Introduction: MRI is a rapidly growing technique with more and more indica-tions and requests in the Republic of Guinea. Its correct prescription is a guar-antee for the satisfaction of the actors, both prescribers, r...Introduction: MRI is a rapidly growing technique with more and more indica-tions and requests in the Republic of Guinea. Its correct prescription is a guar-antee for the satisfaction of the actors, both prescribers, radiologists and pa-tients. The main objective of this study was to evaluate the compliance of MRI examination requests at the Diagnostic Center of the National Social Se-curity Fund (CNSS) in Conakry. Material and Methods: This was a descriptive cross-sectional study of MRI prescription forms sent to the MRI unit of the CNSS Diagnostic Center from February 1 to May 1, 2021. The 8 compliance criteria established by the French High Authority for Health were used to evaluate the compliance of the examination requests. Results: A total of 7003 examination forms were sent to the facility, including 7% (n = 468) of MRIs. 56.2% of MRI requests were performed by specialists. We observed an overall compliance of 10%. Administrative and clinical compliance were missing in 24% and 38%, respectively. More specifically, the purpose of the examination was not mentioned in 60%, followed by the requesting department in 48.1% and the patient’s age in 35.1%. Conclusion: This study allowed us to highlight the gaps in establishing MRI requests. It would be important to organize an awareness campaign for prescribers on the usefulness of correctly filling an MRI request and to design templates to be filled out by prescribers.展开更多
Aim: To study the functional dyspepsia in chronic hemodialysis patients of CNHU-HKM of Cotonou. Methods: This descriptive, analytical and cross-sectional study ran from 1 September 2013 to 28 February 2014 in the Univ...Aim: To study the functional dyspepsia in chronic hemodialysis patients of CNHU-HKM of Cotonou. Methods: This descriptive, analytical and cross-sectional study ran from 1 September 2013 to 28 February 2014 in the University Clinic of Nephrology Dialysis of CNHU-HKM of Cotonou. It included all chronic renal failure patients on hemodialysis for at least 9 months prior to the survey. After identifying the patients with upper gastrointestinal disorders, we had submitted to clinical Rome III criteria for functional dyspepsia. Upper endoscopy was performed in patients with clinical criteria of functional dyspepsia. Clinical factors associated, paraclinical and therapeutic were sought by logistic regression in univariate analysis. Data were analyzed using EPI DATA version 3.1. Results: 1) One hundred and thirty-one haemodialysis patients had participated in the study (sex ratio: 1.5, average age 49.6 ± 12.4 years). 2) The prevalence was 71.8% for upper gastrointestinal disorders, 64.9% for dyspeptic syndrome and 1.5% for functional dyspepsia. 3) They were associated to clinical criteria of functional dyspepsia of Roma III, the presence of high blood pressure, hypocalcaemia, treatment with calcic inhibitors and iron supplementation. Conclusion: Functional dyspepsia is uncommon in hemodialysis. The search of an organic cause is imperative for every dyspepsia.展开更多
<strong>Introduction:</strong><span style="font-family:Verdana;"> Cardiovascular disease has become a major concern for the nephrologist as it is the leading cause of morbidity and mortalit...<strong>Introduction:</strong><span style="font-family:Verdana;"> Cardiovascular disease has become a major concern for the nephrologist as it is the leading cause of morbidity and mortality in patients with chronic kidney disease, and affects all stages of the disease, including the earliest stages of the disease. The goal of this work was to determine the frequency of cardiovascular complications during chronic kidney failure.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Patients and methods:</span></b><span style="font-family:Verdana;"> This was a six-month, descriptive cross-sectional study from March 01 to August 31, 2018. It covered all patients with chronic kidney disease hospitalized in the ward during the study period. Included were all chronic kidney failure patients with at least one cardiac and/or vascular complication diagnosed either on clinical examination, and/or paraclinical examination (Electrocardiogram or cardiac ultrasound, vessel echodoppler, scan)</span><span style="font-family:Verdana;">.</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Res</span></b></span><b><span style="font-family:Verdana;">ults:</span></b><span style="font-family:Verdana;"> During the study period, 84 out of 378 patients or 22.22% had at least one cardiovascular complication. Cardiovascular complications were hypertrophy of the left ventricle with 49/84 (44 at Electrocardiogram and 5 at cardiac echodoppler), valvulopathy with 33.33%, stroke with 50% of cases, obliterating arterial disease of the lower limbs 25%, hypokinetic dilated cardiomyopathy with 9/36 cases and pericarditis with 2/36.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Cardiovascular complications affect both sexes and all ages. They were dominated by enlarged left ventricle, valvulopathy and dilated cardiomyopathy.</span>展开更多
Introduction: Miliary tuberculosis (MT) is a rare form of tuberculosis (TB) and it is a major public health problem in our countries with limited resources. Materials and Methods: It is a retrospective and descriptive...Introduction: Miliary tuberculosis (MT) is a rare form of tuberculosis (TB) and it is a major public health problem in our countries with limited resources. Materials and Methods: It is a retrospective and descriptive study that started from 1st January 2018 to 31 December 2020 at the pneumo-phtisiology service of the CHU-RN of N’Djamena., All records of patients aged at least 15 years treated for miliary tuberculosis confirmed by X-ray chest were included in our study. Results: The prevalence of TD was 1.5% (n = 103) of all TB diagnosed in the service. The sex ratio was 1.34. The average age was 37.7 years with extremes ranging from 19 to 80 years. A low social economic level was found in 75.7%. The principal comorbidity found in this study was HIV with the prevalence of (22.3%). The general signs were dominated by deterioration of general condition (96.1%) and fever (91.3%). The main symptoms were cough (85.4%) and dyspnea (52.4%). The radiology of chest found a homogeneous dissemination and symmetrical in both lung fields in 100% of cases. Our study reported that 14 (13.6%) of death cases were found among patients. Conclusion: TM is a severe form of TB;it affects a young population in our context. Mortality remains high with prevalence of 13.6% of cases. Early management would improve the prognosis.展开更多
