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Endothelial metabolism is a promising target for vascular functional regulation and disease therapy. Glucose is the primary fuel for endothelial metabolism, supporting ATP generation and endothelial cell survival. Multiple studies have discussed the role of endothelial glucose catabolism, such as glycolysis and oxidative phosphorylation, in vascular functional remodeling. However, the role of the first gatekeepers of endothelial glucose utilization, glucose transporters, in the vasculature has long been neglected. Here, this review summarizes glucose transporter studies in vascular research. We mainly focus on GLUT1 and GLUT3 because they are the most critical glucose transporters responsible for most endothelial glucose uptake. Some interesting topics are also discussed, intending to provide directions for endothelial glucose transporter research in the future.

ObjectiveThis study aims to investigate the effect of single urine C peptide/creatinine (UCPCR) in assessing the islet β Cell function of type 2 diabetes mellitus (T2DM) patients with different renal function.MethodsA total of 85 T2DM patients were recruited in this study, all the patients were assigned to one group with estimated glomerular filtration rate (eGFR)≤60 ml·min-1·1.73 m-2 and another group complicated with eGFR>60 ml·min-1·1.73 m-2. Serum creatinine, urine creatinine, serum fasting C-peptide (FCP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C) and 24-hour urinary C-peptide (24hUCP) were measured. The modified homeostasis model assessment-islet β cell function [HOMA-islet (CP-DM)], the modified homeostasis model assessment-insulin resistance [HOMA-IR(CP)] and UCPCR were calculated.ResultsWhen compared with group eGFR ≤60 ml·min-1·1.73 m-2, the levels of UCPCR, FCP, the modified HOMA-IR(CP) and HOMA-islet (CP-DM) were promoted and the concentrations of HbA1C, FPG, creatinine were decreased in the patients of eGFR>60 ml·min-1·1.73 m-2 (P-1·1.73 m-2; UCPCR was positively correlated with FCP and HOMA-IR(CP) in the T2DM patients with different levels of renal function; the cut-off (UCPCR ≤ 1.13 nmol/g) had 88.37% sensitivity and 95.24% specificity [95% confidence interval (CI):0.919-0.997] for identifying severe insulin deficiency in T2DM patients[area under the curve (AUC) 0.978].ConclusionUCPCR can be used to evaluate islets β Cell function in T2DM patients with different renal function status.

The volumetric bar-chart microfluidic chips (V-Chips) driven by chemical reaction-generated gas provide a promising platform for point-of-care (POC) visual biomarker quantitation. However, multiple limitations are encountered in conventional V-Chips, such as costly and complex chip fabrication, complicated assembly, and imprecise controllability of gas production. Herein, we introduced nanomaterial-mediated photothermal effects to V-Chips, and for the first time developed a new type of V-Chip, photothermal bar-chart microfluidic chip (PT-Chip), for visual quantitative detection of biochemicals without any bulky and costly analytical instruments. Immunosensing signals were converted to visual readout signals via photothermal effects, the on-chip bar-chart movements, enabling quantitative biomarker detection on a low-cost polymer hybrid PT-Chip with on-chip scale rulers. Four different human serum samples containing prostate-specific antigen (PSA) as a model analyte were detected simultaneously using the PT-Chip, with the limit of detection of 2.1 ng/mL, meeting clinical diagnostic requirements. Although no conventional signal detectors were used, it achieved comparable detection sensitivity to absorbance measurements with a microplate reader. The PT-Chip was further validated by testing human whole blood without the color interference problem, demonstrating good analytical performance of our method even in complex matrixes and thus the potential to fill a gap in current clinical diagnostics that is incapable of testing whole blood. This new PT-Chip driven by nanomaterial-mediated photothermal effects opens a new horizon of microfluidic platforms for instrument-free diagnostics at the point of care.

Elevated retinol binding protein 4 levels are associated with atherosclerosis in diabetic rats via JAK2/STAT3 signaling pathway

Solving large-scale l1 minimization problem is very important and has attracted much attentions in recent years. In this paper, we present an efficient method for solving this problem. To this end, we first reformulate this problem as a nonnegative constrained minimization problem. Then we propose a modulus-based iterative method to solve the nonnegative constrained minimization problem. Convergence analysis and the choice of near optimal parameter are presented. Experimental results are given to illustrate feasibility and effectiveness of our proposed method.

