Multi-stage development process and model of steam chamber for SAGD production in a heavy oil reservoir with an interlayer.

Steam-assisted gravity drainage (SAGD) is an efficient thermal recovery technique for oil sands and extra heavy oil exploitation. The development of steam chamber goes through multi-stage physical processes for SAGD production in a heavy oil reservoir with an interlayer. In this study, considering the situation that an interlayer is located directly above a pair of horizontal wells, we analyzed the whole process of steam chamber development. We divided the whole process into stages I-V, which are the first rising stage, the first lateral expansion stage, the second rising stage, the second lateral expansion stage and the confinement stage, respectively. Particularly, we further divided stage II into 2 periods and stage IV into 3 periods. These stages and periods can help us understand the development process of steam chamber dominated by an interlayer more profoundly. Based on the divided stages and periods, we established different models of SAGD production by assuming different geometric shapes of steam chamber in different stages and periods. Oval shape was assumed in stages I and III, and inverse triangle shape was hypothesized in stages II, IV and V. The formulas of the front distance of steam chamber and the oil production rate of SAGD were deduced from the established models for different development stages. At the end, we performed two example applications to SAGD production in heavy oil reservoirs with an interlayer. The real oil production rates were matched very well with the theoretical oil production rates calculated by the deduced formulas, which implies the multi-stage development model of steam chamber is of reliability and utility.

Ruxolitinib improves the inflammatory microenvironment, restores glutamate homeostasis, and promotes functional recovery after spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

Necroptosis pathway emerged as potential diagnosis markers in spinal cord injury.

The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.

A porous silicon composite with irregular silver nano-dendritic particles: a rapid optical sensor for trace detection of malachite green in freshwater fish.

This study focused on creating a SERS composite particle specifically designed for detecting malachite green. We synthesized silver nano-dendritic structures on p-type porous silicon using an external electric field, separating them from the silicon wafer. Ultrasonic crushing yielded irregular silver nanodendrite-modified porous silicon composite particles. Upon being tested in an aqueous solution of malachite green, these composite particles demonstrated significant surface-enhanced Raman scattering effects. Our findings highlight the exceptional performance of the SERS substrate composed of porous silicon and irregular silver nano-dendritic particles. It exhibited high sensitivity, specificity, consistent signal strength, and reliability in detecting trace amounts of malachite green in water. Under ideal conditions, the substrate could detect malachite green at concentrations as low as 10-8 M. Moreover, its swift response to trace amounts of malachite green in fish underscores its potential as an effective Raman detector.

Adsorption Characteristics of H2S and SO2 Gases on Cu2O Cluster-Modified Graphene Monolayer for Gas-Sensing Applications.

In this study, the adsorption capability and gas-sensing performance of Cu2O-graphene on SF6-featured decomposers (H2S and SO2) were evaluated based on first-principles calculations. The most stable structure, adsorption energy, band structure, and DOS and PDOS were used to investigate the adsorption mechanism. The findings suggest that all adsorption systems are exothermic and spontaneous. The density of states analysis suggests that the adsorption of H2S and SO2 is chemisorbed. The recovery time shows that the desorption time after H2S adsorption is shorter at a suitable temperature. In contrast, the desorption time of SO2 was quite long in some systems, which reduced the detection efficiency. In summary, Cu2O-graphene could be a promising gas-sensing material for the detection of two-characteristic SF6-decomposition products.

3D Printing of Robust High-Performance Conducting Polymer Hydrogel-Based Electrical Bioadhesive Interface for Soft Bioelectronics.

Electrical bioadhesive interface (EBI), especially conducting polymer hydrogel (CPH)-based EBI, exhibits promising potential applications in various fields, including biomedical devices, neural interfaces, and wearable devices. However, current fabrication techniques of CPH-based EBI mostly focus on conventional methods such as direct casting, injection, and molding, which remains a lingering challenge for further pushing them toward customized practical bioelectronic applications and commercialization. Herein, 3D printable high-performance CPH-based EBI precursor inks are developed through composite engineering of PEDOT:PSS and adhesive ionic macromolecular dopants within tough hydrogel matrices (PVA). Such inks allow the facile fabrication of high-resolution and programmable patterned EBI through 3D printing. Upon successive freeze-thawing, the as-printed PEDOT:PSS-based EBI simultaneously exhibits high conductivity of 1.2 S m-1 , low interfacial impedance of 20 Ω, high stretchability of 349%, superior toughness of 109 kJ m-3 , and satisfactory adhesion to various materials. Enabled by these advantageous properties and excellent printability, the facile and continuous manufacturing of EBI-based skin electrodes is further demonstrated via 3D printing, and the fabricated electrodes display excellent ECG and EMG signal recording capability superior to commercial products. This work may provide a new avenue for rational design and fabrication of next-generation EBI for soft bioelectronics, further advancing seamless human-machine integration.

