Objective Nan'ao County in Guandong Province is a high-risk area of esophageal cancer in Southern China. Of the suspected etiological factors in the environment, N-nitrosamines and their precursors have received t...Objective Nan'ao County in Guandong Province is a high-risk area of esophageal cancer in Southern China. Of the suspected etiological factors in the environment, N-nitrosamines and their precursors have received the greatest attention. Methods Sixty samples of the diet ingested by the inhabitants were collected and detected for volatile N-nitrosamines and their precursors. Five N-nitrosamines detected by Gas Chromatography-Thermal Energy Analyzer were N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosopiperidine and N-nitrosomethyl-benzylamine. Results The average content of 5 volatile N-nitrosamines in the diet was 312.0 μg/kg (median). The daily intake of the nitrosamines was 286.5 μg/head/day. Only the ability to exogenously synthesize N-nitrosopiperidine was powerful among 5 volatile N-nitrosamines. By a computerized stepwise regression analysis and curve fitting, we studied the correlation among the nitrosamines, the precursors and the major food items in the samples. Conclusion It demonstrated that a relatively high content of volatile N-nitrosamines was present in the diet collected in the area.展开更多
The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neuro...The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.展开更多
Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing counte...Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.展开更多
Drought(water shortage)can substantially limit the yield and economic value of rose plants(Rosa spp.).Here,we characterized the effect of exogenous calcium(Ca^(2+))on the antioxidant system and photosynthesis-related ...Drought(water shortage)can substantially limit the yield and economic value of rose plants(Rosa spp.).Here,we characterized the effect of exogenous calcium(Ca^(2+))on the antioxidant system and photosynthesis-related properties of rose under polyethylene glycol 6000(PEG6000)-induced drought stress.Chlorophyll levels,as well as leaf and root biomass,were significantly reduced by drought;drought also had a major effect on the enzymatic antioxidant system and increased concentrations of reactive oxygen species.Application of exogenous Ca^(2+)increased the net photosynthetic rate and stomatal conductance of leaves,enhanced water-use efficiency,and increased the length and width of stomata following exposure to drought.Organ-specific physiological responses were observed under different concentrations of Ca^(2+).Application of 5 mmol·L^(-1)Ca^(2+)promoted photosynthesis and antioxidant activity in the leaves,and application of 10 mmol·L^(-1)Ca^(2+)promoted antioxidant activity in the roots.Application of exogenous Ca^(2+)greatly enhanced the phenotype and photosynthetic capacity of potted rose plants following exposure to drought stress.Overall,our findings indicate that the application of exogenous Ca^(2+)enhances the drought resistance of roses by promoting physiological adaptation and that it could be used to aid the cultivation of rose plants.展开更多
BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which a...BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.展开更多
This study was to investigate the effects of three exogenous substances on chemical constituents of Isatis indigotica leavesand their efficacy in alleviating drought stress, and explore the methods of applying exogeno...This study was to investigate the effects of three exogenous substances on chemical constituents of Isatis indigotica leavesand their efficacy in alleviating drought stress, and explore the methods of applying exogenous substances to efficient cultivationof Isatis indigotica. Polyethylene glycol (PEG) was used to simulate drought stress to deal with seeds of Isatis indigotica at thegermination stage (concentration: 0, 10%, 15%, and 20%). Simultaneous operation of exogenous growth regulators [microbialinoculum (MI), γ-aminobutyric acid (GABA) and salicylic acid (SA)] and PEG were implemented in seeds of Isatis indigotica.The effects of drought stress and the mitigation of exogenous substances were observed by statistics of seed germination potential,germination rate, hypocotyl length, and radicle length of each treatment. The effects of exogenous substances on the content ofalkaloids, crude protein and free amino acids in the leaves of Isatis indigotica grown in a greenhouse were determined after sprayingexogenous substances on the plants. The differences of germination potential, germination rate, hypocotyl length, and radicle lengthamong 15% PEG stress treatment, 10% PEG stress treatment and the control were significant (P<0.05). According to the predesignedgermination standard, the seeds did not germinate under 20% PEG stress treatment. When the PEG concentration was 15%, the resultsof seed germination potential and germination rate after adding MI were significantly different from those under stress alone (P<0.05).When exposed to 10% PEG stress, the supplementation of GABA led to a notable increase in radicle length of Isatis indigotica seeds,showing significant differences compared to other three treatments. The application of MI and GABA under 15% PEG stress resultedin a significant increase in the radicle and hypocotyl length of Isatis indigotica seeds compared to other two treatments. The contentof the total alkaloids in leaves of Isatis indigotica was significantly increased after spraying GABA. Meanwhile, the contents of crudeprotein and the total free amino acids were kept constant after spraying exogenous substances. Application of MI and GABA couldalleviate drought stress of Isatis indigotica. The content of the total alkaloids in leaves of Isatis indigotica could significantly increaseafter spraying GABA.展开更多
Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to p...Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.展开更多
Phosphorus bioavailability has long been a recurring problem in tropical acid soils. A pot experiment was carried out during three (3) successive rice production cycles at Adiopodoumé to evaluate the response of ...Phosphorus bioavailability has long been a recurring problem in tropical acid soils. A pot experiment was carried out during three (3) successive rice production cycles at Adiopodoumé to evaluate the response of the NERICA 5 rice accession to various doses of calcium, magnesium and phosphorous. The experiment was conducted using a randomized split-plot design. The interactive effects of calcium carbonate (0, 25, 50 and 75 kg·Ca·ha<sup>-1</sup>) and magnesium sulfate (0, 25, 50 and 75 kg·Mg·ha<sup>-1</sup>) and Togo natural phosphate (0, 25, 50 and 75 kg·P·ha<sup>-1</sup>) were determined at each production cycle. The results showed that single-dose natural phosphate supplementation for three cropping cycles resulted in an average enrichment of around 2 mg·P·kg<sup>-1</sup> after each trial following its continuous dissolution, with an increase in DSP (33.31% to 70.52%). The study revealed one strategy for managing and enhancing native P with cations and another for exogenous P: there would be a synergy of Ca/Mg on native P, whereas an antagonism would characterize the two parameters in phosphate fertilization.展开更多
Background Sustainable strategies for enteric methane(CH_(4))mitigation of dairy cows have been extensively explored to improve production performance and alleviate environmental pressure.The present study aimed to in...Background Sustainable strategies for enteric methane(CH_(4))mitigation of dairy cows have been extensively explored to improve production performance and alleviate environmental pressure.The present study aimed to investigate the effects of dietary xylooligosaccharides(XOS)and exogenous enzyme(EXE)supplementation on milk production,nutrient digestibility,enteric CH_(4) emissions,energy utilization efficiency of lactating Jersey dairy cows.Forty-eight lactating cows were randomly assigned to one of 4 treatments:(1)control diet(CON),(2)CON with 25 g/d XOS(XOS),(3)CON with 15 g/d EXE(EXE),and(4)CON with 25 g/d XOS and 15 g/d EXE(XOS+EXE).The 60-d experimental period consisted of a 14-d adaptation period and a 46-d sampling period.The enteric CO_(2)and CH_(4) emissions and O2 consumption were measured using two GreenFeed units,which were further used to determine the energy utilization efficiency of cows.Results Compared with CON,cows fed XOS,EXE or XOS+EXE significantly(P<0.05)increased milk yield,true protein and fat concentration,and energy-corrected milk yield(ECM)/DM intake,which could be reflected by the significant improvement(P<0.05)of dietary NDF and ADF digestibility.The results showed that dietary supplementation of XOS,EXE or XOS+EXE significantly(P<0.05)reduced CH_(4) emission,CH_(4)/milk yield,and CH_(4)/ECM.Furthermore,cows fed XOS demonstrated highest(P<0.05)metabolizable energy intake,milk energy output but lowest(P<0.05)of CH_(4) energy output and CH_(4) energy output as a proportion of gross energy intake compared with the remaining treatments.Conclusions Dietary supplementary of XOS,EXE or combination of XOS and EXE contributed to the improvement of lactation performance,nutrient digestibility,and energy utilization efficiency,as well as reduction of enteric CH_(4) emissions of lactating Jersey cows.This promising mitigation method may need further research to validate its long-term effect and mode of action for dairy cows.展开更多
The occurrence of diabetes mellitus(DM)in pancreatitis is being increasingly recognized lately.Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis(AP).The inc...The occurrence of diabetes mellitus(DM)in pancreatitis is being increasingly recognized lately.Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis(AP).The incidence of diabetes after AP varies from 18%to 23%in 3 years and reaches up to 40%over 5 years.The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass,AP-induced autoimmunity,and alterations in the insulin incretin axis.Risk factors associated with increased risk of diabetes includes male sex,recurrent attacks of pancreatitis,presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis.Diagnosis of post-pancreatitis DM(PPDM)is often excluded.Treatment includes a trial of oral antidiabetic drugs in mild diabetes.Often,insulin is required in uncontrolled diabetes.Given the lack of awareness of this metabolic disorder after AP,this review will evaluate current information on epidemiology,risk factors,diagnosis and management of PPDM and identify the knowledge gaps.展开更多
Background Soybean(Glycine max)meal is one of the important protein sources for fish,but the non-starch polysaccharides(NSP)in soybean meal impair the intestinal barrier function.Here we aimed to investigate whether x...Background Soybean(Glycine max)meal is one of the important protein sources for fish,but the non-starch polysaccharides(NSP)in soybean meal impair the intestinal barrier function.Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism.Results Nile tilapia(Oreochromis niloticus)(4.09±0.02 g)were fed with two diets including SM(soybean meal)and SMC(soybean meal+3,000 U/kg xylanase)for 8 weeks.We characterized the effects of xylanase on the gut barrier,and the transcriptome analysis was performed to investigate the underlying mechanism.Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide(LPS)in serum.The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2(MUC2)which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase(perk)/activating transcription factor 4(atf4)signaling pathways.Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut.Notably,dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia,and the data verified that sodium butyrate mirrored the beneficial effects of xylanase.Conclusions Collectively,supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia.The present study reveals the mechanism by which xylanase improves the intestinal barrier,and it also provides a theoretical basis for the application of xylanase in aquaculture.展开更多
