The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel micr...The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.展开更多
The newly developed software,Nucleus++,is an advanced tool for displaying basic nuclear physics properties from NubAsE and integrating comprehensive mass information for each nuclide from Atomic Mass Evaluation.Additi...The newly developed software,Nucleus++,is an advanced tool for displaying basic nuclear physics properties from NubAsE and integrating comprehensive mass information for each nuclide from Atomic Mass Evaluation.Additionally,it allows users to compare experimental nuclear masses with predictions from different mass models.Building on the success and learning experiences of its predecessor,Nucleus,this enhanced tool introduces improved functionality and compatibility.With its user-friendly interface,Nucleus++was designed as a valuable tool for scholars and practitioners in the field of nuclear science.This article offers an in-depth description of Nucleus++,highlighting its main features and anticipated impacts on nuclear science research.展开更多
The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates ...The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined.This study provides the first comprehensive,unbiased,cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens.Within the hypothalamus,pituitary,and ovary,seven,12,and 13 distinct cell types were identified,respectively.Results indicated that the pituitary adenylate cyclase activating polypeptide(PACAP),follicle-stimulating hormone(FSH),and prolactin(PRL)signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone(GnRH),FSH,and luteinizing hormone(LH)within the hypothalamus and pituitary.In the ovary,interactions between granulosa cells and oocytes involved the KIT,CD99,LIFR,FN1,and ANGPTL signaling pathways,which collectively regulate follicular maturation.The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis.Additionally,gene expression analysis revealed that relaxin 3(RLN3),gastrin-releasing peptide(GRP),and cocaine-and amphetamine regulated transcripts(CART,also known as CARTPT)may function as novel endocrine hormones,influencing the HPO axis through autocrine,paracrine,and endocrine pathways.Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP,RLN3,CARTPT,LHCGR,FSHR,and GRPR in the ovaries of Lohmann layers,potentially contributing to their superior reproductive performance.In conclusion,this study provides a detailed molecular characterization of the HPO axis,offering novel insights into the regulatory mechanisms underlying reproductive biology.展开更多
Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impair...Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.展开更多
There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nuc...There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.展开更多
BACKGROUND Intervertebral disc degeneration(IDD)is a main contributor to low back pain.Oxidative stress,which is highly associated with the progression of IDD,increases senescence of nucleus pulposus-derived mesenchym...BACKGROUND Intervertebral disc degeneration(IDD)is a main contributor to low back pain.Oxidative stress,which is highly associated with the progression of IDD,increases senescence of nucleus pulposus-derived mesenchymal stem cells(NPMSCs)and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs(IVDs).Quercetin(Que)has been demonstrated to reduce oxidative stress in diverse degenerative diseases.AIM To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism.METHODS In vitro,NPMSCs were isolated from rat tails.Senescence-associatedβ-galactosidase(SA-β-Gal)staining,cell cycle,reactive oxygen species(ROS),realtime quantitative polymerase chain reaction(RT-qPCR),immunofluorescence,and western blot analyses were used to evaluated the protective effects of Que.Meanwhile the relationship between miR-34a-5p and Sirtuins 1(SIRT1)was evaluated by dual-luciferase reporter assay.To explore whether Que modulates tert-butyl hydroperoxide(TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway,we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression.In vivo,a puncture-induced rat IDD model was constructed,and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo.RESULTS We found that TBHP can cause NPMSCs senescence changes,such as reduced cell proliferation ability,increased SA-β-Gal activity,cell cycle arrest,the accumulation of ROS,and increased expression of senescence-related proteins.While abovementioned senescence indicators were significantly alleviated by Que treatment.Que decreased the expression levels of senescence-related proteins(p16,p21,and p53)and senescence-associated secreted phenotype(SASP),including IL-1β,IL-6,and MMP-13,and it increased the expression of SIRT1.In addition,the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown.In vivo,X-ray,and histological analyses indicated that Que alleviated IDD in a punctureinduced rat model.CONCLUSION In summary,the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway,suggesting that Que may be a potential agent for the treatment of IDD.展开更多
