Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies.

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

Steep-slope vertical-transport transistors built from sub-5 nm Thin van der Waals heterostructures.

Two-dimensional (2D) semiconductor-based vertical-transport field-effect transistors (VTFETs) - in which the current flows perpendicularly to the substrate surface direction - are in the drive to surmount the stringent downscaling constraints faced by the conventional planar FETs. However, low-power device operation with a sub-60 mV/dec subthreshold swing (SS) at room temperature along with an ultra-scaled channel length remains challenging for 2D semiconductor-based VTFETs. Here, we report steep-slope VTFETs that combine a gate-controllable van der Waals heterojunction and a metal-filamentary threshold switch (TS), featuring a vertical transport channel thinner than 5 nm and sub-thermionic turn-on characteristics. The integrated TS-VTFETs were realised with efficient current switching behaviours, exhibiting a current modulation ratio exceeding 1 × 108 and an average sub-60 mV/dec SS over 6 decades of drain current. The proposed TS-VTFETs with excellent area- and energy-efficiency could help to tackle the performance degradation-device downscaling dilemma faced by logic transistor technologies.

CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy-dependent ferroptosis.

Cisplatin is the first-line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy-dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR-508-3p/Bcl-2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.

Engineering Sub-Nanometer Hafnia-Based Ferroelectrics to Break the Scaling Relation for High-Efficiency Piezocatalytic Water Splitting.

Reversible control of ferroelectric polarization is essential to overcome the heterocatalytic kinetic limitation. This can be achieved by creating a surface with switchable electron density; however, owing to the rigidity of traditional ferroelectric oxides, achieving polarization reversal in piezocatalytic processes remains challenging. Herein, sub-nanometer-sized Hf0.5 Zr0.5 O2 (HZO) nanowires with a polymer-like flexibility are synthesized. Oxygen K-edge X-ray absorption spectroscopy and negative spherical aberration-corrected transmission electron microscopy reveal an orthorhombic (Pca21 ) ferroelectric phase of the HZO sub-nanometer wires (SNWs). The ferroelectric polarization of the flexible HZO SNWs can be easily switched by slight external vibration, resulting in dynamic modulation of the binding energy of adsorbates and thus breaking the "scaling relationship" during piezocatalysis. Consequently, the as-synthesized ultrathin HZO nanowires display superb water-splitting activity, with H2 production rate of 25687 µmol g-1  h-1 under 40 kHz ultrasonic vibration, which is 235 and 41 times higher than those of non-ferroelectric hafnium oxides and rigid BaTiO3 nanoparticles, respectively. More strikingly, the hydrogen production rates can reach 5.2 µmol g-1  h-1 by addition of stirring exclusively.

Identification of hub necroptosis-related lncRNAs for prognosis prediction of esophageal carcinoma.

Necroptosis is a newly identified programmed cell death associated with the biological process of various cancers, including esophageal carcinoma (ESCA). Meanwhile, the dysregulation of long non-coding RNAs (lncRNAs) is greatly implicated in ESCA progression and necroptosis regulation. However, the lncRNAs involved in regulating necroptosis in ESCA are still unclear. In this study, we aim to explore the expression profile of necroptosis-related lncRNAs (NRLs), and evaluate their roles in ESCA prognosis and treatment. In the present study, 198 differentially expressed NRLs were identified between the ESCA and adjacent normal tissues through screening the data extracted from the Cancer Genome Atlas (TCGA) database. And, a prognostic panel consisting of 6 NRLs was constructed using the LASSO algorithm and multivariate Cox regression analysis. The ESCA patients with high risks had a markedly reduced survival time and higher mortality prevalence. Moreover, C-index of 6 NRLs-panel was superior to 48 published prognostic models based on lncRNAs or mRNAs for ESCA. There were significant differences between the high-risk and low-risk groups in tumor-related pathways, genetic mutations, and drug sensitivity responses. In vitro analysis revealed that inhibition of PVT1 impeded the proliferation, migration, and colony formation of ESCA cells, increased the expressions of p-RIP1 and p-MLKL and promoted necroptosis. By contrast, PVT1 overexpression resulted in a decrease in necroptotic cell death events, thus promoting tumor progression. Collectively, the established 6-NRLs panel was a promising biomarker for the prognostic prediction of ESCA. Moreover, our current findings provided potential targets for individualized therapy for ESCA patients.

Effect of Hydrophilic Polyurethane on Interfacial Shear Strength of Pisha Sandstone Consolidation under Freeze-Thaw Cycles.

