Optically Readable Organic Electrochemical Synaptic Transistors for Neuromorphic Photonic Image Processing.

Optically readable organic synaptic devices have great potential in both artificial intelligence and photonic neuromorphic computing. Herein, a novel optically readable organic electrochemical synaptic transistor (OR-OEST) strategy is first proposed. The electrochemical doping mechanism of the device was systematically investigated, and the basic biological synaptic behaviors that can be read by optical means are successfully achieved. Furthermore, the flexible OR-OESTs are capable of electrically switching the transparency of semiconductor channel materials in a nonvolatile manner, and thus the multilevel memory can be achieved through optical readout. Finally, the OR-OESTs are developed for the preprocessing of photonic images, such as contrast enhancement and denoising, and feeding the processed images into an artificial neural network, achieving a recognition rate of over 90%. Overall, this work provides a new strategy for the implementation of photonic neuromorphic systems.

Halide perovskite photoelectric artificial synapses: materials, devices, and applications.

In recent years, there has been a research boom on halide perovskites (HPs) whose outstanding performance in photovoltaic and optoelectronic fields is obvious to all. In particular, HP materials find application in the development of artificial synapses. HP-based synapses have great potential for artificial neuromorphic systems, which is due to their outstanding optoelectronic properties, femtojoule-level energy consumption, and simple fabrication process. In this review, we present the physical properties of HPs and describe two types of synaptic devices including two-terminal (2T) memristors and three-terminal (3T) transistors. The HP layer in 2T memristors can realize the change in the device conductance through physical mechanisms dominated by ion migration. On the other hand, HPs in 3T transistors can be used as efficient light-absorbing layers and rely on some special device structures to provide reliable current changes. In the final section of the article, we discuss some of the existing applications of HP-based synapses and bottlenecks to be solved.

Retraction Notice to: A Novel Mechanism of Doxorubicin Resistance and Tumorigenesis Mediated by MicroRNA-501-5p-Suppressed BLID.

[This retracts the article DOI: 10.1016/j.omtn.2018.06.011.].

Artificial Vision Adaption Mimicked by an Optoelectrical In2O3 Transistor Array.

Simulation of biological visual perception has gained considerable attention. In this paper, an optoelectrical In2O3 transistor array with a negative photoconductivity behavior is designed using a side-gate structure and a screen-printed ion-gel as the gate insulator. This paper is the first to observe a negative photoconductivity in electrolyte-gated oxide devices. Furthermore, an artificial visual perception system capable of self-adapting to environmental lightness is mimicked using the proposed device array. The transistor device array shows a self-adaptive behavior of light under different levels of light intensity, successfully demonstrating the visual adaption with an adjustable threshold range to the external environment. This study provides a new way to create an environmentally adaptive artificial visual perception system and has far-reaching significance for the future of neuromorphic electronics.

Combination of pathological and spectroscopic characterization to promote diagnosis of retinal pigment epithelium-Bruch's membrane complex in a diabetic rat model.

Diabetic retinopathy (DR) is a common condition of diabetes, and approaches to detecting early DR using the unique characteristics of the retinal pigment epithelium-Bruch's membrane complex (RBC) have increasingly attracted attention. A diabetic model was established in Sprague-Dawley rats via streptozocin (STZ) injection for 1 (DM1) and 6 months (DM6), confirmed by weekly blood glucose measurement. Serum and retinal tissue-based advanced glycation endproducts (AGE) levels significantly elevated in diabetic rats, and RBC was evaluated by transmission electron microscopy and Raman spectroscopy. The results showed that whole Raman spectra and all marked band intensities could respectively achieve almost equal and accurate discrimination of all animal groups, along with the determination of important molecules from the band data. Further quantitative analyses indicated series of metabolic disturbance due to hyperglycemia were involved while the body self-regulation mechanism still played a role with different effects during the disease progression. Given this, Raman spectroscopy can reliably distinguish the early characterization of DR in addition to providing intrinsic key molecules that is sensitive to identify the early disease progression.

Cytological and spectroscopic characteristics of c-KIT N822K mutation in core binding factor acute myeloid leukemia cells.

