Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration tec...Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.展开更多
To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5...To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.展开更多
Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily p...Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily produced by Fusarium spp.and commonly found in various cereal products.Feeding swine diets contaminated with trichothecene DON can lead to major adverse effects,including reduced feed intake,diminished weight gains,and compromised immune function.Among all animal species,swine are the most sensitive to DON.Here we explore the disruption of gut health by DON,considering aspects such as intestinal histomorphology,epithelial barrier functions,immune system,microflora,and short-chain fatty acid production in the intestines.Numerous additives have been documented for their potential in the detoxification of DON.These additives can alleviate the toxic effects of DON on pigs by modulating the Nrf2-Keap1,mitogen-activated protein kinases(MAPKs)and Nuclear factor kappa-B(NF-κB)signaling pathways.Additionally,there are additives capable of mitigating the toxicity of DON through adsorption or biotransformation.This update has novel potential for advancing our comprehension of the mechanisms linked to DON intestinal toxicity and facilitating the formulation of innovative strategies to mitigate the impact of DON.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ ...The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.展开更多
Test case prioritization and ranking play a crucial role in software testing by improving fault detection efficiency and ensuring software reliability.While prioritization selects the most relevant test cases for opti...Test case prioritization and ranking play a crucial role in software testing by improving fault detection efficiency and ensuring software reliability.While prioritization selects the most relevant test cases for optimal coverage,ranking further refines their execution order to detect critical faults earlier.This study investigates machine learning techniques to enhance both prioritization and ranking,contributing to more effective and efficient testing processes.We first employ advanced feature engineering alongside ensemble models,including Gradient Boosted,Support Vector Machines,Random Forests,and Naive Bayes classifiers to optimize test case prioritization,achieving an accuracy score of 0.98847 and significantly improving the Average Percentage of Fault Detection(APFD).Subsequently,we introduce a deep Q-learning framework combined with a Genetic Algorithm(GA)to refine test case ranking within priority levels.This approach achieves a rank accuracy of 0.9172,demonstrating robust performance despite the increasing computational demands of specialized variation operators.Our findings highlight the effectiveness of stacked ensemble learning and reinforcement learning in optimizing test case prioritization and ranking.This integrated approach improves testing efficiency,reduces late-stage defects,and improves overall software stability.The study provides valuable information for AI-driven testing frameworks,paving the way for more intelligent and adaptive software quality assurance methodologies.展开更多
With the rapid development of artificial intelligence,the intelligence level of software is increasingly improving.Intelligent software,which is widely applied in crucial fields such as autonomous driving,intelligent ...With the rapid development of artificial intelligence,the intelligence level of software is increasingly improving.Intelligent software,which is widely applied in crucial fields such as autonomous driving,intelligent customer service,and medical diagnosis,is constructed based on complex technologies like machine learning and deep learning.Its uncertain behavior and data dependence pose unprecedented challenges to software testing.However,existing software testing courses mainly focus on conventional contents and are unable to meet the requirements of intelligent software testing.Therefore,this work deeply analyzed the relevant technologies of intelligent software testing,including reliability evaluation indicator system,neuron coverage,and test case generation.It also systematically designed an intelligent software testing course,covering teaching objectives,teaching content,teaching methods,and a teaching case.Verified by the practical teaching in four classes,this course has achieved remarkable results,providing practical experience for the reform of software testing courses.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide...Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.展开更多
Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrat...Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.展开更多
Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which...Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.展开更多
