Imaging Assessment of the Efficacy of Chemotherapy in Primary Malignant Bone Tumors: Recent Advances in Qualitative and Quantitative Magnetic Resonance Imaging and Radiomics.

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Changes in information integration and brain networks during propofol-, dexmedetomidine-, and ketamine-induced unresponsiveness.

BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.

Dexmedetomidine ameliorates high glucose-induced epithelial-mesenchymal transformation in HK-2 cells through the Cdk5/Drp1/ROS pathway.

Epithelial-mesenchymal transformation (EMT) plays an important role in the progression of diabetic nephropathy. Dexmedetomidine (DEX) has shown renoprotective effects against ischemic reperfusion injury; however, whether and how DEX prevents high glucose-induced EMT in renal tubular epithelial cells is incompletely known. Here, we conduct in vitro experiments using HK-2 cells, a human tubular epithelial cell line. Our results demonstrate that high glucose increases the expressions of EMT-related proteins, including Vimentin, Slug, Snail and Twist, while decreasing the expression of E-cadherin and increasing Cdk5 expression in HK-2 cells. Both Cdk5 knockdown and inhibition by roscovitine increase the expressions of E-cadherin while decreasing the expressions of other EMT-related markers. DEX inhibits Cdk5 expression without affecting cell viability and changes the expressions of EMT-related markers, similar to effects of Cdk5 inhibition. Furthermore, Cdk5 is found to interact with Drp1 at the protein level and mediate the phosphorylation of Drp1. In addition, Drp1 inhibition with mdivi-1 could also restrain the high glucose-induced EMT process in HK-2 cells. Immunofluorescence results show that roscovitine, Mdivi-1 and DEX inhibit high glucose-induced intracellular ROS accumulation, while the oxidant H 2O 2 eliminates the protective effect of DEX on the EMT process. These results indicate that DEX mitigates high glucose-induced EMT progression in HK-2 cells via inhibition of the Cdk5/Drp1/ROS pathway.

Synthesis of 2D Co-MOF Nanosheets and Low-Temperature Calcination Activation for Lithium-Ion Batteries.

Metal-organic frameworks (MOFs), a novel type of porous crystalline material, have aroused widespread interest in lithium-ion batteries (LIBs). The design and preparation of MOF electrodes with a stable structure and excellent electrochemical performance are primary concerns for improving the capacity of LIBs. Among them, two-dimensional (2D) materials with larger specific surface areas, richer active sites, and higher aspect ratios have great potential. We adopted a facile approach to synthesize unique Co-MOF nanosheets with a 2D flaky morphology and a mesoporous structure. In addition, low-temperature calcination increases the specific surface area and improves the porosity to achieve mass transfer. Sample M2 delivers high specific capacities and long lives (1402.0 mA h g-1 after 100 cycles at 500 mA g-1 and 462.4 mA h g-1 after 300 cycles at 1.0 A g-1) when the calcination temperature is 200 °C. Significant improvements in the cycle life and stability are attributed to the 2D flaky structure of the M2 sample and the available low-temperature calcination activation, which provide a simple strategy for the fabrication of inexpensive and excellent anodes for LIBs.

Application of biochar and alkalis for recovery of sour anaerobic digesters.

Commercial digesters handling complex waste and organic overloading often encounter unbalanced conditions or failures. With limited studies on the digester recovery from an industry-based waste stream, a complex and high-strength digestate containing up to 79 g COD l-1 from acidified commercial digester was investigated for biochar and alkaline treatments. The addition of biochar and calcium hydroxide successfully decomposed excessive volatile fatty acid up to 18.9 ± 2.5 g l-1 and resumed methane production. The maximum methane yield was obtained from the digester amended with biochar (373.4 ± 6.0 ml g COD-1), followed by calcium hydroxide (350.1 ± 2.5 ml g COD-1). Calcium hydroxide treatment showed a shorter lag phase than the biochar by 44%. Methane production could not be recovered by using sodium hydroxide or untreated digester. This study provides a strategic approach to justify the use of alkalis for restoring sour digesters from industry-based waste streams.

