Enhancement of faradaic current in an electrochemical cell integrated into silicon microfluidic channels.

Implantable electrochemical sensors enable fast and sensitive detection of analytes in biological tissue, but are hampered by bio-foulant attack and are unable to be recalibrated in-situ. Herein, an electrochemical sensor integrated into ultra-low flow (nL/min) silicon microfluidic channels for protection from foulants and in-situ calibration is demonstrated. The small footprint (5 µm radius channel cross-section) of the device allows its integration into implantable sampling probes for monitoring chemical concentrations in biological tissues. The device is designed for fast scan cyclic voltammetry (FSCV) in the thin-layer regime when analyte depletion at the electrode is efficiently compensated by microfluidic flow. A 3X enhancement of faradaic peak currents is observed due to the increased flux of analytes towards the electrodes. Numerical analysis of in-channel analyte concentration confirmed near complete electrolysis in the thin-layer regime below 10 nL/min. The manufacturing approach is highly scalable and reproducible as it utilizes standard silicon microfabrication technologies.

1 × 5 broadband photonic crystal power splitter designed by the Powell algorithm.

We propose a novel, to the best of our knowledge, 1×5 broadband power splitter based on the photonic crystal. The Powell algorithm is used to reverse-design the proposed broadband power splitter. The results show that the transmittance of each output port of the broadband photonic crystal power splitter can be adjusted by changing the radii and offsets of the dielectric rods at the junction area of each waveguide. According to the target splitting ratio, the reverse design of the structural parameters using the Powell algorithm significantly improves the optimization efficiency and splitting performance of the broadband power splitter. The designed power splitters have a wide working bandwidth of 1525-1565 nm, a flexible and designable power splitting ratio, excellent splitting performance, and a compact size, which have great application prospects in all-optical communication networks, high-density photon integration, and other fields.

Attomole-Level Multiplexed Detection of Neurochemicals in Picoliter Droplets by On-Chip Nanoelectrospray Ionization Coupled to Mass Spectrometry.

While droplet microfluidics is becoming an effective tool for biomedical research, sensitive detection of droplet content is still challenging, especially for multiplexed analytes compartmentalized within ultrasmall droplets down to picoliter volumes. To enable such measurements, we demonstrate a silicon-based integrated microfluidic platform for multiplexed analysis of neurochemicals in picoliter droplets via nanoelectrospray ionization (nESI)-mass spectrometry (MS). An integrated silicon microfluidic chip comprising downscaled 7 µm-radius channels, a compact T-junction for droplet generation, and an integrated nESI emitter tip is used for segmentation of analytes into picoliter compartments and their efficient delivery for subsequent MS detection. The developed system demonstrates effective detection of multiple neurochemicals encapsulated within oil-isolated plugs down to low picoliter volumes. Quantitative measurements for each neurochemical demonstrate limits of detection at the attomole level. Such results are promising for applications involving label-free and small-volume detection for monitoring a range of brain chemicals.

Characteristics of lymphocyte subsets and cytokine profiles of patients with COVID-19.

