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Deep learning-based hyperspectral image correction and unmixing for brain tumor surgery 基于深度学习的脑肿瘤手术高光谱图像校正和非混合技术

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-28 DOI: 10.1016/j.isci.2024.111273

David Black , Jaidev Gill , Andrew Xie , Benoit Liquet , Antonio Di leva , Walter Stummer , Eric Suero Molina

Hyperspectral imaging for fluorescence-guided brain tumor resection improves visualization of tissue differences, which can ameliorate patient outcomes. However, current methods do not effectively correct for heterogeneous optical and geometric tissue properties, leading to less accurate results. We propose two deep learning models for correction and unmixing that can capture these effects. While one is trained with protoporphyrin IX (PpIX) concentration labels, the other is semi-supervised. The models were evaluated on phantom and pig brain data with known PpIX concentration; the supervised and semi-supervised models achieved Pearson correlation coefficients (phantom, pig brain) between known and computed PpIX concentrations of (0.997, 0.990) and (0.98, 0.91), respectively. The classical approach achieved (0.93, 0.82). The semi-supervised approach also generalizes better to human data, achieving a 36% lower false-positive rate for PpIX detection and giving qualitatively more realistic results than existing methods. These results show promise for using deep learning to improve hyperspectral fluorescence-guided neurosurgery.

用于荧光引导脑肿瘤切除术的高光谱成像技术可改善组织差异的可视化，从而改善患者的预后。然而，目前的方法不能有效校正异质光学和几何组织特性，导致结果不够准确。我们提出了两种用于校正和解除混合的深度学习模型，可以捕捉到这些影响。其中一个是用原卟啉 IX（PpIX）浓度标签训练的，另一个是半监督的。这些模型在已知 PpIX 浓度的模型和猪脑数据上进行了评估；监督和半监督模型在已知和计算的 PpIX 浓度之间的皮尔逊相关系数（模型、猪脑）分别为（0.997，0.990）和（0.98，0.91）。经典方法达到了（0.93, 0.82）。半监督方法对人类数据的泛化效果也更好，PpIX 检测的假阳性率降低了 36%，与现有方法相比，半监督方法得到了更真实的结果。这些结果表明，利用深度学习改进高光谱荧光引导神经外科手术大有可为。

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引用次数: 0

Mice carrying the full-length human immunoglobulin loci produce antigen-specific human antibodies with the lambda light chain 携带全长人类免疫球蛋白基因座的小鼠产生带有λ轻链的抗原特异性人类抗体

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-28 DOI: 10.1016/j.isci.2024.111258

Kazuto Shimoya , Takashi Moriwaki , Kanako Kazuki , Akane Okada , Shigenori Baba , Yuana Masuda , Satoshi Abe , Yasuhiro Kazuki

The development of antibody drugs through animal immunization typically requires the humanization of host antibodies to address concerns about immunogenicity in humans. However, employing an animal model capable of producing human antibodies presents the opportunity to develop antibody drugs without the need for humanization. Despite the ratio of human immunoglobulin (Ig) κ to Igλ usage being approximately 60%:40%, the majority of approved antibody therapeutics are kappa antibodies, and the development of lambda antibodies as therapeutic agents has lagged behind. Therefore, in this study, we developed mice carrying the IGH and IGL loci (IGHL), which can produce human lambda antibodies, using mouse artificial chromosome (MAC) vectors. We demonstrated that IGHL mice consistently retain the human lambda antibody locus integrated on the MAC across generations and can be induced to produce specific antibodies upon antigen stimulation. These findings provide a promising platform for advancing lambda antibody drugs, which have historically been neglected.

通过动物免疫法开发抗体药物通常需要对宿主抗体进行人源化处理，以解决对人类免疫原性的担忧。然而，采用能够产生人类抗体的动物模型则为开发抗体药物提供了无需人源化的机会。尽管人类免疫球蛋白（Ig）κ和Igλ的使用比例约为60%:40%，但大多数获批的抗体治疗药物都是卡帕抗体，而作为治疗药物的λ抗体的开发却相对滞后。因此，在这项研究中，我们利用小鼠人工染色体（MAC）载体培育了携带IGH和IGL基因座（IGHL）的小鼠，它们能产生人类λ抗体。我们证明，IGHL小鼠能跨代持续保留整合在MAC上的人类λ抗体基因座，并能在抗原刺激下诱导产生特异性抗体。这些发现为开发λ抗体药物提供了一个前景广阔的平台，而λ抗体药物在历史上一直被忽视。

