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Digital Accessibility for Students with Disabilities and Inclusive Learning in Education. 残疾学生的数字无障碍与教育中的全纳学习。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-03402-1_44
Elissavet Karageorgou, Styliani Adam, Spyridon Doukakis, Panagiotis Vlamos

The rapid advancement of digital technologies has reshaped education, yet significant barriers persist in ensuring equitable access for students with disabilities. Digital accessibility in education extends beyond technological solutions, requiring institutional commitment, policy reform, and faculty preparedness. This study examines the challenges and opportunities associated with digital accessibility in higher education and workplace inclusion, emphasizing systemic barriers such as inadequate assistive technologies, inaccessible Learning Management Systems (LMSs), and insufficient faculty training. The findings highlight the transformative potential of adaptive learning strategies, including artificial intelligence (AI), extended reality (XR), and human-computer interaction (HCI), in fostering personalized and inclusive learning environments. However, ethical concerns, algorithmic biases, and inconsistent implementation pose substantial obstacles to their effectiveness. The COVID-19 pandemic further exposed critical shortcomings in digital accessibility policies, disproportionately affecting students and employees with disabilities and underscoring the need for inclusive digital literacy initiatives. Addressing these challenges necessitates a holistic approach that integrates universal design principles, strengthens faculty training programs, and fosters interdisciplinary collaboration between educators, policymakers, and technologists. Through this review, sustained investment in assistive technologies is advocated, along with regulatory frameworks mandating digital inclusivity, and the development of digital learning ecosystems. By embedding accessibility as a fundamental component of educational and employment policies, institutions can mitigate the digital divide and advance equitable opportunities for all learners.

数字技术的快速发展重塑了教育,但在确保残疾学生公平获得教育机会方面仍然存在重大障碍。教育中的数字可及性超出了技术解决方案,需要机构承诺、政策改革和教师准备。本研究考察了高等教育和工作场所包容性中与数字可及性相关的挑战和机遇,强调了辅助技术不足、学习管理系统(lms)不可及和教师培训不足等系统性障碍。研究结果强调了适应性学习策略(包括人工智能(AI)、扩展现实(XR)和人机交互(HCI))在培养个性化和包容性学习环境方面的变革潜力。然而,伦理问题、算法偏见和不一致的实施对其有效性构成了实质性障碍。2019冠状病毒病大流行进一步暴露了数字无障碍政策的严重缺陷,对残疾学生和雇员造成了不成比例的影响,凸显了包容性数字扫盲举措的必要性。应对这些挑战需要一种整合通用设计原则的整体方法,加强教师培训计划,并促进教育者、政策制定者和技术专家之间的跨学科合作。通过这一审查,我们提倡对辅助技术进行持续投资,同时建立数字包容性的监管框架,并发展数字学习生态系统。通过将可访问性作为教育和就业政策的基本组成部分,各机构可以缓解数字鸿沟,促进所有学习者的公平机会。
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引用次数: 0
Maternal Caffeine Consumption and Pregnancy Outcomes. 孕妇咖啡因摄入与妊娠结局
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-12741-9_10
Jack E James

Caffeine, a habit-forming substance of no nutritional value, is consumed daily by most pregnant women. This focused narrative review examines evidence of association between maternal caffeine consumption and negative pregnancy outcomes, and assesses whether current advice guidelines are consistent with the available evidence. The majority finding from original empirical studies, systematic reviews, and meta-analyses is that maternal consumption of caffeine is reliably associated with serious negative pregnancy outcomes and negative outcomes in offspring. Evidence of harm is strong for miscarriage, stillbirth, and low birth weight and/or small for gestational age, while being less strong for childhood acute leukemia, childhood overweight and obesity, and childhood behavioural and neurocognitive development. In contrast, preterm birth appears not to be at increased risk. Many studies report significant dose-response associations indicative of causation and the absence of a threshold of consumption below which associations are absent. In general, findings are robust to threats from potential confounding and misclassification. Notwithstanding compelling grounds to the contrary, national and international authorities continue to suggest that "moderate" caffeine consumption during pregnancy is safe. Rather, pregnant women and women contemplating pregnancy should be advised not to consume coffee, tea, sodas, or energy drinks that contain caffeine.