Objective:To determine the impact of major disease epidemics on pharmaceutical manufacturing firms'Research&Development(R&D)investments and economic consequences.Methods:The sample consists of 1582 firm-ye...Objective:To determine the impact of major disease epidemics on pharmaceutical manufacturing firms'Research&Development(R&D)investments and economic consequences.Methods:The sample consists of 1582 firm-year observations from 2009 to 2022 in China,of which,26.6%of pharmaceutical companies are involved in the diagnosis and treatment of prevalent diseases.Linear models using R&D investments,patent applications,operating performances and stock returns as dependent variables are constructed separately to examine the response of pharmaceutical companies to disease epidemics and the resulting economic consequences.Results:The prevalence of five major diseases led to a 17.5%increase in the amount of R&D investment and an 87.8%rise in the ratio of R&D investment to total assets by disease-related pharmaceutical companies,compared to unrelated pharmaceutical companies.Further evidence indicated that the patent applications for disease-related firms increased by 44.3%relative to unrelated firms after the epidemics.Though the impacts of the epidemics on firms’operating performances were insignificant in the short term,a major disease epidemic was associated with an increase in stock returns of 67.4%and 44.6%,respectively,as measured by the capital asset pricing model and Fama-French five-factor model.Additional analysis revealed that the impacts of the epidemics on R&D investments and patent applications were more pronounced for non-state-owned enterprises than state-owned enterprises.Conclusions:This study demonstrates that disease-related pharmaceutical firms respond to the disease epidemics through increasing R&D investment.More patent applications and higher market value are the main gains from the firms’increased investments in R&D following the epidemic,rather than the improvements of short-term operating performances.展开更多
The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptom...The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.展开更多
System Identification becomes very crucial in the field of nonlinear and dynamic systems or practical systems.As most practical systems don’t have prior information about the system behaviour thus,mathematical modell...System Identification becomes very crucial in the field of nonlinear and dynamic systems or practical systems.As most practical systems don’t have prior information about the system behaviour thus,mathematical modelling is required.The authors have proposed a stacked Bidirectional Long-Short Term Memory(Bi-LSTM)model to handle the problem of nonlinear dynamic system identification in this paper.The proposed model has the ability of faster learning and accurate modelling as it can be trained in both forward and backward directions.The main advantage of Bi-LSTM over other algorithms is that it processes inputs in two ways:one from the past to the future,and the other from the future to the past.In this proposed model a backward-running Long-Short Term Memory(LSTM)can store information from the future along with application of two hidden states together allows for storing information from the past and future at any moment in time.The proposed model is tested with a recorded speech signal to prove its superiority with the performance being evaluated through Mean Square Error(MSE)and Root Means Square Error(RMSE).The RMSE and MSE performances obtained by the proposed model are found to be 0.0218 and 0.0162 respectively for 500 Epochs.The comparison of results and further analysis illustrates that the proposed model achieves better performance over other models and can obtain higher prediction accuracy along with faster convergence speed.展开更多
Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifical...Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifically focusing on those seeking assistance due to suicide attempts (TS) versus CLP requests for other reasons (non-TS) between the years 2010 and 2020. Additionally, we aim to assess factors associated with suicide attempts. Method: This retrospective controlled study involves a thorough examination of medical records encompassing 3913 patients who received CLP services at the Hospital de Base (HB) and the Children and Maternity Hospital (HCM) of São José do Rio Preto Medical School Foundation (Funfarme) from June 2010 to June 2020. The patient cohort is categorized into two groups: those with requests for SA (n = 677) and those with requests for other reasons. Results: In the SA group, as opposed to the non SA group, statistically significant differences were observed for gender (predominantly female), employment status (employed), marital status (single), and age (younger). Notably, a higher prevalence of psychiatric antecedents (88.7%, n = 555 vs. 73.6% n = 2018) was found in the SA group, indicating a significant association. The frequency of SA requests remained stable over the years. Among