy.The transient heat equation is solved using a one-dimensional finite difference(FD)method to produce detailed temperature profiles under multiple operating scenarios,including Standard Test Conditions(STC),Bifacial Standard Test Conditions(BSTC),Normal Operating Cell Temperature(NOCT),and Bifacial NOCT(BNOCT).The results offer valuable insights into the interplay between optical and thermal phenomena in bifacial systems,informing the design and optimization of more efficient photovoltaic technologies.
基金funded by the Santa Casa Neuroscience Awards—Prize Melo e Castro for Spinal Cord Injury Research(MC-18-2021)(to AJS and NAS)by the Wings for Life Spinal Cord Research Foundation(WFL-PT-14/23)(to NAS)+2 种基金funded by national funds through the Foundation for Science and Technology(FCT)—projects UIDB/50026/2020,UIDP/50026/2020,and EXPL/MED-PAT/0931/2021-http://doi.org/10.54499/EXPL/MED PAT/0931/2021supported by the Norte Portugal Regional Operational Programme(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund(ERDF)(to SM)the support given by the Portuguese Foundation of Science and Technology to SM(CEECIND/01902/2017-Doi:10.54499/CEECIND/01902/2017/CP1458/CT0024),and NAS(CEECIND/04794/2007)。
文摘The impact of spinal cord injury(SCI)on the immune system is increasingly recognized in a field traditionally focused on motor impairments.SCI can seriously affect the immune system by progressively disrupting the regulatory mechanisms that control immune responses.This dysregulation varies widely among patients and can evolve over time,ranging from systemic inflammatory responses to immunosuppression,greatly contributing to the morbidity and mortality of individuals with SCI(Bao et al.,2011;Brennan et al.,2024).
基金supported by the National Key Research and Development Program of China(Grant No.2022YFA1602501)the National Natural Science Foundation of China(Grant No.12011530060)+1 种基金supported solely by the Russian Science Foundation(Grant No.22-12-00043)supported by the Chinese Academy of Sciences(CAS)Presidents International Fellowship Initiative(PIFI)(Grant Nos.2018VMB0016 and 2022VMC0002),respectively。
文摘We explored a distinct mechanism for matter creation via electron-positron pair production during bound-bound transitions in the deexcitation of muonic atoms.For ions with nuclear charges Z≥24,transitions from low-lying excited states to the 1s-muon state can lead to the production of electron-positron pairs.We show that the Breit interaction determines the transition probabilities for states with nonzero orbital momentum.We show that the pair production arises mainly from the decay of the 2p states.Thus,the Breit interaction governs electron-positron pair production in bound-bound muon transitions.This process offers a unique opportunity to explore quantum electrodynamics in strong fields,as well as a class of nonradiative transitions involving electron-positron pair production.
基金supported by the grants provided by Zhuhai People's Hospital,China(Grant No.:2021KYQD-03)the National Natural Science Foundation of China(Grant No.:22176016).
文摘Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.
基金supported by the International Partnership Program of the Chinese Academy of Sciences (Grant No.025GJHZ2023106GC)。
文摘Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of turbulences in the very early universe in sustaining intense and persistent fluctuations in energy or mass density,which could provide a natural mechanism for PBH formation in the primordial universe. We analyze the mass range and abundance of PBHs produced in the magnetohydrodynamic turbulence induced by the electroweak phase transition. Remarkably, we find that the mass range of the produced PBHs falls within the most viable“asteroid mass” window from the present-day observations, and within natural parameter regions their abundance can be sufficiently large. These findings suggest that PBHs produced during magnetohydrodynamic turbulence in the very early universe may comprise a dominant part of dark matter.
文摘A field study was conducted to investigate the effect of Aquasap, a commercially manufactured biostimulant from seaweed Kappapphycus alvarezii on some hills and foothills banana varieties namely Robusta （AAA）, Njali poovan （AB）, Red banana （AAA） and Nendran （AAB） by applying at 5% through foliar spray at the 3rd, 5th and 7th month of plantation. Both quantitative and quality data of fruits were analyzed along with vegetative growth of the plants. The seaweed biostimulant was found very effective on increasing the weight and nutritional contents of all four banana varieties tested. The highest yield was found in Robusta with 56.58% over control followed by Njali poovan, Red banana and Nendran with 19.08%, 39.35% and 11.46%, respectively. Yield of fruits per hectare of four varieties treated were 76.96, 19.23, 29.68 and 23.37 metric ton （mt）, respectively. Fruits of treated plants also showed less moisture level as compared to control with 240.61%, 62.30%, 61.68% and 37.18% more carbohydrate, 283.71%, 94.07%, 62.87% and 38.93% higher proteins and 153.02%, 47.37%, 58.73% and 31.48% higher minerals respectively as compare to control plants. Therefore, the simple practice of application of eco-friendly seaweed based biostimulant would benefit small and marginal farmers of banana.