BACKGROUND: Abnormalities of lymphocyte subsets and cytokine profiles have been observed in most patients with coronavirus disease (COVID-19). Here, we explore the role of lymphocyte subsets and cytokines on hospital admission in predicting the severity of COVID-19. METHODS: This study included 214 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 19, 2020 to April 30, 2020. Any mutants were not detected in the studied patients. Patients were divided into non-intensive care unit (ICU) (mild/moderate) group and ICU (severe/critical) group, according to the severity of the disease. Clinical and laboratory data, including peripheral lymphocyte subsets and cytokines, were analyzed and compared. Logistic regression was used to analyze the predictive factors for ICU admission. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of selected indicators for the severity of COVID-19. RESULTS: Of the 214 patients enrolled, 161 were non-ICU patients and 53 were ICU patients. Lymphopenia was observed in nearly all of ICU patients (96.2%) and 84.5% of non-ICU patients on hospital admission. The absolute number of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and natural killer (NK) cells were lower in ICU group (659.00 × 106/L, 417.00 × 106/L, 261.00 × 106/L, 140.00 × 106/L, 109.00 × 106/L, 102.00 × 106/L, respectively) than in non-ICU group (1063.00 × 109/L, 717.00 × 106/L, 432.00 × 106/L, 271.00 × 106/L, 133.00 × 106/L, 143.00 × 106/L, respectively). Interleukin (IL)-6 was significantly higher in ICU patients than in non-ICU patients (18.08 pg/mL vs. 3.13 pg/mL, P < 0.001). Multivariate logistic regression analysis showed that age (odds ratio: 1.067 [1.034-1.101]), diabetes mellitus (odds ratio: 9.154 [2.710-30.926]), CD3+ T cells (odds ratio: 0.996 [0.994-0.997]), and IL-6 (odds ratio: 1.006 [1.000-1.013]) were independent predictors for the development of severe disease. ROC curve analysis showed that the area under the ROC curve (AUC) of CD3+ T cells and IL-6 was 0.806 (0.737-0.874) and 0.785 (0.705-0.864), respectively, and the cutoff values were 510.50 × 106/L (sensitivity, 71.7%; specificity, 79.5%) and 6.58 pg/mL (77.4%, 74.5%), respectively. There were no statistical differences among all tested indicators of lymphocyte subsets and cytokines between severe group (n = 38) and critical group (n = 15) on hospital admission or ICU admission, respectively. CONCLUSIONS: The levels of lymphocyte subsets decreased and the level of IL-6 increased significantly in ICU COVID-19 patients compared with non-ICU COVID-19 patients. Therefore, the number of CD3+ T cells and the level of IL-6 on hospital admission may serve as predictive factors for identifying patients with wild-type virus infection who will have severe disease.

Circ_0069718 promotes the progression of breast cancer by up-regulating NFIB through sequestering miR-590-5p.

Researches indicate that circular RNAs are dysregulated in breast cancer (BC) and play a critical role in regulating the malignant phenotype of cancer cells. Herein, the goal of this work was to investigate the role and mechanism of circ_0069718 in BC development. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and western blot. In vitro experiments were performed using cell counting kit-8 assay, colony formation assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, western blot, and transwell assay, respectively. The dual-luciferase reporter and RNA immunoprecipitation assays were used to identify the target relationship between miR-590-5p and circ_0069718 or nuclear factor I/B (NFIB). In vivo experiments were conducted using Xenograft model in mice. Circ_0069718 was up-regulated in BC tissues and cells. Knockdown of circ_0069718 suppressed BC cell apoptosis, migration, and invasion in vitro effectively. Mechanistically, circ_0069718 directly targeted miR-590-5p to up-regulate its target NFIB. Rescue experiments showed that miR-590-5p inhibition reversed the inhibitory effects of circ_0069718 knockdown on BC cell-aggressive oncogenic phenotypes; moreover, miR-590-5p re-expression restrained BC cell proliferation and mobility, which were abolished by NFIB up-regulation. Besides that, circ_0069718 silencing hindered tumor growth via miR-590-5p/NFIB axis in vivo. Circ_0069718 promotes BC progression by up-regulating NFIB through sequestering miR-590-5p, suggesting a potential therapeutic strategy in BC.

A Smart Tongue Depressor-Based Biosensor for Glucose.

The development of new bioelectronic platforms for direct interactions with oral fluid could open up significant opportunities for healthcare monitoring. A tongue depressor is a widely used medical tool that is inserted into the mouth, where it comes into close contact with saliva. Glucose is a typical salivary biomarker. Herein, we report-for the first time-a tongue depressor-based biosensor for the detection of glucose in both phosphate buffer and real human saliva. Carbon nanotubes (CNTs) are attractive electronic materials, with excellent electrochemical properties. The sensor is constructed by printing CNTs and silver/silver chloride (Ag/AgCl) to form three electrodes in an electrochemical cell: Working, reference, and counter electrodes. The enzyme glucose oxidase (GOD) is immobilized on the working electrode. The glucose detection performance of the sensor is excellent, with a detection range of 7.3 µM to 6 mM. The glucose detection time is about 3 min. The discretion between healthy people's and simulated diabetic patients' salivary samples is clear and easy to tell. We anticipate that the biosensor could open up new opportunities for the monitoring of salivary biomarkers and advance healthcare applications.

A Tube-Integrated Painted Biosensor for Glucose and Lactate.

