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Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remain poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta, and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal, and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.
Whether we are memorising facts or reacting to a loud noise, nerve cells in different brain areas must be able to communicate with one another through precise, meaningful signals. Specialized nerve cells known as interneurons act as "traffic lights" to precisely regulate when and where this information flows in neural circuits. Axo-axonic cells are a rare type of inhibitory interneuron that are thought to be particularly important for controlling the passage of information between different groups of excitatory neurons. This is because they only connect to one key part of their target cell the axon-initial segment where the electrical signals needed for brain communication (known as action potentials) are initiated. Since axo-axonic cells are inhibitory interneurons, this connection effectively allows them to 'veto' the generation of these signals at their source. Although axo-axonic cells have been identified in three brain regions using traditional anatomical methods, there were no 'tags' readily available that can reliably identify them. Therefore, much about these cells remained unknown, including how widespread they are in the mammalian brain. To solve this problem, Raudales et al. investigated which genes are switched on in axo-axonic cells but not in other cells, identifying a unique molecular signature that could be used to mark, record, and manipulate these cells. Microscopy imaging of brain tissue from mice in which axo-axonic cells had been identified revealed that they are present in many more brain areas than previously thought, including nearly all regions of the broadly defined cerebral cortex and even the hypothalamus, which controls many innate behaviors. Axo-axonic cells were also 'wired up' differently, depending on where they were located; for example, those in brain areas associated with memory and emotions had wider-ranging input connections than other areas. The finding of Raudales et al. provide, for the first time, a method to directly track and manipulate axo-axonic cells in the brain. Since dysfunction in axo-axonic cells is also associated with neurological disorders like epilepsy and schizophrenia, gaining an insight into their distribution and connectivity could help to develop better treatments for these conditions.
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Neurônios GABAérgicos , Interneurônios , Animais , Interneurônios/fisiologia , Interneurônios/metabolismo , Neurônios GABAérgicos/fisiologia , Neurônios GABAérgicos/metabolismo , Camundongos , Encéfalo/fisiologia , Encéfalo/citologia , Sinapses/fisiologia , Sinapses/metabolismo , Axônios/fisiologia , Axônios/metabolismo , MasculinoRESUMO
PURPOSE: To analyze the association between scoliosis and vertebral refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: A retrospective study was conducted on 269 patients meeting the criteria from January 2014 to October 2022. All patients underwent PKP with complete data and were followed-up for > 12 months. First, it was verified that scoliosis was a risk factor in 269 patients. Second, patients with scoliosis were grouped based on the Cobb angle to evaluate the impact of the post-operative angle. The cox proportional hazards regression analysis and survival analysis were used to calculate the hazard ratio and recurrence time. RESULTS: A total of 56 patients had scoliosis, 18 of whom experienced refractures after PKP. The risk factors for vertebral refractures included a T-score < - 3.0 and presence of scoliosis (both p < 0.001). The results indicated that the vertebral fractured arc (T10 - L4) was highly influential in scoliosis and vertebral fractures. When scoliotic and initially fractured vertebrae were situated within T10 - L4, the risk factors for vertebral refracture included a postoperative Cobb angle of ≥ 20° (p = 0.002) and an increased angle (p = 0.001). The mean recurrence times were 17.2 (10.7 - 23.7) months and 17.6 (7.9 - 27.3) months, respectively. CONCLUSION: Osteoporosis combined with scoliosis significantly increases the risk of vertebral refractures after PKP in patients with OVCFs. A postoperative Cobb angle of ≥ 20° and an increased angle are significant risk factors for vertebral refractures when scoliotic and initially fractured vertebrae are situated within T10 - L4.
