Miracle-dz/UniFAR-FTUs huggingface dataset:
Naturally occurring glycyrrhizin triterpene exerts anticancer effects on colorectal cancer cells via induction of apoptosis and autophagy and suppression of cell migration and invasion by targeting MMP-9 and MMP-2 expression.

PURPOSE The main aim of the current study was to investigate the anticancer properties of naturally occurring triterpene - glycyrrhizin - against human colorectal carcinoma cells along with evaluation of its effects on cells apoptosis, autophagy and cell migration and invasion. METHODS Cell viability was evaluated by CellTiter95® Aqueous One Solution cell viability assay, while the effects on cell apoptosis were observed by fluorescence microscopy using DAPI staining. Effects on autophagy were detected by transmission electron microscopy (TEM) along with western blot method. Transwell assay was performed to monitor the effects on cell migration and invasion. RESULTS Glycyrrhizin induced selective and dose-dependent inhibition of cell growth in SW48 human colorectal carcinoma cells with lesser cytotoxicity in normal colon cells (CCD-18Co). Glycyrrhizin also led to cell apoptotic effects manifested by chromatin condensation and nuclear fragmentation as evidenced by brighter fluorescence. Apoptosis was confirmed by western blot which showed increase in Bax expression and decrease in Bcl-2 expression. TEM analysis showed that glycyrrhizin-treated cells at 12 μM showed autophagosomes indicating onset of autophagy. Western blot assay confirmed the autophagy results which showed glycyrrhizin-treated cells indicated increased expression of Beclin-1, LC3B-I and LC3B-II in a dose-dependent manner. Glycyrrhizin treatment also led to inhibition of both cell migration and invasion. CONCLUSION The results of this study reveal that glycyrrhizin can be developed as a potent anticancer agent against colorectal cancer provided further studied are performed, especially on its toxicity to humans.
MicroRNA-187 suppresses the proliferation migration and invasion of human osteosarcoma cells by targeting MAPK7.

PURPOSE Osteosarcoma is one of the rare but fatal malignancies. The high metastatic rate, late diagnosis, emergence of drug resistance against drugs such as doxorubicin, and the lack of therapeutic targets obstructs the treatment of osteosarcoma. This study was undertaken to investigate the role and therapeutic potential of miR-187 in human osteosarcoma cells. METHODS The WST-1 proliferation assay was used for investigation of cell viability. Transfections were carried out by Lipofectamine 2000 reagent. The qRT-PCR was used for expression analysis. DAPI, acridine orange (AO)/ethidium bromide (EB) and Annexin V/propidium iodide (PI) assay were used for apoptosis. Western blot analysis was used for the determination of protein expression. RESULTS The expression of miR-187 was significantly downregulated in human osteosarcoma cells. Out of all osteosarcoma cell lines the SAOS-2 showed the lowest expression of miR-187 and therefore this cell line was selected for further studies. Overexpression of miR-187 caused significant inhibition in the proliferation of SAOS-2 osteosarcoma cells. The miR-187-triggered growth inhibition was found to be mainly due to induction of G2/M phase cell cycle arrest of the SAOS-2 cells. The G2/M cell cycle arrest was also accompanied by depletion of Cyclin-B1 expression. Additionally, miR-187 enhanced the chemosensitivity of the osteosarcoma cells to doxorubicin. The wound healing and transwell assay showed that miR-187 overexpression resulted in the suppression of migration and invasion of the SAOS-2 osteosarcoma cells. In silico analysis showed that miR-187 exerts its effects by inhibiting mitogen activated protein kinase 7 (MAPK7). The expression of MAPK7 was found to be significantly upregulated in osteosarcoma cells and overexpression of MAPK7 could nullify the effects of miR-187 on the proliferation of the osteosarcoma cells.
Protective effect of rs712 polymorphism in a let-7 microRNA-binding of KRAS gene in breast cancer of a Mexican population.

PURPOSE The rs712 polymorphism in a let-7 microRNA-binding KRAS gene has been associated with different types of cancer, however these associations have been inconsistent. The purpose of this study was to determine the association between rs712 polymorphism in a let-7 microRNA-binding KRAS gene comparing breast cancer (BC) patients with healthy subjects from Mexican population. METHODS The genotyping of the rs712 polymorphism was performed by polymerase chain reaction (PCR) in 437 BC patients and 414 healthy women. RESULTS The observed frequencies of the rs712 polymorphism indicated an associated protective factor for BC in the dominant GT+TT model [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.97, p=0.040). An association between genotype and BC patients was evident in chemotherapy response (allele GT, OR 0.032, 95% CI 0.002-0.505, p=0.014), partial chemotherapy response (genotype GT, OR 0.023, 95% CI 0.001-0.419, p=0.011), and gastric and hematological toxicity (genotype GT, OR 0.115, 95% CI 0.028-0.473, p=0.003), Luminal A BC patients with gastric and hematological toxicity (genotype TT, OR 0.236, 95% CI 0.069-0.805, p=0.021) and tobacco consumption (genotype TT, OR 0.283, 95% CI 0.001-0.802, p=0.037) and Luminal B with metastatic lymph node (genotype GT, OR 0.241, 95% CI 0.093-0.626, p=0.003). CONCLUSION Polymorphism rs712 in KRAS gene was protective factor associated with susceptibility for BC in this sample from Mexican population.
Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease

Exposure to chronic hyperglycemia because of diabetes mellitus can lead to development and progression of diabetic kidney disease (DKD). We recently reported that reduced superoxide production is associated with mitochondrial dysfunction in the kidneys of mouse models of type 1 DKD. We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-derived metabolites in their urine. Here we examined renal superoxide production in a type 2 diabetes animal model, the db/db mouse, and the role of a mitochondrial protectant, MTP-131 (also called elamipretide, SS-31, or Bendavia) in restoring renal superoxide production and ameliorating DKD. We found that 18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2. Administration of MTP-131 significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling.
Sexually dimorphic phrase organization in the song of the indris (Indri indri)

Animal acoustic communication often takes the form of complex sequences, composed of multiple distinct acoustic units, which can vary in their degree of stereotypy. Studies of sequence variation may contribute to our understanding of the structural flexibility of primates' songs, which can provide essential ecological and behavioral information about variability at the individual, population, and specific level and provide insights into the mechanisms and drivers responsible for the evolutionary change of communicative traits. Several methods have been used for investigating different levels of structural information and sequence similarity in acoustic displays. We studied intra and interindividual variation in the song structuring of a singing primate, the indri (Indri indri), which inhabits the montane rain forests of Madagascar. Indri groups emit duets and choruses in which they combine long notes, short single units, and phrases consisting of a variable number of units (from two to six) with slightly descending frequency. Males' and females' contributions to the song differ in the temporal and frequency structure of song units and repertoire size. We calculated the similarity of phrase organization across different individual contributions using the Levenshtein distance, a logic distance that expressed the minimum cost to convert a sequence into another and can measure differences between two sequences of data. We then analyzed the degree of similarity within and between individuals and found that: (a) the phrase structure of songs varied between reproductive males and females: female structuring of the song showed a higher number of phrases if compared to males; (b) male contributions to the song were overall more similar to those of other males than were female contributions to the song of other females; (c) male contributions were more stereotyped than female contributions, which showed greater individual flexibility. The picture emerging from phrase combinatorics in the indris is in agreement with previous findings of rhythmic features and song repertoire size of the indris, which also suggested that female songs are potentially less stereotyped than those of males.
Can prior exposure to stress enhance resilience to ocean warming in two oyster species?

Securing economically and ecologically significant molluscs, as our oceans warm due to climate change, is a global priority. South eastern Australia receives warm water in a strengthening East Australia Current and so resident species are vulnerable to elevated temperature and marine heat waves. This study tested whether prior exposure to elevated temperature can enhance resilience of oysters to ocean warming. Two Australian species, the flat oyster, Ostrea angasi, and the Sydney rock oyster, Saccostrea glomerata, were obtained as adults and “heat shocked” by exposure to a dose of warm water in the laboratory. Oysters were then transferred to elevated seawater temperature conditions where the thermal outfall from power generation was used as a proxy to investigate the impacts of ocean warming. Shell growth, condition index, lipid content and survival of flat oysters and condition of Sydney rock oysters were all significantly reduced by elevated seawater temperature in the field. Flat oysters grew faster than Sydney rock oysters at ambient temperature, but their growth and survival was more sensitive to elevated temperature. “Stress inoculation” by heat shock did little to ameliorate the negative effects of increased temperature, although the survival of heat-shocked flat oysters was greater than non-heat shocked oysters. Further investigations are required to determine if early exposure to heat stress can enhance resilience of oysters to ocean warming.
Contribution of the Potassium Channels KV1.3 and KCa3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries

Collateral artery growth (arteriogenesis) involves the proliferation of vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Whereas the proliferation of ECs is directly related to shear stress, the driving force for arteriogenesis, little is known about the mechanisms of SMC proliferation. Here we investigated the functional relevance of the potassium channels KV1.3 and KCa3.1 for SMC proliferation in arteriogenesis. Employing a murine hindlimb model of arteriogenesis, we found that blocking KV1.3 with PAP-1 or KCa3.1. with TRAM-34, both interfered with reperfusion recovery after femoral artery ligation as shown by Laser-Doppler Imaging. However, only treatment with PAP-1 resulted in a reduced SMC proliferation. qRT-PCR results revealed an impaired downregulation of α smooth muscle-actin (αSM-actin) and a repressed expression of fibroblast growth factor receptor 1 (Fgfr1) and platelet derived growth factor receptor b (Pdgfrb) in growing collaterals in vivo and in primary murine arterial SMCs in vitro under KV1.3. blockade, but not when KCa3.1 was blocked. Moreover, treatment with PAP-1 impaired the mRNA expression of the cell cycle regulator early growth response-1 (Egr1) in vivo and in vitro. Together, these data indicate that KV1.3 but not KCa3.1 contributes to SMC proliferation in arteriogenesis.
Tridirectional Transfer Learning for Predicting Gastric Cancer Morbidity

Our previous study has constructed a deep learning model for predicting gastrointestinal infection morbidity based on environmental pollutant indicators in some regions in central China. This article aims to adapt the prediction model for three purposes: 1) predicting the morbidity of a different disease in the same region; 2) predicting the morbidity of the same disease in a different region; and 3) predicting the morbidity of a different disease in a different region. We propose a tridirectional transfer learning approach, which achieves the abovementioned three purposes by: 1) developing a combined univariate regression and multivariate Gaussian model for establishing the relationship between the morbidity of the target disease and that of the source disease together with the high-level pollutant features in the current source region; 2) using mapping-based deep transfer learning to extend the current model to predict the morbidity of the source disease in both source and target regions; and 3) applying the pattern of the combined model in the source region to the extended model to derive a new combined model for predicting the morbidity of the target disease in the target region. We select gastric cancer as the target disease and use the proposed transfer learning approach to predict its morbidity in the source region and three target regions. The results show that, given only a limited number of labeled samples, our approach achieves an average prediction accuracy of over 80% in the source region and up to 78% in the target regions, which can contribute considerably to improving medical preparedness and response.
A Vibration Control Method for Hybrid-Structured Flexible Manipulator Based on Sliding Mode Control and Reinforcement Learning

The hybrid-structured flexible manipulator has a complex structure and strong coupling between state variables. Meanwhile, the natural frequency of the hybrid-structured flexible manipulator varies with the motion of the telescopic joint, so it is difficult to suppress the vibration quickly. In this article, the tip state signal of the hybrid-structured flexible manipulator is decomposed into elastic vibration signal and tip vibration equilibrium position signal, and a combined control method is proposed to improve tip positioning accuracy and trajectory tracking accuracy. In the proposed combined control method, an improved nominal model-based sliding mode controller (NMBSMC) is used as the main controller to output the driving torque, and an actor-critic-based reinforcement learning controller (ACBRLC) is used as an auxiliary controller to output small compensation torque. The improved NMBSMC can be divided into a nominal model-based sliding mode robust controller and a practical model-based integral sliding mode controller. Two sliding mode controllers with different structures make full use of the mathematical model and the measured data of the actual system to improve the vibration equilibrium position tracking accuracy. The ACBRLC uses the tip elastic vibration signal and the prioritized experience replay method to obtain the small reverse compensation torque, which is superimposed with the output of the NMBSMC to suppress tip vibration and improve the positioning accuracy of the hybrid-structured flexible manipulator. Finally, several groups of experiments are designed to verify the effectiveness and robustness of the proposed combined control method.
Shati/Nat8l deficiency disrupts adult neurogenesis and causes attentional impairment through dopaminergic neuronal dysfunction in the dentate gyrus

Successful completion of daily activities relies on the ability to select the relevant features of the environment for memory and recall. Disruption to these processes can lead to various disorders, such as attention‐deficit hyperactivity disorder (ADHD). Dopamine is a neurotransmitter implicated in the regulation of several processes, including attention. In addition to the higher‐order brain function, dopamine is implicated in the regulation of adult neurogenesis. Previously, we generated mice lacking Shati, an N‐acetyltransferase‐8‐like protein on a C57BL/6J genetic background (Shati/Nat8l−/−). These mice showed a series of changes in the dopamine system and ADHD‐like behavioral phenotypes. Therefore, we hypothesized that deficiency of Shati/Nat8l would affect neurogenesis and attentional behavior in mice. We found aberrant morphology of neurons and impaired neurogenesis in the dentate gyrus of Shati/Nat8l−/− mice. Additionally, research has suggested that impaired neurogenesis might be because of the reduction of dopamine in the hippocampus. Galantamine (GAL) attenuated the attentional impairment observed in the object‐based attention test via increasing the dopamine release in the hippocampus of Shati/Nat8l−/− mice. The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, and dopamine D1 receptor antagonist, SCH23390, blocked the ameliorating effect of GAL on attentional impairment in Shati/Nat8l−/− mice. These results suggest that the ameliorating effect of GAL on Shati/Nat8l−/− attentional impairment is associated with activation of D1 receptors following increased dopamine release in the hippocampus via α7 nicotinic acetylcholine receptor. In summary, Shati/Nat8l is important in both morphogenesis and neurogenesis in the dentate gyrus and attention, possible via modulation of dopaminergic transmission.
Influence of socioeconomic status on the referral process to cardiac rehabilitation following acute coronary syndrome: a cross-sectional study

