Miracle-dz/UniFAR-FTUs huggingface dataset:
The subcellular redistribution of NLRC5 promotes angiogenesis via interacting with STAT3 in endothelial cells

Angiogenesis is a critical step in repair of tissue injury. The pattern recognition receptors (PRRs) recognize pathogen and damage associated molecular patterns (DAMPs) during injury and achieve host defense directly. However, the role of NLR family CARD domain containing 5 (NLRC5), an important member of PPRs, beyond host defense in angiogenesis during tissue repair remains unknown. Methods: In vitro, western blot and real-time PCR (RT-PCR) were used to detect the expression of NLRC5 in endothelial cells (ECs). Immunofluorescence microscopy was used to reveal the subcellular location of NLRC5 in ECs. Cell proliferation, wound healing, tube formation assays of ECs were performed to study the role of NLRC5 in angiogenesis. By using Tie2Cre-NLRC5flox/flox mice and bone marrow transplantation studies, we defined an EC-specific role for NLRC5 in angiogenesis. Mechanistically, co-immunoprecipitation studies and RNA sequencing indicated that signal transducer and activator of transcription 3 (STAT3) was the target of NLRC5 in the nucleus. And Co-IP was used to verify the specific domain of NLRC5 binding with STAT3. ChIP assay determined the genes regulated by interaction of STAT3 and NLRC5. Results: Knockdown of NLRC5 in vitro or in vivo inhibited pathological angiogenesis, but had no effect on physiological angiogenesis. NLRC5 was also identified to bind to STAT3 in the nucleus required the integrated death-domain and nucleotide-binding domain (DD+NACHT domain) of NLRC5. And the interaction of STAT3 and NLRC5 could enhance the transcription of angiopoietin-2 (Ang2) and cyclin D1 (CCND1) to participate in angiogenesis. Conclusions: In the ischemic microenvironment, NLRC5 protein accumulates in the nucleus of ECs and enhances STAT3 transcriptional activity for angiogenesis. These findings establish NLRC5 as a novel modulator of VEGFA signaling, providing a new target for angiogenic therapy to foster tissue regeneration.
SELECTION OF BUFFERS IN LC-MS/MS: AN OVERVIEW

Liquid chromatography-mass spectrometry (LC-MS, or alternatively HPLC-MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (or HPLC) with the mass analysis capabilities of mass spectrometry. LCMS is frequently used in drug development at many different stages including Peptide Mapping, Glycoprotein Mapping, Natural Products Dereplication, Bioaffinity Screening, In Vivo Drug Screening, Metabolic Stability Screening, Metabolite Identification as well as Impurity Identification. Selecting the proper buffer pH is necessary to reproducible separate ionisable compounds by reverse phase liquid chromatography or LC-MS. Selecting an improper pH for ionizable analytes often leads to asymmetric peaks that are broad, tail, split or shoulder. Sharp and symmetrical peaks are necessary in quantitative analysis in order to achieve low detection limits, relative standard deviations (RSD) between injection, and reproducible retention times. In the present article, we have concentrated on the aspect when and why buffering is needed in LC-MS, how to choose buffer pH as well as criteria for selecting buffers for ion pair reagents. A properly buffered mobile phase is very important in a successful reverse phase method for optimal peak shape, detection limit, and consistent resistant times. The selection of proper buffer purely depends on analyte’s functional group and pKa Values.
Mutational spectrum and precision oncology for biliary tract carcinoma

Background: The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. Methods: This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included TP53 (53%), KRAS (26%), ARID1A (18%), LRP1B (14%) and CDKN2A (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. TP53 and KRAS mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Conclusions: Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.
Limb Salvage Resection of Massive Dedifferentiated Thigh Liposarcoma in a Patient Lost to Follow-Up

