Miracle-dz/UniFAR-FTUs huggingface dataset:
Wound Healing Effect of Gintonin Involves Lysophosphatidic Acid Receptor/Vascular Endothelial Growth Factor Signaling Pathway in Keratinocytes

Gintonin, a novel compound of ginseng, is a ligand of the lysophosphatidic acid (LPA) receptor. The in vitro and in vivo skin wound healing effects of gintonin remain unknown. Therefore, the objective of this study was to investigate the effects of gintonin on wound healing-linked responses, especially migration and proliferation, in skin keratinocytes HaCaT. In this study, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, Boyden chamber migration assay, scratch wound healing assay, and Western blot assay were performed. A tail wound mouse model was used for the in vivo test. Gintonin increased proliferation, migration, and scratch closure in HaCaT cells. It also increased the release of vascular endothelial growth factor (VEGF) in HaCaT cells. However, these increases, induced by gintonin, were markedly blocked by treatment with Ki16425, an LPA inhibitor, PD98059, an ERK inhibitor, 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester), a calcium chelator, and U73122, a PLC inhibitor. The VEGF receptor inhibitor axitinib also attenuated gintonin-enhanced HaCaT cell proliferation. Gintonin increased the phosphorylation of AKT and ERK1/2 in HaCaT cells. In addition, gintonin improved tail wound healing in mice. These results indicate that gintonin may promote wound healing through LPA receptor activation and/or VEGF release-mediated downstream signaling pathways. Thus, gintonin could be a beneficial substance to facilitate skin wound healing.
Review of Aluminum Alloy Development for Wire Arc Additive Manufacturing

Processing of aluminum alloys by wire arc additive manufacturing (WAAM) gained significant attention from industry and academia in the last decade. With the possibility to create large and relatively complex parts at low investment and operational expenses, WAAM is well-suited for implementation in a range of industries. The process nature involves fusion melting of a feedstock wire by an electric arc where metal droplets are strategically deposited in a layer-by-layer fashion to create the final shape. The inherent fusion and solidification characteristics in WAAM are governing several aspects of the final material, herein process-related defects such as porosity and cracking, microstructure, properties, and performance. Coupled to all mentioned aspects is the alloy composition, which at present is highly restricted for WAAM of aluminum but received considerable attention in later years. This review article describes common quality issues related to WAAM of aluminum, i.e., porosity, residual stresses, and cracking. Measures to combat these challenges are further outlined, with special attention to the alloy composition. The state-of-the-art of aluminum alloy selection and measures to further enhance the performance of aluminum WAAM materials are presented. Strategies for further development of new alloys are discussed, with attention on the importance of reducing crack susceptibility and grain refinement.
Metabolic Regulation of Sugar Assimilation for Lipid Production in Aspergillus oryzae BCC7051 through Comparative Transcriptome Perspective

Simple Summary Oleaginous fungi are a promising candidate to produce microbial lipids as alternative sources for industrial applications. As lipids are intracellular metabolites with dynamic traits, the fungal ability in utilizing carbon sources for biomass and lipid production is significant in terms of production yield and economic feasibility. This study aimed to explore the metabolic regulation in lipogenesis of oleaginous Aspergillus oryzae BCC7051 at the transcriptional level. Through comparative transcriptome analysis, a set of differentially expressed genes (DEGs) between the xylose- and glucose-grown cultures (C5 and C6 cultures) at fast-growing and lipid-accumulating stages were identified and functionally categorized into transporter proteins and cellular processes. Combining with the growth and lipid phenotypes, the transcriptome results pointed to a crucial link between sugar assimilation, energy, lipid, and other metabolisms in A. oryzae for leveraging the metabolic flux from xylose to fatty acid and lipid biosynthesis in render the oleaginous features. This study provides a remarkable insight in guiding strain optimization and bioprocess development using renewable feedstocks from agroindustrial residues. Abstract Microbial lipid production with cost effectiveness is a prerequisite for the oleochemical sector. In this work, genome-wide transcriptional responses on the utilization of xylose and glucose in oleaginous Aspergillus oryzae were studied with relation to growth and lipid phenotypic traits. Comparative analysis of the active growth (t1) and lipid-accumulating (t2) stages showed that the C5 cultures efficiently consumed carbon sources for biomass and lipid production comparable to the C6 cultures. By pairwise comparison, 599 and 917 differentially expressed genes (DEGs) were identified in the t1 and t2 groups, respectively, in which the consensus DEGs were categorized into polysaccharide-degrading enzymes, membrane transports, and cellular processes. A discrimination in transcriptional responses of DEGs set was also found in various metabolic genes, mostly in carbohydrate, amino acid, lipid, cofactors, and vitamin metabolisms. Although central carbohydrate metabolism was shared among the C5 and C6 cultures, the metabolic functions in acetyl-CoA and NADPH generation, and biosynthesis of terpenoid backbone, fatty acid, sterol, and amino acids were allocated for leveraging biomass and lipid production through at least transcriptional control. This study revealed robust metabolic networks in the oleaginicity of A. oryzae governing glucose/xylose flux toward lipid biosynthesis that provides meaningful hints for further process developments of microbial lipid production using cellulosic sugar feedstocks.
Correlations of Geometry and Infill Degree of Extrusion Additively Manufactured 316L Stainless Steel Components