A novel and recoverable platform of polyurethane (PU) sponge-supported Au nanoparticle catalyst was obtained by a water-based in-situ preparation process. The structure, chemical, and morphology properties of this platform were characterized by XRD, TGA, SEM, FT-IR, and XPS. The Au/PU sponge platform exhibited excellent catalytic performances in catalytic reductions of p-nitrophenol and o-nitroaniline at room temperature, and both catalytic reactions could be completed within 4.5 and 1.5 min, respectively. Furthermore, the strong interaction between Au nanoparticles and the PU sponge enabled the catalyst system to maintain a high catalytic efficiency after 5 recycling times, since the PU sponge reduced the trend of leaching and aggregation of Au nanoparticles. The unique nature of Au nanoparticles and the porous PU sponge along with their strong interaction resulted in a highly efficient, recoverable, and cost-effective multifunctional catalyst. The AuNP/Sponge nanocatalyst platform has great potential for wide environmental and other catalytic applications.

Tuberculosis (TB), one of the deadliest infectious diseases, is caused by Mycobacterium tuberculosis (MTB) and remains a public health problem nowadays. Conventional MTB DNA detection methods require sophisticated infrastructure and well-trained personnel, which leads to increasing complexity and high cost for diagnostics and limits their wide accessibility in low-resource settings. To address these issues, we have developed a low-cost photothermal biosensing method for the quantitative genetic detection of pathogens such as MTB DNA on a paper hybrid device using a thermometer. First, DNA capture probes were simply immobilized on paper through a one-step surface modification process. After DNA sandwich hybridization, oligonucleotide-functionalized gold nanoparticles (AuNPs) were introduced on paper and then catalyzed the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB). The produced oxidized TMB, acting as a strong photothermal agent, was used for the photothermal biosensing of MTB DNA under 808 nm laser irradiation. Under optimal conditions, the on-chip quantitative detection of the target DNA was readily achieved using an inexpensive thermometer as a signal recorder. This method does not require any expensive analytical instrumentation but can achieve higher sensitivity and there are no color interference issues, compared to conventional colorimetric methods. The method was further validated by detecting genomic DNA with high specificity. To the best of our knowledge, this is the first photothermal biosensing strategy for quantitative nucleic acid analysis on microfluidics using a thermometer, which brings fresh inspirations on the development of simple, low-cost, and miniaturized photothermal diagnostic platforms for quantitative detection of a variety of diseases at the point of care.

Peptidoglycan recognition proteins (PGRPs) are important components of insect immune systems, in which they play key roles. We cloned and sequenced two full-length PGRP, named

Paper-based microfluidic devices have undergone rapid development and offered a promising low-cost platform for disease diagnostics in poor-resource areas. Recently, paper-hybrid microfluidic devices have attracted much attention and been applied in various low-cost point-of-care testings, due to multiple merits derived from both paper and other substrates. This chapter summarizes the recent progress of low-cost paper and paper-hybrid microfluidic devices for rapid diagnostics of human diseases. The commonly used fabrication techniques are first introduced, and the applications of numerous paper and paper-hybrid microfluidic devices are then elaborated with an emphasis on rapid disease diagnostics in terms of the nature of biomolecules in three major categories, namely, protein-, gene-, and cell-based diagnostics. Both advantages and disadvantages of using these devices are discussed, followed by the perspectives for broad applications in low-cost diagnostics.

The rotary vector reducer is the core component of industrial robots, and the transmission efficiency is undoubtedly an important indicator of transmission performance. In addition, the assembly dimensional chain leads to clearance between parts, which can have a certain impact on the transmission efficiency. During previous studies, this effect was often ignored. Firstly, the cycloid tooth profile is a relatively large collection of points. Therefore, a more efficient tooth profile model is employed as the basis for the calculation. Secondly, the contact between the cycloid and the pinion is determined by experimental observation to be a point contact rather than a theoretical line contact. Moreover, the dynamics and friction loss models of the cycloid–pinion system are constructed. Finally, the assembly dimensional chain is introduced into the different structural designs. The clearance results were obtained with the extreme value method. The results show that the addition of the pinion sleeve allows the system to have a smoother drive process and a more efficient transmission; this was verified with ADAMS.

Patients arrive in burn centers with many etiologies of burn incidence (such as scald, contact, flame, steam, etc.). Treatment of these injuries depends on the burn depth and surface area of these burns. Moreover, earlier diagnosis and treatment of these burns lead to better patient outcomes. In this study, we show that THz-TDS imaging with a neural network classification algorithm can reproducibly classify burns, independent of their etiology, with an ROC-AUC of 88% in a porcine model.

