Objective: To observe the effects of remote ischemia on cognitive function and neuronal pathological damage in rats with cognitive impairment induced by bilateral common carotid artery occlusion(BCAO).Methods:Male SD ...Objective: To observe the effects of remote ischemia on cognitive function and neuronal pathological damage in rats with cognitive impairment induced by bilateral common carotid artery occlusion(BCAO).Methods:Male SD rats were selected to establish the cognitive impairment model induced by cerebral ischemia reperfusion caused by BCAO.The tests included three groups of rats:a sham group,a model group with vascular cognitive impairment (VCI) , and a remote ischemic conditioning (RIC) group (VCI + RIC group). From 24 h after operation, both hind limbs of rats in VCI + RIC group were treated with RIC. After 28 d, Morris water maze test and HE staining was used to observe the pathological changes of white matter and hippocampus in each group.Results: After 3 d mice in VCI group began to improve gradually. The recovery of rats in the VCI + RIC group was relatively slow,but they started to recover rapidly 2 d after the operation.Morris water maze test showed that the escape latency of rats in VCI group and VCI+RIC group was longer than that in the sham group, and the score of VCI+RIC group was better than that of the VCI group, but there was a significant difference between the two groups(P<0.05).The space exploration experiment was performed at 7 d and 28 d after the operation;the VCI+RIC group outperformed the VCI group in both trials;the difference between the two groups was statistically significant (P<0.05).In the target quadrant exploration time, the difference between the VCI group (33.5±11.3 s) and the VCI+RIC group (41.2±9.7 s) was statistically significant (P<0.05).Results from the hematoxylin and eosin(HE)staining showed that compared with VCI group, cortical cells in VCI + RIC group had loose stroma, thinner nerve fibers, fewer broken cells, and slightly shrunken cells. Compared with VCI group, neurons in VCI + RIC group had a little vacuolar degenera-tion and slightly shrunken cell volume.Conclusion:Cerebral ischemia-reperfusion injury can cause learning and memory impairment in rats, leading to VCI. RIC can significantly improve VCI and play a neuroprotective role.展开更多
Sulfate-reducing bacteria play an important role in the geochemistry of iron(oxyhydr)oxide and arsenic(As)in natural environments;however,the associated reaction processes are yet to be fully understood.In this study,...Sulfate-reducing bacteria play an important role in the geochemistry of iron(oxyhydr)oxide and arsenic(As)in natural environments;however,the associated reaction processes are yet to be fully understood.In this study,batch experiments coupled with geochemical,spectroscopic,microscopic,and thermodynamic analyses were conducted to investigate the dynamic coupling of ferrihydrite transformation and the associated As desorption/redistribution mediated by Desulfovibrio vulgaris(D.vulgaris).The results indicated that D.vulgaris could induce ferrihydrite transformation via S^(2-)-driven and direct reduction processes.In the absence of SO_(4)^(2-),D.vulgaris directly reduced ferrihydrite,and As desorption and re-sorption occurred simultaneously during the partial transformation of ferrihydrite to magnetite.The increase in SO_(4)^(2-)loading promoted the S^(2-)-driven reduction of ferrihydrite and accelerated the subsequent mineralogical transformation.In the low and medium SO_(4)^(2-)treatments,ferrihydrite was completely transformed to a mixture of magnetite and mackinawite,which increased the fraction of As in the residual phase and stabilized As.In the high SO_(4)^(2-)treatment,although the replacement of ferrihydrite by only mackinawite also increased the fraction of As in the residual phase,22.1%of the total As was released into the solution due to the poor adsorption affinity of As to mackinawite and the conversion of As^(5+)to As^(3+).The mechanisms of ferrihydrite reduction,mineralogy transformation,and As mobilization and redistribution mediated by sulfate-reducing bacteria are closely related to the surrounding SO_(4)^(2-)loadings.These results advance our understanding of the biogeochemical behavior of Fe,S,and As,and are helpful for the risk assessment and remediation of As contamination.展开更多
Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiti...Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.展开更多
Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet cl...Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.展开更多
To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hosp...To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest(OHCA)and in-hospital cardiac arrest(IHCA)were 140.7/100,000 and 10.2/1000,respectively.展开更多
