Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy

Simple Summary Multiple types of primary tumors and metastases that present with very little if any immune cell infiltration (so-called immunologically “cold” tumors) do not respond to current immunotherapies. In this study, we show that recently developed intratumoral application-based immunotherapy using mannan-BAM, TLR ligands, and anti-CD40 antibody (MBTA therapy) efficiently suppresses tumor growth in a murine bilateral pheochromocytoma model. Moreover, MBTA therapy increases the recruitment of innate immune cells followed by adaptive immune cells not only to primary (injected) tumors but also distal (non-injected) tumors. We also demonstrated that after successful MBTA therapy of subcutaneous pheochromocytoma, long-term immunological memory is driven by CD4+ T cells. Taken together, this study helps to better understand the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination. Abstract Immunotherapy has become an essential component in cancer treatment. However, the majority of solid metastatic cancers, such as pheochromocytoma, are resistant to this approach. Therefore, understanding immune cell composition in primary and distant metastatic tumors is important for therapeutic intervention and diagnostics. Combined mannan-BAM, TLR ligand, and anti-CD40 antibody-based intratumoral immunotherapy (MBTA therapy) previously resulted in the complete eradication of murine subcutaneous pheochromocytoma and demonstrated a systemic antitumor immune response in a metastatic model. Here, we further evaluated this systemic effect using a bilateral pheochromocytoma model, performing MBTA therapy through injection into the primary tumor and using distant (non-injected) tumors to monitor size changes and detailed immune cell infiltration. MBTA therapy suppressed the growth of not only injected but also distal tumors and prolonged MBTA-treated mice survival. Our flow cytometry analysis showed that MBTA therapy led to increased recruitment of innate and adaptive immune cells in both tumors and the spleen. Moreover, adoptive CD4+ T cell transfer from successfully MBTA-treated mice (i.e., subcutaneous pheochromocytoma) demonstrates the importance of these cells in long-term immunological memory. In summary, this study unravels further details on the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination.
Engagement of Language and Domain General Networks during Word Monitoring in a Native and Unknown Language

Functional neuroimaging studies have highlighted the roles of three networks in processing language, all of which are typically left-lateralized: a ventral stream involved in semantics, a dorsal stream involved in phonology and speech production, and a more dorsal “multiple demand” network involved in many effortful tasks. As lateralization in all networks may be affected by life factors such as age, literacy, education, and brain pathology, we sought to develop a task paradigm with which to investigate the engagement of these networks, including manipulations to selectively emphasize semantic and phonological processing within a single task performable by almost anyone regardless of literacy status. In young healthy participants, we administered an auditory word monitoring task, in which participants had to note the occurrence of a target word within a continuous story presented in either their native language, Portuguese, or the unknown language, Japanese. Native language task performance activated ventral stream language networks, left lateralized but bilateral in the anterior temporal lobe. Unfamiliar language performance, being more difficult, activated left hemisphere dorsal stream structures and the multiple demand network bilaterally, but predominantly in the right hemisphere. These findings suggest that increased demands on phonological processing to accomplish word monitoring in the absence of semantic support may result in the bilateral recruitment of networks involved in speech perception under more challenging conditions.
Probiotics, Prebiotics, and Synbiotics in the Irritable Bowel Syndrome Treatment: A Review

Irritable bowel syndrome is not a life-threatening disease, yet it significantly affects the quality of life and contributes to economic loss. It is estimated that even up to 45% of the world’s population can suffer from the disease. The first attempts to diagnose irritable bowel syndrome were made at the end of the 19th century; however, establishing appropriate diagnostic criteria and treatment methods is still ongoing. To date, little is known about the etiology of irritable bowel syndrome; however, growing attention is drawn to the intestinal microbiota as a factor in the disease development. For this reason, researchers have conducted many studies on therapies that modulate the microbiota, among which probiotics, prebiotics, and synbiotics are widely studied. To date, most studies have examined probiotics; however, there are also several studies demonstrating the efficacy of prebiotics and synbiotics. The aim of this review was to summarize findings on the usefulness of probiotics, prebiotics, and synbiotics in the treatment of irritable bowel syndrome.
Direct One-Step Growth of Bimetallic Ni2Mo3N on Ni Foam as an Efficient Oxygen Evolution Electrocatalyst