Superparamagnetic iron oxide nanoparticles conjugated with Aß oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aß oligomers (AßOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AßOs and promote Aß clearance may have great value for AD treatment. RESULTS: We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with Aß oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aß properties of W20 and XD4 by inhibiting Aß aggregation, attenuating AßO-induced cytotoxicity and increasing microglial phagocytosis of Aß. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice. CONCLUSION: These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.

Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease.

It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against α-syn, and of which only a small part can penetrate the blood-brain barrier, resulting in an extremely low level of effective antibodies in the brain, and limiting the beneficial effect of IVIG on PD mice. Here, we first isolated naturally occurring autoantibodies against α-syn (NAbs-α-syn) from IVIG. Our further investigation results showed that NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-α-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble α-syn, total human α-syn and α-syn oligomers, decreasing the intracellular p-α-synser129 deposits and axonal pathology, inhibiting the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines, increasing the levels of PSD95, synaptophysin and TH in the brain of A53T transgenic mice. These findings suggest that NAbs-α-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD.

Disrupted neural variability during propofol-induced sedation and unconsciousness.

Variability quenching is a widespread neural phenomenon in which trial-to-trial variability (TTV) of neural activity is reduced by repeated presentations of a sensory stimulus. However, its neural mechanism and functional significance remain poorly understood. Recurrent network dynamics are suggested as a candidate mechanism of TTV, and they play a key role in consciousness. We thus asked whether the variability-quenching phenomenon is related to the level of consciousness. We hypothesized that TTV reduction would be compromised during reduced level of consciousness by propofol anesthetics. We recorded functional magnetic resonance imaging signals of resting-state and stimulus-induced activities in three conditions: wakefulness, sedation, and unconsciousness (i.e., deep anesthesia). We measured the average (trial-to-trial mean, TTM) and variability (TTV) of auditory stimulus-induced activity under the three conditions. We also examined another form of neural variability (temporal variability, TV), which quantifies the overall dynamic range of ongoing neural activity across time, during both the resting-state and the task. We found that (a) TTM deceased gradually from wakefulness through sedation to anesthesia, (b) stimulus-induced TTV reduction normally seen during wakefulness was abolished during both sedation and anesthesia, and (c) TV increased in the task state as compared to resting-state during both wakefulness and sedation, but not anesthesia. Together, our results reveal distinct effects of propofol on the two forms of neural variability (TTV and TV). They imply that the anesthetic disrupts recurrent network dynamics, thus prevents the stabilization of cortical activity states. These findings shed new light on the temporal dynamics of neuronal variability and its alteration during anesthetic-induced unconsciousness.

Mitochondria-targeted antioxidant MitoQ reduced renal damage caused by ischemia-reperfusion injury in rodent kidneys: Longitudinal observations of T2 -weighted imaging and dynamic contrast-enhanced MRI.

PURPOSE: To investigate the effect of mitochondria-targeted antioxidant MitoQ in reducing the severity of renal ischemia-reperfusion injury (IRI) in rats using T2 -weighted imaging and dynamic contrast-enhanced MRI (DCE-MRI). METHODS: Ischemia-reperfusion injury was induced by temporarily clamping the left renal artery. Rats were pretreated with MitoQ or saline. The MRI examination was performed before and after IRI (days 2, 5, 7, and 14). The T2 -weighted standardized signal intensity of the outer stripe of the outer medulla (OSOM) was measured. The unilateral renal clearance rate kcl was derived from DCE-MRI. Histopathology was evaluated after the final MRI examination. RESULTS: The standardized signal intensity of the OSOM on IRI kidneys with MitoQ were lower than those with saline on days 5 and 7 (P = 0.004, P < 0.001, respectively). Kcl values of IRI kidneys with MitoQ were higher than those with saline at all time points (P = 0.002, P < 0.001, P = 0.001, P < 0.001). Histopathology showed that renal damage was the most predominant on the OSOM of IRI kidneys with saline, which was less obvious with MitoQ (P < 0.001). CONCLUSIONS: These findings demonstrate that MitoQ can reduce the severity of renal damage in rodent IRI models using T2 -weighted imaging and DCE-MRI. Magn Reson Med 79:1559-1667, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Dynamic Reflection Phase and Polarization Control in Metasurfaces.