Members of the British Textile Machinery Association(BTMA)can look back on 2025 as a year marked by notable technological advances and continued progress in global trade,despite an uncertain and volatile market.“Our ...Members of the British Textile Machinery Association(BTMA)can look back on 2025 as a year marked by notable technological advances and continued progress in global trade,despite an uncertain and volatile market.“Our members have been very active over the past 12 months and this has resulted in new technologies for the production of technical fibres and fabrics,the introduction of AI and machine learning into process control systems and significant advances in materials testing,”says BTMA CEO Jason Kent.“There’s real excitement about what can be achieved in 2026 as we look ahead to upcoming exhibitions such as JEC Composites in Paris in March and Techtextil in Frankfurt in April.”展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raisin...With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raising increasing concerns about their security.Existing fuzz testing methods include random or dictionary-based input generation,which often fail to ensure both syntactic and semantic correctness,and OpenAPIbased approaches,which offer better accuracy but typically lack detailed descriptions of endpoints,parameters,or data formats.To address these issues,this paper proposes the APIDocX fuzz testing framework.It introduces a crawler tailored for dynamic web pages that automatically simulates user interactions to trigger APIs,capturing and extracting parameter information from communication packets.A multi-endpoint parameter adaptation method based on improved Jaccard similarity is then used to generalize these parameters to other potential API endpoints,filling in gaps in OpenAPI specifications.Experimental results demonstrate that the extracted parameters can be generalized with 79.61%accuracy.Fuzz testing using the enriched OpenAPI documents leads to improvements in test coverage,the number of valid test cases generated,and fault detection capabilities.This approach offers an effective enhancement to automated REST API security testing.展开更多
Cloud services,favored by many enterprises due to their high flexibility and easy operation,are widely used for data storage and processing.However,the high latency,together with transmission overheads of the cloud ar...Cloud services,favored by many enterprises due to their high flexibility and easy operation,are widely used for data storage and processing.However,the high latency,together with transmission overheads of the cloud architecture,makes it difficult to quickly respond to the demands of IoT applications and local computation.To make up for these deficiencies in the cloud,fog computing has emerged as a critical role in the IoT applications.It decentralizes the computing power to various lower nodes close to data sources,so as to achieve the goal of low latency and distributed processing.With the data being frequently exchanged and shared between multiple nodes,it becomes a challenge to authorize data securely and efficiently while protecting user privacy.To address this challenge,proxy re-encryption(PRE)schemes provide a feasible way allowing an intermediary proxy node to re-encrypt ciphertext designated for different authorized data requesters without compromising any plaintext information.Since the proxy is viewed as a semi-trusted party,it should be taken to prevent malicious behaviors and reduce the risk of data leakage when implementing PRE schemes.This paper proposes a new fog-assisted identity-based PRE scheme supporting anonymous key generation,equality test,and user revocation to fulfill various IoT application requirements.Specifically,in a traditional identity-based public key architecture,the key escrow problem and the necessity of a secure channel are major security concerns.We utilize an anonymous key generation technique to solve these problems.The equality test functionality further enables a cloud server to inspect whether two candidate trapdoors contain an identical keyword.In particular,the proposed scheme realizes fine-grained user-level authorization while maintaining strong key confidentiality.To revoke an invalid user identity,we add a revocation list to the system flows to restrict access privileges without increasing additional computation cost.To ensure security,it is shown that our system meets the security notion of IND-PrID-CCA and OW-ID-CCA under the Decisional Bilinear Diffie-Hellman(DBDH)assumption.