Introduction The study on earthquake nucleation is widely concerned by seismologists in the world. The experimental and theoretical studies indicate that earthquakes should be preceded by quasi-static slip wit... Introduction The study on earthquake nucleation is widely concerned by seismologists in the world. The experimental and theoretical studies indicate that earthquakes should be preceded by quasi-static slip within a nucleation zone (Oh-naka, 1992; Dodge, Beroza, 1995; Dodge, et al, 1996; Ohnaka, Kuwahara, 1990; Yamashita, Ohnaka, 1991). The earthquake nucleation process means a transition from quasi-static to quasi-dynamic rupture process, and it itself is a short-term precursor. Immediate foreshocks are local dynamic instabilities that occur during the transition from the quasi-static to the quasi-dynamic nucleation of the dynamic instability (Ohnaka, 1992). According to the recent theoretical study, immediate foreshocks can be regarded as the localized fractures accompanied by the quasi-static nucleation process of a large earthquake (Shibazaki, Matsu'ura, 1995). Therefore, foreshocks could occur during the nucleation process. The nucleation of earthquakes can be illuminated through analyzing foreshock activity in detail. Detection of the nucleation process by means of a foreshock study is a potential tool for earthquake predic-tion. The nucleation process of Izu peninsula earthquake with M=7.0 on January 14, 1978 is revealed by Ohnaka with foreshock activities. It was observed that the nucleation zone indicated by foreshocks grew at a rate of 1～40 cm/s before reaching a diameter of 10 km. The depths of foreshocks do not change much more, keep within 10 km. Recently, Hurukawa have studied the nucleation process of Off-Etorofu earthquake with MW=7.9 on December 3, 1995. The results show distinctly the nucleation process before the main shock. In the nucleation process, rupture started at the deepest point of the foreshock area, and then propagated to the shallow depth with the apparent ve-locity of 5～20 cm/s (Hurukawa, 1998). Rastogi and Mandal (1998) studied the rupture nucleation process of five Koyna medium-sized main shocks using the time-space patterns of foreshocks. They found that the nucleation zone grew at a rate of 0.5～10 cm/s until it finally attained a diameter of about 10 km before the occurrence of the main shock and the fracture nucleated at shallow depths and gradually deepened, the main shock occurred at the deepest point of the nucleation zone, that is, at the depth of about 8～11 km. Foreshock distribution showed a good agreement with the preslip model of earthquake nucleation (Rastogi, Mandal, 1998).……展开更多
Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood cl...Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.展开更多
Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affe...Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
West Qinling north boundary fault zone (WQNBFZ) is a major NWW-striking fault in the east boundary of Tibetan Plateau, which is parallel to the Xianshuihe fault zone, Eastern Kunlun fault zone and Haiyuan fault zo... West Qinling north boundary fault zone (WQNBFZ) is a major NWW-striking fault in the east boundary of Tibetan Plateau, which is parallel to the Xianshuihe fault zone, Eastern Kunlun fault zone and Haiyuan fault zone. It is of mainly sinistral strike-slip. England and Molnar (1990) and WANG and MA (1998) proposed that these strike-slip faults divided the east part of Tibetan Plateau into elongate blocks, which slide successively towards the east, accompanied possibly by the clockwise rotation. What is more, the occurrence frequency of earthquakes with M 36.5 along WQNBFZ is also high, such as BC 47 Zhangxian M=6.8 earthquake, the 128 Gangu M=6.5 earth-quake, the 143 Gangu M=7 earthquake, the 734 Tianshui M=7 earthquake, the 1756 Wushan M=6.5 earthquake and the 1936 Kangle M=6.8 earthquake. However, compared with researches on Haiyuan fault zone, Xianshuihe fault zone and Longmenshan fault zone (Institute of Geology of State Seismological Bureau, Seismological Bureau of Ningxia Hui Autonomous Region, 1990; LI, 1993; DENG, et al, 1994; Burchfiel, et al, 1995), the study on WQNBFZ is still weak, although some researches have been done by KANG (1990) and TENG, et al (1991). Based on the field investigation and sample dating, the active features about the Fenghuangshan-Tianshui fault (FTF) of WQNBFZ are discussed in the paper.……展开更多
Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental ...Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.展开更多
This paper presents an efficient numerical technique for solving multi-term linear systems of fractional ordinary differential equations(FODEs)which have been widely used in modeling various phenomena in engineering a...This paper presents an efficient numerical technique for solving multi-term linear systems of fractional ordinary differential equations(FODEs)which have been widely used in modeling various phenomena in engineering and science.An approximate solution of the system is sought in the formof the finite series over the Müntz polynomials.By using the collocation procedure in the time interval,one gets the linear algebraic system for the coefficient of the expansion which can be easily solved numerically by a standard procedure.This technique also serves as the basis for solving the time-fractional partial differential equations(PDEs).The modified radial basis functions are used for spatial approximation of the solution.The collocation in the solution domain transforms the equation into a system of fractional ordinary differential equations similar to the one mentioned above.Several examples have verified the performance of the proposed novel technique with high accuracy and efficiency.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
Context: The advent of Artificial Intelligence (AI) requires modeling prior to its implementation in algorithms for most human skills. This observation requires us to have a detailed and precise understanding of the i...Context: The advent of Artificial Intelligence (AI) requires modeling prior to its implementation in algorithms for most human skills. This observation requires us to have a detailed and precise understanding of the interfaces of verbal and emotional communications. The progress of AI is significant on the verbal level but modest in terms of the recognition of facial emotions even if this functionality is one of the oldest in humans and is omnipresent in our daily lives. Dysfunction in the ability for facial emotional expressions is present in many brain pathologies encountered by psychiatrists, neurologists, psychotherapists, mental health professionals including social workers. It cannot be objectively verified and measured due to a lack of reliable tools that are valid and consistently sensitive. Indeed, the articles in the scientific literature dealing with Visual-Facial-Emotions-Recognition (ViFaEmRe), suffer from the absence of 1) consensual and rational tools for continuous quantified measurement, 2) operational concepts. We have invented a software that can use computer-morphing attempting to respond to these two obstacles. It is identified as the Method of Analysis and Research of the Integration of Emotions (M.A.R.I.E.). Our primary goal is to use M.A.R.I.E. to understand the physiology of ViFaEmRe in normal healthy subjects by standardizing the measurements. Then, it will allow us to focus on subjects manifesting abnormalities in this ability. Our second goal is to make our contribution to the progress of AI hoping to add the dimension of recognition of facial emotional expressions. Objective: To study: 1) categorical vs dimensional aspects of recognition of ViFaEmRe, 2) universality vs idiosyncrasy, 3) immediate vs ambivalent Emotional-Decision-Making, 4) the Emotional-Fingerprint of a face and 5) creation of population references data. Methods: With M.A.R.I.E. enable a rational quantified measurement of Emotional-Visual-Acuity (EVA) of 1) a) an individual observer, b) in a population aged 20 to 70 years old, 2) measure the range and intensity of expressed emotions by 3 Face-Tests, 3) quantify the performance of a sample of 204 observers with hyper normal measures of cognition, “thymia,” (ibid. defined elsewhere) and low levels of anxiety 4) analysis of the 6 primary emotions. Results: We have individualized the following continuous parameters: 1) “Emotional-Visual-Acuity”, 2) “Visual-Emotional-Feeling”, 3) “Emotional-Quotient”, 4) “Emotional-Deci-sion-Making”, 5) “Emotional-Decision-Making Graph” or “Individual-Gun-Trigger”6) “Emotional-Fingerprint” or “Key-graph”, 7) “Emotional-Finger-print-Graph”, 