咖啡因是一种没有营养价值的养成习惯的物质,大多数孕妇每天都要摄入它。这篇集中的叙述性综述研究了母体咖啡因摄入与不良妊娠结局之间的关联证据,并评估了当前的建议指南是否与现有证据一致。最初的实证研究、系统回顾和荟萃分析的主要发现是,母体摄入咖啡因与严重的负面妊娠结局和后代的负面结局可靠地相关。流产、死产、低出生体重和/或胎龄小的危害证据非常明显,而儿童急性白血病、儿童超重和肥胖以及儿童行为和神经认知发育的危害证据则不那么明显。相比之下,早产的风险似乎没有增加。许多研究报告了显著的剂量-反应关联,表明了因果关系,并且没有一个消费阈值,低于这个阈值就没有关联。一般来说,研究结果对潜在混淆和错误分类的威胁是可靠的。尽管有令人信服的相反理由,国家和国际当局继续建议怀孕期间“适度”摄入咖啡因是安全的。相反,孕妇和准备怀孕的女性应该被建议不要饮用含有咖啡因的咖啡、茶、苏打水或能量饮料。
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引用次数: 0
Impact of Prenatal Alcohol Exposure on the Cerebral Circulation: Potential Implications for Stroke. 产前酒精暴露对脑循环的影响:对中风的潜在影响
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-12741-9_2
Partha S Saha, Denise M Arrick, William G Mayhan

Prenatal alcohol exposure (PAE) is recognized as a teratogenic factor that affects neural development, resulting in a range of structural, functional, and cognitive/behavioral abnormalities contributing to the pathogenesis of fetal alcohol spectrum disorder (FASD). FASD is a major preventable cause of developmental delay in humans. There are many molecular and cellular mechanisms by which PAE could contribute to abnormalities seen in individuals with FASD. Understanding these mechanisms will be critical for the development of therapeutic approaches that could benefit not only the developing fetus, but the newborn as they mature into adolescence and adulthood. The goal of this review is to discuss the impact of PAE on neural and vascular development/function and define potential cellular/molecular mechanisms that contribute to the effects of PAE. We believe that an understanding regarding the influence of PAE on cerebral vascular function may provide insights into the pathogenesis of symptoms related to FASD.

产前酒精暴露(PAE)被认为是一种影响神经发育的致畸因素,导致一系列结构、功能和认知/行为异常,从而导致胎儿酒精谱系障碍(FASD)的发病机制。FASD是人类发育迟缓的主要可预防原因。有许多分子和细胞机制可以通过PAE导致FASD患者的异常。了解这些机制对于治疗方法的发展至关重要,这不仅有利于发育中的胎儿,也有利于进入青春期和成年期的新生儿。本综述的目的是讨论PAE对神经和血管发育/功能的影响,并确定PAE作用的潜在细胞/分子机制。我们认为,了解PAE对脑血管功能的影响可能有助于了解FASD相关症状的发病机制。
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引用次数: 0
Regenerative Strategies in Pediatric Dentistry: A Comprehensive Overview of Tissue Engineering from Past to Future. 再生策略在儿童牙科:组织工程的全面概述,从过去到未来。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/5584_2025_877
Belen Şirinoğlu Çapan, Sinem Birant, Burak Gümüştaş, Pınar Ercal, Soner Sismanoglu

Tissue engineering in pediatric dentistry focuses on regenerating damaged dental tissues in children, aiming to restore their natural functions and address challenges associated with immature teeth. This field applies interdisciplinary biological principles to repair and regenerate tissues, using biomaterials, stem cells, and growth factors. Current advancements emphasize the regeneration of the dentin-pulp complex and tooth development through the use of biomaterials such as collagen, which offers structural support for cell growth and favorable interactions in tissue engineering. Additionally, various growth factors like FGF, TGF-β, BMP, and VEGF play vital roles in tissue regeneration by regulating signaling mechanisms in the dentin-pulp complex. Stem cells, particularly dental-derived ones such as DPSCs, SHEDs, and PDLSCs, have shown great potential in regenerating dental tissues in pediatric patients. These multipotent cells are capable of differentiating into various lineages, including odontoblasts, and are essential for the regeneration of both soft and hard dental tissues. While gene therapy, scaffolding techniques, and advanced technologies like three-dimensional (3D) bioprinting hold promise for tissue engineering, challenges remain in clinical implementation due to high costs and the need for further research. However, tissue engineering has already begun revolutionizing pediatric dental treatments, particularly in regenerative endodontics, and offers a minimally invasive alternative to traditional procedures like root canal treatments for young immature teeth. The future of regenerative dentistry in pediatric care lies in improving the application of stem cell-based therapies and bioactive materials to achieve complete tissue regeneration and provide more effective, personalized care for young patients.