the SA group, mood disorders were the most prevalent (39%, n = 372), followed by disorders related to substance use (21.2%, n = 202), and personality disorders (16%, n = 152). A history of previous suicide attempts emerged as a crucial factor for the recurrence of SA (p-value ≤ 0.001). Exogenous intoxication emerged as the most frequently employed method in attempts (79.6%, n = 539), particularly prevalent among patients diagnosed with mood disorders (41%, n = 314). A significant association was observed between the method of attempt and the nosological psychiatric diagnosis (χ<sup>2</sup> = 42.277;p ≤ 0.001). Regarding outcomes, the majority of patients were referred for outpatient follow-up (23%, n = 336) in specialized mental health services or at the Primary Healthcare Unit, highlighting the general hospital’s pivotal role in integrating patients into the broader healthcare network. Conclusion: Variables such as gender (female), age group (young adults), and psychiatric history exhibited stronger associations with suicide attempts compared to the group assisted by CLP for other reasons. Furthermore, a noteworthy correlation between the method employed and the psychiatric diagnosis was identified.展开更多
In recent years, a lot of corporate defaults have had an impact on the capital market. How to prevent corporate default risks has become an important topic of concern for the academic community, enterprises and the go...In recent years, a lot of corporate defaults have had an impact on the capital market. How to prevent corporate default risks has become an important topic of concern for the academic community, enterprises and the government. We took China’s A-share listed companies from 2012 to 2018 as a sample, and used the double difference method to analyze the impact of supply-side structural reforms on corporate default risks. We found that supply-side structural reforms have reduced the risk of corporate default, and the inhibitory effect has gradually increased. In the relationship between supply-side structural reforms and corporate default risks, corporate financing capabilities have played an intermediary role. Supply-side structural reforms can improve the company’s endogenous financing capabilities, thereby reducing the risk of corporate default. However, we also found that the mediating effect of a company’s exogenous financing capability is not significant. At the same time, the regression results show that the digital economy can play a regulatory role. It can not only actively regulate the relationship between supply-side structural reforms and corporate default risks, but also mediate the mediating effect of corporate endogenous financing capabilities. The results of this article provide some evidence for the synergy between supply-side structural reforms and the digital economy.展开更多
As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,t...As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.展开更多
Tool condition monitoring(TCM)is a key technology for intelligent manufacturing.The objective is to monitor the tool operation status and detect tool breakage so that the tool can be changed in time to avoid significa...Tool condition monitoring(TCM)is a key technology for intelligent manufacturing.The objective is to monitor the tool operation status and detect tool breakage so that the tool can be changed in time to avoid significant damage to workpieces and reduce manufacturing costs.Recently,an innovative TCM approach based on sensor data modelling and model frequency analysis has been proposed.Different from traditional signal feature-based monitoring,the data from sensors are utilized to build a dynamic process model.Then,the nonlinear output frequency response functions,a concept which extends the linear system frequency response function to the nonlinear case,over the frequency range of the tooth passing frequency of the machining process are extracted to reveal tool health conditions.In order to extend the novel sensor data modelling and model frequency analysis to unsupervised condition monitoring of cutting tools,in the present study,a multivariate control chart is proposed for TCM based on the frequency domain properties of machining processes derived from the innovative sensor data modelling and model frequency analysis.The feature dimension is reduced by principal component analysis first.Then the moving average strategy is exploited to generate monitoring variables and overcome the effects of noises.The milling experiments of titanium alloys are conducted to verify the effectiveness of the proposed approach in detecting excessive flank wear of solid carbide end mills.The results demonstrate the advantages of the new approach over conventional TCM techniques and its potential in industrial applications.展开更多
[Objective] The research aimed to map QTL for the sensitivity of the traits related outcrosssing of Japonica rice to exogenous GA3 and provide theoretical basis for breeding and improving the high-sensitivity sterile ...[Objective] The research aimed to map QTL for the sensitivity of the traits related outcrosssing of Japonica rice to exogenous GA3 and provide theoretical basis for breeding and improving the high-sensitivity sterile line.[Method] Taking Japonica rice Xiushui 79 and C bao and their recombinant inbred line population 260 lines as test materials,the sensitivity of 4 traits related outcrossing to Exogenous GA3 and their QTL mapping were studied by using composite interval mapping..[Result]Three QTLs,which cont...展开更多
基金The study was supported by grant of the research project of science and technology of the Provincial Higher Education Office, the Provincial Health Office and Li Ka-shing's endowment.
