Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptosis regulation by the tyrosine-protein kinase CSK

C-terminal Src kinase (CSK) is a cytosolic tyrosine-protein kinase with an important role in regulating critical cellular decisions, such as cellular apoptosis, survival, proliferation, cytoskeletal organization and many others. Current knowledge on the CSK mechanisms of action, regulation and functions is still at an early stage, most of CSK’s known actions and functions being mediated by the negative regulation of the SRC family of tyrosine kinases (SFKs) through phosphorylation. As SFKs play a vital role in apoptosis, cell proliferation and survival regulation, SFK inhibition by CSK has a pro-apoptotic effect, which is mediated by the inhibition of cellular signaling cascades controlled by SFKs, such as the MAPK/ERK, STAT3 and PI3K/AKT signaling pathways. Abnormal functioning of CSK and SFK activation can lead to diseases such as cancer, cardiovascular and neurological manifestations. This review describes apoptosis regulation by CSK, CSK inhibition of the SFKs and further explores the clinical relevance of CSK in important pathologies, such as cancer, autoimmune, autoinflammatory, neurologic diseases, hypertension and HIV/AIDS.
Quercetin ameliorates chicken quality by activating the PI3K/PKB/AMPK signaling pathway in broilers

This study was conducted to investigate the effects and mechanism of quercetin on chicken quality in broilers. We selected 480 AA broilers (1 day old) and randomly allotted those to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Compared with the control group, the supplementation with 0.4 g of quercetin significantly increased the pH45min and L* value of the thigh muscle and decreased the shearing force of the thigh muscle and breast muscle and drip loss of the thigh muscle (P < 0.05). The supplementation with 0.6 g/kg of quercetin significantly increased the pH45min and L* value of the thigh muscle, and pH45min of breast muscle and decreased the drip loss of the thigh muscle (P < 0.05). Sensory scores of meat color, tenderness, and juiciness also were improved with increasing quercetin concentration (P < 0.05). The inosinic acid (IMP) content of the breast and thigh muscles of broilers was significantly increased by supplementation with 0.6 g/kg of quercetin (P < 0.05). Supplementation with 0.2, 0.4, and 0.6 g of quercetin significantly reduced mRNA expression of L-FABP (P < 0.05, P < 0.05, and P < 0.05); supplementation with 0.4 and 0.6 g/kg of quercetin significantly increased mRNA expression of PKB and AMPKα1 (P < 0.05 and P < 0.05); supplementation with 0.6 g/kg of quercetin in the diet significantly reduced mRNA expression of SREBP1 and HMGR (P < 0.05 and P < 0.05) and significantly increased mRNA expression of CPT1 and PPARγ (P < 0.05 and P < 0.05); and supplementation with 0.2, 0.4, and 0.6 g/kg of quercetin significantly increased mRNA expression of PI3K, LPL, and Apo A1 and significantly reduced mRNA expression of ACC and FATP1 in the breast muscle of broilers (P > 0.05). PI3k, PKB, AMPK, SREBP1, and L-FABP were significantly and positively correlated with pH45min (P < 0.05); PPARγ was significantly and positively correlated with shear force (P < 0.05); CPT1 was significantly and positively correlated with the L* value (P < 0.05); and HMGR was significantly and positively correlated with drip loss (P < 0.05). In conclusion, quercetin improved the meat quality, protecting it against lipid oxidation and deposition by regulating the PI3K/PKB/AMPKα1 signaling pathway in the breast muscle of broilers.
R&D investment, financing constraints and corporate financial performance: Empirical evidence from China