Solid Electrolyte Interface Film-Forming and Surface-Stabilizing Bifunctional 1,2-Bis((trimethylsilyl)oxy) Benzene as Novel Electrolyte Additive for Silicon-Based Lithium-Ion Batteries.

The application of Si-based anodes in lithium-ion batteries (LIBs) has garnered significant attention due to their high theoretical specific capacity yet is still challenged by the substantial volume expansion of silicon particles during the lithiation process, resulting in the instability of the electrode-electrolyte interphase and deteriorative battery performance. Herein, an ortho(trimethylsilyl)oxybenzene electrolyte additive, 1,2-bis((trimethylsilyl)oxy) benzene (referred to as BTMSB), has been investigated as a bifunctional electrolyte additive for Si-based LIBs. The BTMSB can form a uniform and robust LiF-rich solid electrolyte interphase (SEI) on the surface of Si-based material particles, adapting the huge volume expansion of the Si-based electrode and facilitating lithium-ion transport. Additionally, the BTMSB demonstrates the ability to scavenge hydrofluoric acid (HF) to stabilize the electrode-electrolyte interphase. The SiOx/C∥Li batteries with 2% BTMSB exhibit improved cycle performance and current-rate capabilities, of which the capacity retention retains 69% after 400 cycles. Furthermore, Si-based anode cells with higher theoretical specific capacities (1C = 550 mAh g-1) and NCM523∥SiOx/C pouch cells are constructed and evaluated, displaying superior cycle performance. This work provides valuable insights for the development of effective electrolyte additives and the commercialization of high energy density LIBs with Si-based anodes.

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma.

Tumor-associated lymph vessels and lymph node involvement are critical staging criteria in several cancers. In skin squamous cell carcinoma, lymph vessels play a role in cancer development and metastatic spread. However, their relationship with the cancer stem cell niche at early tumor stages remains unclear. To address this gap, we studied the lymph vessel localization at the cancer stem cell niche and observed an association from benign skin lesions to malignant stages of skin squamous cell carcinoma. By co-culturing lymphatic endothelial cells with cancer cell lines representing the initiation and promotion stages, and conducting RNA profiling, we observed a reciprocal induction of cell adhesion, immunity regulation, and vessel remodeling genes, suggesting dynamic interactions between lymphatic and cancer cells. Additionally, imaging analyses of the cultured cells revealed the establishment of heterotypic contacts between cancer cells and lymph endothelial cells, potentially contributing to the observed distribution and maintenance at the cancer stem cell niche, inducing downstream cellular responses. Our data provide evidence for an association of lymph vessels from the early stages of skin squamous cell carcinoma development, opening new avenues for better comprehending their involvement in cancer progression.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Molecular classification grade 3 endometrial endometrioid carcinoma using a next-generation sequencing-based gene panel.

Over the past two decades, the incidence of endometrial cancer (EC) is increasing, and there is a need for molecular biomarkers to predict prognosis and guide treatment. A recent study from The Cancer Genome Atlas suggested to implement the EC analysis by molecular profile for improving diagnosis, prognosis, and therapeutic treatment. In this study, next-generation sequencing was performed on 70 cases of G3 endometrioid ECs (EECs) using an 11-gene panel (TP53, MLH1, MSH2, MSH6, PMS2, EPCAM, PIK3CA, CTNNB1, KRAS, PTEN, and POL) for molecular classification. The molecular classification based on the 11-gene NGS panel identified four molecular subgroups: POLE-ultramutated (n = 20, 28.6%), MSI-H (n = 27, 38.6%), NSMP (n = 13, 18.6%) and TP53mut (n = 10, 14.3%). The NGS method showed 98.6% (69 of 70 cases, kappa value 98%) in concordance with the cases assessed by immunohistochemistry (IHC). Among the seven dead cases, four were MSI-H tumors, two were TP53mut/p53abn tumors, and one was NSMP tumors with an average overall survival (OS) of 14.7 months. TP53mut subgroup showed that poor OS rates and POLE group have favorable prognosis. Our work suggested that the 11-gene panel is suitable for molecular classification in G3 EECs and for guiding prognosis and treatment decisions.