儿童牙科组织工程研究的重点是再生儿童受损的牙组织,旨在恢复其自然功能并解决与未成熟牙齿相关的挑战。该领域应用跨学科的生物学原理来修复和再生组织,使用生物材料,干细胞和生长因子。目前的进展强调通过使用胶原等生物材料再生牙本质-牙髓复合体和牙齿发育,胶原为细胞生长和组织工程中有利的相互作用提供结构支持。此外,多种生长因子如FGF、TGF-β、BMP和VEGF通过调节牙本质-牙髓复合体的信号机制在组织再生中发挥重要作用。干细胞,特别是牙源性干细胞,如DPSCs、shed和PDLSCs,在儿科患者的牙齿组织再生中显示出巨大的潜力。这些多能细胞能够分化成各种细胞系,包括成牙细胞,并且对于软牙和硬牙组织的再生都是必不可少的。虽然基因疗法、支架技术和三维生物打印等先进技术为组织工程带来了希望,但由于成本高和需要进一步研究,在临床实施方面仍然存在挑战。然而,组织工程已经开始彻底改变儿童牙科治疗,特别是再生牙髓学,并提供了一种微创替代传统手术,如对年轻未成熟牙齿进行根管治疗。再生牙科在儿科护理中的未来在于改进基于干细胞的治疗方法和生物活性材料的应用,以实现完全的组织再生,为年轻患者提供更有效的个性化护理。
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引用次数: 0
Exploring the Complexities of Bone Implants and Stents: Factors Influencing Successful Tissue Integration. 探讨骨植入物和支架的复杂性:影响成功组织整合的因素。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/5584_2025_872
Yelda Yüregir, Seher Yaylacı, Hakan Ceylan

Bone implants and stents are medical devices that are commonly used to treat bone and cardiovascular diseases, respectively. Both require successful integration with the surrounding tissue to achieve long-term success. Osteointegration, the process by which the implant becomes integrated with the surrounding bone, is critical to the success of bone implants, while the stent healing process involves endothelialization, re-endothelialization, and neointimal formation. The healing process of bone is complex and influenced by various factors, including the properties of the implant material, the surgical technique, and patient factors such as age and overall health. Several materials have been developed for bone implants, including metals, ceramics, and polymers. The choice of material depends on the specific application, as each material has unique properties that affect its suitability for a particular use. For example, titanium is commonly used in orthopedic implants due to its biocompatibility, strength, and ability to promote osteointegration. The healing process of stents is influenced by the materials used and the stent design. Drug-eluting stents, which release drugs to reduce restenosis, have been developed to improve the healing process. Endothelialization, the formation of a layer of endothelial cells over the stent, is critical to the prevention of restenosis. Neointimal formation, the formation of new tissue over the stent, can cause restenosis and has been a major concern with bare-metal stents. Factors that affect osteointegration and stent healing process include implant surface properties, such as roughness and topography, as well as the size, shape, and placement of the implant. In addition, patient factors such as age, overall health, and medication use can also affect the healing process. In conclusion, successful integration with the surrounding tissue is critical to the long-term success of bone implants and stents. The choice of implant material, surgical technique, and patient factors all play a role in the healing process, and ongoing research is needed to improve the design and performance of these medical devices.

骨植入物和支架分别是常用的治疗骨骼疾病和心血管疾病的医疗设备。两者都需要与周围组织成功结合才能获得长期的成功。骨整合,即植入物与周围骨整合的过程,对骨植入物的成功至关重要,而支架愈合过程包括内皮化、再内皮化和新内膜形成。骨的愈合过程是复杂的,受多种因素的影响,包括植入材料的特性、手术技术以及患者的年龄和整体健康状况等因素。已经开发了几种用于骨植入的材料,包括金属、陶瓷和聚合物。材料的选择取决于具体的应用,因为每种材料都有独特的性能,影响其对特定用途的适用性。例如,钛因其生物相容性、强度和促进骨整合的能力而常用于骨科植入物。支架的修复过程受支架材料和支架设计的影响。药物洗脱支架,释放药物以减少再狭窄,已被开发用于改善愈合过程。内皮化,即在支架上形成一层内皮细胞,对预防再狭窄至关重要。新内膜形成,即支架上新组织的形成,可引起再狭窄,这一直是裸金属支架的主要问题。影响骨整合和支架愈合过程的因素包括种植体表面特性,如粗糙度和地形,以及种植体的大小、形状和放置位置。此外,患者的年龄、整体健康状况和药物使用等因素也会影响愈合过程。总之,与周围组织的成功融合对于骨植入物和支架的长期成功至关重要。植入材料的选择、手术技术和患者因素都在愈合过程中发挥作用,需要持续的研究来改进这些医疗设备的设计和性能。
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引用次数: 0
Dynamic Changes in Cerebral Oxygenation and Arterial Pressure During Repeated Rapid Hypotension. 反复快速低血压时脑氧合和动脉压的动态变化。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_30
Saya Tokuda, Hyuga Kojima, Hiroki Baba, Hajime Tamiya, Atsuhiro Tsubaki