This study focuses on the effect of part geometry and infill degrees on effective mechanical properties of extrusion additively manufactured stainless steel 316L parts produced with BASF’s Ultrafuse 316LX filament. Knowledge about correlations between infill degrees, mechanical properties and dimensional deviations are essential to enhance the part performance and further establish efficient methods for the product development for lightweight metal engineering applications. To investigate the effective Young’s modulus, yield strength and bending stress, standard testing methods for tensile testing and bending testing were used. For evaluating the dimensional accuracy, the tensile and bending specimens were measured before and after sintering to analyze anisotropic shrinkage effects and dimensional deviations linked to the infill structure. The results showed that dimensions larger than 10 mm have minor geometrical deviations and that the effective Young’s modulus varied in the range of 176%. These findings provide a more profound understanding of the process and its capabilities and enhance the product development process for metal extrusion-based additive manufacturing.
Low-Velocity Impact Analysis of Pineapple Leaf Fiber (PALF) Hybrid Composites

The low-velocity impact behaviour of pineapple leaf fiber, PALF reinforce epoxy composite (P), PALF hybrid (GPG), and four-layer woven glass fiber (GGGG) composite was investigated. As for post-impact analysis, the damage evaluation was assessed through photographic images and X-ray computed tomography, using CT scan techniques. The key findings from this study are that a positive hybrid effect of PALF as a reinforcement was seen where the GPG shows the delayed time taken for damage initiation and propagation through the whole sample compared to GGGG. This clearly shows that the addition of fibers does have comparable composite properties with a fully synthetic composite. Through the visual inspection captured by photographic image, the presence of woven fiber glass mat in GPG presents a different damage mode compared to P. Moreover, CT scan results show extended internal damage at the cross-section of all impacted composite.
Combining Photodynamic Therapy with Immunostimulatory Nanoparticles Elicits Effective Anti-Tumor Immune Responses in Preclinical Murine Models

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8+ T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8+ T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8+ T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors.
The Potential of Tissue-Resident Memory T Cells for Adoptive Immunotherapy against Cancer

Tissue-resident memory T cells (TRM) comprise an important memory T cell subset that mediates local protection upon pathogen re-encounter. TRM populations preferentially localize at entry sites of pathogens, including epithelia of the skin, lungs and intestine, but have also been observed in secondary lymphoid tissue, brain, liver and kidney. More recently, memory T cells characterized as TRM have also been identified in tumors, including but not limited to melanoma, lung carcinoma, cervical carcinoma, gastric carcinoma and ovarian carcinoma. The presence of these memory T cells has been strongly associated with favorable clinical outcomes, which has generated an interest in targeting TRM cells to improve immunotherapy of cancer patients. Nevertheless, intratumoral TRM have also been found to express checkpoint inhibitory receptors, such as PD-1 and LAG-3. Triggering of such inhibitory receptors could induce dysfunction, often referred to as exhaustion, which may limit the effectiveness of TRM in countering tumor growth. A better understanding of the differentiation and function of TRM in tumor settings is crucial to deploy these memory T cells in future treatment options of cancer patients. The purpose of this review is to provide the current status of an important cancer immunotherapy known as TIL therapy, insight into the role of TRM in the context of antitumor immunity, and the challenges and opportunities to exploit these cells for TIL therapy to ultimately improve cancer treatment.
MRI and Targeted Biopsy Essential Tools for an Accurate Diagnosis and Treatment Decision Making in Prostate Cancer

Prostate cancer (PCa) is one of the most frequent causes of cancer death worldwide. Historically, diagnosis was based on physical examination, transrectal (TRUS) images, and TRUS biopsy resulting in overdiagnosis and overtreatment. Recently magnetic resonance imaging (MRI) has been identified as an evolving tool in terms of diagnosis, staging, treatment decision, and follow-up. In this review we provide the key studies and concepts of MRI as a promising tool in the diagnosis and management of prostate cancer in the general population and in challenging scenarios, such as anteriorly located lesions, enlarged prostates determining extracapsular extension and seminal vesicle invasion, and prior negative biopsy and the future role of MRI in association with artificial intelligence (AI).
Tau N-Terminal Inserts Regulate Tau Liquid-Liquid Phase Separation and Condensates Maturation in a Neuronal Cell Model

