Electron Release via Internal Polarization Fields for Optimal S-H Bonding States.

Transition metal dichalcogenides (TMDs) have received considerable attention as promising electrocatalysts for the hydrogen evolution reaction (HER), yet their potential is often constrained by the inertness of the basal planes arising from their poor hydrogen adsorption ability. Here, the relationship between the electronic structure of the WS2 basal plane and HER activity is systemically analyzed to establish a clear insight. The valance state of the sulfur atoms on the basal plane has been tuned to enhance hydrogen adsorption through sequential engineering processes, including direct phase transition and heterostructure that induces work function-difference-induced unidirectional electron transfer. Additionally, an innovative synthetic approach, harnessing the built-in internal polarization field at the W-graphene heterointerface, triggers the in-situ formation of sulfur vacancies in the bottom WSx (x < 2) layers. The resultant modulation of the valance state of the sulfur atom stabilizes the W-S bond, while destabilizing the S-H bond. The electronic structural changes are further amplified by the release and transfer of surplus electrons via sulfur vacancies, filling the valance state of W and S atoms. Consequently, this work provides a comprehensive understanding of the interplay between the electronic structure of the WS2 basal plane and the HER activity, focusing on optimizing S-H bonding state.

Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of Ca2+/Calpain/Cdk5-mediated mitochondrial fragmentation.

Oxidative stress plays an essential role in the progression of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer's disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca2+-mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca2+ accumulation and Ca2+-mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca2+/Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca2+/Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress.

Tunable translation-level CRISPR interference by dCas13 and engineered gRNA in bacteria.

Although CRISPR-dCas13, the RNA-guided RNA-binding protein, was recently exploited as a translation-level gene expression modulator, it has still been difficult to precisely control the level due to the lack of detailed characterization. Here, we develop a synthetic tunable translation-level CRISPR interference (Tl-CRISPRi) system based on the engineered guide RNAs that enable precise and predictable down-regulation of mRNA translation. First, we optimize the Tl-CRISPRi system for specific and multiplexed repression of genes at the translation level. We also show that the Tl-CRISPRi system is more suitable for independently regulating each gene in a polycistronic operon than the transcription-level CRISPRi (Tx-CRISPRi) system. We further engineer the handle structure of guide RNA for tunable and predictable repression of various genes in Escherichia coli and Vibrio natriegens. This tunable Tl-CRISPRi system is applied to increase the production of 3-hydroxypropionic acid (3-HP) by 14.2-fold via redirecting the metabolic flux, indicating the usefulness of this system for the flux optimization in the microbial cell factories based on the RNA-targeting machinery.

Natural transformation of Vibrio natriegens with large genetic cluster enables alginate assimilation for isopentenol production.

Alginate is a major component of brown macroalgae, and its efficient utilization is critical for developing sustainable technologies. Vibrio natriegens is a fast-growing marine bacterium that has gained massive attention due to its potential as an alternative industrial chassis. However, V. natriegens cannot naturally metabolize alginate, limiting its usage in marine biomass conversion. In this study, V. natriegens was engineered to utilize marine biomass, kelp, as a carbon source. A total of 33.8 kb of the genetic cluster for alginate assimilation from Vibrio sp. dhg was integrated into V. natriegens by natural transformation. Engineered V. natriegens was further modified to produce 1.8 mg/L of isopentenol from 16 g/L of crude kelp powder. This study not only presents the very first case in which V. natriegens can be naturally transformed with large DNA fragments but also highlights the potential of this strain for converting marine biomass into valuable products.

Hypothalamic neuronal activation in non-human primates drives naturalistic goal-directed eating behavior.

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating using chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

Development of an assessment method for freely moving nonhuman primates' eating behavior using manual and deep learning analysis.

Purpose: Although eating is imperative for survival, few comprehensive methods have been developed to assess freely moving nonhuman primates' eating behavior. In the current study, we distinguished eating behavior into appetitive and consummatory phases and developed nine indices to study them using manual and deep learning-based (DeepLabCut) techniques. Method: The indices were utilized to three rhesus macaques by different palatability and hunger levels to validate their utility. To execute the experiment, we designed the eating behavior cage and manufactured the artificial food. The total number of trials was 3, with 1 trial conducted using natural food and 2 trials using artificial food. Result: As a result, the indices of highest utility for hunger effect were approach frequency and consummatory duration. Appetitive composite score and consummatory duration showed the highest utility for palatability effect. To elucidate the effects of hunger and palatability, we developed 2D visualization plots based on manual indices. These 2D visualization methods could intuitively depict the palatability perception and hunger internal state. Furthermore, the developed deep learning-based analysis proved accurate and comparable with manual analysis. When comparing the time required for analysis, deep learning-based analysis was 24-times faster than manual analysis. Moreover, temporal and spatial dynamics were visualized via manual and deep learning-based analysis. Based on temporal dynamics analysis, the patterns were classified into four categories: early decline, steady decline, mid-peak with early incline, and late decline. Heatmap of spatial dynamics and trajectory-related visualization could elucidate a consumption posture and a higher spatial occupancy of food zone in hunger and with palatable food. Discussion: Collectively, this study describes a newly developed and validated multi-phase method for assessing freely moving nonhuman primate eating behavior using manual and deep learning-based analyses. These effective tools will prove valuable in food reward (palatability effect) and homeostasis (hunger effect) research.

