Molecular Brain最新文献_第10页

Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice. 脊髓中的Rab11a：完全弗氏佐剂诱导小鼠炎症疼痛的重要因素。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-28 DOI: 10.1186/s13041-023-01057-3

Jun-Xiang Gu, Jian Wang, Fu-Juan Ma, Miao-Miao Liu, Si-Hai Chen, Yi Wei, Yi-Fan Xiao, Pei-Yuan Lv, Xin Liu, Jian-Qiang Qu, Xian-Xia Yan, Tao Chen

{"title":"Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice.","authors":"Jun-Xiang Gu, Jian Wang, Fu-Juan Ma, Miao-Miao Liu, Si-Hai Chen, Yi Wei, Yi-Fan Xiao, Pei-Yuan Lv, Xin Liu, Jian-Qiang Qu, Xian-Xia Yan, Tao Chen","doi":"10.1186/s13041-023-01057-3","DOIUrl":"10.1186/s13041-023-01057-3","url":null,"abstract":"Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a's involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It's shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a's potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study. 新颖性诱导的记忆巩固伴随着Agap3转录的增加：一项跨物种研究。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-25 DOI: 10.1186/s13041-023-01056-4

Kristoffer Højgaard, Bianka Szöllősi, Kim Henningsen, Natsumi Minami, Nobuhiro Nakanishi, Erik Kaadt, Makoto Tamura, Richard G M Morris, Tomonori Takeuchi, Betina Elfving

{"title":"Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study.","authors":"Kristoffer Højgaard, Bianka Szöllősi, Kim Henningsen, Natsumi Minami, Nobuhiro Nakanishi, Erik Kaadt, Makoto Tamura, Richard G M Morris, Tomonori Takeuchi, Betina Elfving","doi":"10.1186/s13041-023-01056-4","DOIUrl":"10.1186/s13041-023-01056-4","url":null,"abstract":"Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41120399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electrophysiological characterization of a Ca_v3.2 calcium channel missense variant associated with epilepsy and hearing loss. 与癫痫和听力损失相关的Cav3.2钙通道错义变体的电生理学特征。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-21 DOI: 10.1186/s13041-023-01058-2

Robin N Stringer, Leos Cmarko, Gerald W Zamponi, Michel De Waard, Norbert Weiss

{"title":"Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss.","authors":"Robin N Stringer, Leos Cmarko, Gerald W Zamponi, Michel De Waard, Norbert Weiss","doi":"10.1186/s13041-023-01058-2","DOIUrl":"10.1186/s13041-023-01058-2","url":null,"abstract":"T-type calcium channelopathies encompass a group of human disorders either caused or exacerbated by mutations in the genes encoding different T-type calcium channels. Recently, a new heterozygous missense mutation in the CACNA1H gene that encodes the Cav3.2 T-type calcium channel was reported in a patient presenting with epilepsy and hearing loss-apparently the first CACNA1H mutation to be associated with a sensorineural hearing condition. This mutation leads to the substitution of an arginine at position 132 with a histidine (R132H) in the proximal extracellular end of the second transmembrane helix of Cav3.2. In this study, we report the electrophysiological characterization of this new variant using whole-cell patch clamp recordings in tsA-201 cells. Our data reveal minor gating alterations of the channel evidenced by a mild increase of the T-type current density and slower recovery from inactivation, as well as an enhanced sensitivity of the channel to external pH change. To what extend these biophysical changes and pH sensitivity alterations induced by the R132H mutation contribute to the observed pathogenicity remains an open question that will necessitate the analysis of additional CACNA1H variants associated with the same pathologies.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of Huntington's disease phenotype progression in male and female heterozygous FDNQ175 mice. 雄性和雌性杂合子FDNQ175小鼠亨廷顿舞蹈症表型进展的比较。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-19 DOI: 10.1186/s13041-023-01054-6

Si Han Li, Tash-Lynn L Colson, Jingwei Chen, Khaled S Abd-Elrahman, Stephen S G Ferguson

