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Cancer is the second leading cause of death worldwide. Traditional approaches, such as surgery, chemotherapy, and radiotherapy have been the main cancer therapeutic modalities in recent years. Cancer immunotherapy is a novel therapeutic modality that potentiates the immune responses of patients against malignancy. Immune checkpoint proteins expressed on T cells or tumor cells serve as a target for inhibiting T cell overactivation, maintaining the balance between self-reactivity and autoimmunity. Tumors essentially hijack the immune checkpoint pathway in order to survive and spread. Immune checkpoint inhibitors (ICIs) are being developed as a result to reactivate the anti-tumor immune response. Recent advances in nanotechnology have contributed to the development of successful, safe, and efficient anticancer drug systems based on nanoparticles. Nanoparticle-based cancer immunotherapy overcomes numerous challenges and offers novel strategies for improving conventional immunotherapies. The fundamental and physiochemical properties of nanoparticles depend on various cancer therapeutic strategies, such as chemotherapeutics, nucleic acid-based treatments, photothermal therapy, and photodynamic agents. The review discusses the use of nanoparticles as carriers for delivering immune checkpoint inhibitors and their efficacy in cancer combination therapy.

In locally advanced oral squamous cell carcinoma (OSCC), namely that showing invasion of the mandible, demonstrating no high-risk (e.g. extranodal extension, positive margin) or intermediate-risk histopathological features (e.g. perineural invasion, lymphovascular invasion), the additional benefit of postoperative radiotherapy (PORT) currently remains uncertain. A retrospective review covering the period between January 1, 2010 and December 31, 2019 was conducted to identify patients from a single UK centre with locally advanced invasive mandibular OSCC defined as pT4a, with no nodal or distant metastasis (N0 M0). The primary outcome was to determine the disease-free survival and overall survival rates in the surgery + PORT group, in comparison to the surgery only group. Twenty-eight eligible patients were identified, with 13 patients in the surgery + PORT group and 15 patients in the surgery only group. A single patient in the surgery + PORT group developed disease recurrence and subsequently died (1/13) (median follow-up 5.24 years, range 2.13-10.71 years). No patient in the surgery only group developed disease recurrence or died (0/15) (median follow-up 5.13 years, range 1.37-10.93 years). It may be reasonable to consider omitting PORT in pT4a pN0 M0 OSCC of the mandible in patients who demonstrate no high- or intermediate-risk histopathological features, following multidisciplinary team discussion.

Fucoidan is a sulfated polysaccharide, derived from various marine brown seaweeds, that has immunomodulatory effects. In this study, we analyzed the effects of five different fucoidans, which were extracted from Ascophyllum nodosum, Undaria pinnatifida, Macrocystis pyrifera, Fucus vesiculosus, and Ecklonia cava, on natural killer (NK) cell activation in mice. Among these, E. cava fucoidan (ECF) promoted an increase in the number of NK cells in the spleen and had the strongest effect on the activation of NK cells. Additionally, we observed that DC stimulation was required for NK cell activation and that ECF had the most potent effect on splenic dendritic cells (DC). Finally, ECF treatment effectively prevented infiltration of CT-26 carcinoma cells in the lungs of BALB/c mice in an NK cell dependent manner. Collectively, these results suggest that ECF could be a suitable candidate for enhancing NK cell-mediated anti-cancer immunity.

Astragalus membranaceus (A. membranaceus) is commonly used in various herbal formulations to treat several human and animal diseases. Polysaccharides, which are the major bioactive components in the A. membranaceus, exhibit various bioactive properties. However, the ability of A. membranaceus polysaccharides (APS) to activate the mucosal immune response has not been examined. We examined the effect of intranasal administration of APS on mucosal immune cell activation and the growth-inhibitory activity against pulmonary metastatic melanoma in mice by combination treatment with immune checkpoint blockade. The intranasal treatment of APS increased the number of lineage-CD11c+ dendritic cell (DCs) in the mesenteric lymph nodes (mLN) through the upregulation of CC-chemokine receptor 7 expression. Moreover, intranasal treatment of APS activated DCs, which further stimulated natural killer (NK) and T cells in the mLN. The APS/anti-PD-L1 antibody combination inhibited the pulmonary infiltration of B16 melanoma cells. The depletion of NK cells and CD8 T cells in mice mitigated the anti-cancer effect of this combination, thereby highlighting the critical role of NK cells and CD8 T cells in mediating anti-cancer immunity. These findings demonstrated that APS could be used as a topical mucosal adjuvant to enhance the immune check point inhibitor anti-cancer effect.