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Lateral flow immunoassays(LFIAs)are low-cost,rapid,and easy to use for pointof-care testing(POCT),but the majority of the available LFIA tests are indicative,rather than quantitative,and their sensitivity in antigen t...Lateral flow immunoassays(LFIAs)are low-cost,rapid,and easy to use for pointof-care testing(POCT),but the majority of the available LFIA tests are indicative,rather than quantitative,and their sensitivity in antigen tests are usually limited at the nanogram range,which is primarily due to the passive capillary fluidics through nitrocellulose membranes,often associated with non-specific bindings and high background noise.To overcome this challenge,we report a Beads-on-a-Tip design by replacing nitrocellulose membranes with a pipette tip loaded with magnetic beads.The beads are pre-conjugated with capture antibodies that support a typical sandwich immunoassay.This design enriches the low-abundant antigen proteins and allows an active washing process to significantly reduce non-specific bindings.To further improve the detection sensitivity,we employed upconversion nanoparticles(UCNPs)as luminescent reporters and SARS-CoV-2 spike(S)antigen as a model analyte to benchmark the performance of this design against our previously reported methods.We found that the key to enhance the immunocomplex formation and signal-to-noise ratio lay in optimizing incubation time and the UCNP-to-bead ratio.We therefore successfully demonstrated that the new method can achieve a very large dynamic range from 500 fg/mL to 10μg/mL,across over 7 digits,and a limit of detection of 706 fg/mL,nearly another order of magnitude lower than the best reported LFIA using UCNPs in COVID-19 spike antigen detection.Our system offers a promising solution for ultra-sensitive and quantitative POCT diagnostics.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
Parallel machining robot is a new type of robotized equipment for high-efficiency machining structural com-ponents with complex geometries.Terminal rigidity is of great importance index for such type of equipment,whic...Parallel machining robot is a new type of robotized equipment for high-efficiency machining structural com-ponents with complex geometries.Terminal rigidity is of great importance index for such type of equipment,which affects their load capacity and working accuracy.Before a parallel machining robot can be used for heavy-load and high-efficiency machining,its terminal rigidity should be evaluated systematically.The present study is to quantitatively reveal the stiffness properties of a previously invented Z4 redundantly actuated parallel ma-chining robot(RAPMR).For this purpose,two critical issues,i.e.,stiffness modelling and index construction,are clarified to carry out stiffness evaluation of the Z4 RAPMR.Firstly,drawing on the screw theory,a semi-analytic stiffness model of the proposed RAPMR is established at a component level.Secondly,a set of virtual work-based stiffness indices is constructed to evaluate the terminal rigidity of parallel robots.Those indices have a consistent physical unit in describing linear and angular terminal rigidity.With these indices,the local and the global stiffness performance of the Z4 RAPMR are predicted.Thirdly,a laboratory prototype of the proposed RAPMR is fabricated.And the experimental test is performed to verify the correctness of the established stiffness model.The present work is expected to provide fundamental information for further light-weight design and rigidity enhancement.展开更多
The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from...The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.展开更多
基金This work was supported by the Focused Research Effort on Chemicals in the Working Environment(FFIKA)from the Danish Government.
文摘Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.
文摘To evaluate the subchronic and chronic toxicity of Fuyanxiao capsules,Sprague-Dawley(SD)rats were used in toxicity studies.In the subchronic toxicity study,50 female rats were randomly divided into a high-dose group(5.4g/kg/day)and a control group,with 15 rats in each,and medium(2.7g/kg/day)and low(1.35g/kg/day)dose groups,with 10 rats in each.The test substance was administered orally(mixed with feed,twice daily)for 90 consecutive days.In the chronic toxicity study,40 female rats were randomly divided into high,medium,and low dose groups and a control group,with 10 rats in each.The test substance was administered orally in the same manner for 180 consecutive days.Clinical signs,body weight,and food consumption were observed and recorded daily.At the end of the terminal phase(the first 10 rats from each group,1 day after the last dose)and the recovery phase(the last 5 rats from the control group and the high-dose group,observed for an additional 28 days after the last dose),blood and urine samples,as well as organs,were collected.Organ coefficients were calculated,and various hematological and urinary indicators were detected,followed by pathological analysis.The results showed that there were no significant differences in body weight,food consumption,or organ coefficients between any of the dose groups and the control group in both subchronic and chronic toxicity studies(P>0.05).Histopathological examination revealed no lesions,suggesting no tissue or organ damage in any of the dose groups.The rats exhibited good mental status,and hematological and urinary physiological indicators were within normal ranges,indicating stable liver and kidney function,hematopoietic system of the bone marrow,and internal environment in all dose groups.Therefore,Fuyanxiao capsule has no obvious subchronic or chronic toxicity in SD rats,and it is safe and reliable to use at reasonable dosage in clinical practice.