THE Chinese attitude to age and aging is quite different from that in the West. The age of 60 in China marks the start of a brand new life, a belief based on the Chinese “horoscope,” which encompasses five astrologi...THE Chinese attitude to age and aging is quite different from that in the West. The age of 60 in China marks the start of a brand new life, a belief based on the Chinese “horoscope,” which encompasses five astrological cycles of twelve years each.展开更多
The development of women’s rights is a specific field in modern national governance.The essence of women-related issues in modern times lies in the political and legal systems based on gender inequality and the unequ...The development of women’s rights is a specific field in modern national governance.The essence of women-related issues in modern times lies in the political and legal systems based on gender inequality and the unequal male-female relationship established by male chauvinism,which has further created domination over and prejudice against women.Since the founding of the New China,especially after the launch of reform and opening-up,the Communist party of China and the state have attached great importance to the protection of gender equality,bringing about the continued improvement of the protection of women’s rights.However,due to various economic and social barriers,there is still a long way to go to achieve full gender equality.To understand the issue of women’s rights from the perspective of national governance and apply the concept of modern national governance to the protection of women’s rights,it is imperative to pay great attention to the substantive equality concept in the protection of women’s right during the national governance process,take empowering women as an important approach,raise women’s gender equality awareness,and recognize,grant,enhance and guarantee women’s individual rights.展开更多
Most urological conditions are represented by male disorders. Analyzing certain epidemiological aspects of female urological disorders at the National University Teaching Hospital of Cotnou, will allow us objectively ...Most urological conditions are represented by male disorders. Analyzing certain epidemiological aspects of female urological disorders at the National University Teaching Hospital of Cotnou, will allow us objectively to have reliable data to optimize the urological management of women. Patients and Methods: This was a retrospective, analytical and descriptive study that was conducted at the CNHU-HKM over a 10-year period from January 2008 to December 2017 on the epidemiological aspects of female urological diseases from the study of patient records. The variable studied was: the age, the profession, the year of admission, the organ affected, and the type of pathology. The confidentiality of the data has been ensured. Results: Female urological disorders over 10 years accounted for 9.62% of all patients received in Urology Department. The age group greater than 50 years was the most common at 31.34%. Traders and housewives were the most numerous (39.93% and 14.55%). Bladder diseases were the most frequent (51.50), dominated by vesico-vaginal fistulas (29.85%). In addition to fistulas, tumoral affections were most prevalent at 27.99% followed by infectious diseases at 8.21%. The lithiasic affections were infrequent at 6.72%. Conclusion: Female urological conditions are infrequent but not negligible, dominated by vesico-vaginal fistulas and tumors in the context of developing countries. The specific evaluation of each pathology group can help optimize management.展开更多
In Benin Republic, few data are available on the prevalence and determinants of arterial hypertension (AH) in people living with the human immunodeficiency virus (PLWHA). The present study was conducted in two outpati...In Benin Republic, few data are available on the prevalence and determinants of arterial hypertension (AH) in people living with the human immunodeficiency virus (PLWHA). The present study was conducted in two outpatient treatment centers for PLWHA in Cotonou and was conducted from June 19 to July 04, 2019 with 314 PLWHA. We performed descriptive statistics and logistic regression for the estimates. The prevalence of high blood pressure (HBP) among PLWHA was 41.4% [CI (95%): (35.9 - 47)]. In univariate analysis: age, smoking, alcoholism, physical inactivity, family history of hypertension, personal history of diabetes, obesity, and total and LDL (low density lipoprotein) hypercholesterolemia were significantly associated with HBP. No association was found with duration of HIV (human immunodeficiency virus) infection, time to ARV (antiretrovirals) exposure, and treatment regimen. In multivariate analysis, age, sex, smoking, family history of hypertension, and total hypercholesterolemia remained associated with HBP. In conclusion, the prevalence of HBP in PLWHA was very high compared with the results in the general population, and the same risk factors described in the general population were found but with a more marked hypertense potential.展开更多
Coronavirus Disease-19 (COVID-19) manifests itself by a respiratory attack that can go from mild to severe forms. The factors favoring the severe forms are age, arterial hypertension, diabetes mellitus, and cancer. We...Coronavirus Disease-19 (COVID-19) manifests itself by a respiratory attack that can go from mild to severe forms. The factors favoring the severe forms are age, arterial hypertension, diabetes mellitus, and cancer. We report 4 cases of COVID-19 on cancer, followed in the Department of Internal Medicine and Medical Oncology of National Teaching Hospital Center Hubert Kougougou Maga (NTHC-HKM). <strong>Case 1:</strong> A hypertensive 65-year-old female patient with a severe form of COVID-19 on an FIGO (International Federation of Gynecology and Obstetrics) IVB endometrioid adenocarcinoma with pulmonary metastasis: unfavorable evolution under treatment with death. <strong>Case 2:</strong> A 56-year-old hypertensive patient with severe COVID-19 with pulmonary metastatic recurrence of SBRIII, HER2 positive invasive ductal carcinoma of the left breast: favorable evolution with cure of COVID-19, subsequent death related to active tumor. <strong>Case 3:</strong> A 37-year-old patient with a moderate form of COVID-19 with hepatocellular carcinoma complicating post alcoholic cirrhosis, CHILD C: favorable evolution with cure of COVID-19, patient lost to follow-up. <strong>Case 4:</strong> A 56-year-old patient, hypertensive, type II diabetic, presenting a severe form of COVID-19 on a field of ovarian serous adenocarcinoma of high grade FIGO IV A with pleuropulmonary metastasis: favorable evolution with cure of COVID-19, subsequent stroke, patient followed in palliative home hospitalization. The diagnosis of COVID-19 in cancer with pulmonary metastases is difficult. The pulmonary location of tumors seems to be a factor favoring severe forms.展开更多