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Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Recidiva , Escoliose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/cirurgia , Fraturas por Compressão/etiologia , Fraturas por Compressão/diagnóstico por imagem , Cifoplastia/métodos , Feminino , Escoliose/cirurgia , Escoliose/etiologia , Escoliose/diagnóstico por imagem , Masculino , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Estudos Retrospectivos , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Fatores de Risco , Pessoa de Meia-Idade , Seguimentos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
Phonation critically depends on precise controls of laryngeal muscles in coordination with ongoing respiration. However, the neural mechanisms governing these processes remain unclear. We identified excitatory vocalization-specific laryngeal premotor neurons located in the retroambiguus nucleus (RAmVOC) in adult mice as being both necessary and sufficient for driving vocal cord closure and eliciting mouse ultrasonic vocalizations (USVs). The duration of RAmVOC activation can determine the lengths of both USV syllables and concurrent expiration periods, with the impact of RAmVOC activation depending on respiration phases. RAmVOC neurons receive inhibition from the preBötzinger complex, and inspiration needs override RAmVOC-mediated vocal cord closure. Ablating inhibitory synapses in RAmVOC neurons compromised this inspiration gating of laryngeal adduction, resulting in discoordination of vocalization with respiration. Our study reveals the circuits for vocal production and vocal-respiratory coordination.
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Tronco Encefálico , Fonação , Respiração , Prega Vocal , Animais , Masculino , Camundongos , Tronco Encefálico/fisiologia , Bulbo/fisiologia , Neurônios/fisiologia , Fonação/fisiologia , Prega Vocal/inervação , Prega Vocal/fisiologia , Camundongos Endogâmicos C57BL , Feminino , Proteínas Proto-Oncogênicas c-fos/genéticaRESUMO
Printable mesoscopic perovskite solar cells (p-MPSCs) do not require the added hole-transport layer needed in traditional p-n junctions but have also exhibited lower power conversion efficiencies of about 19%. We performed device simulation and carrier dynamics analysis to design a p-MPSC with mesoporous layers of semiconducting titanium dioxide, insulating zirconium dioxide, and conducting carbon infiltrated with perovskite that enabled three-dimensional injection of photoexcited electrons into titanium dioxide for collection at a transparent conductor layer. Holes underwent long-distance diffusion toward the carbon back electrode, and this carrier separation reduced recombination at the back contact. Nonradiative recombination at the bulk titanium dioxide/perovskite interface was reduced by ammonium phosphate modification. The resulting p-MPSCs achieved a power conversion efficiency of 22.2% and maintained 97% of their initial efficiency after 750 hours of maximum power point tracking at 55 ± 5°C.
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Adenoid cystic carcinoma (ACC) is a malignant tumor originating in the salivary glands. It most commonly affects the salivary and lacrimal glands, with less frequent occurrences in the esophagus. Esophageal ACC (EACC) typically manifests in the middle or lower parts of the esophagus, with exceedingly rare instances in the upper part. Lung metastasis in EACC is uncommon, and understanding its clinical features and treatment strategies remains challenging. In this study, we present a case of ACC originating in the upper esophagus with lung metastasis. The patient, a middle-aged female, was admitted to the Department of Respiratory and Critical Care Medicine due to an esophageal mass discovered during physical examination that had been present for 4.5 years, along with a newly identified pulmonary nodule for 2 weeks. An X-ray barium meal revealed the presence of a benign esophageal cervical mass. Gastroscopy revealed elevated lesions below the esophageal inlet, and a pathological biopsy confirmed the diagnosis of EACC. The aim of this case report is to enhance understanding of this rare condition and improve clinicians' awareness of the disease. By providing details of the patient's diagnosis, clinical presentation, imaging features and pathological features, we aim to improve diagnostic accuracy and clinical management of similar cases in the future.
