Miracle-dz/UniFAR-FTUs huggingface dataset:
CAV1 - GLUT3 signaling is important for cellular energy and can be targeted by Atorvastatin in Non-Small Cell Lung Cancer

Background: The development of molecular targeted therapies, such as EGFR-TKIs, has positively impacted the management of EGFR mutated NSCLC. However, patients with innate and acquired resistance to EGFR-TKIs still face limited effective therapeutic options. Statins are the most frequently prescribed anti-cholesterol agents and have been reported to inhibit the progression of various malignancies, including in lung. However, the mechanism by which statin exerts its anti-cancer effects is unclear. This study is designed to investigate the anti-proliferative effects and identify the mechanism-of-action of statins in NSCLC. Methods: In this study, the anti-tumoral properties of Atorvastatin were investigated in NSCLC utilizing cell culture system and in vivo models. Results: We demonstrate a link between elevated cellular cholesterol and TKI-resistance in NSCLC, which is independent of EGFR mutation status. Atorvastatin suppresses growth by inhibiting Cav1 expression in tumors in cell culture system and in in vivo models. Subsequent interrogations demonstrate an oncogenic physical interaction between Cav1 and GLUT3, and glucose uptake found distinctly in TKI-resistant NSCLC and this may be due to changes in the physical properties of Cav1 favoring GLUT3 binding in which significantly stronger Cav1 and GLUT3 physical interactions were observed in TKI-resistant than in TKI-sensitive NSCLC cells. Further, the differential effects of atorvastatin observed between EGFR-TKI resistant and sensitive cells suggest that EGFR mutation status may influence its actions. Conclusions: This study reveals the inhibition of oncogenic role of Cav1 in GLUT3-mediated glucose uptake by statins and highlights its potential impact to overcome NSCLC with EGFR-TKI resistance.
Chondrocytes From Device-Minced Articular Cartilage Show Potent Outgrowth Into Fibrin and Collagen Hydrogels

Background: Transplantation of autologous minced cartilage is an established procedure to repair chondral lesions. It relies on the migration of chondrocytes out of cartilage particles into a biomaterial. So far, there is no efficient way to finely mince cartilage. No consensus exists on the nature of the biomaterial to be used to promote chondrocyte migration. Purpose/Hypothesis: This study aimed to investigate the potential clinical use of a custom-made mincing device as well as a possible alternative biomaterial to fibrin glue. The device was tested for its effect on chondrocyte viability and on subsequent chondrocyte migration into either a fibrin or a collagen gel. We hypothesized that device mincing would allow finer cutting and consequently more cell migration and that the gelation mechanism of the collagen biomaterial, which uses the clotting of platelet-rich plasma, would enhance matrix production by outgrown chondrocytes. Study Design: Controlled laboratory study. Methods: Cartilage from 12 patients undergoing knee arthroplasty was taken from the femoral condyles and subsequently either hand minced or device minced. The viability and the degree of outgrowth were quantified with live/dead assay on the generated cartilage particles and on the gels in which these particles were embedded, respectively. Matrix deposition in the biomaterials by the outgrown cells was investigated with histology. Results: The device allowed rapid mincing of the cartilage and produced significantly smaller pieces than hand mincing. The initial chondrocyte viability in cartilage particles dropped by 25% with device mincing as compared with no mincing. However, the viability in hand-minced, device-minced, and unminced samples was no longer different after 7 and 28 days in culture. Outgrowth scores were similar among the 3 groups. Fibrin and collagen biomaterials equally supported chondrocyte outgrowth and survival, but neither promoted matrix deposition after in vitro culture. Conclusion: The outgrowth potential, the viability after 28 days in culture, and the matrix deposition were not different between the mincing techniques and the tested biomaterials, yet device mincing is faster and results in significantly smaller cartilage particles. Clinical Relevance: Device mincing could become the standard method to mince cartilage for second-generation cartilage repair techniques.
The Effect of EVA and TPU Custom Foot Orthoses on Running Economy, Running Mechanics, and Comfort