Developing a simple and direct approach for sensitive, specific, and rapid detection of metabolic compounds is of great importance for a variety of biological, medical, and food applications. Tubes are a highly portable and accessible container shape which are widely used for scientific research in cell biology and chemical synthesis, and which are also of great use in domestic health care applications. Here, we show for the first time the development of a tube-based painted amperometric biosensor for the detection of glucose and lactate. The sensor was prepared by printing carbon graphite and silver/silver chloride inks on the interior wall of the tube and then immobilizing glucose oxidase or lactate oxidase on the sensor. The sensor showed a sensitive, rapid, and reliable detection of glucose and lactate. We anticipate that these results could open new avenues for the development of painted biosensors, and toward advanced biosensor applications.

Wearable Carbon Nanotube-Based Biosensors on Gloves for Lactate.

Developing a simple and direct approach for interfacing a sensor and a target analyte is of great interest for fields such as medical diagnosis, threat detection, food quality control, and environmental monitoring. Gloves provide a unique interface for sensing applications. Here, we show for the first time the development of wearable carbon nanotube (CNT)-based amperometric biosensors painted onto gloves as a new sensing platform, used here for the determination of lactate. Three sensor types were studied, configured as: two CNT electrodes; one CNT electrode, and an Ag/AgCl electrode, and two CNT electrodes and an Ag/AgCl electrode. The sensors are constructed by painting the electrodes using CNT or Ag/AgCl inks. By immobilizing lactate oxidase onto the CNT-based working electrodes, the sensors show sensitive detections of lactate. Comparison of sensor performance shows that a combination of CNT and Ag/AgCl is necessary for highly sensitive detection. We anticipate that these findings could open exciting avenues for fundamental studies of wearable bioelectronics, as well as practical applications in fields such as healthcare and defense.

A retrospective study of SPECT/CT scans using SUV measurement of the normal pelvis with Tc-99m methylene diphosphonate.

OBJECTIVE: To perform quantitative measurement based on the standardized uptake value (SUV) of Tc-99m methylene diphosphonate (MDP) in the normal pelvis using a single-photon emission tomography (SPECT)/computed tomography (CT) scanner. MATERIAL AND METHODS: This retrospective study was performed on 31 patients with cancer undergoing bone SPECT/CT scans with 99mTc-MDP. SUVmax and SUVmean of the normal pelvis were calculated based on the body weight. SUVmax and SUVmean of the bilateral anterior superior iliac spine, posterior superior iliac spine, facies auricularis ossis ilii, ischial tuberosity, and sacrum were also calculated. Furthermore, the correlation of SUVmax and SUVmean of all parts of pelvis with weight, height, and CT was assessed. RESULTS: The data for 31 patients (20 women and 11 men; mean age 58.97±9.12 years; age range 37-87 years) were collected. SUVmax and SUVmean changed from 1.65±0.40 to 3.8±1.0 and from 1.15±0.25 to 2.07±0.58, respectively. The coefficient of variation of SUVmax and SUVmean ranged from 0.22 to 0.31. SUVmax and SUVmean had no statistically significant difference between men and women. SUVmax and SUVmean also showed no significant correlation with weight and height. However, part of SUVmax and SUVmean showed a significant correlation with CT. In addition, SUVmax and SUVmean of the bilateral ischial tuberosity showed a significant correlation with CT values. CONCLUSIONS: Determination of the SUV value of the normal pelvis with 99m Tc-MDP SPECT/CT is feasible and highly reproducible. SUVs of the normal pelvis showed a relatively large variability. As a quantitative imaging biomarker, SUVs might require standardization with adequate reference data for the participant to minimize variability.

Discovery of novel substituted octahydropyrrolo[3,4-c]pyrroles as dual orexin receptor antagonists for insomnia treatment.

A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2 R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency.

Michael acceptor in gambogic acid--Its role and application for potent antitumor agents.

Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clinical application as an anticancer agent. Moreover, the 6-OH forms an intramolecular hydrogen bond with 8-CO, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-molecular hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.

Estimation for two Gompertz populations under a balanced joint progressive Type-II censoring scheme.