To investigate sports compression garment (CG)-induced recovery hemodynamics and their potential impact on subsequent cycling performance. In a randomized crossover design, 13 physically active men (20.9 ± 1.4 years; 65.9 ± 7.8 kg; 173.3 ± 4.8 cm; peak power output 254.2 ± 27.2 W) underwent 2 experimental trials. During each experimental trial, the subjects performed 20-min fatiguing preload cycling followed by 60-min passive recovery wearing either a sports CG (28.6 ± 9.4 mmHg) or gymnastic pants (CON). A 5-min all-out cycling performance test was subsequently conducted and power output and cadence were recorded. Cardiac output (CO) and stroke volume (SV) were measured using Doppler ultrasound (USCOM®). Heart rate (HR), blood lactate [BLa−], ratings of perceived exertion (RPE), leg muscle soreness (LMS), mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored at 5, 15, 30, 45, 60 min during passive recovery. During the subsequent 5-min all-out cycling performance test, power output (215.2 ± 24.0 vs. 210.8 ± 21.5 W, CG vs. CON) and cadence (72.5 ± 3.8 vs. 71.2 ± 4.8 rpm, CG vs. CON) were higher in CG than CON (P

Objective This study examined the impact of a humanoid robot (MEDi®) programmed to teach deep breathing as a coping strategy, on children’s pain and fear as primary and secondary outcomes, respectively, during intravenous (IV) line placement. The completion of IV induction was also examined as an exploratory outcome. Methods In this randomized controlled, two-armed trial, 137 children (4–12 years) were recruited in Short Stay Surgery at a tertiary pediatric hospital. Patients were randomly assigned to standard care (SC) with Ametop© only (N = 60) or SC and robot-facilitated intervention (N = 59) before induction. Pain and fear before, during, and after IV insertion were rated by patients and observers. Results No significant differences were found between groups and there were no changes over time for pain or fear (ps > .05). Exploratory analyses show that patients in the MEDi® group were 5.04 times more likely to complete IV induction, compared to SC, Fisher’s exact test: X2 (1) = 4.85, p = .04, φc = 0.22, odds ratio = 5.04, 95% CI [1.06, 24.00]. Conclusion This study was the first to examine children’s IV induction experience when provided MEDi® support. Reasons for nonsignificance, limitations, and research suggestions were made.

Brown seaweed is an important source of fucoidan, which displays immunomodulatory effects by activating various immune cells. However, these effects of fucoidans from various sources of brown seaweed have not yet been explored in human blood dendritic cells. We studied fucoidans extracted from Ecklonia cava, Macrocystis pyrifera, Undaria pinnatifida, and Fucus vesiculosus for their effects on human monocyte-derived dendritic cells (MODC) and human peripheral blood DC (PBDC) activation. Ecklonia cava fucoidan (ECF) strongly upregulated co-stimulatory molecules, major histocompatibility complex class I and II, and the production of proinflammatory cytokines in MODCs and PBDCs compared to those by the other three fucoidans. Moreover, ECF elicited the strongest effect in the induction of syngeneic T cell proliferation and IFN-γ production compared to those of other fucoidans. These results suggest that ECF could be a suitable candidate molecule for enhancing immune activation in humans compared to that with the other three fucoidans.

Tripartite motif-containing 28 (TRIM28) is an E3 ubiquitin ligase harboring multiple cellular functions. We found that the TRIM28 protein is frequently overexpressed in patients with lung cancer. The stable overexpression of TRIM28 in lung cancer cells and xenograft models significantly increased the proliferation, migration, and invasiveness, whereas knockdown of TRIM28 had the opposite effect. We further observed that TRIM28 regulates the ubiquitin ligases RLIM and MDM2 to target the p53 levels during lung tumorigenesis. These data provide new insights into lung cancer development and potential new therapeutic targets for this disease.