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Carcinoma Adenoide Cístico , Neoplasias Esofágicas , Neoplasias Pulmonares , Pessoa de Meia-Idade , Humanos , Feminino , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Biópsia , Neoplasias Pulmonares/diagnóstico por imagemRESUMO
Placebo analgesia is a widely observed clinical phenomenon. Establishing a robust mouse model of placebo analgesia is needed for careful dissection of the underpinning circuit mechanisms. However, previous studies failed to observe consistent placebo effects in rodent models of chronic pain. We wondered whether strong placebo analgesia can be reverse engineered using general anesthesia-activated neurons in the central amygdala (CeA GA ) that can potently suppress pain. Indeed, in both acute and chronic pain models, pairing a context with CeA GA -mediated pain relief produced robust context-dependent analgesia, exceeding that induced by morphine in the same paradigm. We reasoned that if the analgesic effect was dependent on reactivation of CeA GA neurons by conditioned contextual cues, the analgesia would still be an active treatment, rather than a placebo effect. CeA GA neurons indeed receive monosynaptic inputs from temporal lobe areas that could potentially relay contextual cues directly to CeA GA . However, in vivo imaging showed that CeA GA neurons were not re-activated in the conditioned context, despite mice displaying a strong analgesic phenotype, supporting the notion that the cue-induced pain relief is true placebo analgesia. Our results show that conditioning with activation of a central pain-suppressing circuit is sufficient to engineer placebo analgesia, and that purposefully linking a context with an active treatment could be a means to harness the power of placebo for pain relief.
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Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remains poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.
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Skilled motor behaviors require orderly coordination of multiple constituent movements with sensory cues towards achieving a goal, but the underlying brain circuit mechanisms remain unclear. Here we show that target-guided reach-grasp-to-drink (RGD) in mice involves the ordering and coordination of a set of forelimb and oral actions. Cortex-wide activity imaging of multiple glutamatergic projection neuron (PN) types uncovered a network, involving the secondary motor cortex (MOs), forelimb primary motor and somatosensory cortex, that tracked RGD movements. Photo-inhibition highlighted MOs in coordinating RGD movements. Within the MOs, population neural trajectories tracked RGD progression and single neuron activities integrated across constituent movements. Notably, MOs intratelencephalic, pyramidal tract, and corticothalamic PN activities correlated with action coordination, showed distinct neural dynamics trajectories, and differentially contributed to movement coordination. Our results delineate a cortical network and key areas, PN types, and neural dynamics therein that articulate the serial order and coordination of a skilled behavior.
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Speech generation critically depends on precise controls of laryngeal muscles and coordination with ongoing respiratory activity. However, the neural mechanisms governing these processes remain unknown. Here, we mapped laryngeal premotor circuitry in adult mice and viral-genetically identified excitatory vocal premotor neurons located in the retroambiguus nucleus (RAm VOC ) as both necessary and sufficient for driving vocal-cord closure and eliciting mouse ultrasonic vocalizations (USVs). The duration of RAm VOC activation determines the lengths of USV syllables and post-inspiration phases. RAm VOC -neurons receive inhibitory inputs from the preBötzinger complex, and inspiration needs can override RAm VOC -mediated vocal-cord closure. Ablating inhibitory synapses in RAm VOC -neurons compromised this inspiration gating of laryngeal adduction, resulting in de-coupling of vocalization and respiration. Our study revealed the hitherto unknown circuits for vocal pattern generation and vocal-respiratory coupling. One-Sentence Summary: Identification of RAm VOC neurons as the critical node for vocal pattern generation and vocal-respiratory coupling.
