Exosomes from Cyclic Stretched Periodontal Ligament Cells Induced Periodontal Inflammation through miR-9-5p/SIRT1/NF-κB Signaling Pathway.

Abundant evidence demonstrates that mechanical stress could induce an inflammatory response in periodontal tissue, but the precise mechanism remains unclear. In the past few years, periodontal ligament cells (PDLCs), as the most force-sensitive cells, have been investigated in depth as local immune cells, associated with activation of inflammasomes and secretion of inflammatory cytokines in response to mechanical stimuli. However, this study innovatively inspected the effect of PDLCs on the other immune cells after stretch loading to reveal the detailed mechanism by which mechanical stimuli initiate immunoreaction in periodontium. In the present study, we found that cyclic stretch could stimulate human PDLCs to secret exosomes and that these exosomes could further induce the increase of phagocytic cells in the periodontium in Sprague-Dawley rats and the M1 polarization of the cultured macrophages (including the mouse macrophage cell line RAW264.7 and the bone marrow-derived macrophages from C57BL/6 mice). Furthermore, the exosomal miR-9-5p was detected to be overexpressed after mechanical stimuli in both in vivo and in vitro experiments and could trigger M1 polarization via the SIRT1/NF-κB signaling pathway in the cultured macrophages. In summary, this study revealed that PDLCs could transmit the mechanobiological signals to immune cells by releasing exosomes and simultaneously enhance periodontal inflammation through the miR-9-5p/SIRT1/NF-κB pathway. We hope that our research can improve understanding of force-related periodontal inflammatory diseases and lead to new targets for treatment.

EGR1 modulates EPHB4-induced trophoblast dysfunction in recurrent spontaneous abortion†.

Recurrent spontaneous abortion, defined as at least three unexplained abortions occurring before the 20-24 week of pregnancy, has a great impact on women's quality of life. Ephrin receptor B4 has been associated with trophoblast function in preeclampsia. The present study aimed to verify the hypothesis that ephrin receptor B4 regulates the biological functions of trophoblasts in recurrent spontaneous abortion and to explore the upstream mechanism. Ephrin receptor B4 was overexpressed in mice with recurrent spontaneous abortion. Moreover, ephrin receptor B4 inhibited trophoblast proliferation, migration, and invasion while promoting apoptosis. Downregulation of early growth response protein 1 expression in mice with recurrent spontaneous abortion led to ephrin receptor B4 overexpression. Poor expression of WT1-associated protein in mice with recurrent spontaneous abortion reduced the modification of early growth response protein 1 mRNA methylation, resulting in decreased early growth response protein 1 mRNA stability and expression. Overexpression of WT1-associated protein reduced the incidence of recurrent spontaneous abortion in mice by controlling the phenotype of trophoblasts, which was reversed by early growth response protein 1 knockdown. All in all, our findings demonstrate that dysregulation of WT1-associated protein contributes to the instability of early growth response protein 1, thereby activating ephrin receptor B4-induced trophoblast dysfunction in recurrent spontaneous abortion. Our study provides novel insights into understanding the molecular pathogenesis of recurrent spontaneous abortion.

Improving temperature characteristics of GaN-based ultraviolet laser diodes by using InGaN/AlGaN quantum wells.

Temperature characteristics of GaN-based laser diodes are investigated. It is noted that the characteristic temperature of the threshold current (T0) decreases with decreasing lasing wavelength for GaN-based LDs. The performance deteriorates seriously for UV LDs at high temperature. It is ascribed to the increase of carriers escaping from quantum wells due to the lower potential barrier height. In this Letter, AlGaN is used as the barrier layer in UV LDs instead of GaN to improve the temperature characteristic of the threshold current and slope efficiency by increasing the potential barrier height of quantum wells. Based on this structure, a high output power of 4.6 W is obtained at the injection current of 3.8 A; its lasing wavelength is 386.8 nm.

Sex and Age Differences in Ontogeny of Alloparenting: A Relation to Forebrain DRD1, DRD2, and HTR2A mRNA Expression?

