A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

Fabrication, Characterization, and Antimicrobial Activity of Carvacrol-Loaded Zein Nanoparticles Using the pH-Driven Method.

To reduce the application of synthetic additives in the field of food preservation, this study utilized carvacrol as an antibacterial agent, and zein and sodium caseinate as carriers, to prepare composite nanoparticles loaded with carvacrol by the pH-driven method. The composite nanoparticles of zein/sodium caseinate had an excellent encapsulation efficiency (77.96~82.19%) for carvacrol, and it had remarkable redispersibility. The results of Fourier transform infrared spectroscopy showed that the formation of the composite nanoparticles mainly depended on the hydrogen bond and the hydrophobic zone force, and thermal gravimetric analysis showed that carvacrol was loaded successfully into nanoparticles, and loading efficiency reached 24.9%. Scanning electron microscopy showed that the composite nanoparticles were spherical, with a particle size range of 50~200 nm, and through the free radical scavenging method and the plate counting method to confirm the particle has stronger antioxidant and antibacterial properties, and with the composite nanoparticles with poly (vinyl alcohol) film applied to the preservation of banana together, it was found that PVA film containing 5 wt% CA-loaded composite NPs can significantly extend the storage period of banana. Therefore, when the composite nanoparticles were applied to food packaging, they could effectively inhibit food spoilage and lengthen the shelf life of food, which displays potential application prospects in the food industry.

Genome-Wide Analysis Indicates a Complete Prostaglandin Pathway from Synthesis to Inactivation in Pacific White Shrimp, Litopenaeus vannamei.

Prostaglandins (PGs) play many essential roles in the development, immunity, metabolism, and reproduction of animals. In vertebrates, arachidonic acid (ARA) is generally converted to prostaglandin G2 (PGG2) and H2 (PGH2) by cyclooxygenase (COX); then, various biologically active PGs are produced through different downstream prostaglandin synthases (PGSs), while PGs are inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). However, there is very limited knowledge of the PG biochemical pathways in invertebrates, particularly for crustaceans. In this study, nine genes involved in the prostaglandin pathway, including a COX, seven PGSs (PGES, PGES2, PGDS1/2, PGFS, AKR1C3, and TXA2S), and a PGDH were identified based on the Pacific white shrimp (Litopenaeus vannamei) genome, indicating a more complete PG pathway from synthesis to inactivation in crustaceans than in insects and mollusks. The homologous genes are conserved in amino acid sequences and structural domains, similar to those of related species. The expression patterns of these genes were further analyzed in a variety of tissues and developmental processes by RNA sequencing and quantitative real-time PCR. The mRNA expression of PGES was relatively stable in various tissues, while other genes were specifically expressed in distant tissues. During embryo development to post-larvae, COX, PGDS1, GDS2, and AKR1C3 expressions increased significantly, and increasing trends were also observed on PGES, PGDS2, and AKR1C3 at the post-molting stage. During the ovarian maturation, decreasing trends were found on PGES1, PGDS2, and PGDH in the hepatopancreas, but all gene expressions remained relatively stable in ovaries. In conclusion, this study provides basic knowledge for the synthesis and inactivation pathway of PG in crustaceans, which may contribute to the understanding of their regulatory mechanism in ontogenetic development and reproduction.

AnnoFly: annotating Drosophila embryonic images based on an attention-enhanced RNN model.

MOTIVATION: In the post-genomic era, image-based transcriptomics have received huge attention, because the visualization of gene expression distribution is able to reveal spatial and temporal expression pattern, which is significantly important for understanding biological mechanisms. The Berkeley Drosophila Genome Project has collected a large-scale spatial gene expression database for studying Drosophila embryogenesis. Given the expression images, how to annotate them for the study of Drosophila embryonic development is the next urgent task. In order to speed up the labor-intensive labeling work, automatic tools are highly desired. However, conventional image annotation tools are not applicable here, because the labeling is at the gene-level rather than the image-level, where each gene is represented by a bag of multiple related images, showing a multi-instance phenomenon, and the image quality varies by image orientations and experiment batches. Moreover, different local regions of an image correspond to different CV annotation terms, i.e. an image has multiple labels. Designing an accurate annotation tool in such a multi-instance multi-label scenario is a very challenging task. RESULTS: To address these challenges, we develop a new annotator for the fruit fly embryonic images, called AnnoFly. Driven by an attention-enhanced RNN model, it can weight images of different qualities, so as to focus on the most informative image patterns. We assess the new model on three standard datasets. The experimental results reveal that the attention-based model provides a transparent approach for identifying the important images for labeling, and it substantially enhances the accuracy compared with the existing annotation methods, including both single-instance and multi-instance learning methods. AVAILABILITY AND IMPLEMENTATION: http://www.csbio.sjtu.edu.cn/bioinf/annofly/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Application of the Chinese version of Zelaya's HIV-related stigma scale to undergraduates in mainland China.