The application of selenium nanoparticles(SeNPs)as nanofertilizers may lead to the release of SeNPs into aquatic systems.However,the environmental behavior of SeNPs is rarely studied.In this study,using alginate-coate...The application of selenium nanoparticles(SeNPs)as nanofertilizers may lead to the release of SeNPs into aquatic systems.However,the environmental behavior of SeNPs is rarely studied.In this study,using alginate-coated SeNPs(Alg-SeNPs)and polyvinyl alcohol-coated SeNPs(PVA-SeNPs)as models,we systematically investigated the aggregation and stability of SeNPs under various water conditions.PVA-SeNPs were highly stable in mono-and polyvalent electrolytes,probably due to the strong steric hindrance of the capping agent.Alg-SeNPs only suffered from a limited increase in size,even at 2500 mmol/L NaCl and 200 mmol/L MgCl_(2),while they underwent apparent aggregation in CaCl_(2) and LaCl_(3) solutions.The binding of Ca^(2+) and La^(3+) with the guluronic acid part in alginate induced the formation of cross-linking aggregates.Natural organic matter enhanced the stability of Alg-SeNPs in monovalent electrolytes,while accelerated the attachment of Alg-SeNPs in polyvalent electrolytes,due to the cation bridge effects.The long-term stability of SeNPs in natural water showed that the aggregation sizes of Alg-SeNPs and PVA-SeNPs increased to several hundreds of nanometers or above 10μm after 30 days,implying that SeNPs may be suspended in the water column or further settle down,depending on the surrounding water chemistry.The study may contribute to the deep insight into the fate and mobility of SeNPs in the aquatic environment.The varying fate of SeNPs in different natural waters also suggests that the risks of SeNPs to organisms living in diverse depths in the aquatic compartment should be concerned.展开更多
Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several ...Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors,particularly in the population of young children.To standardize the protocols of preoperative evaluation and sur-gery of young children for epilepsy surgery,the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients.It adopted the modifed Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists,epileptologists,pediatric epilepsy surgeons,and functional neurosurgeons.The survey contents contained:(1)the participants,comprising children aged≤6 years;(2)adopted DRE definition proposed by the International League Against Epilepsy in 2010;and(3)investigated epilepsy surgery,principally referring to curative epilepsy surgeries.The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries.According to the Delphi process,a con-sensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment,sur-gical strategies and techniques,and perioperative and long-term postoperative management,despite controversial opinions on certain items.We hope the results of this consensus will improve the level of surgical treatment and man-agement of intractable epilepsy in young children.展开更多
Stereoelectroencephalography(SEEG)has been widely used in the presurgical evaluation of patients with medically intractable epilepsy.In the past,SEEG was commonly used as a method for mapping and localizing the epilep...Stereoelectroencephalography(SEEG)has been widely used in the presurgical evaluation of patients with medically intractable epilepsy.In the past,SEEG was commonly used as a method for mapping and localizing the epileptogenic zone(EZ).Since 2004,several studies have been conducted to examine the effectiveness of SEEG-guided radiofrequency thermocoagulation(RF-TC)in treating refractory epilepsy.However,the seizure-free and responder rates varied greatly across studies.We aimed to analyze the outcome of 56 patients who were treated with SEEG-guided RF-TC to evaluate the effectiveness of this treatment.SEEG-guided RF-TC can be considered as a treatment for refractory epilepsy.However,due to its limited efficacy,SEEG-guided RF-TC might be regarded as a temporary treatment performed under SEEG rather than a promising treatment for refractory epilepsy.展开更多
Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and...Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and recurrent seizures after previous infections of the central nervous system is high and accounts for1%~5%of the cases of epilepsy.Viral encephalitis(VE)is directly caused by viral infection.The occurrence of seizures after VE is associated with poor prognosis.In survivors of VE,among other neurological sequelae,the risk of developing epilepsy is increased10-fold.The risk of severe neurological sequelae after VE is particularly high in very young children.Studies on seizure occurrence,possible underlying mechanisms,clinical characteristics,and clinical treatment(especially surgical treatment)of VE have yielded only limited detailed data.We reviewed the most recent literature on the clinical features and surgical treatment of post-VE epilepsy.展开更多
For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection o...For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection of the epileptogenic zone because of the proximity of a functional area or the implication of a larger epileptogenic network. Initially, stereoelectroencephalography(SEEG) exploration was a method of electroencephalography recording that was used in the presurgical evaluation of epileptic patients with complex epilepsy. Later, intracerebral electrodes used for SEEG were applied to produce radio frequency thermocoagulation(RF-TC) in epileptic patients. SEEG-guided RF-TC has produced some promising results, especially in the last dacade. Now, it has become popular as a palliative treatment to reduce seizure frequency in patients with drug-resistant focal epilepsy. This article presents a review of SEEG-guided RF-TC.展开更多