Alloparenting refers to the practice of caring for the young by individuals other than their biological parents. The relationship between the dynamic changes in psychological functions underlying alloparenting and the development of specific neuroreceptors remains unclear. Using a classic 10-day pup sensitization procedure, together with a pup preference and pup retrieval test on the EPM (elevated plus maze), we showed that both male and female adolescent rats (24 days old) had significantly shorter latency than adult rats (65 days old) to be alloparental, and their motivation levels for pups and objects were also significantly higher. In contrast, adult rats retrieved more pups than adolescent rats even though they appeared to be more anxious on the EPM. Analysis of mRNA expression using real-time-PCR revealed a higher dopamine D2 receptor (DRD2) receptor expression in adult hippocampus, amygdala, and ventral striatum, along with higher dopamine D1 receptor (DRD1) receptor expression in ventral striatum compared to adolescent rats. Adult rats also showed significantly higher levels of 5-hydroxytryptamine receptor 2A (HTR2A) receptor expression in the medial prefrontal cortex, amygdala, ventral striatum, and hypothalamus. These results suggest that the faster onset of alloparenting in adolescent rats compared to adult rats, along with the psychological functions involved, may be mediated by varying levels of dopamine DRD1, DRD2, and HTR2A in different forebrain regions.

Dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces oxidative damage promoting cell apoptosis primarily via mitochondrial pathway in the hepatopancreas of carp, Cyprinus carpio.

To investigate the mechanisms of BDE-47 on hepatotoxicity in fish, this study examined the effects of dietary exposure to BDE-47 (40 and 4000 ng/g) on carp for 42 days. The results showed that BDE-47 significantly increased carp's condition factor and hepatosomatic index. Pathological results revealed unclear hepatic cord structure, hepatocytes swelling, cellular vacuolization, and inflammatory cell infiltration in the hepatopancreas of carp. Further investigation showed that ROS levels significantly increased on days 7, 14, and 42. Moreover, the activities of antioxidant enzymes SOD, GSH, CAT, and GST increased significantly from 1 to 7 days, and the transcription levels of antioxidant enzymes CAT, Cu-Zn SOD, Mn-SOD, GST, and GPX, and antioxidant pathway genes Keap1, Nrf2, and HO-1 changed significantly at multiple time-points during the 42 days. The results of apoptosis pathway genes showed that the mitochondrial pathway genes Bax, Casp3, and Casp9 were significantly upregulated and Bcl2 was significantly downregulated, while the transcription levels of FADD and PERK were significantly enhanced. These results indicate that BDE-47 induced oxidative damage in hepatopancreas, then it promoted cell apoptosis mainly through the mitochondrial pathway. This study provides a foundation for analyzing the mechanism of hepatotoxicity induced by BDE-47 on fish.

Acidic Gas Determination Using Indium Tin Oxide-Based Gas Sensors.

This work has presented gas sensors based on indium tin oxide (ITO) for the detection of SO2 and NO2. The ITO gas-sensing material was deposited by radio frequency (RF) magnetron sputtering. The properties of gas sensing could be improved by increasing the ratio of SnO2. The response characteristics of the gas sensor for detecting different concentrations of NO2 and SO2 were investigated. In the detection of NO2, the sensitivity was significantly improved by increasing the SnO2 ratio in ITO by 5%, and the response and recovery time were reduced significantly. However, the sensitivity of the sensor decreased with increasing SO2 concentration. From X-ray photoelectron spectroscopy (XPS) analysis, the gas-sensitive response mechanisms were different in the atmosphere of NO2 and SO2. The NO2 was adsorbed by ITO via physisorption but the SO2 had a chemical reaction with the ITO surface. The gas selectivity, temperature dependence, and environmental humidity of ITO-based gas sensors were systematically analyzed. The high detection sensitivity for acidic gas of the prepared sensor presented great potential for acid rain monitoring.

Fabrication of Nitrogen Based Magnetic Conjugated Microporous Polymer for Efficient Extraction of Neonicotinoids in Water Samples.

