TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy.

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and crossed both with a P301S transgenic tau model to study how these manipulations impacted disease phenotypes. We found that TMEM106B deletion accelerated cognitive decline, hind limb paralysis, tau pathology, and neurodegeneration. TMEM106B deletion also increased transcriptional correlation with human AD and the functional pathways enriched in KO:tau mice aligned with those of AD. In contrast, the coding variant protected against tau-associated cognitive decline, synaptic impairment, neurodegeneration, and paralysis without affecting tau pathology. Our findings reveal that TMEM106B is a critical safeguard against tau aggregation, and that loss of this protein has a profound effect on sequelae of tauopathy. Our study further demonstrates that the coding variant is functionally relevant and contributes to neuroprotection downstream of tau pathology to preserve cognitive function.

Generation of a Dcx-CreERT2 knock-in mouse for genetic manipulation of newborn neurons.

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse doublecortin locus as a marker of fate-specified neuroblasts and immature neurons. Our new model places a T2A-CreERT2 cassette immediately downstream of the Dcx coding sequence on the X chromosome, allowing expression of both Dcx and CreERT2 proteins in the endogenous spatiotemporal pattern for this gene. We demonstrate that the new mouse line drives expression of a Cre-dependent reporter throughout the brain in neonatal mice and in known neurogenic niches of adult animals. The line has been deposited with the Jackson Laboratory and should provide an accessible tool for studies targeting fate-restricted neuronal precursors.

Effects of three-dimensional image based insole for healthy volunteers: a pilot clinical trial.

Insoles are used to treat various foot diseases, including plantar foot, diabetic foot ulcers, and refractory plantar fasciitis. In this study, we investigated the effects of 3-dimensional image-based (3-D) insole in healthy volunteers with no foot diseases. Additionally, the comfort of the 3-D insole was compared with that of a custom-molded insole. A single-center, randomized, open clinical trial was conducted to address the effectiveness of insole use in a healthy population with no foot or knee disease. Two types of arch support insoles were evaluated for their effectiveness: a 3-D insole and a custom-molded insole. Fifty Korean volunteers participated in the study and were randomly allocated into the "3-D insole" (n = 40) or "custom-molding insole" (n = 10) groups. All subjects wore 3-D insoles or custom-molded insoles for 2 weeks. The sense of wearing shoes (Visual Analog Scale [VAS] and score) and fatigue of the foot were used to assess the insole effects at the end of the 2-week study period. The 3-D insole groups showed significantly improved sense of wearing shoes (VAS, p = 0.0001; score, p = 0.0002) and foot fatigue (p = 0.0005) throughout the study period. Although the number of subjects was different, the custom-molding insole group showed no significant changes in the sense of wearing shoes (VAS, 0.1188; score, p = 0.1483). Foot fatigue in the 3-D insole group improved significantly (p = 0.0005), which shows that a 3-D insole might have favorable effects on foot health in a healthy population. Trial Registration: Clinical Research Information Service Identifier: KCT0008100.

TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy.

TMEM106B is a risk modifier for a growing list of age-associated dementias including Alzheimer’s and frontotemporal dementia, yet its function remains elusive. Two key questions that emerge from past work are whether the conservative T185S coding variant found in the minor haplotype contributes to protection, and whether the presence of TMEM106B is helpful or harmful in the context of disease. Here we address both issues while extending the testbed for study of TMEM106B from models of TDP to tauopathy. We show that TMEM106B deletion accelerates cognitive decline, hindlimb paralysis, neuropathology, and neurodegeneration. TMEM106B deletion also increases transcriptional overlap with human AD, making it a better model of disease than tau alone. In contrast, the coding variant protects against tau-associated cognitive decline, neurodegeneration, and paralysis without affecting tau pathology. Our findings show that the coding variant contributes to neuroprotection and suggest that TMEM106B is a critical safeguard against tau aggregation.

Study on the Combined Effect of Municipal Solid Waste Incineration Bottom Ash and Waste Shingle in Hot Mix Asphalt.