The“Outline for High-Quality Development of Meteorology(2022-2035)”was published by the State Council of the People’s Republic of China in April 2022(1).This publication highlights the essential role of meteorologi...The“Outline for High-Quality Development of Meteorology(2022-2035)”was published by the State Council of the People’s Republic of China in April 2022(1).This publication highlights the essential role of meteorological disaster warnings,particularly cold spell warnings,in preventing and mitigating disasters.The outline also sets forth stricter expectations for enhancing the overall capacity of society in terms of meteorological disaster preparedness and response.展开更多
CONTINUED TENSIONS IN RELATIONS AMONG THE MAJOR COUNTRIES,In 2023,the international and regional security situation underwent complex and profound changes,with security threats continuing to diversify and the use of f...CONTINUED TENSIONS IN RELATIONS AMONG THE MAJOR COUNTRIES,In 2023,the international and regional security situation underwent complex and profound changes,with security threats continuing to diversify and the use of force to settle disputes increasing.Conflicts and disputes in Eastern Europe,the Middle East,Africa and other regions are recurring and difficult to quell,and instability and uncertainty on a global scale have increased.Relations among major countries continue to be tense due to factors such as the regional turmoil and intensification of strategic competition among major countries by the United States.In its National Security Strategy released in 2022,the Biden administration characterized China as“the only competitor with both strategic intent and a growing capacity to reshape the international order”,and in its National Defense Strategy released that year,it further positioned China as“the most important strategic competitor”.展开更多
Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vacc...Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vaccines and other systemic issues.The Innovation Laboratory for Vaccine Delivery Research(VaxLab),supported by the Bill&Melinda Gates Foundation and established in 2021 at Duke Kunshan University,focuses on enhancing China’s NIP through research and policy advocacy.This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda.Key findings The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage,particularly for non-NIP vaccines like human papillomavirus vaccine(HPV),pneumococcal conjugate vaccine(PCV),Haemophilus influenzae type b vaccine(Hib),and rotavirus vaccines.Key findings include:(i)The COVID-19 vaccination campaign demonstrated China’s capacity for rapid,large-scale immunization efforts,suggesting potential for broader vaccine coverage improvements;(ii)Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access;(iii)The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles;(iv)Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage,especially for remote areas and marginalized populations;(v)Original studies emphasize the influence of caregivers’knowledge,health workers’financial incentives,and concerns about vaccine efficacy on immunization rates;(vi)Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support.Conclusion The articles emphasize the need for government leadership,strategic policymaking,and public awareness to enhance vaccine coverage and equity.The VaxLab will continue strengthening China’s NIP by focusing on vaccine financing,emphasizing diversity,equity,and inclusion,and improving maternal vaccination coverage.Research will extend to Southeast Asian and Western Pacific regions,especially in middle-income countries facing challenges in vaccine financing and delivery.The collective efforts outlined in this collection show a commitment to evolving and adapting immunization strategies to meet global health goals and to provide equitable access to vaccines for all.展开更多
Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary ...Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.展开更多
The mining sector historically drove the global economy but at the expense of severe environmental and health repercussions,posing sustainability challenges[1]-[3].Recent advancements on artificial intelligence(AI)are...The mining sector historically drove the global economy but at the expense of severe environmental and health repercussions,posing sustainability challenges[1]-[3].Recent advancements on artificial intelligence(AI)are revolutionizing mining through robotic and data-driven innovations[4]-[7].While AI offers mining industry advantages,it is crucial to acknowledge the potential risks associated with its widespread use.Over-reliance on AI may lead to a loss of human control over mining operations in the future,resulting in unpredictable consequences.展开更多
To the Editor:The epidemic of diabetes mellitus poses a major public health threat worldwide.In the United States,the prevalence of type 2 diabetes(T2D)affected 13.9%of adults and would continually increase.[1]Diet is...To the Editor:The epidemic of diabetes mellitus poses a major public health threat worldwide.In the United States,the prevalence of type 2 diabetes(T2D)affected 13.9%of adults and would continually increase.[1]Diet is one of the major lifestyle risk factors for T2D,in which dietary iron has generated substantial interest over the past 20 years.[2,3]It is to be noted that dietary vitamins A,B2,B6,E,C,and folic acid were reported to affect the absorption or oxidation of iron in body.[4]However,whether these dietary vitamins play a role in iron-related T2D remains unclear.Further research revealing the holistic role of these dietary vitamins in the association between iron and T2D is needed,which would provide important guidance for decreasing the risk of iron-related T2D.The present study aimed to examine the association between dietary iron and T2D in the National Health and Nutrition Examination Survey(NHANES)and evaluate whether holistic dietary vitamins affect this relationship.展开更多