The accuracy of clinical assessment of partial-thickness burn injuries has remained as low as 60% in the first few days post burn induction. Here, we present the implementation of a wavelet Shannon entropy technique for noninvasive characterization of burn injuries in an in vivo porcine burn study. Supervised machine learning using the support vector machines (SVM) based on the energy to Shannon entropy ratio (ESER) in the wavelet packet transform of the THz-TDS waveform yielded accuracy rates above 91% in differentiation between superficial, intermediate, and full-thickness burn categories.

Aim. The slow coronary flow (SCF) phenomenon was characterized by delayed perfusion of epicardial arteries, and no obvious coronary artery lesion in coronary angiography. The prognosis of patients with slow coronary flow was poor. However, there is lack of rapid, simple, and accurate method for SCF diagnosis. This study aimed to explore the utility of plasma choline as a diagnostic biomarker for SCF. Methods. Patients with coronary artery stenosis Results. Forty-four patients with SCF and 21 patients with NCF were included in this study. TFC in LAD, LCX, and RCA and mean TFC were significantly higher in patients with SCF in comparison with patients with NCF (32.67 ± 8.37 vs. 20.66 ± 3.41, P < 0.01). Plasma choline level was obviously higher in patients with SCF when compared with patients with NCF (754.65 ± 238.18 vs. 635.79 ± 108.25, P=0.007). Plasma choline level had significantly positive correlation with Mean TFC (r = 0.364, P=0.002). Receiver operating characteristic (ROC) analysis showed that choline with or without confounding factor adjustment had an AUC score of 0.65 and 0.77, respectively. Conclusions. TFC were closely related with plasma choline level, and plasma choline can be a suitable and stable diagnostic biomarker for SCF.

A simple, low-cost, and universal gold nanoparticle (AuNP) aggregation-induced photothermal biosensing platform has been developed for the first time and applied for the visual quantitative genetic detection using a common thermometer. By exploiting the photothermal effect of target-induced gold nanoparticle aggregation, visual quantitative biochemical analysis can be achieved by simply recording temperature signals using a common thermometer. Compared to conventional genetic testing methods, it is label- and amplification-free and can be completed in 40 min without the aid of any advanced analytical instruments. Mycobacterium tuberculosis (MTB) DNA was used as a model target to demonstrate the application of this photothermal biosensing platform. Although no costly instrument was used, high sensitivity and specificity were achieved with the limit of detection (LOD) of 0.28 nM, which was nearly 10-fold lower than that of the colorimetric method using a spectrometer. This AuNP aggregation-induced photothermal biosensing strategy provides a simple, low-cost, and universal platform for broad application of visual quantitative detection of nucleic acids and many other biomolecules, particularly in point-of-care (POC) biosensing applications.

Although noble metal nanocatalysts show superior performance to conventional catalysts, they can be problematic when balancing catalytic efficiency and reusability. In order to address this dilemma, we developed a smart paper transformer (s-PAT) to support nanocatalysts, based on easy phase conversion between paper and pulp, for the first time. The pulp phase was used to maintain the high catalytic efficiency of the nanocatalysts and the transformation to paper enabled their high reusability. Herein, as an example of smart paper transformers, a novel chromatography paper-supported Au nanosponge (AuNS/pulp) catalyst was developed through a simple water-based preparation process for the successful reduction of p-nitrophenol to demonstrate the high catalytic efficiency and reusability of the noble metal nanocatalyst/pulp system. The composition, structure, and morphology of the AuNS/pulp catalyst were characterized by XRD, TGA, FE-SEM, ICP, TEM, FT-IR, and XPS. The AuNS/pulp catalyst was transformed into the pulp phase during the catalytic reaction and into the paper phase to recover the catalysts after use. Owing to this smart switching of physical morphology, the AuNS/pulp catalyst was dispersed more evenly in the solution. Therefore, it exhibited excellent catalytic performance for p-nitrophenol reduction. Under optimal conditions, the conversion rate of p-nitrophenol reached nearly 100% within 6 min and the k value of AuNS/pulp (0.0106 s−1) was more than twice that of a traditional chromatography paper-based catalyst (0.0048 s−1). Additionally, it exhibited outstanding reusability and could maintain its high catalytic efficiency even after fifteen recycling runs. Accordingly, the unique phase switching of this smart paper transformer enables Au nanosponge to transform into a highly efficient and cost-effective multifunctional catalyst. The paper transformer can support various nanocatalysts for a wide range of applications, thus providing a new insight into maintaining both high catalytic efficiency and reusability of nanocatalysts in the fields of environmental catalysis and nanomaterials., A smart paper transformer supported nanocatalyst platform is developed based on the facile phase conversion between paper and pulp for both high-efficiency and high-reusability catalysis, with wide applications demonstrated by using Au nanosponge.