8) detecting “misunderstanding” and 9) detecting “error”. This allowed us a taxonomy with coding of the face-emotion pair. Each face has specific measurements and graphics. The EVA improves from ages of 20 to 55 years, then decreases. It does not depend on the sex of the observer, nor the face studied. In addition, 1% of people endowed with normal intelligence do not recognize emotions. The categorical dimension is a variable for everyone. The range and intensity of ViFaEmRe is idiosyncratic and not universally uniform. The recognition of emotions is purely categorical for a single individual. It is dimensional for a population sample. Conclusions: Firstly, M.A.R.I.E. has made possible to bring out new concepts and new continuous measurements variables. The comparison between healthy and abnormal individuals makes it possible to take into consideration the significance of this line of study. From now on, these new functional parameters will allow us to identify and name “emotional” disorders or illnesses which can give additional dimension to behavioral disorders in all pathologies that affect the brain. Secondly, the ViFaEmRe is idiosyncratic, categorical, and a function of the identity of the observer and of the observed face. These findings stack up against Artificial Intelligence, which cannot have a globalist or regionalist algorithm that can be programmed into a robot, nor can AI compete with human abilities and judgment in this domain. *Here “Emotional disorders” refers to disorders of emotional expressions and recognition.展开更多
TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F...TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.展开更多
Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:...Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.展开更多
Anovel accuratemethod is proposed to solve a broad variety of linear and nonlinear(1+1)-dimensional and(2+1)-dimensional multi-term time-fractional partial differential equations with spatial operators of anisotropic ...Anovel accuratemethod is proposed to solve a broad variety of linear and nonlinear(1+1)-dimensional and(2+1)-dimensional multi-term time-fractional partial differential equations with spatial operators of anisotropic diffusivity.For(1+1)-dimensional problems,analytical solutions that satisfy the boundary requirements are derived.Such solutions are numerically calculated using the trigonometric basis approximation for(2+1)-dimensional problems.With the aid of these analytical or numerical approximations,the original problems can be converted into the fractional ordinary differential equations,and solutions to the fractional ordinary differential equations are approximated by modified radial basis functions with time-dependent coefficients.An efficient backward substitution strategy that was previously provided for a single fractional ordinary differential equation is then used to solve the corresponding systems.The straightforward quasilinearization technique is applied to handle nonlinear issues.Numerical experiments demonstrate the suggested algorithm’s superior accuracy and efficiency.展开更多
The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabol...The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.展开更多
Flow records for stations in the Casamance basin are incomplete. Several gaps were noted over the 1980-2021 study period, making this study tedious. The aim of this study is to assess the potential impact of climate c...Flow records for stations in the Casamance basin are incomplete. Several gaps were noted over the 1980-2021 study period, making this study tedious. The aim of this study is to assess the potential impact of climate change on the flow of the Casamance watershed at Kolda. To this end, hydrological series are simulated and then extended using the GR2M rainfall-runoff model, with a monthly time step. Projected climate data are derived from a multi-model ensemble under scenarios SSP2-4.5 (scenario with additional radiative forcing of 4.5 W/m<sup>2</sup> by 2099) and SSP5-8.5 (scenario with additional radiative forcing of 8.5 W/m<sup>2</sup> by 2099). An analysis of the homogeneity of the rainfall data series from the Kolda station was carried out using KhronoStat software. The Casamance watershed was then delimited using ArcGIS to determine the morphometric parameters of the