The nonlinear variation of wave is commonly seen in nearshore area,and the resulting seabed response and liquefaction are of high concern to coastal engineers.In this study,an analytical formula considering the nonlin...The nonlinear variation of wave is commonly seen in nearshore area,and the resulting seabed response and liquefaction are of high concern to coastal engineers.In this study,an analytical formula considering the nonlinear wave skewness and asymmetry is adopted to provide wave pressure on the seabed surface.The liquefaction depth attenuation coefficient and width growth coefficient are defined to quantitatively characterize the nonlinear effect of wave on seabed liquefaction.Based on the 2D full dynamic model of wave-induced seabed response,a detailed parametric study is carried out in order to evaluate the influence of the nonlinear variation of wave loadings on seabed liquefaction.Further,new empirical prediction formulas are proposed to fast predict the maximum liquefaction under nonlinear wave.Results indicate that(1)Due to the influence of wave nonlinearity,the vertical transmission of negative pore water pressure in the seabed is hindered,and therefore,the amplitude decreases significantly.(2)In general,with the increase of wave nonlinearity,the liquefaction depth of seabed decreases gradually.Especially under asymmetric and skewed wave loading,the attenuation of maximum seabed liquefaction depth is the most significant among all the nonlinear wave conditions.However,highly skewed wave can cause the liquefaction depth of seabed greater than that under linear wave.(3)The asymmetry of wave pressure leads to the increase of liquefaction width,whereas the influence of skewedness is not significant.(4)Compared with the nonlinear waveform,seabed liquefaction is more sensitive to the variation of nonlinear degree of wave loading.展开更多
In this study, we analyse the climate variability in the Upper Benue basin and assess its potential impact on the hydrology regime under two different greenhouse gas emission scenarios. The hydrological regime of the ...In this study, we analyse the climate variability in the Upper Benue basin and assess its potential impact on the hydrology regime under two different greenhouse gas emission scenarios. The hydrological regime of the basin is more vulnerable to climate variability, especially precipitation and temperature. Observed hydroclimatic data (1950-2015) was analysed using a statistical approach. The potential impact of future climate change on the hydrological regime is quantified using the GR2M model and two climate models: HadGEM2-ES and MIROC5 from CMIP5 under RCP 4.5 and RCP 8.5 greenhouse gas emission scenarios. The main result shows that precipitation varies significantly according to the geographical location and time in the Upper Benue basin. The trend analysis of climatic parameters shows a decrease in annual average precipitation across the study area at a rate of -0.568 mm/year which represents about 37 mm/year over the time 1950-2015 compared to the 1961-1990 reference period. An increase of 0.7°C in mean temperature and 14% of PET are also observed according to the same reference period. The two climate models predict a warming of the basin of about 2°C for both RCP 4.5 and 8.5 scenarios and an increase in precipitation between 1% and 10% between 2015 and 2100. Similarly, the average annual flow is projected to increase by about +2% to +10% in the future for both RCP 4.5 and 8.5 scenarios between 2015 and 2100. Therefore, it is primordial to develop adaptation and mitigation measures to manage efficiently the availability of water resources.展开更多
Post-disaster recovery and reconstruction provide an effective way to reduce the disaster vulnerability of, and promote leapfrog development in, an affected area. To date, studies that have used administrative boundar...Post-disaster recovery and reconstruction provide an effective way to reduce the disaster vulnerability of, and promote leapfrog development in, an affected area. To date, studies that have used administrative boundaries to investigate the reconstruction of settlement space have not been able to clearly define the real boundaries of land use changes or quantify the degree of response to the ‘Build-Back-Better’ initiative, and have lacked any consideration of the fourth reconstruction stage–development period(10 years). This study constructed a mountain settlement niche and analyzed the characteristics, spatial reconstruction, and drivers of rural settlements during 2009–2019 in the upper reaches of the Minjiang River, southwest China. The results showed the following:(1) Natural factors were the basis for the formation and development of mountain settlement niches. The scale of the settlement niche and its land use structure depended on the physical geography features and the ethnic farming and grazing traditions. The settlement niche provided a realistic boundary for the spatial reconstruction.(2) The layout of residential land around cropland was the common feature of the mountain settlement niche. Of all the land use types, the roads and rural residential lands showed the most change over the 10 years;13,860 residential patches increased in size and 4,742 patches were abandoned.(3) The area of orchards, planted to reconstruct the economy in the mountains, increased by nearly 2.5 times.(4) Collapses, landslides, and debris flow disasters and the ecological red line influenced the spatial reconstruction. While the main focus of post-disaster recovery is spatial reconstruction, initiatives should include economic and spiritual recovery, and should also achieve sustainable development of the region.展开更多
The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models,particularly in their application in advanced therapy medicinal products(ATMPs).In this review,we examine ...The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models,particularly in their application in advanced therapy medicinal products(ATMPs).In this review,we examine the multifaceted impact of these developments,emphasizing the potential of stem cell models to enhance the sophistication of ATMPs and to offer alternatives to animal testing.Stem cell-derived tissues are particularly promising because they can reshape the preclinical landscape by providing more physiologically relevant and ethically sound platforms for drug screening and disease modelling.We also discuss the critical challenges of reproducibility and accuracy in measurements to ensure the integrity and utility of stem cell models in research and application.Moreover,this review highlights the imperative of stem cell models to align with regulatory standards,ensuring using stem cells in ATMPs translates into safe and effective clinical therapies.With regulatory approval serving as a gateway to clinical adoption,the collaborative efforts between scientists and regulators are vital for the progression of stem cell applications from bench to bedside.We advocate for a balanced approach that nurtures innovation within the framework of rigorous validation and regulatory compliance,ensuring that stem cell-base solutions are maximized to promote public trust and patient health in ATMPs.展开更多