基金supported by the National Key Research and Development Program of China(2021YFD1301003)the Beijing University of Agriculture Science and Technology Innovation“Spark Action”Support Program,China(BUA-HHXD2022011)the key research and development Program of Shaanxi Province,China(2022NY-095)。
文摘Mycotoxins are the most widely existing pollutants in both dietary provisions and livestock feed,and they pose a series of hazards for humans and animals.Deoxynivalenol(DON)is a prevalent mycotoxin that is primarily produced by Fusarium spp.and commonly found in various cereal products.Feeding swine diets contaminated with trichothecene DON can lead to major adverse effects,including reduced feed intake,diminished weight gains,and compromised immune function.Among all animal species,swine are the most sensitive to DON.Here we explore the disruption of gut health by DON,considering aspects such as intestinal histomorphology,epithelial barrier functions,immune system,microflora,and short-chain fatty acid production in the intestines.Numerous additives have been documented for their potential in the detoxification of DON.These additives can alleviate the toxic effects of DON on pigs by modulating the Nrf2-Keap1,mitogen-activated protein kinases(MAPKs)and Nuclear factor kappa-B(NF-κB)signaling pathways.Additionally,there are additives capable of mitigating the toxicity of DON through adsorption or biotransformation.This update has novel potential for advancing our comprehension of the mechanisms linked to DON intestinal toxicity and facilitating the formulation of innovative strategies to mitigate the impact of DON.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked for China Agriculture Research System(CARS-46).
文摘The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.
文摘Test case prioritization and ranking play a crucial role in software testing by improving fault detection efficiency and ensuring software reliability.While prioritization selects the most relevant test cases for optimal coverage,ranking further refines their execution order to detect critical faults earlier.This study investigates machine learning techniques to enhance both prioritization and ranking,contributing to more effective and efficient testing processes.We first employ advanced feature engineering alongside ensemble models,including Gradient Boosted,Support Vector Machines,Random Forests,and Naive Bayes classifiers to optimize test case prioritization,achieving an accuracy score of 0.98847 and significantly improving the Average Percentage of Fault Detection(APFD).Subsequently,we introduce a deep Q-learning framework combined with a Genetic Algorithm(GA)to refine test case ranking within priority levels.This approach achieves a rank accuracy of 0.9172,demonstrating robust performance despite the increasing computational demands of specialized variation operators.Our findings highlight the effectiveness of stacked ensemble learning and reinforcement learning in optimizing test case prioritization and ranking.This integrated approach improves testing efficiency,reduces late-stage defects,and improves overall software stability.The study provides valuable information for AI-driven testing frameworks,paving the way for more intelligent and adaptive software quality assurance methodologies.
基金Computer Basic Education Teaching Research Project of Association of Fundamental Computing Education in Chinese Universities(Nos.2025-AFCEC-527 and 2024-AFCEC-088)Research on the Reform of Public Course Teaching at Nantong College of Science and Technology(No.2024JGG015).
文摘With the rapid development of artificial intelligence,the intelligence level of software is increasingly improving.Intelligent software,which is widely applied in crucial fields such as autonomous driving,intelligent customer service,and medical diagnosis,is constructed based on complex technologies like machine learning and deep learning.Its uncertain behavior and data dependence pose unprecedented challenges to software testing.However,existing software testing courses mainly focus on conventional contents and are unable to meet the requirements of intelligent software testing.Therefore,this work deeply analyzed the relevant technologies of intelligent software testing,including reliability evaluation indicator system,neuron coverage,and test case generation.It also systematically designed an intelligent software testing course,covering teaching objectives,teaching content,teaching methods,and a teaching case.Verified by the practical teaching in four classes,this course has achieved remarkable results,providing practical experience for the reform of software testing courses.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
基金supported by the National Natural Science Foundation of China(Nos.82372115,52073139 and 82404553)the Postdoctoral Fellowship Program of Chinese Postdoctoral Science Foundation(No.GZC20231085).