基金supported by the MIUR-ex 60% Project(responsibility of Fabio Ietto)。
文摘Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a difficult task to deal with because the presence of buildings,infrastructures,and human activities usually conceals the morphological signs of these landslide activities.So,in the last decades,numerous researchers have shown new methodologies to deepen the studies of similar instability phenomena.The present research is based on an integrated approach to investigate the landslide boundaries,type of movement,failure surface depth,and vulnerability state of buildings in Rota Greca Village(Calabria region,southern Italy) affected by a slowmoving landslide.For this purpose,multi-source data were acquired through geological and geomorphological surveys,recognition of landslide-induced damage on the built environment,subsurface investigations(e.g.,continuous drill boreholes,Standard Penetration Test,Rock Quality Designation index and inclinometer monitoring),laboratory tests(direct shear tests on undisturbed samples),geophysical survey,and InSAR-derived map of deformation rates.The complete integration of multi-source data allowed for the construction of reliable landslide modelling with relative geotechnical properties.In addition,the cross-comparison between surface deformation data by SAR images and severity damage level collected on the exposed buildings enabled to obtain the vulnerability map of the built area.In particular,the achieved goals highlighted two failure surfaces at about-13 and-25 m depth,causing a high vulnerability value for the buildings allocated in the central portion of the Rota Greca Village.The knowledge acquired by the multi-approach can be used to manage and implement appropriate landslide risk mitigation strategies,providing helpful advice and best practices to state-run organisations and stakeholders for landslide management in urban sites.
文摘Wastewater treatment is a process that is vital to protecting both the environment and human health. At present, the most cost-effective way of treating wastewater is with biological treatment processes such as the activated sludge process, despite their long operating times. However, population increases have created a demand for more efficient means of wastewater treatment, Fluidization has been demonstrated to in- crease the efficiency of many processes in chemical and biochemical engineering, but it has not been widely used in large-scale wastewater treatment. At the University of Western Ontario, the circulating fluidized-bed bioreactor （CFBBR） was developed for treating wastewater. In this process, carrier particles develop a biofilm composed of bacteria and other microbes. The excellent mixing and mass transfer characteristics inherent to fluidization make this process very effective at treating both municipal and industrial wastewater. Studies of lab- and pilot-scale systems showed that the CFBBR can remove over 90% of the influent organic matter and 80% of the nitrogen, and produces less than one-third as much biological sludge as the activated sludge process. Due to its high efficiency, the CFBBR can also be used to treat wastewaters with high organic solid concentrations, which are more difficult to treat with conventional methods because they require longer residence times; the CFBBR can also be used to reduce the system size and footprint. In addition, it is much better at handling and recovering from dynamic loadings （i.e., varying influent volume and concentrations） than current systems. Overall, the CFBBR has been shown to be a very effective means of treating wastewa- ter, and to be capable of treating larger volumes of wastewater using a smaller reactor volume and a shorter residence time. In addition, its compact design holds potential for more geographically localized and isolat- ed wastewater treatment systems.
基金support for the project was provided by Chicken Farmers of Saskatchewan(424357)Canadian Poultry Research Council(424854)+1 种基金Natural Sciences and Engineering Research Council of Canada(424679)Saskatchewan Agriculture Development Fund(426954).
文摘Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.
文摘BACKGROUND The anterior talofibular ligament(ATFL)is the most commonly injured ligament in ankle sprains.While most individuals recover with conservative management,some patients develop persistent pain and instability from chronic ATFL tears.Surgical repair is often required,and minimally invasive techniques are gaining popularity.AIM To evaluate the clinical outcomes of a novel,totally percutaneous(TP)modified Broström repair(MBR)for chronic ATFL insufficiency in a cohort of patients who failed conservative treatment.METHODS This retrospective study analyzed 20 patients(14 males,6 females;mean age,28.7 years)who underwent TP-MBR between 2023 and 2024 at a tertiary trauma center.All patients had persistent pain and instability for at least 3 months despite conservative treatment.Diagnosis was confirmed by magnetic resonance imaging,arthroscopy,and stress testing.TP-MBR was performed using suture anchors and percutaneous ligament advancement.Functional outcomes were assessed using American Orthopaedic Foot and Ankle Society score and Karlsson score at a mean follow-up of 1.5 years.RESULTS All procedures were completed successfully with no intraoperative complications.At a mean follow-up of 1.5 years,patients showed significant improvements in American Orthopaedic Foot and Ankle Society score(from 39.85 to 84.4;P<0.001)and Karlsson scores(from 43.8 to 87.4;P<0.001).All patients returned to pre-injury activity levels with resolution of instability.The technique resulted in minimal tissue trauma,reduced operative time,accelerated recovery,and excellent cosmetic outcomes.No recurrences or major complications occurred.CONCLUSION TP-MBR is a safe and effective alternative to open Broström repair for chronic ATFL tears.It offers the benefits of a minimally invasive approach,including less trauma and faster rehabilitation,making it a valuable option for appropriately selected patients.
