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Supplementary Table S9. The predicted miRNAs that bind with FAM225A according to DIANA Tools

Supplemental Table S1. qRT-PCR primers used in this study Supplemental Table S2. siRNA sequence used in this study Supplemental Table S3. Primers used for shRNA plasmid construction Supplemental Table S4. Primers used for truncation variants plasmid construction Supplemental Table S5. Primers sequence used for ChIP-PCR assay Supplemental Table S6. Probe sequence of TINCR in situ hybridization (ISH) Supplemental Table S7. Clinical characteristics of nasopharyngeal carcinoma patients according to the high and low expression of TINCR Supplemental Table S8. Univariate and multivariable Cox regression analysis of TINCR expression level and survival Supplemental Table S9. The top10 proteins found by mass spectrometry analysis in the antisense-TINCR group (negative control). Supplemental Table S10. The top10 proteins found by mass spectrometry analysis in the TINCR group. The bold portion shows the proteins that overlap antisense-TINCR

Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)–MAPK–MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR–ACLY–PADI1–MAPK–MMP2/9 axis as a potential therapeutic target in NPC.Significance:TINCR-mediated regulation of a PADI1–MAPK–MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.

Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which, FAM225A was one of the most upregulated lncRNAs in NPC. FAM225A significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within FAM225A and enhanced its RNA stability. FAM225A functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically, FAM225A functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target integrin β3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which FAM225A modulates ITGB3 expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC.Significance:These findings demonstrate the clinical significance of the lncRNA FAM225A in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.

Supplementary Table S1. qPCR primers used in this study Supplementary Table S2. The FAM225A expression level and grouping of samples based on GEO dataset (GSE12452) Supplementary Table S3. Primers used for shRNA plasmid construction Supplementary Table S4. Sequence of miRNA mimic or inhibitor used in this study Supplementary Table S5. Probe sequence of FAM225A in situ hybridization (ISH) Supplementary Table S7. Clinical characteristics of nasopharyngeal carcinoma patients according to the high and low expression of FAM225A. Supplementary Table S8. Univariate and multivariable Cox regression analysis of FAM225A expression level and survival. Supplementary Table S10. Inguinal lymph node metastasis in vivo.

Supplemental Figure S1. TINCR is upregulated in six other cancer types. Supplemental Figure S2. GSEA analyses results of TINCR silencing. Supplemental Figure S3. Overexpression of TINCR promotes NPC cell proliferation, metastasis and cisplatin resistance in vitro. Supplemental Figure S4. Overexpression of TINCR reverses the suppressive effects of TINCR knockdown on cell proliferation, cisplatin resistance and metastasis. Supplemental Figure S5. TINCR targets ACLY and impairs its ubiquitination degradation. Supplemental Figure S6. Silencing TINCR has no effects on the expressions of KAT3A and KAT3B. Supplemental Figure S7. The ACLY-binding motif CUGKR is critical for the role of TINCR in maintaining ACLY protein stability and lipid synthesis levels. Supplemental Figure S8. Acetyl-CoA is responsible for TINCR-mediated NPC progression and chemoresistance. Supplemental Figure S9. Correlation between TINCR and PADI1 expression in 16 other cancer types from the TCGA database. Supplemental Figure S10. Silencing TINCR decreases the proteolytic activities of MMP2/9, but had no effects on H3K27ac levels at MMP2/9 promoters. Supplemental Figure S11. IGFBP3 is overexpressed in NPC