BACKGROUND: This cross-sectional study aims to validate the Chinese version of Zelaya's HIV-related Stigma Scale (CVZHSS) among a large undergraduate sample in mainland China, and apply it to measure the level of different dimensions of stigma and their respective determinants. METHODS: From September 10, 2018, to January 9, 2019, a total of 10,665 eligible undergraduates conveniently drawn from 30 provinces in mainland China (except for Tibet) completed the self-designed online questionnaire distributed via sojump.com voluntarily, anonymously and confidentially. Both exploratory and confirmatory factor analyses (EFA and CFA) were first performed to test its construct validity, Cronbach's alpha was then used to assess its internal consistency, and Logistic regression analyses were finally carried out to identify predictors of various dimensions of stigma. RESULTS: As expected from the original model, four factors (i.e., "fear of casual transmission", "moral judgment", "personal stigma" and "perceived community stigma") were extracted using principal component analysis with varimax rotation, accounting for 63.26% of the total variance. The CFA further confirmed the four-factor construct (CFI = 0.92, GFI = 0.91, RMSEA = 0.07). In addition, all the four factors demonstrated acceptable internal consistency with Cronbach's alpha ranging from 0.83 to 0.92. Stigma as measured by "fear of casual transmission" (74.4%), "moral judgement" (61.6%), "personal stigma" (79.0%) and "perceived community stigma"(36.5%) is highly prevalent among undergraduates. Except for non-freshmen, less knowledge about HIV and unsafe sex which were consistently associated with higher levels of stigma in all four dimensions, other eight variables including gender, residential area, major, sexual orientation, having ever being tested perception of HIV risk, willingness to utilize HTC service and awareness of the national AIDS policy played differential roles in affecting different dimensions of stigma. CONCLUSIONS: The CVZHSS is a reliable and valid measurement tool and can be used to identify undergraduates with high levels of stigma. However, the four dimensions (Fear, moral judgement, personal stigma and perceived community stigma) were respectively influenced by different determinants, and thus should be treated independently when designing, implementing and evaluating stigma reduction programs.

[The Effect of p-JAK1/p-STAT3 Signaling Way in Intervening NAFLD by Blueberry Probiotic Serum].

OBJECTIVES: To explore the mechanism of interlukin-22 (IL-22)-mediated phosphor-Janus kinase-1(p-JAK1)/phosphor-signal transducer and activator of transcription 3 (p-STAT3) signaling way in the experiment of improving non-alcholic fatty liver disease (NAFLD) by blueberry probiotic serum. METHODS: The rat serums with low-, medium-, and high-dose of 10% blueberry probiotics, as well as saline were prepared. NAFLD model was built by inducing normal liver cell line L-02 with free fatty acid (FFA).NAFLD model cells were cultured with saline serum (model group), low-, medium-, and high-dose blueberry probiotics serums (low-, medium-, and high-dose serum groups) , respectively .Normal liver cell group (normal group) was cultured with saline serum . Oil Red O staining was used to detect the lipid deposition in the cells; the intracellular level of triglyceride (TG) was quantitatively determined; the gene and protein expressions of IL-22, p-JAK1, p-STAT3, sterol-regulatory element binding protein-1c (SREBP-1c ) were detected by RT-PCR, Western blot and immunofluorescence methods. RESULTS: Twenty-four hours after modeling, a large amount of lipid deposition could be observed in model group. Compared with normal group, model group showed lower gene and protein expression levels of IL-22, p-JAK1 and p-STAT3 (P <0.01), and higher SREBP-1c and TG levels (P <0.01).Compared with model group, TG level and the lipid deposition in low-, medium-, and high-dose blueberry probiotics serum groups were gradually reduced. High-dose serum group showed higher gene and protein expression levels of IL-22, p-JAK1, p-STAT3 and lower SREBP-1c compared with the model, low-, and medium-dose serum groups (P <0.01). No significant [CM(155.3mm]differences in gene and protein levels between low- andmedium-doseserum groups were found (P >0.05). CONCLUSION: The blueberry probiotics could antagonize the NAFLD via p-JAK1/p-STAT3 signaling way.