This study aimed to determine the changes in the time to nadir of mean arterial pressure (MAP) and oxygenated hemoglobin (O₂Hb) in the right and left prefrontal cortices (R-PFC and L-PFC, respectively) during repeated episodes of rapid hypotension. Four cycles of blood pressure reduction were induced via bilateral thigh occlusion at 250 mmHg followed by rapid deflation. Sixteen healthy male university students participated. MAP was recorded beat by beat, and O₂Hb was continuously monitored using near-infrared spectroscopy. The time from deflation to nadir was measured and compared across each deflation cycle. MAP and O₂Hb in the R-PFC and L-PFC reached their nadir values approximately 7 to 8 s post-deflation, with no significant changes observed across repetitions. These findings indicate that the time to nadir of MAP and O₂Hb in the R-PFC and L-PFC remains stable during repeated rapid hypotension.

本研究旨在确定反复发作的快速低血压期间左右前额叶皮层(分别为R-PFC和L-PFC)平均动脉压(MAP)和氧合血红蛋白(O₂Hb)降至最低点的时间变化。通过双侧大腿阻断250 mmHg后快速放压诱导4个周期的血压降低。16名健康的男大学生参与了研究。逐拍记录MAP,用近红外光谱连续监测O₂Hb。从通货紧缩到最低点的时间在每个通货紧缩周期中进行了测量和比较。R-PFC和L-PFC中的MAP和O₂Hb在通缩后约7 ~ 8 s达到最低点,重复次数无显著变化。这些结果表明,在反复快速降压过程中,R-PFC和L-PFC中MAP和O₂Hb降至最低点的时间保持稳定。
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引用次数: 0
Random Acquisition of Spectral Projections in Four-Dimensional Spectral-Spatial EPR Imaging: A Feasibility Study Toward Oxygen Imaging. 四维光谱空间EPR成像中光谱投影的随机获取:氧成像的可行性研究。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_6
Misa Oba, Mai Taguchi, Shingo Matsumoto, Hiroshi Hirata

In continuous-wave electron paramagnetic resonance (CW-EPR) imaging, many spectral projections are required to accurately reconstruct four-dimensional (4D) spectral-spatial data, which are used for oxygen mapping in tumors. The ability to obtain fewer spectral projections with less degradation of the resultant image quality is desirable because acquiring many spectral projections leads to a longer time for EPR imaging acquisition. The algebraic reconstruction technique (ART) is one of the most powerful image-reconstruction techniques for 4D spectral-spatial imaging. ART can be applied to incomplete sets of spectral projections. However, data sets of many spectral projections can provide reconstructed images of higher quality. In this study, we aimed to enhance acquisition speed by randomly collecting spectral projections and subsequently synthesizing those that had not been recorded. We applied this strategy to a numerical phantom and a mouse Hs766T xenograft model to confirm the feasibility of our concept. Random acquisition can prevent image degradation in linewidth mapping, which is the foundation for oxygen mapping with CW-EPR.