This study investigated the positive effect of the combined use of recycled asphalt shingles (RASs) and municipal solid waste incineration (MSWI) bottom ash (B.A.) in asphalt concrete, which contributes to enhanced sustainability in pavement engineering. In addition, unlike traditional approaches that employ individual recycling material in hot mix asphalt (HMA), the combined use of the two waste materials maximizes the mechanical performance of the asphalt mixture. The addition of RAS (with 30-40% aged binder) as an additive generally enhances the strength/stiffness of the asphalt mixture. The high porosity/absorption of MSWI BA results in an additional amount of liquid asphalt binder in the mixture. As an admixture, RAS could supply the additional asphalt binder in the mixture when MSWI BA is used as an aggregate replacement. This research was conducted in two phases: (1) to examine the effect of MSWI BA alone and its optimal asphalt content (OAC), and (2) to assess the combined effect of B.A. and RAS in HMA. Multiple laboratory testing methods were employed for the mechanical performance investigation, including the Marshall stability test, rutting test, and indirect tensile test. The testing results show that the 20% B.A. replacement exhibits the best performance and that it requires an additional asphalt binder of 1.1%. For the combined use of MSWI BA and RAS, 5% RAS shows the best mechanical performance. All mixtures that contain the B.A. and RAS show greater strength than the control specimen (regular HMA).

Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer's circuit dysfunction.

Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease.

Neurodegenerative conditions cause irreversible damage to the brain and have a devastating impact on quality of life. However, these diseases start gradually, meaning that the entire brain is not affected at once. For example, the initial signs of Alzheimer's disease appear only in specific areas. One of the first brain regions to degenerate in Alzheimer's is the entorhinal cortex. In healthy individuals, entorhinal neurons send electrical signals to the hippocampus, a part of the brain important for memory and learning. During Alzheimer's, hippocampal neurons also die off, leading to 'shrinkage' of this brain region and, ultimately, the memory problems that are a hallmark of the disease. Many neurons in the developing brain require electrical input from other cells to survive ­ in other words, if they do not belong to an 'active circuit', they are eliminated. This is crucial for the connection between the entorhinal cortex and the hippocampus, where the circuit's development and maintenance require carefully controlled electrical activity. Abnormal electrical activity is also an early sign of diseases like Alzheimer's, but how this relates to degeneration is still poorly understood. By investigating these questions, Zhao, Grunke, Wood et al. uncovered a potential relationship between electrical activity and degeneration in the adult brain, long after the circuit between the hippocampus and the entorhinal cortex had matured. Mice were genetically engineered so that their entorhinal cortex would carry a protein designed to silence electrical signaling. The communication between the entorhinal cortex and the hippocampus could therefore be shut off by activating the protein with an injected drug. Remarkably, within just a few days of silencing, cells from the entorhinal cortex started to die off. Zhao, Grunke, Wood et al. went on to show that different silencing methods yielded the same results ­ in other words, the degeneration of cells from the entorhinal cortex was not linked to a particular method. This vulnerability to electrical inactivity was also unique to the entorhinal cortex: when neighboring parts of the brain were silenced, the nerve cells in these areas did not die as readily. Interestingly, in one of their experiments, Zhao, Grunke, Wood et al. found that electrical activity of neighboring nerve cells participated in killing the silenced neurons, suggesting that nerve cells in these brain areas might compete to survive. Overall, this work highlights a direct link between electrical activity and nerve cell degeneration in a part of the brain severely affected by Alzheimer's. In the future, Zhao, Grunke, Wood et al. hope that these results will pave the way to a better understanding of the biological mechanisms underpinning such neurodegenerative diseases.

Computed tomographic features of the temporomandibular joint in 10 Jeju horses.

BACKGROUND: The equine temporomandibular joint (TMJ) has a complex anatomical structure that makes diagnosis of TMJ disorders difficult. Computed tomography (CT) is now available in equine medicine; hence, TMJ evaluation has become more convenient. OBJECTIVES: The objectives of this study were to describe the CT features of the TMJ in Jeju horses and to compare these features with those of Thoroughbreds. METHODS: In this report, the TMJs of 10 Jeju horses (mean age: 4.5 ± 1.9 yr; mean body weight: 282.6 ± 40.3 kg) and 6 Thoroughbreds (mean age: 7.3 ± 1.6 yr; mean body weight: 479.7 ± 44.0 kg) were examined using CT. After CT scanning, the Hounsfield units (HU) and height to width ratio (H:W) of the mandibular condyle were measured. RESULTS: The mean H:W in Jeju horses was significantly lower than that in Thoroughbreds. The mean HU in Jeju horses was lower than that in Thoroughbreds; however, the difference was not significant. The most frequent CT finding was an irregular medial margin of the mandibular condyle in both breeds. CONCLUSIONS: In this study, the shape of the mandibular condyle in Jeju horses was flatter than that in Thoroughbreds. This report could be useful in evaluating the TMJ in Jeju horses. Moreover, CT could be a pragmatic choice for the examination of the TMJ in horses.

Temporal and spatially controlled APP transgene expression using Cre-dependent alleles.