A Case of Oropharyngeal Syphilis.

We present a case of a 50-year-old male who complained of a sore throat persisting for 2 months. Upon physical examination, multiple mucous patches were observed in the oropharynx region, but no skin lesions were found. Fiberoptic laryngoscopy confirmed these findings. The Treponema pallidum particle agglutination test and toluidine red unheated serum test (TRUST) were positive with a titer of TRUST 1:64. The patient admitted to engaging in extramarital sexual activities with several females but no males. Based on the clinical manifestations and laboratory test results, a diagnosis of secondary syphilis of the oropharynx was established. He was treated with 2.4 million units of benzathine penicillin G by intramuscular injection once a week for 3 weeks. After 1 month, the lesions completely disappeared without any symptoms. The titer of TRUST reduced to 1:2 in 1-year follow-up. This report aims to enhance physicians' understanding and recognition of oropharyngeal syphilis, enabling timely diagnosis and effective management.

A Powerful Strategy for Carbon Reduction: Recyclable Mono-Material Polyethylene Functional Film.

Given the abundant plastics produced globally, and the negative environmental impacts of disposable plastic products throughout their life cycle, there has been significant attention drawn by the general public and governments worldwide. Mono-material multilayer packaging is a potent strategy to address the challenge of carbon emissions as it offers specific functionalities (such as strength and barrier properties) through its layers and facilitates recycling. In this study, a five-layer co-extruded polyethylene composite film LLDPE/mPE/PVA/mPE/LLDPE was taken as a model to investigate its mechanical properties and barrier properties after four recycling cycles. The result revealed that the longitudinal tensile strength and transvers tensile were, respectively, dropped from 29.66 MPa and 24.9 MPa to 21.972 MPa and 19.222 MPa after the recycling; it is shown that the film still has good mechanical properties after the recycling cycle. However, a noticeable decline in the barrier properties was observed after the second recycling. In contrast to traditional plastics, a mono-material film with a 10 wt.% circulating mass could reduce CO2 emissions by 3692.25 kg for every 1.0 ton of plastic products after four recycling cycles.

Production of Graphene/Inorganic Matrix Composites through the Sintering of Graphene Oxide Flakes Decorated with CuWO4·2H2O Nanoparticles.

There is growing interest in graphene-reinforced inorganic matrix composites, but progress in this field is far behind that of polymer matrices due to difficulties in the processing of carbon materials in aggressive sintering environments, including oxidation and solubility in the host matrix. Copper-tungsten matrices are of particular interest in the power switching field but are difficult to produce due to the mutual insolubility of metals and poor wetting. Herein, composites were produced by decorating graphene oxide flakes with 8 nm diameter CuWO4·2H2O nanoparticles and then sintering them to form the final shape. The oxide nanoparticles were found to self-assemble into platelets on the surfaces of graphene flakes. Upon sintering, the presence of graphene was found to change the grain morphology from elongated needles to a polyhedral shape. It was found that, despite the nanosize of the CuWO4·2H2O particles used, the sintering conditions did not reduce the matrix to a pure metal; the sintered composites were found to be of mixed phase with copper tungstate and copper oxide present. Raman spectroscopy indicated that the graphene oxide became hydrogenated during the sintering process as a result of the reducing hydrogen atmosphere used.

3D-printed epidermal sweat microfluidic systems with integrated microcuvettes for precise spectroscopic and fluorometric biochemical assays.

Systems for capture, storage and analysis of eccrine sweat can provide insights into physiological health status, quantify losses of water, electrolytes, amino acids and/or other essential species, and identify exposures to adverse environmental species or illicit drugs. Recent advances in materials and device designs serve as the basis for skin-compatible classes of microfluidic platforms and in situ colorimetric assays for precise assessments of sweat rate, sweat loss and concentrations of wide-ranging types of biomarkers in sweat. This paper presents a set of findings that enhances the performance of these systems through the use of microfluidic networks, integrated valves and microscale optical cuvettes formed by three dimensional printing in hard/soft hybrid materials systems, for accurate spectroscopic and fluorometric assays. Field studies demonstrate the capability of these microcuvette systems to evaluate the concentrations of copper, chloride, and glucose in sweat, along with the pH of sweat, with laboratory-grade accuracy and sensitivity.

Pacific white shrimp (Litopenaeus vannamei) vitelline membrane outer layer protein 1 (VMO1) is produced in the hepatopancreas and transported into ovarian oocytes during vitellogenesis.

