VisTellAR: Embedding Data Visualization to Short-form Videos Using Mobile Augmented Reality.

With the rise of short-form video platforms and the increasing availability of data, we see the potential for people to share short-form videos embedded with data in situ (e.g., daily steps when running) to increase the credibility and expressiveness of their stories. However, creating and sharing such videos in situ is challenging since it involves multiple steps and skills (e.g., data visualization creation and video editing), especially for amateurs. By conducting a formative study (N=10) using three design probes, we collected the motivations and design requirements. We then built VisTellAR, a mobile AR authoring tool, to help amateur video creators embed data visualizations in short-form videos in situ. A two-day user study shows that participants (N=12) successfully created various videos with data visualizations in situ and they confirmed the ease of use and learning. AR pre-stage authoring was useful to assist people in setting up data visualizations in reality with more designs in camera movements and interaction with gestures and physical objects to storytelling.

Management and outcome of adult generalized tetanus in a Chinese tertiary hospital.

Background: Tetanus is a rare surgical infectious disease with a high reported relevant mortality. It still remains a serious problem in public health, particularly in low-income and middle-income countries. The purpose of this study was to investigate the management and prognosis of adult generalized tetanus in our hospital. Methods: A total of 20 adult generalized tetanus patients were recruited in this retrospective observational study. Patients were retrieved from the hospital data base via discharge diagnosis. Patients were divided into two groups (Severe or Non-severe tetanus group) based on the severity of tetanus by using the Ablett classification. The differences between the two groups were compared. Results: The study included 11 males (55%) and 9 females (45%). All tetanus patients recovered. The median age was 53.5 years [IQR: 19-78]. There were 1 mild (Grade 1) case (5%),5 moderate (Grade 2) cases (25%), 2 severe (Grade 3) cases (10%), and 12 very severe (Grade 4) cases (60%). Nineteen patients (95%) did not have tetanus immunization before. The majority of patients were farmers (60%), and came from rural areas (60%). Thirteen (65%) patients had a history of puncture injury. The rate of wound debridement after admission was 60% overall. Thirteen (65%) patients required mechanical ventilation for a median of 21 [IQR:12-41] days. Autonomic instability occurred in 13 (65%) patients. Pulmonary infections occurred in 12 (60%) patients. Median duration of hospital stay was 29.5 [IQR:12-68] days. More patients in the Severe group needed ICU admission, wound debridement, mechanical ventilation and heavy sedation combined with muscle relaxants (p < 0.05). The hospital stay was significantly longer in patients in the Severe group (p < 0.05). Conclusion: After effective treatment, all adult patients with generalized tetanus in this study were cured and discharged. Severe tetanus requires early ICU treatment, wound debridement and effective treatment of autonomic instability.

[Research progress in signaling pathways related to treatment of functional dyspepsia with traditional Chinese medicine].

Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.

Curcumin Reduces Hypoxia/Reperfusion Injury of Cardiomyocytes by Stimulating Vascular Endothelial Cells to Secrete FGF2.

OBJECTIVE: Endothelial cells (ECs) can provide cell protection for cardiomyocytes (CMs) under hypoxia-reoxygenation (HR) conditions by secreting derived factors. This study aimed to explore the role of curcumin (CUR) in ECs for protecting CMs from HR injury. METHODS: A co-culture system for ECs and CMs was set up, and subjected to HR. The transcription, expression, and secretion of FGF2 were detected by RT-qPCR, western blot, and ELISA, respectively. siRNAs specifically targeting FGF2 were transfected into ECs. FGF2 receptor- specific inhibitors (AZD4547) were used to treat CMs. RESULTS: The co-culture with ECs did not affect the proliferation of CMs, while CUR and ECs co-culture had a synergistic effect on promoting the proliferation of CMs in HR. Furthermore, the co-culture with ECs did not affect the apoptosis and autophagy of CMs in HR. However, the co-culture of ECs after CUR treatment inhibited the apoptosis and autophagy of CMs in HR. CUR treatment significantly enhanced FGF2 mRNA, protein, and secretion levels of ECs in HR. In addition, CUR treatment increased FGF2 levels in the CMs medium in the ECs and CMs co-culture system. The reduction of FGF2 levels in the medium and the inhibition of FGF2 receptors significantly inhibited the proliferation of CMs and significantly promoted the apoptosis and autophagy of CMs in HR. CONCLUSION: Focusing on the protective effects of CUR and ECs on cardiomyocytes is of great significance for the treatment of clinical myocardial HR injury.