The requirement of on-demand microfluidic pumps and instrument-free readout methods remains major challenges for the development of microfluidics. Herein, a new type of microfluidic platform, an on-demand photothermal microfluidic pumping platform, has been developed using the on-chip nanomaterial-mediated photothermal effect as the novel and remotely tunable microfluidic driving force. The photothermal microfluidic pumping performance can be adjusted remotely by tuning the irradiation parameters, without changing on-chip parameters or replacing enzyme or other reagents. In contrast to graphene oxide, Prussian blue nanoparticles with stronger photothermal conversion efficiency were used as the model photothermal agent to demonstrate the proof of concept. The on-chip pumping distance is linearly correlated with both the irradiation time and the nanomaterial concentration. The applications of the photothermal microfluidic pumping have been demonstrated in multiplexed on-chip transport of substances such as gold nanoparticles and visual quantitative bar-chart detection of cancer biomarkers without using specialized instruments. Upon the contact-free irradiation by a laser pointer, the strong on-chip nanomaterial-mediated photothermal effect can serve as a robust and remotely tunable microfluidic pump in a PMMA/PDMS hybrid bar-chart chip to drive ink bars in a visual quantitative readout fashion. This is the first report of the photothermal microfluidic pumping platform, which has great potential for various microfluidic applications.

Chinese chestnut (Castanea mollissima) is an important germplasm resource for the breeding of Castanea species worldwide with vital ecological and economic value. Biotechnology overcomes the limitations of traditional breeding and accelerates germplasm improvement. However, a genetic transformation system for Chinese chestnut has not yet been established. In this study, a stable and efficient Agrobacterium-mediated genetic transformation method for Chinese chestnut is described. Embryogenic calli of C. mollissima cv. ‘Yanshanhongli’ were used as the target material. The sensitivity of embryogenic calli to kanamycin was determined, whereby the proliferation of non-transformed calli was completely inhibited at 180 mg/L. Antibiotic inhibition results for Chinese chestnut embryogenic calli showed that 50 mg/L cefotaxime and 500 μM timentin completely inhibited the growth of Agrobacterium tumefaciens but did not affect the normal growth of Chinese chestnut embryogenic calli. When embryogenic calli were co-cultured for 2 days with Agrobacterium tumefaciens strain AGL1 harboring the PBI121-EGFP plasmid, an embryogenic callus transformation efficiency of 4.55% was obtained, and two transgenic chimera were acquired. This Agrobacterium-mediated transformation system for Chinese chestnut provides a fundamental platform for genetic improvement of core germplasm and for further verification of gene function. A method of Agrobacterium-mediated transformation was established for Chinese chestnut, providing a basis for genetic improvement of core germplasm and an important platform for further verification of gene function in Chinese chestnut.

This work investigated the electrochemical degradation of amoxicillin (AMX) in aqueous solution with Cu-PbO2 electrode. The main influence factors on the degradation of AMX, such as Na2SO4 concentration, initial AMX concentration, current density and initial pH value, were analyzed in detail. Under the optimal conditions, the removal rates of AMX and chemical oxygen demand (COD) reached 99.4% and 46.3% after 150 min treatment. The results indicated that the electrochemical degradation of AMX fitted pseudo-first-order reaction kinetics. Compared with undoped PbO2 electrode, Cu-PbO2 electrode had a smaller crystal size, more proportion of hydroxyl oxygen species, greater AMX and chemical oxygen demand (COD) removal efficiency, higher average current efficiency (ACE) and lower electrical efficiency per log order (EE/O). Electrochemical oxidation using Cu-PbO2 electrodes was an effective way to eliminate amoxicillin in aqueous solution. Moreover, a possible degradation pathway including ring open and mineralization was proposed by intermediate products determined by GC-MS method. This paper could provide basic data and technique reference for the amoxicillin wastewater pollution control.