The automatic and accurate identification of apoptosis facilitates large-scale cell analysis.Most identification approaches using nucleus fluorescence imaging are based on specific morphological parameters.However,the...The automatic and accurate identification of apoptosis facilitates large-scale cell analysis.Most identification approaches using nucleus fluorescence imaging are based on specific morphological parameters.However,these parameters cannot completely describe nuclear morphology,thus limiting the identification accuracy of models.This paper proposes a new feature extraction method to improve the performance of the model for apoptosis identification.The proposed method uses a histogram of oriented gradient(HOG)of high-frequency wavelet coefficients to extract internal and edge texture information.The HOG vectors are classified using support vector machine.The experimental results demonstrate that the proposed feature extraction method well performs apoptosis identification,attaining 95:7% accuracy with low cost in terms of time.We confirmed that our method has potential applications to cell biology research.展开更多
AIM:To evaluate the lateral geniculate nucleus(LGN)volume and height using magnetic resonance imaging(MRI)in glaucoma patients.METHODS:Literatures retrieval was carried out through Pub Med,Web of Science,Embase,and Co...AIM:To evaluate the lateral geniculate nucleus(LGN)volume and height using magnetic resonance imaging(MRI)in glaucoma patients.METHODS:Literatures retrieval was carried out through Pub Med,Web of Science,Embase,and Cochrane Library.Studies that compared the volume and height of LGN in glaucoma patients with that in control subjects were included.The volume and height of LGN were extracted from the included studies.The Review Manager 5.4.1 software was used for the Meta-analysis.RESULTS:This Meta-analysis included 10 crosssectional studies,including the eyes of 223 glaucoma patients and 185 healthy controls.Compared with the control subjects,the volume and height of LGN in glaucoma patients measured by MRI were significantly reduced{-29.13 mm3,95%[confidence interval(CI):-44.82 to-13.43,P=0.0003;-0.61 mm,95%CI:-0.78 to-0.44,P<0.00001,respectively]}.Subgroup analysis demonstrated that the differences of LGN volume and height between glaucoma patients and control subjects in the older group were smaller than that in the younger group,and LGN volume decreased with the increase of glaucoma severity.CONCLUSION:The results demonstrate that the volume and height of LGN are decreased in glaucoma patients,and LGN volume can be considered a parameter of glaucoma severity.展开更多
The role of intercalatus nucleus of Staderini(INS),the most caudal of the perihypoglossal nuclei,is much debated.Last research seems to suggest that this nucleus plays a role as a vertical eyes movements integrator.Th...The role of intercalatus nucleus of Staderini(INS),the most caudal of the perihypoglossal nuclei,is much debated.Last research seems to suggest that this nucleus plays a role as a vertical eyes movements integrator.The few clinical reports present in the literature that describe isolated lesions of the INS have described patients presenting in acute with up-beating vertical spontaneous nystagmus.Isolated acute lesion of INS is,in fact,much rare,and,without other neurological signs,is exceptional.We present a case of acute isolated vertigo with no other neurological signs or symptoms,due to INS ischemia provoked by vertebral artery stenosis.The patient presented with spontaneous vertical up-beating nystagmus that showed at videonystagmographic recording,a clear exponential decay of angular slow-phase velocity,that is considered a typical sign of neural integrator impairment.This case seems to represent a further confirm that INS is part,as a vertical-to-position neural integrator,of the neural circuit controlling the vertical eyes movements.展开更多
In this proceeding,some highlight results on the constraints of the nuclear matter equation of state(EOS)from the data of nucleus resonance and neutron-skin thickness using the Bayesian approach based on the Skyrme-Ha...In this proceeding,some highlight results on the constraints of the nuclear matter equation of state(EOS)from the data of nucleus resonance and neutron-skin thickness using the Bayesian approach based on the Skyrme-Hartree-Fock model and its extension have been presented.Typically,the anti-correlation and positive correlations between the slope parameter and the value of the symmetry energy at the saturation density under the constraint of the neutron-skin thickness and the isovector giant dipole resonance have been discussed respectively.It’s shown that the Bayesian analysis can help to find a compromise for the“PREXII puzzle”and the“soft Tin puzzle”.The possible modifications on the constraints of lower-order EOS parameters as well as the relevant correlation when higher-order EOS parameters are incorporated as independent variables have been further illustrated.For a given model and parameter space,the Bayesian approach serves as a good analysis tool suitable for multi-messengers versus multi-variables,and is helpful for constraining quantitatively the model parameters as well as their correlations.展开更多
Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucl...Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucleus pulposus cells(NPCs)from calcified discs,and clarify the potential mechanism in disc degeneration.Methods Primary NPCs were isolated from calcified and control discs(CAL-NPC and CON-NPC),respectively.The proliferation and extracellular matrix(ECM)metabolism capacities of the cells were evaluated using MTT and Western blotting,respectively.RNA sequencing was used to identify differentially expressed genes(DEGs)in the CAL-NPCs.The biological functions of the DEGs were analyzed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network.The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated.Results The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs.In total,375 DEGs were identified in the CAL-NPCs.The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways.GATA-binding protein 3(GATA3)with the highest verified levels was selected for further studies.Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function,while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes.Conclusion This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.展开更多
The measures of steam curing and early-strengthening agents to promote the precast components to reach the target strength quickly can bring different degrees of damage to the concrete.Based on this,the new nanomateri...The measures of steam curing and early-strengthening agents to promote the precast components to reach the target strength quickly can bring different degrees of damage to the concrete.Based on this,the new nanomaterial CSH-the hydration product of cement effectively solves these measures’disadvantages,such as excessive energy consumption,thermal stress damage,and the introduction of external ions.In this paper,the effect of CSH on the early strength of precast fly ash concrete components was investigated in terms of setting time,workability,and mechanical properties and analyzed at the microscopic level using hydration temperature,XRD,and SEM.The results showed that under the same workability,CSH could significantly reduce the amount of admixture,shorten the final setting time,almost not affect the initial setting time,and accelerate the hydration of cement.At the optimum dose of 5%,the mechanical properties of the specimens were improved by more than 98%within 12 h of hydration,resulting in an earlier release time of 12 h and no risk of strength inversion later.The results of this paper give theoretical support to the behavior of precast components under steam-free curing.展开更多
BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological a...BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.展开更多
Objective To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus ...Objective To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results (1) In response to the application of ginkgolide t3 (0.1, 1, 10 μmol/L; n = 27) into the perfusate for 2 rain, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 μmol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1μmol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L). Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (KDR).展开更多
[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in ...[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.展开更多
Ultrastructural features of nucleus degradation during programmed cell death (PCD) of starchy endosperm cells in rice ( Oryza sativa L.) were observed using transmission electron microscopy. Several distinct morpho...Ultrastructural features of nucleus degradation during programmed cell death (PCD) of starchy endosperm cells in rice ( Oryza sativa L.) were observed using transmission electron microscopy. Several distinct morphological features of PCD have been found in the developing starchy endosperm cells, e.g. nucleus deformation, chromatin condensation, nuclear envelope disruption, and nuclear matrix leakage. DNA ladder displayed a smear of large DNA fragments from nucleus and evident bands of small DNA fragments (140-180 bp) from both nucleus and cytoplasm. In contrast with the rapid nucleus degradation, cell organelles in cytoplasm, such as rough endoplasmic reticulum, amyloplast, and mitochondrion, maintained their metabolic functions for a longer time. Seed reserves were continually synthesized and accumulated in the starchy endosperm cells despite the nucleus degradation during the PCD process. These results suggest that starchy endosperm cells remain active during reserve material synthesis and accumulation in the PCD process. The specific relationships between nucleus and cytoplasm in the developing endosperm cells and the morphological changes of nucleus in the endosperm PCD process were also discussed.展开更多
Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
基金funded by the National Natural Science Foundation of China(Nos.L2224042,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the Frontier Interdisciplinary Project of the Chinese Academy of Sciences(No.XK2022XXC003)+2 种基金the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of he Chinese Academy of Sciences(No.GJJSTD20210004).
文摘The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.