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Methods: Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Results: Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. Conclusion: CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

Hydrothermal Growth of an Al-Doped α-Ga2O3 Nanorod Array and Its Application in Self-Powered Solar-Blind UV Photodetection Based on a Photoelectrochemical Cell.

Herein, we successfully fabricated an Al-doped α-Ga2O3 nanorod array on FTO using the hydrothermal and post-annealing processes. To the best of our knowledge, it is the first time that an Al-doped α-Ga2O3 nanorod array on FTO has been realized via a much simpler and cheaper way than that based on metal-organic chemical vapor deposition, magnetron sputtering, molecular beam epitaxy, and pulsed laser deposition. And, a self-powered Al-doped α-Ga2O3 nanorod array/FTO photodetector was also realized as a photoanode at 0 V (vs. Ag/AgCl) in a photoelectrochemical (PEC) cell, showing a peak responsivity of 1.46 mA/W at 260 nm. The response speed of the Al-doped device was 0.421 s for rise time, and 0.139 s for decay time under solar-blind UV (260 nm) illumination. Compared with the undoped device, the responsivity of the Al-doped device was ~5.84 times larger, and the response speed was relatively faster. When increasing the biases from 0 V to 1 V, the responsivity, quantum efficiency, and detectivity of the Al-doped device were enhanced from 1.46 mA/W to 2.02 mA/W, from ~0.7% to ~0.96%, and from ~6 × 109 Jones to ~1 × 1010 Jones, respectively, due to the enlarged depletion region. Therefore, Al doping may provide a route to enhance the self-powered photodetection performance of α-Ga2O3 nanorod arrays.

Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells.

Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the first step of the serine synthesis pathway (SSP), is overexpressed in multiple types of cancers. The androgen receptor inhibitor enzalutamide (Enza) is the primary therapeutic drug for patients with castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to Enza. The association of SSP with Enza resistance remains unclear. In this study, we found that high expression of PHGDH was associated with Enza resistance in CRPC cells. Moreover, increased expression of PHGDH led to ferroptosis resistance by maintaining redox homeostasis in Enza-resistant CRPC cells. Knockdown of PHGDH caused significant GSH reduction, induced lipid peroxides (LipROS) increase and significant cell death, resulting in inhibiting growth of Enza-resistant CRPC cells and sensitizing Enza-resistant CRPC cells to enzalutamide treatment both in vitro and in vivo. We also found that overexpression of PHGDH promoted cell growth and Enza resistance in CRPC cells. Furthermore, pharmacological inhibition of PHGDH by NCT-503 effectively inhibited cell growth, induced ferroptosis, and overcame enzalutamide resistance in Enza-resistant CRPC cells both in vitro and in vivo. Mechanically, NCT-503 triggered ferroptosis by decreasing GSH/GSSG levels and increasing LipROS production as well as suppressing SLC7A11 expression through activation of the p53 signaling pathway. Moreover, stimulating ferroptosis by ferroptosis inducers (FINs) or NCT-503 synergistically sensitized Enza-resistant CRPC cells to enzalutamide. The synergistic effects of NCT-503 and enzalutamide were verified in a xenograft nude mouse model. NCT-503 in combination with enzalutamide effectively restricted the growth of Enza-resistant CRPC xenografts in vivo. Overall, our study highlights the essential roles of increased PHGDH in mediating enzalutamide resistance in CRPC. Therefore, the combination of ferroptosis inducer and targeted inhibition of PHGDH could be a potential therapeutic strategy for overcoming enzalutamide resistance in CRPC.