We propose the modified Kalman filter(MKF) using the received signal for observation and constructing an inverse process of the conventional Kalman filter(CKF) for polarization de-multiplexing in coherent optical(CO) ...We propose the modified Kalman filter(MKF) using the received signal for observation and constructing an inverse process of the conventional Kalman filter(CKF) for polarization de-multiplexing in coherent optical(CO) orthogonal frequency-division multiplexing(OFDM) transmissions. The MKF can avoid the convergence error problem in CKF without matrix inverse operation and has a faster converging speed and a much larger tolerance to the process and measurement noise covariance, about two orders of magnitude more than those of CKF. We experimentally demonstrate the 12 Gbaud OFDM signal transmission over 480 km standard singlemode fiber. The performance of MKF and CKF outperforms pilot-aided polarization de-multiplexing with better accuracy and nonlinearity tolerance.展开更多
Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a po...Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis.This consensus includes the definition and standard detection techniques of HFOs,the localizing value of pathological HFOs for epileptic foci,and different ways to distinguish physiological from epileptic HFOs.The latest clinical applications of HFOs in epilepsy and the related findings are also discussed.HFOs will advance our understanding of the pathophysiology of epilepsy.展开更多
Conserved effectors produced by phytopathogens play critical roles in plant-microbe interactions.NIS1-like proteins represent a newly identified family of effectors distributed in multiple fungal species.However,their...Conserved effectors produced by phytopathogens play critical roles in plant-microbe interactions.NIS1-like proteins represent a newly identified family of effectors distributed in multiple fungal species.However,their biological functions in a majority of pathogenic fungi remain largely elusive and require further investigation.In this study,we characterized two NIS1-like proteins VmNIS1 and VmNIS2 from Valsa mali,the causal agent of apple Valsa canker.Both of these two proteins were predicted to be secreted.Using agroinfiltration,we found that VmNIS1 induced intense cell death,whereas VmNIS2 suppressed INF1 elicitin-triggered cell death in Nicotiana benthamiana.Treatment of N.benthamiana with VmNIS1 recombinant protein produced by Escherichia coli activated a series of immune responses and enhanced plant disease resistance against Phytophthora capsici.In contrast,VmNIS2 suppressed plant immune responses and promoted P.capsici infection when transiently expressed in N.benthamiana.Both VmNIS1 and VmNIS2 were shown to be highly induced at late stage of V.mali infection.By individually knocking out of these two genes in V.mali,however,only VmNIS2 was shown to be required for pathogen virulence as well as tolerance to oxidative stress.Notably,we further showed that C-terminal extension of VmNIS1 was essential for plant recognition and VmNIS2 may escape plant detection via sequence truncation.Our data collectively indicate that VmNIS1 and VmNIS2 play distinct roles in plant recognition and pathogen virulence,which provided new insights into the function of NIS1-like proteins in plant-microbe interactions.展开更多
Precise control of circulating lipid levels is vital in both health and disease.We recently uncovered that bulk lipids,transported by lipoproteins,enter the circulation initially via the coat protein complex II(COPII)...Precise control of circulating lipid levels is vital in both health and disease.We recently uncovered that bulk lipids,transported by lipoproteins,enter the circulation initially via the coat protein complex II(COPII)in a condensation-dependent manner.Divalent manganese,acting as a signaling messenger,selectively controls COPII condensation to regulate lipid homeostasis in vivo.Here,we present evidence for a manganese-based therapy in murine models of hypolipidemia and hyperlipidemia.展开更多
Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children ...Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children of 3 to 12 months of age,although it can also occur after the age of 1 year.In general,children with ES develop other symptoms of epilepsy,such as tonic,tonic-clonic,or focal seizures,after 3 to 5 years of age.ES in children is often damaging and usually results in developmental regression.First-line treatments for spasm seizures include adrenocorticotropic hormone(ACTH)and vigabatrin.However,many patients fail to respond to these medications,and continued to have spasms associated with progressive neurodevelopmental degeneration.Therefore,it is important to consider whether children with drug resistance meet surgical indications to consider surgical treatment in such conditions.In this study,we reviewed and summarized the importance of preoperative evaluation in order to provide surgical options for treatment of children with ES.展开更多