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
文摘Introduction: MRI is a rapidly growing technique with more and more indica-tions and requests in the Republic of Guinea. Its correct prescription is a guar-antee for the satisfaction of the actors, both prescribers, radiologists and pa-tients. The main objective of this study was to evaluate the compliance of MRI examination requests at the Diagnostic Center of the National Social Se-curity Fund (CNSS) in Conakry. Material and Methods: This was a descriptive cross-sectional study of MRI prescription forms sent to the MRI unit of the CNSS Diagnostic Center from February 1 to May 1, 2021. The 8 compliance criteria established by the French High Authority for Health were used to evaluate the compliance of the examination requests. Results: A total of 7003 examination forms were sent to the facility, including 7% (n = 468) of MRIs. 56.2% of MRI requests were performed by specialists. We observed an overall compliance of 10%. Administrative and clinical compliance were missing in 24% and 38%, respectively. More specifically, the purpose of the examination was not mentioned in 60%, followed by the requesting department in 48.1% and the patient’s age in 35.1%. Conclusion: This study allowed us to highlight the gaps in establishing MRI requests. It would be important to organize an awareness campaign for prescribers on the usefulness of correctly filling an MRI request and to design templates to be filled out by prescribers.
文摘Aim: To study the functional dyspepsia in chronic hemodialysis patients of CNHU-HKM of Cotonou. Methods: This descriptive, analytical and cross-sectional study ran from 1 September 2013 to 28 February 2014 in the University Clinic of Nephrology Dialysis of CNHU-HKM of Cotonou. It included all chronic renal failure patients on hemodialysis for at least 9 months prior to the survey. After identifying the patients with upper gastrointestinal disorders, we had submitted to clinical Rome III criteria for functional dyspepsia. Upper endoscopy was performed in patients with clinical criteria of functional dyspepsia. Clinical factors associated, paraclinical and therapeutic were sought by logistic regression in univariate analysis. Data were analyzed using EPI DATA version 3.1. Results: 1) One hundred and thirty-one haemodialysis patients had participated in the study (sex ratio: 1.5, average age 49.6 ± 12.4 years). 2) The prevalence was 71.8% for upper gastrointestinal disorders, 64.9% for dyspeptic syndrome and 1.5% for functional dyspepsia. 3) They were associated to clinical criteria of functional dyspepsia of Roma III, the presence of high blood pressure, hypocalcaemia, treatment with calcic inhibitors and iron supplementation. Conclusion: Functional dyspepsia is uncommon in hemodialysis. The search of an organic cause is imperative for every dyspepsia.
文摘<strong>Introduction:</strong><span style="font-family:Verdana;"> Cardiovascular disease has become a major concern for the nephrologist as it is the leading cause of morbidity and mortality in patients with chronic kidney disease, and affects all stages of the disease, including the earliest stages of the disease. The goal of this work was to determine the frequency of cardiovascular complications during chronic kidney failure.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Patients and methods:</span></b><span style="font-family:Verdana;"> This was a six-month, descriptive cross-sectional study from March 01 to August 31, 2018. It covered all patients with chronic kidney disease hospitalized in the ward during the study period. Included were all chronic kidney failure patients with at least one cardiac and/or vascular complication diagnosed either on clinical examination, and/or paraclinical examination (Electrocardiogram or cardiac ultrasound, vessel echodoppler, scan)</span><span style="font-family:Verdana;">.</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Res</span></b></span><b><span style="font-family:Verdana;">ults:</span></b><span style="font-family:Verdana;"> During the study period, 84 out of 378 patients or 22.22% had at least one cardiovascular complication. Cardiovascular complications were hypertrophy of the left ventricle with 49/84 (44 at Electrocardiogram and 5 at cardiac echodoppler), valvulopathy with 33.33%, stroke with 50% of cases, obliterating arterial disease of the lower limbs 25%, hypokinetic dilated cardiomyopathy with 9/36 cases and pericarditis with 2/36.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Cardiovascular complications affect both sexes and all ages. They were dominated by enlarged left ventricle, valvulopathy and dilated cardiomyopathy.</span>
文摘Introduction: Miliary tuberculosis (MT) is a rare form of tuberculosis (TB) and it is a major public health problem in our countries with limited resources. Materials and Methods: It is a retrospective and descriptive study that started from 1st January 2018 to 31 December 2020 at the pneumo-phtisiology service of the CHU-RN of N’Djamena., All records of patients aged at least 15 years treated for miliary tuberculosis confirmed by X-ray chest were included in our study. Results: The prevalence of TD was 1.5% (n = 103) of all TB diagnosed in the service. The sex ratio was 1.34. The average age was 37.7 years with extremes ranging from 19 to 80 years. A low social economic level was found in 75.7%. The principal comorbidity found in this study was HIV with the prevalence of (22.3%). The general signs were dominated by deterioration of general condition (96.1%) and fever (91.3%). The main symptoms were cough (85.4%) and dyspnea (52.4%). The radiology of chest found a homogeneous dissemination and symmetrical in both lung fields in 100% of cases. Our study reported that 14 (13.6%) of death cases were found among patients. Conclusion: TM is a severe form of TB;it affects a young population in our context. Mortality remains high with prevalence of 13.6% of cases. Early management would improve the prognosis.