basin, which will be decisive for the rest of the work. Next, monthly evapotranspiration was calculated using the formula proposed by Oudin et al. This, together with rainfall and runoff, forms the input data for the model. The GR2M model was then calibrated and cross-validated using various simulations to assess its performance and robustness in the Casamance watershed. The version of the model with the calibrated parameters will make it possible to extend Casamance river flows to 2099. This simulation of future flows with GR2M shows a decrease in the flow of the Casamance at Kolda with the two scenarios SSP2-4.5 and SSP5-8.5 during the rainy period, and almost zero flows during the dry season from the period 2040-2059.展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the compa...BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.展开更多
This study assessed sediment contamination by heavy metals and pesticide active ingredients linked to chemical inputs used in agricultural activities in the lower Ouémé. Pesticide residues from the organochl...This study assessed sediment contamination by heavy metals and pesticide active ingredients linked to chemical inputs used in agricultural activities in the lower Ouémé. Pesticide residues from the organochlorine, pyrethroid and organophosphorus families were investigated by gas chromatography, and heavy metals (Cd, Pb, As, Ni, Zn, Fe, Mg, Cr and Hg) by atomic absorption spectrophotometry. The metallic pollution indices, the contamination factor (CF) and the ecological risk index were calculated. The results revealed 8 active ingredients in the rainy season and 9 in the dry season. Glyphosate was the active ingredient with the highest concentration at all stations, 9.65 ± 0.84 mg/kg recorded in the dry season at the Aguigadji station. All glyphosate values were above the EQS. DDT, Atrazine and Endosulfan also showed high concentrations in the dry and rainy seasons. Emamectin, Abamectin and Lambda Cyhalothrin also showed high concentrations in the dry season at Aguigadji, Ahlan and Sele. Only glyphosate was recorded at the control station (Toho), but in very low concentrations. Lead showed the highest concentrations at all the stations, 265.96 ± 21.02 mg/Kg in the rainy season and 255.38 ± 79.09 mg/Kg in the dry season, all detected at the Aguigadji station and above the EQS. Zn, Ni, Fe, Cu and Cr were all representative in both the dry and rainy seasons at the contaminated stations. Manganese showed high concentrations in the rainy season. Pb showed very high contamination (FC ≥ 6) at the Aguigadji and Ahlan stations and significant contamination (3 ≤ FC 6) at the Sele station in both the rainy and dry seasons. Ni, Hg and Cd, showed either moderate or significant contamination at the contaminated stations. The risk values showed a considerable ecological Ri (190 ≤ Ri < 380) in the rainy season and a moderate ecological Ri (95 ≤ Ri < 190) in the dry season at these contaminated stations.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
基金国家重点基础研究发展计划(973计划)，Mechanism and Prediction for StrongContinental Earthquakes from China Seismological Bureau
文摘 Introduction The study on earthquake nucleation is widely concerned by seismologists in the world. The experimental and theoretical studies indicate that earthquakes should be preceded by quasi-static slip within a nucleation zone (Oh-naka, 1992; Dodge, Beroza, 1995; Dodge, et al, 1996; Ohnaka, Kuwahara, 1990; Yamashita, Ohnaka, 1991). The earthquake nucleation process means a transition from quasi-static to quasi-dynamic rupture process, and it itself is a short-term precursor. Immediate foreshocks are local dynamic instabilities that occur during the transition from the quasi-static to the quasi-dynamic nucleation of the dynamic instability (Ohnaka, 1992). According to the recent theoretical study, immediate foreshocks can be regarded as the localized fractures accompanied by the quasi-static nucleation process of a large earthquake (Shibazaki, Matsu'ura, 1995). Therefore, foreshocks could occur during the nucleation process. The nucleation of earthquakes can be illuminated through analyzing foreshock activity in detail. Detection of the nucleation process by means of a foreshock study is a potential tool for earthquake predic-tion. The nucleation process of Izu peninsula earthquake with M=7.0 on