Optical metasurfaces are two-dimensional optical elements composed of dense arrays of subwavelength optical antennas and afford on-demand manipulation of the basic properties of light waves. Following the pioneering works on active metasurfaces capable of modulating wave amplitude, there is now a growing interest to dynamically control other fundamental properties of light. Here, we present metasurfaces that facilitate electrical tuning of the reflection phase and polarization properties. To realize these devices, we leverage the properties of actively controlled plasmonic antennas and fundamental insights provided by coupled mode theory. Indium-tin-oxide is embedded into gap-plasmon resonator-antennas as it offers electrically tunable optical properties. By judiciously controlling the resonant properties of the antennas from under- to overcoupling regimes, we experimentally demonstrate tuning of the reflection phase over 180°. This work opens up new design strategies for active metasurfaces for displacement measurements and tunable waveplates.

Li Intercalation in MoS2: In Situ Observation of Its Dynamics and Tuning Optical and Electrical Properties.

Two-dimensional layered materials like MoS2 have shown promise for nanoelectronics and energy storage, both as monolayers and as bulk van der Waals crystals with tunable properties. Here we present a platform to tune the physical and chemical properties of nanoscale MoS2 by electrochemically inserting a foreign species (Li(+) ions) into their interlayer spacing. We discover substantial enhancement of light transmission (up to 90% in 4 nm thick lithiated MoS2) and electrical conductivity (more than 200×) in ultrathin (∼2-50 nm) MoS2 nanosheets after Li intercalation due to changes in band structure that reduce absorption upon intercalation and the injection of large amounts of free carriers. We also capture the first in situ optical observations of Li intercalation in MoS2 nanosheets, shedding light on the dynamics of the intercalation process and the associated spatial inhomogeneity and cycling-induced structural defects.

Personal thermal management by metallic nanowire-coated textile.

Heating consumes large amount of energy and is a primary source of greenhouse gas emission. Although energy-efficient buildings are developing quickly based on improving insulation and design, a large portion of energy continues to be wasted on heating empty space and nonhuman objects. Here, we demonstrate a system of personal thermal management using metallic nanowire-embedded cloth that can reduce this waste. The metallic nanowires form a conductive network that not only is highly thermal insulating because it reflects human body infrared radiation but also allows Joule heating to complement the passive insulation. The breathability and durability of the original cloth is not sacrificed because of the nanowires' porous structure. This nanowire cloth can efficiently warm human bodies and save hundreds of watts per person as compared to traditional indoor heaters.

Correlation of IVIM/DKI Parameters with Hypoxia Biomarkers in Fibrosarcoma Murine Models: Direct Control of MRI and Pathological Sections.

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.

Increased prevalence of CFTR variants and susceptibility to CRS: A real-world study based on Chinese children.

Background: Chronic Rhinosinusitis is a common disease in children. The main function of CFTR is to maintain the thickness of the mucous layer on the surface of the nasal mucosa. CFTR disease-causing variant can cause CFTR protein dysfunction and induce or aggravate chronic infection. However, the carrying status of the CFTR variants in the Chinese population is not clear. Objective: To study the frequency and variants of CFTR in Chinese children with CRS and to analyze the CFTR variants and the clinical characteristics and susceptibility to CRS. Methods: Whole Exome Sequencing was performed to analyze the CFTR genes in a total of 106 CRS children from the Chinese mainland area. The CFTR variants, frequency and clinical data were summarized and analyzed. Results: A total of 31 CFTR variants were detected, of which the carrying rate of 7 sites was significantly higher than that of the population database. 88 patients carried more than 2 variants. 37 people carried variants (MAF < 0.05), of which 91.89% had a history of recurrent upper respiratory infections, 16 had nasal polyps, 5 had bronchiectasis, and 1 was diagnosed with CF-related disorders. Conclusion: The carrying rate of CFTR variants in Chinese CRS children increased, and the highest rates of variants (MAF < 0.05) are p.I556V, p. E217G, c.1210-12[T]. Carrying multiple CFTR variants, especially p.E217G, p.I807 M, p.V920L and c.1210-12[T] may lead to increased susceptibility to CRS. There are CF-related disorders in patients with CRS.

Generation and Characterization of a Novel Knockin Mouse Model Expressing PSEN1 D385A: Implications for Investigating Herbal Drug Effects in γ-Secretase Activity.