To observe the effects of saxagliptin on the expression of mitogen-activated protein kinase 38 (p38MAPK), nephrin and podocin in renal tissue in type 2 diabetic (T2DM) rats, and to explore the possible mechanism of its renal protection. Forty-eight male Sprague–Dawley rats were used for the study and divided into four different groups: normal controls (Group NC), DM controls (Group DM), DM + glibenclamide (Group Su) and DM + saxagliptin (Group Sa). The day drug administration started was defined as week 0. After 12 weeks, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), urea nitrogen (BUN) and creatinine (Cr) in serum were detected, simultaneously albumin and creatinine in urine were measured, respectively, and then urinary albumin/creatinine ratio (UACR) was calculated. The pathological morphology of kidney tissue in different groups was observed, and the expression of nephrin and podocin mRNA and protein in kidney tissue were detected. (1) After 12 weeks, FBG and HbA1c in Group Su and Group Sa were significantly lower than those in Group DM (both P

The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to enlarge the applied range of oridonin and explore its mechanism of action, a series of derivatives were designed and synthesized based on the structure of oridonin. Some of the derivatives were significantly more potent than oridonin against four cancer cell lines. Especially, the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly differentiated PLC/PRF/5 cells, with IC50 values as low as 1.36 μM and 0.78 μM respectively, while the IC50 values of oridonin are 8.12 μM and 7.41 μM. We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase. Moreover, it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins. Furthermore, compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect. Altogether, these results indicated that compound 20 is a promising lead for liver cancer therapeutics.

A series of TiO2 catalyst carriers with ceria additives were prepared by a precipitation method and tested for selective catalytic reduction (SCR) of NO by NH3. These samples were characterized by XRD, N2-BET, NH3-TPD, H2-TPR, TEM, XPS and in situ DRIFTS, respectively. Results showed that the appropriate addition of ceria can enhance the catalytic activity and thermostability of TiO2 catalyst carriers significantly. The maximum catalytic activity of Ti-Ce-Ox-500 is 98.5% at 400 °C with a GHSV of 100 000 h−1 and the high catalytic activity still remains even after the treatment at high temperature for 24 h. The high catalytic performance of Ti-Ce-Ox-500 can be attributed to a series of superior properties, such as larger specific surface area, more Bronsted acid sites, more hydrogen consumption, and the higher proportion of chemisorbed oxygen. Ceria atoms can inhibit the crystalline grain growth and the collapse of small channels caused by high temperatures. Furthermore, in situ DRIFTS in different feed gases show that the SCR reaction over Ti-Ce-Ox-500 follows both E-R and L-H mechanisms.

Carbon dots (CDs) have attracted attention in metal-free afterglow materials, but most CDs were heteroatom-containing and the afterglow emissions are still limited to the short-wavelength region. A universal approach to activate the room-temperature phosphorescence (RTP) of both heteroatom-free and heteroatom-containing CDs was developed by one-step heat treatment of CDs and boric acid (BA). The introduction of an electron-withdrawing boron atom in composites can greatly reduce the energy gap between the singlet and triplet state; the formed glassy state can effectively protect the excited triplet states of CDs from nonradiative deactivation. A universal host for embedding CDs to achieve long-lifetime and multi-color (blue, green, green-yellow and orange) RTP via a low cost, quick and facile process was developed. Based on their distinctive RTP performances, the applications of these CD-based RTP materials in information encryption and decryption are also proposed and demonstrated.

Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 μg of FRIL (p 0.0001) and 0.925 μg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50-100 ng FRIL or 600-800 μg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

BackgroundA variety of studies have demonstrated the role of lipocalin-2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study was aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D).MethodsA total 207 participants with T2D were included in this study. All participants were classified into DNP group and non-DNP (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an enzyme-linked immunosorbent assay method. ResultsSerum LCN2 levels in DNP group were higher than those in NDPN group (p = 0.001). Stratification analysis according to the tertiles of serum LCN2 levels showed that with the LCN2 level elevated, the number of participants with DPN increased, whereas the number of participants with NDPN decreased (trend p = 0.003). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, p = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (OR = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D.Conclusions Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy.

Macamides are a class of bioactive amide alkaloids found only in maca (Lepidium meyenii). Recent studies have shown that macamide-rich extracts possess various biological activities, such as antioxidative, immune-enhancing, and reproductive health-improving activities. In the present study, N-benzyl docosahexaenamide (NB-DHA), a newly identified macamide with the highest degree of unsaturation among all identified macamides, was identified from the maca extract. Microalgae oil, a docosahexaenoic acid-rich substance, was used as the starting material for the synthesis of NB-DHA. The effects of NB-DHA in colitis-induced mice were evaluated. NB-DHA significantly alleviated weight loss, shortening of colon length, and occult blood occurrence in mice with dextran sulfate sodium-induced colitis. Histological analysis revealed that following the administration of NB-DHA in mice with colitis, the infiltration of inflammatory cells and levels of proinflammatory factors, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and myeloperoxidase, decreased, whereas the level of the anti-inflammatory factor IL-10 increased. Furthermore, the decreased expression of intestinal tight junction proteins caused by colitis was upregulated by the administration of NB-DHA. These results indicate that NB-DHA could be developed as a therapeutic agent for ulcerative colitis.

