Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Her...Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environme...Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.展开更多
Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2) production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study...Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2) production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2) overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell.In dilute(0.1 M)NaCl solutions,the NFI/TiO_(2) marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was confirmed.Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic contact.Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine.The scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.展开更多
A bearing fault diagnosis method based on the Markov transitionfield(MTF)and SEnet(SE)-IShufflenetV2 model is proposed in this paper due to the problems of complex working conditions,low fault diagnosis accuracy,and poo...A bearing fault diagnosis method based on the Markov transitionfield(MTF)and SEnet(SE)-IShufflenetV2 model is proposed in this paper due to the problems of complex working conditions,low fault diagnosis accuracy,and poor generalization of rolling bearing.Firstly,MTF is used to encode one-dimensional time series vibration sig-nals and convert them into time-dependent and unique two-dimensional feature images.Then,the generated two-dimensional dataset is fed into the SE-IShufflenetV2 model for training to achieve fault feature extraction and classification.This paper selects the bearing fault datasets from Case Western Reserve University and Paderborn University to experimentally verify the effectiveness and superiority of the proposed method.The generalization performance of the proposed method is tested under the variable load condition and different signal-to-noise ratios(SNRs).The experimental results show that the average accuracy of the proposed method under different working conditions is 99.2%without adding noise.The accuracy under different working conditions from 0 to 1 HP is 100%.When the SNR is 0 dB,the average accuracy of the proposed method can still reach 98.7%under varying working conditions.Therefore,the bearing fault diagnosis method proposed in this paper is characterized by high accuracy,strong anti-noise ability,and generalization.Moreover,the proposed method can also overcome the influence of variable working conditions on diagnosis accuracy,providing method support for the accurate diagnosis of bearing faults under strong noise and variable working conditions.展开更多
Pecan is an extremely important crop cultivated worldwide for edible nuts and nut oil.Considering the changes in precipitation and soil moisture caused by climate change and worsening global water scarcity,it is impor...Pecan is an extremely important crop cultivated worldwide for edible nuts and nut oil.Considering the changes in precipitation and soil moisture caused by climate change and worsening global water scarcity,it is important to understand the mechanism of pecan response to drought.To this end,this study investigated the response of pecan to drought stress and rehydration using physiological and transcriptomic analyses.Superoxide dismutase(SOD)enzyme activity in leaves was significantly upregulated during drought stress,suggesting that it might play an important role in drought response.Weighted gene co-expression network analysis of the transcriptome data was used to screen for a key drought-responsive gene,CiNAC2,which was overexpressed in Arabidopsis thaliana for functional validation.The analysis of stomatal apertures and the water loss rate in leaves showed that CiNAC2 might respond to drought stress via mediating stomatal aperture size.In addition,CiNAC2 could promote root growth under drought conditions.CiSOD1 was verified as a direct target gene of CiNAC2 by yeast one-hybrid assay dual-luciferase reporter assay.Yeast one-hybrid analysis confirmed that CiNAC2 bound to the promoters of CiSOD1.Transient expression in Nicotiana benthamiana epidermis showed that CiNAC2 upregulated the expression of CiSOD1.These results demonstrated that CiNAC2 enhanced drought stress tolerance via promoting SOD activity in pecan and provided a theoretical basis for breeding drought-resistant varieties in pecan.展开更多
The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was establishe...The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.展开更多