{"title":"Comparison of Huntington's disease phenotype progression in male and female heterozygous FDNQ175 mice.","authors":"Si Han Li, Tash-Lynn L Colson, Jingwei Chen, Khaled S Abd-Elrahman, Stephen S G Ferguson","doi":"10.1186/s13041-023-01054-6","DOIUrl":"10.1186/s13041-023-01054-6","url":null,"abstract":"Huntington's Disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment due to the expansion of a polyglutamine (CAG) repeat in the N-terminal region of the huntingtin (Htt) protein. The creation of HD mouse models represents a critical step in the research for HD treatment. Among the currently available HD mouse models, the zQ175 knock-in mouse line is the first to display robust disease phenotype on a heterozygous background. The newer FDNQ175 mouse model is derived from the zQ175 mouse line and presents a more aggressive phenotype. Moreover, increasing evidence has implicated sex as a contributing factor in the progression of HD symptoms. Here, we compared the progression of HD phenotypes in male and female heterozygous FDNQ175 mice. We found that both male and female heterozygous mice showed deficits in forelimb grip strength and cognition as early as 6 months of age. However, female FDNQ175 mice were less vulnerable to HD-associated decline in limb coordination and movement. Neither male nor female FDNQ175 mice exhibited reduced locomotor activity in the open field or exhibit consistent differences in anxiety at 6-12 months of age. Both male and female FDNQ175 mice exhibited increased numbers of huntingtin aggregates with age and 8-month-old female FDNQ175 mice had significantly more aggregates than their male counterparts. Taken together, our results provide further evidence that sex can influence the progression of HD phenotype in preclinical animal models and must be taken into consideration for future HD research.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recombinase-independent AAV for anterograde transsynaptic tracing. 重组非依赖性AAV用于顺行经突触追踪。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-15 DOI: 10.1186/s13041-023-01053-7

Islam Faress, Valentina Khalil, Haruka Yamamoto, Szilard Sajgo, Keisuke Yonehara, Sadegh Nabavi

引用次数: 0

Changes in oligodendroglial subpopulations in Parkinson's disease. 帕金森病少突胶质细胞亚群的变化。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-09-14 DOI: 10.1186/s13041-023-01055-5

Eun-Jin Bae, Dayana Pérez-Acuña, Ka Hyun Rhee, Seung-Jae Lee

引用次数: 0

Inhibitory insula-ACC projections modulate affective but not sensory aspects of neuropathic pain. 抑制性脑岛ACC投射调节神经性疼痛的情感而非感觉方面。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-08-21 DOI: 10.1186/s13041-023-01052-8

Heloísa Alonso-Matielo, Zizhen Zhang, Eder Gambeta, Junting Huang, Lina Chen, Gabriel Oliveira de Melo, Camila Squarzoni Dale, Gerald W Zamponi

{"title":"Inhibitory insula-ACC projections modulate affective but not sensory aspects of neuropathic pain.","authors":"Heloísa Alonso-Matielo, Zizhen Zhang, Eder Gambeta, Junting Huang, Lina Chen, Gabriel Oliveira de Melo, Camila Squarzoni Dale, Gerald W Zamponi","doi":"10.1186/s13041-023-01052-8","DOIUrl":"10.1186/s13041-023-01052-8","url":null,"abstract":"The insula and anterior cingulate cortex (ACC) are brain regions that undergo structural and functional reorganization in neuropathic pain states. Here, we aimed to study inhibitory parvalbumin positive (PV+) posterior insula (pIC) to posterior ACC (pACC) projections, and to evaluate the effects of direct optogenetic manipulation of such projections on mechanical nociception and spontaneous ongoing pain in mice with Spared Nerve Injury (SNI). CTB488 tract-tracing in male PVCrexAi9 mice revealed a small proportion of PV+ projections from the pIC to the pACC. Electrophysiological analysis confirmed the existence of synaptic inputs into the pACC by pIC GABAergic cells. Optogenetic stimulation of these pathways did not change mechanical nociception, but induced conditioned place preference behavior responses. Our results suggest the presence of inhibitory projections between the pIC and the pACC which are able to selectively modulate affective aspects of neuropathic pain.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10060348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD. 在AD小鼠模型中分析酪氨酸激酶抑制剂作为AD治疗剂。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-08-14 DOI: 10.1186/s13041-023-01051-9

Hyun-Ju Lee, Jeong-Woo Hwang, Jin-Hee Park, Yoo Joo Jeong, Ji-Yeong Jang, Hyang-Sook Hoe