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引用次数: 0

Autophagy in reproduction and pregnancy-associated diseases 自噬在生殖和妊娠相关疾病中的作用

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-28 DOI: 10.1016/j.isci.2024.111268

Asmita Singh , Maira L. Perez , Oleksandr Kirsanov , Elizabeth Padilla-Banks , Carlos M. Guardia

As advantageous as sexual reproduction is during progeny generation, it is also an expensive and treacherous reproductive strategy. The viviparous eukaryote has evolved to survive stress before, during, and after pregnancy. An important and conserved intracellular pathway for the control of metabolic stress is autophagy. The autophagy process occurs in multiple stages through the coordinated action of autophagy-related genes. This review summarizes the evidence that autophagy is an integral component of reproduction. Additionally, we discuss emerging in vitro techniques that will enable cellular and molecular studies of autophagy and its associated pathways in reproduction. Finally, we discuss the role of autophagy in the pathogenesis and progression of several pregnancy-related disorders such as preterm birth, preeclampsia, and intra-uterine growth restriction, and its potential as a therapeutic target.

虽然有性生殖在后代产生过程中具有优势，但它也是一种昂贵而危险的生殖策略。胎生真核生物在妊娠前、妊娠中和妊娠后都在进化以应对压力。自噬是控制代谢应激的一个重要而保守的细胞内途径。自噬过程通过自噬相关基因的协调作用分多个阶段进行。本综述总结了自噬是生殖不可或缺的组成部分的证据。此外，我们还讨论了新出现的体外技术，这些技术将有助于对自噬及其在生殖过程中的相关途径进行细胞和分子研究。最后，我们讨论了自噬在早产、子痫前期和宫内生长受限等几种妊娠相关疾病的发病机制和进展中的作用，以及自噬作为治疗靶点的潜力。

引用次数: 0

Combined TLR2/TLR4 activation equip non-mucosal dendritic cells to prime Th1 cells with gut tropism 联合激活 TLR2/TLR4 使非黏膜树突状细胞具备肠道趋向性 Th1 细胞的能力

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-26 DOI: 10.1016/j.isci.2024.111232

Sara Zúquete , Mariana Ferreira , Inês L.S. Delgado , Paula Gazalle , Stephanie Andaluz , Maria Teresa Rosa , Ana Catarina Mendes , Dulce Santos , Sofia Nolasco , Luís Graça , Alexandre Leitão , Afonso P. Basto

Activated CD4⁺ T cells located at mucosal surfaces orchestrate local effector immune mechanisms. When properly polarized, these cells contribute to block infections at early stages and may be essential to restrain the local growth of mucosal tumors, playing a critical role in host protection. How CD4⁺ T cells simultaneously integrate gut-homing instructions and Th polarization signals transmitted by TLR activated dendritic cells (DCs) is unknown. Here, we show that the combined activation through TLR2, which alone does not induce a clear Th polarization, and TLR4, which alone does not imprint mucosal tropism, equip non-mucosal DCs to prime gut-homing CD4⁺ T cells with reinforced Th1 polarization. These results show that targeting DCs with combined innate stimuli with distinct properties is a rational strategy to program the outcome of T cell polarization and simultaneously control their tissue tropism. Exploring this strategy could enhance the efficacy of vaccines and immune cell therapies.

位于粘膜表面的活化 CD4+ T 细胞协调着局部效应免疫机制。当这些细胞被适当极化时，它们有助于在早期阶段阻断感染，并可能对抑制粘膜肿瘤的局部生长至关重要，在保护宿主方面发挥着关键作用。CD4+ T细胞如何同时整合肠道归巢指令和TLR激活的树突状细胞（DCs）传递的Th极化信号尚不清楚。在这里，我们发现通过 TLR2 和 TLR4 的联合激活（TLR2 本身并不能诱导明确的 Th 极化，而 TLR4 本身并不能印记粘膜趋向性），非粘膜 DC 可使肠道归巢的 CD4+ T 细胞强化 Th1 极化。这些结果表明，以具有不同特性的综合先天刺激物为靶点的直流细胞是一种合理的策略，它能对 T 细胞极化的结果进行编程，同时控制它们的组织滋养性。探索这种策略可以提高疫苗和免疫细胞疗法的疗效。