Custom made foot orthoses (CFO) with specific material properties have the potential to alter ground reaction forces but their effect on running mechanics and comfort remains to be investigated. We determined if CFO manufactured from ethyl-vinyl acetate (EVA) and expanded thermoplastic polyurethane (TPU) materials, both compared to standardized footwear (CON), improve running economy (RE), running mechanics, and comfort at two running speeds. Eighteen well-trained, male athletes ran on an instrumented treadmill for 6 min at high (HS) and low (LS) speeds corresponding to and 15% lower than their first ventilatory threshold (13.8 ± 1.1 and 11.7 ± 0.9 km.h−1, respectively) in three footwear conditions (CON, EVA, and TPU). RE, running mechanics and comfort were determined. Albeit not reaching statistical significance (P = 0.11, η2 = 0.12), RE on average improved in EVA (+2.1 ± 4.8 and +2.9 ± 4.9%) and TPU (+0.9 ± 5.9 and +0.9 ± 5.3%) compared to CON at LS and HS, respectively. Braking force was decreased by 3.4 ± 9.1% at LS and by 2.7 ± 9.8% at HS for EVA compared to CON (P = 0.03, η2 = 0.20). TPU increased propulsive loading rate by 20.2 ± 24 and 16.4 ± 23.1% for LS and HS, respectively compared to CON (P = 0.01, η2 = 0.25). Both arch height (P = 0.06, η2 = 0.19) and medio-lateral control (P = 0.06, η2 = 0.16) showed a trend toward improved comfort for EVA and TPU vs. CON. Compared to shoes only, mainly EVA tended to improve RE and comfort at submaximal running speeds. Specific CFO-related running mechanical adjustments included a reduced braking impulse occurring in the first 25% of contact time with EVA, whereas wearing TPU increased propulsive loading rate.
The Temporal Experience of Pleasure Scale (TEPS): Measurement Invariance Across Gender in Chinese University Students

The Temporal Experience of Pleasure Scale (TEPS) is a self-report instrument assessing pleasure experience. The present study aimed to confirm the factor model of the Chinese version of TEPS and test measurement invariance of the scale across gender in Chinese university students. Participants were 2977 (51% female) undergraduates aged from 16 to 27 years (Mean age = 18.9 years). Results indicated that the revised four-factor structure of the TEPS had acceptable fit in the total sample and in gender groups. Furthermore, configural, metric and partial scalar invariance across gender were established. Two of the items (item 4 and 8) demonstrated different intercepts and women scored higher than men on both items. With partial scalar invariance demonstrated, test of differences in latent means indicated that men had lower levels of pleasure when compared with women. To our knowledge, this study is the first attempt to test the measurement invariance of the TEPS across gender, which provides support for future research that involves examining hedonic capacity in Chinese men and women.
Increasing the low lipid phosphate phosphatase 1 activity in breast cancer cells decreases transcription by AP-1 and expressions of matrix metalloproteinases and cyclin D1/D3

Metastasis is the leading cause of mortality in breast cancer patients and lysophosphatidate (LPA) signaling promotes this process. LPA signaling is attenuated by lipid phosphate phosphatase-1 (LPP1) whose activity is decreased in cancers. Consequently, increasing LPP1 levels suppresses breast tumor growth and metastasis. This study shows that increasing LPP1 in breast cancer cells decreases transcription through cFos and cJun. This decreases production of cyclin D1/D3 and matrix metalloproteinases (MMPs), which provides new insights into the role of LPP1 in controlling tumor growth and metastasis. Methods: Invasiveness was determined by a Matrigel invasion assay. MMP expression was measured by qPCR, multiplex LASER bead technology and gelatin zymography. Levels of cJUN, cFOS, FRA1, cyclin D1, and cyclin D3 were determined by qPCR and western blotting. Collagen was determined by Picro-Sirius Red staining. Results: Increasing LPP1 expression inhibited invasion of MDA-MB-231 breast cancer cells through Matrigel. This was accompanied by decreases in expression of MMP-1, -3, -7, -9, -10, -12 and -13, which are transcriptionally regulated by the AP-1 complex. Increasing LPP1 attenuated the induction of mRNA of MMP-1, -3, cFOS, and cJUN by EGF or TNFα, but increased FRA1. LPP1 expression also decreased the induction of protein levels for cFOS and cJUN in nuclei and cytoplasmic fractions by EGF and TNFα. Protein levels of cyclin D1 and D3 were also decreased by LPP1. Although FRA1 in total cell lysates or cytoplasm was increased by LPP1, nuclear FRA1 was not affected. LPP1-induced decreases in MMPs in mouse tumors created with MDA-MB-231 cells were accompanied by increased collagen in the tumors and fewer lung metastases. Knockdown of LPP1 in MDA-MB-231 cells increased the protein levels of MMP-1 and -3. Human breast tumors also have lower levels of LPP1 and higher levels of cJUN, cFOS, MMP-1, -7, -8, -9, -12, -13, cyclin D1, and cyclin D3 relative to normal breast tissue. Conclusion: This study demonstrated that the low LPP1 expression in breast cancer cells is associated with high levels of cyclin D1/D3 and MMPs as a result of increased transcription by cFOS and cJUN. Increasing LPP1 expression provides a novel approach for decreasing transcription through AP-1, which could provide a strategy for decreasing tumor growth and metastasis.
Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice

Mesenchymal stem cell-derived exosomes (MSC-Exo) have robust anti-inflammatory effects in the treatment of neurological diseases such as epilepsy, stroke, or traumatic brain injury. While astrocytes are thought to be mediators of these effects, their precise role remains poorly understood. To address this issue, we investigated the putative therapeutic effects and mechanism of MSC-Exo on inflammation-induced alterations in astrocytes. Methods: Lipopolysaccharide (LPS)-stimulated hippocampal astrocytes in primary culture were treated with MSC-Exo, which were also administered in pilocarpine-induced status epilepticus (SE) mice. Exosomal integration, reactive astrogliosis, inflammatory responses, calcium signaling, and mitochondrial membrane potentials (MMP) were monitored. To experimentally probe the molecular mechanism of MSC-Exo actions on the inflammation-induced astrocytic activation, we inhibited the nuclear factor erythroid-derived 2, like 2 (Nrf2, a key mediator in neuroinflammation and oxidative stress) by sgRNA (in vitro) or ML385 (Nrf2 inhibitor) in vivo. Results: MSC-Exo were incorporated into hippocampal astrocytes as well as attenuated reactive astrogliosis and inflammatory responses in vitro and in vivo. Also, MSC-Exo ameliorated LPS-induced aberrant calcium signaling and mitochondrial dysfunction in culture, and SE-induced learning and memory impairments in mice. Furthermore, the putative therapeutic effects of MSC-Exo on inflammation-induced astrocytic activation (e.g., reduced reactive astrogliosis, NF-κB deactivation) were weakened by Nrf2 inhibition. Conclusions: Our results show that MSC-Exo ameliorate inflammation-induced astrocyte alterations and that the Nrf2-NF-κB signaling pathway is involved in regulating astrocyte activation in mice. These data suggest the promising potential of MSC-Exo as a nanotherapeutic agent for the treatment of neurological diseases with hippocampal astrocyte alterations.
Predictive value of interim FDG-PET/CT findings in patients with diffuse large B-cell lymphoma treated with R-CHOP

Objectives: To examine the prognostic value of interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings after 2–4 cycles of rituximab, plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL) receiving standardized treatment. Results: After a median 3.36 years (range 0.33 to 9.14 years), 24 of the 80 patients had documented relapse. In Interim-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (50.0% vs. 86.4%; p = 0.0012). In End-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (25.0% vs. 84.7%; p < 0.0001). The positive predictive value (PPV) and negative predictive value (NPV) of Interim-PET for predicting relapse or disease progression were 57.1% and 75.8%, respectively, while those for End-PET were 75.0% and 75.0%, respectively. Methods: Eighty DLBCL patients treated with first-line 6–8 R-CHOP courses regardless of interim imaging findings were enrolled. Each underwent FDG-PET/CT scanning at staging, and again during (Interim-PET) and at the end of (End-PET) therapy. PET positivity or negativity at Interim-PET and End-PET as related to progression-free survival (PFS) was examined using Kaplan–Meier analysis. Conclusion: Mid-treatment FDG-PET/CT findings may be useful for determining disease status in patients with DLBCL undergoing induction R-CHOP chemotherapy, though are not recommended for treatment decisions as part of routine clinical practice.
Exploiting the Zonulin Mouse Model to Establish the Role of Primary Impaired Gut Barrier Function on Microbiota Composition and Immune Profiles