January 14, 1978 is revealed by Ohnaka with foreshock activities. It was observed that the nucleation zone indicated by foreshocks grew at a rate of 1～40 cm/s before reaching a diameter of 10 km. The depths of foreshocks do not change much more, keep within 10 km. Recently, Hurukawa have studied the nucleation process of Off-Etorofu earthquake with MW=7.9 on December 3, 1995. The results show distinctly the nucleation process before the main shock. In the nucleation process, rupture started at the deepest point of the foreshock area, and then propagated to the shallow depth with the apparent ve-locity of 5～20 cm/s (Hurukawa, 1998). Rastogi and Mandal (1998) studied the rupture nucleation process of five Koyna medium-sized main shocks using the time-space patterns of foreshocks. They found that the nucleation zone grew at a rate of 0.5～10 cm/s until it finally attained a diameter of about 10 km before the occurrence of the main shock and the fracture nucleated at shallow depths and gradually deepened, the main shock occurred at the deepest point of the nucleation zone, that is, at the depth of about 8～11 km. Foreshock distribution showed a good agreement with the preslip model of earthquake nucleation (Rastogi, Mandal, 1998).……
基金supported in part by the National Institutes of Health grant 5R01NS117364-02(to JT)。
文摘Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
文摘 West Qinling north boundary fault zone (WQNBFZ) is a major NWW-striking fault in the east boundary of Tibetan Plateau, which is parallel to the Xianshuihe fault zone, Eastern Kunlun fault zone and Haiyuan fault zone. It is of mainly sinistral strike-slip. England and Molnar (1990) and WANG and MA (1998) proposed that these strike-slip faults divided the east part of Tibetan Plateau into elongate blocks, which slide successively towards the east, accompanied possibly by the clockwise rotation. What is more, the occurrence frequency of earthquakes with M 36.5 along WQNBFZ is also high, such as BC 47 Zhangxian M=6.8 earthquake, the 128 Gangu M=6.5 earth-quake, the 143 Gangu M=7 earthquake, the 734 Tianshui M=7 earthquake, the 1756 Wushan M=6.5 earthquake and the 1936 Kangle M=6.8 earthquake. However, compared with researches on Haiyuan fault zone, Xianshuihe fault zone and Longmenshan fault zone (Institute of Geology of State Seismological Bureau, Seismological Bureau of Ningxia Hui Autonomous Region, 1990; LI, 1993; DENG, et al, 1994; Burchfiel, et al, 1995), the study on WQNBFZ is still weak, although some researches have been done by KANG (1990) and TENG, et al (1991). Based on the field investigation and sample dating, the active features about the Fenghuangshan-Tianshui fault (FTF) of WQNBFZ are discussed in the paper.……
基金supported by the National Natural Science Foundation of China,Nos.82071190 and 82371438(to LC)Innovative Strong School Project of Guangdong Medical University,No.4SG21230G(to LC)Scientific Research Foundation of Guangdong Medical University,No.GDMUM2020017(to CL)。
文摘Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.
基金funded by the National Key Research and Development Program of China(No.2021YFB2600704)the National Natural Science Foundation of China(No.52171272)the Significant Science and Technology Project of the Ministry of Water Resources of China(No.SKS-2022112).
文摘This paper presents an efficient numerical technique for solving multi-term linear systems of fractional ordinary differential equations(FODEs)which have been widely used in modeling various phenomena in engineering and science.An approximate solution of the system is sought in the formof the finite series over the Müntz polynomials.By using the collocation procedure in the time interval,one gets the linear algebraic system for the coefficient of the expansion which can be easily solved numerically by a standard procedure.This technique also serves as the basis for solving the time-fractional partial differential equations(PDEs).The modified radial basis functions are used for spatial approximation of the solution.The collocation in the solution domain transforms the equation into a system of fractional ordinary differential equations similar to the one mentioned above.Several examples have verified the performance of the proposed novel technique with high accuracy and efficiency.
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.