Enterprises are a deeply significant pillar of social and economic development. The excellent economic interests of enterprises play an essential role in promoting social and economic development. Business is a major innovation force in improving a country’s independent innovation capacity, which in turn is a key factor in shaping its core competitiveness. As the fuel of technological innovation for enterprises, Research and development (R&D) can accelerate their development and enhance their competitiveness. By using Chinese A-share listed companies from 2007 to 2019 as a sample, this study attempts to examine the specific impact of R&D investment by Chinese companies on corporate performance. Key to the development of R&D activities, R&D investment is directly related to the source of funding, the quality of financing channels and the extent of financing restrictions. The current study explains why enterprise innovation cannot be separated from the input and support of capital, technology, professional talent and other factors from the perspective of enterprise financing constraints. By using Chinese A-share listed companies from 2007 to 2019 as a sample, the study not only examined the impact of R&D investment on corporate performance, but also considered specific mediating mechanisms and heterogeneity analysis of R&D investment on corporate performance. Finally, the study found a significant positive correlation between R&D investment and the performance of listed companies, and this positive correlation was more pronounced when funding constraints were lower. According to the study, mediation effect analysis shows that R&D investment can improve corporate performance by boosting total factor productivity. Additional research has also shown that higher levels of internal control quality can improve the boosting effect of R&D investment on corporate performance. Moreover, R&D investment by SOEs is more conducive to improving the performance of their enterprises than that of non-SOE enterprises. In addition, this study provides empirical evidence of the knowledge effect and positive externality of R&D investment for firms, examines the impact of R&D investment on corporate performance from the perspective of financing constraints, and enriches the related literature on R&D investment, financing constraints and corporate performance.
High-resolution surface electromyographic activities of facial muscles during mimic movements in healthy adults: A prospective observational study

Objectives Surface electromyography (sEMG) is a standard tool in clinical routine and clinical or psychosocial experiments also including speech research and orthodontics to measure the activity of selected facial muscles to objectify facial movements during specific facial exercises or experiments with emotional expressions. Such muscle-specific approaches neglect that facial muscles act more as an interconnected network than as single facial muscles for specific movements. What is missing is an optimal sEMG setting allowing a synchronous measurement of the activity of all facial muscles as a whole. Methods A total of 36 healthy adult participants (53% women, 18–67 years) were included. Electromyograms were recorded from both sides of the face using an arrangement of electrodes oriented by the underlying topography of the facial muscles (Fridlund scheme) and simultaneously by a geometric and symmetrical arrangement on the face (Kuramoto scheme). The participants performed a standard set of different facial movement tasks. Linear mixed-effects models and adjustment for multiple comparisons were used to evaluate differences between the facial movement tasks, separately for both applied schemes. Data analysis utilized sEMG amplitudes and also their maximum-normalized values to account for amplitude differences between the different facial movements. Results Surface electromyography activation characteristics showed systematic regional distribution patterns of facial muscle activation for both schemes with very low interindividual variability. The statistical significance to discriminate between the different sEMG patterns was good for both schemes (significant comparisons for sEMG amplitudes: 87.3%, both schemes, normalized values: 90.9%, Fridlund scheme, 94.5% Kuramoto scheme), but the Kuramoto scheme performed considerably superior. Conclusion Facial movement tasks evoke specific patterns in the complex network of facial muscles rather than activating single muscles. A geometric and symmetrical sEMG recording from the entire face seems to allow more specific detection of facial muscle activity patterns during facial movement tasks. Such sEMG patterns should be explored in more clinical and psychological experiments in the future.
Recursive optical flow estimation-adaptive filtering approach

This paper presents a new approach towards the problem of recursive optical flow estimation from image sequences based on the differential framework proposed by Horn and Schunck (1981). We show that gain is achieved both from computational and accuracy points of view when treating the estimation task recursively. Incorporation of the temporal axis into the estimation process is done by combining a temporal smoothness assumption on the optical flow. RLS and LMS recursive optical flow estimation algorithms are derived and tested.
Factors associated with HIV-1 resistance to integrase strand transfer inhibitors in Spain: Implications for dolutegravir-containing regimens

Integrase strand transfer inhibitor (INSTI)-containing regimens in HIV-1-infected patients have experienced a global increase. Recently, WHO has emphasized the need to fast-track the transition to dolutegravir (DTG)-based antiretroviral (ARV) treatments. However, continued surveillance of INSTI resistance is recommended. In this study, clinical, epidemiological, and virological features associated with INSTI resistance diagnosed in Spain were analyzed. Samples collected between 2008 and 2021 from HIV-1-infected patients were analyzed in integrase, protease, and reverse transcriptase using Sanger population sequencing. ARV drug resistance was evaluated with the Stanford University HIVdb program. Among 2,696 patients, 174 (6.5%) had INSTI resistance, all of them to first-generation INSTIs, and 71 (2.6%) had also resistance to second-generation INSTIs. Of these, only 5 individuals were exposed to DTG as the only INSTI, in whom resistance development was associated with poor treatment adherence and/or resistance to other ARV classes. Of newly HIV-1-diagnosed individuals, 0.92% harbored INSTI-resistant viruses, with low prevalences maintained along time, and only one had low-level resistance to DTG. Persons who inject drugs, age over 39 years, resistance to other ARV classes, and longer time from diagnosis were associated with INSTI resistance (p < 0.001). Non-subtype B INSTI-resistant viruses lacked the Q148H + G140S resistance pathway and showed lower INSTI resistance levels than subtype B viruses. In conclusion, INSTI resistance is uncommon and associated with long-term infections, older age and additional resistance to other ARV drug classes, and is rare in newly diagnosed HIV-1 infections. Our results also support the preferential use of DTG-containing regimens in first-line treatments, although surveillance of INSTI resistance is encouraged.
The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