文摘THE Chinese attitude to age and aging is quite different from that in the West. The age of 60 in China marks the start of a brand new life, a belief based on the Chinese “horoscope,” which encompasses five astrological cycles of twelve years each.
基金funded by the provincial-level joint project of the School of Marxism,Fudan University:“The Origin of Family,Private Ownership and the State:Study on Textual Logics and Ideological Implication”(Project No.:XWH6064203).
文摘The development of women’s rights is a specific field in modern national governance.The essence of women-related issues in modern times lies in the political and legal systems based on gender inequality and the unequal male-female relationship established by male chauvinism,which has further created domination over and prejudice against women.Since the founding of the New China,especially after the launch of reform and opening-up,the Communist party of China and the state have attached great importance to the protection of gender equality,bringing about the continued improvement of the protection of women’s rights.However,due to various economic and social barriers,there is still a long way to go to achieve full gender equality.To understand the issue of women’s rights from the perspective of national governance and apply the concept of modern national governance to the protection of women’s rights,it is imperative to pay great attention to the substantive equality concept in the protection of women’s right during the national governance process,take empowering women as an important approach,raise women’s gender equality awareness,and recognize,grant,enhance and guarantee women’s individual rights.
文摘Most urological conditions are represented by male disorders. Analyzing certain epidemiological aspects of female urological disorders at the National University Teaching Hospital of Cotnou, will allow us objectively to have reliable data to optimize the urological management of women. Patients and Methods: This was a retrospective, analytical and descriptive study that was conducted at the CNHU-HKM over a 10-year period from January 2008 to December 2017 on the epidemiological aspects of female urological diseases from the study of patient records. The variable studied was: the age, the profession, the year of admission, the organ affected, and the type of pathology. The confidentiality of the data has been ensured. Results: Female urological disorders over 10 years accounted for 9.62% of all patients received in Urology Department. The age group greater than 50 years was the most common at 31.34%. Traders and housewives were the most numerous (39.93% and 14.55%). Bladder diseases were the most frequent (51.50), dominated by vesico-vaginal fistulas (29.85%). In addition to fistulas, tumoral affections were most prevalent at 27.99% followed by infectious diseases at 8.21%. The lithiasic affections were infrequent at 6.72%. Conclusion: Female urological conditions are infrequent but not negligible, dominated by vesico-vaginal fistulas and tumors in the context of developing countries. The specific evaluation of each pathology group can help optimize management.
文摘In Benin Republic, few data are available on the prevalence and determinants of arterial hypertension (AH) in people living with the human immunodeficiency virus (PLWHA). The present study was conducted in two outpatient treatment centers for PLWHA in Cotonou and was conducted from June 19 to July 04, 2019 with 314 PLWHA. We performed descriptive statistics and logistic regression for the estimates. The prevalence of high blood pressure (HBP) among PLWHA was 41.4% [CI (95%): (35.9 - 47)]. In univariate analysis: age, smoking, alcoholism, physical inactivity, family history of hypertension, personal history of diabetes, obesity, and total and LDL (low density lipoprotein) hypercholesterolemia were significantly associated with HBP. No association was found with duration of HIV (human immunodeficiency virus) infection, time to ARV (antiretrovirals) exposure, and treatment regimen. In multivariate analysis, age, sex, smoking, family history of hypertension, and total hypercholesterolemia remained associated with HBP. In conclusion, the prevalence of HBP in PLWHA was very high compared with the results in the general population, and the same risk factors described in the general population were found but with a more marked hypertense potential.
文摘Coronavirus Disease-19 (COVID-19) manifests itself by a respiratory attack that can go from mild to severe forms. The factors favoring the severe forms are age, arterial hypertension, diabetes mellitus, and cancer. We report 4 cases of COVID-19 on cancer, followed in the Department of Internal Medicine and Medical Oncology of National Teaching Hospital Center Hubert Kougougou Maga (NTHC-HKM). <strong>Case 1:</strong> A hypertensive 65-year-old female patient with a severe form of COVID-19 on an FIGO (International Federation of Gynecology and Obstetrics) IVB endometrioid adenocarcinoma with pulmonary metastasis: unfavorable evolution under treatment with death. <strong>Case 2:</strong> A 56-year-old hypertensive patient with severe COVID-19 with pulmonary metastatic recurrence of SBRIII, HER2 positive invasive ductal carcinoma of the left breast: favorable evolution with cure of COVID-19, subsequent death related to active tumor. <strong>Case 3:</strong> A 37-year-old patient with a moderate form of COVID-19 with hepatocellular carcinoma complicating post alcoholic cirrhosis, CHILD C: favorable evolution with cure of COVID-19, patient lost to follow-up. <strong>Case 4:</strong> A 56-year-old patient, hypertensive, type II diabetic, presenting a severe form of COVID-19 on a field of ovarian serous adenocarcinoma of high grade FIGO IV A with pleuropulmonary metastasis: favorable evolution with cure of COVID-19, subsequent stroke, patient followed in palliative home hospitalization. The diagnosis of COVID-19 in cancer with pulmonary metastases is difficult. The pulmonary location of tumors seems to be a factor favoring severe forms.