Low-Temperature, Universal Synthetic Route for Mesoporous Metal Oxides by Exploiting Synergistic Effect of Thermal Activation and Plasma.

Mesoporous metal oxides exhibit excellent physicochemical properties and are widely used in various fields, including energy storage/conversion, catalysis, and sensors. Although several soft-template approaches are reported, high-temperature calcination for both metal oxide formation and template removal is necessary, which limits direct synthesis on a plastic substrate for flexible devices. Here, a universal synthetic approach that combines thermal activation and oxygen plasma to synthesize diverse mesoporous metal oxides (V2O5, V6O13, TiO2, Nb2O5, WO3, and MoO3) at low temperatures (150-200 °C), which can be applicable to a flexible polymeric substrate is introduced. As a demonstration, a flexible micro-supercapacitor is fabricated by directly synthesizing mesoporous V2O5 on an indium-tin oxide-coated colorless polyimide film. The energy storage performance is well maintained under severe bending conditions.

Fiber support prevents colloid-facilitated contamination induced by dissolution-precipitation of a calcium phosphate adsorbent.

During the adsorptive removal of hazardous metal contaminants, dissolution-precipitation of sparingly soluble adsorbents may result in the formation of toxic colloidal suspensions, triggering secondary pollution. Therefore, we studied the prevention of colloid-facilitated contamination in a model adsorption system of dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) and Cd2+ as an adsorbent and adsorbate. Upon adding pure DCPD powder into a 500 mg L-1 Cd2+ solution of pH â‰Œ 7.0, aggregates of spheroidal Cd-bearing primary particles, within 0.040-0.95 µm size range, were generated via dissolution-precipitation. The accumulated volume of these submicron particles (10.8%) was greater than that of the submicron particles from the exposure of DCPD to deionized water (4.48%). While the Cd-carrying submicron particles, which are responsible for colloidal recontamination, appeared to form via homogeneous nucleation, their formation was suppressed using polyacrylonitrile fibers (PANFs) as supporting substrates. Thus, heterogeneous nucleation on PANFs formed hexagonal columnar microparticles of a new phase, pentacadmium dihydrogen tetrakis (phosphate) tetrahydrate (Cd5H2(PO4)4·4H2O). Together with dissolution-precipitation on the native DCPD, nucleation and growth on the PANFs accelerated the depletion of the dissolved species, reducing the degree of supersaturation along the DCPD-water interface. Although the PANFs decreased the Cd adsorption capacity to 56.7% of that of DCPD, they prevented the formation of small aggregates of Cd-bearing particles. Other sparingly soluble adsorbents can be compounded with PANF to prevent the generation of toxic colloids.

Facile synthesis of porous transition metal hydroxides from a poly(4-vinyl pyridine) film by controlling pH.

Non-noble transition metal hydroxides have been widely used in electrochemical devices because of low cost and multiple redox states. In particular, self-supported porous transition metal hydroxides are used to improve the electrical conductivity, as well as achieving fast electron and mass transfer and a large effective surface area. Herein, we introduce facile synthesis of self-supported porous transition metal hydroxides using a poly(4-vinyl pyridine) (P4VP) film. We used metal cyanide as a transition metal precursor capable of forming metal hydroxide anions in aqueous solution, which is the seed for transition metal hydroxides. To increase the coordination between P4VP and the transition metal cyanide precursors, we dissolved the precursors in buffer solutions with various pH. When the P4VP film was immersed in the precursor solution with lower pH, the metal cyanide precursors were sufficiently coordinated with the protonated nitrogen in P4VP. When reactive ion etching was performed on the precursor-containing P4VP film, the P4VP region without coordination was etched out and became pores. Then, the coordinated precursors were aggregated as metal hydroxide seeds and became the metal hydroxide backbone, resulting in the formation of porous transition metal hydroxide structures. We successfully fabricated various self-supported porous transition metal hydroxides (Ni(OH)2, Co(OH)2, and FeOOH). Finally, we prepared a pseudo-capacitor based on self-supported porous Ni(OH)2, which showed a good specific capacitance (780 F g-1 at 5 A g-1).

