Hovesanchez0119

Lipotoxicity is an important factor in the development and progression of nonalcoholic steatohepatitis. Excessive accumulation of saturated fatty acids can increase the substrates of the mitochondrial electron transport chain in hepatocytes and cause the generation of reactive oxygen species, resulting in oxidative stress, mitochondrial dysfunction, loss of mitochondrial membrane potential, impaired triphosphate (ATP) production, and fracture and fragmentation of mitochondria, which ultimately leads to hepatocellular inflammatory injuries, apoptosis, and necrosis. In this study, we systematically investigated the effects and molecular mechanisms of empagliflozin on lipotoxicity in palmitic acid-treated LO2 cell lines. We found that empagliflozin protected hepatocytes and inhibited palmitic acid-induced lipotoxicity by reducing oxidative stress, improving mitochondrial functions, and attenuating apoptosis and inflammation responses. The mechanistic study indicated that empagliflozin significantly activated adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα) through Calcium/Calmodulin dependent protein kinase kinase beta (CAMKK2) instead of liver kinase B1 (LKB1) or TGF-beta activated kinase (TAK1). The activation of empagliflozin on AMPKα not only promoted FoxO3a phosphorylation and thus forkhead box O 3a (FoxO3a) nuclear translocation, but also promoted Nrf2 nuclear translocation. Furthermore, empagliflozin significantly upregulated the expressions of antioxidant enzymes superoxide dismutase (SOD) and HO-1. In addition, empagliflozin did not attenuate lipid accumulation at all. These results indicated that empagliflozin mitigated lipotoxicity in saturated fatty acid-induced hepatocytes, likely by promoting antioxidant defense instead of attenuating lipid accumulation through enhanced FoxO3a and Nrf2 nuclear translocation dependent on the CAMKK2/AMPKα pathway. The CAMKK2/AMPKα pathway might serve as a promising target in treatment of lipotoxicity in nonalcoholic steatohepatitis.The development of targeted therapies (BRAF/MEK inhibitors) and immunotherapy have had a major impact on the treatment of melanoma. However, the majority of patients with advanced melanomas succumb to their disease. The mechanisms of resistance to both targeted therapies and immunotherapies are numerous and have been well-described. These include the alternative activation of BRAF/MEK signaling, novel compensating mutations in additional oncogenes, and loss of neoantigens. There has been limited development of small molecules that target alternative pathways in melanoma in the last two decades. We have previously identified triphenylmethanes as a class that shows activity against a wide variety of tumors. We have synthesized a novel triphenylmethane, indolium 1, and demonstrated its efficacy against an aggressive vemurafenib-resistant melanoma in vivo. Indolium 1 has a novel mechanism of action against melanoma, in that it results in induction of the tumor-suppressor EPHA3. We believe that pre-IND studies are warranted for this novel compound, given its mechanism of action and ability to inhibit the growth of vemurafenib resistant melanoma in vivo.Food is processed to make it safe, to make its shelf-life more stable, and to make it more desirable [...].Kelp and laver are large economic macroalgae in China, which are rich in nutrients, especially Mn and Zn. Excessive intake of Mn and Zn can be harmful to the human body. Therefore, it is necessary to develop a convenient and efficient method to detect the contents of Mn and Zn in macroalgae. In this experiment, red carbon dots (R-CDs) doped with N and S elements were prepared by the thermal solvent method. The obtained R-CDs displayed excitation wavelength-independent fluorescent emission in the red spectral region. The R-CDs were used to construct a fluorescent probe for specific recognition of Mn2+ and Zn2+, achieving high-sensitivity detection of Mn2+ and Zn2+. The detection results showed a good linear relationship between fluorescence intensity and Mn2+ concentration, and the calculated detection limit was 0.23 nmol/L. For the detection of Zn2+, the detection limit was estimated as 19.1 nmol/L. At the same time, the content distribution of Mn and Zn elements in macroalgae produced in Fujian was investigated by the constructed fluorescence probe. It was found that kelp, laver, and their products are rich in Mn and Zn elements, and the content of Mn and Zn elements in laver is higher than that in kelp, which can be used as the optimal food supplement for Mn and Zn elements.Wearable biosensors for continuous health monitoring, particularly those used for glucose detection, have a limited operational lifetime due to biodegradation and fouling. As a result, patients must change sensors frequently, increasing cost and patient discomfort. Arrays of multiple sensors, where the individual devices can be activated on demand, increase overall operational longevity, thereby reducing cost and improving patient outcomes. This work demonstrates the feasibility of this approach via decomposition of combustible nitrocellulose membranes that protect the individual sensors from exposure to bioanalytes using a current pulse. Metal contacts, connected by graphene-loaded PEDOTPSS polymer on the surface of the membrane, deliver the required energy to decompose the membrane. Nitrocellulose membranes with a thickness of less than 1 µm consistently transfer on to polydimethylsiloxane (PDMS) wells. An electrical energy as low as 68 mJ has been shown to suffice for membrane decomposition.Tea, after water, is the most frequently consumed beverage in the world. The fermentation of tea leaves has a pivotal role in its quality and is usually monitored using the laboratory analytical instruments and olfactory perception