Supplementary Figure S1. FAM225A is overexpressed in NPC and other tumor types. Supplementary Figure S2. Silencing METTL3 resulted in the decreased m6A level of total RNA. Supplementary Figure S3. FAM225A promotes NPC cell proliferation, migration and invasion in vitro. Supplementary Figure S4. FISH assay showed that FAM225A was mainly located in cytoplasmic. Supplementary Figure S5. FAM225A acts as a ceRNA for miR-590-3p and miR-1275. Supplementary Figure S6. The expression of FAM225A is negatively correlated with miR-590-3p and miR-1275 expression. Supplementary Figure S7. Silencing of miR-590-3p and miR-1275 endows NP69 and N2Tert cells with carcinogenicity in vitro. Supplementary Figure S8. miR-590-3p/miR-1275 are responsible for FAM225A-mediated proliferation, migration and invasion. Supplementary Figure S9. Correlation between FAM225A and ITGB3 expression in 12 other cancer types from the TCGA database. Supplementary Figure S10. FAM225A promotes NPC cell metastasis in vivo. Supplementary Figure S11. ITGB3 is responsible for FAM225A-meidated tumorigenesis and metastasis in vivo.

BackgroundThe current ECG criteria for diagnosing left bundle branch block (LBBB) still cannot fully differentiate between true and false blocks. The absence or presence of an LBBB is key in improving the response rate of clinical cardiac resynchronization therapy (CRT).MethodsWe hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We performed high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT and whose preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the bottom of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We compared the clinical characteristics, the real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, the QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio between the two groups. Through ROC correlation analysis of Nw/LVd and t-LBBB, the sensitivity, specificity, and cut-off value of Nw/LVd diagnostic authenticity were obtained.ResultsTwenty-five patients were recruited to the t-LBBB group, and 12 to the f-LBBB group. In the t-LBBB group, the first peak of the QRS notch corresponded to the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak corresponded to the depolarization of the left ventricular free wall. In the f-LBBB group, the first peak corresponded to the depolarization of the right ventricle and most of the left ventricle, the second peak corresponded to the depolarization of the latest, locally-activated myocardium of the left ventricle, and the trough was caused by the off-peak delayed activation of the left ventricle. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms,PPConculuionUsing the current diagnostic criteria of LBBB, increasing the Nw/LVd value can diagnose LBBB more effectively.

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.

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.

The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database (GES12452, GSE12349, and GSE61218) and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3′-UTR, then IGF2BP2 bound and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect. These results together demonstrate the role of VIRMA as an m6A writer that modulates E2F7 expression to control the transcription program of NPC, unveiling an m6A modulator that is essential for NPC tumorigenesis and metastasis.

Background Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. Methods Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. Results It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. Conclusions Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.

Background Conditional survival (CS) provides dynamic prognostic estimates by considering the patients existing survival time. Since CS for endemic nasopharyngeal carcinoma (NPC) is lacking, we aimed to assess the CS of endemic NPC and establish a web‐based calculator to predict individualized, conditional site‐specific recurrence risk. Methods Using an NPC‐specific database with a big‐data intelligence platform, 10,058 endemic patients with non‐metastatic stage I–IVA NPC receiving intensity‐modulated radiotherapy with or without chemotherapy between April 2009 and December 2015 were investigated. Crude CS estimates of conditional overall survival (COS), conditional disease‐free survival (CDFS), conditional locoregional relapse‐free survival (CLRRFS), conditional distant metastasis‐free survival (CDMFS), and conditional NPC‐specific survival (CNPC‐SS) were calculated. Covariate‐adjusted CS estimates were generated using inverse probability weighting. A prediction model was established using competing risk models and was externally validated with an independent, non‐metastatic stage I–IVA NPC cohort undergoing intensity‐modulated radiotherapy with or without chemotherapy (n = 601) at another institution. Results The median follow‐up of the primary cohort was 67.2 months. The 5‐year COS, CDFS, CLRRFS, CDMFS, and CNPC‐SS increased from 86.2%, 78.1%, 89.8%, 87.3%, and 87.6% at diagnosis to 87.3%, 87.7%, 94.4%, 96.0%, and 90.1%, respectively, for an existing survival time of 3 years since diagnosis. Differences in CS estimates between prognostic factor subgroups of each endpoint were noticeable at diagnosis but diminished with time, whereas an ever‐increasing disparity in CS between different age subgroups was observed over time. Notably, the prognoses of patients that were poor at diagnosis improved greatly as patients survived longer. For individualized CS predictions, we developed a web‐based model to estimate the conditional risk of local (C‐index, 0.656), regional (0.667), bone (0.742), lung (0.681), and liver (0.711) recurrence, which significantly outperformed the current staging system (P < 0.001). The performance of this web‐based model was further validated using an external validation cohort (median follow‐up, 61.3 months), with C‐indices of 0.672, 0.736, 0.754, 0.663, and 0.721, respectively. Conclusions We characterized the CS of endemic NPC in the largest cohort to date. Moreover, we established a web‐based calculator to predict the CS of site‐specific recurrence, which may help to tailor individualized, risk‐based, time‐adapted follow‐up strategies.

Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted de novo lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)–MAPK–MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR–ACLY–PADI1–MAPK–MMP2/9 axis as a potential therapeutic target in NPC. Significance: TINCR-mediated regulation of a PADI1–MAPK–MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.

As the most predominant RNA epigenetic regulation in eukaryotic cells, N(6)-methyladenosine (m(6)A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m(6)A regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms’ tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide m(6)A target of WTAP. WTAP-mediated m(6)A modification of DIAPH1-AS1 enhanced its stability relying on the m(6)A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 m(6)A methylation is required for NPC tumorigenesis and metastasis.

A coded-exposure-pixel image sensor for computational imaging applications is presented. Each frame exposure time is divided into ${N}$ subframes. Within each subframe, each pixel sorts photo-generated charge into two charge taps depending on that pixel’s 1-bit binary code. ${N}$ global updates of arbitrary pixel-wise codes are implemented in each frame to enable ${N}$ short global pixel-specific subexposures within one frame. To make these subexposures global, two latches per pixel are utilized in a pipelined fashion. The code for the next subframe is loaded into latch 1 in a row parallel fashion, while the code for the current subframe is being applied by latch 2 globally for photo-generated charge sorting during the current subexposure. A $280^{H}\times 176^{V}$ image sensor prototype with $11.2{\text{-}}\mu \text{m}$ pixel pitch has been fabricated in a $0.11{\text{-}}\mu \text{m}$ CMOS image sensor (CIS) technology. The image sensor has been demonstrated in two computational photography applications, each using only a single frame of a video: 1) computing both albedo (a measure of reflectivity) and 3-D depth maps by means of structured-light imaging and 2) computing surface normals (3-D orientations) map by means of photometric stereo imaging. These demonstrations experimentally validate some of the unique capabilities of this computational image sensor, such as accurate 3-D visual scene reconstruction using only one camera, while maintaining its native specifications: the full spatial resolution and the maximum frame rate.

Traditional Chinese medicine (TCM) has wide application and important functions in curing many diseases, but a great number of herb residues are usually generated after its manufacture and usage. Without proper and timely treatment, these traditional Chinese medicinal herb (TCMH) residues will cause some environmental pollution. In addition to treatment, bioresources utilization of TCMH residues is also important for its great potential as a suitable feedstock for the production of energy, materials, and chemicals. In this situation, advanced and well-designed solid waste management is important to make the TCM industry environmentally friendly and economically attractive. In this review article, the recent progress focusing on various methods for TCMH residues treatment and bioresources utilization are introduced in detail. In particular, the technologies for thermochemical conversion and biochemical conversion of TCMH residues are mainly focused on in order to show how to fulfill effective and efficient bioresources utilization. Besides, some other technologies which are suitable for the treatment and bioresources utilization of TCMH residues are presented as well. Finally, some industrial prospects are given from the economic, operational, and environmental aspects for the further development of treatment and bioresources utilization of TCMH residues. Overall, this work can provide some systematical and comprehensive information for the development of technologies that help sustainably manage the herb residues generated in the TCM industry.