In this study,an integrated technology is proposed for the absorption and utilization of CO_(2)in alkanolamine solution for the preparation of BaCO_(3)in a high-gravity environment.The effects of absorbent type,high-g...In this study,an integrated technology is proposed for the absorption and utilization of CO_(2)in alkanolamine solution for the preparation of BaCO_(3)in a high-gravity environment.The effects of absorbent type,high-gravity factor,gas/liquid ratio,and initial BaCl2concentration on the absorption rate and amount of CO_(2)and the preparation of BaCO_(3)are investigated.The results reveal that the absorption rate and amount of CO_(2)follow the order of ethyl alkanolamine(MEA)>diethanol amine(DEA)>N-methyldiethanolamine(MDEA),and thus MEA is the most effective absorbent for CO_(2)absorption.The absorption rate and amount of CO_(2)under high gravity are higher than that under normal gravity.Notably,the absorption rate at 75 min under high gravity is approximately 2 times that under normal gravity.This is because the centrifugal force resulting from the high-speed rotation of the packing can greatly increase gas-liquid mass transfer and micromixing.The particle size of BaCO_(3)prepared in the rotating packed bed is in the range of 57.2—89 nm,which is much smaller than that prepared in the bubbling reactor(>100.3 nm),and it also has higher purity(99.6%)and larger specific surface area(14.119 m^(2)·g^(-1)).It is concluded that the high-gravity technology has the potential to increase the absorption and utilization of CO_(2)in alkanolamine solution for the preparation of BaCO_(3).This study provides new insights into carbon emissions reduction and carbon utilization.展开更多
BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate...BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.展开更多
The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.Howev...The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.展开更多
In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers ar...In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology.PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity.Accordingly,early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction.On the other hand,recent studies have indicated that PTPN2 has many different roles in different cancer types,which is associated with the complexity of its regulatory network.PTPN2 dephosphorylates and inactivates EGFR,SRC family kinases,JAK1 and JAK3,and STAT1,STAT3,and STAT5 in cell type-and context-dependent manners,which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype.While PTPN2 has been suggested as a potential therapeutic target in cancer treatment,to the best of ourknowledge,no clear treatment protocol has referred to PTPN2.Although there are only few studies that investigated PTPN2 expression in the GI system cancers,which is a potential limitation,the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors,especially in tumors resistant to therapy.展开更多
BACKGROUND Due to saliva and salivary glands are reservoir to severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),aerosols and saliva droplets are primary sources of cross-infection and are responsible for the...BACKGROUND Due to saliva and salivary glands are reservoir to severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),aerosols and saliva droplets are primary sources of cross-infection and are responsible for the high human–human transmission of SARS-CoV-2.However,there is no evidence about how SARSCoV-2 interacts with oral structures,particularly resin composites.AIM To evaluate the interaction of SARS-CoV-2 proteins with monomers present in resin composites using in silico analysis.METHODS Four SARS-CoV-2 proteins[i.e.main protease,3C-like protease,papain-like protease(PLpro),and glycoprotein spike]were selected along with salivary amylase as the positive control,and their binding affinity with bisphenol-A glycol dimethacrylate,bisphenol-A ethoxylated dimethacrylate,triethylene glycol dimethacrylate,and urethane dimethacrylate was evaluated.Molecular docking was performed using AutoDock Vina and visualised in Chimera UCSF 1.14.The best ligand–protein model was identified based on the binding energy(ΔG–kcal/moL).RESULTS Values for the binding energies ranged from-3.6 kcal/moL to-7.3 kcal/moL.The 3-monomer chain had the lowest binding energy(i.e.highest affinity)to PLpro and the glycoprotein spike.Non-polymerised monomers and polymerised chains interacted with SARS-CoV-2 proteins via hydrogen bonds and hydrophobic interactions.Those findings suggest an interaction between SARS-CoV-2 proteins and resin composites.CONCLUSION SARS-CoV-2 proteins show affinity to non-polymerised and polymerised resin composite chains.展开更多
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金supported by the National Natural Science Foundation of China,Nos.82271283(to XC),91854115(to JW),31970044(to JW)the Natural Science Foundation of Beijing,No.7202001(to XC)the Scientific Research Project of Beijing Educational Committee,No.KM202010005022(to XC)。
文摘Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.
基金supported by the National Research Foundation of Korea(NRF)grants(2022R1A2C4001228,2022M3H4A4097524,2022M3I3A1082499,and 2021M3I3A1084818)the Technology Innovation Program(20026415)of the Ministry of Trade,Industry&Energy(MOTIE,Korea)the supports from Nanopac for fabrication of scaled-up reactor.
