Dual-response fluorescence sensing of H2PO4- and CO32- using AJP filter paper based on a pH-stable CdII-based luminescent metal-organic framework.

A new CdII-based luminescent metal-organic framework (LMOF) with the formula {[Cd(BIBT)(NDC)]·solvents}n (JXUST-32, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2NDC = 2,6-naphthalenedicarboxylic acid) was successfully synthesized by a solvothermal method. JXUST-32 shows a two-dimensional (4,4)-connected network and exhibits significant fluorescence red shift and slight enhancement for H2PO4- and CO32- sensing with detection limits of 0.11 and 0.12 µM, respectively. In addition, JXUST-32 has good thermal stability, chemical stability and recyclability. Significantly, JXUST-32 represents a fluorescence red-shift dual response MOF sensor for H2PO4- and CO32- detection and the analytes can be identified by the naked eye, aerosol jet printing filter paper, light-emitting diode beads and luminescent films.

Selective recognition of Hg2+ ions in aqueous solution by a CdII-based metal-organic framework with good stability and vacant coordination sites.

A novel water-stable CdII-based metal-organic framework, namely {[Cd(BIBT)(TDC)]·2H2O}n (JXUST-28, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2TDC = 2,5-thiophenedicarboxylic acid), was synthesized using a mixed-ligand strategy. Structural analysis demonstrates that JXUST-28 exhibits a two-dimensional layer structure with 4-connected sql topology. Intriguingly, JXUST-28 presents good stability in boiling water (at least 5 days), common organic solvents and aqueous solutions with different pH values of 2-12 (more than 24 hours). Furthermore, fluorescence experiments revealed that JXUST-28 could sense Hg2+ ions in aqueous solution via a quenching effect with a detection limit of 0.097 µM. Meanwhile, JXUST-28 can also be regenerated at least 5 times to detect Hg2+ ions. In addition, light-emitting diode lamps, luminescent films, and test papers of JXUST-28 have been successfully developed for practical applications.

Corrigendum: Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

[This corrects the article DOI: 10.3389/fonc.2021.766939.].

A risk prediction model for selecting high-risk population for computed tomography lung cancer screening in China.

OBJECTIVE: Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer. MATERIALS AND METHODS: Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively. RESULTS: By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. CONCLUSIONS: We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

BACKGROUND: About 15% of lung cancers in men and 53% in women are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in non-smokers in China. METHODS: A large-sample size, population-based study was conducted under the framework of the Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. RESULTS: A total of 214,764 eligible subjects were included, with a mean age of 55.19 years. Subjects were randomly divided into the training (107,382) and validation (107,382) sets. Elder age, being male, a low education level, family history of lung cancer, history of tuberculosis, and without a history of hyperlipidemia were the independent risk factors for lung cancer. Using these six variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.753, 0.752, and 0.755 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a moderate predictive discrimination, with the AUC was 0.668, 0.678, and 0.685 for the 1-, 3- and 5-year lung cancer risk. CONCLUSIONS: We developed and validated a simple and non-invasive lung cancer risk model in non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in non-smokers.

Evaluation of a Low-Dose Computed Tomography Lung Cancer Screening Program in Henan, China.

Importance: Lung cancer screening has been widely implemented in Europe and the US. However, there is little evidence on participation and diagnostic yields in population-based lung cancer screening in China. Objective: To assess the participation rate and detection rate of lung cancer in a population-based screening program and the factors associated with participation. Design, Setting, and Participants: This cross-sectional study used data from the Cancer Screening Program in Urban China from October 2013 to October 2019, with follow-up until March 10, 2020. The program is conducted at centers in 8 cities in Henan Province, China. Eligible participants were aged 40 to 74 and were evaluated for a high risk for lung cancer using an established risk score system. Main Outcomes and Measures: Overall and group-specific participation rates by common factors, such as age, sex, and educational level, were calculated. Differences in participation rates between those groups were compared. The diagnostic yield of both screening and nonscreening groups was calculated. Results: The study recruited 282 377 eligible participants and included 55 428 with high risk for lung cancer; the mean (SD) age was 55.3 (8.1) years, and 34 966 participants (63.1%) were men. A total of 22 260 participants underwent LDCT (participation rate, 40.16%; 95% CI, 39.82%-40.50%). The multivariable logistic regression model showed that female sex (odds ratio [OR], 1.64; 95% CI, 1.52-1.78), former smoking (OR, 1.26; 95% CI, 1.13-1.41), lack of physical activity (OR, 1.19; 95% CI, 1.14-1.24), family history of lung cancer (OR, 1.73; 95% CI, 1.66-1.79), and 7 other factors were associated with increased participation of LDCT screening. Overall, at 6-year follow-up, 78 participants in the screening group (0.35%; 95% CI, 0.29%-0.42%) and 125 in the nonscreening group (0.38%; 95% CI, 0.33%-0.44%) had lung cancer detected, which resulted in an odds ratio of 0.93 (95% CI, 0.70-1.23; P = .61). Conclusions and Relevance: The low participations rate in the program studied suggests that an improved strategy is needed. These findings may provide useful information for designing effective population-based lung cancer screening strategies in the future.

The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7-96.4) and 95.7% (95%CI: 91.3-97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), but higher than LBC (80.4% [95%CI: 74.5-85.2] and 88.8% [95%CI: 83.0-92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2-83.0]) and CIN3+ (70.5% [95%CI: 65.7-74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), but lower than LBC (84.5% [95%CI: 80.1-88.0] 79.8% [95%CI: 75.4-83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

The relative survival and cure fraction of gastric cancer estimated through flexible parametric models using data from population-based cancer registration during 2003-2012 in Linzhou, China.

PURPOSE: The proportion of cured gastric cancer patients has drawn the attention of patients, physicians, and healthcare providers after comprehensive prevention and control measures were carried out for several years. Therefore, the relative survival and cure fraction were estimated in our study. METHODS: Population-based cancer registration data were used to estimate survival and cure fraction. A total of 7585 gastric cancer cases (ICD10:C16.0 ~ C16.9) were extracted and included in the final analysis. Cases were diagnosed in 2003-2012 and followed until the end of 2017. Relative survival was calculated as the ratio between the observed survival through the life-table method. The expected survival was estimated by the Ederer II method. The cure fraction was estimated using flexible parametric cure models stratified by age and calendar period when the cases were diagnosed. RESULTS: The 5-year relative survival of cardia gastric cancer increased with the calendar period of 2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012 (27.5%, 28.3%, 33.5%, 38.2%, and 46.8%, respectively). The increasing trend along with the calendar periods was also observed in cure proportion of cardia gastric cancer (24.8%, 25.2%, 31.7%, 36.0%, and 43.1%, respectively). Notable improvement of cure proportion was observed in the period of 2011-2012, compared with the initial period of 2003-2004. There was an improvement of 79.8% among all gastric cancer subjects, and it was 74.1% and 55.7% in cardia gastric and noncardia gastric cancer subjects, respectively. The median survival of "uncured" patients showed no significant improvement along with the calendar periods in all age groups. CONCLUSIONS: Notable improvement of gastric cancer relative survival and cure proportion was observed in Linzhou during 2003-2012.

Evaluation of p16/Ki-67 dual staining in the detection of cervical precancer and cancer in China.

Background This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining in the detection of cervical intraepithelial neoplasia grade 2 or 3 or worse (CIN2+/CIN3+) in Chinese women. Methods Cervical exfoliated cells were collected from 537 eligible women and were used for liquid-based cytology (LBC), p16/Ki-67 dual staining, and human papillomavirus (HPV) DNA testing. All women received colposcopy with biopsies taken at abnormal sites. Histopathological diagnoses were used as the gold standard. Results p16/Ki-67 staining had a positivity rate of 43.58% overall; the rate increased significantly with histological severity (p <0.001). The sensitivities of p16/ki-67 for detecting CIN2+ and CIN3+ were 88.10% and 91.30%, respectively. Compared with high-risk HPV (HR-HPV), sensitivity of p16/Ki-67 was lower for detecting CIN2+ (88.10% versus 95.71%), but similar for detecting CIN3+ (91.30% versus 96.27%). Specificities of p16/Ki-67 were 85.02% for detecting CIN2+ and 76.86% for detecting CIN3+, values similar to those for LBC (84.71% for CIN2+, 80.05% for CIN3+) but higher than those for HR-HPV (62.77% for CIN2+, 71.25% for CIN3+). All the tests performed better in women>30 years. With respect to the performance of triage for women with ASC-US, sensitivities of p16/Ki-67 were 86.36% for detecting CIN2+ and 83.33% for detecting CIN3+, values similar to those of HR-HPV. However, specificities of p16/Ki-67 were both higher than those of HR-HPV (85.96% versus 67.54% for CIN2+, 79.84% versus 62.90% for CIN3+). Conclusion P16/Ki-67 dual staining could probably provide an optional method for China's national cervical cancer screening, and could also be considered as an efficient method of triage for managing women with ASC-US.