Lee, DCW, Ali, A, Sheridan, S, Chan, DKC, and Wong, SHS. Wearing compression garment enhances central hemodynamics? a systematic review and meta-analysis. J Strength Cond Res 36(8): 2349-2359, 2022-Compression garments (CG) are believed to enhance exercise performance and recovery by improving central hemodynamic responses. However, evidence is inconclusive. We performed a systematic review and meta-analysis to determine the effect of wearing CG at rest or after a physiological challenge on central hemodynamic responses, including cardiac output, stroke volume (SV), heart rate (HR), systolic blood pressure, diastolic blood pressure (DBP), and systemic vascular resistance in healthy individuals. The English language searches of the electronic databases SPORTDiscus, MEDLINE, and Web of Science were conducted from November 2018-February 2019. The studies involved were limited to the following: (a) original articles; (b) randomized controlled trials; (c) monitoring of central hemodynamic responses (either at rest or after a physiological challenge: maximal exercise or orthostatic challenge); and (d) healthy individuals. Of the 786 studies identified, 12 were included in the systematic review and meta-analysis. Meta-analysis was performed by the restricted maximum likelihood method. The results indicated that the effect size (ES) of wearing CG on improving central hemodynamic responses was large overall (Hedges' g = 0.55) and was large in SV (Hedges' g = 1.09) and HR (Hedges' g = 0.65). Subgroup analysis showed that the ESs in "post-physiological challenge" was large in overall (Hedges' g = 0.98), SV (Hedges' g = 1.78), HR (Hedges' g = 1.10), and DBP (Hedges' g = 0.75). Their ESs in "at rest" were not significant in all central hemodynamic responses, apart from a significant medium ES observed in SV (Hedges' g = 0.44). Healthy individuals who wear CG have marked improvement in central hemodynamic responses, particularly after a physiological challenge. More pronounced effects of CG are observed in increasing SV and reducing HR.

Na-ion solid state batteries operating at room temperature are typically supposed to have a metallic Na anode for sufficiently high energy density. The less known but due to easy processing very promising Na-conducting Na5YSi4O12 glass ceramic is investigated regarding it`s interface resistance in contact with metallic Na electrodes. Two types of this material, with and without P-addition, are investigated. The surface is treated by polishing to induce a defined roughness. Highly polished surfaces lead to incomplete covering with Na metal by application of pressure sufficiently low to avoid the breaking of ceramic. In contrast, surfaces with higher roughness could be covered more homogeneously with Na and thus exhibited significantly reduced interface resistance. These measurements reveal the intrinsically small interface resistance between Na5YSi4O12 glass ceramics and metallic Na, which makes Na5YSi4O12 to promising electrolyte for Na-ion solid state batteries. It is found that prolonged contact of the electrolyte with humid air, like several days or weeks, leads to a strongly increased interface resistance. Thus, storage conditions and surface treatment of the samples after air contact need to be considered carefully.

The ubiquitin system, present in all eukaryotes, contributes to regulating multiple types of cellular protein processes such as cell signaling, cell cycle, and receptor trafficking, and it affects the immune response. In most types of cancer, unusual events in ubiquitin-mediated signaling pathway modulation can lead to a variety of clinical outcomes, including tumor formation and metastasis. Similarly, ubiquitination acts as a core component, which contributes to the alteration of cell signaling activity, dictating biosignal turnover and protein fates. As lung cancer acquires the most commonly mutated proteins, changes in the ubiquitination of the proteins contribute to the development of lung cancer. Various inhibitors targeting the ubiquitin system have been developed for clinical applications in lung cancer treatment. In this review, we summarize the current research advances in therapeutics for lung cancer by targeting the ubiquitin system.

The transdermal delivery of functional biomolecules has been widely achieved by microneedles in a non-invasive manner. However, establishing a simple and universal way to assure a stable loading of a large number of drugs is still imperative, particularly for the delivery of nucleic acid-based drugs. To address this issue, here, we present a universally applicable RNA membrane-coating system as a novel platform to manufacture purpose-oriented microneedles. Customization of RNA membrane-based microneedles is realized by large surface area, high cargo capacity, and controllable material properties of the RNA membrane and 3D-printing of customized scaffold microneedles in a purpose-oriented manner. In addition, simple covering with the RNA membrane facilitates the fabrication of RNA-coated microneedles regardless of the configuration and material of the scaffold. This study demonstrates the successful delivery of RNA along with various types of drugs by purpose-oriented microneedles. Taken together, our approach provides a general route towards the fabrication of tailor-made microneedles for efficient transdermal drug delivery.