Immobilized lipase for sustainable hydrolysis of acidified oil to produce fatty acid.

Acidified oil is obtained from by-product of crops oil refining industry, which is considered as a low-cost material for fatty acid production. Hydrolysis of acidified oil by lipase catalysis for producing fatty acid is a sustainable and efficient bioprocess that is an alternative of continuous countercurrent hydrolysis. In this study, lipase from Candida rugosa (CRL) was immobilized on magnetic Fe3O4@SiO2 via covalent binding strategy for highly efficient hydrolysis of acidified soybean oil. FTIR, XRD, SEM and VSM were used to characterize the immobilized lipase (Fe3O4@SiO2-CRL). The enzyme properties of the Fe3O4@SiO2-CRL were determined. Fe3O4@SiO2-CRL was used to catalyze the hydrolysis of acidified soybean oil to produce fatty acids. Catalytic reaction conditions were studied, including amount of catalyst, reaction time, and water/oil ratio. The results of optimization indicated that the hydrolysis rate reached 98% under 10 wt.% (oil) of catalyst, 3:1 (v/v) of water/oil ratio, and 313 K after 12 h. After 5 cycles, the hydrolysis activity of Fe3O4@SiO2-CRL remained 55%. Preparation of fatty acids from high-acid-value by-products through biosystem shows great industrial potential.

uxSense: Supporting User Experience Analysis with Visualization and Computer Vision.

Analyzing user behavior from usability evaluation can be a challenging and time-consuming task, especially as the number of participants and the scale and complexity of the evaluation grows. We propose UXSENSE, a visual analytics system using machine learning methods to extract user behavior from audio and video recordings as parallel time-stamped data streams. Our implementation draws on pattern recognition, computer vision, natural language processing, and machine learning to extract user sentiment, actions, posture, spoken words, and other features from such recordings. These streams are visualized as parallel timelines in a web-based front-end, enabling the researcher to search, filter, and annotate data across time and space. We present the results of a user study involving professional UX researchers evaluating user data using uxSense. In fact, we used uxSense itself to evaluate their sessions.

Effect of Glutaraldehyde Multipoint Covalent Treatments on Immobilized Lipase for Hydrolysis of Acidified Oil.

Immobilized lipase is a green and sustainable catalyst for hydrolysis of acidified oil. Glutaraldehyde is widely used for lipase immobilization while the appropriate strategy optimizes the catalytic performance of lipase. In this research, lipase from Candida rugosa (CRL) was immobilized on spherical silica (SiO2) by glutaraldehyde multipoint covalent treatments, including covalent binding method and adsorption-crosslinking method. The enzymatic stability properties and performance in hydrolysis of refined oil and acidified oil were studied. We confirmed that the residual activity decreased while the stability increased because of the influence on secondary structure of lipase after multipoint covalent treatments. In the comparison of different immobilization strategies in multipoint covalent treatment, SiO2-CRL (covalent binding method) showed lower loading capacity than SiO2-CRL (adsorption-crosslinking method), resulting in low activity. However, SiO2-CRL (covalent binding method) showed better reusability and stability. Immobilized lipase via covalent binding method was more potential in the application of catalytic hydrolysis of acidified oils.