文摘Objective Nan'ao County in Guandong Province is a high-risk area of esophageal cancer in Southern China. Of the suspected etiological factors in the environment, N-nitrosamines and their precursors have received the greatest attention. Methods Sixty samples of the diet ingested by the inhabitants were collected and detected for volatile N-nitrosamines and their precursors. Five N-nitrosamines detected by Gas Chromatography-Thermal Energy Analyzer were N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosopiperidine and N-nitrosomethyl-benzylamine. Results The average content of 5 volatile N-nitrosamines in the diet was 312.0 μg/kg (median). The daily intake of the nitrosamines was 286.5 μg/head/day. Only the ability to exogenously synthesize N-nitrosopiperidine was powerful among 5 volatile N-nitrosamines. By a computerized stepwise regression analysis and curve fitting, we studied the correlation among the nitrosamines, the precursors and the major food items in the samples. Conclusion It demonstrated that a relatively high content of volatile N-nitrosamines was present in the diet collected in the area.
文摘The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.
基金supported by National Natural Science Foundation of China(31901964)the Science and Technology Project of Hebei Education Department,China(BJK2022012)+3 种基金the Innovation Ability Training Project for Graduate Student of Hebei Province,China(CXZZBS2023071)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the Key Research and Development Project of Hebei Province,China(21326308D-02-03)the Earmarked Fund for the China Agricultural Research System,China(CARS-27).
文摘Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000400)Innovative Program for Graduate Student of Qingdao Agricultural University(Grant No.QNYCX22045).
文摘Drought(water shortage)can substantially limit the yield and economic value of rose plants(Rosa spp.).Here,we characterized the effect of exogenous calcium(Ca^(2+))on the antioxidant system and photosynthesis-related properties of rose under polyethylene glycol 6000(PEG6000)-induced drought stress.Chlorophyll levels,as well as leaf and root biomass,were significantly reduced by drought;drought also had a major effect on the enzymatic antioxidant system and increased concentrations of reactive oxygen species.Application of exogenous Ca^(2+)increased the net photosynthetic rate and stomatal conductance of leaves,enhanced water-use efficiency,and increased the length and width of stomata following exposure to drought.Organ-specific physiological responses were observed under different concentrations of Ca^(2+).Application of 5 mmol·L^(-1)Ca^(2+)promoted photosynthesis and antioxidant activity in the leaves,and application of 10 mmol·L^(-1)Ca^(2+)promoted antioxidant activity in the roots.Application of exogenous Ca^(2+)greatly enhanced the phenotype and photosynthetic capacity of potted rose plants following exposure to drought stress.Overall,our findings indicate that the application of exogenous Ca^(2+)enhances the drought resistance of roses by promoting physiological adaptation and that it could be used to aid the cultivation of rose plants.
文摘BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.
基金the Doctoral Research Initiation Foundation of Changzhi Medical College(BS202005)。
文摘This study was to investigate the effects of three exogenous substances on chemical constituents of Isatis indigotica leavesand their efficacy in alleviating drought stress, and explore the methods of applying exogenous substances to efficient cultivationof Isatis indigotica. Polyethylene glycol (PEG) was used to simulate drought stress to deal with seeds of Isatis indigotica at thegermination stage (concentration: 0, 10%, 15%, and 20%). Simultaneous operation of exogenous growth regulators [microbialinoculum (MI), γ-aminobutyric acid (GABA) and salicylic acid (SA)] and PEG were implemented in seeds of Isatis indigotica.The effects of drought stress and the mitigation of exogenous substances were observed by statistics of seed germination potential,germination rate, hypocotyl length, and radicle length of each treatment. The effects of exogenous substances on the content ofalkaloids, crude protein and free amino acids in the leaves of Isatis indigotica grown in a greenhouse were determined after sprayingexogenous substances on the plants. The differences of germination potential, germination rate, hypocotyl length, and radicle lengthamong 15% PEG stress treatment, 10% PEG stress treatment and the control were significant (P<0.05). According to the predesignedgermination standard, the seeds did not germinate under 20% PEG stress treatment. When the PEG concentration was 15%, the resultsof seed germination potential and germination rate after adding MI were significantly different from those under stress alone (P<0.05).When exposed to 10% PEG stress, the supplementation of GABA led to a notable increase in radicle length of Isatis indigotica seeds,showing significant differences compared to other three treatments. The application of MI and GABA under 15% PEG stress resultedin a significant increase in the radicle and hypocotyl length of Isatis indigotica seeds compared to other two treatments. The contentof the total alkaloids in leaves of Isatis indigotica was significantly increased after spraying GABA. Meanwhile, the contents of crudeprotein and the total free amino acids were kept constant after spraying exogenous substances. Application of MI and GABA couldalleviate drought stress of Isatis indigotica. The content of the total alkaloids in leaves of Isatis indigotica could significantly increaseafter spraying GABA.