A simple and economical synthetic route for direct one-step growth of bimetallic Ni2Mo3N nanoparticles on Ni foam substrate (Ni2Mo3N/NF) and its catalytic performance during an oxygen evolution reaction (OER) are reported. The Ni2Mo3N/NF catalyst was obtained by annealing a mixture of a Mo precursor, Ni foam, and urea at 600 °C under N2 flow using one-pot synthesis. Moreover, the Ni2Mo3N/NF exhibited high OER activity with low overpotential values (336.38 mV at 50 mA cm−2 and 392.49 mV at 100 mA cm−2) and good stability for 5 h in Fe-purified alkaline electrolyte. The Ni2Mo3N nanoparticle surfaces converted into amorphous surface oxide species during the OER, which might be attributed to the OER activity.
Identification of a Common Epitope in Nucleocapsid Proteins of Euro-America Orthotospoviruses and Its Application for Tagging Proteins

The NSs protein and the nucleocapsid protein (NP) of orthotospoviruses are the major targets for serological detection and diagnosis. A common epitope of KFTMHNQIF in the NSs proteins of Asia orthotospoviruses has been applied as an epitope tag (nss-tag) for monitoring recombinant proteins. In this study, a monoclonal antibody TNP MAb against the tomato spotted wilt virus (TSWV) NP that reacts with TSWV-serogroup members of Euro-America orthotospoviruses was produced. By truncation and deletion analyses of TSWV NP, the common epitope of KGKEYA was identified and designated as the np sequence. The np sequence was successfully utilized as an epitope tag (np-tag) to monitor various proteins, including the green fluorescence protein, the coat protein of the zucchini yellow mosaic virus, and the dust mite chimeric allergen Dp25, in a bacterial expression system. The np-tag was also applied to investigate the protein–protein interaction in immunoprecipitation. In addition, when the np-tag and the nss-tag were simultaneously attached at different termini of the expressed recombinant proteins, they reacted with the corresponding MAbs with high sensitivity. Here, we demonstrated that the np sequence and TNP MAb can be effectively applied for tagging and detecting proteins and can be coupled with the nss-tag to form a novel epitope-tagging system for investigating protein–protein interactions.
Insights into the Mechanisms of Heat Priming and Thermotolerance in Tobacco Pollen

Global warming leads to a progressive rise in environmental temperature. Plants, as sessile organisms, are threatened by these changes; the male gametophyte is extremely sensitive to high temperature and its ability to preserve its physiological status under heat stress is known as acquired thermotolerance. This latter can be achieved by exposing plant to a sub-lethal temperature (priming) or to a progressive increase in temperature. The present research aims to investigate the effects of heat priming on the functioning of tobacco pollen grains. In addition to evaluating basic physiological parameters (e.g., pollen viability, germination and pollen tube length), several aspects related to a correct pollen functioning were considered. Calcium (Ca2+) level, reactive oxygen species (ROS) and related antioxidant systems were investigated, also to the organization of actin filaments and cytoskeletal protein such as tubulin (including tyrosinated and acetylated isoforms) and actin. We also focused on sucrose synthase (Sus), a key metabolic enzyme and on the content of main soluble sugars, including UDP-glucose. Results here obtained showed that a pre-exposure to sub-lethal temperatures can positively enhance pollen performance by altering its metabolism. This can have a considerable impact, especially from the point of view of breeding strategies aimed at improving crop species.
Deviant Peer Affiliation and Non-Suicidal Self-Injury among Chinese Adolescents: Depression as a Mediator and Sensation Seeking as a Moderator

Non-suicidal self-injury (NSSI) is an emerging health problem among adolescents. Although previous studies have shown that deviant peer affiliation is an important risk factor for this behavior, the reasons for this relationship are unclear. Based on the integrated theoretical model of the development and maintenance of NSSI and the social development model of delinquency prevention, this study tested whether depression mediated the relationship between deviant peer affiliation and NSSI and whether this mediating effect was moderated by sensation seeking. A sample of 854 Chinese adolescents (31.50% male; Mage = 16.35; SD = 1.15) anonymously completed questionnaires on the study variables. Results of regression-based analyses showed that depression mediated the association between deviant peer affiliation and NSSI, and this effect was stronger among adolescents who reported high sensation seeking. The results demonstrate the role of individual differences in the link between affiliation with deviant peers and NSSI, and have implications for preventing and treating this risky behavior.
Targeting Intracellular Mycobacteria Using Nanosized Niosomes Loaded with Antibacterial Agents