Rylene dyes exhibit superior photophysical properties including outstanding chemical and photochemical stabilities as well as high fluorescence quantum yields (FQYs). However, the rylene chromophores have some limitations, such as high hydrophobicity and low solubility in aqueous solution, as a fluorescent tag for biological system. Herein, we present a general method to load the rylene dyes into triblock copolymer nanoparticles (NPs) and stabilize the core. The rylene dyes in confined hydrophobic core fairly preserve their FQYs in aqueous environment. Lumogen probe nanoparticles (PNPs) were prepared with four different commercial rylenes (Lumogen Violet, Yellow, Orange and Red) in the spectral region of visible and infrared (400–750 nm) and their photophysical properties were characterized. They exhibited enhanced photostability compared to commercial fluorescent dyes. Also the internalization of Lumogen PNPs in HeLa cell was confirmed by cell uptake test. These results indicate the Lumogen PNPs can be widely applicable in fluorescence detection and imaging such as flow cytometry and fluorescence microscopy.

Pluronic® triblock copolymers, which spontaneously form nano-sized aggregates in water, have been considered as promising carriers for bioimaging and drug delivery. However, their use for applications in pharmacology and diagnostics is hindered by instability of polymer aggregates which are easily dissociated into unimers. Here we report a general method for stabilizing Pluronic® F127 micelles via semi-interpenetrating network (sIPN). The formation of sIPN within a core stabilizes the micelle upon temperature and concentration changes. We determined optimized methods for the preparation of F127 sIPN in the regime of chemical components. Importantly, F127 sIPNs are able to load various organic fluorescence probes, covering a panchromatic range of photoluminescence (350–850 nm; entire UV–Vis-NIR), without compromising their photophysical properties. Moreover, efficient cellular uptake of the fluorescence probes loaded sIPN is observed in human and mouse cells. After intravenous injection into mice, an infrared dye-loaded sIPNs are incorporated in multiple organs and have longer lifetime than a commercially available imaging probe. With the improvement of stability, Pluronic micelles with sIPN can be a powerful tool for building functional nanoprobes and in vivo fluorescence imaging for cancer cells and live animals.

Pluronic F127 forms spherical micelle with a defined number of molecules aggregated in aqueous environments. Such self-assembled micelles dissociate into unimers below certain concentration and temperature. We stabilized the micelles by semi-interpenetrating network (sIPN) formation within the hydrophobic core in the presence of a fluorescent dye. Additionally, by varying the mixing ratio of negatively charged and pristine F127s we prepared thermally stable polymeric nanoparticles with discrete surface charges within nearly same sizes. Using the nanomaterials with prescribed number of charges, we demonstrate that the electrophoretic mobility of nanoparticles is solely depending on number of surface charges. Finally, the aggregation number (Nagg) of F127 was further determined by electrophoresis.

Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma (POLG) plays an important role in mtDNA replication, and proofreading and mutations in POLG have been linked with increased mtDNA deletions. SSBP1 is also a crucial gene for mtDNA replication. Here, we describe a patient diagnosed with Pearson syndrome with large mtDNA deletions that were not detected in the somatic cells of the mother. Exome sequencing was used to evaluate the nuclear factors associated with the patient and his family, which revealed a paternal POLG mutation (c.868C &gt, T) and a maternal SSBP1 mutation (c.320G &gt, A). The patient showed lower POLG and SSBP1 expression than his healthy brothers and the general population of a similar age. Notably, c.868C in the wild-type allele was highly methylated in the patient compared to the same site in both his healthy brothers. These results suggest that the co- deficient expression of POLG and SSBP1 genes could contribute to the development of mtDNA deletion.

We elucidated the proper routes for injecting lipid-DNA micelles formulated with an oligonucleotide immune adjuvant in naive and tumor-bearing mice. We report herein that after assessing six ways of administering an immunostimulatory nanoparticle (INP), several of the injection routes effectively induced dendritic cell-mediated immune-stimulation in vivo, making them amenable to cancer immunotherapies and vaccines using such DNA materials.