文摘The“Outline for High-Quality Development of Meteorology(2022-2035)”was published by the State Council of the People’s Republic of China in April 2022(1).This publication highlights the essential role of meteorological disaster warnings,particularly cold spell warnings,in preventing and mitigating disasters.The outline also sets forth stricter expectations for enhancing the overall capacity of society in terms of meteorological disaster preparedness and response.
文摘CONTINUED TENSIONS IN RELATIONS AMONG THE MAJOR COUNTRIES,In 2023,the international and regional security situation underwent complex and profound changes,with security threats continuing to diversify and the use of force to settle disputes increasing.Conflicts and disputes in Eastern Europe,the Middle East,Africa and other regions are recurring and difficult to quell,and instability and uncertainty on a global scale have increased.Relations among major countries continue to be tense due to factors such as the regional turmoil and intensification of strategic competition among major countries by the United States.In its National Security Strategy released in 2022,the Biden administration characterized China as“the only competitor with both strategic intent and a growing capacity to reshape the international order”,and in its National Defense Strategy released that year,it further positioned China as“the most important strategic competitor”.
文摘Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vaccines and other systemic issues.The Innovation Laboratory for Vaccine Delivery Research(VaxLab),supported by the Bill&Melinda Gates Foundation and established in 2021 at Duke Kunshan University,focuses on enhancing China’s NIP through research and policy advocacy.This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda.Key findings The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage,particularly for non-NIP vaccines like human papillomavirus vaccine(HPV),pneumococcal conjugate vaccine(PCV),Haemophilus influenzae type b vaccine(Hib),and rotavirus vaccines.Key findings include:(i)The COVID-19 vaccination campaign demonstrated China’s capacity for rapid,large-scale immunization efforts,suggesting potential for broader vaccine coverage improvements;(ii)Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access;(iii)The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles;(iv)Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage,especially for remote areas and marginalized populations;(v)Original studies emphasize the influence of caregivers’knowledge,health workers’financial incentives,and concerns about vaccine efficacy on immunization rates;(vi)Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support.Conclusion The articles emphasize the need for government leadership,strategic policymaking,and public awareness to enhance vaccine coverage and equity.The VaxLab will continue strengthening China’s NIP by focusing on vaccine financing,emphasizing diversity,equity,and inclusion,and improving maternal vaccination coverage.Research will extend to Southeast Asian and Western Pacific regions,especially in middle-income countries facing challenges in vaccine financing and delivery.The collective efforts outlined in this collection show a commitment to evolving and adapting immunization strategies to meet global health goals and to provide equitable access to vaccines for all.
基金supported by the National Nature Science Foundation of China,the National Key Research and Development Program of China(302001109,2016YFD0300508,2017YFD0301602,2018YFD0301105)the Fujian and Taiwan Cultivation Resources Development and Green Cultivation Coordination Innovation Center,China(Fujian 2011 Project,2015-75)the Natural Science Foundation of Fujian Province,China(2022J01142)。
文摘Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.
文摘The mining sector historically drove the global economy but at the expense of severe environmental and health repercussions,posing sustainability challenges[1]-[3].Recent advancements on artificial intelligence(AI)are revolutionizing mining through robotic and data-driven innovations[4]-[7].While AI offers mining industry advantages,it is crucial to acknowledge the potential risks associated with its widespread use.Over-reliance on AI may lead to a loss of human control over mining operations in the future,resulting in unpredictable consequences.
基金supported by grants from the National Natural Science Foundation of China(Nos.82073536 and 81573134)the National Natural Science Foundation of Guangxi(No.2022GXNSFAA035634)
文摘To the Editor:The epidemic of diabetes mellitus poses a major public health threat worldwide.In the United States,the prevalence of type 2 diabetes(T2D)affected 13.9%of adults and would continually increase.[1]Diet is one of the major lifestyle risk factors for T2D,in which dietary iron has generated substantial interest over the past 20 years.[2,3]It is to be noted that dietary vitamins A,B2,B6,E,C,and folic acid were reported to affect the absorption or oxidation of iron in body.[4]However,whether these dietary vitamins play a role in iron-related T2D remains unclear.Further research revealing the holistic role of these dietary vitamins in the association between iron and T2D is needed,which would provide important guidance for decreasing the risk of iron-related T2D.The present study aimed to examine the association between dietary iron and T2D in the National Health and Nutrition Examination Survey(NHANES)and evaluate whether holistic dietary vitamins affect this relationship.
基金financially supported by the National Key Research and Development Program of China(Grant Nos.2021YFB2600700 and 2022YFC3102302)the Central Public-Interest Scientific Institution Basal Research Fund(Grant No.Y221007)+2 种基金the National Natural Science Foundation of China(Grant No.52271274)the Key Laboratory of Ministry of Education for Coastal Disaster and Protection,Hohai University(Grant No.202205)the Key Project of NSFC-Shandong Joint Research Funding POW3C(Grant No.U1906230).