Dedifferentiated liposarcoma (DDL) is a rare soft tissue tumor that represents a non-lipogenic progression of well-differentiated liposarcoma (WDL). Unlike WDL, DDL has the propensity for metastasis and is associated with an increased incidence of local recurrence. For DDL of the extremities that is resectable with acceptable functional outcomes, treatment includes primary surgical resection with negative margins. Although rare due to advances in reconstructive techniques, amputation for DDL of the extremities should be considered in which appropriate tumor resection cannot be performed without adequate preservation of limb function. We present the clinical progression of a patient with a large DDL of the right thigh who was initially lost to follow-up, but ultimately underwent delayed definitive therapy with the intent for limb salvage. This case illustrates the importance of assessing neurovascular, osseous, and soft tissue involvement to properly predict and preserve limb function while achieving adequate tumor resection.
Validity and Reliability of the Malay Versions of Bloating Severity (BSQ-M) and Quality of Life (BLQoL-M) Questionnaires

Abdominal bloating (AB) is a prevalent and bothersome symptom, but there are no specific measures for severity and quality of life (QoL) other than the Bloating Severity Questionnaire (BSQ) and Bloating Quality of Life (BLQoL). We aimed to translate the BSQ and BLQoL into the Malay language and to validate them using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) approaches. The 12-item BSQ has two components, seven-item severity in general (SevGen) and five-item severity in the past 24 h (Sev24), and BLQOL has five items. Translation to the Malay language (BSQ-M and BLQoL-M) was performed using standard forward and backward processes. EFA followed by CFA were performed in participants with AB due to functional bowel disorders, with the purpose of examining the validity and reliability of the questionnaires translated into Malay. After EFA with 152 participants, all the items of BSQ-M remained in the model. Total variance extracted was 53.26% for BSQ-M and 58.79% for BLQoL-M. The internal consistency based on Cronbach’s alpha values was 0.52 for SevGen, 0.86 for Sev24, and 0.81 for BLQoL-M. After performing CFA with another 323 participants, the final measurement model for BSQ-M and BLQoL-M fit the data well in terms of several fit indices (BSQ-M: root mean square error of approximation (RMSEA) = 0.050, Comparative Fit Index (CFI) = 0.966, Tucker–Lewis Fit Index (TLI) = 0.956, and standardized root mean squared residual (SRMR) = 0.051; BLQoL-M: RMSEA = 0.071, CFI = 0.985, TLI = 0.962, SRMR = 0.021). The composite reliability for BSQ-M and BLQoL-M were satisfactory (SevGen = 0.83, Sev24 = 0.89, BLQoL = 0.80). The intraclass correlation (ICC) results showed excellent stability for BSQ-M and BLQoL-M, ranging from 0.74 to 0.93. The Malay language versions of BSQ-M and BLQoL-M are valid and reliable instruments for measuring the severity and QoL of AB for the Asian population with functional bowel disorders.
Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs

Using T‐cell chimeric antigen receptors (CAR‐T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor‐associated antigens (TAAs) can be mistargeted, resulting in severe side effects. An approach using a collection of T cells expressing a diverse, 106‐member combinatorial cellular library of CARs, in which members can be specifically enriched based on avidity for cell membrane antigens, is reported. Using CD38 as the target antigen, an efficient and effective selection of CARs specifically recognizing CD38+ tumor cells is demonstrated. These selected CAR‐T's produce cytokines known to be associated with T cell activation in a CD38 expression‐dependent manner. This avidity‐based selection endows the engineered T cells with minimal off‐tumor effects, while retaining robust antitumor efficacy both in vitro and in vivo. The described method may facilitate the application of CAR‐T therapy to TAAs previously considered undruggable.
STABILITY CONSTANTS OF MIXED LIGAND COMPLEXES OF TRANSITION METAL (II) IONS WITH 2-{(E)-((2,6-DIMETHYL PHENYL) IMINO)METHYL}PHENOL AND 1-{(E)-((2,6-DICHLORO-3- METHYLPHENYL)IMINO)METHYL}NAPHTHALEN-2-OL

