Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report.

BACKGROUND: Gastric stromal tumors, originating from mesenchymal tissues, are one of the most common tumors of the digestive tract. For stromal tumors originating from the muscularis propria, compared with conventional endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR) can remove deep lesions and digestive tract wall tumors completely. However, this technique has major limitations such as perforation, postoperative bleeding, and post-polypectomy syndrome. Herein, we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR. Feasible treatment options to address this complication are described. CASE SUMMARY: A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography, located at the upper gastric curvature adjacent to the stomach fundus, with a smooth surface mucosa and poor mobility. The lesion was 19.3 mm × 16.1 mm in size and originated from the fourth ultrasound layer. Computed tomography (CT) revealed no significant evidence of lymph node enlargement or distant metastasis. Using conventional ESD technology for mucosal pre-resection, exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis. Based on its morphology and immunohistochemical expression of CD117 and DOG-1, the lesion was proven to be consistent with a gastric stromal tumor. Six days after exposed EFTR, CT showed a large amount of encapsulated fluid and gas accumulation around the stomach. In addition, gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding. Based on these findings, the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor. The patient received combined treatments, such as hemostasis under gastroscopy, gastrointestinal decompression, and abdominal drainage. All examinations were normal within six months of follow-up. CONCLUSION: This patient developed serous surface bleeding in the gastric cavity following exposed EFTR. Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice. The combined treatment may replace certain surgical techniques.

ILC2s: Unraveling the innate immune orchestrators in allergic inflammation.

The prevalence rate of allergic diseases including asthma, atopic rhinitis (AR) and atopic dermatitis (AD) has been significantly increasing in recent decades due to environmental changes and social developments. With the study of innate lymphoid cells, the crucial role played by type 2 innate lymphoid cells (ILC2s) have been progressively unveiled in allergic diseases. ILC2s, which are a subset of innate lymphocytes initiate allergic responses. They respond swiftly during the onset of allergic reactions and produce type 2 cytokines, working in conjunction with T helper type 2 (Th2) cells to induce and sustain type 2 immune responses. The role of ILC2s represents an intriguing frontier in immunology; however, the intricate immune mechanisms of ILC2s in allergic responses remain relatively poorly understood. To gain a comphrehensive understanding of the research progress of ILC2, we summarize recent advances in ILC2s biology in pathologic allergic inflammation to inspire novel approaches for managing allergic diseases.

Involvement and repair of epithelial barrier dysfunction in allergic diseases.

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.

Spatially-Resolved Thermometry of Filamentary Nanoscale Hot Spots in TiO2 Resistive Random Access Memories to Address Device Variability.

Resistive random access memories (RRAM), based on the formation and rupture of conductive nanoscale filaments, have attracted increased attention for application in neuromorphic and in-memory computing. However, this technology is, in part, limited by its variability, which originates from the stochastic formation and extreme heating of its nanoscale filaments. In this study, we used scanning thermal microscopy (SThM) to assess the effect of filament-induced heat spreading on the surface of metal oxide RRAMs with different device designs. We evaluate the variability of TiO2 RRAM devices with area sizes of 2 × 2 and 5 × 5 µm2. Electrical characterization shows that the variability indicated by the standard deviation of the forming voltage is ∼2 times larger for 5 × 5 µm2 devices than for the 2 × 2 µm2 ones. Further knowledge on the reason for this variability is gained through the SThM thermal maps. These maps show that for 2 × 2 µm2 devices the formation of one filament, i.e., hot spot at the device surface, happens reliably at the same location, while the filament location varies for the 5 × 5 µm2 devices. The thermal information, combined with the electrical, interfacial, and geometric characteristics of the device, provides additional insights into the operation and variability of RRAMs. This work suggests thermal engineering and characterization routes to optimize the efficiency and reliability of these devices.

Differences in the healthcare needs of older adults attending primary health centers in urban and rural areas of Taiwan.

PURPOSE: As the older adult population in Taiwan continues to increase, primary health centers (PHCs) play a crucial role in geriatric care. This study explored the differences in the PHC experiences and usage needs of older adults in urban versus rural areas. METHODS: A qualitative study was conducted. Twenty-one older adults were recruited from PHCs in northern, central, southern, and eastern Taiwan. Semistructured interviews were used to collect data, and the interview guidelines included their reasons for visiting PHCs, the health-care services they received, their evaluation of the services, and the advantages and disadvantages of these centers. The data were analyzed using thematic content analysis. RESULTS: The PHC usage needs of older adults in urban areas differ from those of older adults in rural areas in the following 3 aspects: (1) Medical services: older adults in rural areas demand clinics specializing in various medical domains, mobile and home medical care, and case management, whereas those in urban areas demand mobile health examinations. (2) Environment and transportation: older adults in rural areas demand diverse medical equipment, shuttle services, and accessible facilities, whereas those in urban areas demand recreational facilities. (3) Active aging: older adults in rural areas demand health education courses, and those in urban areas demand diverse senior citizen courses as well as opportunities to volunteer and build interpersonal relationships. CONCLUSION: The older adults in urban and rural areas had different PHC usage needs. The older adults in rural areas generally focused on medical care and transportation services in PHCs, whereas those in urban areas generally focused on health promotion as a means of social participation and active aging.

