Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-25-3p promotes endothelial cell angiogenesis in aging mice via TULA-2/SYK/VEGFR-2 downregulation

In aging, the regulation of angiogenesis is a dynamic and complex process. We aimed to identify and characterize microRNAs that regulate angiogenesis during aging. We showed that, in response to vascular endothelial senescence, microRNA-25-3p (miR-25-3p) plays the role of an angiogenic microRNA by targeting TULA-2 (T-cell ubiquitin ligand-2)/SYK (spleen tyrosine kinase)/VEGFR-2 (vascular endothelial growth factor receptor 2) signaling in vitro and in vivo. Mechanistic studies demonstrated that miR-25-3p inhibits a TULA-2/SYK/VEGFR-2 signaling pathway in endothelial cells. In old endothelial cells (OECs), upregulation of miR-25-3p inhibited the expression of TULA-2, which caused downregulation of the interaction between TULA-2 and SYK and increased phosphorylation of SYK Y323. The increased SYK Y323 phosphorylation level upregulated the phosphorylation of VEGFR-2 Y1175, which plays a vital role in angiogenesis, while miR-25-3p downregulation in YECs showed opposite effects. Finally, a salvage study showed that miR-25-3p upregulation promoted capillary regeneration and hindlimb blood flow recovery in aging mice with hindlimb ischemia. These findings suggest that miR-25-3p acts as an agonist of TULA-2/SYK/VEGFR-2 and mediates the endothelial cell angiogenesis response, which shows that the miR-25-3p/TULA-2 pathway may be potential therapeutic targets for angiogenesis during aging.
Constitutive relationship and governing physical properties for magnetophoresis

Significance The motion of magnetic particles under magnetic field, referred to as magnetophoresis, is fundamental to nature. While several empirical observations have been gathered, the multitude and complexity of magnetic-field-induced interactions on magnetic particles have prevented the full understanding of this phenomenon. The magnetophoresis is central to several advanced technologies such as magnetic drug targeting, bioseparation, and imaging, yet the efficient targeting of magnetic particles is hampered for the lack of a theoretical framework. We present a fundamental approach utilizing a detailed force balance on magnetic particles to develop a constitutive relationship for magnetophoresis that includes contributions from magnetic diffusion, magnetic convection, and residual magnetization. The application of this theory will enable the predictive design of magnetic targeting applications. Magnetophoresis is an important physical process with application to drug delivery, biomedical imaging, separation, and mixing. Other than empirically, little is known about how the magnetic field and magnetic properties of a solution affect the flux of magnetic particles. A comprehensive explanation of these effects on the transport of magnetic particles has not been developed yet. Here we formulate a consistent, constitutive equation for the magnetophoretic flux of magnetic nanoparticles suspended in a medium exposed to a stationary magnetic field. The constitutive relationship accounts for contributions from magnetic diffusion, magnetic convection, residual magnetization, and electromagnetic drift. We discovered that the key physical properties governing the magnetophoresis are magnetic diffusion coefficient, magnetic velocity, and activity coefficient, which depend on relative magnetic energy and the molar magnetic susceptibility of particles. The constitutive equation also reveals previously unknown ballistic and diffusive limits for magnetophoresis wherein the paramagnetic particles either aggregate near the magnet or diffusive away from the magnet, respectively. In the diffusive limit, the particle concentration is linearly proportional to the relative magnetic energy of the suspension of paramagnetic particles. The region of the localization of paramagnetic particles near the magnet decreases with increasing the strength of the magnet. The dynamic accumulation of nanoparticles, measured as the thickness of the nanoparticle aggregate, near the magnet compares well with the theoretical prediction. The effect of convective mixing on the rate of magnetophoresis is also discussed for the magnetic targeting applications.
A High Quality Asian Genome Assembly Identifies Features of Common Missing Regions

The current human reference genome (GRCh38), with its superior quality, has contributed significantly to genome analysis. However, GRCh38 may still underrepresent the ethnic genome, specifically for Asians, though exactly what we are missing is still elusive. Here, we juxtaposed GRCh38 with a high-contiguity genome assembly of one Korean (AK1) to show that a part of AK1 genome is missing in GRCh38 and that the missing regions harbored ~1390 putative coding elements. Furthermore, we found that multiple populations shared some certain parts in the missing genome when we analyzed the “unmapped” (to GRCh38) reads of fourteen individuals (five East-Asians, four Europeans, and five Africans), amounting to ~5.3 Mb (~0.2% of AK1) of the total genomic regions. The recovered AK1 regions from the “unmapped reads”, which were the estimated missing regions that did not exist in GRCh38, harbored candidate coding elements. We verified that most of the common (shared by ≥7 individuals) missing regions exist in human and chimpanzee DNA. Moreover, we further identified the occurrence mechanism and ethnic heterogeneity as well as the presence of the common missing regions. This study illuminates a potential advantage of using a pangenome reference and brings up the need for further investigations on the various features of regions globally missed in GRCh38.
Porphyromonas gingivalis and Its Systemic Impact: Current Status