基金supported in part by the National Key R&D Program of China(No.2021YFA1601500)CAS Project for Young Scientists in Basic Research(No.YSBR-002)+5 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB34000000)the Regional Development Youth Program of the Chinese Academy of Sciences(People’s Character[2023]No.15)Argonne National Laboratory was performed with the support of the US Department of EnergyOffice of Nuclear Physicsunder Contract No.DE-AC02-06CH11357support of France's IN2P3。
文摘The newly developed software,Nucleus++,is an advanced tool for displaying basic nuclear physics properties from NubAsE and integrating comprehensive mass information for each nuclide from Atomic Mass Evaluation.Additionally,it allows users to compare experimental nuclear masses with predictions from different mass models.Building on the success and learning experiences of its predecessor,Nucleus,this enhanced tool introduces improved functionality and compatibility.With its user-friendly interface,Nucleus++was designed as a valuable tool for scholars and practitioners in the field of nuclear science.This article offers an in-depth description of Nucleus++,highlighting its main features and anticipated impacts on nuclear science research.
基金supported by the Natural Science Foundation of Sichuan Province(2022NSFSC1767)National Natural Science Foundation of China(32360828)。
文摘The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined.This study provides the first comprehensive,unbiased,cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens.Within the hypothalamus,pituitary,and ovary,seven,12,and 13 distinct cell types were identified,respectively.Results indicated that the pituitary adenylate cyclase activating polypeptide(PACAP),follicle-stimulating hormone(FSH),and prolactin(PRL)signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone(GnRH),FSH,and luteinizing hormone(LH)within the hypothalamus and pituitary.In the ovary,interactions between granulosa cells and oocytes involved the KIT,CD99,LIFR,FN1,and ANGPTL signaling pathways,which collectively regulate follicular maturation.The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis.Additionally,gene expression analysis revealed that relaxin 3(RLN3),gastrin-releasing peptide(GRP),and cocaine-and amphetamine regulated transcripts(CART,also known as CARTPT)may function as novel endocrine hormones,influencing the HPO axis through autocrine,paracrine,and endocrine pathways.Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP,RLN3,CARTPT,LHCGR,FSHR,and GRPR in the ovaries of Lohmann layers,potentially contributing to their superior reproductive performance.In conclusion,this study provides a detailed molecular characterization of the HPO axis,offering novel insights into the regulatory mechanisms underlying reproductive biology.
基金supported by grants from the Shenzhen Science and Technology Program(No.2021-22154)National Natural Science Foundation of China(No.82205271,No.82374564,and No.82074566)+1 种基金Wuhan Medical Research Project(No.WZ21Q09)Key Chinese Medicine Project of Hubei Provincial Natural Science Foundation(No.2023AFD112).
文摘Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.
基金support by the National Nature Science Foundation of China,Nos.81830033,61761166004(both to JGZ)。
文摘There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.
基金Supported by the National Natural Science Foundation of China,No.82172462,No.81972136the Traditional Chinese Medicine Science and Technology Development Plan Project of Jiangsu Province,No.YB2020085Cross Cooperation Project of Northern Jiangsu People’s Hospital,No.SBJC21014.
文摘BACKGROUND Intervertebral disc degeneration(IDD)is a main contributor to low back pain.Oxidative stress,which is highly associated with the progression of IDD,increases senescence of nucleus pulposus-derived mesenchymal stem cells(NPMSCs)and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs(IVDs).Quercetin(Que)has been demonstrated to reduce oxidative stress in diverse degenerative diseases.AIM To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism.METHODS In vitro,NPMSCs were isolated from rat tails.Senescence-associatedβ-galactosidase(SA-β-Gal)staining,cell cycle,reactive oxygen species(ROS),realtime quantitative polymerase chain reaction(RT-qPCR),immunofluorescence,and western blot analyses were used to evaluated the protective effects of Que.Meanwhile the relationship between miR-34a-5p and Sirtuins 1(SIRT1)was evaluated by dual-luciferase reporter assay.To explore whether Que modulates tert-butyl hydroperoxide(TBHP)-induced senescence of NPMSCs via the miR-34a-5p/SIRT1 pathway,we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression.In vivo,a puncture-induced rat IDD model was constructed,and X rays and histological analysis were used to assess whether Que could alleviate IDD in vivo.RESULTS We found that TBHP can cause NPMSCs senescence changes,such as reduced cell proliferation ability,increased SA-β-Gal activity,cell cycle arrest,the accumulation of ROS,and increased expression of senescence-related proteins.While abovementioned senescence indicators were significantly alleviated by Que treatment.Que decreased the expression levels of senescence-related proteins(p16,p21,and p53)and senescence-associated secreted phenotype(SASP),including IL-1β,IL-6,and MMP-13,and it increased the expression of SIRT1.In addition,the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown.In vivo,X-ray,and histological analyses indicated that Que alleviated IDD in a punctureinduced rat model.CONCLUSION In summary,the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs via the miR-34a/SIRT1 signaling pathway,suggesting that Que may be a potential agent for the treatment of IDD.