Regio-specific enzymatic glucosylation of triterpenoids from Antrodia camphorata and their biological activities.

The bacterial glycosyltransferase YjiC1 was used to glycosylate triterpenoids from the medicinal fungus Antrodia camphorata. Eleven new compounds were obtained from enzymatic reactions. Glucosylation could increase the inhibitory activities against COX-2, and improve the anti-inflammatory activities of Antrodia ergostanes on acute lung injury mice, especially (25R)-antcin C 7-O-ß-D-glucoside.

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals.

Preservation of red blood cell antigenicity in a new storage solution in vitro.

INTRODUCTION: Red blood cell (RBC) storage solution is used for suspending and preserving RBCs for later use in in vitro immunohematology testing. Proper RBC preservation is crucial for obtaining accurate results in RBC phenotyping and pretransfusion antibody screening tests. Haemolysis or RBC antigen degradation during storage can result in inaccurate RBC phenotyping, thereby decreasing the sensitivity of pretransfusion antibody screening and identification assays. The conventional RBC storage solutions usually contain adenosine, adenine, and antibiotics. We designed an RBC storage solution and determined whether it could preserve RBC integrity for 70 days. MATERIALS AND METHODS: The new storage solution has a different formula from that of the conventional solution-in particular, it is strengthened with polyethylene glycol (PEG). The extent of haemolysis and hemagglutination reactivity of the RBC antigen systems, Rh, Duffy, Kidd, Lewis, MNS, P1, and the rare antigen Mia (which has a low prevalence antigen in most parts of the world but a higher prevalence in Taiwan), in the new RBC storage solution was compared with that of the conventionally preserved RBC storage solution. RESULTS: The RBCs preserved in the new solution for 70 days retained a similar haemolysis grade as those preserved in the control solution for 28 days. Although both solutions largely preserved RBC antigenicity, the decline in RBC hemagglutination scores in new solution often occurred later than that in the control solution in most antigen phenotyping assays, especially labile antigens such as D, P1, and M. CONCLUSION: The new solution reduces haemolysis more effectively and preserves antigenicity throughout the 70-day storage period. Moreover, Mia antigen is more stable in the experimental group.

Resistive Switching Crossbar Arrays Based on Layered Materials.

Resistive switching (RS) devices are metal/insulator/metal cells that can change their electrical resistance when electrical stimuli are applied between the electrodes, and they can be used to store and compute data. Planar crossbar arrays of RS devices can offer a high integration density (>108  devices mm- 2 ) and this can be further enhanced by stacking them three-dimensionally. The advantage of using layered materials (LMs) in RS devices compared to traditional phase-change materials and metal oxides is that their electrical properties can be adjusted with a higher precision. Here, the key figures-of-merit and procedures to implement LM-based RS devices are defined. LM-based RS devices fabricated using methods compatible with industry are identified and discussed. The focus is on small devices (size < 9 µm2 ) arranged in crossbar structures, since larger devices may be affected by artifacts, such as grain boundaries and flake junctions. How to enhance device performance, so to accelerate the development of this technology, is also discussed.

Structure and Physical Properties of the Layered Titanium-Based Pnictide Oxides (EuF)2Ti2Pn2O (Pn = Sb, Bi).