Comparative lifetime experiments are remarkable when the study is to ascertain the relative merits of two competing products regarding the duration of their service life. This paper considers the comparative lifetime experiments of two Gompertz populations under a balanced joint progressive Type-II censoring scheme. The lifetime distributions of the units are assumed to follow the Gompertz distribution with a common shape but different scale parameters. The maximum likelihood estimates of the unknown parameters are derived. The existence of the maximum likelihood estimates is proved. Expectation-maximization and stochastic expectation-maximization algorithms are provided to calculate the estimates. The bootstrap-p, bootstrap-t, and approximate confidence intervals are established. To obtain the Bayesian estimates, it is assumed that the prior of scale parameters is a Beta-Gamma distribution and the prior of the common shape parameter is an independent Gamma distribution. Under squared error loss and LINEX loss functions, the Metropolis-Hastings algorithm is provided to compute the Bayes estimates and the credible intervals. Further, the statistical inferences with order restriction are studied when it is known a priori that the expectation of the lifespan of one population is shorter than that of the other population. A wide range of simulation experiments is conducted to evaluate the performance of the proposed methods. Finally, the lifetimes of white organic light-emitting diodes and the breaking strengths of jute fiber of gauge lengths are analyzed to illustrate the practical application of the proposed model and methods.

Highly Localized Chemical Sampling at Subsecond Temporal Resolution Enabled with a Silicon Nanodialysis Platform at Nanoliter per Minute Flows.

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100 µm spatial resolution and subsecond temporal resolution at high recovery rates. These performance metrics, which are 100-1000× superior to existing MD approaches, are enabled by a 100× reduction of the microfluidic channel cross-section, a corresponding drastic 100× reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with high spatiotemporal resolution for clinical, biomedical, and pharmaceutical applications.

A lasso and random forest model using flow cytometry data identifies primary myelofibrosis.

Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical Philadelphia-Negative (Ph-negative) myeloproliferative neoplasms (MPNs). Differentiating between these types based on morphology and molecular markers is challenging. This study aims to clarify the application of flow cytometry in the diagnosis and differential diagnosis of classical MPNs. This study retrospectively analyzed the immunophenotypes, clinical characteristics, and laboratory findings of 211 Ph-negative MPN patients, including ET, PV, pre-PMF, overt PMF, and 47 controls. Compared to ET and PV, PMF differed in white blood cells, hemoglobin, blast cells in the peripheral blood, abnormal karyotype, and WT1 gene expression. PMF also differed from controls in CD34+ cells, granulocyte phenotype, monocyte phenotype, percentage of plasma cells, and dendritic cells. Notably, the PMF group had a significantly lower plasma cell percentage compared with other groups. A lasso and random forest model select five variables (CD34+CD19+cells and CD34+CD38- cells on CD34+cells, CD13dim+CD11b- cells in granulocytes, CD38str+CD19+/-plasma, and CD123+HLA-DR-basophils), which identify PMF with a sensitivity and specificity of 90%. Simultaneously, a classification and regression tree model was constructed using the percentage of CD34+CD38- on CD34+ cells and platelet counts to distinguish between ET and pre-PMF, with accuracies of 94.3% and 83.9%, respectively. Flow immunophenotyping aids in diagnosing PMF and differentiating between ET and PV. It also helps distinguish pre-PMF from ET and guides treatment decisions.

ResNet diagnosis of rotor faults in oil transfer pumps.

To address rotor imbalance and misalignment in oil transfer pumps, an innovative diagnostic framework using Residual Network (ResNet) is proposed. The model incorporates advanced signal processing algorithms and strategic sensor placement to enhance diagnostic efficacy. A fault simulation test rig captured vibration signals from eight key measurement points on the pump. One-dimensional and multi-dimensional signal processing techniques generated comprehensive datasets for training and validating the model. Sensor placement optimization, focusing on the bearing seat's axial direction, inlet flange's vertical direction, and outlet flange's axial direction, increased rotor fault sensitivity. Time-frequency data processed via Short-Time Fourier Transform (STFT) achieved the highest diagnostic accuracy, surpassing 98 %. This study highlights the importance of optimal signal processing and precise sensor placement in improving the accuracy of diagnosing rotor faults in oil transfer pumps, thus enhancing the operational reliability and efficiency of energy transportation systems.

Microbial Relationship of Carious Deciduous Molars and Adjacent First Permanent Molars.