Objective:This study aimed to employ time‐resolved spectroscopy(TRS)to explore age‐related differences in prefrontal cortex(PFC)activity while subjects performed a working memory task.Methods:We employed TRS to meas...Objective:This study aimed to employ time‐resolved spectroscopy(TRS)to explore age‐related differences in prefrontal cortex(PFC)activity while subjects performed a working memory task.Methods:We employed TRS to measure PFC activity in ten healthy younger and ten healthy older subjects while they performed a working memory(WM)task.All subjects performed the Sternberg test(ST)in which the memory‐set size varied between one and six digits.Using TRS,we recorded changes in cerebral blood oxygenation as a measure of changes in PFC activity during the task.In order to identify left/right asymmetry of PFC activity during the working memory task,we calculated the laterality score,i.e.,Δoxy‐Hb(rightΔoxy‐Hb—leftΔoxy‐Hb);positive values indicate greater activity in the right PFC,while negative values indicate greater activity in the left PFC.Results:During the ST,statistical analyses showed no significant differences between the younger and older groups in accuracy for low memory‐load and high memory‐load.In high memory‐load tasks,however,older subjects were slower than younger subjects(P<0.05).We found that the younger group showed right lateral responses with a stronger right than left activation in the frontal pole,whereas the older group showed bilateral responses(P<0.05).Conclusions:The present results are consistent with the hemispheric asymmetry reduction in older adults(HAROLD)model;working memory tasks cause asymmetrical PFC activation in younger adults,while older adults tend to show reduced hemispheric lateralization.展开更多
Near-infrared(NIR)-absorbing polymerized small molecule acceptors(PSMAs)based on a Y-series backbone(such as PY-IT)have been widely developed to fabricate efficient all-polymer solar cells(all-PSCs).However,medium-ban...Near-infrared(NIR)-absorbing polymerized small molecule acceptors(PSMAs)based on a Y-series backbone(such as PY-IT)have been widely developed to fabricate efficient all-polymer solar cells(all-PSCs).However,medium-bandgap PSMAs are often overlooked,while they as the third component can be expected to boost power conversion efficiencies(PCEs)of all-PSCs,mainly due to their up-shifted lowest unoccupied molecular orbital(LUMO)energy level,complimentary absorption,and diverse intermolecular interaction compared to the NIR-absorbing host acceptor.Herein,an IDIC-series medium-bandgap PSMA(P-ITTC)is developed and introduced as the third component into D18/PY-IT host,which can not only form complementary absorption and cascade energy level,but also finely optimize active layer morphology.Therefore,compared to the D18/PY-IT based parental all-PSCs,the ternary all-PSCs based on D18/PY-IT:P-ITTC obtain an increased exciton dissociation,charge transport,carrier lifetime,as well as suppressed charge recombination and energy loss.As a result,the ternary all-PSCs achieve a high PCE of 17.64%with a photovoltage of 0.96 V,both of which are among the top values in layer-by-layer typed all-PSCs.This work provides a method for the design and selection of the medium-bandgap third component to fabricate efficient all-PSCs.展开更多
Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empi...Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empirical studies[5]suggest that they are a key neural substrate for spatial navigation.In humans,grid cells can be indirectly measured by gridlike representations(GLRs)at the level of fMRI BOLD responses[6]and local field potentials[7].展开更多
基金Natural Science Foundation of Inner Mongolia Autonomous Region(2021MS08169).
文摘Objective: To observe the effects of remote ischemia on cognitive function and neuronal pathological damage in rats with cognitive impairment induced by bilateral common carotid artery occlusion(BCAO).Methods:Male SD rats were selected to establish the cognitive impairment model induced by cerebral ischemia reperfusion caused by BCAO.The tests included three groups of rats:a sham group,a model group with vascular cognitive impairment (VCI) , and a remote ischemic conditioning (RIC) group (VCI + RIC group). From 24 h after operation, both hind limbs of rats in VCI + RIC group were treated with RIC. After 28 d, Morris water maze test and HE staining was used to observe the pathological changes of white matter and hippocampus in each group.Results: After 3 d mice in VCI group began to improve gradually. The recovery of rats in the VCI + RIC group was relatively slow,but they started to recover rapidly 2 d after the operation.Morris water maze test showed that the escape latency of rats in VCI group and VCI+RIC group was longer than that in the sham group, and the score of VCI+RIC group was better than that of the VCI group, but there was a significant difference between the two groups(P<0.05).The space exploration experiment was performed at 7 d and 28 d after the operation;the VCI+RIC group outperformed the VCI group in both trials;the difference between the two groups was statistically significant (P<0.05).In the target quadrant exploration time, the difference between the VCI group (33.5±11.3 s) and the VCI+RIC group (41.2±9.7 s) was statistically significant (P<0.05).Results from the hematoxylin and eosin(HE)staining showed that compared with VCI group, cortical cells in VCI + RIC group had loose stroma, thinner nerve fibers, fewer broken cells, and slightly shrunken cells. Compared with VCI group, neurons in VCI + RIC group had a little vacuolar degenera-tion and slightly shrunken cell volume.Conclusion:Cerebral ischemia-reperfusion injury can cause learning and memory impairment in rats, leading to VCI. RIC can significantly improve VCI and play a neuroprotective role.
基金supported by the National Key Research and Development Plan of China (No.2019YFC1805300)Postdoctoral Science Foundation (No.2022M711476)+1 种基金the National Nature Science Foundation of China (No.41830861)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (No.2017ZT07Z479)。
文摘Sulfate-reducing bacteria play an important role in the geochemistry of iron(oxyhydr)oxide and arsenic(As)in natural environments;however,the associated reaction processes are yet to be fully understood.In this study,batch experiments coupled with geochemical,spectroscopic,microscopic,and thermodynamic analyses were conducted to investigate the dynamic coupling of ferrihydrite transformation and the associated As desorption/redistribution mediated by Desulfovibrio vulgaris(D.vulgaris).The results indicated that D.vulgaris could induce ferrihydrite transformation via S^(2-)-driven and direct reduction processes.In the absence of SO_(4)^(2-),D.vulgaris directly reduced ferrihydrite,and As desorption and re-sorption occurred simultaneously during the partial transformation of ferrihydrite to magnetite.The increase in SO_(4)^(2-)loading promoted the S^(2-)-driven reduction of ferrihydrite and accelerated the subsequent mineralogical transformation.In the low and medium SO_(4)^(2-)treatments,ferrihydrite was completely transformed to a mixture of magnetite and mackinawite,which increased the fraction of As in the residual phase and stabilized As.In the high SO_(4)^(2-)treatment,although the replacement of ferrihydrite by only mackinawite also increased the fraction of As in the residual phase,22.1%of the total As was released into the solution due to the poor adsorption affinity of As to mackinawite and the conversion of As^(5+)to As^(3+).The mechanisms of ferrihydrite reduction,mineralogy transformation,and As mobilization and redistribution mediated by sulfate-reducing bacteria are closely related to the surrounding SO_(4)^(2-)loadings.These results advance our understanding of the biogeochemical behavior of Fe,S,and As,and are helpful for the risk assessment and remediation of As contamination.
基金supported by the National Natural Science Foundation of China (Grants 31771549 to Y.C.,82103251 to J.Z.,82203153 to K.Z.,and 82203574 to S.W.)the 1.3.5 Project for Disciplines of Excellence (Grants ZYGD18021,ZYJC18009,ZYJC21002,and ZYJC21015)+1 种基金the China Postdoctoral Science Foundation (Grants 2020TQ0210 and 2021M692268 to J.Z.)Natural Science Foundation of Sichuan Province (Grant 2022NSFSC1438 to J.Z.).
文摘Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.
基金supported by grants from the National Natural Science Foundation of China(No.81672314)the Key Natural Science Project of Anhui Provincial Education Department(No.KJ2020A1244,KJ2020A0578,and KJ2018A0221)National Innovation Program for College Students(Nos.201810367021 and 201710367036).
文摘Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
文摘To the Editor:Cardiac arrest(CA)is one of the leading causes of adult death globally.According to the latest American Heart Association reports,[1]the incidences of Emergency Medical Service-assessed adult out-of-hospital cardiac arrest(OHCA)and in-hospital cardiac arrest(IHCA)were 140.7/100,000 and 10.2/1000,respectively.
基金supported by the National Natural Science Foundation of China(Nos.22076198,42192571,and 21827815).
文摘The application of selenium nanoparticles(SeNPs)as nanofertilizers may lead to the release of SeNPs into aquatic systems.However,the environmental behavior of SeNPs is rarely studied.In this study,using alginate-coated SeNPs(Alg-SeNPs)and polyvinyl alcohol-coated SeNPs(PVA-SeNPs)as models,we systematically investigated the aggregation and stability of SeNPs under various water conditions.PVA-SeNPs were highly stable in mono-and polyvalent electrolytes,probably due to the strong steric hindrance of the capping agent.Alg-SeNPs only suffered from a limited increase in size,even at 2500 mmol/L NaCl and 200 mmol/L MgCl_(2),while they underwent apparent aggregation in CaCl_(2) and LaCl_(3) solutions.The binding of Ca^(2+) and La^(3+) with the guluronic acid part in alginate induced the formation of cross-linking aggregates.Natural organic matter enhanced the stability of Alg-SeNPs in monovalent electrolytes,while accelerated the attachment of Alg-SeNPs in polyvalent electrolytes,due to the cation bridge effects.The long-term stability of SeNPs in natural water showed that the aggregation sizes of Alg-SeNPs and PVA-SeNPs increased to several hundreds of nanometers or above 10μm after 30 days,implying that SeNPs may be suspended in the water column or further settle down,depending on the surrounding water chemistry.The study may contribute to the deep insight into the fate and mobility of SeNPs in the aquatic environment.The varying fate of SeNPs in different natural waters also suggests that the risks of SeNPs to organisms living in diverse depths in the aquatic compartment should be concerned.
