Self-Powered Biomimetic Pressure Sensor Based on Mn-Ag Electrochemical Reaction for Monitoring Rehabilitation Training of Athletes.

Self-powered pressure detection using smart wearable devices is the subject of intense research attention, which is intended to address the critical need for prolonged and uninterrupted operations. Current piezoelectric and triboelectric sensors well respond to dynamic stimuli while overlooking static stimuli. This study proposes a dual-response potentiometric pressure sensor that responds to both dynamic and static stimuli. The proposed sensor utilizes interdigital electrodes with MnO2/carbon/polyvinyl alcohol (PVA) as the cathode and conductive silver paste as the anode. The electrolyte layer incorporates a mixed hydrogel of PVA and phosphoric acid. The optimized interdigital electrodes and sandpaper-like microstructured surface of the hydrogel electrolyte contribute to enhanced performance by facilitating an increased contact area between the electrolyte and electrodes. The sensor features an open-circuit voltage of 0.927 V, a short-circuit current of 6 µA, a higher sensitivity of 14 mV/kPa, and outstanding cycling performance (>5000 cycles). It can accurately recognize letter writing and enable capacitor charging and LED lighting. Additionally, a data acquisition and display system employing the proposed sensor, which facilitates the monitoring of athletes' rehabilitation training, and machine learning algorithms that effectively guide rehabilitation actions are presented. This study offers novel solutions for the future development of smart wearable devices.

Colocalization of protein and microRNA markers reveals unique extracellular vesicle subpopulations for early cancer detection.

Extracellular vesicles (EVs) play important roles in cell-cell communication but are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm with very limited amounts of cargos encapsulated. The technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) reported in the present work permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, thus enables colocalization assessment for selected protein and microRNA (miRNA) markers in the EVs produced by various cell lines, or present in clinical sera samples. EV subpopulations marked by the colocalization of unique protein and miRNA combinations were discovered to be able to detect early-stage (stage I or II) breast cancer (BC). NOBEL-SPA can be adapted to analyze other types of cargo molecules or other small submicron biological particles. Study of the sorting of specific cargos to heterogeneous vesicles under different physiological conditions can help discover distinct vesicle subpopulations valuable in clinical examination and therapeutics development and gain better understanding of their biogenesis.

Lung Fibroblasts Take up Breast Cancer Cell-derived Extracellular Vesicles Partially Through MEK2-dependent Macropinocytosis.

Extracellular vesicles (EV) have emerged as critical effectors in the cross-talk between cancer and normal cells by transferring intracellular materials between adjacent or distant cells. Previous studies have begun to elucidate how cancer cells, by secreting EVs, adapt normal cells at a metastatic site to facilitate cancer cell metastasis. In this study, we utilized a high-content microscopic screening platform to investigate the mechanisms of EV uptake by primary lung fibroblasts. A selected library containing 90 FDA-approved anticancer drugs was screened for the effect on fibroblast uptake of EVs from MDA-MB-231 breast cancer cells. Among the drugs identified to inhibit EV uptake without exerting significant cytotoxicity, we validated the dose-dependent effect of Trametinib (a MEK1/2 inhibitor) and Copanlisib (a PI3K inhibitor). Trametinib suppressed macropinocytosis in lung fibroblasts and inhibited EV uptake with a higher potency comparing with Copanlisib. Gene knockdown and overexpression studies demonstrated that uptake of MDA-MB-231 EVs by lung fibroblasts required MEK2. These findings provide important insights into the mechanisms underlying lung fibroblast uptake of breast cancer cell-derived EVs, which could play a role in breast cancer metastasis to the lungs and suggest potential therapeutic targets for preventing or treating this deadly disease. SIGNIFICANCE: Through a phenotypic screen, we found that MEK inhibitor Trametinib suppressed EV uptake and macropinocytosis in lung fibroblasts, and that EV uptake is mediated by MEK2 in these cells. Our results suggest that MEK2 inhibition could serve as a strategy to block cancer EV uptake by lung fibroblasts.

Recent development of manganese dioxide-based materials as zinc-ion battery cathode.