文摘The nonlinear variation of wave is commonly seen in nearshore area,and the resulting seabed response and liquefaction are of high concern to coastal engineers.In this study,an analytical formula considering the nonlinear wave skewness and asymmetry is adopted to provide wave pressure on the seabed surface.The liquefaction depth attenuation coefficient and width growth coefficient are defined to quantitatively characterize the nonlinear effect of wave on seabed liquefaction.Based on the 2D full dynamic model of wave-induced seabed response,a detailed parametric study is carried out in order to evaluate the influence of the nonlinear variation of wave loadings on seabed liquefaction.Further,new empirical prediction formulas are proposed to fast predict the maximum liquefaction under nonlinear wave.Results indicate that(1)Due to the influence of wave nonlinearity,the vertical transmission of negative pore water pressure in the seabed is hindered,and therefore,the amplitude decreases significantly.(2)In general,with the increase of wave nonlinearity,the liquefaction depth of seabed decreases gradually.Especially under asymmetric and skewed wave loading,the attenuation of maximum seabed liquefaction depth is the most significant among all the nonlinear wave conditions.However,highly skewed wave can cause the liquefaction depth of seabed greater than that under linear wave.(3)The asymmetry of wave pressure leads to the increase of liquefaction width,whereas the influence of skewedness is not significant.(4)Compared with the nonlinear waveform,seabed liquefaction is more sensitive to the variation of nonlinear degree of wave loading.
文摘In this study, we analyse the climate variability in the Upper Benue basin and assess its potential impact on the hydrology regime under two different greenhouse gas emission scenarios. The hydrological regime of the basin is more vulnerable to climate variability, especially precipitation and temperature. Observed hydroclimatic data (1950-2015) was analysed using a statistical approach. The potential impact of future climate change on the hydrological regime is quantified using the GR2M model and two climate models: HadGEM2-ES and MIROC5 from CMIP5 under RCP 4.5 and RCP 8.5 greenhouse gas emission scenarios. The main result shows that precipitation varies significantly according to the geographical location and time in the Upper Benue basin. The trend analysis of climatic parameters shows a decrease in annual average precipitation across the study area at a rate of -0.568 mm/year which represents about 37 mm/year over the time 1950-2015 compared to the 1961-1990 reference period. An increase of 0.7°C in mean temperature and 14% of PET are also observed according to the same reference period. The two climate models predict a warming of the basin of about 2°C for both RCP 4.5 and 8.5 scenarios and an increase in precipitation between 1% and 10% between 2015 and 2100. Similarly, the average annual flow is projected to increase by about +2% to +10% in the future for both RCP 4.5 and 8.5 scenarios between 2015 and 2100. Therefore, it is primordial to develop adaptation and mitigation measures to manage efficiently the availability of water resources.
基金financially supported by the National Natural Science Foundation of China (Grant No. 42171085)The Second Tibetan Plateau Scientific Expedition and Research Program (STEP) (Grant No.2019QZKK0307)。
文摘Post-disaster recovery and reconstruction provide an effective way to reduce the disaster vulnerability of, and promote leapfrog development in, an affected area. To date, studies that have used administrative boundaries to investigate the reconstruction of settlement space have not been able to clearly define the real boundaries of land use changes or quantify the degree of response to the ‘Build-Back-Better’ initiative, and have lacked any consideration of the fourth reconstruction stage–development period(10 years). This study constructed a mountain settlement niche and analyzed the characteristics, spatial reconstruction, and drivers of rural settlements during 2009–2019 in the upper reaches of the Minjiang River, southwest China. The results showed the following:(1) Natural factors were the basis for the formation and development of mountain settlement niches. The scale of the settlement niche and its land use structure depended on the physical geography features and the ethnic farming and grazing traditions. The settlement niche provided a realistic boundary for the spatial reconstruction.(2) The layout of residential land around cropland was the common feature of the mountain settlement niche. Of all the land use types, the roads and rural residential lands showed the most change over the 10 years;13,860 residential patches increased in size and 4,742 patches were abandoned.(3) The area of orchards, planted to reconstruct the economy in the mountains, increased by nearly 2.5 times.(4) Collapses, landslides, and debris flow disasters and the ecological red line influenced the spatial reconstruction. While the main focus of post-disaster recovery is spatial reconstruction, initiatives should include economic and spiritual recovery, and should also achieve sustainable development of the region.
基金Supported by São Paulo Research Foundation/FAPESP,No.2020/11564-6 and No.2019/27001-3the National Council for Scientific and Technological Development/CNPq,No.400030/2018-7Network NanoHealth/FAPERJ,No.E-26/10.000981/2019 and No.E-26/010.000210/2019/FAPERJ。
文摘The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models,particularly in their application in advanced therapy medicinal products(ATMPs).In this review,we examine the multifaceted impact of these developments,emphasizing the potential of stem cell models to enhance the sophistication of ATMPs and to offer alternatives to animal testing.Stem cell-derived tissues are particularly promising because they can reshape the preclinical landscape by providing more physiologically relevant and ethically sound platforms for drug screening and disease modelling.We also discuss the critical challenges of reproducibility and accuracy in measurements to ensure the integrity and utility of stem cell models in research and application.Moreover,this review highlights the imperative of stem cell models to align with regulatory standards,ensuring using stem cells in ATMPs translates into safe and effective clinical therapies.With regulatory approval serving as a gateway to clinical adoption,the collaborative efforts between scientists and regulators are vital for the progression of stem cell applications from bench to bedside.We advocate for a balanced approach that nurtures innovation within the framework of rigorous validation and regulatory compliance,ensuring that stem cell-base solutions are maximized to promote public trust and patient health in ATMPs.
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