Hypoxia-inducible factor (HIF)-1&alpha, plays an important role in cancer progression. In various cancers, including thyroid cancer, overexpression of HIF-1&alpha, is related to poor prognosis or treatment response. However, few studies have investigated the role of HIF-1&alpha, inhibition in thyroid cancer progression. We evaluated the utility of the HIF-1&alpha, inhibitor IDF-11774 in vitro utilizing two thyroid cancer cell lines, K1 and BCPAP. Both cell lines were tested to elucidate the effects of IDF-11774 on cell proliferation and migration using soft agar and invasion assays. Here, we found that a reduction of HIF-1&alpha, expression in BCPAP cells was observed after treatment with IDF-11774 in a dose-dependent manner. Moreover, cell proliferation, migration, and anchorage-independent growth were effectively inhibited by IDF-11774 in BCPAP cells but not in K1 cells. Additionally, invasion of BCPAP but not K1 cells was controlled with IDF-11774 in a dose-dependent manner. Our findings suggest that promoting the degradation of HIF-1&alpha, could be a strategy to manage progression and that HIF-1&alpha, inhibitors are potent drugs for thyroid cancer treatment.

Background: Despite their proven efficacy to reduce cardiovascular disease, statin medication use remains low in individuals at high risk of cardiovascular disease considering their widespread availability and safety. Our objective was to explore the perspectives of patients and family physicians with regard to the barriers and facilitators of statin use in primary care. Methods: In this qualitative descriptive study, we conducted 2 focus groups with patients (number, n = 8/6) and individual semistructured interviews with family physicians (n = 17) from community settings. Interviewers asked participants about barriers to and facilitators of statin use. Focus groups and interviews were digitally recorded, transcribed, and analyzed in duplicate using conventional content analysis. Results: Patients were averse to taking statins for a variety of reasons: medication avoidance and burden; inadequate buy-in for statin therapy; and difficulty remembering to take statins regularly. Family physicians perceived similar barriers and reported other barriers: lack of resources such as inadequate tracking systems; specialist-primary care provider guideline discordance; and lack of continuity and relationship. Patients expressed that key facilitators were patient education and support; splitting tablets to increase cost-effectiveness; and changing to a different statin or lower dose in those with side effects. Family physicians described several similar strategies to facilitate therapy as well as shared decision making and clinical decision support tools as enablers for improvement. Conclusions: We identified several important barriers to and facilitators of statin use at the patient and prescriber level. This information offers insight into strategies to improve statin use and the development of innovative programs and interventions. Résumé: Introduction: En dépit de leur efficacité prouvée pour réduire les maladies cardiovasculaires, l’utilisation des statines reste faible chez les individus exposés à un risque élevé de maladies cardiovasculaires si l’on considère leur grande disponibilité et leur innocuité. Notre objectif était d’examiner les perspectives des patients et des médecins de famille en ce qui concerne les obstacles et les facilitateurs de l’utilisation des statines en soins primaires. Méthodes: Dans la présente étude qualitative descriptive, nous avons mené 2 groupes de discussion composés de patients (nombre, n = 8/6) et des entrevues semi-structurées individuelles avec des médecins de famille (n = 17) en milieu communautaire. Les intervieweurs ont demandé aux participants quels étaient les obstacles et les facilitateurs de l’utilisation des statines. Les groupes de discussion et les entrevues étaient enregistrés numériquement, transcrits et analysés en duplicata à l’aide de l’analyse de contenu traditionnelle. Résultats: Les patients se sont opposés à la prise de statines pour plusieurs raisons : l’évitement et le fardeau des médicaments, l’adhésion insuffisante au traitement par statines et la difficulté à se souvenir de prendre régulièrement les statines. Les médecins de famille ont perçu des obstacles similaires et ont rapporté d’autres obstacles dont le manque de ressources telles que les systèmes de suivi inadéquats, la divergence entre les orientations des spécialistes et des prestataires de soins primaires, et le manque de continuité et de relation. Les patients ont exprimé que les principaux facilitateurs étaient l’éducation et le soutien offerts aux patients; le fractionnement des comprimés pour améliorer l’efficience; le changement vers une statine différente ou une dose plus faible chez ceux qui présentent des effets secondaires. Les médecins de famille ont décrit plusieurs stratégies semblables pour faciliter le traitement ainsi que la prise de décision partagée et les outils d’aide à la décision clinique qui facilitent l’amélioration. Conclusions: Nous avons déterminé plusieurs obstacles et facilitateurs importants de l’utilisation des statines au point de vue du patient et du prescripteur. Ces informations offrent un aperçu des stratégies pour améliorer l’utilisation des statines et l’élaboration d’interventions et de programmes innovateurs.