We report two novel titanium-based pnictide oxide compounds (EuF)2Ti2Pn2O (Pn = Sb, Bi), which are synthesized by replacing Sr2+ in (SrF)2Ti2Pn2O [Liu, R. H. Structure and Physical Properties of the Layered Pnictide-Oxides: (SrF)2Ti2Pn2O (Pn = As, Sb) and (SmO)2Ti2Sb2O. Chem. Mater. 2010, 22, 1503-1508] with Eu2+ using a solid-state reaction. (EuF)2Ti2Sb2O exhibits an obvious anomaly in resistivity and heat capacity at T ∼ 195 K, which may arise from the spin-density wave/charge-density wave instability. Similar features are also observed in BaTi2Pn2O, (SrF)2Ti2Pn2O, and Na2Ti2Pn2O (Pn = As and Sb) [Liu, R. H. Structure and Physical Properties of the Layered Pnictide-Oxides: (SrF)2Ti2Pn2O (Pn = As, Sb) and (SmO)2Ti2Sb2O. Chem. Mater. 2010, 22, 1503-1508, Ozawa, T. C. Chemistry of layered d-metal pnictide oxides and their potential as candidates for new superconductors. Sci. Technol. Adv. Mater. 2008, 9, 033003, Wang, X. F. Structure and physical properties for a new layered pnictide-oxide: BaTi2As2O. J. Phys.: Condens. Matter. 2010, 22, 075702, and Xu, H. C. Electronic structure of the BaTi2As2O parent compound of the titanium-based oxypnictide superconductor. Phys. Rev. B 2014, 89, 155108]. Magnetic susceptibility measurements indicate an antiferromagnetic transition at T ∼ 2.5 K for (EuF)2Ti2Sb2O. In particular, the electronic specific heat coefficients of both (EuF)2Ti2Sb2O and (EuF)2Ti2Bi2O are significantly enhanced compared to those of (SrF)2Ti2Pn2O, Na2Ti2Pn2O, and BaTi2Pn2O,1,5,6 which may be due to a strong electron correlation effect in this system. Thus, (EuF)2Ti2Pn2O (Pn = Sb, Bi) may provide new platforms for studying density wave, magnetic ordering, and electron correlation effects.

Difficulties and countermeasures in implementing age-friendly policies in primary health centers in Taiwan.

BACKGROUND: Taiwan is predicted to become a super-aged society by 2025, and primary health centers (PHCs) are set to play a crucial role in the care of older adults. The Taiwanese government has developed an age-friendly verification framework for PHC. The aims of this study were to explore the difficulties faced by PHC staff in the implementation of age-friendly policies and their solution strategies. METHODS: This study adopted a qualitative research method. The first stage involved conducting five focus groups with the responsible staff of PHCs (n = 41) that have been certified "age-friendly." The focus groups covered the effectiveness, difficulties, and resources of PHCs in regards to the introduction of age-friendly policies. In the second stage, in-depth interviews were conducted with executives of PHCs (n = 5), both certified and not certified as age-friendly, to further compare the difficulties faced by these two types of PHCs, thereby gaining perspectives for solution strategies. The principles of grounded theory were used for data analysis. RESULTS: Four major PHC strategies are employed in the promotion of age-friendliness. First, organizational management, through which managers apply management methods and analyze the present PHC-related health concerns; second, resource utilization, which refers to the tallying, linking, and integrating of resources; third, business operation process, in which work efficiency is improved through the combination of business operations and staff training; finally, hardware improvement, which is achieved through comprehensive cataloging of facility environments. CONCLUSION: The implementation of age-friendliness in PHCs requires the efforts of both the service units and government. With resources provided by the government, PHCs can integrate management methods, businesses operations, and essential resources. Moreover, PHC executives can lead their teams in promoting age-friendly policies, and closely monitor their effectiveness.

The Associations between Physical Activity, Functional Fitness, and Life Satisfaction among Community-Dwelling Older Adults.

Previous studies showed physical activity had benefits for older adults' life satisfaction, but the mechanism was unclear. This study aimed to investigate whether older adults with more physical activity had better functional fitness and life satisfaction, and whether functional fitness mediated the relationship between physical activity and life satisfaction. A cross-sectional study design was employed, and 623 older adults (73.71 ± 5.91 years) were recruited. Physical activity, functional fitness, life satisfaction, and demographic characteristics were collected. Compared with older adults with low physical activity, those with high (B = 0.41, p = 0.025) and moderate (B = 0.40, p = 0.041) physical activity had better life satisfaction; those with high physical activity had better lower limb muscle strength (B = 1.71, p = 0.001), upper (B = 2.91, p = 0.032) and lower (B = 3.12, p = 0.006) limb flexibility, cardiorespiratory endurance (B = 6.65, p = 0.008), and dynamic balance ability (B = −1.12, p < 0.001). Functional fitness did not mediate the relationship between physical activity and life satisfaction. Promoting physical activity may be useful for increasing older adults' functional fitness and life satisfaction, but the effects on functional fitness only occurred at a high level of physical activity, and the effect of physical activity on life satisfaction was not mediated by functional fitness.

HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth.