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引用次数: 0

Flowtigs: Safety in flow decompositions for assembly graphs Flowtigs：装配图流量分解的安全性

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-25 DOI: 10.1016/j.isci.2024.111208

Francisco Sena , Eliel Ingervo , Shahbaz Khan , Andrey Prjibelski , Sebastian Schmidt , Alexandru Tomescu

A decomposition of a network flow is a set of weighted walks whose superposition equals the flow. In this article, we give a simple and linear-time-verifiable complete characterization (flowtigs) of walks that are safe in such general flow decompositions, i.e., that are subwalks of any possible flow decomposition. We provide an O(mn)-time algorithm that identifies all maximal flowtigs and represents them inside a compact structure. On the practical side, we study flowtigs in the use-case of metagenomic assembly. By using the species abundances as flow values of the metagenomic assembly graph, we can model the possible assembly solutions as flow decompositions into weighted closed walks. On simulated data, compared to reporting unitigs or maximal safe walks based only on the graph structure, reporting flowtigs results in a notably more contiguous assembly. On real data, we frame flowtigs as a heuristic and provide an algorithm that is guided by this heuristic.

网络流的分解是一组加权行走，其叠加等于流。在本文中，我们给出了一个简单且可线性时间验证的完整描述（flowtigs），即在这种一般流分解中安全的行走，也就是任何可能的流分解的子行走。我们提供了一种 O(mn)-time 算法，它能识别所有最大 flowtigs 并将其表示在一个紧凑的结构中。在实际应用方面，我们研究了元基因组组装中的 flowtigs。通过使用物种丰度作为元基因组组装图的流值，我们可以将可能的组装方案建模为加权封闭行走的流分解。在模拟数据上，与仅根据图结构报告单元图或最大安全走行相比，报告 flowtigs 可明显提高组装的连续性。在真实数据上，我们将 flowtigs 定义为一种启发式，并提供了一种以这种启发式为指导的算法。

引用次数: 0

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-24 eCollection Date: 2024-11-15 DOI: 10.1016/j.isci.2024.111251

Nicole C Miranda, Luiz M Oliveira, Thiago S Moreira, Jan-Marino Ramirez, Franck Kalume, Ana C Takakura

Parkinson's disease (PD) is a chronic neurodegenerative disorder affecting the motor system, with non-classic symptoms such as sleep disturbances and respiratory dysfunctions. These issues reflect a complex pathophysiological interaction that severely impacts quality of life. Using a 6-hydroxydopamine (6-OHDA) mouse model of PD, we investigated these connections by analyzing sleep patterns and respiratory parameters during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Our findings revealed altered breathing, including reduced respiratory frequency and increased apneas during both NREM and REM. To address these abnormalities, we employed chemogenetic stimulation of cholinergic neurons in the laterodorsal tegmental nucleus (LDTg), a key region for sleep-wake regulation and respiratory modulation. This intervention normalized respiratory function. These results highlight the critical role of LDTg cholinergic neurons in the coordinating sleep and breathing, suggesting that targeting these neurons could offer a therapeutic strategy for managing PD-related respiratory complications.

帕金森病（PD）是一种影响运动系统的慢性神经退行性疾病，伴有睡眠障碍和呼吸功能障碍等非典型性症状。这些问题反映了复杂的病理生理学相互作用，严重影响生活质量。我们利用 6-羟基多巴胺（6-OHDA）多发性硬化症小鼠模型，通过分析非快速眼动（NREM）和快速眼动（REM）睡眠期间的睡眠模式和呼吸参数，研究了这些联系。我们的发现揭示了呼吸的改变，包括非快速眼动睡眠和快速眼动睡眠期间呼吸频率降低和呼吸暂停增加。为了解决这些异常现象，我们采用化学方法刺激了背侧被盖核胆碱能神经元（LDTg），这是睡眠-觉醒调节和呼吸调节的关键区域。这种干预使呼吸功能恢复正常。这些结果凸显了LDTg胆碱能神经元在协调睡眠和呼吸中的关键作用，表明针对这些神经元的治疗策略可用于控制与帕金森病相关的呼吸系统并发症。

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引用次数: 0

Unveiling the bidirectional link between electric vehicle sales and charging infrastructure: Evidence from 95 cities in China. 揭示电动汽车销售与充电基础设施之间的双向联系：来自中国 95 个城市的证据。

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-24 eCollection Date: 2024-11-15 DOI: 10.1016/j.isci.2024.111245