Although a large number of mouse models have been made to study Alzheimer's disease, only a handful allow experimental control over the location or timing of the protein being used to drive pathology. Other fields have used the Cre and the tamoxifen-inducible CreER driver lines to achieve precise spatial and temporal control over gene deletion and transgene expression, yet these tools have not been widely used in studies of neurodegeneration. Here, we describe two strategies for harnessing the wide range of Cre and CreER driver lines to control expression of disease-associated amyloid precursor protein (APP) in modeling Alzheimer's amyloid pathology. We show that CreER-based spatial and temporal control over APP expression can be achieved with existing lines by combining a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder using a Cre-to-tTA converter line. We then describe a new mouse line that places APP expression under direct control of Cre recombinase using an intervening lox-stop-lox cassette. Mating this allele with a CreER driver allows both spatial and temporal control over APP expression, and with it, amyloid onset. This article has an associated First Person interview with the first author of the paper.

Extensive accumulation of misfolded protein aggregates during natural aging and senescence.

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells, Caenorhabditis elegans, and mouse tissues collected at different times from youth to old age. Our results show a significant accumulation of misfolded protein aggregates in aged samples as compared to young materials. Indeed, aged samples have between 1.3 and 2.5-fold (depending on the biological system) higher amount of insoluble proteins than young samples. These insoluble proteins exhibit the typical characteristics of disease-associated aggregates, including insolubility in detergents, protease resistance, and staining with amyloid-binding dye as well as accumulation in aggresomes. We identified the main proteins accumulating in the aging brain using proteomic studies. These results show that the aged brain contain large amounts of misfolded and likely non-functional species of many proteins, whose soluble versions participate in cellular pathways that play fundamental roles in preserving basic functions, such as protein quality control, synapsis, and metabolism. Our findings reveal a putative role for protein misfolding and aggregation in aging.

Multi-Component Intervention Program on Habitual Physical Activity Parameters and Cognitive Function in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

Age-related dementia refers to a state in which someone experiences multiple cognitive function impairment due to degenerative brain disease, and which causes difficulties in their daily life or social life. Dementia is the most common and serious obstacle in later life. Early intervention in the case of patients who are in the mild cognitive impairment (MCI) stage among the high-risk group can maintain and improve their cognitive function. The purpose of the current trial is aimed at investigating the association between a multi-component (exercise with cognitive) intervention program and habitual physical activity parameters on cognitive functions in MCI patients. Neuropsychological cognitive and depression assessments were performed by neuropsychologists according to normalized methods, including the Korean mini-mental State examination (K-MMSE) and modified Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and cognitive assessment tool (attention, processing speed), and the Korean version of the geriatric depression scale (SGDS-K), both at baseline and at a 12 weeks follow-up. The 12-week multi-component intervention improved cognitive function and habitual physical activity parameters in patients with MCI relative to controls. A multi-component intervention program for patients with MCI is considered to be an effective method of dementia prevention by improving global (ADAS-Cog) and frontal (trail-making test, digit symbol substitution test) cognition and habitual physical activity parameters such as moderate to vigorous physical activity and step count. In addition, it is important to encourage habitual physical activities to ensure that exercise intervention strategies are carried out at the duration and intensity required for improving physical and cognitive wellbeing and obtaining health benefits.

Drug screening by uniform patient derived colorectal cancer hydro-organoids.

As the importance of organoids increases, the need to develop organoid culture systems suitable for basic biological and clinical applications is being emphasized. However, there is still an unmet need to produce functionally complex and scalable uniform organoids. Here, we demonstrate a scalable organoid production platform with 8 well strips and a total of 8 × 9 microwells per strip using organoids derived from colorectal cancer tissue. The new culture platform is a format in which single cells are self-organized into organoids in culture medium supplemented with 2% Matrigel. It is functionally compatible with existing 96 well plates and Matrigel based conventional organoid culture methods. The consistency, uniformity and reproducibility of organoid produced on the new platform have been significantly improved compared to those of conventional plates. Importantly, Hydro-organoids are functionally identical to conventional Matrigel organoids, but show better consistency in drug screening. Our results show the possibility that Hydro-organoids can be used in high-throughput assays and incorporated into drug screening models to predict clinical outcomes.

Gene therapy using Aß variants for amyloid reduction.