基金supported by the Key-Area Research and Development Program of Guangdong Province[grant numbers 21202107201900005,21202107201900003].
文摘Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.
文摘Phosphorus bioavailability has long been a recurring problem in tropical acid soils. A pot experiment was carried out during three (3) successive rice production cycles at Adiopodoumé to evaluate the response of the NERICA 5 rice accession to various doses of calcium, magnesium and phosphorous. The experiment was conducted using a randomized split-plot design. The interactive effects of calcium carbonate (0, 25, 50 and 75 kg·Ca·ha<sup>-1</sup>) and magnesium sulfate (0, 25, 50 and 75 kg·Mg·ha<sup>-1</sup>) and Togo natural phosphate (0, 25, 50 and 75 kg·P·ha<sup>-1</sup>) were determined at each production cycle. The results showed that single-dose natural phosphate supplementation for three cropping cycles resulted in an average enrichment of around 2 mg·P·kg<sup>-1</sup> after each trial following its continuous dissolution, with an increase in DSP (33.31% to 70.52%). The study revealed one strategy for managing and enhancing native P with cations and another for exogenous P: there would be a synergy of Ca/Mg on native P, whereas an antagonism would characterize the two parameters in phosphate fertilization.
基金the Key Program for International S&T Cooperation Projects of China(2022YFE0130100)Central Public-interest Scientific Institution Basal Research Fund of Chinese Academy of Agricultural Sciences(Y2022GH12).
文摘Background Sustainable strategies for enteric methane(CH_(4))mitigation of dairy cows have been extensively explored to improve production performance and alleviate environmental pressure.The present study aimed to investigate the effects of dietary xylooligosaccharides(XOS)and exogenous enzyme(EXE)supplementation on milk production,nutrient digestibility,enteric CH_(4) emissions,energy utilization efficiency of lactating Jersey dairy cows.Forty-eight lactating cows were randomly assigned to one of 4 treatments:(1)control diet(CON),(2)CON with 25 g/d XOS(XOS),(3)CON with 15 g/d EXE(EXE),and(4)CON with 25 g/d XOS and 15 g/d EXE(XOS+EXE).The 60-d experimental period consisted of a 14-d adaptation period and a 46-d sampling period.The enteric CO_(2)and CH_(4) emissions and O2 consumption were measured using two GreenFeed units,which were further used to determine the energy utilization efficiency of cows.Results Compared with CON,cows fed XOS,EXE or XOS+EXE significantly(P<0.05)increased milk yield,true protein and fat concentration,and energy-corrected milk yield(ECM)/DM intake,which could be reflected by the significant improvement(P<0.05)of dietary NDF and ADF digestibility.The results showed that dietary supplementation of XOS,EXE or XOS+EXE significantly(P<0.05)reduced CH_(4) emission,CH_(4)/milk yield,and CH_(4)/ECM.Furthermore,cows fed XOS demonstrated highest(P<0.05)metabolizable energy intake,milk energy output but lowest(P<0.05)of CH_(4) energy output and CH_(4) energy output as a proportion of gross energy intake compared with the remaining treatments.Conclusions Dietary supplementary of XOS,EXE or combination of XOS and EXE contributed to the improvement of lactation performance,nutrient digestibility,and energy utilization efficiency,as well as reduction of enteric CH_(4) emissions of lactating Jersey cows.This promising mitigation method may need further research to validate its long-term effect and mode of action for dairy cows.
文摘The occurrence of diabetes mellitus(DM)in pancreatitis is being increasingly recognized lately.Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis(AP).The incidence of diabetes after AP varies from 18%to 23%in 3 years and reaches up to 40%over 5 years.The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass,AP-induced autoimmunity,and alterations in the insulin incretin axis.Risk factors associated with increased risk of diabetes includes male sex,recurrent attacks of pancreatitis,presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis.Diagnosis of post-pancreatitis DM(PPDM)is often excluded.Treatment includes a trial of oral antidiabetic drugs in mild diabetes.Often,insulin is required in uncontrolled diabetes.Given the lack of awareness of this metabolic disorder after AP,this review will evaluate current information on epidemiology,risk factors,diagnosis and management of PPDM and identify the knowledge gaps.