The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of Porphyromonas gingivalis in atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about Porphyromonas gingivalis and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which Porphyromonas gingivalis is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that Porphyromonas gingivalis should be regarded as a modifiable factor for several diseases.
Nanomaterials for Treating Bacterial Biofilms on Implantable Medical Devices

Bacterial biofilms are involved in most device-associated infections and remain a challenge for modern medicine. One major approach to addressing this problem is to prevent the formation of biofilms using novel antimicrobial materials, device surface modification or local drug delivery; however, successful preventive measures are still extremely limited. The other approach is concerned with treating biofilms that have already formed on the devices; this approach is the focus of our manuscript. Treating biofilms associated with medical devices has unique challenges due to the biofilm’s extracellular polymer substance (EPS) and the biofilm bacteria’s resistance to most conventional antimicrobial agents. The treatment is further complicated by the fact that the treatment must be suitable for applying on devices surrounded by host tissue in many cases. Nanomaterials have been extensively investigated for preventing biofilm formation on medical devices, yet their applications in treating bacterial biofilm remains to be further investigated due to the fact that treating the biofilm bacteria and destroying the EPS are much more challenging than preventing adhesion of planktonic bacteria or inhibiting their surface colonization. In this highly focused review, we examined only studies that demonstrated successful EPS destruction and biofilm bacteria killing and provided in-depth description of the nanomaterials and the biofilm eradication efficacy, followed by discussion of key issues in this topic and suggestion for future development.
Actinide Association with Groundwater Colloids in a Coastal Plain Aquifer

Trace levels of Pu, Am, Cm, and U in an acidic plume have been traveling through a surface aquifer underlying the Savannah River Site, Aiken, SC, at rates appreciably greater than anticipated. The objective of this study was to determine the extent to which each of these actinides was associated with groundwater colloids, a potential cause for the apparent enhanced transport. Contaminated groundwater was recovered along a 1.02 km transect at approximately the rate of groundwater flow, passed though an ultrafiltration system, and then chemically characterized. The filterable (>500 molecular weight) fraction of nuclides increased with reported nuclide distribution coefficients (Kd values): Pu > Th > U > Am = Cm > Ra > tritium. The filterable fractions of the strongersorbing nuclides (Pu and Th) increased, whereas those of the weaker-sorbing nuclides (Am, Cm, and Ra) generally decreased with increasing pH (3.4 to 4.0) and distance from the point source. Uranium was equally divided between the dissolved and filterable fractions throughout the transect. At the farthest sampling point in the contaminant plume (0.55 km), all the Pu and Th and none of the Am and Cm were in the filterable fraction. Plutonium appears to have a much greater potential than Am or Cm for moving through the study site in association with mobile colloids. However, Am and Cm pose a much greater threat than Pu of migrating through this system, because almost all of the Pu and relatively little of the Am and Cm were retained by the matrix.
Atypical Functional Covariance Connectivity Between Gray and White Matter in Children With Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder with atypical gray matter (GM) and white matter (WM) functional developmental course. However, the functional co‐developmental pattern between GM and WM in ASD is unclear. Here, we utilized a functional covariance connectivity method to explore the concordance pattern between GM and WM function in individuals with ASD. A multi‐center resting‐state fMRI dataset composed of 105 male children with ASD and 102 well‐matched healthy controls (HCs) from six sites of the ABIDE dataset was utilized. GM and WM ALFF maps were calculated for each subject. Voxel by voxel functional covariance connectivity of the ALFF values across subjects was calculated between GM and WM for children with ASD and HCs. A Z‐test combining FDR multi‐comparison correction was then employed to determine whether the functional covariance is significantly different between the two groups. A “bundling” strategy was utilized to ensure that the GM/WM clusters showing atypical functional covariance were larger than 5 voxels. Finally, canonical correlation analysis was conducted to explore whether the atypical GM/WM functional covariance is related to ASD symptoms. Results showed atypical functional covariance connections between specific GM and WM regions, whereas the ALFF values of these regions indicated no significant difference between the two groups. Canonical correlation analysis revealed a significant relationship between the atypical functional covariance and stereotyped behaviors of ASD. The results indicated an altered functional co‐developmental pattern between WM and GM in ASD.
Hybrid Dietary-Blood Inflammatory Profiles and Postmenopausal Breast Cancer: A Case-Control Study