Background: Presenilin (PSEN, PS) is essential for γ-secretase function, and mutations can disrupt amyloid-ß (Aß) production in familial Alzheimer's disease. Targeting γ-secretase is complex due to its broad involvement in physiological processes. Objective: Our aim was to create a novel knockin (KI) mouse model expressing PSEN1 D385A mutation and investigate the efficacy of a Geniposide and Ginsenoside Rg1 combination (NeuroProtect modified formula, NP-2) in restoring γ-secretase activity. Methods: Using gene manipulation, we established the PS1 D385A KI mouse model and confirmed the mutation, mRNA, and protein levels using Southern blotting, northern blotting, and western blotting, respectively. In vitro γ-secretase assay was conducted to measure γ-secretase activity, while histological analyses examined neurogenesis effects. NP-2 administration evaluated its impact on γ-secretase activity. Results: The PS1 D385A KI homozygotes displayed severe cerebral hemorrhage, postnatal lethality, developmental disorders, reduced proliferation of neural progenitor cells, and disrupted γ-secretase function. The mutation abolished PS1 protein self-shearing, leading to compromised γ-secretase activity. NP-2 intervention effectively restored γ-secretase activity in the heterozygous mice. Conclusions: PS1 D385A mutant disrupted PS1 protein self-cleaving, impairing γ-secretase activity in KI mice. NP-2 restored γ-secretase function, offering potential for novel AD treatment strategies despite the challenges posed by γ-secretase's complex role in physiological processes.

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.

The NeuroProtect Formula: A Preventive Approach to AD Targeting the HIF-1/PI3K-AKT Signaling Pathway Evaluated through In Vivo, In Vitro, and Network Pharmacology Approaches.

OBJECTIVE: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow down disease progression. This study aimed to investigate the potential of the NeuroProtect (NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD. We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models. METHODS: To predict functional pathways and potential downstream targets of NP intervention, we employed network pharmacology. The preventative impact of the NP formula was assessed using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression. RESULTS: Network pharmacology analysis revealed 145 drug-disease interactions and identified 5 core active targets associated with AD. Molecular docking results demonstrated strong binding affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1 and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP formula significantly ameliorated pathological changes, decreased the Aß42/Aß40 ratio in the hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula's ability to reverse the inhibitory effects of Aß25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a, Stat3, and Vegfa. CONCLUSION: Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as a key target.

Histomorphological analysis of perfusion parameters and CNS lymphatic vessels in mice: an experimental method study.

To investigate the distribution and characteristics of lymphatic vessels within the central nervous system, we focus on the meninges of the spinal cord and brain parenchyma in mice. Additionally, we aim to provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels, while optimizing the perfusion parameters to improve histomorphological quality. Male C57BL/6J mice were randomly divided into four groups, with each group assigned a specific perfusion parameter based on perfusion volumes and temperatures. Immunofluorescence staining of lymphatics and blood vessels was performed on both meningeal and the brain tissue samples. Statistical analysis was performed using one-way analysis of variance to compare the groups, and a significant level of P < 0.05 was considered statistically significant. Our study reports the presence of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice. We highlight the crucial role of high perfusion volume of paraformaldehyde with low temperature in fixation for achieving optimal results. We provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice, which contribute to our understanding of the distribution and characteristics of lymphatic vessels within the central nervous system. Further research is warranted to explore the functional implications of these lymphatic vessels and their potential therapeutic significance in neurodegenerative and neuroinflammatory diseases.

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

Electro-optical modulation of a silicon waveguide with an "epsilon-near-zero" material.

Accumulating electrons in transparent conductive oxides such as indium tin oxide (ITO) can induce an "epsilon-near-zero" (ENZ) in the spectral region near the important telecommunications wavelength of λ = 1.55 µm. Here we theoretically demonstrate highly effective optical electro-absorptive modulation in a silicon waveguide overcoated with ITO. This modulator leverages the combination of a local electric field enhancement and increased absorption in the ITO when this material is locally brought into an ENZ state via electrical gating. This leads to large changes in modal absorption upon gating. We find that a 3 dB modulation depth can be achieved in a non-resonant structure with a length under 30 µm for the fundamental waveguide modes of either linear polarization, with absorption contrast values as high as 37. We also show a potential for 100 fJ/bit modulation, with a sacrifice in performance.