基金supported by the National Key Research and Development Program of China(2019YFE0115000).
文摘Background Soybean(Glycine max)meal is one of the important protein sources for fish,but the non-starch polysaccharides(NSP)in soybean meal impair the intestinal barrier function.Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism.Results Nile tilapia(Oreochromis niloticus)(4.09±0.02 g)were fed with two diets including SM(soybean meal)and SMC(soybean meal+3,000 U/kg xylanase)for 8 weeks.We characterized the effects of xylanase on the gut barrier,and the transcriptome analysis was performed to investigate the underlying mechanism.Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide(LPS)in serum.The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2(MUC2)which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase(perk)/activating transcription factor 4(atf4)signaling pathways.Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut.Notably,dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia,and the data verified that sodium butyrate mirrored the beneficial effects of xylanase.Conclusions Collectively,supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia.The present study reveals the mechanism by which xylanase improves the intestinal barrier,and it also provides a theoretical basis for the application of xylanase in aquaculture.
基金supported by the National Natural Science Foundation of China (No.71903030)the Natural Science Foundation of Fujian Province (No.2020J01562)the Funds for Distinguished Young Scientists of Fujian Agriculture and Forestry University (No.XJQ2020S3).
文摘Objective:To determine the impact of major disease epidemics on pharmaceutical manufacturing firms'Research&Development(R&D)investments and economic consequences.Methods:The sample consists of 1582 firm-year observations from 2009 to 2022 in China,of which,26.6%of pharmaceutical companies are involved in the diagnosis and treatment of prevalent diseases.Linear models using R&D investments,patent applications,operating performances and stock returns as dependent variables are constructed separately to examine the response of pharmaceutical companies to disease epidemics and the resulting economic consequences.Results:The prevalence of five major diseases led to a 17.5%increase in the amount of R&D investment and an 87.8%rise in the ratio of R&D investment to total assets by disease-related pharmaceutical companies,compared to unrelated pharmaceutical companies.Further evidence indicated that the patent applications for disease-related firms increased by 44.3%relative to unrelated firms after the epidemics.Though the impacts of the epidemics on firms’operating performances were insignificant in the short term,a major disease epidemic was associated with an increase in stock returns of 67.4%and 44.6%,respectively,as measured by the capital asset pricing model and Fama-French five-factor model.Additional analysis revealed that the impacts of the epidemics on R&D investments and patent applications were more pronounced for non-state-owned enterprises than state-owned enterprises.Conclusions:This study demonstrates that disease-related pharmaceutical firms respond to the disease epidemics through increasing R&D investment.More patent applications and higher market value are the main gains from the firms’increased investments in R&D following the epidemic,rather than the improvements of short-term operating performances.
基金the financial support of Isfahan University of Medical Sciences by grant No.#199180.
文摘The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.
文摘System Identification becomes very crucial in the field of nonlinear and dynamic systems or practical systems.As most practical systems don’t have prior information about the system behaviour thus,mathematical modelling is required.The authors have proposed a stacked Bidirectional Long-Short Term Memory(Bi-LSTM)model to handle the problem of nonlinear dynamic system identification in this paper.The proposed model has the ability of faster learning and accurate modelling as it can be trained in both forward and backward directions.The main advantage of Bi-LSTM over other algorithms is that it processes inputs in two ways:one from the past to the future,and the other from the future to the past.In this proposed model a backward-running Long-Short Term Memory(LSTM)can store information from the future along with application of two hidden states together allows for storing information from the past and future at any moment in time.The proposed model is tested with a recorded speech signal to prove its superiority with the performance being evaluated through Mean Square Error(MSE)and Root Means Square Error(RMSE).The RMSE and MSE performances obtained by the proposed model are found to be 0.0218 and 0.0162 respectively for 500 Epochs.The comparison of results and further analysis illustrates that the proposed model achieves better performance over other models and can obtain higher prediction accuracy along with faster convergence speed.