基金This work is supported by the Key Project of the National Natural Science Foundation of China(Grant Number 62135003)the Science and Technology Program of Guangzhou(Grant No.202201010704)Special Carrier Program of Qingyuan Hitech Industrial Development Zone.
文摘The automatic and accurate identification of apoptosis facilitates large-scale cell analysis.Most identification approaches using nucleus fluorescence imaging are based on specific morphological parameters.However,these parameters cannot completely describe nuclear morphology,thus limiting the identification accuracy of models.This paper proposes a new feature extraction method to improve the performance of the model for apoptosis identification.The proposed method uses a histogram of oriented gradient(HOG)of high-frequency wavelet coefficients to extract internal and edge texture information.The HOG vectors are classified using support vector machine.The experimental results demonstrate that the proposed feature extraction method well performs apoptosis identification,attaining 95:7% accuracy with low cost in terms of time.We confirmed that our method has potential applications to cell biology research.
基金Supported by National Natural Science Foundation of China (No.81860170)。
文摘AIM:To evaluate the lateral geniculate nucleus(LGN)volume and height using magnetic resonance imaging(MRI)in glaucoma patients.METHODS:Literatures retrieval was carried out through Pub Med,Web of Science,Embase,and Cochrane Library.Studies that compared the volume and height of LGN in glaucoma patients with that in control subjects were included.The volume and height of LGN were extracted from the included studies.The Review Manager 5.4.1 software was used for the Meta-analysis.RESULTS:This Meta-analysis included 10 crosssectional studies,including the eyes of 223 glaucoma patients and 185 healthy controls.Compared with the control subjects,the volume and height of LGN in glaucoma patients measured by MRI were significantly reduced{-29.13 mm3,95%[confidence interval(CI):-44.82 to-13.43,P=0.0003;-0.61 mm,95%CI:-0.78 to-0.44,P<0.00001,respectively]}.Subgroup analysis demonstrated that the differences of LGN volume and height between glaucoma patients and control subjects in the older group were smaller than that in the younger group,and LGN volume decreased with the increase of glaucoma severity.CONCLUSION:The results demonstrate that the volume and height of LGN are decreased in glaucoma patients,and LGN volume can be considered a parameter of glaucoma severity.
文摘The role of intercalatus nucleus of Staderini(INS),the most caudal of the perihypoglossal nuclei,is much debated.Last research seems to suggest that this nucleus plays a role as a vertical eyes movements integrator.The few clinical reports present in the literature that describe isolated lesions of the INS have described patients presenting in acute with up-beating vertical spontaneous nystagmus.Isolated acute lesion of INS is,in fact,much rare,and,without other neurological signs,is exceptional.We present a case of acute isolated vertigo with no other neurological signs or symptoms,due to INS ischemia provoked by vertebral artery stenosis.The patient presented with spontaneous vertical up-beating nystagmus that showed at videonystagmographic recording,a clear exponential decay of angular slow-phase velocity,that is considered a typical sign of neural integrator impairment.This case seems to represent a further confirm that INS is part,as a vertical-to-position neural integrator,of the neural circuit controlling the vertical eyes movements.