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Background: Anoikis resistance is a prerequisite for the successful development of osteosarcoma (OS) metastases, whether the expression of anoikis-related genes (ARGs) correlates with OS prognosis remains unclear. This study aimed to investigate the feasibility of using ARGs as prognostic tools for the risk stratification of OS. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided transcriptome information relevant to OS. The GeneCards database was used to identify ARGs. Differentially expressed ARGs (DEARGs) were identified by overlapping ARGs with common differentially expressed genes (DEGs) between OS and normal samples from the GSE16088, GSE19276, and GSE99671 datasets. Anoikis-related clusters of patients were obtained by consistent clustering, and gene set variation analysis (GSVA) of the different clusters was completed. Next, a risk model was created using Cox regression analyses. Risk scores and clinical features were assessed for independent prognostic values, and a nomogram model was constructed. Subsequently, a functional enrichment analysis of the high- and low-risk groups was performed. In addition, the immunological characteristics of OS samples were compared between the high- and low-risk groups, and their sensitivity to therapeutic agents was explored. Results: Seven DEARGs between OS and normal samples were obtained by intersecting 501 ARGs with 68 common DEGs. BNIP3 and CXCL12 were significantly differentially expressed between both clusters (P<0.05) and were identified as prognosis-related genes. The risk model showed that the risk score and tumor metastasis were independent prognostic factors of patients with OS. A nomogram combining risk score and tumor metastasis effectively predicted the prognosis. In addition, patients in the high-risk group had low immune scores and high tumor purity. The levels of immune cell infiltration, expression of human leukocyte antigen (HLA) genes, immune response gene sets, and immune checkpoints were lower in the high-risk group than those in the low-risk group. The low-risk group was sensitive to the immune checkpoint PD-1 inhibitor, and the high-risk group exhibited lower inhibitory concentration values by 50% for 24 drugs, including AG.014699, AMG.706, and AZD6482. Conclusion: The prognostic stratification framework of patients with OS based on ARGs, such as BNIP3 and CXCL12, may lead to more efficient clinical management.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Anoikis/genética , Osteossarcoma/genética , Prognóstico , Nomogramas , Neoplasias Ósseas/genéticaRESUMO
The phase segregation in mixed halide perovskites is recently found to improve the photoluminescence quantum yield (PLQY) of the perovskites by concentrating the carriers. However, how phase segregation affects the photoinduced carrier dynamics is unclear. Herein, we find that the phase segregation in CH3NH3PbBrxI3-x mixed halide perovskite thin film is morphology-dependent by showing I-rich domains mainly along the grain boundaries. Ultrafast transient absorption (TA) and photoluminescence upconversion (PL-UC) spectroscopy measurements uncover that the carrier accumulation in the low energy I-rich domains includes two carrier transfer pathways. Carrier transfer from the Br-rich domain and the mixed phase to the I-rich domain is realized by consecutive hole (â¼0.5 ps) and electron (<12.4 ps) transfer and energy transfer (<12.4 ps), respectively. The finding reveals the carrier funneling dynamic mechanism in phase-segregated halide perovskite films and provides a guideline for the applications of mixed halide perovskites in color-conversion devices or high-efficiency LEDs.
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Developing a hydrogen economy to replace traditional fossil fuels is essential for sustainable human development. As two promising H2 production strategies, photocatalytic and electrocatalytic water splitting with large reaction energy barriers still face the great challenges of poor solar-to-hydrogen efficiency and large electrochemical overpotentials, respectively. Herein, a new strategy is proposed to disassemble the difficult pure water splitting into two parts that are easy to implement, namely mixed halide perovskite photocatalytic HI splitting for H2 production, and simultaneous electrocatalytic I3 - reduction and O2 production. The efficient charge separation, abundant H2 production active sites, and a small HI splitting energy barrier contribute to the superior photocatalytic H2 production activity of MoSe2 /MAPbBr3- x Ix (CH3 NH3 + = MA). Subsequent electrocatalytic I3 - reduction and O2 production reactions only need a small voltage of 0.92 V to drive, which is far lower than that of the electrocatalytic pure water splitting (>1.23 V). The molar ratio of H2 (6.99 mmol g-1 ) to O2 (3.09 mmol g-1 ) produced during the first photocatalytic and electrocatalytic cycle is close to 2:1, and the continuous circulation of I3 - /I- between the photocatalytic and electrocatalytic systems can achieve efficient and robust pure water splitting.
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The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection-neuron-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PTFezf2) and intratelencephalic-projecting (ITPlxnD1) types across dorsal cortex of mice during different brain states and behaviors. ITPlxnD1 and PTFezf2 neurons showed distinct activation patterns during wakeful resting, during spontaneous movements and upon sensory stimulation. Distinct ITPlxnD1 and PTFezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of ITsPlxnD1 and PTsFezf2 in subnetwork nodes disrupted distinct components of this behavior. Lastly, ITPlxnD1 and PTFezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and projection-neuron-type specific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks.