Facile and sensitive methods for detecting neonicotinoids (NEOs) in aquatic environments are crucial because they are found in extremely low concentrations in complex matrices. Herein, nitrogen-based magnetic conjugated microporous polymers (Fe3O4@N-CMP) with quaternary ammonium groups were synthesized for efficient magnetic solid-phase extraction (MSPE) of NEOs from tap water, rainwater, and lake water. Fe3O4@N-CMP possessed a suitable specific surface area, extended π-conjugated system, and numerous cationic groups. These properties endow Fe3O4@N-CMP with superior extraction efficiency toward NEOs. The excellent adsorption capacity of Fe3O4@N-CMP toward NEOs was attributed to its π-π stacking, Lewis acid-base, and electrostatic interactions. The proposed MSPE-HPLC-DAD approach based on Fe3O4@N-CMP exhibited a wide linear range (0.1-200 µg/L), low detection limits (0.3-0.5 µg/L), satisfactory precision, and acceptable reproducibility under optimal conditions. In addition, the established method was effectively utilized for the analysis of NEOs in tap water, rainwater, and lake water. Excellent recoveries of NEOs at three spiked levels were in the range of 70.4 to 122.7%, with RSDs less than 10%. This study provides a reliable pretreatment method for monitoring NEOs in environmental water samples.

Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.

Stability of collagen heterotrimer with same charge pattern and different charged residue identities.

Salt bridges are important factors in maintaining the stability of proteins, and their contribution to protein folding has received much attention. Although the interaction energies, or stabilizing contributions, of individual salt bridges have been measured in various proteins, a systematic assessment of various types of salt bridges in a relatively uniform environment is still a valuable analysis. Here, we used a collagen heterotrimer as a host-guest platform to construct 48 heterotrimers with the same charge pattern. A variety of salt bridges were formed between the oppositely charged residues Lys, Arg, Asp, and Glu. The melting temperature (Tm) of the heterotrimers was measured with circular dichroism. The atomic structures of 10 salt bridges were shown in three x-ray crystals of heterotrimer. Molecular dynamics simulation based on the crystal structures indicated that strong, intermediate, and weak salt bridges have distinctive N-O distances. A linear regression model was used to predict the stability of heterotrimers with high accuracy (R2 = 0.93). We developed an online database to help readers understand how a salt bridge stabilizes collagen. This work will help us better understand the stabilizing mechanism of salt bridges in collagen folding and provide a new strategy to design collagen heterotrimers.

Astrocytic aryl hydrocarbon receptor mediates chronic kidney disease-associated mental disorders involving GLT1 hypofunction and neuronal activity enhancement in the mouse brain.

Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP+ reactive astrocytes were increased accompanied with the reduction of glutamate transporter 1 (GLT1) on perineuronal astrocytic processes (PAPs) in the anterior cingulate cortex (ACC) in CKD mice, and these alterations were attenuated in both neural lineage-specific and astrocyte-specific Ahr conditional knockout mice (nAhrCKO and aAhrCKO). By using chronic I3S treatment in primary astrocytes and glia-neuron (GN) mix cultures to mimic the CKD brain microenvironment, we also found significant reduction of GLT1 expression and activity in an AhR-dependent manner. Chronic I3S treatment induced AhR-dependent pro-oxidant Nox1 and AhR-independent anti-oxidant HO-1 expressions. Notably, AhR mediates chronic I3S-induced neuronal activity enhancement and synaptotoxicity in GN mix, not neuron-enriched cortical culture. In CKD mice, neuronal activity enhancement was observed in ACC and hippocampal CA1, and these responses were abrogated by both nAhrCKO and aAhrCKO. Finally, intranasal AhR antagonist CH-223191 administration significantly ameliorated the GLT1/PAPs reduction, increase in c-Fos+ neurons, and memory impairment in the CKD mice. Thus, astrocytic AhR plays a crucial role in the CKD-induced disturbance of neuron-astrocyte interaction and mental disorders.

Enhanced Oxygen Evolution Reaction Performance on NiSx@Co3O4/Nickel Foam Electrocatalysts with Their Photothermal Property.