Objective The objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients. Methods We conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated. Results Adjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P<0.001) and HF-RA (r=0.677, P<0.001). The receiver operating characteristic curve analysis revealed that the area under the curve was 0.804 (P<0.001), and the optimal AGEs cut-off value was 4.156mmol/L. Subgroup analysis for T2D patients revealed an increase in TGF-β, IL-6 and SCTX in the osteoporosis group, while a decreased PINP in the osteoporosis group compared to the other two subgroups. AGEs were positively associated with FBG, HbA1c, HOMA-IR, S-CTX, IL-6 and TGF-β in T2D patients, and negatively associated with PINP. Conclusions RA-adjusted FRAX is a relevant clinical tool in evaluating fracture risk of postmenopausal T2D patients. Our study analyzed the relationship between AGEs and FRAX-RA, and explored the threshold value of AGEs for predicting fracture risk in postmenopausal T2D patients. AGEs were also associated with serum bone turnover markers and inflammation factors, indicating that the increasing level of AGEs in postmenopausal T2D patients accelerated the expression of inflammatory factors, which led to bone metabolism disorders and a higher risk of osteoporotic fractures.
Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications

Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie’s disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.
Distinct and redundant roles for zebrafish her genes during mineralization and craniofacial patterning

The Notch pathway is a cell-cell communication system which is critical for many developmental processes, including craniofacial development. Notch receptor activation induces expression of several well-known canonical targets including those encoded by the hes and her genes in mammals and zebrafish, respectively. The function of these genes, individually and in combination, during craniofacial development is not well understood. Here, we used zebrafish genetics to investigate her9 and her6 gene function during craniofacial development. We found that her9 is required for osteoblasts to efficiently mineralize bone, while cartilage is largely unaffected. Strikingly, gene expression studies in her9 mutants indicate that although progenitor cells differentiate into osteoblasts at the appropriate time and place, they fail to efficiently lay down mineralized matrix. This mineralization role of her9 is likely independent of Notch activation. In contrast, her9 also functions redundantly with her6 downstream of Jagged1b-induced Notch activation during dorsoventral craniofacial patterning. These studies disentangle distinct and redundant her gene functions during craniofacial development, including an unexpected, Notch independent, requirement during bone mineralization.
Yinchen Linggui Zhugan decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease by modulation of SIRT1/Nrf2 signaling pathway and gut microbiota

Yinchen Linggui Zhugan decoction (YLZD) is an effective and classical traditional herbal prescription for treating the nonalcoholic fatty liver disease (NAFLD) and has been proven to be effective in the regulation of lipid metabolism disorder and attenuate inflammation for a NAFLD rat model. However, the exact underlying mechanism has not been elucidated. In the current study, a NAFLD rat model was established using a high-fat diet (HFD) for 10 weeks, followed by YLZD treatment with 1.92 g/kg/day for 4 weeks to explore the mechanisms of YLZD. Our results showed that YLZD decreased the hepatic lipid deposition, restored the liver tissue pathological lesions, inhibited the expression of oxidative stress, and decreased the inflammatory cytokines levels. Meanwhile, the genes and proteins expressions of SIRT1/Nrf2 signaling pathway together with downstream factors including HO-1 and NQO1 were elevated in the YLZD treated NAFLD rats. For further elaborating the upstream mechanism, short-chain fatty acids (SCFAs) in serum and feces were measured by liquid chromatograph mass spectrometer and gas chromatograph mass spectrometer, and the differences in gut microbiota of rats in each group were analyzed through high-throughput sequencing of 16S rRNA. The results demonstrated that the contents of butyric acid (BA) and total SCFAs in YLZD-treated NAFLD rats were significantly increased in serum and feces. 16S rRNA sequencing analysis illustrated that YLZD intervention led to a modification of the gut microbiota composition, with a decrease of Oribacterium, Lactobacillus and the ratio of Firmicutes/Bacteroides, as well as the increase in SCFAs-producing bacteria such as Christensenellaceae, Clostridia, Muribaculaceae, and Prevotellaceae. Spearman rank correlation analysis indicated that BA and total SCFAs were negatively co-related with oxidative stress-related factors and inflammatory cytokines, while they were positively co-related with SIRT1/Nrf2 pathway related genes and proteins. Furthermore, in vitro study confirmed that BA effectively reduced oxidative stress by activating SIRT1/Nrf2 signaling pathway in L02 cells. Together, the present data revealed YLZD could ameliorate HFD-induced NAFLD in rats by the modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.
Effects of rumen-protected methionine supplementation on production performance, apparent digestibility, blood parameters, and ruminal fermentation of lactating Holstein dairy cows