The microtubule-associated protein tau can undergo liquid–liquid phase separation (LLPS) to form membraneless condensates in neurons, yet the underlying molecular mechanisms and functions of tau LLPS and tau droplets remain to be elucidated. The human brain contains mainly 6 tau isoforms with different numbers of microtubule-binding repeats (3R, 4R) and N-terminal inserts (0N, 1N, 2N). However, little is known about the role of N-terminal inserts. Here we observed the dynamics of three tau isoforms with different N-terminal inserts in live neuronal cell line HT22. We validated tau LLPS in cytoplasm and found that 2N-tau forms liquid-like, hollow-shell droplets. Tau condensates became smaller in 1N-tau comparing with 2N-tau, while no obvious tau accumulated dots were shown in 0N-tau. The absence of N-terminal inserts significantly affected condensate colocalization of tau and p62. The results reveal insights into the tau LLPS assembly mechanism and functional effects of N-terminal inserts in tau.
A Molecular Simulation Study of Carbon Dioxide Uptake by a Deep Eutectic Solvent Confined in Slit Nanopores

Molecular dynamics simulations were performed to study the behavior of CO2 in varying amounts of a common deep eutectic solvent (DES), choline chloride and ethylene glycol (termed ethaline), confined in slit-like pores of width H = 5.2 nm with graphite or rutile walls at T = 318 K. In the absence of DES, CO2 adsorbs to the pore walls, but increasing amounts of ethaline inside the pores quickly displace carbon dioxide into the gas/liquid interfaces, and into dissolution within the confined DES. This process is driven by strong interactions of the ethaline components with the pore walls, especially in the case of rutile systems, which also cause the local ratio of choline chloride:ethylene glycol inside the pores to depart from the bulk value of 1:2. As the amount of DES inside the pores increases, the diffusivity of CO2 reaches a maximum in partially filled pores and decays to the values observed in pores filled with DES, which are similar to the diffusion coefficients of CO2 in the bulk DES. The average n.
ABO Incompatible Liver Transplantation in Children: A 20 Year Experience from Centres in the TransplantChild European Reference Network

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children.
RNA-Seq-Based Profiling of pl Mutant Reveals Transcriptional Regulation of Anthocyanin Biosynthesis in Rice (Oryza sativa L.)

Purple-colored leaves in plants attain much interest for their important biological functions and could be a potential source of phenotypic marker in selecting individuals in breeding. The transcriptional profiling helps to precisely identify mechanisms of leaf pigmentation in crop plants. In this study, two genetically unlike rice genotypes, the mutant purple leaf (pl) and wild (WT) were selected for RNA-sequencing and identifying the differentially expressed genes (DEGs) that are regulating purple leaf color. In total, 609 DEGs were identified, of which 513 and 96 genes were up- and down-regulated, respectively. The identified DEGs are categorized into metabolic process, carboxylic acid biosynthesis, phenylpropanoids, and phenylpropanoid biosynthesis process enrichment by GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed their association with phenylpropanoid synthesis, flavonoid synthesis, and phenylalanine metabolism. To explore molecular mechanism of purple leaf color, a set of anthocyanin biosynthetic and regulatory gene expression patterns were checked by qPCR. We found that OsPAL (Os02g0626100, Os02g0626400, Os04g0518400, Os05g0427400 and Os02g0627100), OsF3H (Os03g0122300), OsC4HL (Os05g0320700), and Os4CL5 (Os08g0448000) are associated with anthocyanin biosynthesis, and they were up-regulated in pl leaves. Two members of regulatory MYB genes (OsMYB55; Os05g0553400 and Os08g0428200), two bHLH genes (Os01g0196300 and Os04g0300600), and two WD40 genes (Os11g0132700 and Os11g0610700) also showed up-regulation in pl mutant. These genes might have significant and vital roles in pl leaf coloration and could provide reference materials for further experimentation to confirm the molecular mechanisms of anthocyanin biosynthesis in rice.
Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial

Simple Summary Recently, tumour local thermal ablation has been investigated in pancreatic ductal adenocarcinoma (PDAC), hypothesizing that it may add local efficacy to the chemotherapy systemic activity inducing changes of tumour microenvironment and increased intra-tumour drug efficacy. In this phase II randomized controlled trial we investigated the efficacy of thermal ablation with the HybridTherm probe under endoscopic ultrasound-guidance (EUS) as complement to chemotherapy (HTP-CT arm) versus standard chemotherapy alone (CT arm), in locally advanced and borderline resectable PDAC. A sample size of 33 patients per arm was calculated to verify a 20% improved 6-months progression-free survival (6-PFS) rate with HTP-CT. We randomized 17 and 20 patients to HTP-CT and CT arms, respectively. Although not significantly, we found an improved 6-PFS rate in the HTP-CT arm. However, the overall survival was similar between the two arms. Thus, as the study is underpowered, further investigation of EUS-guided thermal ablation in selected patients is suggested. Abstract Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms (p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients (p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients (p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.
Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Monocentric Retrospective Survey

Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS−) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density—BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS− RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = −0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = −0.45, p = 0.01, r = −0.40, p = 0.03, r = −0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = −0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS− RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values.