The balanced interplay between epithelial barrier, immune system, and microbiota maintains gut homeostasis, while disruption of this interplay may lead to inflammation. Paracellular permeability is governed by intercellular tight-junctions (TJs). Zonulin is, to date, the only known physiological regulator of intestinal TJs. We used a zonulin transgenic mouse (Ztm) model characterized by increased small intestinal permeability to elucidate the role of a primary impaired gut barrier on microbiome composition and/or immune profile. Ztm exhibit an altered gene expression profile of TJs in the gut compared to wild-type mice (WT): Claudin-15, Claudin-5, Jam-3, and Myosin-1C are decreased in the male duodenum whereas Claudin-15, Claudin-7, and ZO-2 are reduced in the female colon. These results are compatible with loss of gut barrier function and are paralleled by an altered microbiota composition with reduced abundance of the genus Akkermansia, known to have positive effects on gut barrier integrity and strengthening, and an increased abundance of the Rikenella genus, associated to low-grade inflammatory conditions. Immune profile analysis shows a subtly skewed distribution of immune cell subsets toward a pro-inflammatory phenotype with more IL-17 producing adaptive and innate-like T cells in Ztm. Interestingly, microbiota “normalization” involving the transfer of WT microbiota into Ztm, did not rescue the altered immune profile. Our data suggest that a primary impaired gut barrier causing an uncontrolled trafficking of microbial products leads to a latent pro-inflammatory status, with a skewed microbiota composition and immune profile that, in the presence of an environmental trigger, as we have previously described (1), might promote the onset of overt inflammation and an increased risk of chronic disease.
Differential mechanisms underlying responses of soil bacterial and fungal communities to nitrogen and phosphorus inputs in a subtropical forest

Atmospheric nitrogen (N) deposition and phosphorus (P) addition both can change soil bacterial and fungal community structure with a consequent impact on ecosystem functions. However, which factor plays an important role in regulating responses of bacterial and fungal community to N and P enrichments remains unclear. We conducted a manipulative experiment to simulate N and P inputs (10 g N · m−2 · yr−1 NH4NO3 or 10 g P · m−2 · yr−1 NaH2PO4) and compared their effects on soil bacterial and fungal species richness and community composition. The results showed that the addition of N significantly increased NH4+ and Al3+ by 99.6% and 57.4%, respectively, and consequently led to a decline in soil pH from 4.18 to 3.75 after a 5-year treatment. P addition increased Al3+ and available P by 27.0% and 10-fold, respectively, but had no effect on soil pH. N addition significantly decreased bacterial species richness and Shannon index and resulted in a substantial shift of bacterial community composition, whereas P addition did not. Neither N nor P addition changed fungal species richness, Shannon index, and fungal community composition. A structural equation model showed that the shift in bacterial community composition was related to an increase in soil acid cations. The principal component scores of soil nutrients showed a significantly positive relationship with fungal community composition. Our results suggest that N and P additions affect soil bacterial and fungal communities in different ways in subtropical forest. These findings highlight how the diversity of microbial communities of subtropical forest soil will depend on future scenarios of anthropogenic N deposition and P enrichment, with a particular sensitivity of bacterial community to N addition.
Automatic Respiratory Gating Hepatic DCEUS-based Dual-phase Multi-parametric Functional Perfusion Imaging using a Derivative Principal Component Analysis

Purpose: Angiogenesis in liver cancers can be characterized by hepatic functional perfusion imaging (FPI) on the basis of dynamic contrast-enhanced ultrasound (DCEUS). However, accuracy is limited by breathing motion which results in out-of-plane image artifacts. Current hepatic FPI studies do not correct for these artifacts and lack the evaluation of correction accuracy. Thus, a hepatic DCEUS-based dual-phase multi-parametric FPI (DM-FPI) scheme using a derivative principal component analysis (PCA) respiratory gating is proposed to overcome these limitations. Materials and Methods: By considering severe 3D out-of-plane respiratory motions, the proposed scheme's accuracy was verified with in vitro DCEUS experiments in a flow model mimicking a hepatic vein. The feasibility was further demonstrated by considering in vivo DCEUS measurements in normal rabbit livers, and hepatic cavernous hemangioma and hepatocellular carcinoma in patients. After respiratory kinetics was extracted through PCA of DCEUS sequences under free-breathing condition, dual-phase respiratory gating microbubble kinetics was identified by using a derivative PCA zero-crossing dual-phase detection, respectively. Six dual-phase hemodynamic parameters were estimated from the dual-phase microbubble kinetics and DM-FPI was then reconstructed via color-coding to quantify 2.5D angiogenic hemodynamic distribution for live tumors. Results: Compared with no respiratory gating, the mean square error of respiratory gating DM-FPI decreased by 1893.9 ± 965.4 (p < 0.05), and mean noise coefficients decreased by 17.5 ± 7.1 (p < 0.05), whereas correlation coefficients improved by 0.4 ± 0.2 (p < 0.01). DM-FPI observably removed severe respiratory motion artifacts on PFI and markedly enhanced the accuracy and robustness both in vitro and in vivo. Conclusions: DM-FPI precisely characterized and distinguished the heterogeneous angiogenic hemodynamics about perfusion volume, blood flow and flow rate within two anatomical sections in the normal liver, and in benign and malignant hepatic tumors. DCEUS-based DM-FPI scheme might be a useful tool to help clinicians diagnose and provide suitable therapies for liver tumors.
Predictive values of neutrophil-lymphocyte ratio as an early indicator for severe acute pancreatitis in the emergency department patients