The W-OH type polyurethane (W-OH) has been proven to be an economical and environmentally friendly slope protection solution for slope maintenance in Pisha sandstone areas. However, the Pisha area belongs to a typical temperate continental climate with large diurnal temperature changes in winter, spring, and autumn and freezing and thawing occurring alternately between days and nights. Under freeze-thaw cycle conditions, the effect of slope treatment largely depends on the interface shear strength between W-OH-treated Pisha sandstone and pristine sandstone. Therefore, this paper studies the interfacial shear strength and long-term durability of Bisha sandstone consolidation (W-OH-treated Pisha sandstone) and Pisha sandstone under freeze-thaw cycles. First, the effects of different W-OH concentrations and different water contents on the freeze-thaw cycle interface were studied using a direct shear test. Based on the experimental results, the W-OH material was further modified with ethylene vinyl acetate (EVA). Finally, the damaged surface of the sample was observed through an ultra-depth-of-field microscope, and the damage mechanism of the interface caused by the freeze-thaw cycles was further discussed. The experimental results show that the peak shear strength at the interface increases with the increase in W-OH concentration and decreases with the increase in freeze-thaw cycles. The cohesion at the interface generally increases with the increase in W-OH concentration and reaches a maximum value of 43.6 kPa when the W-OH concentration is 10%. At the same time, under the condition of high water content, the curing of the W-OH material has no significant effect on the bonding performance of the interface. Using EVA to modify the W-OH material can improve the freeze-thaw durability of the interface. After modification, the interfacial cohesion of the sample increases with the increase in the EVA concentration and can reach 162% of the original. Using an ultra-depth-of-field microscope, it was found that the repeated solidification-melting action of water between the interfaces makes the consolidated body on the damaged surface fall off, resulting in cracks. As the water content between the interfaces increases, the damage to the material is greater. However, the addition of EVA can fill the uncovered pores of W-OH cement, thereby improving the cohesion at the interface and effectively alleviating the freeze-thaw damage caused by the high water content at the interface. The results of this study can provide some theoretical references for slope treatment in the Pisha sandstone area using W-OH materials.

Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis.

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Van der Waals Nonlinear Photodetector with Quadratic Photoresponse.

With unique electronic and optical attributes and dangling-bond-free surface, two-dimensional (2D) materials have broadened the functionalities of photodetectors. Here, we report a quadratically nonlinear photodetector (QNPD) composed of a van der Waals (vdW) stacked GaSe/InSe heterostructure. Compared with the reported 2D material-based photodetectors, the extra second-harmonic generation (SHG) process in GaSe/InSe leads to the quadratically nonlinear function between photocurrent and optical intensity, extending the photodetection wavelength from 900 to 1750 nm. The QNPD is highly sensitive to the variation of optical intensity with improved spatial resolution. With the light-light interaction in SHG converted into electrical signal directly, we also demonstrate the QNPD as an autocorrelator for measuring ultrafast pulse widths and an optoelectronic mixer of two modulated pulses for signal processings. The simultaneous involvement of light-light interaction and photoelectric conversion in the vdW stacked QNPD promises its potential to simplify the optoelectronic systems.

Waveguide-Integrated MoTe2 p-i-n Homojunction Photodetector.

Two-dimensional (2D) materials, featuring distinctive electronic and optical properties and dangling-bond-free surfaces, are promising for developing high-performance on-chip photodetectors in photonic integrated circuits. However, most of the previously reported devices operating in the photoconductive mode suffer from a high dark current or a low responsivity. Here, we demonstrate a MoTe2 p-i-n homojunction fabricated directly on a silicon photonic crystal (PC) waveguide, which enables on-chip photodetection with ultralow dark current, high responsivity, and fast response speed. The adopted silicon PC waveguide is electrically split into two individual back gates to selectively dope the top regions of the MoTe2 channel in p- or n-types. High-quality reconfigurable MoTe2 (p-i-n, n-i-p, n-i-n, p-i-p) homojunctions are realized successfully, presenting rectification behaviors with ideality factors approaching 1.0 and ultralow dark currents less than 90 pA. Waveguide-assisted MoTe2 absorption promises a sensitive photodetection in the telecommunication O-band from 1260 to 1340 nm, though it is close to MoTe2's absorption band-edge. A competitive photoresponsivity of 0.4 A/W is realized with a light on/off current ratio exceeding 104 and a record-high normalized photocurrent-to-dark-current ratio of 106 mW-1. The ultrasmall capacitance of p-i-n homojunction and high carrier mobility of MoTe2 promise a high dynamic response bandwidth close to 34.0 GHz. The proposed device geometry has the advantages of employing a silicon PC waveguide as the back gates to build a 2D material p-i-n homojunction directly and simultaneously to enhance light-2D material interaction. It provides a potential pathway to develop 2D material-based photodetectors, laser diodes, and electro-optic modulators on silicon photonic chips.