Numerous aggregation inhibitors have been developed with the goal of blocking or reversing toxic amyloid formation in vivo. Previous studies have used short peptide inhibitors targeting different amyloid ß (Aß) amyloidogenic regions to prevent aggregation. Despite the specificity that can be achieved by peptide inhibitors, translation of these strategies has been thwarted by two key obstacles: rapid proteolytic degradation in the bloodstream and poor transfer across the blood-brain barrier. To circumvent these problems, we have created a minigene to express full-length Aß variants in the mouse brain. We identify two variants, F20P and F19D/L34P, that display four key properties required for therapeutic use: neither peptide aggregates on its own, both inhibit aggregation of wild-type Aß in vitro, promote disassembly of pre-formed fibrils, and diminish toxicity of Aß oligomers. We used intraventricular injection of adeno-associated virus (AAV) to express each variant in APP/PS1 transgenic mice. Lifelong expression of F20P, but not F19D/L34P, diminished Aß levels, plaque burden, and plaque-associated neuroinflammation. Our findings suggest that AAV delivery of Aß variants may offer a novel therapeutic strategy for Alzheimer's disease. More broadly our work offers a framework for identifying and delivering peptide inhibitors tailored to other protein-misfolding diseases.

Beyond Strict Regulations to Achieve Environmental and Economic Health-An Optimal PM2.5 Mitigation Policy for Korea.

Growing concern about particulate matter (PM2.5) pressures Korea to reduce the health risks associated with its high dependency on fossil fuels. The Korean economy relies heavily on large thermal power plants-a major source of PM2.5 emissions. Although air quality regulations can negatively impact local economies, the Korean government announced two strict air quality mitigation policies in 2019. We develop a regional static computable general equilibrium model to simulate the economic and environmental impacts of these polices under alternative hypothetical scenarios. We separate two regions, Chungcheongnam-do, the most polluted region, and the rest of the country, in our model. As policy options, we introduce a regional development tax and a tradable market for PM emission permits, similar to an air pollution tax and a carbon permits market, respectively. The results show that allowing higher tax rates and a tradable permits market gives the optimal combination, with the PM2.5 emissions reduced by 2.35% without sacrificing economic growth. Since alternative options present, for example, a 0.04% loss of gross domestic product to reduce PM emissions by the same amount, our results here may present a new policy paradigm for managing air pollutants such as PM2.5.

Emission characteristics of particulate matter, odors, and volatile organic compounds from the grilling of pork.

Meat-grilling restaurants are considered to be residential emission sources of air pollutants. To investigate the emission characteristics of particulate matter (PM), odors, and volatile organic compounds (VOCs) from the grilling of meat, a grilling apparatus equipped with butane gas burners was used to grill pork belly and marinated pork ribs in a laboratory setting. When grilling the pork belly, the emission factor for PM with a diameter of 2.5 µm or below (PM2.5) was 754 mg-PM·kg-meat-1, accounting for 99% of total suspended particles (TSPs), while that of the marinated pork ribs was 137 mg-PM·kg-meat-1 (96% of TSPs). Ammonia and acetaldehyde were the most common odors emitted during grilling at 43-88 mg·kg-meat-1 and 22-30 mg·kg-meat-1, respectively. Aldehydes were the most significant contributor to total odor intensity (36%-67%). Benzene, vinyl acetate, and hexene were the most abundant VOCs for the pork belly, while butane, vinyl acetate, and n-dodecane were the most abundant for the marinated ribs. Among the VOCs emitted from the pork grilling process, hexene, butane, and toluene were the dominant ozone precursors. The information obtained in this study is useful for furthering the understanding of the characteristics of air pollutants emitted from actual meat-grilling restaurants. Additionally, knowledge of the PM, odor, and VOC emission characteristics and their emission factors is useful for establishing management strategies for air pollutants from meat-grilling restaurants.

Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder.

In this study, hydrogen generation powder samples were prepared using zinc carbonate as a precursor, at a temperature varying from 400 to 700 °C in H2 atmosphere, and were characterized in terms of antioxidant activity. The concentration of dissolved hydrogen obtained by the powder samples was measured using a dissolved hydrogen meter as a function of time. In addition, the antioxidant activity of the samples was evaluated based on the Oyaizu's method, removal rate of ·OH radicals, and ferric reducing antioxidant power. Finally, the hydrogen mask pack was fabricated using the hydrogen generation powder sample and gel-type emulsion. In the clinical test on the mask pack, the effect of the mask on skin aging was characterized and compared to that of a commercial sample. The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer.

Porous SnO2 nanostructure with a high specific surface area for improved electrochemical performance.