Background: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons that lead to brain dysfunction. Recurrent seizures or status epilepticus can cause irreversible brain damage. The JAK2-STAT3 signal transduction pathway is stimulated by cytokines and involved in various pathological processes including inflammation, apoptosis and immune regulation in central system diseases. Keap1/Nrf2 is an important anti-oxidative stress pathway, which can reduce the toxic effects of oxygen free radicals and endogenous toxins on neurons. Genistein (Gen) can modulate inflammation and neuronal apoptosis, and may thereby have antiepileptic effects. This study aimed to explore the regulation of Genistein on JAK2/STAT3 and Keap1/Nrf2 signaling pathway and the protective effects on brain injury after epilepsy. Methods: Pentylenetetrazole (PTZ) was used to induce epilepsy in developing rats and Genistein was used for pretreatment of epilepsy. The seizure latency, grade scores and duration of the first generalized tonic-clonic seizure (GTCs) were recorded. Hippocampus tissue was sampled at 24 hours post-epilepsy. Immunofluorescence staining was used to observe the number of mature neurons, activated microglia and astrocytes in the hippocampal CA1 region. Western blot and qRT-PCR were used to determine the protein and mRNA levels of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, Nrf2, HO-1, NQO1, caspase3, Bax and Bcl2 in the hippocampus. Results: Immunofluorescence showed that the number of neurons significantly decreased, and activated microglia and astrocytes significantly increased after epilepsy; Western blot and q-PCR showed that the expressions of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, caspase3 and Bax significantly increased, while Nrf2, HO-1, NQO1 and Bcl-2 were significantly reduced after epilepsy. These effects were reversed by Genistein treatment. Moreover, Genistein was found to prolong seizure latency and reduce seizure intensity score and duration of generalized tonic-clonic seizures(GTCs). Conclusions: Genistein can activate the Keap1/Nrf2 antioxidant stress pathway and attenuate the activation of microglia and astrocytes. Genistein also inhibits the JAK2-STAT3 inflammation pathway and expression of apoptotic proteins, and increases the number of surviving neurons, thus having a protective effect on epilepsy-induced brain damage.

Quantum error mitigation (QEM) is crucial for obtaining reliable results on quantum computers by suppressing quantum noise with moderate resources. It is a key for successful and practical quantum algorithm implementations in the noisy intermediate scale quantum (NISQ) era. Since quantum-classical hybrid algorithms can be executed with moderate and noisy quantum resources, combining QEM with quantum-classical hybrid schemes is one of the most promising directions toward practical quantum advantages. In this paper, we show how the variational quantum-neural hybrid eigensolver (VQNHE) algorithm, which seamlessly combines the expressive power of a parameterized quantum circuit with a neural network, is inherently noise resilient with a unique QEM capacity, which is absent in vanilla variational quantum eigensolvers (VQE). We carefully analyze and elucidate the asymptotic scaling of this unique QEM capacity in VQNHE from both theoretical and experimental perspectives. Finally, we consider a variational basis transformation for the Hamiltonian to be measured under the VQNHE framework, yielding a powerful tri-optimization setup that further enhances the quantum-neural hybrid error mitigation capacity., Comment: 4.5 pages, 3 figures, with supplemental materials