文摘Researchers have widely acknowledged the therapeutic value of epilepsy surgery for drug-resistant epilepsy.None-theless,there is a substantial gap in the surgical treatment for appropriate candidates owing to several factors,particularly in the population of young children.To standardize the protocols of preoperative evaluation and sur-gery of young children for epilepsy surgery,the China Association Against Epilepsy has appointed an expert task force to standardize the protocols of preoperative evaluation and surgery in pediatric epilepsy patients.It adopted the modifed Delphi method and performed two rounds of surveys through an anonymous inquiry among 75 experts from four subgroups including pediatric neurologists,epileptologists,pediatric epilepsy surgeons,and functional neurosurgeons.The survey contents contained:(1)the participants,comprising children aged≤6 years;(2)adopted DRE definition proposed by the International League Against Epilepsy in 2010;and(3)investigated epilepsy surgery,principally referring to curative epilepsy surgeries.The neuromodulation therapies were excluded because of the differences in treatment mechanisms from the above-mentioned surgeries.According to the Delphi process,a con-sensus was achieved for most aspects by incorporating two rounds of surveys including preoperative assessment,sur-gical strategies and techniques,and perioperative and long-term postoperative management,despite controversial opinions on certain items.We hope the results of this consensus will improve the level of surgical treatment and man-agement of intractable epilepsy in young children.
文摘Stereoelectroencephalography(SEEG)has been widely used in the presurgical evaluation of patients with medically intractable epilepsy.In the past,SEEG was commonly used as a method for mapping and localizing the epileptogenic zone(EZ).Since 2004,several studies have been conducted to examine the effectiveness of SEEG-guided radiofrequency thermocoagulation(RF-TC)in treating refractory epilepsy.However,the seizure-free and responder rates varied greatly across studies.We aimed to analyze the outcome of 56 patients who were treated with SEEG-guided RF-TC to evaluate the effectiveness of this treatment.SEEG-guided RF-TC can be considered as a treatment for refractory epilepsy.However,due to its limited efficacy,SEEG-guided RF-TC might be regarded as a temporary treatment performed under SEEG rather than a promising treatment for refractory epilepsy.
文摘Encephalitis is an acute inflammatory process of the brain parenchyma,which is often caused by viral infection.It is an vital cause of acute symptomatic seizures and subsequent epilepsy.The incidence of unprovoked and recurrent seizures after previous infections of the central nervous system is high and accounts for1%~5%of the cases of epilepsy.Viral encephalitis(VE)is directly caused by viral infection.The occurrence of seizures after VE is associated with poor prognosis.In survivors of VE,among other neurological sequelae,the risk of developing epilepsy is increased10-fold.The risk of severe neurological sequelae after VE is particularly high in very young children.Studies on seizure occurrence,possible underlying mechanisms,clinical characteristics,and clinical treatment(especially surgical treatment)of VE have yielded only limited detailed data.We reviewed the most recent literature on the clinical features and surgical treatment of post-VE epilepsy.
基金Supported by Tsinghua University Initiative Scientific Research Program(No.2015THZ01)
文摘For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection of the epileptogenic zone because of the proximity of a functional area or the implication of a larger epileptogenic network. Initially, stereoelectroencephalography(SEEG) exploration was a method of electroencephalography recording that was used in the presurgical evaluation of epileptic patients with complex epilepsy. Later, intracerebral electrodes used for SEEG were applied to produce radio frequency thermocoagulation(RF-TC) in epileptic patients. SEEG-guided RF-TC has produced some promising results, especially in the last dacade. Now, it has become popular as a palliative treatment to reduce seizure frequency in patients with drug-resistant focal epilepsy. This article presents a review of SEEG-guided RF-TC.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.61420106011,61871408,and 61871082)
文摘We propose the modified Kalman filter(MKF) using the received signal for observation and constructing an inverse process of the conventional Kalman filter(CKF) for polarization de-multiplexing in coherent optical(CO) orthogonal frequency-division multiplexing(OFDM) transmissions. The MKF can avoid the convergence error problem in CKF without matrix inverse operation and has a faster converging speed and a much larger tolerance to the process and measurement noise covariance, about two orders of magnitude more than those of CKF. We experimentally demonstrate the 12 Gbaud OFDM signal transmission over 480 km standard singlemode fiber. The performance of MKF and CKF outperforms pilot-aided polarization de-multiplexing with better accuracy and nonlinearity tolerance.