文摘Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifically focusing on those seeking assistance due to suicide attempts (TS) versus CLP requests for other reasons (non-TS) between the years 2010 and 2020. Additionally, we aim to assess factors associated with suicide attempts. Method: This retrospective controlled study involves a thorough examination of medical records encompassing 3913 patients who received CLP services at the Hospital de Base (HB) and the Children and Maternity Hospital (HCM) of São José do Rio Preto Medical School Foundation (Funfarme) from June 2010 to June 2020. The patient cohort is categorized into two groups: those with requests for SA (n = 677) and those with requests for other reasons. Results: In the SA group, as opposed to the non SA group, statistically significant differences were observed for gender (predominantly female), employment status (employed), marital status (single), and age (younger). Notably, a higher prevalence of psychiatric antecedents (88.7%, n = 555 vs. 73.6% n = 2018) was found in the SA group, indicating a significant association. The frequency of SA requests remained stable over the years. Among the SA group, mood disorders were the most prevalent (39%, n = 372), followed by disorders related to substance use (21.2%, n = 202), and personality disorders (16%, n = 152). A history of previous suicide attempts emerged as a crucial factor for the recurrence of SA (p-value ≤ 0.001). Exogenous intoxication emerged as the most frequently employed method in attempts (79.6%, n = 539), particularly prevalent among patients diagnosed with mood disorders (41%, n = 314). A significant association was observed between the method of attempt and the nosological psychiatric diagnosis (χ<sup>2</sup> = 42.277;p ≤ 0.001). Regarding outcomes, the majority of patients were referred for outpatient follow-up (23%, n = 336) in specialized mental health services or at the Primary Healthcare Unit, highlighting the general hospital’s pivotal role in integrating patients into the broader healthcare network. Conclusion: Variables such as gender (female), age group (young adults), and psychiatric history exhibited stronger associations with suicide attempts compared to the group assisted by CLP for other reasons. Furthermore, a noteworthy correlation between the method employed and the psychiatric diagnosis was identified.
文摘In recent years, a lot of corporate defaults have had an impact on the capital market. How to prevent corporate default risks has become an important topic of concern for the academic community, enterprises and the government. We took China’s A-share listed companies from 2012 to 2018 as a sample, and used the double difference method to analyze the impact of supply-side structural reforms on corporate default risks. We found that supply-side structural reforms have reduced the risk of corporate default, and the inhibitory effect has gradually increased. In the relationship between supply-side structural reforms and corporate default risks, corporate financing capabilities have played an intermediary role. Supply-side structural reforms can improve the company’s endogenous financing capabilities, thereby reducing the risk of corporate default. However, we also found that the mediating effect of a company’s exogenous financing capability is not significant. At the same time, the regression results show that the digital economy can play a regulatory role. It can not only actively regulate the relationship between supply-side structural reforms and corporate default risks, but also mediate the mediating effect of corporate endogenous financing capabilities. The results of this article provide some evidence for the synergy between supply-side structural reforms and the digital economy.
基金the Natural Science Foundation of Hubei Province,China(2021CFB468)Sci-tech Innovation Foundation of Huazhong Agriculture University(2662020LXPY007)National Key Research and Development Program of China(2021YFD1400800).
文摘As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.
文摘Tool condition monitoring(TCM)is a key technology for intelligent manufacturing.The objective is to monitor the tool operation status and detect tool breakage so that the tool can be changed in time to avoid significant damage to workpieces and reduce manufacturing costs.Recently,an innovative TCM approach based on sensor data modelling and model frequency analysis has been proposed.Different from traditional signal feature-based monitoring,the data from sensors are utilized to build a dynamic process model.Then,the nonlinear output frequency response functions,a concept which extends the linear system frequency response function to the nonlinear case,over the frequency range of the tooth passing frequency of the machining process are extracted to reveal tool health conditions.In order to extend the novel sensor data modelling and model frequency analysis to unsupervised condition monitoring of cutting tools,in the present study,a multivariate control chart is proposed for TCM based on the frequency domain properties of machining processes derived from the innovative sensor data modelling and model frequency analysis.The feature dimension is reduced by principal component analysis first.Then the moving average strategy is exploited to generate monitoring variables and overcome the effects of noises.The milling experiments of titanium alloys are conducted to verify the effectiveness of the proposed approach in detecting excessive flank wear of solid carbide end mills.The results demonstrate the advantages of the new approach over conventional TCM techniques and its potential in industrial applications.
基金Supported by Universities Discipline Innovation and Intellectual Introduction Program Funded Projects(B08025)Key Projects of Basic Scienceand Technology Platform of Ministry of Education(505005)Ministry ofAgriculture Project"948"(2006-G8(4)-31-1)~~
文摘[Objective] The research aimed to map QTL for the sensitivity of the traits related outcrosssing of Japonica rice to exogenous GA3 and provide theoretical basis for breeding and improving the high-sensitivity sterile line.[Method] Taking Japonica rice Xiushui 79 and C bao and their recombinant inbred line population 260 lines as test materials,the sensitivity of 4 traits related outcrossing to Exogenous GA3 and their QTL mapping were studied by using composite interval mapping..[Result]Three QTLs,which cont...