The frequency of N822K mutation is high in the A-loop region of c-KIT which is highly associated with poor prognosis of core binding factor acute myeloid leukemia. The current work used common assays including cell cycle, apoptosis, clone formation and western blot to perform cytological detection for HL60 (wild type), NB4 (carrying t[15;17] chromosome translocation) and Kasumi-1 (with c-KIT N822K mutation); and meanwhile, the laser tweezers Raman spectroscopy (LTRS) was also used to perform label-free detection of single living cells. The results demonstrated that Kasumi-1 cell line bearing c-KIT N822K mutation has a stable cell cycle, while there was a significant difference between early and late apoptosis within 48 hours. The LTRS detection initially reflected the spectral differences induced by genetic abnormalities and highlighted progressive patterns of DNA and amino acids band contents which were appropriately consistent with that of cell clone ratio and the c-KIT phosphorylation level. It is concluded that methodology of LTRS-based single living cell characterization could be potential and effective to reveal gene mutation-induced cell differentiation.

Study on the chemodrug-induced effect in nasopharyngeal carcinoma cells using laser tweezer Raman spectroscopy.

To explore the effect in nasopharyngeal carcinoma (NPC) cells after treatment with chemodrugs, Raman profiles were characterized by laser tweezer Raman spectroscopy. Two NPC cell lines (CNE2 and C666-1) were treated with gemcitabine, cisplatin, and paclitaxel, respectively. The high-quality Raman spectra of cells without or with treatments were recorded at the single-cell level with label-free laser tweezers Raman spectroscopy (LTRS) and analyzed for the differences of alterations of Raman profiles. Tentative assignments of Raman peaks indicated that the cellular specific biomolecular changes associated with drug treatment include changes in protein structure (e.g. 1655 cm-1), changes in DNA/RNA content and structure (e.g. 830 cm-1), destruction of DNA/RNA base pairs (e.g. 785 cm-1), and reduction in lipids (e.g. 970 cm-1). Besides, both principal components analysis (PCA) combined with linear discriminant analysis (LDA) and the classification and regression trees (CRT) algorithms were employed to further analyze and classify the spectral data between control group and treated group, with the best discriminant accuracy of 96.7% and 90.0% for CNE2 and C666-1 group treated with paclitaxel, respectively. This exploratory work demonstrated that LTRS technology combined with multivariate statistical analysis has promising potential to be a novel analytical strategy at the single-cell level for the evaluation of NPC-related chemotherapeutic drugs.

Fabrication of Fe3O4/Au@ATP@Ag Nanorod sandwich structure for sensitive SERS quantitative detection of histamine.

We have successfully prepared a highly sensitive sandwich nanosensor combined Fe3O4 and Au@ATP@Ag nanorods for histamine detection based on surface-enhanced Raman spectroscopy (SERS). The Fe3O4 beads with -COOH served as a capture part to enrich histamine. The Au@ATP@Ag core-shell nanorods functionalized with Nalpha,Nalpha-Bis(carboxymethyl)-l-lysine (AB-NTA) were then used to connect with the imidazolyl group of histamine, simultaneously the internal standard 4-aminothiophenol (4-ATP) in the core-shell structure was used as the SERS signal. PLS regression model based on concentration range 10-3-10-8mol/L showed a linear trend with R2 = 0.9907. Our new approach can quickly and reliably determine histamine in fish sample and RAW264.7 cell lysates. This protocol for histamine extraction and SERS analysis enables the development of ultra-sensitive method for histamine detection.

Serum analysis method combining cellulose acetate membrane purification with surface-enhanced Raman spectroscopy for non-invasive HBV screening.

A highly sensitive, non-invasive, and rapid HBV (Hepatitis B virus) screening method combining membrane protein purification with silver nanoparticle-based surface-enhanced Raman scattering (SERS) spectroscopy was developed in this study. Reproducible serum protein SERS spectra were obtained from cellulose acetate membrane-purified human serum from 94 HBV patients and 89 normal groups. Tentative assignments of serum protein SERS spectra showed that the HBV patients primarily led to specific biomedical changes of serum protein. Principal components analysis and linear discriminate analysis were introduced to analyse the obtained spectra, with the diagnostic sensitivity of 92.6% and specificity of 77.5% were achieved for differentiating HBV patients from normal groups.

The Impact of Opening a Medical Step-Down Unit on Medically Critically Ill Patient Outcomes and Throughput: A Difference-in-Differences Analysis.

OBJECTIVE: To understand the impact of adding a medical step-down unit (SDU) on patient outcomes and throughput in a medical intensive care unit (ICU). DESIGN: Retrospective cohort study. SETTING: Two academic tertiary care hospitals within the same health-care system. PATIENTS: Adults admitted to the medical ICU at either the control or intervention hospital from October 2013 to March 2014 (preintervention) and October 2014 to March 2015 (postintervention). INTERVENTIONS: Opening a 4-bed medical SDU at the intervention hospital on April 1, 2014. MEASUREMENTS AND MAIN RESULTS: Using standard summary statistics, we compared patients across hospitals. Using a difference-in-differences approach, we quantified the association of opening an SDU and outcomes (hospital mortality, hospital and ICU length of stay [LOS], and time to transfer to the ICU) after adjustment for secular trends in patient case-mix and patient-level covariates which might impact outcome. We analyzed 500 (245 pre- and 255 postintervention) patients in the intervention hospital and 678 (323 pre- and 355 postintervention) in the control hospital. Patients at the control hospital were younger (60.5-60.6 vs 64.0-65.4 years, P < .001) with a higher severity of acute illness at the time of evaluation for ICU admission (Sequential Organ Failure Assessment score: 4.9-4.0 vs 3.9-3.9, P < .001). Using the difference-in-differences methodology, we identified no association of hospital mortality (odds ratio [95% confidence interval]: 0.81 [0.42 to 1.55], P = .52) or hospital LOS (% change [95% confidence interval]: -8.7% [-28.6% to 11.2%], P = .39) with admission to the intervention hospital after SDU opening. The ICU LOS overall was not associated with admission to the intervention hospital in the postintervention period (-23.7% [-47.9% to 0.5%], P = .06); ICU LOS among survivors was significantly reduced (-27.5% [-50.5% to -4.6%], P = .019). Time to transfer to ICU was also significantly reduced (-26.7% [-44.7% to -8.8%], P = .004). CONCLUSIONS: Opening our medical SDU improved medical ICU throughput but did not affect more patient-centered outcomes of hospital mortality and LOS.

Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer.

Exosomal transfer of oncogenic miRNAs can enhance recipient cell growth, metastasis and chemoresistance. Currently we found that microRNA-501-5p (miR-501) was overexpressed in doxorubicin-resistant gastric cancer (GC) SGC7901/ADR cell-secreted exosomes (ADR Exo) than that in SGC7901 cell-secreted exosomes (7901 Exo). ADR Exo was internalized by SGC7901, and a Cy3-miR-501 mimic was transferred from SGC7901/ADR to SGC7901 via exosomes. ADR Exo conferred doxorubicin resistance, proliferation, migration and invasion abilities to negative control miRNA inhibitor-expressing GC cells, whereas it inhibited apoptosis. MiR-501 knockdown or BH3-like motif-containing protein, cell death inducer (BLID) overexpression could reverse the effects of ADR Exo on recipient cells. SGC7901 cells cocultured with SGC7901/ADR prior to treatment with GW4869 or transfection of a miR-501 inhibitor were sensitive to doxorubicin and exhibited attenuated proliferation, migration and invasion and increased apoptosis. The intratumoral injection of ADR Exo into negative control miRNA inhibitor-expressing SGC7901 cells induced rapid subcutaneous tumor growth and resistance to doxorubicin compared to that of miR-501 knockdown or BLID-overexpressing cells. This effect is possibly achieved by exosomal miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/-3 and phosphorylation of Akt. Exosomal miR-501 might be a therapeutic target for GC.

Rapid discrimination of colon cancer cells with single base mutation in KRAS gene segment using laser tweezers Raman spectroscopy.

Laser tweezers Raman spectroscopy (LTRS) as a label-free and noninvasive technology has been proven to be an ideal tool for analysis of single living cells, which provides important fingerprint information without interference from surrounding environments. For the first time, LTRS system was successfully used to examine the colon cancer cells with single base mutation in KRAS gene segment, including DKS-8 (KRAS wild-type [WT]) and DLD-1 (KRAS mutant-type [MT]), HKE-3 (KRAS WT) and HCT-116 (KRAS MT). Spectra changes of some vital biomolecules due to the gene mutation state were sensitively recorded by our home-made LTRS system. As a result of the comparison between DKS-8 and DLD-1 cells, an index of 97.5% of correct classification was obtained by combining LTRS with principle component analysis coupled with linear discriminant analysis (PCA-LDA) statistical analysis, while an index of 97.0% of correct classification was achieved between HKE-3 and HCT-116 cells. Moreover, between WT cells (DKS-8 and HKE-3) vs MT cells (DLD-1 and HCT-116), the index of correct classification was 81.2%, which was quite encouraging. Our preliminary results showed that the LTRS system coupled with PCA-LDA analysis will have a great potential for further applications in the rapid and label-free detection of circulating tumor cells in liquid biopsy.

A Novel Mechanism of Doxorubicin Resistance and Tumorigenesis Mediated by MicroRNA-501-5p-Suppressed BLID.

Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood. In this study, we identified that BLID (BH3-like motif-containing protein, cell death inducer) was directly regulated by miR-501 at the post-transcriptional level in multiple gastric cancer cell lines. Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR-501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin, and enhanced cell proliferation, migration, and invasion. Subcutaneous injection of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of xenograft tumors and resistance to doxorubicin treatment, unlike injection of negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least partially by directly targeting BLID and subsequent inactivation of caspase-9 and caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin resistance and enhances the tumorigenesis of gastric cancer cells by suppressing BLID. miR-501 might be a potential target for doxorubicin resistance and gastric cancer therapy.

Facile Ag-Film Based Surface Enhanced Raman Spectroscopy Using DNA Molecular Switch for Ultra-Sensitive Mercury Ions Detection.

Heavy metal pollution has long been the focus of attention because of its serious threat to human health and the environment. Surface enhanced Raman spectroscopy (SERS) has shown great potential for metal detection owing to many advantages, including, requiring fewer samples, its minimal damage to specimen, and its high sensitivity. In this work, we proposed a simple and distinctive method, based on SERS, using facile silver film (Ag-film) combined with a DNA molecular switch, which allowed for the highly specific detection of heavy metal mercury ions (Hg2+). When in the presence of Hg2+ ions, the signals from Raman probes attach to single-stranded DNA, which will be dramatically enhanced due to the specific structural change of DNA strands-resulting from the interaction between Hg2+ ions and DNA bases. This SERS sensor could achieve an ultralow limit of detection (1.35 × 10-15 M) for Hg2+ detection. In addition, we applied this SERS sensor to detect Hg2+ in real blood samples. The results suggested that this SERS platform could be a promising alternative tool for Hg2+ detection in clinical, environmental, and food inspection.

Horizontal transfer of exosomal CXCR4 promotes murine hepatocarcinoma cell migration, invasion and lymphangiogenesis.

Exosomes have been demonstrated as an important factor to influence cancer invasion and metastasis. Previous studies have shown that CXC chemokine recepter-4 (CXCR4) and stromal cell-derived factor-1α (SDF-1α) mediates matrix metalloproteinases (MMPs) secretions to facilitate lymph node metastasis of hepatocarcinoma cells. In this study, we demonstrated that exosomes containing elevated CXCR4 from high lymph node metastatic mouse hepatocarcinoma Hca-F cells were able to promote the migration and invasion of a paired syngeneic Hca-P cells that have low metastatic potential. Such impact on enhanced migratory and invasive capacities of Hca-P cells was triggered by the internalization of exosomes isolated from Hca-F cells. This was possibly due to the horizontal transferring of CXCR4 via exosomes. The lymphatic endothelial cells (LECs) increased the migration and invasion of Hca-F cells probably by expressing SDF-1α which bound with CXCR4 in the Hca-F cells and subsequently enhanced the secretions of MMP-9, MMP-2 and vascular endothelial growth factor C (VEGF-C). Exosomal CXCR4 from Hca-F cells promoted LECs proliferative rate and lymphatic tube formation ability. Our findings suggest that horizontal transfer of exosomal CXCR4 can promote murine hepatocarcinoma cell migration, invasion and lymphangiogenesis, and exosomal CXCR4 might be a novel therapeutic target against tumor lymphatic metastasis.

miR-501 is upregulated in cervical cancer and promotes cell proliferation, migration and invasion by targeting CYLD.