{"title":"Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD.","authors":"Hyun-Ju Lee, Jeong-Woo Hwang, Jin-Hee Park, Yoo Joo Jeong, Ji-Yeong Jang, Hyang-Sook Hoe","doi":"10.1186/s13041-023-01051-9","DOIUrl":"10.1186/s13041-023-01051-9","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ deposition, tauopathy, neuroinflammation, and impaired cognition. The recent identification of associations between protein kinases and AD pathology has spurred interest in tyrosine kinase inhibitors (TKIs) as potential strategic therapeutic agents for AD. In the present study, we investigated whether the TKIs ibrutinib, PD180970, and cabozantinib, which have different on-targets, selectively regulate AD pathology in 3.5- to 4-month-old 5xFAD mice (a model of the early phase of AD). Ibrutinib (10 mg/kg, i.p.) effectively reduced amyloid-β (Aβ) plaque number, tau hyperphosphorylation and neuroinflammation in 5xFAD mice. Surprisingly, PD180970 (10 mg/kg, i.p.) did not alter Aβ plaque number or neuroinflammatory responses and exacerbated tau hyperphosphorylation in 5xFAD mice. Cabozantinib (10 mg/kg, i.p.) had no effect on amyloidopathy but partially relieved tau hyperphosphorylation and astrogliosis. Taken together, our results suggest that not all TKIs have therapeutic effects on AD pathology in a mouse model of AD. Consequently, optimization of drug dosage, injection periods and administration routes should be considered when repurposing TKIs as novel AD therapeutics.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10366413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress. ipsc衍生的TDP-43基因突变运动神经元对氧化应激的特异性易感性

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-07-26 DOI: 10.1186/s13041-023-01050-w

Asako Onda-Ohto, Minami Hasegawa-Ogawa, Hiromasa Matsuno, Tomotaka Shiraishi, Keiko Bono, Hiromi Hiraki, Yumi Kanegae, Yasuyuki Iguchi, Hirotaka James Okano

{"title":"Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress.","authors":"Asako Onda-Ohto, Minami Hasegawa-Ogawa, Hiromasa Matsuno, Tomotaka Shiraishi, Keiko Bono, Hiromi Hiraki, Yumi Kanegae, Yasuyuki Iguchi, Hirotaka James Okano","doi":"10.1186/s13041-023-01050-w","DOIUrl":"https://doi.org/10.1186/s13041-023-01050-w","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology, induced the differentiation of these cells into motor and sensory neurons, and analyzed factors that are assumed to be altered in or associated with ALS (cell morphology, TDP-43 localization and aggregate formation, cell death, TDP-43 splicing function, etc.). We aimed to clarify the pathological alterations caused solely by TDP-43 mutation, i.e., the changes in human iPSC-derived neurons with TDP-43 mutation compared with those with the same genetic background except TDP-43 mutation. Oxidative stress induced by hydrogen peroxide administration caused the death of TDP-43 mutant-expressing motor neurons but not in sensory neurons, indicating the specific vulnerability of human iPSC-derived motor neurons with TDP-43 mutation to oxidative stress. In our model, we observed aggregate formation in a small fraction of TDP-43 mutant-expressing motor neurons, suggesting that aggregate formation seems to be related to ALS pathology but not the direct cause of cell death. This study provides basic knowledge for elucidating the pathogenesis of ALS and developing treatments for the disease.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity. C1ql1-Bai3信号是成熟浦肯野细胞攀爬纤维突触形成与神经元活动协调所必需的。

IF 3.6 3区医学

Molecular Brain Pub Date : 2023-07-24 DOI: 10.1186/s13041-023-01048-4

Takahiro Aimi, Keiko Matsuda, Michisuke Yuzaki

{"title":"C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity.","authors":"Takahiro Aimi, Keiko Matsuda, Michisuke Yuzaki","doi":"10.1186/s13041-023-01048-4","DOIUrl":"https://doi.org/10.1186/s13041-023-01048-4","url":null,"abstract":"Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated by multiple CFs by increased expression of the synaptic organizer C1ql1 in CFs or Bai3, a receptor for C1ql1, in PCs. In the adult cerebellum, CFs are known to have transverse branches that run in a mediolateral direction without forming synapses with PCs. Electrophysiological, Ca2+-imaging and immunohistochemical studies showed that overexpression of C1ql1 or Bai3 caused these CF transverse branches to elongate and synapse on the distal dendrites of mature PCs. Mature PCs were also reinnervated by multiple CFs when the glutamate receptor GluD2, which is essential for the maintenance of synapses between granule cells and PCs, was deleted. Interestingly, the effect of GluD2 knockout was not observed in Bai3 knockout PCs. In addition, C1ql1 levels were significantly upregulated in CFs of GluD2 knockout mice, suggesting that endogenous, not overexpressed, C1ql1-Bai3 signaling could regulate the reinnervation of mature PCs by CFs. Furthermore, the effects of C1ql1 and Bai3 overexpression required neuronal activity in the PC and CF, respectively. C1ql1 immunoreactivity at CF-PC synapses was reduced when the neuronal activity of CFs was suppressed. These results suggest that C1ql1-Bai3 signaling may mediate CF synaptogenesis in mature PCs, potentially in concert with neuronal activity.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10367388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1