文摘Albumin,owing to its high abundance and excellent biocompatibility,is widely used as a drug carrier to enhance delivery efficiency and reduce systemic toxicity.The Michael addition between albumin thiols and maleimide-functionalized prodrugs is a common in situ macromolecular prodrug strategy.However,the resulting reversible adducts are susceptible to retro-Michael reactions in vivo,leading to premature drug release and off-target effects.To address this limitation,a gemcitabine prodrug(GAB)bearing a chloroacetamide group was designed to form irreversible covalent bonds with albumin via nucleophilic substitution.A maleimide-based prodrug(GAM)was synthesized as a control.Compared to GAM,GAB showed faster and stronger albumin binding in plasma,enhanced blood circulation time,improved tumor accumulation,and superior in vivo antitumor efficacy.Moreover,GAB exhibited a better safety profile,with reduced cytotoxicity in normal tissues and no observable systemic toxicity.These advantages are attributed to the stable albumin-drug conjugate formed by GAB,which improves drug retention and targeted delivery.This study presents an effective and generalizable albumin-hitchhiking strategy for constructing irreversible prodrugs,offering a promising approach to enhance the therapeutic index of chemotherapeutic agents.
基金funding from Deutsche Forschungsgemeinschaft (DFG)supported by an MCIN Ry C Programme MCIN/ AEI/10.13039/501100011033+2 种基金by the ‘European Union Next Generation EU/PRTR’ under grant no. RYC2021-032345-Isupported by the AEI (grant no. PID2019-107463RJ-I00/ AEI/10.13039/501100011033)the Regional Research and Development Programme of the Government of Navarre (call 2019, project Nitro Healthy, PC068)
文摘Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.
基金supported by the National Natural Science Foundation of China (Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi (No.2023010)。
文摘Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.
文摘Members of the British Textile Machinery Association(BTMA)can look back on 2025 as a year marked by notable technological advances and continued progress in global trade,despite an uncertain and volatile market.“Our members have been very active over the past 12 months and this has resulted in new technologies for the production of technical fibres and fabrics,the introduction of AI and machine learning into process control systems and significant advances in materials testing,”says BTMA CEO Jason Kent.“There’s real excitement about what can be achieved in 2026 as we look ahead to upcoming exhibitions such as JEC Composites in Paris in March and Techtextil in Frankfurt in April.”
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
基金supported by the Open Foundation of Key Laboratory of Cyberspace Security,Ministry of Education of China(KLCS20240211)。
文摘With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raising increasing concerns about their security.Existing fuzz testing methods include random or dictionary-based input generation,which often fail to ensure both syntactic and semantic correctness,and OpenAPIbased approaches,which offer better accuracy but typically lack detailed descriptions of endpoints,parameters,or data formats.To address these issues,this paper proposes the APIDocX fuzz testing framework.It introduces a crawler tailored for dynamic web pages that automatically simulates user interactions to trigger APIs,capturing and extracting parameter information from communication packets.A multi-endpoint parameter adaptation method based on improved Jaccard similarity is then used to generalize these parameters to other potential API endpoints,filling in gaps in OpenAPI specifications.Experimental results demonstrate that the extracted parameters can be generalized with 79.61%accuracy.Fuzz testing using the enriched OpenAPI documents leads to improvements in test coverage,the number of valid test cases generated,and fault detection capabilities.This approach offers an effective enhancement to automated REST API security testing.
基金supported in part by the National Science and Technology Council of Taiwan under the contract numbers NSTC 114-2221-E-019-055-MY2 and NSTC 114-2221-E-019-069.
文摘Cloud services,favored by many enterprises due to their high flexibility and easy operation,are widely used for data storage and processing.However,the high latency,together with transmission overheads of the cloud architecture,makes it difficult to quickly respond to the demands of IoT applications and local computation.To make up for these deficiencies in the cloud,fog computing has emerged as a critical role in the IoT applications.It decentralizes the computing power to various lower nodes close to data sources,so as to achieve the goal of low latency and distributed processing.With the data being frequently exchanged and shared between multiple nodes,it becomes a challenge to authorize data securely and efficiently while protecting user privacy.To address this challenge,proxy re-encryption(PRE)schemes provide a feasible way allowing an intermediary proxy node to re-encrypt ciphertext designated for different authorized data requesters without compromising any plaintext information.Since the proxy is viewed as a semi-trusted party,it should be taken to prevent malicious behaviors and reduce the risk of data leakage when implementing PRE schemes.This paper proposes a new fog-assisted identity-based PRE scheme supporting anonymous key generation,equality test,and user revocation to fulfill various IoT application requirements.Specifically,in a traditional identity-based public key architecture,the key escrow problem and the necessity of a secure channel are major security concerns.We utilize an anonymous key generation technique to solve these problems.The equality test functionality further enables a cloud server to inspect whether two candidate trapdoors contain an identical keyword.In particular,the proposed scheme realizes fine-grained user-level authorization while maintaining strong key confidentiality.To revoke an invalid user identity,we add a revocation list to the system flows to restrict access privileges without increasing additional computation cost.To ensure security,it is shown that our system meets the security notion of IND-PrID-CCA and OW-ID-CCA under the Decisional Bilinear Diffie-Hellman(DBDH)assumption.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金financially supported by ARC Linkage project(LP210200642)ARC Center of Excellence for Quantum Biotechnology(grant no.CE230100021)+1 种基金National Health and Medical Research Council Investigator Fellowship—(grant no.APP2017499)Chan Zuckerberg Initiative Deep Tissue Imaging Phase 2(grant no.DT12-0000000182).