文摘Context: The advent of Artificial Intelligence (AI) requires modeling prior to its implementation in algorithms for most human skills. This observation requires us to have a detailed and precise understanding of the interfaces of verbal and emotional communications. The progress of AI is significant on the verbal level but modest in terms of the recognition of facial emotions even if this functionality is one of the oldest in humans and is omnipresent in our daily lives. Dysfunction in the ability for facial emotional expressions is present in many brain pathologies encountered by psychiatrists, neurologists, psychotherapists, mental health professionals including social workers. It cannot be objectively verified and measured due to a lack of reliable tools that are valid and consistently sensitive. Indeed, the articles in the scientific literature dealing with Visual-Facial-Emotions-Recognition (ViFaEmRe), suffer from the absence of 1) consensual and rational tools for continuous quantified measurement, 2) operational concepts. We have invented a software that can use computer-morphing attempting to respond to these two obstacles. It is identified as the Method of Analysis and Research of the Integration of Emotions (M.A.R.I.E.). Our primary goal is to use M.A.R.I.E. to understand the physiology of ViFaEmRe in normal healthy subjects by standardizing the measurements. Then, it will allow us to focus on subjects manifesting abnormalities in this ability. Our second goal is to make our contribution to the progress of AI hoping to add the dimension of recognition of facial emotional expressions. Objective: To study: 1) categorical vs dimensional aspects of recognition of ViFaEmRe, 2) universality vs idiosyncrasy, 3) immediate vs ambivalent Emotional-Decision-Making, 4) the Emotional-Fingerprint of a face and 5) creation of population references data. Methods: With M.A.R.I.E. enable a rational quantified measurement of Emotional-Visual-Acuity (EVA) of 1) a) an individual observer, b) in a population aged 20 to 70 years old, 2) measure the range and intensity of expressed emotions by 3 Face-Tests, 3) quantify the performance of a sample of 204 observers with hyper normal measures of cognition, “thymia,” (ibid. defined elsewhere) and low levels of anxiety 4) analysis of the 6 primary emotions. Results: We have individualized the following continuous parameters: 1) “Emotional-Visual-Acuity”, 2) “Visual-Emotional-Feeling”, 3) “Emotional-Quotient”, 4) “Emotional-Deci-sion-Making”, 5) “Emotional-Decision-Making Graph” or “Individual-Gun-Trigger”6) “Emotional-Fingerprint” or “Key-graph”, 7) “Emotional-Finger-print-Graph”, 8) detecting “misunderstanding” and 9) detecting “error”. This allowed us a taxonomy with coding of the face-emotion pair. Each face has specific measurements and graphics. The EVA improves from ages of 20 to 55 years, then decreases. It does not depend on the sex of the observer, nor the face studied. In addition, 1% of people endowed with normal intelligence do not recognize emotions. The categorical dimension is a variable for everyone. The range and intensity of ViFaEmRe is idiosyncratic and not universally uniform. The recognition of emotions is purely categorical for a single individual. It is dimensional for a population sample. Conclusions: Firstly, M.A.R.I.E. has made possible to bring out new concepts and new continuous measurements variables. The comparison between healthy and abnormal individuals makes it possible to take into consideration the significance of this line of study. From now on, these new functional parameters will allow us to identify and name “emotional” disorders or illnesses which can give additional dimension to behavioral disorders in all pathologies that affect the brain. Secondly, the ViFaEmRe is idiosyncratic, categorical, and a function of the identity of the observer and of the observed face. These findings stack up against Artificial Intelligence, which cannot have a globalist or regionalist algorithm that can be programmed into a robot, nor can AI compete with human abilities and judgment in this domain. *Here “Emotional disorders” refers to disorders of emotional expressions and recognition.
基金supported by the National Natural Science Foundation of China,No.82072941(to QHX)Liaoning Province Key R&D Program Guidance Project,No.2020JH2/10300044Science and Technology Plan Project of Shenyang,No.20-205-4-050(both to XHS)。
文摘TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.
基金supported by Natural Science Foundation of Hainan Province(820MS135)Hainan Provincial Health Commission 2023 Provincial Key Clinical Discipline(Clinical Medical Center)Construction Unit Fund Project(Qiongwei Yihan[2022]No.341)Hainan Provincial Health Technology Innovation Joint Project(WSJK2024MS209).
文摘Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.
基金the National Key Research and Development Program of China(No.2021YFB2600704)the National Natural Science Foundation of China(No.52171272)the Significant Science and Technology Project of the Ministry of Water Resources of China(No.SKS-2022112).
文摘Anovel accuratemethod is proposed to solve a broad variety of linear and nonlinear(1+1)-dimensional and(2+1)-dimensional multi-term time-fractional partial differential equations with spatial operators of anisotropic diffusivity.For(1+1)-dimensional problems,analytical solutions that satisfy the boundary requirements are derived.Such solutions are numerically calculated using the trigonometric basis approximation for(2+1)-dimensional problems.With the aid of these analytical or numerical approximations,the original problems can be converted into the fractional ordinary differential equations,and solutions to the fractional ordinary differential equations are approximated by modified radial basis functions with time-dependent coefficients.An efficient backward substitution strategy that was previously provided for a single fractional ordinary differential equation is then used to solve the corresponding systems.The straightforward quasilinearization technique is applied to handle nonlinear issues.Numerical experiments demonstrate the suggested algorithm’s superior accuracy and efficiency.
