Miracle-dz/UniFAR-FTUs huggingface dataset:
5-Chloro-2-Guanidinobenzimidazole (ClGBI) Is a Non-Selective Inhibitor of the Human HV1 Channel

5-chloro-2-guanidinobenzimidazole (ClGBI), a small-molecule guanidine derivative, is a known effective inhibitor of the voltage-gated proton (H+) channel (HV1, Kd ≈ 26 μM) and is widely used both in ion channel research and functional biological assays. However, a comprehensive study of its ion channel selectivity determined by electrophysiological methods has not been published yet. The lack of selectivity may lead to incorrect conclusions regarding the role of hHv1 in physiological or pathophysiological responses in vitro and in vivo. We have found that ClGBI inhibits the proliferation of lymphocytes, which absolutely requires the functioning of the KV1.3 channel. We, therefore, tested ClGBI directly on hKV1.3 using a whole-cell patch clamp and found an inhibitory effect similar in magnitude to that seen on hHV1 (Kd ≈ 72 μM). We then further investigated ClGBI selectivity on the hKV1.1, hKV1.4-IR, hKV1.5, hKV10.1, hKV11.1, hKCa3.1, hNaV1.4, and hNaV1.5 channels. Our results show that, besides HV1 and KV1.3, all other off-target channels were inhibited by ClGBI, with Kd values ranging from 12 to 894 μM. Based on our comprehensive data, ClGBI has to be considered a non-selective hHV1 inhibitor; thus, experiments aiming at elucidating the significance of these channels in physiological responses have to be carefully evaluated.
Numerical study of tie spatially induced group velocity dispersion

We have studied, by numerical simulations, the spatially-induced group velocity dispersion in the propagation of ultrashort-pulsed Bessel beams in free space- The simulation results have confirmed the existence of the spatially-induced dispersions in the propagation of a truncated Bessel beam which can be constructed in practice- It is shown that the spatially-induced dispersion is observed when the diffraction length of truncated Bessel beams is longer than the dispersion length of spatially-induced group velocity dispersion-
Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3–5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b–4 patients on LPD (0.6–0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.
ROK and RSK2-kinase pathways differ between senescent human renal and mesenteric arteries

Objective: Small arteries from different organs vary with regard to the mechanisms that regulate vasoconstriction. This study investigated the impact of advanced age on the regulation of vasoconstriction in isolated human small arteries from kidney cortex and periintestinal mesenteric tissue. Methods: Renal and mesenteric tissues were obtained from patients (mean age 71 ± 9 years) undergoing elective surgery. Furthermore, intrarenal and mesenteric arteries from young and aged mice were studied. Arteries were investigated by small vessel myography and western blot. Results: Human intrarenal arteries (h-RA) showed higher stretch-induced tone and higher reactivity to α1 adrenergic receptor stimulation than human mesenteric arteries (h-MA). Rho-kinase (ROK) inhibition resulted in a greater decrease in Ca2+ and depolarization-induced tone in h-RA than in h-MA. Basal and α1 adrenergic receptor stimulation-induced phosphorylation of the regulatory light chain of myosin (MLC20) was higher in h-RA than in h-MA. This was associated with higher ROK-dependent phosphorylation of the regulatory subunit of myosin light-chain-phosphatase (MLCP), MYPT1-T853. In h-RA phosphorylation of ribosomal S6-kinase II (RSK2-S227) was significantly higher than in h-MA. Stretch-induced tone and RSK2 phosphorylation was also higher in interlobar arteries (m-IAs) from aged mice than in respective vessels from young mice and in murine mesenteric arteries (m-MA) from both age groups. Conclusion: Vasoconstriction in human intrarenal arteries shows a greater ROK-dependence than in mesenteric arteries. Activation of RSK2 may contribute to intrarenal artery tone dysregulation associated with aging. Compared with h-RA, h-MA undergo age-related remodeling leading to a reduction of the contractile response to α1 adrenergic stimulation.
2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department

Background: Sepsis/septic shock is a life-threatening and time-dependent condition that requires timely management to reduce mortality. This review aims to update physicians with regard to the main pillars of treatment for this insidious condition. Methods: PubMed, Scopus, and EMBASE were searched from inception with special attention paid to November 2021–January 2023. Results: The management of sepsis/septic shock is challenging and involves different pathophysiological aspects, encompassing empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload. In cases of refractory shock, vasopressin (rather than epinephrine) should be combined with NE to reach an acceptable level of pressure control. If mechanical ventilation is indicated, the tidal volume should be reduced from 10 to 6 mL/kg. Heparin is administered to prevent venous thromboembolism, and glycemic control is recommended. The efficacy of other treatments (e.g., proton-pump inhibitors, sodium bicarbonate, etc.) is largely debated, and such treatments might be used on a case-to-case basis. Conclusions: The management of sepsis/septic shock has significantly progressed in the last few years. Improving knowledge of the main therapeutic cornerstones of this challenging condition is crucial to achieve better patient outcomes.
Relationship of speed and unilateral vertical jump performance of basketball athletes