Binary and ternary complexes of the type M-Y and M-X-Y [M = Co(II), Ni(II), Cu(II) and Zn(II); X = 2-{(E)-[(2,6dimethylphenyl)imino]methyl}phenol and Y = 1-{(E)-[(2,6-dichloro-3-methylphenyl)imino]methyl}naphthalen-2-ol] have been examined pH-metrically at 27 ± 0.5 o C and at constant ionic strength, μ = 0.1 M (KCl) in 75 : 25 (v/v) 1,4-dioxne-water medium. The stability constants for Binary (M-Y) and ternary (M-X-Y) systems were calculated.
Brown seaweed Cystoseira schiffneri as a promising source of sulfated fucans: Seasonal variability of structural, chemical, and antioxidant properties

Abstract A fucoidan, sulfated polysaccharide, was extracted from the brown seaweed Cystoseira schiffneri during 4 harvest periods (December, April, July, and September) and studied for its structural and chemical properties. The Cystoseira schiffneri fucoidan (CSF) showed important variation in sulfate content ranging from 7.8% in December to 34.8% in July. This was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopies showing characteristic signals of sulfated polysaccharides. Molecular mass of the CSF varied as a function of season from 3,745 in December to 26,390 Da in July. Gas chromatography–mass spectroscopy showed that CSF fractions were “mannogalactofucans” composed mainly of mannose, fucose, and galactose with low levels of other monosaccharides. Moreover, interesting in vitro antioxidant activities that depend on the harvest season were noted for CSF. Thus, the present work might contribute to establish criteria for extracting bioactive fucoidans from an endemic Tunisian seaweed C. schiffneri.
Homo‐ and copolymerization of norbornene derivatives with ethene by ansa‐fluorenylamidodimethyltitanium activated with methylaluminoxane

(t-BuNSiMe2Flu)TiMe2 (1) activated with Me3Al-free methylaluminoxane (dried MAO) which conducts vinyl addition polymerization of norbornene (N) with very high activity was applied for homopolymerization of N derivatives (i.e., 5-vinyl-2-norbornene (5V2N), 5-ethylidene-2-norbornene (5E2N), dicyclopentadiene (DCPD)) at 40 °C. The activities for the N derivatives were about two orders of magnitude lower than that for N and decreased in the following order: 5E2N ≫ 5V2N ≫ DCPD. Copolymerization of ethene (E) and 5E2N under an atmospheric pressure of E was then conducted by 1-dried MAO. The copolymerization proceeded with better activity than the homopolymerization of 5E2N and gave poly(E-co-5E2N) with narrow molecular weight distribution. The content of the ethylidene group in poly(E-co-5E2N) was controlled by the feed ratio of 5E2N/E. The Tg value of the copolymer changed from 70 °C to 155 °C according to the 5E2N content from 27 mol % to 68 mol %. The addition of N as a third monomer to the E-5E2N copolymerization improved the activity and raised the Tg values of the terpolymer above 200 °C. The content of 5E2N was controlled by the 5E2N/N ratio with keeping the high Tg values. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4581–4587, 2007
Origin of Visible Light Photoactivity of Reduced Graphene Oxide/TiO2 by in Situ Hydrothermal Growth of Undergrown TiO2 with Graphene Oxide

Graphene-related–TiO2 (G–TiO2) nanocomposites show enhanced photocatalytic performance, not only due to promoting photogenerated electrons migration but also by extending optical absorption to the visible light range. However, little is known about the origin of the visible light activity, which seems to depend much on the precursor of the titanium source. In this study, an efficient visible light active G–TiO2-413 was prepared by hydrothermally treating a graphene oxide (GO) suspension and TiO2 sol with undergrown TiO2 nanoparticles at 413 K. According to XRD, DRS, TEM, FTIR, Raman, and ESR analyses, when in situ growing TiO2 nanoparticles from hydrolyzed titanium alkoxides in hydrothermal conditions, a strong chemical interaction appears at the interface of GO sheets and the underdeveloped loosely packed polymeric Ti–O–Ti skeletons, so as to facilitate retaining more alkoxyl groups, inducing crystal disorders, and creating oxygen vacancies. All of these contribute to the significantly enhanced visible l.
Private Insurance and Mental Health among Older Adults with Multiple Chronic Conditions: A Longitudinal Analysis by Race and Ethnicity