The carcinogenesis process is associated with inflammation, which can be modified by diet. There is limited evidence regarding the inflammatory status and diet in association with breast cancer (BC). The aim of this study was to investigate the association of hybrid dietary-blood inflammatory profiles (HD-BIPs) with postmenopausal breast cancer occurrence. The case-control study was conducted among 420 women (230 controls, 190 primary BC cases) aged 40–79 years from north-eastern Poland. Blood levels of C-reactive protein (CRP), interleukin-6 (IL-6) and leukocyte count were marked in 129 postmenopausal women (82 controls, 47 cases). The 62-item food frequency questionnaire (FFQ-6) was used to the dietary data collection. Two HD-BIPs were found using the Principal Component Analysis (PCA). The “Pro-healthy/Neutral-inflammatory” profile was characterized by the frequent consumption of wholemeal cereals/coarse groats, legumes, vegetables, fruits, nuts/seeds and fish. The “Unhealthy/Pro-inflammatory” profile was characterized by the frequent consumption of red/processed meats, animal fats, sugar/honey/sweets, refined cereals/fine groats, and an increased concentration of CRP, IL-6 and granulocyte-to-lymphocyte ratio. The lower odds ratio (OR) of breast cancer was associated with the higher adherence to the “Pro-healthy/Neutral-inflammatory” profile (OR = 0.38; 95% Cl: 0.18–0.80; p < 0.01 for the higher level vs. lower level, crude model; OR for one-point score increment: 0.61; 95% Cl: 0.42–0.87; p < 0.01, adjusted model). The higher OR of breast cancer was associated with the higher adherence to the “Unhealthy/Pro-inflammatory” profile (OR = 3.07; 95%Cl: 1.27–7.44; p < 0.05 for the higher level v.s. lower level, adjusted model; OR for one-point score increment: 1.18; 95%Cl: 1.02–1.36; p < 0.05, adjusted model). This study revealed that the consumption of highly processed, high in sugar and animal fat foods should be avoided because this unhealthy diet was positively associated with postmenopausal breast cancer occurrence through its pro-inflammatory potential. Instead, the frequent consumption of low-processed plant foods and fish should be recommended since this pro-healthy diet was inversely associated with the cancer occurrence even though its anti-inflammatory potential has not been confirmed in this study sample.
2D Octagon-Structure Carbon and Its Polarization Resolved Raman Spectra

We predict a new phase of two-dimensional carbon with density functional theory (DFT). It was found to be semimetal with two Dirac points. The vibrational properties and the polarization resolved Raman spectra of the carbon monolayer are predicted. There are five Raman active modes: 574 cm−1 (Eg), 1112 cm−1 (B1g), 1186 cm−1 (B2g), 1605 cm−1 (B2g) and 1734 cm−1 (A1g). We consider the incident light wave vector to be perpendicular and parallel to the plane of the carbon monolayer. By calculating Raman tensor of each Raman active mode, we obtained polarization angle dependent Raman intensities. Our results will help materials scientists to identify the existence and orientation of octagon-structure carbon monolayer when they are growing it.
Human papillomavirus prevalence and integration status in tissue samples of bladder cancer in Chinese population.

BACKGROUND Human papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer. METHODS Frozen tissue samples collected from 146 patients aged 32 to 89 years-old with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, gender and age group of patients. RESULTS Mean age of 146 patients was 66.64 ± 10.06 years and 83.56% were male. Overall HPV infection rate was 28.77% (37.5% in female and 27% in male), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% co-infections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, 39. All HPV were European lineage (A). HPV16 was more prevalent in female (p=0.04). CONCLUSION HPV infection may contribute a causative role both in men and women with bladder cancer. HPV18, followed by HPV 33, 16 and 39 genotypes potentially represent the predominant oncogenic risk types of bladder carcinogenesis.
Die neuen WHO-Empfehlungen für schnelle Diagnostik und Therapie resistenter Tuberkulose in Deutschland, Österreich und der Schweiz

Zusammenfassung Die erfreulicherweise zunehmende Evidenz hat in den letzten Jahren mehrfache Änderungen der internationalen Empfehlungen für die Diagnostik und Therapie der resistenten Tuberkulose notwendig gemacht. In diesem Jahr hat die WHO umfassende Empfehlungen veröffentlicht, die die Entwicklungen der letzten Jahre berücksichtigen. Die aktuelle deutsche Tuberkuloseleitlinie erschien im Jahr 2017 und weicht in einigen Bereichen von diesen Empfehlungen ab. Hier werden die Neuerungen der WHO-Empfehlungen von 2020 für schnelle Diagnostik und die Therapie resistenter Tuberkulose zusammengefasst und relevante Abweichungen für Deutschland, Österreich und die Schweiz kommentiert. Eine Neubewertung der Literatur findet derzeit im Rahmen der Aktualisierung der deutschsprachigen AWMF-2k-Leitlinie statt.
A Genetic Screen to Identify New Molecular Players Involved in Photoprotection qH in Arabidopsis thaliana