Block Copolymer-Directed Facile Synthesis of N-Doped Mesoporous Graphitic Carbon for Reliable, High-Performance Zn Ion Hybrid Supercapacitor.

Ordered mesoporous carbons (OMCs) are promising materials for cathode materials of a Zn ion hybrid capacitor (Zn HC) due to their high surface area and interconnected porous structure. Graphitization of the framework and nitrogen doping have been used to improve the energy storage performance of the OMCs by enhancing electrical conductivity, pseudocapacitive reaction sites, and surface affinity toward aqueous electrolytes. Thus, when both methods are simultaneously implemented to the OMCs, the Zn HC would have improved energy storage performance. Herein, we introduce a facile synthetic method for N-doped mesoporous graphitic carbon (N-mgc) by utilizing polystyrene-block-poly(2-vinlypyridine) copolymer (PS-b-P2VP) as both soft-template and carbon/nitrogen sources. Co-assembly of PS-b-P2VP with Ni precursors for graphitization formed a mesostructured composite, which was converted to N-doped graphitic carbon through catalytic pyrolysis. After selective removal of Ni, N-mgc was prepared. The obtained N-mgc exhibited interconnected mesoporous structure with high nitrogen content and high surface area. When N-mgc was employed as a cathode material in Zn ion HC, excellent energy storage performance was achieved: a high specific capacitance (43 F/g at 0.2 A/g), a high energy density of 19.4 Wh/kg at a power density of 180 W/kg, and reliable cycle stability (>3000 cycles).

Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis.

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726, p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.

Disease characteristics of idiopathic transverse myelitis with serum neuronal and astroglial damage biomarkers.

Despite its close association with CNS inflammatory demyelinating disorders (CIDDs), pathogenic characteristics of idiopathic transverse myelitis (ITM) remain largely unknown. Here, we investigated serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in patients with ITM to unravel the disease characteristics of ITM. We prospectively recruited 70 patients with ITM, 62 with AQP4 + NMOSD and 85 with RRMS-including 31 patients with acute TM attacks-along with 30 HCs. We measured sNfL and sGFAP levels using single-molecular arrays and compared these levels per lesion volume between the disease groups during attacks. Compared to HCs, ITM patients showed higher sNfL and sGFAP during acute attacks (sNfL: p < 0.001, sGFAP: p = 0.024), while those in remission (sNfL: p = 0.944, sGFAP: p > 0.999) did not, regardless of lesion extents and presence of multiple attacks. ITM patients demonstrated lower sGFAP/volume (p = 0.011) during acute attacks and lower sGFAP (p < 0.001) in remission compared to AQP4 + NMOSD patients. These findings suggest that both neuronal and astroglial damages occur in patients with acute ITM attacks at a similar level to those with RRMS, distinct from AQP4 + NMOSD. However, active neuroinflammatory process was not remarkable during remission in this cohort.

Facile Fabrication of Titanium Nitride Nanoring Broad-Band Absorbers in the Visible to Near-Infrared by Shadow Sphere Lithography.

Plasmonic broad-band absorbers have received much attention because of their high absorption and potential applications for light-absorbing devices such as thermophotovoltaics, solar energy harvesting, and thermal emitters. However, the fabrication of complex structures in a large area and thermostability remains a great challenge. Here, we report a titanium nitride nanoring broad-band absorber that has over 95% average absorption in the visible and near-infrared regions (400-900 nm). Nanoring structures in a large area (inch2) are fabricated by shadow sphere lithography, which can innovatively increase fabrication efficiency. The nanoring absorber showed over 2.3 times higher-temperature increases than flat film under the irradiation of light. These large-scale and broad-band absorbers have potential applications for solar energy conversion devices such as thermophotovoltaics and photothermal devices.

Determination of the Unilaterally Damaged Region May Depend on the Asymmetry of Carotid Blood Flow Velocity in Hemiparkinsonian Monkey: A Pilot Study.

The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson's disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.

Soft Template-Assisted Fabrication of Mesoporous Graphenes for High-Performance Energy Storage Systems.

Graphene is a promising active material for electric double layer supercapacitors (EDLCs) due to its high electric conductivity and lightweight nature. However, for practical uses as a power source of electronic devices, a porous structure is advantageous to maximize specific energy density. Here, we propose a facile fabrication approach of mesoporous graphene (m-G), in which self-assembled mesoporous structures of poly(styrene)-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) are exploited as both mesostructured catalytic template and a carbon source. Notably, the mesostructured catalytic template is sufficient to act as a rigid support without structural collapse, while PS-b-P2VP converts to graphene, generating m-G with a pore diameter of ca. 3.5 nm and high specific surface area of 186 m2/g. When the EDLCs were prepared using the obtained m-G and ionic liquids, excellent electrochemical behaviors were achieved even at high operation voltages (0 ∼ 3.5 V), including a large specific capacitance (130.2 F/g at 0.2 A/g), high-energy density of 55.4 W h/kg at power density of 350 W/kg, and excellent cycle stability (>10,000 cycles). This study demonstrates that m-G is a promising material for high-performance energy storage devices.