在连续波电子顺磁共振(CW-EPR)成像中,需要许多光谱投影来精确重建四维(4D)光谱空间数据,这些数据用于肿瘤中的氧定位。能够获得更少的光谱投影和更少的图像质量下降是可取的,因为获得更多的光谱投影会导致EPR成像采集的时间更长。代数重建技术(ART)是四维光谱空间成像中最强大的图像重建技术之一。ART可以应用于光谱投影的不完全集。然而,许多光谱投影的数据集可以提供更高质量的重建图像。在本研究中,我们的目标是通过随机收集光谱投影并随后合成未记录的光谱投影来提高采集速度。我们将这一策略应用于数值幻影和小鼠Hs766T异种移植模型,以证实我们概念的可行性。随机采集可以防止线宽映射中图像的退化,这是利用CW-EPR进行氧映射的基础。
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引用次数: 0
The Role of Nitric Oxide in Regulating Microvascular Oxygen Pressure During Diaphragm Contraction in Rats. 一氧化氮在大鼠膈肌收缩时微血管氧压调节中的作用。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_17
Kazuki Hotta, Narumi Fukuzaki, Rin Kataoka, Kota Izawa, Shuri Arai, Kentaro Kamiya, Atsuhiko Matsunaga

Background: The diaphragm muscle is the primary muscle involved in inspiration and is unique to mammals. Because the diaphragm is a constantly active muscle, its contraction may depend on oxidative phosphorylation and O2 supply to create adenosine triphosphate. This study aimed to evaluate the role of intrinsic vasodilator nitric oxide (NO) in diaphragm O2 dynamics.

Methods: Wistar male rats (n = 6, 10 wks old, 311 ± 14 g) were mechanically ventilated under isoflurane anesthesia. The diaphragm was exposed to measure microvascular partial O2 pressure (PO2mv) by phosphorescence quenching technique during electrical stimulation-induced diaphragm contractions (6 V, 2 ms, 2 Hz, 180 s). The 180 s of muscle contractions and PO2mv measurement were repeated 10 min after endothelial NO synthase inhibition by the intra-arterial infusion of nitro-l-arginine methyl ester (L-NAME; eNOS inhibitor). The PO2mv change during the transition from rest to contraction was fitted to a nonlinear regression model. Time delay, time constant (tau), rate constant (K), and nadir in PO2mv were calculated and compared before and after eNOS inhibition. [Results] Diaphragm PO2mv decreased during contractions both before and after eNOS inhibition. The time delay and K were not different before and after L-NAME. However, the L-NAME administration decreased the tau and nadir in PO2mv (tau, 7.61 [5.18-13.41] vs. 3.36 [1.81-5.57] s; nadir, 7.45 [1.41-14.85] vs. 3.93 [0.89-9.47] mmHg; before vs. after eNOS inhibition, median [25-75 percentiles], P < 0.05, respectively).

Discussion: The time constant in PO2mv is determined by oxygen supply to the capillaries and oxygen utilization. The faster time constant and lower nadir in PO2mv possibly indicate the slower and lower oxygen supply to diaphragm capillaries after eNOS inhibition.

Conclusion: The NO has a crucial role in the diaphragm oxygen dynamics of intact rats.

背景:膈肌是参与吸气的主要肌肉,是哺乳动物所特有的。因为横膈膜是一个持续活跃的肌肉,它的收缩可能依赖于氧化磷酸化和氧气供应来产生三磷酸腺苷。本研究旨在评价内源性血管扩张剂一氧化氮(NO)在隔膜氧动力学中的作用。方法:Wistar雄性大鼠(n = 6, 10周龄,311±14 g)在异氟醚麻醉下机械通气。在电刺激膈肌收缩(6 V, 2 ms, 2 Hz, 180 s)时,用磷光猝灭技术测量膈肌微血管分氧压(PO2mv)。动脉内灌注硝基-l-精氨酸甲酯(L-NAME; eNOS抑制剂)抑制内皮NO合成酶10 min后,重复180 s肌肉收缩和PO2mv测量。用非线性回归模型拟合了从静止到收缩过程中PO2mv的变化。计算并比较eNOS抑制前后的时间延迟、时间常数(tau)、速率常数(K)和PO2mv最低点。[结果]eNOS抑制前后膈肌PO2mv均降低。L-NAME前后的时间延迟和K值没有差异。然而,L-NAME给药降低PO2mv的tau和最低点(tau, 7.61[5.18-13.41]对3.36 [1.81-5.57]s;最低点,7.45[1.41-14.85]对3.93 [0.89-9.47]mmHg; eNOS抑制前与后,中位数[25-75百分位数],P讨论:PO2mv的时间常数由毛细血管供氧和氧气利用决定。较快的时间常数和较低的PO2mv最低点可能表明eNOS抑制后膈毛细血管供氧减慢和减少。结论:一氧化氮在大鼠横膈膜氧动力学中起重要作用。
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引用次数: 0
Patients Admitted to the ICU Who Cannot Be Mobilized for the First Time Within 72 Hours Have Low Regional Cerebral Oxygen Saturation. 72小时内不能第一次活动的ICU患者局部脑氧饱和度低。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-10389-5_31
Ryota Imai, Atsuhiro Tsubaki, Takafumi Abe, Seigo Yamaguchi