(1) Epidemiological studies have shown that deciduous molar caries are related to and more severe than permanent molar caries. This study aimed to investigate whether caries subtypes in deciduous molars were associated with caries in first permanent molars and to explore taxonomic and functional profiles of the microbiota involved in different subtypes. (2) 42 mixed-dentition children were recruited and were divided into DMC (carious deciduous molars but caries-free first permanent molars; n = 14), C (carious deciduous and first permanent molars; n = 13), and control (n = 15) groups. Metagenomic sequencing was performed for supragingival plaque samples obtained separately from deciduous and first permanent molars. (3) The microbiota of deciduous molars in the DMC and C groups differed not only in species-based beta diversity but also in compositional and functional profiles. In the C group-like subtype, 14 caries-related species and potential pathways were identified that could be responsible for the caries relationship between the deciduous and permanent molars. In the DMC group-like subtype, the overall functional structure, the levels of Leptotrichia wadei, Streptococcus anginosus, and Stomatobaculum longum and KOs in sugar transporters and fermentation, quorum sensing, and TCA cycle in their first permanent molars surprisingly resembled those of the C group rather than the control group. This suggested that these clinically sound first permanent molars were at a greater risk for caries. (4) Classification of deciduous molar caries according to the microbiota could serve as a caries risk predictor for adjacent first permanent molars.

Highly localized chemical sampling at sub-second temporal resolution enabled with a silicon nanodialysis platform at exceedingly slow flows.

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and in pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100µm spatial resolution and sub-second temporal resolution at high recovery rates. These performance metrics, which are 100X-1000X superior to existing MD approaches, are enabled by a 100X reduction of the microfluidic channel cross-section, a corresponding drastic 100X reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with unprecedented spatio-temporal resolution for clinical, biomedical, and pharmaceutical applications.

PILRA is associated with immune cells infiltration in atrial fibrillation based on bioinformatics and experiment validation.

Background and aims: inflammation plays an important role in atrial fibrillation (AF). In this study, we investigated the significance of immune cell infiltration in AF and identified the potential Hub genes involved in the regulation of immune cell infiltration in AF. Methods: we obtained AF datasets from the GEO database and analyzed them for obtaining differentially expressed genes (DEGs) by R software. Then, we performed GO, KEGG, and GSEA enrichment analyses of DEGs. The Hub genes of AF were determined by least absolute shrinkage selection operator (LASSO) regression analysis and weighted gene co-expression network analysis (WGCNA). Their validation was verified by using quantitative polymerase chain reaction (qPCR) in the AF rat model. Finally, we used a single sample GSEA (ssGSEA) to analyze immune cell infiltration and its relationship with hub genes. Results: We obtained 298 DGEs from the heatmap and found that DGEs were closely related to inflammation, immunity, and cytokine interactions by enrichment analyses. We obtained 10 co-expression modules by WGCNA. Among them, the module including CLEC4A, COTL1, EVI2B, FCER1G, GAPT, HCST, NCF2, PILRA, TLR8, and TYROBP had the highest correlation with AF. Four Hub genes (PILRA, NCF2, EVI2B, GAPT) were obtained further by LASSO analysis. The results suggested that the expression level of PILRA was significantly elevated in the rats with AF by qPCR, compared to the rats without AF. The results revealed that the infiltration of neutrophils, macrophages, monocytes, mast cells, immature B cells, myeloid-derived suppressor cell (MDSC), dendritic cell, and T cells and their partial subpopulations were closely related to AF by ssGSEA analysis, and PILRA was positively correlated with immature B cell, monocyte, macrophage, mast cell, dendritic cell, and T cells and their partial subpopulations by Spearman correlation analysis. Conclusions: PILRA was closely related to multiple types of immune cell infiltration, which may be associated with AF. PILRA may be a novel target of intervention for AF.

Promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine, a selective norepinephrine reuptake inhibitor.

Reboxetine, the first selective norepinephrine (NA) reuptake inhibitor used in the treatment of depression, mainly acts by binding to the NA transporter and blocking reuptake of extracellular NA. Recently, some other pharmacological targets beyond the NA transporter are being demonstrated for reboxetine. Peroxisome proliferator activated receptor α (PPARα) is a member of the nuclear hormone receptor family of ligand-dependent transcription factors. Previous reports have demonstrated the role of hippocampal PPARα in the pathophysiology of depression. Here we assume that hippocampal PPARα may participate in the antidepressant mechanism of reboxetine. Therefore, the chronic social defeat stress (CSDS) model of depression, various behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated genetic knockdown methods were used together in the present study. Our results showed that repeated reboxetine treatment markedly restored the decreasing effects of CSDS on the expression of hippocampal PPARα, brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (pCREB). Pharmacological blockade of PPARα notably prevented the antidepressant-like effects of reboxetine in the CSDS model. Furthermore, genetic knockdown of hippocampal PPARα also fully abolished the antidepressant-like effects of reboxetine in the CSDS model. Taken together, promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine.