High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Chloroplast biogenesis involves spatial coordination of nuclear and organellar gene expression in Chlamydomonas.

The localization of translation can direct the polypeptide product to the proper intracellular compartment. Our results reveal translation by cytosolic ribosomes on a domain of the chloroplast envelope in the unicellular green alga Chlamydomonas (Chlamydomonas reinhardtii). We show that this envelope domain of isolated chloroplasts retains translationally active ribosomes and mRNAs encoding chloroplast proteins. This domain is aligned with localized translation by chloroplast ribosomes in the translation zone, a chloroplast compartment where photosystem subunits encoded by the plastid genome are synthesized and assembled. Roles of localized translation in directing newly synthesized subunits of photosynthesis complexes to discrete regions within the chloroplast for their assembly are suggested by differences in localization on the chloroplast of mRNAs encoding either subunit of the light-harvesting complex II or the small subunit of Rubisco. Transcription of the chloroplast genome is spatially coordinated with translation, as revealed by our demonstration of a subpopulation of transcriptionally active chloroplast nucleoids at the translation zone. We propose that the expression of chloroplast proteins by the nuclear-cytosolic and organellar genetic systems is organized in spatially aligned subcompartments of the cytoplasm and chloroplast to facilitate the biogenesis of the photosynthetic complexes.

Mixed Mutual Transfer for Long-Tailed Image Classification.

Real-world datasets often follow a long-tailed distribution, where a few majority (head) classes contain a large number of samples, while many minority (tail) classes contain significantly fewer samples. This imbalance creates an information disparity between head and tail classes, which can negatively impact the performance of deep networks. Some transfer knowledge techniques attempt to mitigate this gap by generating additional minority samples, either through oversampling the tail classes or transferring knowledge from the head classes to the tail classes. However, these methods often restrict the diversity of the generated minority samples, primarily focusing on transferring information only to the tail classes. This paper introduces a simple yet effective method for long-tailed classification, called mixed mutual transfer (MMT), which facilitates the mutual transfer of knowledge between head and tail classes by blending samples. The core idea of our method is to create new samples by blending head and tail samples. Head samples are selected using a uniform sampler that retains the long-tailed distribution, while tail samples are selected using a differential sampler that reverses the long-tailed distribution to alleviate imbalance. Our approach aims to diversify both tail and head classes. During the training phase, we utilize the generated samples to update the original dataset for training deep networks. Mixed mutual transfer simultaneously enhances the performance of both head and tail classes. Experimental results on various class-imbalanced datasets show that the proposed method significantly outperforms existing methods, demonstrating its effectiveness in improving the performance of long-tailed deep networks.

Adaptive Top-K Algorithm for Medical Conversational Diagnostic Model.

With advancements in computing technology and the rapid progress of data science, machine learning has been widely applied in various fields, showing great potential, especially in digital healthcare. In recent years, conversational diagnostic systems have been used to predict diseases through symptom checking. Early systems predicted the likelihood of a single disease by minimizing the number of questions asked. However, doctors typically perform differential diagnoses in real medical practice, considering multiple possible diseases to address diagnostic uncertainty. This requires systems to ask more critical questions to improve diagnostic accuracy. Nevertheless, such systems in acute medical situations need to process information quickly and accurately, but the complexity of differential diagnosis increases the system's computational cost. To improve the efficiency and accuracy of telemedicine diagnostic systems, this study developed an optimized algorithm for the Top-K algorithm. This algorithm dynamically adjusts the number of the most likely diseases and symptoms by real-time monitoring of case progress, optimizing the diagnostic process, enhancing accuracy (99.81%), and increasing the exclusion rate of severe pathologies. Additionally, the Top-K algorithm optimizes the diagnostic model through a policy network loss function, effectively reducing the number of symptoms and diseases processed and improving the system's response speed by 1.3-1.9 times compared to the state-of-the-art differential diagnosis systems.

scQCEA: a framework for annotation and quality control report of single-cell RNA-sequencing data.