Based on the principle of heterogeneous catalysis for water electrolysis, electrocatalysts with appropriate electronic structure and photothermal property are expected to drive the oxygen evolution reaction effectively. Herein, amorphous NiSx-coupled nanourchin-like Co3O4 was prepared on nickel foam (NiSx@Co3O4/NF) and investigated as a electrocatalyst for photothermal-assisted oxygen evolution reaction. The experimental investigations and simulant calculations jointly revealed NiSx@Co3O4/NF to be of suitable electronic structure and high near-infrared photothermal conversion capability to achieve the oxygen evolution reaction advantageously both in thermodynamics and in kinetics. Relative to Co3O4/NF and NiSx/NF, better oxygen evolution reaction activity, kinetics, and stability were achieved on NiSx@Co3O4/NF in 1.0 M KOH owing to the NiSx/Co3O4 synergetic effect. In addition, the oxygen evolution reaction performance of NiSx@Co3O4/NF can be obviously enhanced under near-infrared light irradiation, since NiSx@Co3O4 can absorb the near-infrared light to produce electric and thermal field. For the photothermal-mediated oxygen evolution reaction, the overpotential and Tafel slope of NiSx@Co3O4/NF at 50 mA cm-2 were reduced by 23 mV and 13 mV/dec, respectively. The present work provides an inspiring reference to design and develop photothermal-assisted water electrolysis using abundant solar energy.

Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.

Ubiquitin E3 ligase AtCHYR2 functions in glucose regulation of germination and post-germinative growth in Arabidopsis thaliana.

KEY MESSAGE: Cytoplasm-localized RING ubiquitin E3 ligase AtCHYR2 involved in plant glucose responses during germination and post-germinative growth. CHY ZINC FINGER AND RING PROTEIN (CHYR) containing both a CHY zinc finger and a C3H2C3-type RING domain plays important roles in plant drought tolerance and the abscisic acid (ABA) response; however, their functions in sugar signaling pathways are less studied. Here, we report a glucose (Glc) response gene AtCHYR2, a homolog of RZFP34/CHYR1, which is induced by various abiotic stresses, ABA, and sugar treatments. In vitro, we demonstrated that AtCHYR2 is a cytoplasm-localized RING ubiquitin E3 ligase. Overexpression of AtCHYR2 led to hypersensitivity to Glc and enhanced Glc-mediated inhibition of cotyledon greening and post-germinative growth. Contrastingly, AtCHYR2 loss-of-function plants were insensitive to Glc-regulated seed germination and primary root growth, suggesting that AtCHYR2 is a positively regulator of the plant glucose response. Additionally, physiological analyses showed that overexpression AtCHYR2 increased stomata aperture and photosynthesis under normal condition, and promoted accumulation of endogenous soluble sugar and starch in response to high Glc. Genome-wide RNA sequencing analysis showed that AtCHYR2 affects a major proportion of Glc-responsive genes. Particularly, sugar marker gene expression analysis suggested that AtCHYR2 enhances the Glc response via a signaling pathway dependent on glucose metabolism. Taken together, our findings show that a novel RING ubiquitin E3 ligase, AtCHYR2, plays an important role in glucose responses in Arabidopsis.

Cold stress causes liver damage by inducing ferroptosis through the p38 MAPK/Drp1 pathway.

Acute extreme cold exposure impairs human health and even causes hypothermia which threatens human life. Liver, as a hub in metabolism and thermogenesis, is vital for cold acclimatization. Although accumulating evidence has suggested that cold exposure can cause liver damage, the underlying mechanisms remain poorly understood. This study investigated the role and underlying mechanisms of ferroptosis in cold stress-induced liver damage. To evaluate the role of ferroptosis in cold stress-induced liver damage, rats were pretreated with ferroptosis inhibitor liproxstatin-1 (Lip-1) before exposed to -10 °C for 8 h. Core body temperature was recorded. The levels of ferroptosis-related indicators were examined with the corresponding assay kits or by western blotting. Hepatic pathological changes were analyzed by hematoxylin-eosin staining and ultrastructural observation. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess liver function. Rats were also pretreated with p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or Dynamin-related protein 1 (Drp1) inhibitor Mdivi-1 to determine the underlying mechanisms. We found that Lip-1 inhibited ferroptosis, attenuated hepatic pathological damages and blocked the increased ALT and AST levels in cold-exposed rats. Moreover, Mdivi-1 inhibited mitochondrial fission and suppressed ferroptosis. Furthermore, SB203580 and Mdivi-1 administration alleviated cold stress-induced liver injury. Our results suggested that cold stress caused liver damage partially by inducing ferroptosis through the p38 MAPK/Drp1 pathway. These findings might provide an effective preventive and therapeutic target for cold stress-induced liver injury.