Jianfeng Guo, Binbin Xu, Qi Cao, Siyao Liu, Fu Gu, Xuemei Zhang

Constructing electric vehicle charging piles (EVCPs) is crucial for promoting electric vehicle (EV) sales. Yet, empirical evidence on the bidirectional relationship between EV sales and public EVCPs is limited, with most related works relying on simulations. We empirically investigate this relationship using panel vector autoregression (PVAR) across 95 Chinese cities from 2018 to 2022. Results show EVCPs significantly boost EV sales, especially in colder regions. Higher air pollution and purchase subsidies inhibit the promoting impact of EV sales on EVCPs. The propelling effect of EVCPs on EV sales is impaired in higher housing prices regions. A significant and positive bidirectional relationship exists between EVCPs and battery electric vehicles (BEVs) sales exists, but not with plug-in hybrid electric vehicles (PHEVs) present. Our findings have implications for stakeholders, such as the construction of fast charging infrastructure under lower temperatures, and differentiated charging demands of EVs with different powertrains need to be addressed.

建设电动汽车充电桩（EVCP）对促进电动汽车（EV）销售至关重要。然而，有关电动汽车销售与公共电动汽车充电桩之间双向关系的实证证据非常有限，大多数相关研究都是通过模拟来进行的。我们使用面板向量自回归（PVAR）对 2018 年至 2022 年中国 95 个城市的这一关系进行了实证研究。结果显示，EVCPs 极大地促进了电动汽车的销售，尤其是在寒冷地区。较高的空气污染和购车补贴抑制了电动汽车销售对 EVCPs 的促进作用。在房价较高的地区，EVCPs 对电动汽车销售的促进作用受到削弱。EVCPs与电池电动汽车（BEV）的销售之间存在重要的正向双向关系，但与插电式混合动力电动汽车（PHEV）之间不存在这种关系。我们的研究结果对利益相关者具有启示意义，例如在较低温度下建设快速充电基础设施，以及需要解决不同动力系统的电动汽车的差异化充电需求。

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引用次数: 0

Evolution of queen pheromone receptor tuning in four honeybee species (Hymenoptera, Apidae, Apis) 四种蜜蜂（膜翅目，鳞翅目，蜂科）蜂王信息素受体调谐的进化

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-24 DOI: 10.1016/j.isci.2024.111243

Julia Mariette , Julie Carcaud , Thierry Louis , Eleanor Lacassagne , Ilana Servais , Nicolas Montagné , Thomas Chertemps , Emmanuelle Jacquin-Joly , Camille Meslin , Frédéric Marion-Poll , Jean-Christophe Sandoz

Honeybees (genus: Apis) use a plethora of pheromones for intraspecific communication. The primary compound produced by the queen’s mandibular glands, 9-ODA, is involved in mating in all Apis species. It is the ligand of the most highly expressed olfactory receptor in males of Apis mellifera: AmelOR11. Putative orthologs are found in the genomes of other Apis species: Apis dorsata, Apis florea, and Apis cerana. Modeling of OR11 proteins shows high structure conservation except for AflorOR11. Using heterologous expression in Drosophila and calcium imaging, a broad odorant screening revealed that all OR11 respond predominantly to 9-ODA, but also to secondary ligands, except AflorOR11, which remains specific to 9-ODA. Secondary ligands were confirmed by optical imaging of male antennal lobes in A. mellifera. This work supports a conserved queen sex pheromone detection channel in honeybees, albeit with an extended response spectrum possibly playing a role in reproductive isolation among species.

蜜蜂（蜂属）使用大量信息素进行种内交流。蜂王下颚腺产生的主要化合物 9-ODA 参与所有蜂类的交配。它是雄蜂嗅觉受体 AmelOR11 的配体。在其他蜂类的基因组中也发现了推测的直向同源物：Apis dorsata、Apis florea 和 Apis cerana。OR11 蛋白的建模显示，除 AflorOR11 外，其他 OR11 蛋白的结构保持高度一致。利用果蝇中的异源表达和钙成像技术，广泛的气味筛选显示，所有 OR11 主要对 9-ODA 有反应，但也对次级配体有反应，只有 AflorOR11 除外，它仍然对 9-ODA 有特异性反应。通过对 A. mellifera 的雄性触角叶进行光学成像，确认了次要配体。这项工作支持蜜蜂中保守的蜂王性信息素检测通道，尽管其反应谱较广，可能在物种间的生殖隔离中发挥作用。