We examined the expression and the potential biological function of HBO1 in non-small cell lung cancer (NSCLC). TCGA and Oncomine databases showed that HBO1 transcripts were elevated in NSCLC. Furthermore, in local NSCLC tumor tissues HBO1 expression was higher than that in matched adjacent lung tissues. In primary and immortalized NSCLC cells, HBO1 shRNA robustly inhibited cell viability, proliferation and migration. Moreover, HBO1 knockout by CRISPR/Cas9 induced significant anti-tumor activity in NSCLC cells. Conversely, ectopic HBO1 overexpression in primary NSCLC cells increased proliferation and migration. H3-H4 histone acetylation and expression of several potential oncogenic genes (CCR2, MYLK, VEGFR2 and OCIAD2) were significantly decreased in NSCLC cells with HBO1 silencing or knockout. They were however increased after HBO1 overexpression. Intratumoral injection of HBO1 shRNA-expressing adeno-associated virus hindered the growth of A549 cell xenografts and primary NSCLC cell xenografts in nude mice. H3-H4 histone acetylation as well as expression of HBO1 and HBO1-dependent genes were decreased in HBO1-silenced NSCLC xenograft tissues. An HBO1 inhibitor WM-3835 potently inhibited NSCLC cell growth. Together, HBO1 overexpression promotes NSCLC cell growth.

Endoplasmic Reticulum Stress Mediates Renal Tubular Vacuolation in BK Polyomavirus-Associated Nephropathy.

Objective: This study aimed to explore the molecular mechanism of cytoplasmic vacuolation caused by BK polyomavirus (BKPyV) and thus search for potential target for drug repurposing. Methods: Morphological features of BK polyomavirus-associated nephropathy (BKPyVAN) were studied under light and electron microscopes. Microarray datasets GSE75693, GSE47199, and GSE72925 were integrated by ComBat, and differentially expressed genes (DEGs) were analyzed using limma. Furthermore, the endoplasmic reticulum (ER)-related genes obtained from GenCLiP 2.0 were intersected with DEGs. GO and KEGG enrichment pathways were performed with intersection genes by R package clusterProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was analyzed with a dataset (GSE140989) downloaded from Gene Expression Omnibus (GEO) as control for gene set variation analysis (GSVA). Immunohistochemistry and electron microscopy of kidney sections from drug-induced ERS mouse models were performed to explore the association of ERS and renal tubular vacuolation. Protein-protein interaction (PPI) network of the intersection genes was constructed to identify hub target. AutoDock was used to screen Food and Drug Administration (FDA)-approved drugs that potentially targeted hub gene. Results: Light and electron microscopes exhibited obvious intranuclear inclusions, vacuoles, and virus particles in BKPyV-infected renal tubular cells. Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated genes. GO analysis with the intersection genes illustrated that ERS-related pathways were significantly involved, and KEGG analysis showed a prominent enrichment of MAPK, Toll-like receptor, and chemokine signaling pathways. GSVA analysis of the proximal tubule revealed similar pathways enrichment. An electron microscope image of the kidney from ERS mouse models showed an obvious renal tubular vacuolation with prominent activation of ERS markers verified by immunohistochemistry. Furthermore, DDIT3 was identified as the hub gene based on PPI analysis, and ZINCOOOOO1531009 (Risedronate) was indicated to be a potential drug for DDIT3. Conclusion: ERS was involved in renal tubular cytoplasmic vacuolation in BKPyVAN recipients. Risedronate was screened as a potential drug for BKPyVAN by targeting DDIT3.

Nano-Memristors with 4 mV Switching Voltage Based on Surface-Modified Copper Nanoparticles.

The development of memristors operating at low switching voltages <50 mV can be very useful to avoid signal amplification in many types of circuits, such as those used in bioelectronic applications to interact with neurons and nerves. Here, it is reported that 400 nm-thick films made of dalkyl-dithiophosphoric (DDP) modified copper nanoparticles (CuNPs) exhibit volatile threshold-type resistive switching (RS) at ultralow switching voltage of ≈4 mV. The RS is observed in small nanocells with a lateral size of <50 nm-2 , during hundreds of cycles, and with an ultralow variability. Atomistic calculations reveal that the switching mechanism is related to the modification of the Schottky barriers and insulator-to-metal transition when ionic movement is induced via external bias. The devices are also used to model integrate-and-fire neurons for spiking neural networks and it is concluded that circuits employing DDP-CuNPs consume around ten times less power than similar neurons implemented with a memristor that switches at 40 mV.

Constructing van der Waals heterostructures by dry-transfer assembly for novel optoelectronic device.