Older adults with multiple chronic conditions have a higher risk than those without multiple conditions of developing a mental health condition. Individuals with both physical and mental conditions face many substantial burdens. Many such individuals also belong to racial and ethnic minority groups. Private insurance coverage can reduce the risks of developing mental illnesses by increasing healthcare utilization and reducing psychological stress related to financial hardship. This study examines the association between private insurance and mental health (i.e., depressive symptoms and cognitive impairment) among older adults in the United States with multiple chronic conditions by race and ethnicity. We apply a multivariate logistic model with individual fixed-effects to 12 waves of the Health and Retirement Study. Among adults with multiple chronic conditions in late middle age nearing entry to Medicare and of all racial and ethnic groups, those without private insurance have a stronger probability of having depressive symptoms. Private insurance and Medicare can mediate the risk of cognitive impairment among non-Hispanic Whites with multiple chronic conditions and among Blacks regardless of the number of chronic conditions. Our study has implications for policies aiming to reduce disparities among individuals coping with multiple chronic conditions.
Discordance in Retinal and Choroidal Vascular Densities in Patients with Type 2 Diabetes Mellitus on Optical Coherence Tomography Angiography

Purpose In the present study, the retinal and choroidal vascular densities (VDs) in type 2 diabetes mellitus (DM) patients were analyzed using optical coherence tomography angiography (OCTA). Methods The study included 282 eyes of 152 patients with type 2 DM (114 without retinopathy, 79 nonproliferative diabetic retinopathy (NPDR), 48 severe NPDR, and 41 proliferative diabetic retinopathy (PDR) eyes). The superficial and deep retinal vessel, choriocapillaris, and choroidal VDs were measured using a binarization method on OCTA images. VDs were compared based on retinopathy severity. Correlations among densities were analyzed. Results Retinal and choriocapillaris VDs were lower in PDR than in NPDR (all P < 0.05). Correlation analysis showed significant positive correlations among densities of superficial and deep retinal vessels and choriocapillaris (all P < 0.001). Choroidal VD showed a negative correlation with superficial and deep retinal vessels and choriocapillaris (all P < 0.001). Retinal and choriocapillaris VDs showed a negative correlation with diabetic retinopathy (DR) grade (all P < 0.001); however, the choroidal VD showed a weak positive correlation (P=0.030). Conclusion Choroidal VD increased as retinal and choriocapillaris VDs decreased, indicating that the outer layer of the choroid is less affected by DR severity and VD of larger choroidal vessels may even be increased as a compensatory mechanism for decreased retinal and choriocapillaris VDs in type 2 DM patients.
Pattern Recognition of the COVID-19 Pandemic in the United States: Implications for Disease Mitigation

The novel coronavirus (COVID-19) pandemic presents a severe threat to human health worldwide. The United States (US) has the highest number of reported COVID-19 cases, and over 16 million people were infected up to the 12 December 2020. To better understand and mitigate the spread of the disease, it is necessary to recognize the pattern of the outbreak. In this study, we explored the patterns of COVID-19 cases in the US from 1 March to 12 December 2020. The county-level cases and rates of the disease were mapped using a geographic information system (GIS). The overall trend of the disease in the US, as well as in each of its 50 individual states, were analyzed by the seasonal-trend decomposition. The disease curve in each state was further examined using K-means clustering and principal component analysis (PCA). The results showed that three clusters were observed in the early phase (1 March–31 May). New York has a unique pattern of the disease curve and was assigned one cluster alone. Two clusters were observed in the middle phase (1 June–30 September). California, Texas and Florida were assigned in the same cluster, which has the pattern different from the remaining states. In the late phase (1 October–12 December), California has a unique pattern of the disease curve and was assigned a cluster alone. In the whole period, three clusters were observed. California, Texas and Florida still have similar patterns and were assigned in the same cluster. The trend analysis consolidated the patterns identified from the cluster analysis. The results from this study provide insight in making disease control and mitigation strategies.
Recent Advances in Molybdenum-Based Materials for Lithium-Sulfur Batteries