Photosynthesis is a biological process which converts light energy into chemical energy that is used in the Calvin–Benson cycle to produce organic compounds. An excess of light can induce damage to the photosynthetic machinery. Therefore, plants have evolved photoprotective mechanisms such as non-photochemical quenching (NPQ). To focus molecular insights on slowly relaxing NPQ processes in Arabidopsis thaliana, previously, a qE-deficient line—the PsbS mutant—was mutagenized and a mutant with high and slowly relaxing NPQ was isolated. The mutated gene was named suppressor of quenching 1, or SOQ1, to describe its function. Indeed, when present, SOQ1 negatively regulates or suppresses a form of antenna NPQ that is slow to relax and is photoprotective. We have now termed this component qH and identified the plastid lipocalin, LCNP, as the effector for this energy dissipation mode to occur. Recently, we found that the relaxation of qH1, ROQH1, protein is required to turn off qH. The aim of this study is to identify new molecular players involved in photoprotection qH by a whole genome sequencing approach of chemically mutagenized Arabidopsis thaliana. We conducted an EMS-mutagenesis on the soq1 npq4 double mutant and used chlorophyll fluorescence imaging to screen for suppressors and enhancers of qH. Out of 22,000 mutagenized plants screened, the molecular players cited above were found using a mapping-by-sequencing approach. Here, we describe the phenotypic characterization of the other mutants isolated from this genetic screen and an additional 8000 plants screened. We have classified them in several classes based on their fluorescence parameters, NPQ kinetics, and pigment content. A high-throughput whole genome sequencing approach on 65 mutants will identify the causal mutations thanks to allelic mutations from having reached saturation of the genetic screen. The candidate genes could be involved in the formation or maintenance of quenching sites for qH, in the regulation of qH at the transcriptional level, or be part of the quenching site itself.
Epitaxial Growth of GaN on Magnetron Sputtered AlN/Hexagonal BN/Sapphire Substrates

Magnetron sputtering is adopted to deposit ~25 nm thick AlN on the surface of hexagonal BN(h-BN)/sapphire substrates, followed by epitaxial GaN growth on top of the AlN/h-BN/sapphire substrate using a metal–organic chemical vapor deposition system. Compared to GaN grown on the h-BN/sapphire surface directly, this method results in a continuous and smooth GaN film with a smaller root mean square roughness. Besides, the introduction of the sputtered AlN layer reduces the dislocation density of GaN by 35.7%. We provide a pathway of GaN epitaxy on the h-BN surface, which significantly improves its surface morphology and crystal quality.
Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004–1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042–1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943–0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan–Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient’s background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.
Direct and Bicarbonate-Induced Iron Deficiency Differently Affect Iron Translocation in Kiwifruit Roots

Bicarbonate-induced iron (Fe) deficiency (+Bic) is frequently observed in kiwifruit orchards, but more research attention has been paid to direct Fe deficiency (-Fe) in plants, including kiwifruit. Here we compared the differences of kiwifruit plants between -Fe and +Bic in: (1) the traits of 57Fe uptake and translocation within plants, (2) Fe forms in roots, and (3) some acidic ions and metabolites in roots. The concentration of 57Fe derived from nutrient solution (57Fedfs) in roots was less reduced in +Bic than -Fe treatment, despite similar decrease in shoots of both treatments. +Bic treatment increased 57Fedfs distribution in fine roots but decreased it in new leaves and stem, thereby displaying the inhibition of 57Fedfs translocation from roots to shoots and from fine roots to xylem of coarse roots. Moreover, +Bic imposition induced the accumulation of water-soluble Fe and apoplastic Fe in roots. However, the opposite was observed in -Fe-treated plants. Additionally, the cell wall Fe and hemicellulose Fe in roots were less reduced by +Bic than -Fe treatment. +Bic treatment also triggered the reduction in H+ extrusion and the accumulation of NH4+, succinic acid, and some amino acids in roots. These results suggest that, contrary to -Fe, +Bic treatment inhibits Fe translocation to shoots by accumulating water-soluble and apoplastic Fe and slowing down the release of hemicellulose Fe in the cell wall in kiwifruit roots, which may be related to the decreased H+ extrusion and the imbalance between C and N metabolisms.