In birds, vitelline membrane outer layer protein 1 (VMO1) is an exogenous protein that can be absorbed by eggs as a barrier to prevent the mixing of yolk and egg white. However, researches on VMO1 are limited in birds but not other non-avian species until now. In this study, we first identified a novel Vmo1 cDNA (Lv-Vmo1) in Pacific white shrimp (Litopenaeus vannamei), the most important cultured shrimp in the world. We further analyzed its gene organization, phylogenetic relationship and protein structure. The Lv-Vmo1 transcript was specifically expressed in the hepatopancreas without sexual dimorphism. During ovarian development in female, the hepatopancreatic Lv-Vmo1 mRNA levels showed a significant increase. By in situ hybridization, Lv-Vmo1 mRNA was present in three cell types of the hepatopancreas but neither oocytes nor follicle cells of the ovary. In contrast, immunofluorescence revealed that Lv-VMO1 protein was distributed in the cytoplasms of both hepatopancreatic cells and ovarian oocytes. Western blot showed that Lv-VMO1 protein was produced in the hepatopancreas and transported to the ovary via hemolymph circulation. Identification of a species-specific egg-entry guide protein is the key to the receptor-mediated ovarian transduction of cargo, a novel gene editing approach in oviparous animals. This study lays the mechanism for exogenous transport into penaeid shrimp eggs by VMO1, as a foundation for achieving exogenous protein-mediated incorporation into oocytes.

Associations of Antidepressants With Atrial Fibrillation and Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

Background: Several published studies have disagreements on whether the use of antidepressants is associated with increased risk of arrhythmias. In this study, we performed this meta-analysis to assess the association of antidepressants with cardiac arrhythmias in patients who require antidepressants. Methods: The PubMed and Embase databases were systematically searched until December 2021 to find studies that investigated the association between antidepressant use and cardiac arrhythmias. Studies that assessed the effects of any antidepressant on arrhythmias in patients who require antidepressants compared with those who require no antidepressants were included. We used a random-effects model to pool the adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The stability of the results was examined by omitting an individual study at a time. Results: A total of 3,396 studies were screened and 6 studies with 2,626,746 participants were finally included in this meta-analysis. When compared with no antidepressants, the use of antidepressants was significantly associated with an increased risk of atrial fibrillation (RR = 1.37, 95% CI: 1.16-1.61). However, there was no difference in the risk of ventricular arrhythmias or sudden cardiac death (RR = 1.33, 95% CI: 0.88-2.01) between the two studied groups. In the subgroup analysis, tricyclic antidepressants (RR = 1.12, 95% CI: 0.89-1.41), selective serotonin reuptake inhibitors (RR = 1.46, 95% CI: 0.63-3.38), and selective serotonin reuptake inhibitors (RR = 0.99, 95% CI: 0.97-1.01) did not increase the risk of ventricular arrhythmias and/or sudden cardiac death. Conclusion: Recently published data suggested that the use of antidepressants did not increase the risk of ventricular arrhythmias or sudden cardiac death. Antidepressants were associated with an increased risk of atrial fibrillation but that still needs further confirmation.

Protective effect of endothelial progenitor cell-derived exosomal microRNA-382-3p on sepsis-induced organ damage and immune suppression in mice.

OBJECTIVE: To explore the role of endothelial progenitor cell (EPC)-derived exosomal microRNA-382-3p (miR-382-3p) in septic injury in mice. METHODS: A murine model of sepsis was introduced by cecal ligation and puncture (CLP). The model mice were treated with EPC-derived exosomes (Exos). The lung, kidney and liver tissues of mice were collected and stained with hematoxylin and eosin. The lymphocytes in murine spleen tissues, and the proportion and phenotype of the T helper cells (Ths) were examined by flow cytometry. The exosomal miRNAs were screened using a microarray analysis. The expressions of miR-382-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) were measured to explore possible mechanism of Exos in septic injury in mice. RESULTS: EPC-derived Exos alleviated CLP-induced tissue damage in the lung, kidney and liver tissues in septic mice. They also restored the number of lymphocytes and the concentration of Ths, and reduced the imbalance in Th1 and Th2 cells in mice. The Exos mainly contained miR-382-3p, and miR-382-3p directly targeted BTRC mRNA. Either downregulation of miR-382-3p or upregulation of BTRC blocked the protective roles of Exos in septic injury and immune suppression. Overexpression of BTRC increased the phosphorylation of nuclear factor kappa B (NF-κB) inhibitor α (IκBα) and NF-κB. CONCLUSION: EPC-derived exosomal miR-382-3p alleviates sepsis-induced organ damage and immune suppression in septic mice through regulating BTRC and the IκBα/NF-κB axis.