This study aimed to evaluate the effects of reducing dietary CP and supplementing rumen protected-methionine (RPM) on production performance, blood parameters, digestibility of nutrients or ruminal fermentation in lactating Holstein dairy cows. A total of 96 lactating cows were randomly assigned to 1 of 2 treatments: a diet containing 17.3% CP without RPM (control group; CON; n = 49) or a diet containing 16.4% CP and supplemented with 15.0 g/d of RPM (treatment group; RPM; n = 47). No effect was observed in the RPM group on milk yield, milk composition and digestibility of nutrients. The results of blood parameters showed that cows in the RPM group exhibited lower blood urea nitrogen concentration than in CON group. Rumen microbial crude protein (MCP) was higher in the RPM group compared to the CON group. Ruminal volatile fatty acid (VFA) concentrations were not different between treatments except for butyrate and isovalerate, which were higher in the RPM group than the CON group 2 h after feeding. In conclusion, reducing dietary CP with RPM supplementation did not limit milk yield, milk composition or digestibility of nutrients, but could improve nitrogen utilization, synthesis of MCP and partially increase VFA production 2 h after feeding cows.
5-HT1A and 5-HT2B receptor interaction and co-clustering regulates serotonergic neuron excitability

Many psychiatric diseases including depression, schizophrenia and anxiety have been associated with serotonin (5-HT) neuron dysfunction. Pacemaker-like firing of raphe 5-HT neurons was proposed to be under unique 5-HT1A receptor-mediated autoinhibition. We previously showed that 5-HT2B receptors were expressed by 5-HT neurons together with 5-HT1A receptors. However, functional consequences on 5-HT neurons of putative interaction between these receptors are unknown. Using co-immunoprecipitation, BRET, confocal and super-resolution microscopy in hippocampal and 5-HT neurons, we present converging evidence that 5-HT1A and 5-HT2B receptors can form heterodimers and co-cluster at the surface of dendrites. 5-HT2B receptor clusters were redistributed upon 5-HT1A receptor expression supporting functional interactions between the two receptors. Furthermore, 5-HT2B receptor expression prevented agonist-induced internalization of 5-HT1A receptors, whereas 5-HT1A receptors mimicked the clustering effect of 5-HT2B receptor stimulation on its surface expression. The functional impact of this interaction in-vivo was assessed by recording 5-HT neuron excitability from mice lacking 5-HT2B receptors in 5-HT neurons. Upon 5-HT1A receptor stimulation, the firing activity of 5-HT neurons was increased in the absence of 5-HT2B receptors and decreased in their presence through regulation of SK channels, thus demonstrating functional output of this interaction in controlling 5-HT neuron firing activity.
Attention-Based Deep Learning Methods for Predicting Gas Turbine Emissions

Predictive emissions monitoring systems (PEMS) for gas turbines are critical for monitoring harmful pollutants being released into the atmosphere, while reducing the use of expensive continuous emissions monitoring systems (CEMS) which require daily maintenance to achieve accurate readings. We consider two attention-based deep learning models, FT-Transformer and SAINT, and compare with classical tree-based XGBoost to predict emissions from gas turbines. We find that the attention-based models outperform XGBoost for both prediction tasks, i