Adsorption of Greenhouse Decomposition Products on Ag2O-SnS2 and CuO-SnS2 Surfaces.

In this paper, based on density functional theory, the adsorption mechanism and gas sensitivity of Ag2O/CuO-modified SnS2 were analyzed. The results were analyzed according to the adsorption energy, total density of states, partial density of states, and frontier molecular orbital theory. The results show that the adsorption of all gas molecules is exothermic. NH3, Cl2, and C2H2 gases are chemisorbed on the modified SnS2 surfaces. After gas adsorption, the energy gap of the base changes by more than 10%, which fully shows that the conductivity changes greatly after gas adsorption, which can be reflected in the macroscopic resistance change. Ag2O-SnS2 is suitable as a gas sensor for NH3 gas sensors in terms of moderate adsorption distance, large adsorption energy, charge transfer, and frontier molecular orbital theory, while CuO-SnS2 is more suitable as a C2H2 gas sensor.

Efficacy and safety of a basal insulin + 2-3 oral antihyperglycaemic drugs regimen versus a twice-daily premixed insulin + metformin regimen after short-term intensive insulin therapy in individuals with type 2 diabetes: The multicentre, open-label, randomized controlled BEYOND-V trial.

AIM: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China. MATERIALS AND METHODS: This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). RESULTS: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group. CONCLUSIONS: Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

Convolutional Neural Network with Multiscale Fusion and Attention Mechanism for Skin Diseases Assisted Diagnosis.

Melanoma segmentation based on a convolutional neural network (CNN) has recently attracted extensive attention. However, the features captured by CNN are always local that result in discontinuous feature extraction. To solve this problem, we propose a novel multiscale feature fusion network (MSFA-Net). MSFA-Net can extract feature information at different scales through a multiscale feature fusion structure (MSF) in the network and then calibrate and restore the extracted information to achieve the purpose of melanoma segmentation. Specifically, based on the popular encoder-decoder structure, we designed three functional modules, namely MSF, asymmetric skip connection structure (ASCS), and calibration decoder (Decoder). In addition, a weighted cross-entropy loss and two-stage learning rate optimization strategy are designed to train the network more effectively. Compared qualitatively and quantitatively with the representative neural network methods with encoder-decoder structure, such as U-Net, the proposed method can achieve advanced performance.

The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients.

Background: Cardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences. Methods: In this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN <100 ms). All patients' clinical data were collected and the correlation of clinical variables with HRV were analyzed by correlation and logistic regression analysis. The area below the ROC curve was used to evaluate the predictive performance of serum calcium on HRV. Results: In this study, declines in HRV were present in 37.0% of T2DM patients. Significant differences in albumin-adjusted serum calcium levels (CaA) (8.86 ± 0.27 vs. 9.13 ± 0.39 mg/dl, p <0.001) and E/A (0.78 ± 0.22 vs. 0.83 ± 0.26, p = 0.029) were observed between declined HRV and normal HRV groups. Bivariate linear correlation analysis showed that CaA and E/A were positively correlated with HRV parameters including SDNN (p < 0.001), SDNN index (p < 0.001), and Triangle index (p < 0.05). The AUC in the ROC curve for the prediction of CaA on HRV was 0.730 (95% CI (0.750-0.815), p < 0.001). The cutoff value of CaA was 8.87 mg/dl (sensitivity 0.644, specificity 0.814). The T2DM patients with CaA <8.87 mg/dl had significantly lower HRV parameters (SDNN, SDNN index, rMSSD, and triangle index) than those with CaA ≥8.87 mg/dl (p < 0.01, respectively). Multivariate logistic regression analysis showed a significantly increased risk of declined HRV in subjects with CaA level <8.87 mg/dl [OR (95% CI), 0.049 (0.024-0.099), p < 0.001]. Conclusions: Declined HRV is associated with a lower CaA level and worse cardiac function. The serum calcium level can be used for risk evaluation of declined HRV in T2DM patients even within the normocalcemic range.