BACKGROUND Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors, including diabetes, which results in an increased atherosclerotic burden, but the precise mechanisms for the occurrence and development of diabetic atherosclerosis have not been fully elucidated. AIM To summarize the potential role of retinol binding protein 4 (RBP4) in the pathogenesis of diabetic atherosclerosis, particularly in relation to the RBP4-Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. METHODS Male Wistar rats were randomly divided into three groups, including a control group (NC group), diabetic rat group (DM group), and diabetic atherosclerotic rat group (DA group). The contents of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), fasting insulin (FINS), fasting plasma glucose, and hemoglobin A1c (HbA1c) were measured. Moreover, the adipose and serum levels of RBP4, along with the expression levels of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, phosphorylated STAT3 (p-STAT3), B-cell lymphoma-2 (Bcl-2), and Cyclin D1 in aortic tissues were also measured. Besides, homeostasis model assessment of insulin resistance (HOMA-IR) and atherogenic indexes (AI) were calculated. RESULTS Compared with the NC and DM groups, the levels LDL-c, TG, TC, FINS, HOMA-IR, RBP4, and AI were upregulated, whereas that of HDL-c was downregulated in the DA group (P < 0.05); the mRNA levels of JAK2, STAT3, Cyclin D1, and Bcl-2 in the DA group were significantly increased compared with the NC group and the DM group; P-JAK2, p-JAK2/JAK2 ratio, p-STAT3, p-STAT3/STAT3 ratio, Cyclin D1, and Bcl-2 at protein levels were significantly upregulated in the DA group compared with the NC group and DM group. In addition, as shown by Pearson analysis, serum RBP4 had a positive correlation with TG, TC, LDL-c, FINS, HbA1C, p-JAK2, p-STAT3, Bcl-2, Cyclin D1, AI, and HOMA-IR but a negative correlation with HDL-c. In addition, multivariable logistic regression analysis showed that serum RBP4, p-JAK2, p-STAT3, and LDL-c were predictors of the presence of diabetic atherosclerosis. CONCLUSION RBP4 could be involved in the initiation or progression of diabetic atherosclerosis by regulating the JAK2/STAT3 signaling pathway.

Safety-critical systems are those systems whose failure would cause significant property loss or crisis. These systems possibly contain complex predicates, which represent the conditions of system state transformation. Predicate testing is critical to ensuring system safety. However, it is difficult to generate appropriate test cases for complex predicates. To resolve the issue, predicate testing criteria based on major clause are proposed. Major clause of predicate is a clause that directly determines the value of predicate, and the preponderances of testing criteria based on major clause is that not only guarantee the rigor of testing, but also reduce the testing cost. This paper presents an approach that using different test criteria based on major clause to automatically generate corresponding test case constraint set for predicates in safety-critical systems. Firstly, the complex predicate is modeled as an abstract syntax tree (AST). Secondly, truth table for predicates is generated by extracting AST and further filtered based on predicate testing criteria (such as PC, RACC and CACC). Finally, testing case constraints set is generated by a random algorithm to satisfy certain test criteria. Our experimental results show that the constraint set generated by our method is reasonable and our approach is correct. By introducing variants into the empirical system, our approach shows the validity of different test criteria.

MicroRNA-217 (miR-217) has been recently reported to be abnormally expressed during atherosclerosis. Nonetheless, it still remains unknown whether miR-217 can regulate inflammation, proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) in high-glucose condition. Sprague Dawley rats were used for establishing diabetic animal models. miR-217 mimics and miR-217 inhibitors were transfected into VSMCs. The miR-217 and ROCK1 expressions were measured by quantitative reverse transcription-polymerase chain reaction and Western blot. VSMCs' proliferation, migration, cell cycle, and apoptosis were validated using the Cell Counting Kit-8 assay, Transwell assay, and flow cytometry analysis, respectively. The binding sites between miR-217 and the 3'-untranslated region of ROCK1 were predicted via miRanda, PicTar, TargetScan, and microT databases, and the targeting relationship was confirmed by dual-luciferase reporter experiments. miR-217 was found to be upregulated in VSMCs treated by high glucose and aorta VSMCs of diabetic rats. Transfection of miR-217 mimics significantly induced VSMCs cycle arrest, inhibition of proliferation, reduction of migration, and enhancement of apoptosis. The bioinformatics analysis and dual-luciferase reporter experiments identified ROCK1 as a direct target of miR-217. miR-217 inhibits excessive proliferation and migration of VSMCs induced by high glucose by targeting ROCK1.