Mobilization of critically ill patients within 72 hours of admission is associated with improved outcomes. Recently, the predictive value of regional cerebral oxygen saturation (rSO2) measured via near-infrared spectroscopy (NIRS) has been emphasized. This study aimed to evaluate the differences in rSO2 values depending on the availability of mobilization within 72 hours in the ICU. Eighty patients admitted to the emergency center between June 2020 and December 2022 were analyzed. Patients were assessed based on whether they could be mobilized within 72 hours (early mobilization group, EM) or later (non-early mobilization group, non-EM). During mobilization, prefrontal rSO2 values were monitored. Regarding patient background, significant differences were noted between the groups, including delayed release in non-EM patients. rSO2 values varied significantly, with the lowest values in the first half of end-sitting in both groups (non-EM 56.5 ± 4.8%, EM 58.6 ± 4.3%, p < 0.05). The rSO2 value was also lower in the non-EM group than in the EM group (P < 0.014). A weak correlation was observed between rSO2 and the number of days to first mobilization (r = -0.251, p = 0.025). The rSO2 value may serve as a potential marker to guide the timing of mobilization in ICU patients.

在入院72小时内动员危重患者与改善预后相关。近年来,近红外光谱(NIRS)测量区域脑氧饱和度(rSO2)的预测价值得到了重视。本研究旨在评估在ICU内72小时内可活动性对rSO2值的影响。对2020年6月至2022年12月期间急诊中心收治的80名患者进行了分析。根据患者是否可以在72小时内(早期动员组,EM)或更晚(非早期动员组,非EM)进行评估。在活动期间,监测前额叶rSO2值。关于患者背景,两组之间存在显著差异,包括非em患者的延迟释放。rSO2值差异显著,两组的最低值均在坐位前半段(非EM组56.5±4.8%,EM组58.6±4.3%),非EM组的p 2值也低于EM组(p 2和第一次活动的天数(r = -0.251, p = 0.025)。rSO2值可作为指导ICU患者运动时机的潜在指标。
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引用次数: 0
The Role of Architectural Forces in Ion Selectivity. 结构力在离子选择性中的作用。
4区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-07523-9_1
Benoît Roux

A theoretical framework is presented to clarify the role of architectural and structural forces in ion selectivity. It expresses the relative free energy of bound ions in terms of a reduced subsystem corresponding to the local degrees of freedom coupled to the rest of the protein. The latter is separated into a first contribution that includes all the forces keeping the ion and the coordinating ligands confined to a microscopic sub-volume but do not prevent the ligands from adapting to a smaller ion, while the second contribution regroups the remaining forces that serve to dictate the precise geometry of the coordinating ligands best adapted to a given ion. The theoretical framework makes it possible to delineate two important limiting cases. In the limit where the geometric forces are dominant (rigid binding site), selectivity is controlled via the cavity size according to the familiar "snug-fit" mechanism of host-guest chemistry. In the limit where the geometric forces are negligible, the ion and ligands behave as a dynamical "confined droplet" that is free and adapt to the ion's size. In this case, selectivity is controlled by the number and the chemical type of ion-coordinating ligands.

提出了一个理论框架来阐明建筑和结构力在离子选择性中的作用。它表示结合离子的相对自由能,以一个简化的子系统的形式表示,该子系统对应于与蛋白质其余部分耦合的局部自由度。后者被分为第一个贡献,包括所有保持离子和配体限制在微观亚体积内的力,但不阻止配体适应更小的离子,而第二个贡献重新组合了剩余的力,这些力决定了最适合给定离子的配体的精确几何形状。理论框架使得描述两个重要的极限情况成为可能。在几何力占主导地位的极限情况下(刚性结合位点),根据熟悉的主客体化学“紧密配合”机制,选择性通过空腔大小来控制。在几何力可以忽略不计的极限下,离子和配体表现为动态的“受限液滴”,它是自由的,并适应离子的大小。在这种情况下,选择性是由离子配位体的数量和化学类型控制的。
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引用次数: 0
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