Abstract Basketball is a sport practiced around the world in this way, performances tests especially with low-cost and accessible are suggested to adjust the training. The 00aim of present study was to evaluate and correlate the speed and jump performance of lower limbs of basketball athletes from the Praia Grande, city of São Paulo, Brazil. Twelve male athletes (6.92 ± 2.57 years of pratice) from the Basketball team of Praia Grande City, aged 18.7 ± 0.6 years, height 1.85 ± 0.06, body mass 83.66 ± 10.16 kg were evaluated. The athletes were submitted to test sessions using the protocol for evaluating the maximum speed of 20 meters and the unilateral vertical jump. The speed on 20 meter test was 3.53 ± 0.20 seconds. Although an asymmetry of 17.81 ± 14.64% was found, no statistical difference (p = 0.817) was found between the dominant (36.50 ± 7.36 cm) and non-dominant (35.92 ± 5.63 cm) of vertical jump performance. Additionally, correlation between 20-meter test and values jump was found to dominant leg (p = 0.042) but not to non-dominant leg (p = 0.704). In conclusion, although asymmetry was found between members of the dominant and non-dominant side of the pitch, did not show any difference in the vertical jump.
Comparación de diferentes algoritmos metaheurísticos en la estimación de parámetros del modelo relacional general de cromatografía líquida en columna Comparison between different metaheuristic algorithms in parameter estimation of the general relational model of column liquid chromatography

Optimization, scaling and parameter estimation are inverse problems that appear in many biotechnological processes. In the solution of inverse problems, different techniques such as metaheuristics algorithms, have been used. These algorithms efficiently search for and find good solutions to a problem with a reasonable computational cost. In this pape, four well-known metaheuristic algorithms (Genetic Algorithm, Differential Evolution, Ant Colony Optimization and Particle Swarm Optimization) are applied to the problem of parameter estimation in the liquid chromatography separation process. The effectiveness of each method is analyzed and performance comparison based on different statistical criteria is made. The procedure allows to obtain estimated values close to the real parameters, with a good fit of the curves generated by the model to syntetically generated experimental data. The algorithm that performs better is Differential Evolution.
Combination Therapy of Low-dose Steroids, Tacrolimus and Mycophenolate Mofetil in Primary Membranous Nephropathy: A Single-center Retrospective Cohort Study

ABSTRACT Background: Primary membranous nephropathy (pMN) is the most common pathological type of nephrotic syndrome in adults. Therefore, it is imperative to find a better combination therapy with fewer adverse effects for patients with pMN. Methods: This study enrolled 84 patients with biopsy-proven pMN and nephrotic syndrome. Thirty patients in the low-dose multitarget regimen (LDMT) group received low-dose glucocorticoids along with tacrolimus and mycophenolate mofetil, and 54 patients in the prednisone plus intravenous cyclophosphamide regimen (PC) group received corticosteroids plus intravenous cyclophosphamide. The clinical efficacy and safety of the LDMT and PC regimens in treating pMN in adults were analyzed and compared. Results: The cumulative complete remission rate was 6.67%, 56.30%, and 83.14% at the 6th, 12th, and 24th month after treatment in the LDMT group, and 16.67%, 60.84%, and 81.02% in the PC group, respectively (P = 0.620). The generalized estimating equation analysis showed that the longer the treatment duration, the better the improvements in serum albumin and urinary protein levels, and hyperlipidemia (P = 0.0001). However, the serum creatinine levels in both groups remained stable during the treatment period. Meanwhile, the relapse rates were comparable between the two groups (21.43% vs. 22.00%, P = 0.953). Moreover, patients in the LDMT group showed fewer adverse events than those in the PC group (46.67% vs. 72.22%, P = 0.020). Conclusions: These data indicated that the low-dose multitarget regimen, which might be an alternative treatment choice for patients with pMN, had a more favorable safety profile and non-inferior efficacy compared with prednisone plus intravenous cyclophosphamide.
A study on the public attention in the Belt and Road Initiative

This paper constructs residents’ attentiveness index of the Belt and Road Initiative by big data, and combines social and economic factors to study the spatial and temporal distribution of initiative attentiveness, we can find that (1) the attentiveness of the initiative will be greatly affected by large government conferences, and there is a mismatch between the areas covered by the initiative and the areas. (2) both per capita GDP and the proportion of fiscal investment in GDP have a significantly positive impact on the initiative attentiveness of residents, while CPI has a significantly negative Population size and unemployment rates do not have a significant impact on the initiative’s attentiveness. (3) the impact of initiative attentiveness has obvious regional differences. This paper breaks the habitual cognition of the attention of the initiative, and combines the social and economic conditions, and puts forward some suggestions, such as expanding the boundary of the Belt and Road, taking multiple measures to mobilize the social forces to build the Belt and Road, and treating the different policies.
Trapdoor Fault Activation: A Step Toward Caldera Collapse at Sierra Negra, Galápagos, Ecuador