基金Supported by National Natural Science Foundation of China (11922514)。
文摘In this proceeding,some highlight results on the constraints of the nuclear matter equation of state(EOS)from the data of nucleus resonance and neutron-skin thickness using the Bayesian approach based on the Skyrme-Hartree-Fock model and its extension have been presented.Typically,the anti-correlation and positive correlations between the slope parameter and the value of the symmetry energy at the saturation density under the constraint of the neutron-skin thickness and the isovector giant dipole resonance have been discussed respectively.It’s shown that the Bayesian analysis can help to find a compromise for the“PREXII puzzle”and the“soft Tin puzzle”.The possible modifications on the constraints of lower-order EOS parameters as well as the relevant correlation when higher-order EOS parameters are incorporated as independent variables have been further illustrated.For a given model and parameter space,the Bayesian approach serves as a good analysis tool suitable for multi-messengers versus multi-variables,and is helpful for constraining quantitatively the model parameters as well as their correlations.
基金funded by the Youth Research Fund of the Peking Union Medical College Hospital(No.pumch201911708).
文摘Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucleus pulposus cells(NPCs)from calcified discs,and clarify the potential mechanism in disc degeneration.Methods Primary NPCs were isolated from calcified and control discs(CAL-NPC and CON-NPC),respectively.The proliferation and extracellular matrix(ECM)metabolism capacities of the cells were evaluated using MTT and Western blotting,respectively.RNA sequencing was used to identify differentially expressed genes(DEGs)in the CAL-NPCs.The biological functions of the DEGs were analyzed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network.The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated.Results The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs.In total,375 DEGs were identified in the CAL-NPCs.The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways.GATA-binding protein 3(GATA3)with the highest verified levels was selected for further studies.Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function,while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes.Conclusion This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.
文摘The measures of steam curing and early-strengthening agents to promote the precast components to reach the target strength quickly can bring different degrees of damage to the concrete.Based on this,the new nanomaterial CSH-the hydration product of cement effectively solves these measures’disadvantages,such as excessive energy consumption,thermal stress damage,and the introduction of external ions.In this paper,the effect of CSH on the early strength of precast fly ash concrete components was investigated in terms of setting time,workability,and mechanical properties and analyzed at the microscopic level using hydration temperature,XRD,and SEM.The results showed that under the same workability,CSH could significantly reduce the amount of admixture,shorten the final setting time,almost not affect the initial setting time,and accelerate the hydration of cement.At the optimum dose of 5%,the mechanical properties of the specimens were improved by more than 98%within 12 h of hydration,resulting in an earlier release time of 12 h and no risk of strength inversion later.The results of this paper give theoretical support to the behavior of precast components under steam-free curing.
基金the Natural Science Foundation of Shandong Province,No.ZR2019MC020。
文摘BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.
文摘Objective To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results (1) In response to the application of ginkgolide t3 (0.1, 1, 10 μmol/L; n = 27) into the perfusate for 2 rain, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 μmol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1μmol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L). Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (KDR).
基金Supported by Natural Science Foundation of Jiangsu Province(BK2009235)~~
文摘[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.
文摘Ultrastructural features of nucleus degradation during programmed cell death (PCD) of starchy endosperm cells in rice ( Oryza sativa L.) were observed using transmission electron microscopy. Several distinct morphological features of PCD have been found in the developing starchy endosperm cells, e.g. nucleus deformation, chromatin condensation, nuclear envelope disruption, and nuclear matrix leakage. DNA ladder displayed a smear of large DNA fragments from nucleus and evident bands of small DNA fragments (140-180 bp) from both nucleus and cytoplasm. In contrast with the rapid nucleus degradation, cell organelles in cytoplasm, such as rough endoplasmic reticulum, amyloplast, and mitochondrion, maintained their metabolic functions for a longer time. Seed reserves were continually synthesized and accumulated in the starchy endosperm cells despite the nucleus degradation during the PCD process. These results suggest that starchy endosperm cells remain active during reserve material synthesis and accumulation in the PCD process. The specific relationships between nucleus and cytoplasm in the developing endosperm cells and the morphological changes of nucleus in the endosperm PCD process were also discussed.
基金supported by the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.