Triboelectric Nanogenerators: Enhancing Performance by Increasing the Charge-Generating Layer Compressibility.

Triboelectric nanogenerators (TENGs) have received significant attention for next-generation wearable electronics due to their simple device structure and low cost. Although the performance of TENGs is intimately tied to compressibility effects in the charge-generating layer, achieving high compressibility with conventional elastomers is challenging because molecular entanglements place a lower bound on the softness of cross-linked networks. Here, we demonstrate that bottlebrush elastomers are efficient charge-generating layers that improve the output performance of TENGs, including voltage, current, and surface potential, by minimizing entanglements and decreasing the compressive modulus (E). For example, a cross-linked bottlebrush with poly(dimethylsiloxane) side chains yielded TENGs with an output voltage (120 V) more than two times larger than a linear PDMS network (55 V). In conclusion, this study highlights the advantage of designing new charge-generating layers with improved compressibility to enhance TENG performance.

Trend and Seasonality of Diabetic Foot Amputation in South Korea: A Population-Based Nationwide Study.

The number of lower extremity amputations in diabetic foot patients in Korea is increasing annually. In this nationwide population-based retrospective study, we investigated the data of 420,096 diabetes mellitus patients aged ≥18 years using the Korean Health Insurance Review and Assessment Service claim database. We aimed to study the seasonal and monthly trends in diabetic foot amputations in Korea. After applying the inclusion criteria, 8156 amputation cases were included. The analysis showed an increasing trend in monthly amputation cases. In terms of seasonality, the monthly frequency of amputation was commonly observed to be lower in February and September every year. Diabetic foot amputations frequently occurred in March, July, and November. There was no difference between the amputation frequency and mean temperature/humidity. This study is meaningful as it is the first nationwide study in Korea to analyze the seasonal and monthly trends in diabetic foot amputation in relation to climatic factors. In conclusion, we recognize an increased frequency of amputation in March, July, and November and recommend intensive educational program on foot care for all diabetes patients and their caregivers. This could improve wound management and amputation prevention guidelines for diabetic foot patients in the Far East with information on dealing with various seasonal changes.

Quality of life of patients with multiple sclerosis and neuromyelitis optica spectrum disorders: Cross-sectional and longitudinal analysis.

BACKGROUND: Multiple sclerosis (MS) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (NMOSD), which have different pathogenic mechanisms, both negatively affect patients during their lifetime. We aimed to analyze and compare the quality of life (QoL) of patients with MS and NMOSD, its longitudinal course, and associated factors between the two diseases. METHODS: Between June 2018 and April 2020, patients with MS and NMOSD who visited a tertiary hospital were prospectively enrolled. The EuroQoL-5 Dimension (EQ-5D) utility index, of which low values represent poor QoL, Expanded Disability Status Scale (EDSS), and the Hospital Anxiety and Depression Scale (HADS) were collected at enrollment and at follow-up with a 6-12-month interval. At baseline, the degree of QoL and its determinants were analyzed and compared between the MS and NMOSD groups. We also analyzed the longitudinal alteration of the EQ-5D utility indices over time and the factors associated with the follow-up QoL. RESULTS: During the study period, 171 patients (MS, 120; NMOSD, 51) were included. The median age was 46 years, and median EDSS score and follow-up duration were 2.5 and 8 months, respectively. At baseline, the EQ-5D utility indices were low and comparable between the MS and NMOSD groups (median: 0.86 vs. 0.82, p = 0.823). A higher HADS total score (more severe anxiety/depression symptoms) showed an independent and significant association with the baseline EQ-5D utility index in both disease groups. Longitudinally, the EQ-5D utility indices remained low. Although they did not significantly change over time at a group level, more than 50% of patients showed a longitudinal change in their EQ-5D indices in both disease groups. Of note, a higher HADS total score at enrollment was an independent predictor for poor QoL at follow-up in both disease groups. CONCLUSIONS: The QoL was similarly impaired between patients with MS and those with NMOSD and remained low during the follow-up period. A higher total scale of HADS was an independent risk factor for a lower QoL at baseline and at follow-up in both disease conditions, suggesting that clinicians should pay more attention to anxiety and depression in patients with MS and those with NMOSD in the long term.

XperCT-guided Intra-cisterna Magna Injection of Streptozotocin for Establishing an Alzheimer's Disease Model Using the Cynomolgus Monkey (Macaca fascicularis).

Till date, researchers have been developing animal models of Alzheimer's disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM. Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.