The 2018 Sierra Negra eruption resulted in meter‐scale subsidence due to basaltic magma extraction from a deflating reservoir. The eruption was also characterized by dike intrusions, >4 MW earthquakes, and sulfur dioxide emissions. We use a combination of Interferometric Synthetic Aperture Radar, Digital Elevation Model, Global Positioning System and seismic data to assess conditions required to trigger episodic caldera collapse at Sierra Negra. The 2018 effusive eruption was mainly sourced from a horizontal sill located at ∼2 km depth, with a minimum erupted bulk volume of 0.19 km3. The modeled reservoir is bound by a C‐shaped ring of seismicity, suggesting trapdoor fault slip. Two >4.5 MW earthquakes (5 and 22 July 2018) produced localized subsidence north of the southern trapdoor fault. After removing the modeled subsidence signal, distributed normal trapdoor fault slip explains the location of residual displacement. Furthermore, distributed fault models indicate slip occurred along the northern, central and southern segments of the trapdoor fault during the entire eruption, until 25 August 2018. Theoretical models of caldera collapse estimate that an erupted volume of 0.19 km3 is too small to trigger full‐scale caldera collapse, given the caldera aspect ratio (depth/diameter) of 0.22. Nonetheless, the spatial distribution and duration of seismicity and slip suggest trapdoor fault activation is the initial stage of caldera collapse at Sierra Negra, which may lead to full‐scale caldera collapse during larger eruptions. Alternatively, hundreds of medium‐sized eruptions, similar to that of 2018, may have triggered fault slip events over the past millennia.
Bone Morphogenetic Protein-4 Impairs Retinal Endothelial Cell Barrier, a Potential Role in Diabetic Retinopathy

Bone Morphogenetic Protein 4 (BMP4) is a secreted growth factor of the Transforming Growth Factor beta (TGFβ) superfamily. The goal of this study was to test whether BMP4 contributes to the pathogenesis of diabetic retinopathy (DR). Immunofluorescence of BMP4 and the vascular marker isolectin-B4 was conducted on retinal sections of diabetic and non-diabetic human and experimental mice. We used Akita mice as a model for type-1 diabetes. Proteins were extracted from the retina of postmortem human eyes and 6-month diabetic Akita mice and age-matched control. BMP4 levels were measured by Western blot (WB). Human retinal endothelial cells (HRECs) were used as an in vitro model. HRECs were treated with BMP4 (50 ng/mL) for 48 h. The levels of phospho-smad 1/5/9 and phospho-p38 were measured by WB. BMP4-treated and control HRECs were also immunostained with anti-Zo-1. We also used electric cell-substrate impedance sensing (ECIS) to calculate the transcellular electrical resistance (TER) under BMP4 treatment in the presence and absence of noggin (200 ng/mL), LDN193189 (200 nM), LDN212854 (200 nM) or inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2; SU5416, 10 μM), p38 (SB202190, 10 μM), ERK (U0126, 10 μM) and ER stress (Phenylbutyric acid or PBA, 30 μmol/L). The impact of BMP4 on matrix metalloproteinases (MMP2 and MMP9) was also evaluated using specific ELISA kits. Immunofluorescence of human and mouse eyes showed increased BMP4 immunoreactivity, mainly localized in the retinal vessels of diabetic humans and mice compared to the control. Western blots of retinal proteins showed a significant increase in BMP4 expression in diabetic humans and mice compared to the control groups (p < 0.05). HRECs treated with BMP4 showed a marked increase in phospho-smad 1/5/9 (p = 0.039) and phospho-p38 (p = 0.013). Immunofluorescence of Zo-1 showed that BMP4-treated cells exhibited significant barrier disruption. ECIS also showed a marked decrease in TER of HRECs by BMP4 treatment compared to vehicle-treated HRECs (p < 0.001). Noggin, LDN193189, LDN212854, and inhibitors of p38 and VEGFR2 significantly mitigated the effects of BMP4 on the TER of HRECs. Our finding provides important insights regarding the role of BMP4 as a potential player in retinal endothelial cell dysfunction in diabetic retinopathy and could be a novel target to preserve the blood–retinal barrier during diabetes.
Mimicked Mixing-Induced Heterogeneities of Industrial Bioreactors Stimulate Long-Lasting Adaption Programs in Ethanol-Producing Yeasts