Feasibility Study on the Bamboo Grid Instead of Geogrid for Soil-Rock Mixture Subgrade Reinforcing.

To promote the application of the bamboo grid in the soil-rock mixture subgrade in mountain areas, the mechanical properties of bamboo reinforcement were investigated in this study, and the reinforcement effect and interface characteristics of uniaxial/biaxial bamboo grid on the soil-rock mixture under different vertical loads was comparatively analyzed. The results show that the tensile force (2% elongation) of the bamboo reinforcement is 50.21 kN/m, and its average tensile strength is 236.01 MPa. Moreover, bamboo reinforcement has excellent shear and flexural properties. In general, the reinforcement effect of the biaxial bamboo grid on the soil-rock mixed subgrade is better than that of the uniaxial bamboo grid. In the case of using a uniaxial bamboo grid, its pull-out curve is generally a strain-softening type. As for the biaxial bamboo grid, due to the existence of bite force, its pull-out curve usually presents a strain-hardening type. Compared with the uniaxial bamboo grid, the friction coefficient of the reinforcement-soil interface using the biaxial bamboo grid is higher, and the interfacial shear stress is increased by 72.2-91.2%.

A panel of necroptosis-related genes predicts the prognosis of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) has become one of the deadliest malignancies in the world. Since necroptosis plays a crucial role in regulating the immune system, it is necessary to develop novel prognostic biomarkers associated with necroptosis and explore its potential role in PAAD. The transcriptome RNA-seq data of PAAD were downloaded from the TCGA and GTEx databases. A prognostic signature was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression, and its prognostic value was evaluated by nomogram and validated in an independent GEO cohort. We identified a total of 24 differentially expressed NRGs in PAAD, and constructed a prognostic signature with 5 NRGs, which showed good performance in predicting the prognosis of PAAD patients. The ROC curves for 1-, 3-, and 5-year survival rate were 0.652, 0.778, and 0.817, respectively. This prognostic signature showed consistent prognosis prediction in an independent patient cohort. Furthermore, the correlations between 5-NRGs signature and TMB, MSI, histopathological classification, immune infiltration, immune types, and immunomodulators were all significant. Notably, the expression profiles of the five NRGs in exosomes of serum were consistent with their expression in tumor tissues. These data suggested that the 5-NRGs signature is a promising biomarker for predicting the prognosis of PAAD.

Influence of Multiple Factors on the Workability and Early Strength Development of Alkali-Activated Fly Ash and Slag-Based Geopolymer-Stabilized Soil.

The complexity of composite geopolymer materials results in instability in the setting and hardening of geopolymer-stabilized soil. In order to determine the appropriate mix proportion scheme for composite geopolymer-stabilized soil, this study investigated the effects of two preparation methods, fly ash/slag ratio and alkali activator modulus, on workability and strength development trends in alkali-excited fly ash and slag-based geopolymer-stabilized soil. The results showed that the high ambient temperatures created by the one-step method were more conducive to the setting and hardening of the geopolymer-stabilized soil; its 3 d/28 d UCS (unconfined compression strength) ratio was 62.43-78.60%, and its 7 d/28 d UCS ratio was 70.37-83.63%. With increases of the alkali activator modulus or the proportion of fly ash, the setting time of stabilized soil was gradually prolonged, and its fluidity increased. Meanwhile, the strength development of stabilized soil was significantly affected by the proportion of fly ash and the alkali activator modulus; the maximum UCS value was obtained at II-2-O, prepared by the one-step method, with an alkali activator modulus of 1.2 and a fly ash/slag ratio of 20/80. Specifically, the 3, 7, and 28 d UCS values of II-2-O were 1.65, 1.89, and 2.26 MPa, respectively, and its 3 d/28 d UCS ratio and 7 d/28 d UCS ratio were 73.01% and 83.63%, respectively. These results will be of great importance in further research on (and construction guidance of) composite geopolymer-stabilized soil.

Electrically Tunable Second Harmonic Generation in Atomically Thin ReS2.