Exploring a shared genetic signature and immune infiltration between spontaneous intracerebral hemorrhage and Helicobacter pylori infection.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity, disability and mortality. Helicobacter pylori is a major pathogen responsible for chronic gastritis, leading to gastric ulcers and ultimately gastric cancer. Although it remains controversial whether H. pylori infection causes peptic ulcers under various traumatic stimuli, some related studies suggest that H. pylori infection may be an important factor in delaying peptic ulcer healing. However, the linking mechanism between ICH and H. pylori infection remain unclear. The purpose of this study was to examine the genetic features and pathways shared in ICH and H. pylori infection, and compare immune infiltration. METHODS: We used microarray data for ICH and H. pylori infection from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed on both datasets using the R software and the limma package to find the common differentially expressed genes (DEGs). In addition, we performed functional enrichment analysis on DEGs, determined protein-protein interactions (PPIs), identified Hub genes using the STRING database and Cytoscape software, and constructed microRNA-messenger RNA (miRNA-mRNA) interaction networks. Additionally, immune infiltration analysis was performed with the R software and related R packages. RESULTS: A total of 72 DEGs were identified between ICH and H. pylori infection, including 68 upregulated genes and 4 downregulated genes. Functional enrichment analysis revealed that multiple signaling pathways are closely linked to both diseases. In addition, the cytoHubba plugin identified 15 important hub genes, namely PLEK, NCF2, CXCR4, CXCL1, FGR, CXCL12, CXCL2, CD69, NOD2, RGS1, SLA, LCP1, HMOX1, EDN1, and ITGB3.Also, the correlation analysis of immune cell fractions revealed a limited link between their immune-related common genes and immune cells. CONCLUSION: Through bioinformatics methods, this study revealed that there are common pathways and hub genes between ICH and H. pylori infection. Thus, H. pylori infection may have common pathogenic mechanisms with the development of peptic ulcer after ICH. This study provided new ideas for early diagnosis and prevention of ICH and H. pylori infection.

Cardiac glycoside neriifolin exerts anti-cancer activity in prostate cancer cells by attenuating DNA damage repair through endoplasmic reticulum stress.

Prostate cancer (PCa) is one of the most common cancers in men. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa. Thus, new therapeutic approaches for PCa resistance to current treatments are urgently needed. Here, we report that cardiac glycoside neriifolin suppresses the malignancy of cancer cells via increasing DNA damage and apoptosis through activation of endoplasmic reticulum stress (ERS) in prostate cancers. We found that cardiac glycoside neriifolin markedly inhibited the cell growth and induced apoptosis in prostate cancer cells. Transcriptome sequence analysis revealed that neriifolin significantly induced DNA damage and double strand breaks (DSBs), validated with attenuation expression of genes in DSBs repair and increasing phosphorylated histone H2AX (γ-H2AX) foci formation, a quantitative marker of DSBs. Moreover, we found that neriifolin also activated ERS, evidenced by upregulation and activation of ERS related proteins, including eukaryotic initiation factor 2α (eIF2α), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and C/EBP homologous protein (CHOP) as well as downregulation of CCAATenhancerbinding protein alpha (C/EBP-α), a transcriptional factor that forms heterodimers with CHOP. In addition, neriifolin treatment dramatically inhibited the by tumor growth, which were reversed by CHOP loss or overexpression of C/EBP-α in nude mice. Mechanistically, neriifolin suppressed the tumor growth by increasing DNA damage and apoptosis through CHOP-C/EBP-α signaling axis of ERS in prostate cancers. Taken together, these results suggest that cardiac glycoside neriifolin may be a potential tumor-specific chemotherapeutic agent in prostate cancer treatment.

Curcuminoids Attenuate Myocardial Ischemia-Reperfusion Injury by Regulating Total RNA M6a Levels: In Vitro Study.

OBJECTIVE: Myocardial ischemia-reperfusion (IR) injury is an unresolved medical problem with a high incidence. This study aims to analyze the novel molecular mechanism by which curcuminoids protect cardiomyocytes from IR injury. METHODS: A IR model In Vitro of rat cardiomyocytes H9c2 cells was structured. Curcumin (CUR) and its derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) treated H9c2 cells, and reactive oxygen species (ROS) production, viability, apoptosis, mitochondrial membrane potential (MMP), oxidative stress and total RNA m6A levels of H9c2 cells were detected by using DCFH-DA stain, CCK-8, flow cytometry, Hoechst 33342 stain, TMRM stain, ELISA and RTqPCR. FB23 was used in rescue experiments. RESULTS: IR significantly increased ROS production, decreased cell viability, and induced apoptosis, MMP loss, and oxidative stress. In addition, IR induced an increase in total RNA m6A levels and changes in m6A-related proteins expression. CUR (10 µM), DMC (10 µM) and BDMC (10 µM), significantly inhibited IR-induced ROS production, apoptosis, MMP loss and oxidative stress, and enhanced cell viability. Furthermore, CUR, DMC and BDMC altered the expression pattern of m6A-related proteins and reduced IR-induced total m6A levels. There was no significant difference in the effects of the three. CUR's protective effect was partially reduced by FB23. CONCLUSION: Curcuminoids attenuate myocardial IR injury by regulating total RNA m6A levels.