基金the National Key R&D Program(No.2018YFC1314500)the National Natural Science Foundation of China(No.81701297,81801124).
文摘Studies in animal models of epilepsy and pre-surgical patients have unanimously found a strong correlation between high-frequency oscillations(HFOs,>80 Hz)and the epileptogenic zone,suggesting that HFOs can be a potential biomarker of epileptogenicity and epileptogenesis.This consensus includes the definition and standard detection techniques of HFOs,the localizing value of pathological HFOs for epileptic foci,and different ways to distinguish physiological from epileptic HFOs.The latest clinical applications of HFOs in epilepsy and the related findings are also discussed.HFOs will advance our understanding of the pathophysiology of epilepsy.
基金supported by China Postdoctoral Science Foundation(2021 M690128)the Open Project Program of State Key Laboratory of Crop Stress Biology for Arid Areas(CSBAA2020011)+1 种基金National Natural Science Foundation-Xinjiang Joint Foundation of China(U1903206)Major Scientific and Technological Projects of Shaanxi Province(2020zdzx03-03-01).
文摘Conserved effectors produced by phytopathogens play critical roles in plant-microbe interactions.NIS1-like proteins represent a newly identified family of effectors distributed in multiple fungal species.However,their biological functions in a majority of pathogenic fungi remain largely elusive and require further investigation.In this study,we characterized two NIS1-like proteins VmNIS1 and VmNIS2 from Valsa mali,the causal agent of apple Valsa canker.Both of these two proteins were predicted to be secreted.Using agroinfiltration,we found that VmNIS1 induced intense cell death,whereas VmNIS2 suppressed INF1 elicitin-triggered cell death in Nicotiana benthamiana.Treatment of N.benthamiana with VmNIS1 recombinant protein produced by Escherichia coli activated a series of immune responses and enhanced plant disease resistance against Phytophthora capsici.In contrast,VmNIS2 suppressed plant immune responses and promoted P.capsici infection when transiently expressed in N.benthamiana.Both VmNIS1 and VmNIS2 were shown to be highly induced at late stage of V.mali infection.By individually knocking out of these two genes in V.mali,however,only VmNIS2 was shown to be required for pathogen virulence as well as tolerance to oxidative stress.Notably,we further showed that C-terminal extension of VmNIS1 was essential for plant recognition and VmNIS2 may escape plant detection via sequence truncation.Our data collectively indicate that VmNIS1 and VmNIS2 play distinct roles in plant recognition and pathogen virulence,which provided new insights into the function of NIS1-like proteins in plant-microbe interactions.
基金The work is supported by the National Natural Science Foundation of China(NSFC:32125021,92254308,91957119,91954001,31571213 to X.W.C,32100947 to X.W.,and 62027901 to J.T.)the National Key R&D Program(2021YFA0804802).
文摘Precise control of circulating lipid levels is vital in both health and disease.We recently uncovered that bulk lipids,transported by lipoproteins,enter the circulation initially via the coat protein complex II(COPII)in a condensation-dependent manner.Divalent manganese,acting as a signaling messenger,selectively controls COPII condensation to regulate lipid homeostasis in vivo.Here,we present evidence for a manganese-based therapy in murine models of hypolipidemia and hyperlipidemia.
文摘Epileptic spasm(ES)is one of the most common types of seizures in children.It is primarily characterized by brief axial contractions lasting less than 2 s and recurring in short clusters.It usually occurs in children of 3 to 12 months of age,although it can also occur after the age of 1 year.In general,children with ES develop other symptoms of epilepsy,such as tonic,tonic-clonic,or focal seizures,after 3 to 5 years of age.ES in children is often damaging and usually results in developmental regression.First-line treatments for spasm seizures include adrenocorticotropic hormone(ACTH)and vigabatrin.However,many patients fail to respond to these medications,and continued to have spasms associated with progressive neurodevelopmental degeneration.Therefore,it is important to consider whether children with drug resistance meet surgical indications to consider surgical treatment in such conditions.In this study,we reviewed and summarized the importance of preoperative evaluation in order to provide surgical options for treatment of children with ES.