文摘Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2) production can reduce the carbon footprint associated with transportation of water,waste,and energy carrier.This study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2) overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell.In dilute(0.1 M)NaCl solutions,the NFI/TiO_(2) marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was confirmed.Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic contact.Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine.The scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.
基金supported by Hebei Natural Science Foundation under Grant No.E2024402079Key Laboratory of Intelligent Industrial Equipment Technology of Hebei Province(Hebei University of Engineering)under Grant No.202206.
文摘A bearing fault diagnosis method based on the Markov transitionfield(MTF)and SEnet(SE)-IShufflenetV2 model is proposed in this paper due to the problems of complex working conditions,low fault diagnosis accuracy,and poor generalization of rolling bearing.Firstly,MTF is used to encode one-dimensional time series vibration sig-nals and convert them into time-dependent and unique two-dimensional feature images.Then,the generated two-dimensional dataset is fed into the SE-IShufflenetV2 model for training to achieve fault feature extraction and classification.This paper selects the bearing fault datasets from Case Western Reserve University and Paderborn University to experimentally verify the effectiveness and superiority of the proposed method.The generalization performance of the proposed method is tested under the variable load condition and different signal-to-noise ratios(SNRs).The experimental results show that the average accuracy of the proposed method under different working conditions is 99.2%without adding noise.The accuracy under different working conditions from 0 to 1 HP is 100%.When the SNR is 0 dB,the average accuracy of the proposed method can still reach 98.7%under varying working conditions.Therefore,the bearing fault diagnosis method proposed in this paper is characterized by high accuracy,strong anti-noise ability,and generalization.Moreover,the proposed method can also overcome the influence of variable working conditions on diagnosis accuracy,providing method support for the accurate diagnosis of bearing faults under strong noise and variable working conditions.
基金supported by the National Key R&D Program of China(Grant No.2022YFD220040203)Jiangxi Forestry Bureau forestry Science and technology innovation special project“Introduction test and Screening of pecan clones”innovation special project[Grant No.(2020)04]。
文摘Pecan is an extremely important crop cultivated worldwide for edible nuts and nut oil.Considering the changes in precipitation and soil moisture caused by climate change and worsening global water scarcity,it is important to understand the mechanism of pecan response to drought.To this end,this study investigated the response of pecan to drought stress and rehydration using physiological and transcriptomic analyses.Superoxide dismutase(SOD)enzyme activity in leaves was significantly upregulated during drought stress,suggesting that it might play an important role in drought response.Weighted gene co-expression network analysis of the transcriptome data was used to screen for a key drought-responsive gene,CiNAC2,which was overexpressed in Arabidopsis thaliana for functional validation.The analysis of stomatal apertures and the water loss rate in leaves showed that CiNAC2 might respond to drought stress via mediating stomatal aperture size.In addition,CiNAC2 could promote root growth under drought conditions.CiSOD1 was verified as a direct target gene of CiNAC2 by yeast one-hybrid assay dual-luciferase reporter assay.Yeast one-hybrid analysis confirmed that CiNAC2 bound to the promoters of CiSOD1.Transient expression in Nicotiana benthamiana epidermis showed that CiNAC2 upregulated the expression of CiSOD1.These results demonstrated that CiNAC2 enhanced drought stress tolerance via promoting SOD activity in pecan and provided a theoretical basis for breeding drought-resistant varieties in pecan.
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
文摘The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.