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引用次数: 0

Early synaptic dysfunction of striatal parvalbumin interneurons in a mouse model of Parkinson's disease. 帕金森病小鼠模型中纹状体旁突触中间神经元的早期突触功能障碍

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-24 eCollection Date: 2024-11-15 DOI: 10.1016/j.isci.2024.111253

Quansheng He, Xiaowen Zhang, Hongyu Yang, Dahui Wang, Yousheng Shu, Xuan Wang

In Parkinson's disease (PD), the loss of dopaminergic signaling remodels striatal circuits, causing abnormal network activity. The timing and impact on various striatal cell types during this reorganization are unclear. Here we demonstrate that dopamine depletion rapidly reduces parvalbumin (PV) expression. At the synaptic input level, PV interneurons shift toward inhibition in the excitation-inhibition balance early on, a week before a similar shift in spiny projection neurons (SPNs). At the cellular level, both PV interneurons and SPNs experience a significant decrease in their spiking and bursting rates, respectively, which corresponds to a reduction in gamma and beta (early beta) oscillations during the early stage of PD. Importantly, the pharmacogenetic activation of PV interneurons reverses gamma deficits and suppresses beta (late beta) oscillation in the striatum of parkinsonian mice. Collectively, our findings underscore the vulnerability of PV interneurons to dopamine depletion and their responsibility for the evolution of abnormal activities in parkinsonian striatum.

在帕金森病（PD）中，多巴胺能信号的缺失会重塑纹状体回路，导致异常的网络活动。目前还不清楚这种重组的时间和对纹状体各种细胞类型的影响。在这里，我们证明了多巴胺耗竭会迅速降低副发光体（PV）的表达。在突触输入水平上，PV中间神经元很早就在兴奋-抑制平衡中转向抑制，比棘突投射神经元（SPNs）的类似转变早一周。在细胞水平上，中枢神经间元和脊髓投射神经元的尖峰跃动率和爆发率都分别显著下降，这与帕金森病早期伽马和β（早期β）振荡的减少相对应。重要的是，帕金森病小鼠纹状体中PV中间神经元的药物基因激活可逆转伽马缺陷并抑制β（晚期β）振荡。总之，我们的研究结果强调了PV中间神经元对多巴胺耗竭的脆弱性，以及它们对帕金森病纹状体异常活动演变的责任。

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引用次数: 0

Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets 白细胞介素-2 受体信号转导是影响调节性 T 细胞亚群分布的检查点

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2024-10-24 DOI: 10.1016/j.isci.2024.111248

Acacia N. Shouse , Alejandro V. Villarino , Thomas R. Malek

Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs). Unexpectedly, ablation of IL-2R signaling in cTregs resulted in increased proliferation, expression of eTreg genes, and enhanced capacity to develop into eTregs. Thus, IL-2R signaling normally acts as a checkpoint to maintain cTreg homeostasis while restraining their development into eTregs. Loss of IL-2R signaling also alters the distribution of eTreg subsets, with increased IFNγR1⁺ eTregs and CXCR5⁺ PD-1⁺ T follicular regulatory (T_FR) cells but decreased intestinal RORγt⁺ T_R17 cells. These changes lower eTreg suppressive function supporting expansion of IFNγ-secreting T effector cells. Thus, IL-2R signaling also safeguards Treg function and licenses differentiation of specialized eTregs.

调节性T细胞（Tregs）需要IL-2才能在外周存活，但IL-2如何塑造Treg的异质性仍未明确。在这里，我们发现抑制胸腺后Tregs的IL-2R信号转导会导致循环Tregs（cTregs）的优先早期损失。与效应Tregs（eTregs）相比，cTregs的基因表达更依赖于IL-2R信号。意想不到的是，消减 cTregs 的 IL-2R 信号会导致 eTregs 的增殖、基因表达和发展成 eTregs 的能力增强。因此，IL-2R 信号通常作为一个检查点维持 cTreg 的平衡，同时限制它们发育成 eTregs。IL-2R 信号的缺失也改变了 eTreg 亚群的分布，IFNγR1+ eTregs 和 CXCR5+ PD-1+ T 滤泡调节（TFR）细胞增多，但肠 RORγt+ TR17 细胞减少。这些变化降低了 eTreg 的抑制功能，支持了分泌 IFNγ 的 T 效应细胞的扩增。因此，IL-2R 信号还能保障 Treg 的功能并许可特化 eTreg 的分化。

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引用次数: 0

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