The development of advanced cathode materials for zinc-ion batteries (ZIBs) is a critical step in building large-scale green energy conversion and storage systems in the future. Manganese dioxide is one of the most well-studied cathode materials for zinc-ion batteries due to its wide range of crystal forms, cost-effectiveness, and well-established synthesis processes. This review describes the recent research progress of manganese dioxide-based ZIBs, and the reaction mechanism, electrochemical performance, and challenges of manganese dioxide-based ZIBs materials are systematically introduced. Optimization strategies for high-performance manganese dioxide-based materials for ZIBs with different crystal forms, nanostructures, morphologies, and compositions are discussed. Finally, the current challenges and future research directions of manganese dioxide-based cathodes in ZIBs are envisaged.

Characterization of hypoxia-responsive states in ovarian cancer to identify hot tumors and aid adjuvant therapy.

BACKGROUNDS: The hypoxia-responsive state of cancer is a complex pathophysiological process involving numerous genes playing different roles. Due to the rapid proliferation of cancer cells and chaotic angiogenesis, the clinical features of hypoxia-responsive states are not yet clear in patients with ovarian cancer. METHODS: Based on the RNA expression levels of 14 hypoxic markers, our study screened out hypoxia-related genes and construct a hypoxic score pattern to quantify the hypoxia-responsive states of a single tumor. Combining clinical prognosis, tumor mutation burden, microsatellite instability, the expression level of the immune checkpoint, IC50, and other indicators to evaluate the impact of different hypoxia-responsive states on clinical prognosis and therapeutic sensitivity. RESULTS: Our study identified a subgroup with an active hypoxia-responsive state and they have a worse clinical prognosis but exhibit higher immunogenicity and higher sensitivity to immunotherapy. CONCLUSIONS: This work revealed that hypoxia-responsive states played an important role in formation of tumor immunogenicity. Evaluating the hypoxia-responsive state will contribute to guiding more effective immunotherapy strategies.

Non-Equilibrium Assembly of Atomically-Precise Copper Nanoclusters.

Accurate structure control in dissipative assemblies is vital for precise biological functions. However, the accuracy and functionality of current artificial dissipative assembly are far from this objective. Herein, we introduce a novel approach by harnessing complex chemical reaction networks (CRN) rooted in coordination chemistry to create well-defined dissipative assemblies. We designed atomically-precise Cu nanocluster (CuNCs), specifically Cu11 (µ9 -Cl)(µ3 -Cl)3 L6 Cl clusters (L = 4-methyl-piperazine-1-carbodithioate). Cu(I)-ligand ratio change and dynamic Cu(I)-Cu(I) metallophilic/coordination interactions enable the reorganization of CuNCs into metastable CuL2 , finally converting into the equilibrium [CuL·Y]Cl complexes (Y = MeCN or H2 O) via Cu(I) oxidation/reorganization and ligand exchange process. Upon adding fuels (ascorbic acid, AA), the system goes further dissipative cycles. We observed that the encapsulated/bridging halide ions exert a subtle influence on the optical properties of CuNCs and topological changes of polymeric networks when integrating CuNCs as crosslink sites. CuNCs duration and switch period could be controlled by varying the ions, AA concentration, O2 pressure and pH. The unique Cu(I)-Cu(I) metallophilic and coordination interactions provide a versatile toolbox for designing delicate life-like materials, paving the way for tailored dissipative assemblies with precise structures and functionalities. Furthermore, these CuNCs can be employed as modular units within polymers for materials mechanics or functionalization studies, expanding their potential applications. This article is protected by copyright. All rights reserved.

CXCL10 and Nrf2-upregulated mesenchymal stem cells reinvigorate T lymphocytes for combating glioblastoma.

BACKGROUND: Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods. METHODS: In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encoding Cxcl10, Nrf2 (an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments' efficacy and mechanism. RESULTS: CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+ T cells, interferon-γ+ cytotoxic T lymphocytes (CTLs), GzmB+ CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+ and exhausted CD4+ T cells. CONCLUSIONS: MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.

Modified intraoperative temperature management prevents prolonged length of stay after head and neck surgery with free flap reconstruction.