External validation of the GAP model in Chinese patients with idiopathic pulmonary fibrosis.

INTRODUCTION: The GAP model was widely used as a simple risk "screening" method for patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We sought to validate the GAP model in Chinese patients with IPF to evaluate whether it can accurately predict the risk for mortality. METHODS: A total of 212 patients with IPF diagnosed at China-Japan Friendship Hospital from 2015 to 2019 were enrolled. The latest follow-up ended in September 2022. Cumulative mortality of each GAP stage was calculated and compared based on Fine-Gray models for survival, and lung transplantation was treated as a competing risk. The performance of the model was evaluated in terms of both discrimination and calibration. RESULTS: The cumulative mortality in patients with GAP stage III was significantly higher than that in those with GAP stage I or II (Gray's test p < 0.0001). The Harrell c-index for the GAP calculator was 0.736 (95% CI: 0.667-0.864). The discrimination for the GAP staging system were similar with that for the GAP calculator. The GAP model overestimated the mortality rate at 1- and 2-year in patients classified as GAP stage I (6.90% vs. 1.77% for 1-year, 14.20% vs. 6.78% for 2-year). CONCLUSIONS: Our findings indicated that the GAP model overestimated the mortality rate in mild group.

Blood monocyte counts as a prognostic biomarker and predictor in Chinese patients with idiopathic pulmonary fibrosis.

Objectives: We sought to evaluate the prognostic value of blood routine parameters and biochemical parameters, especially inflammation-related biomarkers, and establish an inflammation-related prognostic model in Chinese patients with idiopathic pulmonary fibrosis (IPF). Material/methods: Patients diagnosed as IPF at Beijing Chaoyang Hospital and aged 40 years and older were consecutively enrolled from June 2000 to March 2015, and finally, a total of 377 patients were enrolled in the derivation cohort. The follow-up ended in December 2016. We used Cox proportional hazard model to calculate the hazard ratio (HR) and establish the prognostic model. The discrimination and calibration of the prognostic model were evaluated in an independent validation cohort enrolled from China-Japan Friendship Hospital between January 2015 and December 2019. Results: Multivariate analysis revealed that patients with elevated monocyte-to-red blood cell count ratio (MRR) and monocyte counts showed increased risk of mortality. The clinical-physiological-biomarker (CPB) index and CPB stage we established in this study were a significant predictor, and the C-index for CPB index and CPB stage in the validation cohort was 0.635 (95% CI: 0.558-0.712) and 0.619 (95% CI: 0.544-0.694), respectively. Patients in CPB stage III had the poorest survival. Conclusion: We developed and validated a new inflammation-related prognostic model (CPB index and CPB stage) which was integration of age, gender, FVC (%, predicted), DLCO (%, predicted), Charlson Comorbidity Index, and blood monocyte counts. This prediction model exhibited strong ability in predicting mortality in Chinese patients with IPF.