Mechanical and Electrical Properties of Graphene Oxide Reinforced Copper-Tungsten Composites Produced via Ball Milling of Metal Flakes.

Copper-tungsten (Cu-W) composites are widely used in high-power and -temperature electrical applications. The combination of these metals, however, leads to compromised physical and electrical properties. Herein, we produce Cu-W-graphene oxide (Cu-W-GO) composites to address this challenge. To ensure uniform density composites, the as-received metal powders were flattened into a flake morphology by ball milling and then mixed with up to 0.5 wt.% GO flakes. The green forms were processed using spark plasma sintering. The GO was found to be well-dispersed amongst the metallic phases in the final composite. The addition of GO reduced the relative density of the composites slightly (4.7% decrease in relative density at 0.5 wt% GO loading for the composites processed at 1000 °C). X-ray diffraction confirmed good phase purity and that no carbide phases were produced. GO was found to improve the mechanical properties of the Cu-W, with an optimal loading of 0.1 wt.% GO found for ultimate compression strength and strain to failure, and 0.3 wt.% optimal loading for the 0.2% offset yield strength. Significantly, the electrical conductivity increased by up to 25% with the addition of 0.1 wt.% GO but decreased with higher GO loadings.

Mechanism of the Huangguoshu waterfall forest environment's promotive effect on human health in Guizhou, China.

Background: The aim of this study was to investigate the specific mechanisms underlying the human health-promoting effects of the forest environment at Huangguoshu Falls, Guizhou, China. Methods: Ninety-five participants were recruited and an eye tracker was used to record fixation and sweep indices. A questionnaire was also used to evaluate the effects of different subject environments on human emotions, perceived recovery and preferences. Thereafter, 24 participants with chronic fatigue syndrome (CFS) were recruited and the participants' fatigue and stress-related scale indices and inflammatory factor levels were examined. Serum metabolites of the participants under different time waterfall forest interventions were detected by ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS). Results: Eye tracking paradigm analysis showed that the "waterfall" element was the most interesting element for participants and that the "charm" of the waterfall forest environment could be well perceived by participants. Scores on the Fatigue Scale, Anxiety Scale and Depression Scale decreased as the duration of treatment in the waterfall forest environment increased. Levels of inflammatory factors decreased after treatment in the waterfall forest environment. At the same time the level of antioxidants, represented by L-ascorbic acid, increased significantly. Conclusions: The charm of the Huangguoshu waterfall scenery could be perceived by the participants and have a positive modulating effect on mood and cognitive function. In addition, the unique mixture of negative oxygen ions in this environment can increase the content of endogenous antioxidants and balance the metabolism of choline and amino acids.

Effects of short-term waterfall forest aerosol air exposure on rat lung proteomics.

Background: Chronic exposure to airborne microparticles has been shown to increase the incidence of several chronic diseases. Previous studies have found that waterfall forest aerosols contribute to a diminished immune stress response in patients with asthma. However, the specific effects of short-term waterfall forest aerosol exposure on lung proteins have not been fully elucidated. Methods: This study used liquid chromatography-tandem mass spectrometry (LC-MS) to analyze changes in protein expression in the lungs of rats exposed to short-term waterfall forest aerosol environments. Specific protein markers were identified using bioconductivity analysis screening and validated using immunohistochemistry. Results: Waterfall forest aerosol environment exposure on day 5 downregulated the expression of the classical inflammatory pathway nuclear factor κB (NF-κB) signaling pathway. As the waterfall forest aerosol environment increased due to the duration of exposure, it was involved in oxidative phosphorylation and then hormone signaling in lung cells from the very beginning. In contrast, at day 15 of exposure, there is an effect on the regulation of the immune-related high-affinity IgE receptor pathway. In addition, iron-sulfur Rieske protein (Uqcrfs1), mitochondrial Tu translation elongation factor (Tufm) and ribosomal protein L4 (Rpl4) were identified as possible bioindicators for the evaluation of air quality. Conclusions: These results provide a comprehensive proteomic analysis that supports the positive contribution of a good air quality environment to lung health.

