Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous ...cell carcinoma (HNSC) is urgently required.
Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed.
We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters.
This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.
Nowadays, traditional Chinese medicine plays an important role in curing many diseases, and its market expands quickly due to the potential great profits it can bring. To be an attractive industry, ...both economic and environmental aspects should be considered. As wastewater is usually generated from traditional Chinese medicine processing and utilization, its treatment is one of the hot research topics in environmental engineering currently. Many technologies can be applied for the treatment of this wastewater, but the technical background and performance vary greatly especially for different kinds of wastewater. In this situation, a systematical and comprehensive summary for the development of these technologies is necessary. In this review article, the sources of wastewater from the processing and utilization of traditional Chinese medicine are introduced firstly to show where this wastewater comes from. And then, the recent advances on the technologies for the treatment of this wastewater are introduced in detail to show what technologies can be applied. At last, the future outlook for the development of these treatment technologies is given to discuss how to fulfill their industrial application. Overall, this review article can present some important information for building a clean and sustainable traditional Chinese medicine industry.
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•Traditional Chinese medicine processing and utilization generate wastewater.•Potential sources of different kinds of wastewater are introduced.•Technologies for this wastewater treatment are discussed systematically.•Outlook for fulfilling industrial application of different technologies is given.•Effective and efficient technologies integration is shown comprehensively.
PurposeExamining the influence of ethnic food tourists' perception of hygiene on their attitudinal loyalty formation is the purpose of this study. Specifically, How to demonstrate touristsʼ ...perception of ethnic food hygiene is the key question, and moreover, the study also investigates whether and how the stages of attitudinal loyalty in this study, which are perceived authenticity, positive emotion, and perceived value, are illustrated in this mechanism and are affected by tourist perceptions of hygiene?Design/methodology/approachBy engaging in the critical debate around the topic of hygiene perception, this study explores the influence of this factor on tourist's attitudinal loyalty, including the cognitive, affective and conative aspects, to ethnic food through the adoption of perceived authenticity, positive emotion and perceived value. A survey was conducted at the Xijiang Miao Village, a very popular ethnic tourism destination in China.FindingsThis study reveals that ethnic food tourists' perceptions of hygiene have five dimensions. One of these plays a direct predictor role in developing effective conative loyalty (perceived value). Tourists' perceptions of authenticity and positive emotion representing cognitive and affective loyalty are confirmed in their direct effect on conative loyalty as well. The five dimensions of perceptions of hygiene identified have varying degrees of influence on the three stages of attitudinal loyalty.Originality/valueThe unique contribution of this study lies in two points: (1) it has discovered the way that tourists' perceptions of the hygienic preparation of ethnic food in the ethnic destination is constructed, and (2) it investigated the relationship between tourists' perceptions of hygiene and the three stages of attitudinal loyalty.
With the current rapid economic development, restaurant practitioners need to pay attention to the issue of how fine-dining restaurants can achieve sustainable operations in the presence of fierce ...competition. Fine-dining restaurants have gradually become a reflection of consumers’ self-image; therefore, this study combines the VAB framework, self-congruity theory, and generational theory to investigate the relationships among perceived quality, customers’ self-image congruity, and their willingness to pay a price premium (WTP-PP). Current research uses generation as a moderator to explore the intergenerational differences between Gen X and Gen Y. We adopted Smart-PLS to conduct SEM and MGA. The results of this study showed that the quality of the atmosphere and food induced actual, ideal, and ideal social self-image congruity, while the quality of the service could not only induce the above three aspects of self-consistency but also induce social self-image congruity and have a significant positive impact on WTP-PP. Meanwhile, WTP-PP was also significantly affected by actual self-image congruity and ideal self-image congruity. Furthermore, Gen Yers cared more about the atmosphere quality than Gen X. Contrarily, Gen Xers valued food quality more than Gen Y.
Rab GTPase 3C (RAB3C) is a peripheral membrane protein that is involved in membrane trafficking (vesicle formation) and cell movement. Recently, researchers have noted the exocytosis of RAB proteins, ...and their dysregulation is correlated with drug resistance and the altered tumor microenvironment in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in the carcinogenicity of colorectal cancer (CRC) remain unknown. Researchers have used various in silico datasets to evaluate the expression profiles of RAB family members. We confirmed that RAB3C plays a key role in CRC progression. Its overexpression promotes exocytosis and is related to the resistance to several chemotherapeutic drugs. We established a proteomic dataset based on RAB3C, and found that dystrophin is one of the proteins that is upregulated with the overexpression of RAB3C. According to our results, RAB3C‐induced dystrophin expression promotes vesicle formation and packaging. A connectivity map predicted that the cannabinoid receptor 2 (CB2) agonists reverse RAB3C‐associated drug resistance, and that these agonists have synergistic effects when combined with standard chemotherapy regimens. Moreover, we found high dystrophin expression levels in CRC patients with poor survival outcomes. A combination of the dystrophin and RAB3C expression profiles can serve as an independent prognostic factor in CRC and is associated with several clinicopathological parameters. In addition, the RAB3C–dystrophin axis is positively correlated with the phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha isoform (PIK3CA) genetic alterations in CRC patients. These findings can be used to provide novel combined therapeutic options for the treatment of CRC.
The authors found that RAB3C overexpression induces dystrophin expression to promote vesicle formation and packaging for increased exocytosis, is related to drug resistance and is correlated with PIK3CA/KRAS mutation status in colon cancer. RAB3C‐based omics profiles identified inhibitors that directly interact with dystrophin and found synergy with existing chemotherapy regimens.
Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. It has been reported playing roles in multiple malignant behaviors including ...proliferation, migration, metastasis and chemoresistance. However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported yet.
circZKSCAN1 level was detected in HCC tissue microarrays to clarify its prognostic values. Gain and loss function experiments were applied to investigate the role of circZKSCAN1 in HCC stemness. Bioinformatic analysis was used to predict the possible downstream RNA binding protein and further RNA immunoprecipitation sequencing was carried out to identify the RBP-regulated genes.
The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC. Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and β-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restrain the transcriptional activity of Wnt signaling. In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1.
Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5-circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment.
The in-situ utilization of sludge mixed liquor was innovatively applied in microbial fuel cell and membrane bioreactor (MFC-MBR) coupling system. MFC-MBR coupling systems with different return flow ...ratio were designed to investigate the effects of return flow on bioelectricity generation and subsequently membrane fouling mitigation. The results indicated that bioelectricity generation was largely enhanced with the increasing return flow ratio. Furthermore, the slow growth of the transmembrane pressure (TMP) was found in MFC-MBR coupling systems that with return flow ratios of 0.50 and 0.75, respectively (0.66 kPa/d and 0.57 kPa/d). It was evident from the declined absolute value of zeta potential in systems with return flow ratio, which enlarged the flocculation of sludge particles and was in accordance with the particle size distribution. The increase rate of soluble microbial products (SMP) and extracellular polymeric substances (EPS) were also significantly dropped while the ratio of protein to polysaccharide in SMP and EPS rose in MFC-MBR coupling systems with return flow. Importantly, Bacteroidetes and Chlorobiaceae were more abundant in MFC-MBR coupling systems with higher return flow ratios. Thus, MFC-MBR coupling system with internal reflux of sludge mixed liquor was effective in improving bioelectricity generation and minimizing membrane fouling.
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•The recirculation of sludge mixture can boost bioelectricity generation of MFC-MBR.•MFC-MBR with mixed liquor recirculation obviously improved COD and NH4+-N removal.•Sludge flocs size and zeta potential increased in MFC-MBR with return flow.•Recirculation contributed to the decrease of SMP\EPS content and the rise of PN/PS.•Membrane fouling was greatly mitigated in MFC-MBR with higher recirculation ratios.
In this study, bacterial cellulose was synthesized by Taonella mepensis from traditional Chinese medicinal herb residues hydrolysate. To overcome the inhibitory effect of fermentation environment, ...in-situ fermentation with gellan gum adding was carried out for the first time. After 10 days' static fermentation, both high-acyl gellan gum and low-acyl gellan gum adding showed certain beneficial effects for bacterial cellulose production that the highest bacterial cellulose yield (0.866 and 0.798 g/L, respectively) was 59% and 47% higher than that (0.543 g/L) without gellan gum adding. Besides, gellan gum based bacterial cellulose showed some better texture characteristics. Gellan gum was loaded in the nano network of bacterial cellulose, and gellan gum adding had some influence on the crystal structure and thermal degradation behaviors of bacterial cellulose but affected little on its functional groups. Overall, this in-situ fermentation technology is attractive for bacterial cellulose production from low-cost but inhibitory substrates.
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•Traditional Chinese medicinal herb residues hydrolysate was used as substrate.•Bacterial cellulose was produced by in-situ fermentation with gellan gum adding.•The effect of both high-acyl gellan gum and low-acyl gellan gum was evaluated.•Gellan gum adding can overcome the inhibition of fermentation environment.•Bacterial cellulose yield and performance can be promoted by gellan gum adding.
Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant disease with the complex immune microenvironment, which ultimately influence clinic outcomes of patients. However, the spatial ...expression patterns of diverse immune cells among tumor microenvironment remain to be further deciphered.
Spatial transcriptomics sequencing (ST) was implemented on two portions of HCC specimens. Differentially expressed genes, cell cycle phases, epithelial-mesenchymal features, pseudo-time and immune infiltration analysis were applied to demonstrate the intratumor heterogeneity and define the specific immune-related regions, and the results were further validated by a second analysis on another ST study.
and
experiments were conducted to confirm the functional mechanisms of key molecules such as CCL15, CCL19 and CCL21. Clinical tissue samples were used to assess their potential prognostic and therapeutic values.
Totally, 7553 spots were categorized into 15 subsets by hierarchical clustering, and malignant subsets with intratumor heterogeneity phenotypes were identified. Spatial heterogeneity from distinct sectors highlights specific chemokines: CCL15 is remarkable in the core region of the carcinoma sector and facilitates the immunosuppressive microenvironment by recruiting and polarizing M2-like macrophages
and
; High expression of CCL15 and CD163 respectively predicts poor prognosis of HCC patients, and the combined application of them has better predictive value. CCL19 and CCL21, sharing similar spatial expression patterns, are highly-correlated and prominent in the immune infiltration enrichment and recruit CD3
T cells and CD20
B cells to inhibit the growth of HCC, indicating a good prognosis of HCC patients.
Taken together, our studies preliminarily reveal intratumor heterogeneity of HCC based on ST techniques and unravel the previously unexplored spatial expression patterns in the immune microenvironment. We also highlight the clinical significance and spatial discrepancy of key molecules, providing novel insight for further developing therapeutic strategies in HCC.
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