Tin oxide (SnO2) has been attractive as an alternative to carbon-based anode materials because of its fairly high theoretical capacity during cycling. However, SnO2 has critical drawbacks, such as poor cycle stability caused by a large volumetric variation during the alloying/de-alloying reaction and low capacity at a high current density due to its low electrical conductivity. In this study, we synthesized a porous SnO2 nanostructure (n-SnO2) that has a high specific surface area as an anode active material using the Adams fusion method. From the Brunauer-Emmett-Teller analysis and transmission electron microscopy, the as-prepared SnO2 sample was found to have a mesoporous structure with a fairly high surface area of 122 m2 g-1 consisting of highly-crystalline nanoparticles with an average particle size of 5.5 nm. Compared to a commercial SnO2, n-SnO2 showed significantly improved electrochemical performance because of its increased specific surface area and short Li+ ion pathway. Furthermore, during 50 cycles at a high current density of 800 mA g-1, n-SnO2 exhibited a high initial capacity of 1024 mA h g-1 and enhanced retention of 53.6% compared to c-SnO2 (496 mA h g-1 and 23.5%).

Enhanced electrochemical performance of MoS2/graphene nanosheet nanocomposites.

Molybdenum disulfide (MoS2) is attractive as an anode material for next-generation batteries, because of its layered structure being favorable for the insertion/deinsertion of Li+ ions, and its fairly high theoretical capacity. However, since the MoS2 anode material has exhibited disadvantages, such as low electrical conductivity and poor cycling stability, to improve the electrochemical performance of MoS2 in this study, a nanocomposite structure consisting of MoS2 and GNS (MoS2/GNS) as an anode for LIBs was prepared, by controlling the weight ratios of MoS2/GNS. The X-ray diffraction patterns and electron microscopic analysis showed that the nanocomposite electrode structure consisted of well-formed MoS2 nanoparticles and GNS. Compared to MoS2-only, the MoS2/GNS composites exhibited high retention and improved capacity at high current densities. In particular, among these nanocomposite samples, MoS2/GNS(8 : 2) with an appropriate portion of GNS exhibited the best LIB performance, due to the lowest interfacial resistance and highest Li-ion diffusivity.

Cycling system for decomposition of gaseous benzene by hydrogen peroxide with naturally Fe-containing activated carbon.

For the removal of volatile organic compounds (VOCs) from environmental systems, gaseous benzene, a model VOC, was adsorbed on naturally Fe-containing activated carbon and subsequently, decomposed in the presence of de-ionized water, and low (0.03%, pH 6.5) and high (30%, pH 2.5) concentration H2O2 solutions. The intermediates produced during benzene decomposition were analyzed and compared using gas chromatography-mass spectrometry. After the decomposition process, the activated carbon sample was air dried. Three cycles were carried out with de-ionized water and low and high concentration H2O2 solutions as oxidants. The adsorption capacity of the activated carbon sample treated with DI water gradually decreased as the number of cycles increased. On the other hand, the benzene adsorption capacity of the activated carbon samples treated with the H2O2 solutions was improved due to the relatively higher specific surface areas of these samples. After treatment with the low-concentration H2O2 solution, intermediates such as glyoxylic acid, oxalic acid, phenol, malonic acid, and pyrocatechol were observed. After treatment with high-concentration H2O2 solution, intermediates such as glyoxylic acid, formic acid, and acetic acid were formed. With increasing H2O2 concentration, the number and the molecular weight of the intermediate formed by the oxidative degradation of benzene, simultaneously decreased. The Fenton reaction induced by naturally Fe-containing activated carbon and H2O2 could lead to more efficient decomposition of benzene.

Facile one-pot synthesis of Ge/TiO2 nanocomposite structures with improved electrochemical performance.

Germanium (Ge) as an alternative to graphite exhibits a fairly high theoretical energy density and improved Li+ ion diffusivity. However, the seriously deteriorated electrochemical performance of Ge during cycling and the difficulty in the preparation of Ge-based nanostructures can hinder the utilization of Ge as an anode. Thus, in this study, a nanocomposite structure with Ge and TiO2 (Ge/TiO2) was synthesized using a facile one-pot method with different ratios of a Ge source with a dominant GeO2 phase and titanium isopropoxide. From X-ray diffraction, electron microscopy, and X-ray photoelectron spectroscopy, the Ge/TiO2 nanocomposites were found to be spherical structures homogeneously consisting of the reduced Ge as an active material and amorphous TiO2 as a matrix. In particular, the Ge/TiO2 nanocomposite with an appropriate amount of TiO2 exhibited improved electrochemical properties, i.e., a coulombic efficiency of 97% and a retention of 61% for 100 cycles, compared to commercial Ge (a coulombic efficiency of 82% and a retention of 16%). This demonstrates that the amorphous TiO2 matrix could relieve a volumetric expansion of the Ge active material in the nanocomposite electrode generated during the cycling process.