Proteasomal deubiquitylase activity enhances cell surface recycling of the epidermal growth factor receptor in non-small cell lung cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases. METHODS: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models. RESULTS: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice. CONCLUSION: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer.

Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway.

BACKGROUND: Hepatic stellate cell (HSC) hyperactivation is a central link in liver fibrosis development. HSCs perform aerobic glycolysis to provide energy for their activation. Focal adhesion kinase (FAK) promotes aerobic glycolysis in cancer cells or fibroblasts, while FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions. AIM: To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs. METHODS: Mouse liver fibrosis models were established by administering CCl4, and the effect of FRNK on the degree of liver fibrosis in the model was evaluated. Transforming growth factor-ß1 was used to activate LX-2 cells. Tyrosine phosphorylation at position 397 (pY397-FAK) was detected to identify activated FAK, and the expression of the glycolysis-related proteins monocarboxylate transporter 1 (MCT-1) and enolase1 (ENO1) was assessed. Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region, which were validated with chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The pY397-FAK level was increased in human fibrotic liver tissue. FRNK knockout promoted liver fibrosis in mouse models. It also increased the activation, migration, proliferation and aerobic glycolysis of primary hepatic stellate cells (pHSCs) but inhibited pHSC apoptosis. Nevertheless, opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells. Mechanistically, the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK. CONCLUSION: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis. FRNK might be a potential target for liver fibrosis treatment.

Biological functions of miRNA-188-5p/XRCC5 in the metastasis of glioma.

PURPOSE: The purpose of this study was to uncover the influence of microRNA-188-5p (miRNA-188-5p) on the metastasis of glioma, thus providing a new direction in the early diagnosis and prediction of disease progression. METHODS: MiRNA-188-5p levels in 44 glioma tissues and paracancerous ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Its influence on pathological indicators and prognosis in glioma patients was analyzed. In glioma cell lines, regulatory effects of miRNA-188-5p on cell phenotypes were examined by cell counting kit-8 (CCK-8), wound healing and Transwell assay, respectively. Moreover, the interaction between miRNA-188-5p and XRCC5, as well as their involvement in the development of glioma were finally illustrated. RESULTS: MiRNA-188-5p was downregulated in glioma samples. Glioma patients expressing a low level of miRNA-188-5p had a higher rate of distant metastasis and worse prognosis. Overexpression of miRNA-188-5p remarkably attenuated proliferative and migratory abilities of glioma cells. XRCC5 was the downstream gene of miRNA-188-5p, and its level was negatively regulated by miRNA-188-5p. Besides, XRCC5 was upregulated in glioma samples. Moreover, XRCC5 was responsible for the inhibitory effects of miRNA-188-5p on the metastasis of glioma. CONCLUSIONS: MiRNA-188-5p is linked to distant metastasis and prognosis in glioma patients, and it inhibits the proliferative and migratory abilities of glioma cells by binding XRCC5 and then negatively regulating its level.

Waterfall Forest Environment Regulates Chronic Stress via the NOX4/ROS/NF-κB Signaling Pathway.

Background: Forest therapy has been proven to have beneficial effects on people with depression and anxiety. However, it remains unknown whether the waterfall forest environment (WF) affects the physical and psychological health of patients with chronic fatigue and how the WF regulates chronic stress. Methods: Twenty-four patients with chronic fatigue were randomly divided into two groups: the WF group and the urban (U) group. Scores on the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 (FS-14) were evaluated before and after environmental intervention. Detection of physiological indexes and inflammatory factor levels and immunological analysis were also performed. In addition, the chronic stress rat model was constructed, and the effects of the WF on hopelessness and liver damage of rats were investigated. Results: Patients with chronic fatigue in the WF group showed a significant decrease in FS-14, HAMA, and HAMD scores compared with the U group. The expression levels of glutathione peroxidase and superoxide dismutase were remarkably higher in the WF group than in the U group. However, the expression levels of malondialdehyde and inflammatory factors (IL-1ß, TNF-α, IL-6, and IL-10) were remarkably decreased after the intervention of the WF. In addition, animal experiments confirmed that the WF improved hopelessness, liver damage, and excitability of neurons of chronic stress rats. Mechanistically, the WF reduced the liver damage caused by chronic stress in rats by inhibiting the NOX4/ROS/NF-κB signaling pathway. Conclusions: Collectively, the WF had a positive effect on immune enhancement and physical and psychological health in patients with chronic fatigue and might inhibit chronic stress by regulating the NOX4/ROS/NF-κB signaling pathway.