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Córtex Cerebral , Neurônios , Camundongos , Animais , Neurônios/fisiologia , Interneurônios , Encéfalo , Glicoproteínas de Membrana , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
OBJECTIVE: Therapy of very severe osteoporotic compression fractures (VSOVCF) has been a growing challenge for spine surgeons. Opinions vary regarding the optimal surgical procedure for the treatment of VSOVCF and which internal fixation method is more effective is still under debate, and research on this topic is lacking. This retrospective study was conducted to compare the efficacy and safety of various pedicle screw fixation methods for treating VSOVCF. METHODS: This single-center retrospective comparative study was conducted between January 2015 and September 2020. Two hundred and one patients were divided into six groups according to different surgical methods: 45 patients underwent long-segment fixation (Group 1); 39 underwent short-segment fixation (Group 2); 30 received long-segment fixation with cement-reinforced screws (Group 3); 32 received short-segment fixation with cement-reinforced screws (Group 4); 29 had long-segment fixation combined with kyphoplasty (PKP) (Group 5); and 26 cases had short-segment fixation combined with PKP (Group 6). The clinical records were reviewed and the visual analogue scale (VAS) score and the Oswestry Disability Index (ODI) score were used for clinical evaluation. The vertebral height (VH), fractured vertebral body height (FVBH), and Cobb's angle were objectively calculated and analyzed on lateral plain radiographs. Student's t-tests and one-way ANOVA among groups were conducted to analyze the continuous, and the chi-squared test was used to compare the dichotomous or categorical variables. The difference was considered statistically significant when the P-value was less than 0.05. RESULTS: The six groups had similar distributions in age, gender, course of the disease, follow-up period, and injured level. In the postoperative assessment of the VAS score, the surgical intervention most likely to rank first in terms of pain relief was the short-segment fixation with cement-reinforced screws (Group 4). For the functional evaluation, the surgical intervention that is most likely to rank first in terms of ODI score was a short-segment fixation with cement-reinforced screws (Group 4), followed by long-segment fixation (Group 1). The long-segment fixation with cement-reinforced screws was the first-ranked surgical intervention for the maintenance of Cobb's angle and vertebral height, whereas the short-segment fixation performed the worst. The highest overall complication rate was in Group 6 with an incidence of 42.3% (11/26), followed by Group 2 with an incidence of 38.5% (15/39). CONCLUSION: For the treatment of VSOVCF, the short-segment fixation with cement-reinforced screws is the most effective and optimal procedure, and should be used as the preferred surgical method if surgeons are proficient in using cemented screws; otherwise, directly and unquestionably use long-segment fixation to achieve satisfactory clinical results.
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Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Parafusos Pediculares , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Coluna Vertebral , Cifoplastia/métodos , Cimentos Ósseos/uso terapêutico , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: The diffusion tensor imaging (DTI) parameters (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) are commonly used to provide quantitative information on tissues. This study aimed to evaluate the predictive value of preoperative DTI of the spinal nerve roots in the surgical outcome of lumbar disc herniation (LDH). METHODS: A total of 117 LDH patients were included. According to the postoperative improvement rate, the patients were dichotomized into the unfavorable group (N.=35) and favorable group (N.=82). RESULTS: The favorable group had a younger age (P=0.005) and a shorter disease course (P<0.001) than the unfavorable group. The favorable group had higher affected side FA and ADC and lower healthy/affected FA and ADC ratio than the unfavorable group (all P<0.05). Logistic regression analysis showed that younger age, shorter disease course, higher affected side FA and ADC, lower healthy/affected FA and ADC ratio, and lower healthy side ADC were the independent factors associated with positive surgical outcome. ROC analysis showed that the affected side FA had an excellent predictive performance for the surgical outcome (AUC=0.900). The Healthy/affected FA ratio had a good predictive performance (AUC=0.846). The overall predictive accuracy ranged from 0.91 to 0.92. However, ADC had poor predictive performance (AUC ranged from 0.626 to 0.663). CONCLUSIONS: These results suggested the preoperative affected side FA value had an excellent predictive performance for the surgical outcome of LDH patients. The LDH patients with a higher preoperative affected side FA value were more likely to have a positive surgical outcome.