Since the first successful exfoliation of graphene, the superior physical and chemical properties of two-dimensional (2D) materials, such as atomic thickness, strong in-plane bonding energy and weak inter-layer van der Waals (vdW) force have attracted wide attention. Meanwhile, there is a surge of interest in novel physics which is absent in bulk materials. Thus, vertical stacking of 2D materials could be critical to discover such physics and develop novel optoelectronic applications. Although vdW heterostructures have been grown by chemical vapor deposition, the available choices of materials for stacking is limited and the device yield is yet to be improved. Another approach to build vdW heterostructure relies on wet/dry transfer techniques like stacking Lego bricks. Although previous reviews have surveyed various wet transfer techniques, novel dry transfer techniques have been recently been demonstrated, featuring clean and sharp interfaces, which also gets rid of contamination, wrinkles, bubbles formed during wet transfer. This review summarizes the optimized dry transfer methods, which paves the way towards high-quality 2D material heterostructures with optimized interfaces. Such transfer techniques also lead to new physical phenomena while enable novel optoelectronic applications on artificial vdW heterostructures, which are discussed in the last part of this review.

Functional Characterization and Protein Engineering of a Triterpene 3-/6-/2'-O-Glycosyltransferase Reveal a Conserved Residue Critical for the Regiospecificity.

Engineering the function of triterpene glucosyltransferases (GTs) is challenging due to the large size of the sugar acceptors. In this work, we identified a multifunctional glycosyltransferase AmGT8 catalyzing triterpene 3-/6-/2'-O-glycosylation from the medicinal plant Astragalus membranaceus. To engineer its regiospecificity, a small mutant library was built based on semi-rational design. Variants A394F, A394D, and T131V were found to catalyze specific 6-O, 3-O, and 2'-O glycosylation, respectively. The origin of regioselectivity of AmGT8 and its A394F variant was studied by molecular dynamics and hydrogen deuterium exchange mass spectrometry. Residue 394 is highly conserved as A/G and is critical for the regiospecificity of the C- and O-GTs TcCGT1 and GuGT10/14. Finally, astragalosides III and IV were synthesized by mutants A394F, T131V and P192E. This work reports biocatalysts for saponin synthesis and gives new insights into protein engineering of regioselectivity in plant GTs.

Consideration factors of older adults seeking medical treatment at outpatient services in Taiwan.

BACKGROUND: Taiwan will become a super-aged society by 2025, leading to the more frequent use of outpatient services by older adults for medical treatment compared with other age groups. Understanding the outpatient service consideration factors of older adults seeking medical treatment can improve health care quality. This study explored the selection factors and crucial considerations of older adults for outpatient services. METHODS: Qualitative study was conducted. Purposive sampling was used to recruit 16 older adults over 65 years of age with chronic disease who were patients of an internal medicine department and regularly returned for checkups. Data including reasons for receiving medical treatment, factors affecting their choice of hospitals, and health care and environmental considerations were collected through structured interviews. RESULTS: The older adults identified four factors. (1) The care of doctors: The doctors possessed professional skill, allocate sufficient consultation time, and undertake effective communication. (2) The care of other medical professionals: Other medical professionals provided services in a cordial manner. (3) The accessibility and convenience of outpatient services: Convenient transportation and registration as well as short consultation wait time. (4) Environment and equipment: The hospital had the novel facilities and satisfactory barrier-free equipment. CONCLUSIONS: The older adults cared most about the adequacy of diagnosis and treatment by doctors and other medical professionals. In addition, they reported having higher satisfaction with hospitals that provide comprehensive medical facilities, fast and convenient medical procedures, and short wait times.

In Situ Observation of Low-Power Nano-Synaptic Response in Graphene Oxide Using Conductive Atomic Force Microscopy.

Multiple studies have reported the observation of electro-synaptic response in different metal/insulator/metal devices. However, most of them analyzed large (>1 µm2 ) devices that do not meet the integration density required by industry (1010  devices/mm2 ). Some studies emploied a scanning tunneling microscope (STM) to explore nano-synaptic response in different materials, but in this setup there is a nanogap between the insulator and one of the metallic electrodes (i.e., the STM tip), not present in real devices. Here, it is demonstrated how to use conductive atomic force microscopy to explore the presence and quality of nano-synaptic response in confined areas <50 nm2 . Graphene oxide (GO) is selected due to its easy fabrication. Metal/GO/metal nano-synapses exhibit potentiation and paired pulse facilitation with low write current levels <1 µA (i.e., power consumption ≈3 µW), controllable excitatory post-synaptic currents, and long-term potentiation and depression. The results provide a new method to explore nano-synaptic plasticity at the nanoscale, and point to GO as an important candidate for the fabrication of ultrasmall (<50 nm2 ) electronic synapses fulfilling the integration density requirements of neuromorphic systems.