Objective To evaluate the association between socioeconomic status (SES) and referral to cardiac rehabilitation (CR) after incident acute coronary syndrome (ACS) by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate in CR, (3) and assigned CR setting. Design Cross-sectional study. Setting Department of Cardiology at a Danish University Hospital from 1 January 2011 to 31 December 2014. Participants A total of 1229 patients assessed for CR during hospitalisation with ACS were prospectively registered in the Rehab-North Register from 2011 to 2014. SES was assessed using data from national registers, concerning: personal income, occupational status, educational level and civil status. Patients were excluded if one of the following criteria was fulfilled: (1) missing data on SES, or (2) acceptable reason for not informing patients about CR (treatment with coronary artery bypass grafting, transfer to another hospital, still under treatment or death). Main outcome measures Outcomes were defined by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate, and (3) assigned CR setting (in-hospital/community centre) after ACS. Results A total of 854 (69.5 %) patients were referred to CR. After adjustment for age, gender, ACS diagnosis (ST-elevated myocardial infarction, non-ST-elevated myocardial infarction, unstable angina pectoris) and comorbidity, high income had the strongest association of referral to CR in all three phases (informed about CR: OR 2.17, 95% CI 1.01 to 4.64; willingness to participate in CR: OR 1.55, 95% CI 1.02 to 2.35; assigned in-hospital CR: OR 1.47, 95% CI 0.91 to 2.36). Educational level showed similar tendencies, however not statistically significant. The results did not vary according to gender. Conclusion This is the first study to investigate the referral process to CR using a three-phase structure. It suggests income and education to influence all phases in the referral process to CR after ACS.
Safety and efficacy of toripalimab in advanced gastric cancer: A new clinical trial bringing hope for immunotherapy in gastric cancer

Epidemiological data indicate that gastric cancer (GC) remains highly prevalent in the world, although its global incidence is declining [1]. It is the third leading cause of cancer death and a significant health burden in China [2-4]. At the time of diagnosis, around 50% of GC cases are already locally advanced or metastatic [5, 6] and can no longer be considered for curative surgical treatment [7]. The prognosis for these patients is poor [4]. Previous studies efforts have mainly focused on the improvements in chemotherapy and targeted therapy of advanced GC. So far, scientists have only found a few reagents that have shown to be effective against GC. However, the survival of GC patients treated with these reagents is marginal [8]. Therefore, novel therapeutic approaches to treat GC are urgently required. The success of immunotherapeutic strategies in other solid tumors, such as programmed death-1 (PD-1) blockade therapy, allow us to assert that immunotherapies can be a promising treatment strategies for advanced GC. Indeed, clinical trials (KEYNOTE-012 [9] and KEYNOTE-059 [10]) have shown that pembrolizumab, a humanized antibody PD-1 antibody, has a favorable safety profile and robust anti-tumor activity in programmed cell death ligand 1(PD-L1) positive advanced GC patients. Recently, another PD-1 antibody, nivolumab, has also been demonstrated to have similar efficacy in treating chemotherapy-refractory PD-L1 non-selected
What Drives Customer Satisfaction, Loyalty, and Happiness in Fast-Food Restaurants in China? Perceived Price, Service Quality, Food Quality, Physical Environment Quality, and the Moderating Role of Gender

The fast-food service industry has been growing rapidly across China over the last few decades. In accordance with the rising consumption level in the country, Chinese customers care increasingly about their food choices. The purpose of this study is to investigate the factors that can influence customer satisfaction, loyalty, and happiness, with a particular focus on the moderating role of gender. Data were collected through an online survey completed by customers who visited Western fast-food restaurants (KFC, McDonalds, etc.) in China. The structural equation model was applied to test 12 hypotheses. Results showed that perceived price, food, service, and physical environment quality positively affected customer satisfaction. Perceived price can significantly influence customers’ judgement of the quality dimensions of a restaurant. Moreover, customer satisfaction and happiness can lead to a sense of loyalty. Happiness functions as a mediator between satisfaction and loyalty. Nonetheless, our findings indicated that customers’ perceptions of food quality based on price and satisfaction levels based on service quality differ significantly between the genders, which demonstrated that gender moderation exists in food consumption. This study will contribute to a better understanding of managerial and theoretical perspectives, which will be beneficial for subsequent research.