基金Supported by the Strategic Research Foundation Grant-aided Project for Private Universities(No.S1411017)a Grant-in-Aid for Exploratory Research(No.25560356)from the Ministry of Education,Culture,Sports,Sciences,and Technology of Japan
文摘Objective:This study aimed to employ time‐resolved spectroscopy(TRS)to explore age‐related differences in prefrontal cortex(PFC)activity while subjects performed a working memory task.Methods:We employed TRS to measure PFC activity in ten healthy younger and ten healthy older subjects while they performed a working memory(WM)task.All subjects performed the Sternberg test(ST)in which the memory‐set size varied between one and six digits.Using TRS,we recorded changes in cerebral blood oxygenation as a measure of changes in PFC activity during the task.In order to identify left/right asymmetry of PFC activity during the working memory task,we calculated the laterality score,i.e.,Δoxy‐Hb(rightΔoxy‐Hb—leftΔoxy‐Hb);positive values indicate greater activity in the right PFC,while negative values indicate greater activity in the left PFC.Results:During the ST,statistical analyses showed no significant differences between the younger and older groups in accuracy for low memory‐load and high memory‐load.In high memory‐load tasks,however,older subjects were slower than younger subjects(P<0.05).We found that the younger group showed right lateral responses with a stronger right than left activation in the frontal pole,whereas the older group showed bilateral responses(P<0.05).Conclusions:The present results are consistent with the hemispheric asymmetry reduction in older adults(HAROLD)model;working memory tasks cause asymmetrical PFC activation in younger adults,while older adults tend to show reduced hemispheric lateralization.
基金M.Xiao thanks for the financial support from the Scientific Research Project of Education Department of Hunan Province(23B0167)the Open Funds of the State Key Laboratory of Luminescent Materials and Devices(South China University of Technology)(2023-skllmd-13)and NSFC(52403251)+4 种基金Q.Fan thanks for the support from the NSFC(22209131)W.Peng thanks for the support from Changzhou Leading Innovative Talent Introduction and Cultivation Project(CQ20230070)Jiangsu Enterprise Practice Project for Teachers of Higher Vocational Colleges(2024QYSJ058)the"Blue Project"of Jiangsu Province's Colleges,the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(24KJB430006)J.Jia thanks the financial support from Guangdong Academy of Sciences(GDAS)'Project of Science and Technology Development(No.2022GDASZH-2022010111)。
文摘Near-infrared(NIR)-absorbing polymerized small molecule acceptors(PSMAs)based on a Y-series backbone(such as PY-IT)have been widely developed to fabricate efficient all-polymer solar cells(all-PSCs).However,medium-bandgap PSMAs are often overlooked,while they as the third component can be expected to boost power conversion efficiencies(PCEs)of all-PSCs,mainly due to their up-shifted lowest unoccupied molecular orbital(LUMO)energy level,complimentary absorption,and diverse intermolecular interaction compared to the NIR-absorbing host acceptor.Herein,an IDIC-series medium-bandgap PSMA(P-ITTC)is developed and introduced as the third component into D18/PY-IT host,which can not only form complementary absorption and cascade energy level,but also finely optimize active layer morphology.Therefore,compared to the D18/PY-IT based parental all-PSCs,the ternary all-PSCs based on D18/PY-IT:P-ITTC obtain an increased exciton dissociation,charge transport,carrier lifetime,as well as suppressed charge recombination and energy loss.As a result,the ternary all-PSCs achieve a high PCE of 17.64%with a photovoltage of 0.96 V,both of which are among the top values in layer-by-layer typed all-PSCs.This work provides a method for the design and selection of the medium-bandgap third component to fabricate efficient all-PSCs.
基金supported by STI2030-Major Projects(2022ZD0205000)the National Natural Science Foundation of China(32020103009 and 32200861)+1 种基金a Ministry Key Project(GW0890006)NA acknowledges funding via DFG grant Project number 429281110.
文摘Dear Editor,Electrophysiological studies have found that the entorhinal cortex(EC)contains grid cells that fire at the vertices of equilateral triangles tiling the entire environment[1-3].Theoretical models[4]and empirical studies[5]suggest that they are a key neural substrate for spatial navigation.In humans,grid cells can be indirectly measured by gridlike representations(GLRs)at the level of fMRI BOLD responses[6]and local field potentials[7].