Bioequivalence study of domperidone dry suspension in healthy Chinese subjects under fasted and fed conditions: An open-label, randomized, single-dose, crossover trial.

BACKGROUND: Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration approval of a new generic dry suspension formulation of domperidone by comparing the safety and pharmacokinetic profiles between the test and branded reference formulation in the context of fasted and fed condition. MATERIALS AND METHODS: This was designed as a randomized, open-label, single-dose, two-period, two-treatment crossover study. 32 and 28 eligible healthy subjects were enrolled in the fasted and fed study, respectively. Each subject was randomly assigned to receive either the test or reference formulation in the first period, followed by a 1-week washout period and dosing of the alternate formulation in the second period. A series of blood samples were collected at scheduled timepoints within 48 hours after administration during each treatment period. Plasma concentrations of domperidone were determined by validated HPLC-MS/MS. Pharmacokinetic parameters, including Cmax, tmax, AUC0-t, AUC0-∞, and T1/2, were acquired based on the concentration vs. time profiles by non-compartmental analysis using WinNonlin software. Then the geometric mean ratios (GMR) of Cmax, AUC0-t, and AUC0-∞ between the two formulations and corresponding 90% confidence intervals (CIs) were calculated for bioequivalence determination. Safety was assessed as routine. RESULTS: The two formulations showed similar pharmacokinetic profiles. Under fasted condition, the GMR and corresponding 90% CIs of AUC0-t, AUC0-∞, and Cmax were 101.48% (96.79 - 106.38%), 101.17% (96.66 - 105.90%), and 104.61% (96.73 - 113.14%), respectively. Under fed condition, the GMR and corresponding 90% CIs were 105.46% (99.19 - 112.12%), 104.21% (98.19 - 110.61%), and 112.78% (103.64 - 122.73%), respectively, for AUC0-t, AUC0-∞, and Cmax. All values fell within the accepted bioequivalence range of 80 - 125%. Both the test and the reference products were well tolerated without any serious or unexpected adverse reactions. CONCLUSION: Pharmacokinetic bioequivalence was established between the two dry suspension formulations of domperidone in healthy Chinese subjects. Both products were safe and well tolerated.

Group citizenship behaviour in healthcare organization, doctor-patient relationship, work engagement and turnover intention: A moderated mediation model.

The effective functioning of health care organisations depends on the inter-professional collaboration among healthcare professionals from diverse backgrounds, representing different work units, to provide quality services. This study aims to understand how group citizenship behaviour (GCB) that supports other work groups may moderate the relationship between doctor-patient relationship (DPR), Work Engagement (WE) and Turnover Intention (TI). The data for this study were collected through two waves of questionnaire survey at a tertiary public hospital in China. The hypothesised model was tested by Hayes' PROCESS macro. There were significant differences of perceived GCB across different professional units with work units practicing a multidisciplinary working approach and working in the high-stake working environment reported higher levels of GCB. The results show that WE mediates the relationships between DPR and TI and GCB accentuates the positive relationship between DPR and WE. Specifically, the path between DPR and WE was stronger for individuals with high perceived GCB than those with low perceived GCB. The study contributes to the development of Job Demands-Resources model with integrating GCB into the model and enriching the challenge job demand conceptualisation by focussing on DPR in Chinese health care setting. In practice, the hospital administrators should encourage GCB to improve organizational effectiveness and doctors' attitudes.

Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity.

Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response. In this review, the molecular mechanisms involved in tumor vascular microenvironment-modulated immune reactions are summarized. In addition, the evidence of pre-clinical and clinical studies for the combined targeting of pro-angiogenic signaling and immune checkpoint molecules with therapeutic potential are highlighted. The heterogeneity of endothelial cells in tumors that regulate tissue-specific immune responses is also discussed. The crosstalk between tumor endothelial cells and immune cells in individual tissues is postulated to have a unique molecular signature and may be considered as a potential target for the development of new immunotherapeutic approaches.