BACKGROUND: Systematic description of library quality and sequencing performance of single-cell RNA sequencing (scRNA-seq) data is imperative for subsequent downstream modules, including re-pooling libraries. While several packages have been developed to visualise quality control (QC) metrics for scRNA-seq data, they do not include expression-based QC to discriminate between true variation and background noise. RESULTS: We present scQCEA (acronym of the single-cell RNA sequencing Quality Control and Enrichment Analysis), an R package to generate reports of process optimisation metrics for comparing sets of samples and visual evaluation of quality scores. scQCEA can import data from 10X or other single-cell platforms and includes functions for generating an interactive report of QC metrics for multi-omics data. In addition, scQCEA provides automated cell type annotation on scRNA-seq data using differential gene expression patterns for expression-based quality control. We provide a repository of reference gene sets, including 2348 marker genes, which are exclusively expressed in 95 human and mouse cell types. Using scRNA-seq data from 56 gene expressions and V(D)J T cell replicates, we show how scQCEA can be applied for the visual evaluation of quality scores for sets of samples. In addition, we use the summary of QC measures from 342 human and mouse shallow-sequenced gene expression profiles to specify optimal sequencing requirements to run a cell-type enrichment analysis function. CONCLUSIONS: The open-source R tool will allow examining biases and outliers over biological and technical measures, and objective selection of optimal cluster numbers before downstream analysis. scQCEA is available at https://isarnassiri.github.io/scQCEA/ as an R package. Full documentation, including an example, is provided on the package website.

A wheat WRKY transcription factor TaWRKY17 enhances tolerance to salt stress in transgenic Arabidopsis and wheat plant.

WRKY transcription factors are essential to plant growth, development, resistance, and the regulation of metabolic pathways. In this study, we characterized TaWRKY17, a WRKY transcription factor from wheat, which was differentially expressed in various wheat organs and was up-regulated by salt, drought, hydrogen peroxide (H2O2) and abscisic acid (ABA) treatment. To analyze TaWRKY17 function under salt stress, we obtained stable T3 generation transgenic Arabidopsis and wheat TaWRKY17 overexpression plants. TaWRKY17 overexpression in Arabidopsis and wheat caused a significant plant salt-stress tolerance enhancement. Under salt stress, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities were elevated in transgenic Arabidopsis and wheat plants compared with the wild type (WT), whereas H2O2 and malondialdehyde (MDA) accumulation was reduced in the transgenic lines. Moreover, ABA/reactive oxygen species (ROS)-related, and stress-response genes were regulated in the transgenic wheat plants, increasing tolerance to salt stress. The transgenic wheat plants were highly sensitive to ABA during seed germination and early seedling growth. In addition, TaWRKY17 virus-induced gene silencing (VIGS) decreased salt tolerance. These results showed that TaWRKY17 enhances salt tolerance by regulating ABA/ROS-related, and stress-response genes and increasing anti-oxidative stress capabilities. Therefore, this gene could be a target for the genetic modification of wheat.

An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome.

Hepatitis B virus (HBV) is one of the smallest human DNA viruses and its 3.2 Kb genome encodes multiple overlapping open reading frames, making its viral transcriptome challenging to dissect. Previous studies have combined quantitative PCR and Next Generation Sequencing to identify viral transcripts and splice junctions, however the fragmentation and selective amplification used in short read sequencing precludes the resolution of full length RNAs. Our study coupled an oligonucleotide enrichment protocol with state-of-the-art long read sequencing (PacBio) to identify the repertoire of HBV RNAs. This methodology provides sequencing libraries where up to 25 % of reads are of viral origin and enable the identification of canonical (unspliced), non-canonical (spliced) and chimeric viral-human transcripts. Sequencing RNA isolated from de novo HBV infected cells or those transfected with 1.3 × overlength HBV genomes allowed us to assess the viral transcriptome and to annotate 5' truncations and polyadenylation profiles. The two HBV model systems showed an excellent agreement in the pattern of major viral RNAs, however differences were noted in the abundance of spliced transcripts. Viral-host chimeric transcripts were identified and more commonly found in the transfected cells. Enrichment capture and PacBio sequencing allows the assignment of canonical and non-canonical HBV RNAs using an open-source analysis pipeline that enables the accurate mapping of the HBV transcriptome.

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.