基金supported by the National Natural Science Foundation of China,Nos.81974134(to XX)and 82000895(to HL)National Key Research and Development Program of China,Nos.2021YFA1101200&2021YFA1101202National Natural Science Foundation of Hunan Province,China,No.2022JJ30071(to HL)。
文摘The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.
文摘Flow records for stations in the Casamance basin are incomplete. Several gaps were noted over the 1980-2021 study period, making this study tedious. The aim of this study is to assess the potential impact of climate change on the flow of the Casamance watershed at Kolda. To this end, hydrological series are simulated and then extended using the GR2M rainfall-runoff model, with a monthly time step. Projected climate data are derived from a multi-model ensemble under scenarios SSP2-4.5 (scenario with additional radiative forcing of 4.5 W/m<sup>2</sup> by 2099) and SSP5-8.5 (scenario with additional radiative forcing of 8.5 W/m<sup>2</sup> by 2099). An analysis of the homogeneity of the rainfall data series from the Kolda station was carried out using KhronoStat software. The Casamance watershed was then delimited using ArcGIS to determine the morphometric parameters of the basin, which will be decisive for the rest of the work. Next, monthly evapotranspiration was calculated using the formula proposed by Oudin et al. This, together with rainfall and runoff, forms the input data for the model. The GR2M model was then calibrated and cross-validated using various simulations to assess its performance and robustness in the Casamance watershed. The version of the model with the calibrated parameters will make it possible to extend Casamance river flows to 2099. This simulation of future flows with GR2M shows a decrease in the flow of the Casamance at Kolda with the two scenarios SSP2-4.5 and SSP5-8.5 during the rainy period, and almost zero flows during the dry season from the period 2040-2059.
基金Supported by the Guangdong Esophageal Cancer Institute Science and Technology Program,No.M202013Guangdong Medical Research Foundation,No.A2021369.
文摘BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.
文摘This study assessed sediment contamination by heavy metals and pesticide active ingredients linked to chemical inputs used in agricultural activities in the lower Ouémé. Pesticide residues from the organochlorine, pyrethroid and organophosphorus families were investigated by gas chromatography, and heavy metals (Cd, Pb, As, Ni, Zn, Fe, Mg, Cr and Hg) by atomic absorption spectrophotometry. The metallic pollution indices, the contamination factor (CF) and the ecological risk index were calculated. The results revealed 8 active ingredients in the rainy season and 9 in the dry season. Glyphosate was the active ingredient with the highest concentration at all stations, 9.65 ± 0.84 mg/kg recorded in the dry season at the Aguigadji station. All glyphosate values were above the EQS. DDT, Atrazine and Endosulfan also showed high concentrations in the dry and rainy seasons. Emamectin, Abamectin and Lambda Cyhalothrin also showed high concentrations in the dry season at Aguigadji, Ahlan and Sele. Only glyphosate was recorded at the control station (Toho), but in very low concentrations. Lead showed the highest concentrations at all the stations, 265.96 ± 21.02 mg/Kg in the rainy season and 255.38 ± 79.09 mg/Kg in the dry season, all detected at the Aguigadji station and above the EQS. Zn, Ni, Fe, Cu and Cr were all representative in both the dry and rainy seasons at the contaminated stations. Manganese showed high concentrations in the rainy season. Pb showed very high contamination (FC ≥ 6) at the Aguigadji and Ahlan stations and significant contamination (3 ≤ FC 6) at the Sele station in both the rainy and dry seasons. Ni, Hg and Cd, showed either moderate or significant contamination at the contaminated stations. The risk values showed a considerable ecological Ri (190 ≤ Ri < 380) in the rainy season and a moderate ecological Ri (95 ≤ Ri < 190) in the dry season at these contaminated stations.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