In our previous study, we showed that Rehmannia glutinosa polysaccharide (RGP) treatment induced activation of dendritic cells (DCs) in human and mouse subjects. In this study, we evaluated the effect of RGP as a mucosal adjuvant for inducting activation of DCs in the mediastinal lymph node (mLN) in the mouse. The C57BL/6 mice were intranasally (i.n.) treated with RGP and activation of DC in the mLN was analyzed. The treatment with RGP induced a substantial increase in the number of DCs in the mLN due to the up-regulation of C-C motif chemokine receptor 7 (CCR7) in the DCs. Moreover, the expression of co-stimulatory molecules in the mLN DCs and the concentration of pro-inflammatory cytokines in the lung were up-regulated by RGP treatment. Also, RGP treatment induced interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production in the mLN T cells. The combination treatment of RGP and ovalbumin (OVA) induced OVA-specific TCR transgenic I (OT-I) and OT-II cell proliferation in the mLN. Finally, the combination treatment of RGP and tyrosinase-related protein 2 (TRP2) peptide, a melanoma self-antigen, protected mice from melanoma challenge. Thus, these data demonstrated that RGP can be used as a mucosal adjuvant for inducing activation of immune responses in the lung.

Objectives While previous studies have demonstrated an ergogenic effect of sport compression garments in exercise performance and recovery, the possible underlying mechanisms remain unclear. Claims for improved venous return from wearing sport compression garments with a low compression pressure remain unproven. The aim of this study was to determine the pressure profile exerted by low-pressure sports compression tights, and to investigate using a non-invasive Doppler ultrasound cardiac output monitor (USCOM), whether the compression applied will influence haemodynamic responses during an orthostatic challenge. Design A randomized-crossover design. Methods Thirty-three healthy participants (18 male and 15 female) underwent two trials, each consisting of lying supine and 70° head-up tilt wearing either a low-pressure sports compression tights (CT) or track pants (CON). Stroke volume (SV) and cardiac output (CO) were measured non-invasively using USCOM; heart rate (HR) and non-invasive blood pressure were measured, and systemic vascular resistance (SVR) was derived. Results The SV and CO was lower at 70° head-up tilt than in supine but wearing CT attenuated the decline in SV (25.9 ± 11.6 cm3 CT vs. 35.9 ± 11.4 cm3 CON, p 0.05) was similar in both trials. Conclusions Healthy individuals wearing low-pressure sports compression tights experienced less severe haemodynamic disturbance such as decreases in CO, SV, HR and SVR during an orthostatic challenge.

Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand‐independent manner via Plexin B1. SEMA3C expression levels increase in castration‐resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition. SEMA3C inhibition delays CRPC and enzalutamide‐resistant progression. Plexin B1 sema domain‐containing:Fc fusion proteins suppress RTK signaling and cell growth and inhibit CRPC progression of LNCaP xenografts post‐castration in vivo. SEMA3C inhibition represents a novel therapeutic strategy for treatment of advanced prostate cancer.

We present electrical spin injection and detection in p-type Ge channels using Ni/Al2O3/Ge on glass tunneling contacts. The entire structure is integrated on a glass substrate. We investigate the temperature dependence of the Hanle effect in a composite p-type Ge on glass (GeOG), using three-terminal configuration Hanle measurements; from these measurements, we observe spin accumulation up to room temperature. A spin signal of 0.3 V and a spin lifetime of 34 ps are obtained at room temperature.

This study evaluated the morphological changes of the lower limb and associated hemodynamic responses to different lower-body compression pressures (COMPs) in physically active, healthy individuals at rest. Each of the 32 participants underwent three trials with three different degrees of lower-body compression applied: “Low” (2.2±1.4 mmHg), “Medium” (12.9±3.9 mmHg), and “High” (28.8±8.3 mmHg). In each COMP, a cross-sectional area of leg muscles (CSAmuscle), subcutaneous fat (CSAfat), superficial vessels (SupV), deep arteries (DA), and deep veins (DV) at the calf, knee, and thigh levels were measured using magnetic resonance imaging (MRI). Additionally, blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR) were measured using Doppler ultrasound (USCOM®). With High COMP, calf CSAmuscle and SupV were smaller (p