miR-21-5p/PRKCE axis implicated in immune infiltration and poor prognosis of kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC or ccRCC) is the most notorious subtype of renal cell carcinoma for its poor prognosis. Mounting evidence has highlighted the key role of PRKCE in the initiation and development of several types of human cancer, including kidney renal clear cell carcinoma (KIRC). However, the mechanism of PRKCE aberrant expression and the specific clinical correlation of PRKCE expression with immune cell infiltration in KIRC remains elusive. Therefore, we analyzed the relationship between PRKCE and KIRC using many databases, including Oncomine, TCGA, GTEx, TIMER, and GEO. We found that PRKCE decreased in KIRC tumor tissue compared to normal tissue. The Kaplan-Meier Plotter analysis and Univariate and Multivariate Cox analyses were used to evaluate the association between PRKCE and clinicopathological variables and prognosis. Low PRKCE expression was associated with poor survival and histologic grade, T stage, pathologic stage, and M stage. Besides, the C-indexes and calibration plots of the nomogram based on multivariate analysis showed an effective predictive performance for KIRC patients. In addition, PRKCE may be positively correlated with inflammation and negatively correlated with proliferation, metastasis, and invasion as identified by CancerSEA. Moreover, overexpression of PRKCE suppressed ACHN and Caki-1 cell proliferation, migration, and invasion in vitro. Additionally, methylation level data acquired from UALCAN, DiseaseMeth, CCLE, LinkedOmics, and MEXPRESS was used to investigate the relationship between PRKCE expression and PRKCE methylation level. Furthermore, upstream potential miRNA predictions were further performed to explore the mechanism of PRKCE decreased expression in KIRC using multiple online databases available on publicly assessable bioinformatics platforms. High PRKCE methylation levels and hsa-miR-21-5p may contribute to PRKCE low expression in KIRC. Finally, an analysis of immune infiltration indicated that PRKCE was associated with immune cell infiltration. Importantly, PRKCE may affect prognosis partially by regulating immune infiltration in KIRC. In summary, PRKCE may serve as a novel prognostic biomarker reflecting immune infiltration level and a novel therapeutic target in KIRC.

Donor with HLA-C2 is associated with acute rejection following liver transplantation in Southern Chinese.

Apart from presenting peptides to T cells, class I HLA molecules serve as ligands for killer cell immunoglobulin-like receptor (KIRs) and regulate the response of natural killer (NK) cells. The role played by HLA and KIR in the acute rejection (AR) following liver transplantation has been controversial. In this retrospective study, we assessed the influence of class I HLA alleles, HLA matching between donor-recipient pairs, recipient KIR and donor HLA ligands on AR following liver transplantation in southern Chinese. In total, 143 recipients and 78 donors obtained from a single transplant center were included in the study cohort. Thirty-three recipients with histologically confirmed AR were observed. We found that the incidence of AR did not correlate with donor or recipient class I HLA alleles and HLA matching. Neither recipient KIR gene nor the KIR genotype was associated with AR, moreover, high-resolution genotyping of 14 functional KIR genes of recipients showed that no KIR allele was independently associated with AR. However, the frequency of HLA-C2+ donor significantly increased in AR group compared with NAR group (52.9% vs. 24.6%, p = 0.03). In the presence of HLA-C2 by the donor allograft, AR was more frequently observed in recipients with normal expressed KIR2DS4 (43.8% vs. 15.0%, p = 0.03). Donor with HLA-C2 is therefore a major determinant of AR, which can confer risk effect in liver transplantation. Our findings can provide valuable clues for better understanding pathogenesis of AR and have important clinical implications in liver transplantation for Chinese.

CAF-derived exosomes transmitted Gremlin-1 promotes cancer progression and decreases the sensitivity of hepatoma cells to sorafenib.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of metastasis. An increasing number of studies have reported that cancer-associated fibroblasts (CAFs) have emerged as the largest component of the stroma and play a critical role in tumor-promoting processes. However, the effects of CAFs on cancer progression and the sensitivity of hepatoma cells to sorafenib are not well characterized. Here, we identified the proteome of CAF-derived exosomes, and unveiled that exosomal Gremlin-1 derived from CAFs contributes to epithelial-mesenchymal transition (EMT) of hepatoma cells and the decrease of the sorafenib sensitivity through regulating Wnt/ß-catenin and BMP signaling pathways. Compared to control subjects, the level of plasma exosomal Gremlin-1 was significantly increased in HCC patients. Further studies indicated that plasma exosomal Gremlin-1 may predict sorafenib response in HCC patients. Collectively, our findings uncover CAFs-derived Gremlin-1-rich exosomes promote EMT and decrease the sensitivity of hepatoma cells to sorafenib by Wnt/ß-catenin and BMP signaling.