CONTEXT: Acute pancreatitis is an acute inflammatory disease presenting with a wide range of severity. AIMS: We investigated the predictive values of the neutrophil-lymphocyte ratio (NLR) as an indicator for severe acute pancreatitis in the emergency department patients. SETTINGS AND DESIGN: This retrospective study was conducted on patients with acute pancreatitis who were diagnosed in the emergency department, from January 2008 to December 2017. SUBJECTS AND METHODS: Patients were classified into either mild-to-moderate severe group or severe group according to the Revised Atlanta Classification for Acute Pancreatitis. Clinical features and laboratory blood test parameters were considered as independent variables. STATISTICAL ANALYSIS USED: Independent variables were analyzed using the Chi-square test and Mann–Whitney U-test to determine statistically significant differences between the two groups. Logistic regression analysis and receiver operating characteristic analysis were performed to evaluate the predictive values of significantly different variables. RESULTS: Of the 672 patients, 52 (7.7%) were classified into the severe group. Tachycardia, fever, prevalence of liver cirrhosis and chronic alcoholism, white blood cell count, NLR, C-reactive protein (CRP), blood urea nitrogen (BUN), creatinine, aspartate transaminase, and total bilirubin were significantly higher in the severe group. Among them, NLR (adjusted odds ratio [aOR]: 1.13; 95% confidence interval [CI]: 1.081–1.181), CRP (aOR: 1.011; 95% CI: 1.004–1.017), BUN (aOR: 1.036; 95% CI: 1.004–1.069), and creatinine (aOR: 1.703; 95% CI: 1.008–2.877) were significant in the logistic regression analysis. NLR showed relatively high sensitivity (82.7%) and specificity (70%) and showed the highest area under the curve (0.821). CONCLUSIONS: The increase in NLR was associated with severe acute pancreatitis. NLR is expected to be useful as a prognostic factor in patients with acute pancreatitis who are visiting the emergency department.
Identification and evaluation of Lonicera japonica flos introduced to the Hailuogou area based on ITS sequences and active compounds

Lonicera japonica flos (LJF), the dried flower buds of L. japonica Thunb. , have been used in traditional Chinese herbal medicine for thousands of years. Recent studies have reported that LJF has many medicinal properties because of its antioxidative, hypoglycemic, hypolipidemic, anti-allergic, anti-inflammatory, and antibacterial effects. LJF is widely used in China in foods and healthcare products, and is contained in more than 30% of current traditional Chinese medicine prescriptions. Because of this, many Chinese villages cultivate LJF instead of traditional crops due to its high commercial value in the herbal medicine market. Since 2005, the flower buds of L. japonica are the only original LJF parts considered according to the Chinese Pharmacopoeia of the People’s Republic of China. However, for historical and commercial reasons, some closely related species of Lonicera Linn. continue to be mislabeled and used as LJF. Currently, there are hundreds of commercial varieties of LJF on the market and it is difficult to choose fine LJF varieties to cultivate. In this study, a total of 21 varieties labeled as LJF on the market were planted in the Hailuogou area. In order to choose the optimum variety, internal transcribed spacer (ITS) sequence alignment analysis was used to test whether the 21 varieties were genuine LJF or not. Cluster analysis of active components based on the content of chlorogenic acid and luteoloside in flower buds, stems and leaves was used to evaluate the quality of the varieties. Results demonstrated that four of the varieties were L. macranthoides Hand. -Mazz. , while the other 17 varieties were L. japonica, and genuine LJF. The ITS sequence analysis was proven to be highly effective in identifying LJF and Lonicerae flos. Among the 17 L. japonica varieties, the amounts of chlorogenic acid and luteoloside in flower buds, stems and leaves were significantly different. Based on the cluster analysis method, the variety H11 was observed to have the highest level of active components, and is therefore recommended for large-scale planting in the Hailuogou area.