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Imagem de Tensor de Difusão , Deslocamento do Disco Intervertebral , Humanos , Imagem de Tensor de Difusão/métodos , Estudos Prospectivos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/complicações , Vértebras Lombares/cirurgia , Raízes Nervosas Espinhais/diagnóstico por imagem , Raízes Nervosas Espinhais/cirurgia , Resultado do TratamentoRESUMO
Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects. How these different drugs exert these anxiolytic effects is not well understood. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that is activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNST GA ). A majority of ovBNST GA neurons express neurotensin receptor 1 (Ntsr1) and innervate brain regions known to regulate anxiety and stress responses. Optogenetic activation ovBNST GA or ovBNST Ntsr1 neurons significantly attenuated anxiety-like behaviors in both naïve animals and mice with inflammatory pain, while inhibition of these cells increased anxiety. Notably, activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety through modulation of the autonomic nervous system. Our study identifies ovBNST GA /ovBNST Ntsr1 neurons as one of the brain's endogenous anxiolytic centers and a potential therapeutic target for treating anxiety-related disorders. HIGHLIGHTS: General anesthetics and anxiolytics activate a population of neurons in the ovBNSTAnesthesia-activated ovBNST neurons bidirectionally modulate anxiety-like behaviorMost anesthesia-activated ovBNST neurons express neurotensin receptor 1 ovBNST Ntsr1 neuron activation shifts autonomic responses to an anxiolytic state.
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Objective: Postmenopausal osteoporosis (PMOP), a chronic systemic metabolic disease prevalent in middle-aged and elderly women, heavily relies on bone mineral density (BMD) measurement as the diagnostic indicator. In this study, we investigated serum microRNAs (miRNAs) as a possible screening tool for PMOP. Methods: This investigation recruited 83 eligible participants from 795 community-dwelling postmenopausal women between June 2020 and August 2021. The miRNA expression profiles in the serum of PMOP patients were evaluated via miRNA microarray (six PMOP patients and four postmenopausal women without osteoporosis (n-PMOP) as controls). Subsequently, results were verified in independent sample sets (47 PMOP patients and 26 n-PMOP controls) using quantitative real-time PCR. In addition, the target genes and main functions of the differentially expressed miRNAs were explored by bioinformatics analysis. Results: Four highly expressed miRNAs in the serum of patients (hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p) showed acceptable disease-independent discrimination performance (area under the curve range: 0.747-0.902) in the training set and verification set, outperforming traditional bone turnover markers. Among four key miRNAs, hsa-miR-144-5p is the only one that can simultaneously predict changes in BMD in lumbar spine 1-4, total hip, and femoral neck (ß = -0.265, p = 0.022; ß = -0.301, p = 0.005; and ß = -0.324, p = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to YY1, VIM, and YWHAE genes, which are extensively involved in bone metabolism processes. Conclusions: Bone-metabolism-related serum miRNAs, such as hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p, can be used as novel biomarkers for PMOP diagnosis independent of radiological findings and traditional bone turnover markers. Further study of these miRNAs and their target genes may provide new insights into the epigenetic regulatory mechanisms of the onset and progression of the disease.
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RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.