文摘Lateral flow immunoassays(LFIAs)are low-cost,rapid,and easy to use for pointof-care testing(POCT),but the majority of the available LFIA tests are indicative,rather than quantitative,and their sensitivity in antigen tests are usually limited at the nanogram range,which is primarily due to the passive capillary fluidics through nitrocellulose membranes,often associated with non-specific bindings and high background noise.To overcome this challenge,we report a Beads-on-a-Tip design by replacing nitrocellulose membranes with a pipette tip loaded with magnetic beads.The beads are pre-conjugated with capture antibodies that support a typical sandwich immunoassay.This design enriches the low-abundant antigen proteins and allows an active washing process to significantly reduce non-specific bindings.To further improve the detection sensitivity,we employed upconversion nanoparticles(UCNPs)as luminescent reporters and SARS-CoV-2 spike(S)antigen as a model analyte to benchmark the performance of this design against our previously reported methods.We found that the key to enhance the immunocomplex formation and signal-to-noise ratio lay in optimizing incubation time and the UCNP-to-bead ratio.We therefore successfully demonstrated that the new method can achieve a very large dynamic range from 500 fg/mL to 10μg/mL,across over 7 digits,and a limit of detection of 706 fg/mL,nearly another order of magnitude lower than the best reported LFIA using UCNPs in COVID-19 spike antigen detection.Our system offers a promising solution for ultra-sensitive and quantitative POCT diagnostics.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
基金Supported by National Natural Science Foundation of China(Grant No.52375009)Fujian Provincial Young and Middle-Aged Teacher Education Research Project of China(Grant No.JAT220029).
文摘Parallel machining robot is a new type of robotized equipment for high-efficiency machining structural com-ponents with complex geometries.Terminal rigidity is of great importance index for such type of equipment,which affects their load capacity and working accuracy.Before a parallel machining robot can be used for heavy-load and high-efficiency machining,its terminal rigidity should be evaluated systematically.The present study is to quantitatively reveal the stiffness properties of a previously invented Z4 redundantly actuated parallel ma-chining robot(RAPMR).For this purpose,two critical issues,i.e.,stiffness modelling and index construction,are clarified to carry out stiffness evaluation of the Z4 RAPMR.Firstly,drawing on the screw theory,a semi-analytic stiffness model of the proposed RAPMR is established at a component level.Secondly,a set of virtual work-based stiffness indices is constructed to evaluate the terminal rigidity of parallel robots.Those indices have a consistent physical unit in describing linear and angular terminal rigidity.With these indices,the local and the global stiffness performance of the Z4 RAPMR are predicted.Thirdly,a laboratory prototype of the proposed RAPMR is fabricated.And the experimental test is performed to verify the correctness of the established stiffness model.The present work is expected to provide fundamental information for further light-weight design and rigidity enhancement.
基金supported by the National Natural Science Foundation of China(No.52388102)the Sichuan Science and Technology Program(No.2024NSFTD0011)the Fundamental Research Funds for the State Key Laboratory of Rail Transit Vehicle System of Southwest Jiaotong University(No.2023TPL-T11).
文摘The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.