Enhanced Visualization of Retinal Microvasculature via Deep Learning on OCTA Image Quality.

PURPOSE: To investigate the impact of denoising on the qualitative and quantitative parameters of optical coherence tomography angiography (OCTA) images of the optic nerve and macular area. METHODS: OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device for 48 participants (48 eyes). Multiple image averaging (MIA) and denoising techniques were used to improve the quality of the OCTA images. The peak signal-to-noise ratio (PSNR) as an image quality parameter and vessel density (VD) as a quantitative parameter were obtained from single-scan, MIA, and denoised OCTA images. The parameters were compared, and the correlation was analyzed between different imaging protocols. RESULTS: In the optic nerve area, there were significant differences in the PSNR and VD in all measured regions between the three groups (P < 0.0001). The PSNR of the denoised group was significantly higher than that of the other two groups (P < 0.0001). The VD in the denoised group was significantly lower than that in the single-scan group in all measured regions (P < 0.0001). In the macular area, there were significant differences in the PSNR and VD in all measured regions among the three groups. The PSNR of the denoised group was significantly higher than that of the other two groups (P < 0.0001). The VD in the denoised group was significantly lower than that in the single-scan group in all measured regions. The VD around the optic nerve in the denoised group was correlated with that in the single-scan group (R = 0.9403, P < 0.0001), but the VD in the MIA group was not correlated with that in the single-scan group (R = 0.2505, P = 0.2076). The VD around the fovea in the denoised and MIA images was correlated with that in the single-scan group (R = 0.7377, P < 0.0001; R = 0.7005, P = 0.0004, respectively). CONCLUSION: Denoising could provide an easy and quick way to improve image quality parameters, such as PSNR. It shows great potential in improving the sensitivity of OCTA images as retinal disease markers.

The Perspective and Challenge of Nanomaterials in Oil and Gas Wastewater Treatment.

Oil and gas wastewater refers to the waste stream produced in special production activities such as drilling and fracturing. This kind of wastewater has the following characteristics: high salinity, high chromaticity, toxic and harmful substances, poor biodegradability, and a difficulty to treat. Interestingly, nanomaterials show great potential in water treatment technology because of their small size, large surface area, and high surface energy. When nanotechnology is combined with membrane treatment materials, nanofiber membranes with a controllable pore size and high porosity can be prepared, which provides more possibilities for oil-water separation. In this review, the important applications of nanomaterials in wastewater treatment, including membrane separation technology and photocatalysis technology, are summarized. Membrane separation technology is mainly manifested in ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO). It also focuses on the application of semiconductor photocatalysis technology induced by TiO2 in the degradation of oil and gas wastewater. Finally, the development trends of nanomaterials in oil and gas wastewater treatment are prospected.

Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V).

INTRODUCTION: Many Chinese patients who are uncontrolled by oral antidiabetic drugs (OADs) receive short-term intensive insulin therapy (IIT) in hospital to rapidly relieve glucose-associated toxicity and to preserve/improve ß-cell function. However, evidence for optimizing insulin algorithms for maintenance treatment after IIT is lacking. This study will compare the efficacy and safety of basal insulin-based treatment versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term in-hospital IIT. METHODS: This 26-week randomized, multicenter, positive-controlled, open-label, parallel-group study will enroll approximately 400 male and female patients aged 18-70 years with poorly-controlled T2DM (HbA1c > 7.5%) despite treatment with metformin plus at least one other OAD for 8 or more weeks. During a run-in period of 7-10 days, patients will be treated in-hospital with IIT comprising insulin glargine (Lantus®) once daily and insulin glulisine (Apidra®) three times daily; both regimens will be titrated daily to achieve the glycemic goal. Eligible patients will then be randomized in a 1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin (NovoLog® Mix 70/30) for 24 weeks, with metformin maintained throughout the study in both treatment groups. The primary endpoint is HbA1c change from baseline to week 24. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction. DISCUSSION: Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT. This will assist physicians by providing a wider choice of treatments. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03359837 (registered on 2 December 2017).

eNOS Uncoupling: A Therapeutic Target For Ischemic Foot of Diabetic Rat.