The present study aimed to investigate the association between intraoperative body temperature and prolonged length of stay (PLOS) after free flap reconstruction. A total of 753 patients who underwent head and neck surgery with free flap reconstruction were collected and randomly assigned into primary and validation cohorts. In the primary cohort, univariable and multivariable analyses were conducted to evaluate associations between intraoperative time-weighted (TW) temperature (TW average [TWA] temperature, TW hypothermia and TW hyperthermia) and PLOS. Nomograms were developed with and without intraoperative TW temperature, and validated in the validation cohort. Severe intraoperative TW hypothermia (OR = 1.004; 95% CI: 1.000, 1.007; p = 0.032) was identified as an independent risk factor for PLOS. Intraoperative TWA temperature and TW hypothermia showed linear related predictive effect for PLOS. The nomogram incorporating intraoperative TW temperature showed higher C-index (0.652, 95% CI: 0.591, 0.713) and improved net reclassification improvement for non-event (0.277, 95% CI: 0.118, 0.435; p < 0.001). Lower TWA temperature with mild TW hypothermia had a preventive effect on PLOS with a linear association, which may provide a modified range for intraoperative temperature management. The proposed nomogram incorporating intraoperative TW temperature could be used to develop personalized preventive strategies for PLOS after free flap reconstruction. IRB NUMBER: SYSEC-KY-KS-2022-037. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

Preoperative flurbiprofen diminishes the rate of reoperation after free flap reconstruction: A retrospective study.

This study aimed to evaluate the association between preoperative flurbiprofen, a non-selective COX inhibitor, and reoperation for flap crisis after free flap reconstruction. In this retrospective study, patients who underwent head and neck surgery with free flap reconstructions were collected. To identify risk factors for reoperation from demographic features and perioperative variables, univariate and multivariate logistic analyses were conducted. After propensity score matching (PSM), univariate and adjusted multivariate analyses were employed to explore the impact of preoperative flurbiprofen on reoperation after free flap reconstruction. This study comprised 437 patients, 33 of whom underwent reoperations for flap crisis. After multivariate analysis, radiotherapy history (P = 0.005; odds ratio [OR] = 0.225; 95% CI, 0.080-0.636) and preoperative flurbiprofen (P = 0.038; OR = 5.059; 95% CI, 1.094-23.386) were identified as independent factors for reoperation. PSM was achieved, and preoperative flurbiprofen was found to diminish the reoperation rate (P = 0.046; OR = 4.765; 95% CI, 1.029-22.202) without increasing bleeding complications. Within the limitations of the study, flurbiprofen should be administered preoperatively to reduce the rate of reoperations for flap crisis whenever appropriate.

Nomogram incorporating potent inflammatory indicators for overall survival estimation of patients with primary oral squamous cell carcinoma.

Background: Inflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC). Methods: 469 patients' inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed. Results: A high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P<0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246-4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P<0.001) and AUC. Conclusions: LMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.

Flexible In-Ga-Zn-N-O synaptic transistors for ultralow-power neuromorphic computing and EEG-based brain-computer interfaces.

Designing low-power and flexible artificial neural devices with artificial neural networks is a promising avenue for creating brain-computer interfaces (BCIs). Herein, we report the development of flexible In-Ga-Zn-N-O synaptic transistors (FISTs) that can simulate essential and advanced biological neural functions. These FISTs are optimized to achieve ultra-low power consumption under a super-low or even zero channel bias, making them suitable for wearable BCI applications. The effective tunability of synaptic behaviors promotes the realization of associative and non-associative learning, facilitating Covid-19 chest CT edge detection. Importantly, FISTs exhibit high tolerance to long-term exposure under an ambient environment and bending deformation, indicating their suitability for wearable BCI systems. We demonstrate that an array of FISTs can classify vision-evoked EEG signals with up to ∼87.9% and 94.8% recognition accuracy for EMNIST-Digits and MindBigdata, respectively. Thus, FISTs have enormous potential to significantly impact the development of various BCI techniques.

Cancer-cell-secreted extracellular vesicles target p53 to impair mitochondrial function in muscle.

Skeletal muscle loss and weakness are associated with bad prognosis and poorer quality of life in cancer patients. Tumor-derived factors have been implicated in muscle dysregulation by inducing cachexia and apoptosis. Here, we show that extracellular vesicles secreted by breast cancer cells impair mitochondrial homeostasis and function in skeletal muscle, leading to decreased mitochondrial content and energy production and increased oxidative stress. Mechanistically, miR-122-5p in cancer-cell-secreted EVs is transferred to myocytes, where it targets the tumor suppressor TP53 to decrease the expression of TP53 target genes involved in mitochondrial regulation, including Tfam, Pgc-1α, Sco2, and 16S rRNA. Restoration of Tp53 in muscle abolishes mitochondrial myopathology in mice carrying breast tumors and partially rescues their impaired running capacity without significantly affecting muscle mass. We conclude that extracellular vesicles from breast cancer cells mediate skeletal muscle mitochondrial dysfunction in cancer and may contribute to muscle weakness in some cancer patients.

Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice.

Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150flox/flox mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response.

Altered structural covariance of locus coeruleus in individuals with significant memory concern and patients with mild cognitive impairment.

The locus coeruleus (LC) is the site where tau accumulation is preferentially observed pathologically in Alzheimer's disease (AD) patients, but the changes in gray matter co-alteration patterns between the LC and the whole brain in the predementia phase of AD remain unclear. In this study, we estimated and compared the gray matter volume of the LC and its structural covariance (SC) with the whole brain among 161 normal healthy controls (HCs), 99 individuals with significant memory concern (SMC) and 131 patients with mild cognitive impairment (MCI). We found that SC decreased in MCI groups, which mainly involved the salience network and default mode network. These results imply that seeding from LC, the gray matter network disruption and disconnection appears early in the MCI group. The altered SC network seeding from the LC can serve as an imaging biomarker for discriminating the patients in the potential predementia phase of AD from the normal subjects.

Genetic liability to multi-site chronic pain increases the risk of cardiovascular disease.

BACKGROUND: Observational studies have shown associations between multi-site chronic pain (MCP) and cardiovascular disease. However, it remains unclear whether these associations are causal. Therefore, this study aimed to assess the causal associations between MCP and cardiovascular disease and identify possible mediators between them. METHODS: A two-sample Mendelian randomisation analysis was applied in this study. The summary data for MCP were obtained from a genome-wide association study that included 387 649 individuals from the UK Biobank, whereas summary-level data for cardiovascular disease and its subtypes were obtained from relevant genome-wide association studies. Finally, summary-level data for common cardiovascular risk factors and inflammatory biomarkers were leveraged to identify possible mediators. RESULTS: Genetic liability to multi-site chronic pain is associated with higher risks for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), and stroke, with a combined odds ratio (OR) of 1.537 (per site increment in MCP; 95% confidence interval [CI]: 1.271-1.858; P=0.0001) for CAD, 1.604 (95% CI: 1.277-2.014; P=0.0005) for MI, 1.722 (95% CI: 1.423-2.083; P<0.00001) for HF, and 1.332 (95% CI: 1.093-1.623; P=0.00001) for stroke. Genetic liability to MCP was found to be associated with mental disorders, smoking initiation, physical activity, BMI, and lipid metabolites. Multivariable Mendelian randomisation suggested a mediating role for mental disorders, smoking initiation, physical activity, and BMI in the relationship between multi-site chronic pain and cardiovascular disease. CONCLUSIONS: Our findings provide new insights into the role of multi-site chronic pain in cardiovascular disease. Additionally, we identified several modifiable risk factors for reducing cardiovascular disease.

The value of quantitative plaque analysis based on coronary computed tomography angiography in predicting the percutaneous coronary intervention outcome of chronic total occlusion lesions.

Background: Due to the uncertainty of the success of percutaneous coronary intervention (PCI) and the complexity of selecting suitable treatment cases, the interventional outcome of coronary chronic total occlusion (CTO) remains challenging. The purpose of this study was to evaluate the role of quantitative plaque analysis based on coronary computed tomography angiography (CCTA) in predicting the CTO-PCI outcome. Methods: We retrospectively included 78 patients with CTO (80 lesions) confirmed by invasive coronary angiography from July 2016 to December 2018. All patients underwent PCI treatment according to standard practice. A total of 47 lesions in 47 patients were successfully treated with PCI. PCI failed in the remaining 33 lesions in 31 patients. The following conventional CCTA morphologic parameters were evaluated and compared between the PCI-success and PCI-failure groups: stump morphology; occlusion length, tortuous course; CTO lesion calcium; bridging collateral vessel; retrograde collateral vessel; the appearance of the occluded distal segment; and quantitative CTO plaque characteristics, including total plaque volume, calcified plaque (CP) volume, noncalcified plaque (NCP) volume, low-density noncalcified plaque (LDNCP) volume, and plaque length. Univariate and multivariate logistic regression analyses were performed to determine independent parameters predictive of CTO-PCI outcomes. The predictive performances were assessed using receiver operating characteristic curve analysis. Results: The blunt stump was the only independent CCTA morphologic parameter to predict the outcome of CTO-PCI [odds ratio (OR): 10.807; P<0.001]. NCP volume (OR: 1.018; P<0.001), CP volume (OR: 1.026; P=0.049), and plaque length (OR: 1.058; P=0.037) were independent quantitative CTO plaque characteristics predictive of CTO-PCI outcomes. The plaque-based model combining NCP volume with CP volume and plaque length had a higher area under the curve (AUC =0.96) than did the morphology-based model that included blunt stump (AUC 0.68) in predicting the outcomes of CTO-PCI (P<0.001). Conclusions: The CCTA-based plaque characteristics, including NCP volume, CP volume, and plaque length, outperformed morphologic parameters in predicting the CTO-PCI outcomes.

Microglial IL-1RA ameliorates brain injury after ischemic stroke by inhibiting astrocytic CXCL1-mediated neutrophil recruitment and microvessel occlusion.

Acute ischemic stroke (AIS), one of the leading causes of mortality worldwide, is characterized by a rapid inflammatory cascade resulting in exacerbation of ischemic brain injury. Microglia are the first immune responders. However, the role of postischemic microglial activity in ischemic brain injury remains far from being fully understood. Here, using the transgenic mouse line CX3 CR1creER :R26iDTR to genetically ablate microglia, we showed that microglial deletion exaggerated ischemic brain injury. Associated with this worse outcome, there were increased neutrophil recruitment, microvessel blockade and blood flow stagnation in the acute phase, accompanied by transcriptional upregulation of chemokine (C-X-C motif) ligand 1 (CXCL1). Our study showed that microglial interleukin-1 receptor antagonist (IL-1RA) suppressed astrocytic CXCL1 expression induced by oxygen and glucose deprivation and inhibited neutrophil migration. Furthermore, neutralizing antibody therapy against CXCL1 or the administration of recombinant IL-1RA protein reduced brain infarct volume and improved motor coordination performance of mice after ischemic stroke. Our study suggests that microglia protect against acute ischemic brain injury by secreting IL-1RA to inhibit astrocytic CXCL1 expression, which reduces neutrophil recruitment and neutrophil-derived microvessel occlusion.

Synaptic and Gradual Conductance Switching Behaviors in CeO2/Nb-SrTiO3 Heterojunction Memristors for Electrocardiogram Signal Recognition.

The synaptic properties of memristors have been widely studied. However, researchers are still committed to solving various challenges, including the study of highly reliable memristors with comprehensive synaptic functions and memristors that simulate highly complex neurological learning rules. In this work, we report a CeO2/Nb-SrTiO3 heterojunction memristor whose conductance could be gradually tuned under both positive and negative pulse trains. Due to the gradual conductance switching behavior and the high switching ratio (105), the CeO2/Nb-SrTiO3 heterojunction memristor could dutifully mimic biosynaptic functions, including excitatory/inhibitory postsynaptic current (EPSC/IPSC), paired-pulse facilitation and depression (PPF/PPD), spike amplitude-dependent plasticity (SADP), spike duration-dependent plasticity (SDDP), spike rate-dependent plasticity (SRDP), paired/triplet spiking-time-dependent plasticity (STDP), and Bienenstock-Cooper-Munro (BCM) rules. Moreover, a convolutional neural network based on the memristors is constructed to identify the electrocardiogram (ECG) data sets to realize the diagnosis of diseases with a recognition accuracy of 93%. Besides, the recognition accuracy of the handwriting digit reaches 96%. These studies broaden the research scope of high-level synaptic behavior and lay a foundation for the future full synaptic memristor networks.

THE EFFECTS OF EARLY-PHASE FUROSEMIDE USE ON THE PROGRESSION OF OLIGURIC ACUTE KIDNEY INJURY ACROSS DIFFERENT CENTRAL VENOUS PRESSURE: A RETROSPECTIVE ANALYSIS.