In this study, the CNTs were successfully compounded in PbO

Conventional colorimetric enzyme-linked immunosorbent assay (ELISA) is a time-consuming laboratory assay that is not very sensitive and consumes a large amount of samples. Herein, the development of a reusable, cost-effective, and eco-friendly poly(methyl methacrylate) (PMMA)/paper hybrid plug-and-play (PnP) device for high-sensitivity immunoassay by analyte enrichment and efficient passing-through washing has been reported. The PMMA device has multiple slots where a pre-patterned paper substrate can be inserted. The sample flows back-and-forth through a low-cost, 3D paper substrate within the PMMA channels, thereby enhancing the amount of analyte adsorbed and dramatically increasing the sensitivity while decreasing the assay time. After the enrichment assay, the paper substrate can simply be pulled out of the device, and the results can be qualitatively viewed with the naked eye or scanned through a simple desktop scanner for quantitative analysis. The paper substrate can be replaced with a new substrate so that the device can be reused. The limits of detection (LODs) of 200 pg/mL for immunoglobulin G (IgG) and 270 pg/mL for hepatitis B surface antigen (HBsAg) were obtained. This IgG assay is at least 10 times more sensitive than commercial ELISA kits. In addition, the PnP ELISA exhibited a significant increase in the linear dynamic range from 3 orders of magnitude in a common paper-based device to a wide range of six orders of magnitude in the PnP hybrid device. This reusable PnP device has great potential for the low-cost yet high-sensitivity detection of infectious diseases, cancers, and other important biomolecules. A reusable, cost-effective, and environment-friendly PnP device has been developed for high-sensitivity immunoassays (biochemical tests that measure proteins or other substances through their properties as antigens or antibodies). Immunoassays are widely used in the diagnosis, screening, and monitoring of diseases. However, such techniques as enzyme-linked immunosorbent assay (ELISA), which are extensively applied in developed countries, are not widely available in developing nations owing to limited funding and lack of skilled manpower. They are also time consuming and lacking in sensitivity. A team headed by XiuJun Li at the University of Texas at El Paso produced a low-cost device using poly(methyl methacrylate) (PMMA or Perspex) that is 10 times more sensitive than commercial ELISA kits. The authors believe that their PMMA device offers considerable potential for application in detecting infectious diseases and cancers in resource-poor settings.

As a class of crystalline porous materials, metal-organic frameworks (MOFs) have attracted increasing attention. Due to the nanoscale framework structure, adjustable pore size, large specific surface area, and good chemical stability, MOFs have been applied widely in many fields such as biosensors, biomedicine, electrocatalysis, energy storage and conversions. Especially when they are combined with aptamer functionalization, MOFs can be utilized to construct high-performance biosensors for numerous applications ranging from medical diagnostics and food safety inspection, to environmental surveillance. Herein, this article reviews recent innovations of aptamer-functionalized MOFs-based biosensors and their bio-applications. We first briefly introduce different functionalization methods of MOFs with aptamers, which provide a foundation for the construction of MOFs-based aptasensors. Then, we comprehensively summarize different types of MOFs-based aptasensors and their applications, in which MOFs serve as either signal probes or signal probe carriers for optical, electrochemical, and photoelectrochemical detection, with an emphasis on the former. Given recent substantial research interests in stimuli-responsive materials and the microfluidic lab-on-a-chip technology, we also present the stimuli-responsive aptamer-functionalized MOFs for sensing, followed by a brief overview on the integration of MOFs on microfluidic devices. Current limitations and prospective trends of MOFs-based biosensors are discussed at the end.

Geometric information and discontinuity characterization of rock masses are the key aspects of the analysis of the evolution and failure mechanisms of rockfalls. With the advantageous use of terrestrial laser scanning (TLS), the accurate three-dimensional (3D) spatial information of rock slopes can be obtained without contact. By conducting a fuzzy K-means algorithm in this study, the automatic identification of discontinuity sets is achieved, and dominant occurrences of rock mass discontinuities in each local region can be acquired in great detail. This automatic identification method permits the user to visually identify the discontinuity sets and acquire their spacial distribution features, e.g. occurrences, spacings, trace lengths and their geometric compounding relationships. At the same time, based on the shortest distance (SD) algorithm and the surface-to-plane volume calculation algorithm, the distributions, shapes, volumes and scars of the rockfalls can be accurately detected over the monitored time interval. These methods are able to provide adequate investigations and quantitative assessment for the rockfall failure mechanisms and evolutions of the Hongshiyan post failure rock slope after the 2014 Ludian earthquake. The topography of the landslide surface, mechanical properties, scales and the structural features of the discontinuities have a significant effect on the failure mechanisms, distributions and volumes of rockfalls. The main failure mechanisms of the rockfall investigated in this rock slope can be divided into plane failure, wedge failure and toppling failure. The plane and wedge failures mainly occurred in the landslide surface while the toppling failures are mainly observed along the edge of the post failure slope, which is obviously responded by preferred discontinuities. The reverse-dip stratified structure characteristics and the excavation disturbances during the recovering and slope treatment stage induce numerous progressive and continuous failures of rockfalls. The results are beneficial for the design and optimization of rockfall treatments.