基金supported by Research Project Supported by Horizon Europe Framework Programme(101183092)Shanxi Scholarship Council of China(2023-128)+2 种基金National Natural Science Foundation of China(22208328)Fundamental Research Program of Shanxi Province(20210302124618)Small and mediumsized oriented scientific and technological enterprises innovation ability improvement project of Shandong Province(2023TSGC0004)。
文摘In this study,an integrated technology is proposed for the absorption and utilization of CO_(2)in alkanolamine solution for the preparation of BaCO_(3)in a high-gravity environment.The effects of absorbent type,high-gravity factor,gas/liquid ratio,and initial BaCl2concentration on the absorption rate and amount of CO_(2)and the preparation of BaCO_(3)are investigated.The results reveal that the absorption rate and amount of CO_(2)follow the order of ethyl alkanolamine(MEA)>diethanol amine(DEA)>N-methyldiethanolamine(MDEA),and thus MEA is the most effective absorbent for CO_(2)absorption.The absorption rate and amount of CO_(2)under high gravity are higher than that under normal gravity.Notably,the absorption rate at 75 min under high gravity is approximately 2 times that under normal gravity.This is because the centrifugal force resulting from the high-speed rotation of the packing can greatly increase gas-liquid mass transfer and micromixing.The particle size of BaCO_(3)prepared in the rotating packed bed is in the range of 57.2—89 nm,which is much smaller than that prepared in the bubbling reactor(>100.3 nm),and it also has higher purity(99.6%)and larger specific surface area(14.119 m^(2)·g^(-1)).It is concluded that the high-gravity technology has the potential to increase the absorption and utilization of CO_(2)in alkanolamine solution for the preparation of BaCO_(3).This study provides new insights into carbon emissions reduction and carbon utilization.
基金Supported by Hebei Province Medical Science Research Project Plan,No.20230755.
文摘BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
基金funded by the National Natural Science Foundation of China(Grant Nos.32202502,U21A20230,32070331,32102380 and 32072580)National Key Research and Development Program(Grant No.2018YFD1000800)+3 种基金the Key-Area Research and Development Program of Guangdong Province(Grant No.2022B0202080001)the Special Fund for Seed Industry of Guangdong Province Rural Revitalization Strategy(Grant No.2022-NPY00-024)Tibet Autonomous Region of Lhasa City Science and Technology Project(Grant No.LSKJ202310)the Science and Technology Project of Bijie City(Grant No.BKK2022-3)。
文摘The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.
文摘In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology.PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity.Accordingly,early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction.On the other hand,recent studies have indicated that PTPN2 has many different roles in different cancer types,which is associated with the complexity of its regulatory network.PTPN2 dephosphorylates and inactivates EGFR,SRC family kinases,JAK1 and JAK3,and STAT1,STAT3,and STAT5 in cell type-and context-dependent manners,which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype.While PTPN2 has been suggested as a potential therapeutic target in cancer treatment,to the best of ourknowledge,no clear treatment protocol has referred to PTPN2.Although there are only few studies that investigated PTPN2 expression in the GI system cancers,which is a potential limitation,the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors,especially in tumors resistant to therapy.
文摘BACKGROUND Due to saliva and salivary glands are reservoir to severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),aerosols and saliva droplets are primary sources of cross-infection and are responsible for the high human–human transmission of SARS-CoV-2.However,there is no evidence about how SARSCoV-2 interacts with oral structures,particularly resin composites.AIM To evaluate the interaction of SARS-CoV-2 proteins with monomers present in resin composites using in silico analysis.METHODS Four SARS-CoV-2 proteins[i.e.main protease,3C-like protease,papain-like protease(PLpro),and glycoprotein spike]were selected along with salivary amylase as the positive control,and their binding affinity with bisphenol-A glycol dimethacrylate,bisphenol-A ethoxylated dimethacrylate,triethylene glycol dimethacrylate,and urethane dimethacrylate was evaluated.Molecular docking was performed using AutoDock Vina and visualised in Chimera UCSF 1.14.The best ligand–protein model was identified based on the binding energy(ΔG–kcal/moL).RESULTS Values for the binding energies ranged from-3.6 kcal/moL to-7.3 kcal/moL.The 3-monomer chain had the lowest binding energy(i.e.highest affinity)to PLpro and the glycoprotein spike.Non-polymerised monomers and polymerised chains interacted with SARS-CoV-2 proteins via hydrogen bonds and hydrophobic interactions.Those findings suggest an interaction between SARS-CoV-2 proteins and resin composites.CONCLUSION SARS-CoV-2 proteins show affinity to non-polymerised and polymerised resin composite chains.