Application of machine learning and its effects on the development of a nursing guidance mobile app for sarcopenia.

BACKGROUND: Aging leads to changes in the body system, such as sarcopenia. This can result in several health issues, particularly physical and mobility dysfunction. Asian people typically have little awareness of sarcopenia. Thus, this study incorporated nursing instruction into the mobile application design to allow users to easily learn about sarcopenia. OBJECTIVE: This study evaluated a model for predicting high-risk populations for sarcopenia in home settings. We further developed a sarcopenia nursing guidance mobile application and assessed the effectiveness of this application in influencing sarcopenia-related knowledge and self-care awareness among participants. METHODS: Using a one-group pretest-posttest design, data were collected from 120 participants at a teaching hospital in northern Taiwan. This study used an artificial intelligence algorithm to evaluate a model for predicting high-risk populations for sarcopenia. We developed and assessed the sarcopenia nursing guidance mobile application using a questionnaire based on the Mobile Application Rating Scale. RESULTS: The application developed in this study enhanced participants' sarcopenia-related knowledge and awareness regarding self-care. After the three-month intervention, the knowledge and awareness was effectively increase, total score was from 4.15 ± 2.35 to 6.65 ± 0.85 and were significant for all questionnaire items (p values < 0.05). On average, 96.1% of the participants were satisfied with the mobile app. The artificial intelligence algorithm positively evaluated the home-use model for predicting high-risk sarcopenia groups. CONCLUSIONS: The mobile application of the sarcopenia nursing guidance for public use in home settings may help alleviate sarcopenia symptoms and reduce complications by enhancing individuals' self-care awareness and ability. TRIAL REGISTRATION: NCT05363033, registered on 02/05/2022.

VisProDom: an interactive Shiny/R application for displaying protein domains with transcriptional features.

BACKGROUND: Both the protein domains and transcript structures influence protein functional variation. The genomic location of both protein domains and transcript structural features can be described using the genomic coordinates of their encoded sequences. However, the coordinates of protein domains and transcriptional features often differ greatly, and it is difficult to view them in combination at the genome-wide level. In this paper, we describe the development of a new tool that allows users to visualize domains and transcript features together, using either built-in or uploaded genome datasets, and export publication-ready figures.  RESULTS: We developed a user-friendly, independent R package and Shiny web application named "VisProDom". VisProDom consists of a genome-wide database containing entire annotated transcripts merged with annotated protein domains from the Pfam database. The built-in dataset includes 82 files, which merge genome general feature format (GFF) annotations with rpsblast tabular outputs from protein sequence searches in the Pfam database. Multiple genomes can be simultaneously screened for protein domains or transcript names. VisProDom includes step-by-step introductions and clickable elements for ease of use. CONCLUSION: VisProDom can display hundreds of transcripts alongside protein domains and export figures in a publication-ready format. This makes it a valuable tool for molecular evolution and comparative genomics.

The protective role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under inflammatory environment.

Inflammation and alveolar bone destruction constitute the main pathological process of periodontitis. However, the molecular mechanisms of bone destruction under the inflammation environment remain unclear. This study aims to explore the role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under the inflammation environment. Mouse pre-osteoblasts MC3T3-E1 were pretreated with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS). The Ephrin-B2/EphB4 signaling was activated, and the osteogenic differentiation of cells was examined. The results showed that activation of Ephrin-B2/EphB4 signaling promoted the expression levels of osteogenic differentiation-related genes, and also relieved the inhibitory effect of Pg-LPS on osteogenesis. Noticeably, the effect of Ephrin-B2/EphB4 signaling might be related to the mitogen-activated protein kinase (MAPK) pathway. While applying Ephrin-B2-Fc and EphB4-Fc to periodontitis mice, we observed the reduction of alveolar crest destruction. The current study revealed the possible role of Ephrin-B2/EphB4 signaling in reducing bone destruction in periodontitis and suggested its potential values for further research.