Lithium-sulfur (Li-S) batteries as power supply systems possessing a theoretical energy density of as high as 2600 Wh kg−1 are considered promising alternatives toward the currently used lithium-ion batteries (LIBs). However, the insulation characteristic and huge volume change of sulfur, the generation of dissolvable lithium polysulfides (LiPSs) during charge/discharge, and the uncontrollable dendrite formation of Li metal anodes render Li-S batteries serious cycling issues with rapid capacity decay. To address these challenges, extensive efforts are devoted to designing cathode/anode hosts and/or modifying separators by incorporating functional materials with the features of improved conductivity, lithiophilic, physical/chemical capture ability toward LiPSs, and/or efficient catalytic conversion of LiPSs. Among all candidates, molybdenum-based (Mo-based) materials are highly preferred for their tunable crystal structure, adjustable composition, variable valence of Mo centers, and strong interactions with soluble LiPSs. Herein, the latest advances in design and application of Mo-based materials for Li-S batteries are comprehensively reviewed, covering molybdenum oxides, molybdenum dichalcogenides, molybdenum nitrides, molybdenum carbides, molybdenum phosphides, and molybdenum metal. In the end, the existing challenges in this research field are elaborately discussed.
Effects of non-ionic surfactants and related compounds on the cooperative and molecular dynamics of their aqueous solutions

This study presents an investigation of the dynamics of aqueous non-ionic surfactant solutions and related systems. Various systems were studied, starting from water + 1,4-dioxane, which represents a simple binary mixture, up to non-ionic microemulsions featuring percolation transitions and a high degree of structuring. For a better understanding of surfactant + water binary systems the present study was based on a set of oligomeric model compounds which allow the investigation of increasing degrees of internal freedom on the dynamics of hydrogen-bond networks. A careful evaluation of existing literature data showed major discrepancies and a quite incomplete coverage. Therefore, thermodynamic properties, especially the densities and heat capacities were determined and analyzed. The dielectric investigations revealed that compounds without H-bond donor groups like 1,4-dioxane and oligo(ethylene glycol) dimethyl ethers cause a quite pronounced microheterogenous structure and show cooperative relaxation of water-rich domains even at high concentration of the organic solute. In contrast to this, compounds with groups acting as H-bond donors can be incorporated easily into the H-bond network and large effects on the relaxation times where found. The dielectric properties of pentaethylene glycol monododecyl ether (C12E5) + water binary mixtures in the isotropic-micellar, lamellar and hexagonal phase were studied. Two dielectric dispersion steps were resolved and assigned to intermolecular cooperative dynamics of water at the micellar interface and in remaining bulk water domains. From the quantitative analysis of the bulk water response, which was further investigated by heavy water as a substitute for H$_2$O, the ratio of slow water molecules per mole surfactant was calculated. Additionally, the effective dipole moment of water dipoles incorporated in the relaxation process of water at the interface was determined and found considerably lower than that of pure water. Further work was carried out on percolating KCl-'doted' water/n-octane/C12E5 W/O microemulsions, and critical exponents were obtained that agree well with the universal parameters predicted by dynamic percolation theory. Some properties do not follow a scaling law, a fact that points out the importance of specific interactions for non-ionic microemulsion.