Background: Pathogenic intracellular mycobacteria are challenging to treat because of the waxy and complex cell wall characterizing the genus. Niosomes are vesicles with biomimetic cell membrane composition, which allow them to efficiently bind to the eukaryotic cells and deliver their cargo into the cytoplasm. The objective of this study was to develop a new platform based on niosomes loaded with antimicrobial agents to target intracellular mycobacteria. Nanoniosomes were fabricated and loaded with antibiotics and lignin–silver nanoparticles. The efficacy of these nanoniosomes was tested against the intracellular pathogen Mycobacterium abscessus used as a model of infection of human-derived macrophages (THP-1). The cytotoxicity and the immunological response of the agents were tested on THP-1 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the secretion of pro- and anti-inflammatory cytokines, respectively. Results: M. abscessus was susceptible to the nanoniosomes in infected THP-1 macrophages, suggesting that the nanoniosomes were internalized due to their fusion to the macrophage cellular membrane. Moreover, nanoniosomes showed no upregulation of pro-inflammatory cytokines when exposed to THP-1 macrophages. Conclusions: Nanoniosomes improved drug efficacy while decreasing toxicity and should be considered for further testing in the treatment of intracellular pathogenic mycobacteria or as a new platform for precise intracellular delivery of drugs.
Towards realistic organ models for 3D printing and visualization

Abstract Three-dimensional visualizations and 3D-printed organs are used increasingly for teaching, surgery planning, patient education, and interventions. Hence, pipelines for the creation of the necessary geometric data from CT or MR images on a per-patient basis are needed. Furthermore, modern 3D printing techniques enable new possibilities for the models with regard to color, softness, and textures. However, to utilize these new features, the respective information has to be derived from the medical images in addition to the geometry of the relevant organ structures. In this work, we propose an automatable pipeline for the creation of realistic, patientspecific 3D-models for visualization and 3D printing in the context of liver surgery and discuss remaining challenges.
Unconventional Approaches to Prepare Triazine-Based Liquid Crystal Dendrimers

Most triazine-based liquid crystalline (LC) dendrimers reported thus far are the main-chain LC macromolecules with long flexible chains at their periphery and attached to internal rigid or semi-rigid frameworks. Their formation of mesogenic phases often depends on the intermolecular face-to-face π–π interactions between dendritic molecules, which are unusual. Their mesogenic phases can also be formed by incorporation of mesogenic units to the dendritic skeletons through long flexible chains, as most side-chain LC dendrimers, in which the peripheral mesogenic units generally play the important roles. For main-chain triazine-based dendrimers, their morphology is maintained by restricted freedom of rigid or semi-rigid connecting units, and their formations of LC phases are therefore not straightforward to be controlled. In this review, we thus describe modulating of the intermolecular face-to-face π–π interactions between the triazine-based dendritic molecules, with the aim of forming LC phases through molecular design.
Selective Targeting of Class I Histone Deacetylases in a Model of Human Osteosarcoma

Simple Summary Osteosarcoma is the predominant form of primary bone cancer and outcomes for patients with metastatic disease have not improved for several decades. Recent genomic and pharmacological studies have implicated dysregulated histone deacetylases as druggable targets to treat several types of cancers, including osteosarcoma. This study aimed to assess the inhibitory effects of 4SC-202, a next-generation inhibitor for class I histone deacetylases, on human osteosarcoma cell growth in vitro and in vivo. We demonstrated that the anti-tumor effect of 4SC-202 involves combined cell-cycle arrest and apoptosis, as well as a reduction in cell invasion and migration. Moreover, 4SC-202 revised the global transcriptome and induced distinct signatures of gene expression in vitro. Additionally, 4SC-202 decreased tumor growth of established human tumor xenografts in immunodeficient mice in vivo. Our study suggests that 4SC-202 may be exploited as a valuable drug to promote more effective treatment of patients. Abstract Dysregulation of histone deacetylases (HDACs) is associated with the pathogenesis of human osteosarcoma, which may present an epigenetic vulnerability as well as a therapeutic target. Domatinostat (4SC-202) is a next-generation class I HDAC inhibitor that is currently being used in clinical research for certain cancers, but its impact on human osteosarcoma has yet to be explored. In this study, we report that 4SC-202 inhibits osteosarcoma cell growth in vitro and in vivo. By analyzing cell function in vitro, we show that the anti-tumor effect of 4SC-202 involves the combined induction of cell-cycle arrest at the G2/M phase and apoptotic program, as well as a reduction in cell invasion and migration capabilities. We also found that 4SC-202 has little capacity to promote osteogenic differentiation. Remarkably, 4SC-202 revised the global transcriptome and induced distinct signatures of gene expression in vitro. Moreover, 4SC-202 decreased tumor growth of established human tumor xenografts in immunodeficient mice in vivo. We further reveal key targets regulated by 4SC-202 that contribute to tumor cell growth and survival, and canonical signaling pathways associated with progression and metastasis of osteosarcoma. Our study suggests that 4SC-202 may be exploited as a valuable drug to promote more effective treatment of patients with osteosarcoma and provide molecular insights into the mechanism of action of class I HDAC inhibitors.
Treatment with PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia Lowers Plasma Levels of Platelet-Activating Factor and Its Precursors: A Combined Metabolomic and Lipidomic Approach

Introduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p < 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value < 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9i.
Clean: Minimize Switch Queue Length via Transparent ECN-proxy in Campus Networks

Campus networks are widely deployed for organizations like universities and large companies. Applications and network-based services require campus networks to guarantee short queue and provide low latency and large bandwidth. However, the widely adopted packet-loss-based congestion control mechanism in client hosts builds up long queues in the switch buffer, which is prone to packet loss in burst scenarios, resulting in great network delay. Therefore, a scheme for efficiently controlling queue length of shallow buffer switches in campus networks is urgently needed. Explicit Congestion Notification(ECN) as an explicit feedback mechanism is widely adopted in data center networks to build lossless networks. In this paper, we propose Clean, an efficient queue length control scheme based on transparent ECN-proxy for campus networks. Clean is able to exert fine-grained control over arbitrary client TCP stacks by enforcing per-flow congestion control in the access point(AP). It allows the campus network switches to maintain a low queue length, resulting in high throughput, low latency and zero packet loss. Evaluation results demonstrate that Clean reduces the maximum queue length of the switch by 86% and reduces the 99th percentile latency by 85%. Clean also achieves zero packet loss in burst scenarios.
Deciphering the Endophytic and Rhizospheric Microbial Communities of a Metallophyte Commelina communis in Different Cu-Polluted Soils

Metallophytes microbiota play a key role in plant growth and resistance to heavy metal stress. Comparing to the well-studied single or some specific plant growth-promoting (PGP) bacterial strains, our current understanding of the structural and functional variations of microbiome of metallophytes is still limited. Here, we systematically investigated the endophytic and rhizosphere bacterial community profiles of a metallophyte Commelina communis growing in different Cu-polluted soils by high-throughput sequencing technology. The results showed that the rhizosphere communities of C. communis exhibited a much higher level of diversity and richness than the endosphere communities. Meanwhile, shifts in the bacterial community composition were observed between the rhizosphere and endosphere of C. communis, indicating plant compartment was a strong driver for the divergence between rhizosphere and endosphere community. Among the environmental factors, soil Cu content, followed by OM, TP and TN, played major roles in shaping the bacterial community structure of C. communis. At the highly Cu-contaminated site, Pseudomonas and Sphingomonas were the predominant genera in the endophytic and rhizospheric bacterial communities, respectively, which might enhance copper tolerance as PGP bacteria. In summary, our findings will be useful to better understand metallophyte–microbe interactions and select suitable bacterial taxa when facilitating phytoremediation.
Modeling and Understanding of Rear Junction Double-Side Passivated Contact Solar Cells with Selective Area TOPCon on Front

Device modeling is performed to propose > 25% efficient industry-compatible rear junction double-side passivated contacts solar cell structure with full area p-TOPCon on the rear and selective area n-TOPCon under the front grid pattern (selective TOPCon). This design enables the use of thicker TOPCon (>100nm) on the front for traditional screen-printed contacts without incurring metal-induced damage, high parasitic absorption loss, and compromise in lateral transport or carrier collection on the front. Rear junction design with appropriate bulk lifetime and resistivity combination eliminate the need for heavy doping in the front field region because carriers can flow through the bulk Si without appreciable FF loss. High VOC is maintained because high-quality Si surface passivation in the field region by Al2O3/SiN gives J0 comparable to the TOPCon. Our device modeling specifies the practically achievable properties and parameters for each region, including full area rear p-TOPCon, selective area front n-TOPCon, bulk and contacts, to achieve 25.4% efficiency screen-printed bifacial rear junction selective TOPCon cells.