AIM: To determine the relationship between eNOS uncoupling and diabetic ischemic foot and whether reversing eNOS uncoupling by Dihydrofolate reductase (DHFR) transfection or folic acid (FA) supplementation can be beneficiary in diabetic ischemic foot. METHODS: The bilateral common iliac artery of diabetic rats were ligated to establish the diabetic ischemic foot animal model. DHFR transfection was implemented via femoral artery and muscle injection of in vivo transfection reagent mixture (GenEscortIII) every 4 days during the 2 weeks intervention. The color doppler flow imaging (CDFI) of femoral artery for RI measurement, triceps and quadriceps structure and histology, eNOS coupling status, DHFR expression level, superoxide, peroxynitrite (ONOO- ) and nitric oxide (NO) production in the presence or absence of L-NAME (eNOS inhibitor) were examined among wild type rats (WT), diabetic sham rats (DM), rats of diabetic ischemic foot (DF) or DF with DHFR transfection (DFT) or DF with FA supplementation (DFF). RESULTS: Dihydroethidium (DHE) fluorescence, as an index of superoxide production was enhanced in the femoral arteries of diabetic rats and even more in those of ischemic foot from diabetic rats. However, the DHE fluorescence was diminished in the presence of L-NAME suggesting eNOS uncoupling is the source of superoxide overproduction which further led to increased peroxynitrite production and decreased NO. bioavailability. Subsequently, the hind limb muscle became atrophic and the local collateral circulation was defective due to endothelial dysfunction related to eNOS uncoupling. However, all of the above and hemodynamic index (RI) of femoral artery were resumed via restoration of DHFR protein expression by folic acid treatment or DHFR transfection. CONCLUSIONS: eNOS uncoupling is involved in diabetic ischemic foot due to DHFR suppression. DHFR restoration can reverse eNOS uncoupling and resume the endothelial dysfunction and pathological changes (increased vasculature resistance, hind limb muscle atrophy and defective collateral circulation) associated with eNOS uncoupling in diabetic ischemic foot. All of which enlightens a novel therapeutic strategy for future diabetic ischemic foot treatments.

Stiff Self-Healing Coating Based on UV-Curable Polyurethane with a "Hard Core, Flexible Arm" Structure.

Two series of ultraviolet (UV)-cured self-healing polyurethane (PU) oligomers were synthesized through a prepolymer process from isophorone diisocyanate (IPDI) or 1,6-hexamethylene diisocyanate (HDI), polycarbonate diol (PCDL) of varying molecular weight (500, 1000, and 2000 Da), and chemically modified cyclotriphosphazene as hard cores were introduced. The synthesized oligomers contained rigid aromatic rings as "hard cores" and long fatty chains as "flexible arms". Nuclear magnetic resonance spectrometer (H NMR) and Fourier transform infrared spectroscopy were used to characterize the structures of the oligomers. In addition, the UV-cured self-healing PU coatings were prepared by designing some coating formulations with the PU oligomers. The self-healing properties and mechanical properties of the UV-cured coatings were investigated. The results revealed that the coatings had self-healing properties based on hydrogen bonds. As the molecular weight of PCDL decreased, the coatings exhibited increased hardness, tensile strength, and glass transition temperature. Furthermore, the coatings exhibited excellent thermostability. The results proved the application prospects of the self-healing coatings with high repair efficiency and excellent mechanical properties.

Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer.

Pancreatic cancer (PC) is the most lethal type of gastrointestinal cancer, and early detection and monitoring is an urgent problem. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity is a main problem in the traditional CellSearch System for detecting CTCs, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically high detection rate of CTCs in PC patients (90%). The diagnostic rate of PC reached 97.5% when combining CTCs ≥ 2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). In addition, we analyzed the role of chromosomal instability in CTCs detection. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed a shorter 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, the triploid CTC number but not the overall CTC counts could be a predictor of chemo-sensitivity. Moreover, circulating tumor microembolus (CTMs) were found in stage IV patients, and were positively related to the poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs and triploid CTC could be used to predict prognosis or the response to the chemotherapy of PC patients. CTM is a potential indicator of the chemotherapeutic effect in advanced PC patients.