Purpose To develop predictive models with dosimetric and clinical variables for temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Materials and methods Data of 8194 NPC patients who received IMRT-based treatment were retrospectively reviewed. TLI was diagnosed by magnetic resonance imaging. Dosimetric factors were selected by penalized regression and machine learning, with area under the receiver operating curve (AUC) calculated. Cox proportional hazards models containing the most predictive dosimetric factor with/without clinical variables were performed. A nomogram was generated as a visualization of Cox regression for predicting TLI-free survival. Results During median follow-up of 66.8 months (interquartile range [IQR] 54.2–82.2 months), 12.1% of patients (989/8194) developed TLI. Median latency from IMRT to TLI was 36 months (IQR 28–47 months). D0.5cc (dose delivered to 0.5-cm3 temporal-lobe volume) was the most predictive dosimetric factor (AUC: 0.799). Tolerance dose for 5% and 50% probabilities to develop TLI in 5 years were 65.06 Gy (95% confidence interval [CI]: 64.19–65.92) and 89.75 Gy (95% CI: 87.39–92.11), respectively. A nomogram comprising age, T stage, and D0.5cc significantly outperformed the model with only D0.5cc in predicting TLI (C-index: 0.78 vs. 0.737 in train set; 0.775 vs. 0.73 in test set; both P Conclusions D0.5cc of 65.06 Gy was the tolerance dose of the temporal lobe. Reducing D0.5cc decreased risk of TLI, especially in older patients with advanced T stage. The nomogram could predict TLI precisely and allow individualized follow-up management.

Objectives To screen subgroup potentially benefiting from cumulative cisplatin dose (CCD) ≥ 200 mg/m2 during concurrent chemoradiotherapy (CCRT) of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) receiving induction chemotherapy (IC) and CCRT. Materials and Methods In total, 2 063 patients with non-disseminated LA-NPC diagnosed from 2009 to 2015 receiving IC plus CCRT were enrolled. Patients were restaged based on proposed stage groupings and risk groupings was established. After propensity score matching, survival outcomes were compared within different risk groupings with 200 mg/m2 CCD. Post-IC gross primary tumor (GTVp) and lymph node (GTVnd) volumes were calculated from planning computed tomography. The role of risk groupings and post-IC tumor volume to CCD was explored. Results Compared with the low-risk group, the high-risk group showed poor survival outcomes in terms of 5-year progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). CCD ≥ 200 mg/m2 improved survival in terms of 5-year PFS, OS and DMFS in the high-risk group but not in the low-risk group. High-risk patients with unfavorable response to IC benefited from CCD ≥ 200 mg/m2 with respect to PFS and DMFS; while those in low-risk group or with favorable response to IC didn’t. Conclusions Risk groupings was effective for risk stratification. Combining risk groupings and post-IC tumor volume is a simple and useful method to guide individualized CCD treatment of CCRT for patients with LA-NPC receiving IC and CCRT. CCD ≥ 200 mg/m2 may be indicated for high-risk patients with unfavorable response to IC.

BACKGROUND The current study was performed to investigate whether circulating cell-free Epstein-Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with nasopharyngeal carcinoma (NPC). METHODS The authors identified a total of 1984 nondisseminated NPC patients from an institutional big-data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination). RESULTS During follow-up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%-96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1-9.5 months). In addition, of the 278 cfEBV DNA-positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long-term monitoring. CONCLUSIONS Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases.

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.

The diagnostic accuracy of existing transfer learning-based bearing fault diagnosis methods is high in the source condition, but accuracy in the target condition is not guaranteed. These methods mainly focus on the whole distribution of bearing source domain data and target condition data, ignoring the transfer learning of each kind of bearing fault data, which may lead to lower diagnostic accuracy. To overcome these limitations, we propose a transfer learning fault diagnosis model based on a deep Fully Convolutional Conditional Wasserstein Adversarial Network (FCWAN). The proposed model addresses the described problems separately: (1) A random-sampling map classification and difference classifier are used to handle the first limitation. (2) A label is introduced into the domain of adversarial learning to strengthen the supervision of the learning process and the effect of category field alignment, thus overcoming the second limitation. Experimental results demonstrate the superiority of this method over existing methods.

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.

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. Methods: 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. Results: 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