of tea tasters. Developing electronic sensing platforms (ESPs), in terms of an electronic nose (e-nose), electronic tongue (e-tongue), and electronic eye (e-eye) equipped with progressive data processing algorithms, not only can accurately accelerate the consumer-based sensory quality assessment of tea, but also can define new standards for this bioactive product, to meet worldwide market demand. Using the complex data sets from electronic signals integrated with multivariate statistics can, thus, contribute to quality prediction and discrimination. The latest achievements and available solutions, to solve future problems and for easy and accurate real-time analysis of the sensory-chemical properties of tea and its products, are reviewed using bio-mimicking ESPs. These advanced sensing technologies, which measure the aroma, taste, and color profiles and input the data into mathematical classification algorithms, can discriminate different teas based on their price, geographical origins, harvest, fermentation, storage times, quality grades, and adulteration ratio. Although voltammetric and fluorescent sensor arrays are emerging for designing e-tongue systems, potentiometric electrodes are more often employed to monitor the taste profiles of tea. The use of a feature-level fusion strategy can significantly improve the efficiency and accuracy of prediction models, accompanied by the pattern recognition associations between the sensory properties and biochemical profiles of tea.Better diagnostics are always essential for the treatment and prevention of a disease. Existing technologies for detecting infectious and non-infectious diseases are mostly tedious, expensive, and do not meet the World Health Organization's (WHO) ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end user) criteria. Hence, more accurate, sensitive, and faster diagnostic technologies that meet the ASSURED criteria are highly required for timely and evidenced-based treatment. Presently, the diagnostics industry is finding interest in microfluidics-based biosensors, as this integration comprises all qualities, such as reduction in the size of the equipment, rapid turnaround time, possibility of parallel multiple analysis or multiplexing, etc. Microfluidics deal with the manipulation/analysis of fluid within micrometer-sized channels. Biosensors comprise biomolecules immobilized on a physicochemical transducer for the detection of a specific analyte. In this review article, we provide an outline of the history of microfluidics, current practices in the selection of materials in microfluidics, and how and where microfluidics-based biosensors have been used for the diagnosis of infectious and non-infectious diseases. Our inclination in this review article is toward the employment of microfluidics-based biosensors for the improvement of already existing/traditional methods in order to reduce efforts without compromising the accuracy of the diagnostic test. This article also suggests the possible improvements required in microfluidic chip-based biosensors in order to meet the ASSURED criteria.Evaluation of sympathetic nerve activity (SNA) using skin sympathetic nerve activity (SKNA) signal has attracted interest in recent studies. However, signal noises may obstruct the accurate location for the burst of SKNA, leading to the quantification error of the signal. In this study, we use the Teager-Kaiser energy (TKE) operator to preprocess the SKNA signal, and then candidates of burst areas were segmented by an envelope-based method. Since the burst of SKNA can also be discriminated by the high-frequency component in QRS complexes of electrocardiogram (ECG), a strategy was designed to reject their influence. Finally, a feature of the SKNA energy ratio (SKNAER) was proposed for quantifying the SKNA. The method was verified by both sympathetic nerve stimulation and hemodialysis experiments compared with traditional heart rate variability (HRV) and a recently developed integral skin sympathetic nerve activity (iSKNA) method. The results showed that SKNAER correlated well with HRV features (r = 0.60 with the standard deviation of NN intervals, 0.67 with low frequency/high frequency, 0.47 with very low frequency) and the average of iSKNA (r = 0.67). SKNAER improved the detection accuracy for the burst of SKNA, with 98.2% for detection rate and 91.9% for precision, inducing increases of 3.7% and 29.1% compared with iSKNA (detection rate 94.5% (p < 0.01), precision 62.8% (p < 0.001)). The results from the hemodialysis experiment showed that SKNAER had more significant differences than aSKNA in the long-term SNA evaluation (p < 0.001 vs. p = 0.07 in the fourth period, p < 0.01 vs. p = 0.11 in the sixth period). The newly developed feature may play an important role in continuously monitoring SNA and keeping potential for further clinical tests.We synthesized core-shell-shaped nanocomposites composed of a single-walled carbon nanotube (SWCNT) and heptadecafluorooctanesulfonic acid-doped polypyrrole (C8F-doped-PPy)/phenyllatic acid (PLA), i.e., C8F-doped-PPy/PLA@SWCNT, for detecting acetone gas with high sensitivity and humidity stability. The obtained nanocomposites have the structural features of a sensing material as a C8F-doped-PPy layer surrounding a single-stranded SWCNT, and a PLA layer on the outer surface of the PPy as a specific sensing layer for acetone. PLA was chemically combined with the positively charged PPy backbone and provided the ability to reliably detect acetone gas at concentrations as low as 50 ppb even at 25 °C, which is required for medical diagnoses via human breath analysis. selleck compound When C8F was contained in the pyrrole monomer in a ratio of 0.1 mol, it was able to stably detect an effective signal in a relative humidity (RH) of 0-80% range.