Electrical tuning of second-order nonlinearity in optical materials is attractive to strengthen and expand the functionalities of nonlinear optical technologies, though its implementation remains elusive. Here, we report the electrically tunable second-order nonlinearity in atomically thin ReS2 flakes benefiting from their distorted 1T crystal structure and interlayer charge transfer. Enabled by the efficient electrostatic control of the few-atomic-layer ReS2, we show that second harmonic generation (SHG) can be induced in odd-number-layered ReS2 flakes which are centrosymmetric and thus without intrinsic SHG. Moreover, the SHG can be precisely modulated by the electric field, reversibly switching from almost zero to an amplitude more than 1 order of magnitude stronger than that of the monolayer MoS2. For the even-number-layered ReS2 flakes with the intrinsic SHG, the external electric field could be leveraged to enhance the SHG. We further perform the first-principles calculations which suggest that the modification of in-plane second-order hyperpolarizability by the redistributed interlayer-transferring charges in the distorted 1T crystal structure underlies the electrically tunable SHG in ReS2. With its active SHG tunability while using the facile electrostatic control, our work may further expand the nonlinear optoelectronic functions of two-dimensional materials for developing electrically controllable nonlinear optoelectronic devices.

Dual-Ferroelectric-Coupling-Engineered Two-Dimensional Transistors for Multifunctional In-Memory Computing.

In-memory computing featuring a radical departure from the von Neumann architecture is promising to substantially reduce the energy and time consumption for data-intensive computation. With the increasing challenges facing silicon complementary metal-oxide-semiconductor (CMOS) technology, developing in-memory computing hardware would require a different platform to deliver significantly enhanced functionalities at the material and device level. Here, we explore a dual-gate two-dimensional ferroelectric field-effect transistor (2D FeFET) as a basic device to form both nonvolatile logic gates and artificial synapses, addressing in-memory computing simultaneously in digital and analog spaces. Through diversifying the electrostatic behaviors in 2D transistors with the dual-ferroelectric-coupling effect, rich logic functionalities including linear (AND, OR) and nonlinear (XNOR) gates were obtained in unipolar (MoS2) and ambipolar (MoTe2) FeFETs. Combining both types of 2D FeFETs in a heterogeneous platform, an important computation circuit, i.e., a half-adder, was successfully constructed with an area-efficient two-transistor structure. Furthermore, with the same device structure, several key synaptic functions are shown at the device level, and an artificial neural network is simulated at the system level, manifesting its potential for neuromorphic computing. These findings highlight the prospects of dual-gate 2D FeFETs for the development of multifunctional in-memory computing hardware capable of both digital and analog computation.

Evolution of the Interfacial Layer and Its Impact on Electric-Field-Cycling Behaviors in Ferroelectric Hf1-xZrxO2.

Doped HfO2 thin films, which exhibit robust ferroelectricity even with aggressive thickness scaling, could potentially enable ultralow-power logic and memory devices. The ferroelectric properties of such materials are strongly intertwined with the voltage-cycling-induced electrical and structural changes, leading to wake-up and fatigue effects. Such field-cycling-dependent behaviors are crucial to evaluate the reliability of HfO2-based functional devices; however, its genuine nature remains elusive. Herein, we demonstrate the coupling mechanism between the dynamic change of the interfacial layer and wake-up/fatigue phenomena in ferroelectric Hf1-xZrxO2 (HZO) thin films. Comprehensive atomic-resolution microscopy studies have revealed that the interfacial layer between the HZO and neighboring nonoxide electrode experienced a thickness/composition evolution during electrical cycling. Two theoretical models associated with the depolarization field are adopted, giving consistent results with the thickening of the interfacial layer during electrical cycling. Furthermore, we found that the electrical properties of the HZO devices can be manipulated by controlling the interface properties, e.g., through the choice of electrode match and hybrid cycling process. Our results unambiguously reveal the relationship between the interfacial layer and field-cycling behaviors in HZO, which would further permit the reliability improvement in HZO-based ferroelectric devices through interface engineering.

Experimental Investigation of Unconfined Compression Strength and Microstructure Characteristics of Slag and Fly Ash-Based Geopolymer Stabilized Riverside Soft Soil.