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Edição de RNA , RNA , Animais , Humanos , Camundongos , Ratos , RNA/análise , RNA/genética , RNA/metabolismo , Análise de Sequência de RNA , Transcriptoma/genética , Comportamento Animal , Encéfalo/citologia , Encéfalo/metabolismo , Neurônios , Biossíntese de ProteínasRESUMO
OBJECTIVE: Prevention of fragility fractures is one of the public health priorities worldwide, whilst the incidence of osteoporotic vertebral compression fractures (OVCF) continues to rise and lacks the corresponding accurate prediction model. This study aimed to screen potential causes and risk factors for primary non-traumatic osteoporotic vertebral compression fractures (NTOVCF) in the elderly by characterizing a patient population with NTOVCF and comparing it with a population of osteoporotic patients. METHODS: Between January 2013 and January 2022, 208 elderly patients with unequivocal evidence of bone fragility manifested as painful NTOVCF were enrolled, and compared with 220 patients with osteoporosis and no fractures. The demographic data, bone turnover markers, blood routine, serum biochemical values, and radiological findings were investigated. Differences between the fracture and non-fracture groups were analyzed, and variables significant in univariate analysis and correlation analysis were included in the logistic analysis to build the risk prediction model for osteoporotic vertebral fractures. Univariate analysis using student's t-tests for continuous variables or a chi-squared test for categorical variables was conducted to identify risk factors. RESULTS: No significant differences were revealed regarding age, gender, BMI, smoking, alcohol consumption, blood glucose, propeptide of type I procollagen (P1NP), and N-terminal middle segment osteocalcin (N-MID) (P > 0.05). Parathyroid Hormone (PTH), 25(OH)D, serum albumin (ALB), hemoglobin (HB), bone mineral density (BMD), and cross-sectional area (CSA) of the paraspinal muscle in the fracture group were significantly lower than those in the control group; however, b-C-terminal telopeptide of type I collagen (ß-CTX), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-prostatic acid phosphatase (NACP), and fatty degeneration ratio (FDR) were significantly higher than those in the control group (P < 0.05). Logistic regression analysis showed that ALB, HB, CSA, and BMD were negatively correlated with NTOVCF, while ß-CTX, HDL-C, NACP, and FDR were positively correlated with NTOVCF. CONCLUSION: Decreased physical activity, anemia, hypoproteinemia, imbalances in bone metabolism, abnormal lipid metabolism, and degenerative and decreased muscle mass, were all risk factors for OVCF in the elderly, spontaneous fractures may be the consequence of cumulative declines in multiple physiological systems over the lifespan. Based on this risk model, timely detection of patients with high OVCF risk and implementation of targeted preventive measures is expected to improve the effect of fracture prevention.
Assuntos
Doenças Ósseas Metabólicas , Fraturas por Compressão , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Feminino , Humanos , Idoso , Fraturas por Osteoporose/epidemiologia , Densidade Óssea , Fatores de Risco , China/epidemiologia , ColesterolRESUMO
Objective: Dysphagia after cerebral infarction (DYS) has been detected in several brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we used two rs-fMRI measures to investigate the changes in brain function activity in DYS and their correlations with dysphagia severity. Method: In this study, a total of 22 patients with DYS were compared with 30 patients without dysphagia (non-DYS) and matched for baseline characteristics. Then, rs-fMRI scans were performed in both groups, and regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) values were calculated in both groups. The two-sample t-test was used to compare ReHo and fALFF between the groups. Pearson's correlation analysis was used to determine the correlations between the ReHo and fALFF of the abnormal brain regions and the scores of the Functional Oral Intake Scale (FOIS), the Standardized Bedside Swallowing Assessment (SSA), the Videofluoroscopic Swallowing Study (VFSS), and the Penetration-Aspiration Scale (PAS). Results: Compared with the non-DYS group, the DYS group showed decreased ReHo values in the left thalamus, the left parietal lobe, and the right temporal lobe and significantly decreased fALFF values in the right middle temporal gyrus and the inferior parietal lobule. In the DYS group, the ReHo of the right temporal lobe was positively correlated with the SSA score and the PAS score (r = 0.704, p < 0.001 and r = 0.707, p < 0.001, respectively) but negatively correlated with the VFSS score (r = -0.741, p < 0.001). The ReHo of the left parietal lobe was positively correlated with SSA and PAS (r = 0.621, p = 0.002 and r = 0.682, p < 0.001, respectively) but negatively correlated with VFSS (r = -0.679, p = 0.001). Conclusion: The changes in the brain function activity of these regions are related to dysphagia severity. The DYS group with high ReHo values in the right temporal and left parietal lobes had severe dysphagia.