SCARNA10 regulates p53 acetylation-dependent transcriptional activity.

The tumor suppressor p53 is involved in variety of cell progresses including cell cycle arrest, apoptosis, DNA repair, senescence, cell metabolism and ferroptosis. Here, we identified lncRNA SCARNA10 (Small Cajal Body-Specific RNA 10) as a novel cellular factor that interacts with the DNA binding domain (DBD) of p53. Upon binding the DBD of p53 and CREB-binding protein (CBP), SCARNA10 promotes the acetylation of p53, and activates p53-mediated transcriptional activation. Overexpress or knockdown SCARNA10 leads to up (or down)-regulation of p53-mediated transcriptional activation, whereas not affecting p53 protein levels. Moreover, SCARNA10 directly activates transcription by increasing the acetylation of p53 C-terminal domain (CTD) without affecting p53 phosphorylation at Ser15. These results indicate that SCARNA10 is a novel factor which regulates p53 acetylation-dependent transcriptional activity and tumor suppression.

Genomic Landscapes of Epstein-Barr Virus in Pulmonary Lymphoepithelioma-Like Carcinoma.

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome data set of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared with the reference genome (NC_007605), a total of 3,995 variations were detected across pLELC-derived EBV sequences, with the mutational hot spots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC (P < 2.56 × 10-05, Bonferroni correction), with the top signal of single nucleotide polymorphism (SNP) coordinate T7327C (OR = 1.22, P = 2.39 × 10-15) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. IMPORTANCE Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare, distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences data set from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV's role in pLELC tumorigenesis.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Association of body fat percentage with kidney stone Disease: a cross-sectional and longitudinal study among bus drivers.

BACKGROUND: The association between body fat percentage (BFP) and kidney stone disease (KSD) among bus drivers has not been explored in the existing literature. Thus, this study was conducted to explore the influence of BFP on the risk of KSD as well as KSD development for bus drivers to fill the research gap. METHODS: A cross-sectional and longitudinal cohort study was designed. In total, 3433 bus drivers were included in the cross-sectional analyses, and 1864 bus drivers without KSD at baseline and with regular follow-up were included in the longitudinal cohort study. RESULTS: During a median follow-up of 2.9 years, KSD occurred in 15.0% of bus drivers. Multivariate logistic analysis found that each 5% higher BFP was not only significantly related with higher odds of KSD (odds ratio [OR] = 1.48), but also associated with higher odds of developing KSD (OR = 1.27). The risk of prevalent KSD in obesity group based on BFP was 2.47 times of the normal group; and the corresponding risk of developing KSD was 1.61 times. For obesity bus drives with age < 40, the corresponding risk increased to 4.54 times. CONCLUSION: Bus drivers were reported to have a high prevalence of KSD as well as development of KSD. As a significant predictive factor for KSD, BFP can be used to monitor and prevent bus drivers from kidney stone formation. Bus drivers in obesity group based on BFP, especially with age < 40 years should become priority subjects for targeted prevention.

Genomic landscape of Epstein-Barr virus in familial nasopharyngeal carcinoma.

To better understand the genomic characteristics of Epstein-Barr virus (EBV) in familial nasopharyngeal carcinoma (NPC), we sequenced the EBV genomes by whole-genome capture in 38 unrelated patients with NPC family history in first-degree relatives and 47 healthy controls, including 13 with family history and 34 without. Compared with type 1 reference genome, mutation hotspots were observed in the latent gene regions of EBV in familial NPC cases. Population structure analysis showed that one cluster has a higher frequency in familial cases than in controls (OR=5.33, 95 % CI 2.50-11.33, P=1.42×10-5), and similar population structure composition was observed among familial and sporadic NPC cases in high-endemic areas. By genome-wide association analysis, four variants were found to be significantly associated with familial NPC. Consistent results were observed in the meta-analysis integrating two published case-control EBV sequencing studies in NPC high-endemic areas. High-risk haplotypes of EBV composed of 34 variants were associated with familial NPC risk (OR=13.85, 95 % CI 4.13-46.44, P=2.06×10-5), and higher frequency was observed in healthy blood-relative controls with NPC family history (9/13, 69.23 %) than those without family history (16/34, 47.06%). This study suggested the potential contribution of EBV high-risk subtypes to familial aggregation of NPC.

Burden, trends, and risk factors for breast cancer in China from 1990 to 2019 and its predictions until 2034: an up-to-date overview and comparison with those in Japan and South Korea.

BACKGROUND: The difference in epidemiological characteristics of breast cancer (BC) across countries is valuable for BC management and prevention. The study evaluated the up-to-date burden, trends, and risk factors of BC in China, Japan and South Korea during 1990-2019 and predicted the BC burden until 2034. METHODS: Data on incident cases, deaths, disability-adjusted life-years (DALYs) and age-standardized rate (ASR) of BC were extracted from the Global Burden of Disease Study 2019. Trend analysis and prediction until 2034 were conducted by estimated annual percentage change and a Bayesian age-period-cohort model, respectively. Besides, the attributable burden to BC risk factors was also estimated. RESULTS: In 2019, the number of BC incident cases, deaths and DALYs in China were 375,484, 96,306 and 2,957,453, respectively. The ASR of incidence increased, while that of death and DALYs decreased for Chinese females and Japanese and South Korean males during 1990-2019. High body-mass-index (BMI) was the largest contributor to Chinese female BC deaths and DALYs, while alcohol use was the greatest risk factor for Japanese and South Korean as well as Chinese males. The incident cases and deaths were expected to continue increase during 2020-2034 (except for Japanese female incident cases). CONCLUSIONS: China had the greatest burden of BC among the three countries. Incident cases and deaths of BC were projected to increase over the next 15 years in China, particularly among Chinese males. Effective prevention and management strategies are urgently necessary for BC control in China.

Blood pressure states transitions among bus drivers: the application of multi-state Markov model.

PURPOSE: To explore the transition patterns among different levels of blood pressure for bus drivers. METHODS: A follow-up study was conducted to investigate the transition probabilities of three blood pressure states, the sojourn time in each state, the survival probabilities, and the risk factors affecting hypertension progression. Based on 5618 blood pressure measurements of 1883 Chinese bus drivers from 2017 to 2021, a multi-state Markov model was established. RESULTS: The mean age of participants was 41.43 ± 6.71 years, and 82.37% were male. The probabilities from normal state to hypertension within 1-year follow-up were 4.60% (male) and 2.13% (female); however, the corresponding changes over a 3-year follow-up had a significant increase to 20.27% (male) and 7.98% (female). The sojourn time of normal state and elevated state was 1.82 ± 0.09 years and 1.98 ± 0.08 years, respectively. The male participants, the increasing age, BMI, CHOL and TG were risk factors for progression from normal state to elevated state, and/or from elevated state to hypertensive state (HR: 1.04-2.53). CONCLUSIONS: Early preventive measures on the progression of hypertension should be taken for Chinese bus drivers, and at least one physical examination per year is strongly recommended. The government and bus companies should pay more attention to these kinds of bus drivers with high probabilities of hypertension: male, older than 40 years, with the higher values of BMI and blood lipid. The derived findings of sojourn time, transition probabilities and survival probabilities can provide reference for health professionals to make targeted intervention to reduce bus drivers' hypertension occurrence.

Association between HLA alleles and Epstein-Barr virus Zta-IgA serological status in healthy males from southern China.

BACKGROUND: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta-IgA, in healthy males from NPC endemic area. METHODS: HLA alleles of 1078 healthy males in southern China from the 21-RCCP study were imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in blood samples were measured using an enzyme-linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta-IgA serological status and its potential joint association with smoking. The binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0. RESULTS: HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; p = 1.82 × 10-4 ). Compared with non-smokers without HLA-DRB1*09:01, the effect size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA-DRB1 alleles. CONCLUSIONS: Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher risk of being Zta-IgA seropositive, which indicates the necessity of smoking cessation in certain high-risk populations and also provide clues for further research on the etiology of NPC.

Automated classification of protein subcellular localization in immunohistochemistry images to reveal biomarkers in colon cancer.