To solve the issues of insufficient early strength of cement stabilized soil and high resource cost, high reduction cost, and high environmental cost induced by the application of cement, the slag and fly ash-based geopolymer was adopted as the stabilizer to treat riverside soft soil. This study mainly investigated the effects of stabilizer content, slag-to-fly ash ratio, and alkaline activator content on the strength of geopolymer stabilized soils with different curing ages. Unconfined compressive strength (UCS), scanning electron microscope (SEM), and X-ray energy spectrum analysis (EDS) tests were carried out. The results show that the stabilizer content, slag-fly ash ratio, and alkaline activator content have a decisive influence on the UCS of geopolymer-stabilized soil. The mix-proportions scheme of geopolymer stabilized riverside soft soil, with a geopolymer content of 15%, a slag-fly ash ratio of 80:20, and an alkaline activator content of 30%, is considered optimum. It is proven by SEM that the uniformly distributed gelatinous products formed in the geopolymer-stabilized soil bind the soil particles tightly. Moreover, the EDS analysis confirms that the gelatinous products are mainly composed of C-S-H gel and sodium-based aluminosilicate (N-A-S-H).

Strain-Engineered Nano-Ferroelectrics for High-Efficiency Piezocatalytic Overall Water Splitting.

Developing nano-ferroelectric materials with excellent piezoelectric performance for piezocatalysts used in water splitting is highly desired but also challenging, especially with respect to reaching large piezo-potentials that fully align with required redox levels. Herein, heteroepitaxial strain in BaTiO3 nanoparticles with a designed porous structure is successfully induced by engineering their surface reconstruction to dramatically enhance their piezoelectricity. The strain coherence can be maintained throughout the nanoparticle bulk, resulting in a significant increase of the BaTiO3 tetragonality and thus its piezoelectricity. Benefiting from high piezoelectricity, the as-synthesized blue-colored BaTiO3 nanoparticles possess a superb overall water-splitting activity, with H2 production rates of 159 µmol g-1 h-1 , which is almost 130 times higher than that of the pristine BaTiO3 nanoparticles. Thus, this work provides a generic approach for designing highly efficient piezoelectric nanomaterials by strain engineering that can be further extended to various other perovskite oxides, including SrTiO3 , thereby enhancing their potential for piezoelectric catalysis.

Emerging Opportunities for 2D Semiconductor/Ferroelectric Transistor-Structure Devices.

Semiconductor technology, which is rapidly evolving, is poised to enter a new era for which revolutionary innovations are needed to address fundamental limitations on material and working principle level. 2D semiconductors inherently holding novel properties at the atomic limit show great promise to tackle challenges imposed by traditional bulk semiconductor materials. Synergistic combination of 2D semiconductors with functional ferroelectrics further offers new working principles, and is expected to deliver massively enhanced device performance for existing complementary metal-oxide-semiconductor (CMOS) technologies and add unprecedented applications for next-generation electronics. Herein, recent demonstrations of novel device concepts based on 2D semiconductor/ferroelectric heterostructures are critically reviewed covering their working mechanisms, device construction, applications, and challenges. In particular, emerging opportunities of CMOS-process-compatible 2D semiconductor/ferroelectric transistor structure devices for the development of a rich variety of applications are discussed, including beyond-Boltzmann transistors, nonvolatile memories, neuromorphic devices, and reconfigurable nanodevices such as p-n homojunctions and self-powered photodetectors. It is concluded that 2D semiconductor/ferroelectric heterostructures, as an emergent heterogeneous platform, could drive many more exciting innovations for modern electronics, beyond the capability of ubiquitous silicon systems.

Anisotropic Ion Migration and Electronic Conduction in van der Waals Ferroelectric CuInP2S6.

Van der Waals (vdW) thio- and seleno-phosphates have recently gained considerable attention for the use as "active" dielectrics in two-dimensional/quasi-two-dimensional electronic devices. Bulk ionic conductivity in these materials has been identified as a key factor for the control of their electronic properties. However, direct evidence of specific ion species' migration at the nanoscale, particularly under electric fields, and its impact on material properties has been elusive. Here, we report on direct evidence of a phase-selective anisotropic Cu-ion-hopping mechanism in copper indium thiophosphate (CuInP2S6) through detailed scanning probe microscopy measurements. A two-step Cu-hopping path including a first intralayer hopping (in-plane) and second interlayer hopping (out-of-plane) crossing the vdW gap is unveiled. Evidence of electrically controlled Cu ion migration is further verified by nanoscale energy-dispersive X-ray spectroscopy (EDS) mapping. These findings offer new insight into anisotropic ionic manipulation in layered vdW ferroelectric/dielectric materials for emergent vdW electronic device design.