Commercial-scale bioreactors create an unnatural environment for microbes from an evolutionary point of view. Mixing insufficiencies expose individual cells to fluctuating nutrient concentrations on a second-to-minute scale while transcriptional and translational capacities limit the microbial adaptation time from minutes to hours. This mismatch carries the risk of inadequate adaptation effects, especially considering that nutrients are available at optimal concentrations on average. Consequently, industrial bioprocesses that strive to maintain microbes in a phenotypic sweet spot, during lab-scale development, might suffer performance losses when said adaptive misconfigurations arise during scale-up. Here, we investigated the influence of fluctuating glucose availability on the gene-expression profile in the industrial yeast Ethanol Red™. The stimulus–response experiment introduced 2 min glucose depletion phases to cells growing under glucose limitation in a chemostat. Even though Ethanol Red™ displayed robust growth and productivity, a single 2 min depletion of glucose transiently triggered the environmental stress response. Furthermore, a new growth phenotype with an increased ribosome portfolio emerged after complete adaptation to recurring glucose shortages. The results of this study serve a twofold purpose. First, it highlights the necessity to consider the large-scale environment already at the experimental development stage, even when process-related stressors are moderate. Second, it allowed the deduction of strain engineering guidelines to optimize the genetic background of large-scale production hosts.
Impact of dental bullying on bruxism associated with poor sleep quality among adolescents.

This study aimed to investigate the impact of school bullying and oral health-related verbal bullying on the occurrence of bruxism associated with poor sleep quality among adolescents. This cross-sectional study was nested in a cohort study performed with a sample of children from southern Brazil. Possible sleep bruxism was determined by the question: "Has anyone told you that you grind your teeth in your sleep? " Sleep quality was determined by answering the following question: "How would you classify the quality of your sleep? ". The outcome was created by combining occurrence of sleep bruxism and poor sleep quality. The Sense of Coherence (SOC) was assessed using the SOC-13 scale. Bullying was investigated using the victim scale of the Olweus Bullying Questionnaire and oral health-related verbal bullying using an item from the Child Perceptions Questionnaire-11-14. Demographic, socioeconomic, psychosocial, and clinical data were also collected. Poisson regression models with robust variance were used. Results were expressed as prevalence ratio (PR) and 95% confidence intervals (95% CI). A total of 429 adolescents with a mean age of 12.6 (standard deviation 1.3) years were evaluated. The prevalence of bruxism associated with poor sleep quality was 23.7%. Victims of school bullying (PR 2.06; 95%CI: 1.01-4.22) and oral health-related verbal bullying (PR 1.87; 95%CI: 1.18-2.95) presented higher prevalence of bruxism associated with poor sleep quality. Factors such as skin color and SOC were also associated with the outcome. These findings suggest an association between episodes of bullying and bruxism related to poor sleep quality.
Comparative Analysis of Image Registration Using Pixel, Wavelet and Translation Method

Image Registration is the process of estimating an optimal transformation between two images. There are many application of image registration now a day such as in FMRI motion correction, geometric distortion in EPI, alignment of images obtained at different time or with imaging parameters, formation of composite functional maps, mapping of PET/SPECT to MRI image. In this work the image registration analysis is done using the affine transformation model in our proposed three method image registration using ‘pixel’, ‘wavelet’ and ‘translation’ method. A comparative experiment in between these methods based on the analysis time and root mean square deviation. If the image is displaced from its place which means it can be rotated, displaced from its original axis vertically or horizontally this method can detect the displacement and can get the original image. At first we do a random rotation and then we find an image which is larger in size from the original image. Then we again rotate the image by reshaping the size of the image. The registered is finding from again rotating the image in a loop and tries to find a relation between them. From this relation we get the value at which the image was rotated or displaced from the original image. Then we reverse the process and get the final result.
Principles of Logic Design with Nanoscale Thin Film Memristive Systems for High Performance Digital Circuit Applications

The characteristic pinched hysteresis behavior of memristors has been reported by stacks of a variety of materials. This paper aims to examine the principles of logic design using such two terminal memristive systems for high performance digital circuit applications. As against logic design with standard CMOS, the benefits of logic design with memristors have been stated. The realization and operation of memristor based AND and OR hybrid logic gates obtained by integrating memristors with standard CMOS logic have been discussed. The IMPLY and MAGIC logic families have been demonstrated by covering MAGIC NOR and NAND logic gate implementation with MAGIC NOR in detail. A qualitative comparison has been drawn towards the end of the paper to conclude on the suitability and application space for each of the logic families studied in this paper. This work also describes the hybrid CMOS-memristive logic family known as MRL (Memristor Ratioed Logic). With the addition of CMOS inverters, this logic family's OR and AND logic gates, which are based on memristive components, are given a full logic structure and signal restoration. The MRL family, in contrast to earlier memristor-based logic families, is compatible with conventional CMOS logic.