BACKGROUND: Protein biomarkers play important roles in cancer diagnosis. Many efforts have been made on measuring abnormal expression intensity in biological samples to identity cancer types and stages. However, the change of subcellular location of proteins, which is also critical for understanding and detecting diseases, has been rarely studied. RESULTS: In this work, we developed a machine learning model to classify protein subcellular locations based on immunohistochemistry images of human colon tissues, and validated the ability of the model to detect subcellular location changes of biomarker proteins related to colon cancer. The model uses representative image patches as inputs, and integrates feature engineering and deep learning methods. It achieves 92.69% accuracy in classification of new proteins. Two validation datasets of colon cancer biomarkers derived from published literatures and the human protein atlas database respectively are employed. It turns out that 81.82 and 65.66% of the biomarker proteins can be identified to change locations. CONCLUSIONS: Our results demonstrate that using image patches and combining predefined and deep features can improve the performance of protein subcellular localization, and our model can effectively detect biomarkers based on protein subcellular translocations. This study is anticipated to be useful in annotating unknown subcellular localization for proteins and discovering new potential location biomarkers.

Depolymerization-Induced Electrochemiluminescence of Insoluble Porphyrin in Aqueous Phase.

Exploring efficient and robust electrochemiluminescence (ECL) performance of liposoluble porphyrins in aqueous phase for analytical purposes especially for important biological targets is still very challenging. In this work, a novel depolymerization-induced electrochemiluminescence (DIECL) of porphyrin and ß-cyclodextrin (ß-CD) self-assembly through a coreactant route was discovered. Among the studied meso-tetrasubstituted porphyrins, self-assembly of 5,10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (THPP) and ß-CD (THPP@ß-CD) exhibits the best DIECL behavior with high efficiency (21.8%) as well as good reproducibility and stability. A mechanistic study suggests that the facile complexation of porphyrins with amphiphilic ß-CD via hydrogen bonding interaction greatly improves the water insolubility and the aggregation-caused deficient ECL of liposoluble porphyrins in aqueous solution. Furthermore, because of the strong hydrogen bonding between the hydroxyl groups on THPP@ß-CD and a highly electronegative substrate, such THPP@ß-CD is found to serve as an efficient luminophore for recognition of most electronegative fluoride (F-) in the aqueous phase with high sensitivity and selectivity, together with a low limit of detection (0.74 µΜ). The simplicity of this THPP@ß-CD and its unique DIECL property in current work provides a new guide for the ECL applications of liposoluble porphyrins in aqueous phase.

Nasopharyngeal Epstein-Barr virus DNA loads in high-risk nasopharyngeal carcinoma families: Familial aggregation and host heritability.

Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, environmental factor, and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein-Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have two or more relatives affected with NPC, in 116 high-risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent-offspring pairs and sibling-sibling pairs (P < .001), but not in distant kin relationship pairs. Interestingly, after excluding the shared environmental factor within families, host genetics contributes significantly to NP EBV loads with a heritability of 56.41% (P = 1.00 × 10-7 ), and its effect was slightly elevated (68.86%, P = 3.40 × 10-6 ) in families with more NPC cases (≥3). These findings indicate that additional host-genetic variants involved in the EBV local NP mucosal behavior may be especially important for the development of NPC.

Dissolved organic matter and bacterial population changes during the treatment of solid potato waste in a microbial fuel cell.

This study investigated the effect of mixed feeding of anaerobically cultured waste activated sludge (WAS) on the performance of microbial fuel cells (MFCs) in the treatment of solid potato waste. The maximum current densities of the four MFCs was estimated as 36, 5, 10 and 150 mA/m2, with the columbic efficiencies of 6.1, 0.3, 0.9 and 31.1%, respectively. Composition changes of dissolved organic matter (DOM) coupled with its interrelation with electricity generation and total and viable bacterial population at the end of the operation were investigated. The experimental results demonstrated that mixing WAS into solid potato enhanced the presence of the tyrosine-like aromatic amino acids and aromatic protein-like substances from the beginning of the operation and promoted hydrolysis and humification of the solid potato. In the final solution of the anodic chamber, more viable bacteria were detected for the reactors treating solid potato alone and the mixed feedstock with the smaller amount of sludge, where distinct electricity generation was observed.