USE1 has been demonstrated to play crucial roles in the development and progression of human lung cancer. However, the antitumor efficacy of RNA interference (RNAi) targeting of USE1 has not yet been evaluated as a possible clinical application. We here synthesized USE1 targeting bubbled RNA-based cargo (BRC) composed of densely packed multimeric pre-siRNAs with specific Dicer cleavage sites to enable efficient siRNA release upon entry to target cells. The physical entanglement and continuous networking of RNAs via hybridization during enzymatic replication serve as a driving force for the self-assembly of BRCs. These molecules effectively suppressed the transcription of their target genes, leading to tumor growth suppression in vitro and in vivo. Moreover, their repeated intravenous administration efficiently inhibited the growth of A549 tumor xenografts. Based on these findings of a reduced cancer cell viability following a USE1 knockdown, we further explored cell cycle arrest and apoptosis pathways. The observed tumor cell growth suppression was found to be controlled by cell cycle arrest and apoptosis signals induced by the USE1 reduction. These results suggest that USE1 BRCs may have future clinical applications as an RNAi-based cancer therapy.

Motivation Cancer classification based on gene expression profiles has provided insight on the causes of cancer and cancer treatment. Recently, machine learning-based approaches have been attempted in downstream cancer analysis to address the large differences in gene expression values, as determined by single-cell RNA sequencing (scRNA-seq). Results We designed cancer classifiers that can identify 21 types of cancers and normal tissues based on bulk RNA-seq as well as scRNA-seq data. Training was performed with 7398 cancer samples and 640 normal samples from 21 tumors and normal tissues in TCGA based on the 300 most significant genes expressed in each cancer. Then, we compared neural network (NN), support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF) methods. The NN performed consistently better than other methods. We further applied our approach to scRNA-seq transformed by kNN smoothing and found that our model successfully classified cancer types and normal samples. Availability and implementation Cancer classification by neural network. Supplementary information Supplementary data are available at Bioinformatics online.

Background Efficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment. Methods Thermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT. Results Near-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells. Conclusion These results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases. Electronic supplementary material The online version of this article (10.1186/s40425-019-0702-1) contains supplementary material, which is available to authorized users.

Sepsis is an infection- or toxin-mediated systemic inflammatory syndrome. Previous studies have shown that melatonin, the primary hormone produced by the pineal gland, attenuates the effect of polymicrobial infection-mediated septic shock in animals. However, the mechanism of the anti-septic effect of melatonin during polymicrobial infection has not been well-studied. In this study, we investigated how melatonin protects mice from polymicrobial sepsis. Melatonin treatment inhibited peripheral tissue inflammation and tissue damage in a cecal ligation puncture (CLP)-induced polymicrobial sepsis model, consequently reducing the mortality of the mice. We found that macrophages and neutrophils expressed melatonin receptors. Upon depletion of neutrophils, melatonin-induced protection against polymicrobial infection failed in the mice, but melatonin treatment in macrophage-depleted mice attenuated the mice mortality resulting from polymicrobial sepsis. Moreover, melatonin treatment promoted the development of the neutrophil extracellular trap (NET), which contributed to anti-bacterial activity during polymicrobial infection, whereas the phagocytic activities of neutrophils were inhibited by melatonin. The data from this study support previously unexplained antiseptic effects of melatonin during a polymicrobial infection and could be potentially useful for human patients with sepsis.

UBA6 is an alternative enzyme for ubiquitin activation in vertebrates that plays a pivotal role in early mouse development. Previously, we reported that the Uba6 brain-specific knockout (NKO) mouse is a novel autism spectrum disorder (ASD) mouse model that displays decreased social behavior and communication. To determine the therapeutic impact of environmental stimulation in ASDs, we investigated the behavioral and molecular changes of the NKO and control mice after exposure to environmental enrichment and paired housing in different developmental phases. Our results demonstrated that early paired housing could diminish the ASD phenotypes of NKO mice such as impaired nest building and social interaction and anxiety. Additionally, increased histone acetylation in the amygdala was observed in NKO mice after paired housing without a change in Ube3a levels. Our data suggest that paired housing at an early time point can play a crucial role in ameliorating ASD behavior and can be applied in other ASD animal models or clinical settings.