BACKGROUND: Cervical cancer is the common gynecological deadly malignancy worldwide. Here we attempted to evaluate the effects and mechanisms of microRNA-501-5p (miR-501) on the cell proliferation, migration, invasion and the clinical significance in the cervical cancer. METHODS: Cervical cancer HeLa cells were transfected with miR-501 mimic or inhibitor or siRNA against Cylindromatosis (CYLD) using Lipofectamine 2000. miR-501 expression was assessed in HeLa cells and cervical cancer specimens by real-time qRT-PCR. The functional roles of miR-501 were determined by CCK-8, colony formation, scratch wound healing and transwell assays. The apoptosis rate was detected by flow cytometry assay. CYLD, BCL-2, BAX, NF-κB p65 and phosphorylated p65 (p-p65) proteins were examined by Western blotting. CYLD expression was evaluated by immunohistochemistry in cervical cancer tissues. RESULTS: miR-501 was upregulated, whereas CYLD protein was downregulated in cervical cancer tissues compared to normal cervical tissues. miR-501 overexpression and CYLD protein downregulation were positively correlated with poor differentiation, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. CYLD was downregulated by miR-501 at both mRNA and protein levels in HeLa cells. miR-501 promoted cell proliferation, migration and invasion in cervical cancer, while inhibited the apoptosis. This is possibly due to the downregulation of CYLD and subsequent activation of NF-κB p65. CONCLUSIONS: miR-501 upregulation and CYLD downregulation are associated with the development and progression of cervical cancer. miR-501 promotes cervical cancer cell proliferation, migration and invasion possibly via downregulating CYLD and subsequently activating NF-κB p65. miR-501 might be a potential therapeutic target for cervical cancer.

The Impact of Adding a Physician Assistant to a Critical Care Outreach Team.

RATIONALE: Hospitals are increasingly using critical care outreach teams (CCOTs) to respond to patients deteriorating outside intensive care units (ICUs). CCOT staffing is variable across hospitals and optimal team composition is unknown. OBJECTIVES: To assess whether adding a critical care medicine trained physician assistant (CCM-PA) to a critical care outreach team (CCOT) impacts clinical and process outcomes. METHODS: We performed a retrospective study of two cohorts-one with a CCM-PA added to the CCOT (intervention hospital) and one with no staffing change (control hospital)-at two facilities in the same system. All adults in the emergency department and hospital for whom CCOT consultation was requested from October 1, 2012-March 16, 2013 (pre-intervention) and January 5-March 31, 2014 (post-intervention) were included. We performed difference-in-differences analyses comparing pre- to post-intervention periods in the intervention versus control hospitals to assess the impact of adding the CCM-PA to the CCOT. MEASUREMENTS AND MAIN RESULTS: Our cohort consisted of 3,099 patients (control hospital: 792 pre- and 595 post-intervention; intervention hospital: 1114 pre- and 839 post-intervention). Intervention hospital patients tended to be younger, with fewer comorbidities, but with similar severity of acute illness. Across both periods, hospital mortality (p = 0.26) and hospital length of stay (p = 0.64) for the intervention vs control hospitals were similar, but time-to-transfer to the ICU was longer for the intervention hospital (13.3-17.0 vs 11.5-11.6 hours, p = 0.006). Using the difference-in-differences approach, we found a 19.2% reduction (95 confidence interval: 6.7%-31.6%, p = 0.002) in the time-to-transfer to the ICU associated with adding the CCM-PA to the CCOT; we found no difference in hospital mortality (p = 0.20) or length of stay (p = 0.52). CONCLUSIONS: Adding a CCM-PA to the CCOT was associated with a notable reduction in time-to-transfer to the ICU; hospital mortality and length of stay were not impacted.