Osteoblastic protein kinase D1 contributes to the prostate cancer cells dormancy via GAS6-circadian clock signaling.

Disseminated prostate cancer (PCa) is known to have a strong propensity for bone marrow. These disseminated tumor cells (DTCs) can survive in bone marrow for years without obvious proliferation, while maintaining the ability to develop into metastatic lesions. However, how DTCs kept dormant and recur is still uncertain. Here, we focus on the role of osteoblastic protein kinase D1 (PKD1) in PCa (PC-3 and DU145) dormancy using co-culture experiments. Using flow cytometry, western blotting, and immunofluorescence, we observed that in co-cultures osteoblasts could induce a dormant state in PCa cells, which is manifested by a fewer cell divisions, a decrease Ki-67-positive populations and a lower ERK/p38 ratio. In contrast, silencing of PKD1 gene in osteoblasts impedes co-cultured prostate cancer cell's dormancy ability. Mechanismly, protein kinase D1 (PKD1) in osteoblasts induces PCa dormancy via activating CREB1, which promoting the expression and secretion of growth arrest specific 6 (GAS6). Furthermore, GAS6-induced dormancy signaling significantly increased the expression of core circadian clock molecules in PCa cells, and a negative correlation of circadian clock proteins (BMAL1, CLOCK and DEC2) with recurrence-free survival is observed in metastatic prostate cancer patients. Interestingly, the expression of cell cycle factors (p21, p27, CDK1 and PCNA) which regulated by circadian clock also upregulated in response to GAS6 stimulation. Taken together, we provide evidence that osteoblastic PKD1/CREB1/GAS6 signaling regulates cellular dormancy of PCa cells, and highlights the importance of circadian clock in PCa cells dormancy.

A Novel N-Arylpyridone Compound Alleviates the Inflammatory and Fibrotic Reaction of Silicosis by Inhibiting the ASK1-p38 Pathway and Regulating Macrophage Polarization.

Silicosis is one of the potentially fatal occupational diseases characterized by respiratory dysfunction, chronic interstitial inflammation, and fibrosis, for which treatment options are limited. Previous studies showed that a novel N-arylpyridone compound named AKEX0011 exhibited anti-inflammatory and anti-fibrotic effects in bleomycin-induced pulmonary fibrosis; however, it is unknown whether it could also be effective against silicosis. Therefore, we sought to investigate the preventive and therapeutic roles of AKEX0011 in a silicosis rodent model and in a silica-stimulated macrophage cell line. In vivo, our results showed that AKEX0011 ameliorated silica-induced imaging lung damages, respiratory dysfunction, reduced the secretion of inflammatory and fibrotic factors (TNF-α, IL-1ß, IL-6, TGF-ß, IL-4, and IL-10), and the deposition of fibrosis-related proteins (collagen I, fibronectin, and α-SMA), regardless of early or advanced therapy. Specifically, we found that AKEX0011 attenuated silicosis by inhibiting apoptosis, blocking the ASK1-p38 MAPK signaling pathway, and regulating polarization of macrophages. In vitro, AKEX0011 inhibited macrophages from secreting inflammatory cytokines and inhibited apoptosis of macrophages in pre-treated and post-treated models, concurrent with blocking the ASK1-p38 pathway and inhibiting M1 polarization. Collectively, AKEX0011, as a novel N-arylpyridone compound, exerted protective effects for silica-induced pulmonary inflammation and fibrosis both in vivo and in vitro, and hence, it could be a strong drug candidate for the treatment of silicosis.