ABSTRACT: Background: Furosemide is a commonly used loop diuretic in critical care. However, its effect on the progression of oliguric acute kidney injury across different central venous pressure (CVP) remains unknown. This study therefore aims to investigate the association between furosemide 6-12h (defined as the use of furosemide within 6 h after the diagnosis of AKI according to the urine output [UO] criteria set by the Kidney Disease: Improving Global Outcomes [KDIGO] guidelines) and the progression of AKI across different CVP 6-12h (defined as CVP within 6 h after the diagnosis of AKI by the KDIGO UO criteria) levels. Methods: Patients involved in this study were identified from the Medical Information Mart for Intensive Care IV database with the following criteria: (i) adults with UO <0.5 mL/kg per hour for the first 6 h upon admission to the intensive care unit (ICU) (meeting stage 1 AKI by UO) and (ii) CVP 6-12h ranging from 0 to 30 mm Hg. From there on, the target primary outcome would be progression to stage 3 AKI by UO among these chosen patients. The secondary outcome was 28-d mortality since ICU admission. The risks of severe-stage AKI progression and 28-d mortality were respectively examined against furosemide 6-12h (vs. without furosemide 6-12h ) within the full cohort and across different subgroups of CVP 6-12h , using multivariate adjusted logistic regression and inverse probability treatment weighting (IPTW). Sensitivity analyses were performed to assess the robustness of our findings. Results: One thousand one hundred eighty patients were ultimately selected for this study, of whom 643 (54.5%) progressed to stage 3 AKI from stage 1 based on the UO criteria by KDIGO. Multivariate analysis showed that furosemide 6-12h is significantly associated with this severe-stage progression within the full cohort (odds ratio [OR] was 0.62 at 95% confidence interval [CI] of 0.43-0.90, P = 0.011). After dividing the patients into CVP 6-12h subgroups according to their CVP during the early phases, lower risk of AKI progression was observed only in furosemide 6-12h application at CVP 6-12h of ≥12 mm Hg (adjusted OR was 0.40 at 95% CI of 0.25-0.65, P < 0.001), as confirmed by the IPTW analysis (OR was 0.47 at 95% CI of 0.29-0.76, P = 0.002). The robustness of these findings was confirmed by sensitivity analyses. In addition, for patients with CVP 6-12h ≥12 mm Hg, furosemide 6-12h is also significantly associated with lower risk of 28-d mortality (adjusted OR was 0.47 at 95% CI of 0.25-0.92, P = 0.026) in the multivariate logistic regression analysis, and there was a similar trend in the IPTW analysis (adjusted OR was 0.55 at 95% CI of 0.28-1.10, P = 0.092). Conclusions: Among the identified early-stage AKI patients in critical care, the use of furosemide was associated only with lower risk of oliguric AKI progression and 28-d mortality within the high CVP group. These findings suggest the potential of CVP as a guidance or reference point in the usage of furosemide among early-stage oliguric AKI patients in the ICU.

Perioperative Risk Factors Associated With Unplanned Reoperation Following Vascularized Free Flaps Reconstruction of the Oral Squamous Cell Carcinoma.

OBJECTIVES: To find out the occurrence rate and risk factors of unplanned reoperation (any unscheduled surgery within 30 d after the initial surgery) in patients who have received oral squamous cell carcinoma (OSCC) surgery and vascularized free flap reconstruction. PATIENTS AND METHODS: We organized a retrospective study of 1058 patients who underwent OSCC resection and reconstruction with vascularized free flaps from 2011 to 2019. Clinical characteristics, reasons for unplanned reoperation, flap types, and previous treatment were compared between the unplanned reoperation group and the control group. Univariate and multivariate analyses were performed to identify perioperative risk factors for unplanned reoperation. The related perioperative factors that may influence perioperative infusion were included in propensity score matching to investigate the independent contribution of intraoperative colloid infusion on unplanned reoperation. RESULTS: The overall rate of unplanned reoperation in OSCC patients was 11% (n=115). Flap necrosis and bleeding were the most common causes. Higher American Society of Anesthesiologists (ASA) grade [odds ratio (OR)=1.709, P=0.009], postoperative anemia (OR=0.983, P=0.011) and excessive intraoperative colloid input (OR=1.55, P=0.037) were identified as risk factors for unplanned reoperation. Propensity score matching was applied, and the difference of unplanned reoperation incidence between the matched groups was statistically significant (14.59% versus 8.54%; P=0.025). The multivariate analyses after propensity score matching confirmed that the intraoperative rate of colloid infusion of more than 2.3 mL/kg/h (OR=1.756, P=0.042) and prior radiotherapy (OR=2.78, P=0.001) are independent risk factors for unplanned reoperation. CONCLUSION: High intraoperative colloid infusion rate and prior radiotherapy may increase the risk of unplanned reoperation in patients who underwent OSCC surgery and vascularized free flap reconstruction.