Incidence and mortality of liver cancer in Henan province in 2015.

OBJECTIVE: Liver cancer is one of the most common types of cancer. We aimed to use the cancer registration data in 2015 to estimate the incidence and mortality of liver cancer in Henan province. METHODS: The data from 37 population-based cancer registries in Henan province were collected for this study. The pooled data were stratified by area, sex, and age group. New cases of liver cancer and deaths due to the disease were estimated using age-specific rates and provincial population in 2015. All incidence and death rates were age standardized to the 2000 Chinese standard population and Segi's population, which were expressed per 100,000 populations. RESULTS: After clearance and assessment, data from 30 population-based cancer registries (5 in urban and 25 in rural areas) were included in the analysis. All 30 cancer registries encompassed a total population of 23,421,609 (3,507,984 in urban and 19,913,625 in rural areas), accounting for 21.84% of the provincial population. The proportion of morphological verification (MV%), percentage of cancer cases identified with death certification only (DCO%), and mortality-to-incidence ratio (M/I) were 38.55%, 2.34%, and 0.81, respectively. Approximately 31,639 new cases of liver cancer were diagnosed and 26,057 deaths from liver cancer occurred in Henan in 2015. The crude incidence rate of liver cancer was 27.05/100,000 (36.24/100,000 in men and 17.35/100,000 in women). Age-standardized incidence rates by Chinese standard population and world standard population were 21.10/100,000 and 20.95/100,000, respectively. Liver cancer was more common in men than in women. The incidence rates in urban (26.31/100,000) and rural (27.18/100,000) areas were similar. The crude mortality rate of liver cancer was 21.98/100,000 (29.33/100,000 in males and 14.22/100,000 in females). Age-standardized mortality rates by Chinese standard population and world standard population were 16.93/100,000 and 16.90/100,000, respectively. There was no distinct difference in mortality rates of liver cancer between urban (22.55/100,000) and rural (21.87/100,000) areas. CONCLUSIONS: Liver cancer has posed a heavy burden on people in Henan province. Comprehensive measures should be conducted to prevent the increase in the incidence of liver cancer.

Novel sesquilignan and lignan glycoside from the twigs and leaves of Illicium majus.

A novel sesquilignan compound (1), possesing an unusual carbon skeleton of aryltetralin unit linked with a C6-C3 unit and a five-membered ring by a C-7″ and C-4 linkage pattern via an oxygen atom, and a new lignan glycoside (2) have been isolated from the twigs and leaves of Illicium majus. Their structures were determined by spectroscopic analysis and chemical methods. The absolute configurations of 1 and 2 are confirmed by observing the circular dichroism. At 10 µM, Compounds 1 and 2 showed in Vitro inhibitory activity against the release of ß-glucuronidase in rat polymorphonuclear leukocytes induced by platelet-activating factor.

Genetic epidemiological analysis of esophageal cancer in high-incidence areas of China.

Genetic epidemiological studies have shown that genetic susceptibility to esophageal cancer (EC) is an important cause of its high incidence within families in some areas of China. The purpose of this study was to obtain evidence of a genetic basis of EC in Xin-an and Xin-xiang counties in China. Familial aggregation and complex segregation analyses were performed of 79 EC families in these counties. The heritability of EC was examined using Falconer's method and complex segregation analysis was conducted with the SEGREG program in Statistical Analysis for Genetic Epidemiology (SAGE version 5.3.1). The results showed that the distribution of EC in families did not fit well into a binomial distribution. The heritability of EC among first-degree and second- degree relatives was 67.0±7.31% and 43.1%±9.80%, respectively, and the summing up powered heritability was 53.2±6.74%. The segregation ratio was 0.045. Complex segregation analysis showed that the genetic model of EC was additive. The current results provide evidence for an inherited propensity to EC in certain high-risk groups in China, and support efforts to identify the genes that confer susceptibility to this disease.

Bioinformatic prediction of SNPs within miRNA binding sites of inflammatory genes associated with gastric cancer.

Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-κB and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

[Clinical manifestations and gene mutations of a Chinese family with MYH9-related syndrome].

OBJECTIVE: To explore the method for early diagnosis and pathogenesis of MYH9-related syndrome through analysis of the clinical manifestation and gene mutation of a Chinese family with MYH9-related syndrome. METHODS: Peripheral blood samples were collected from a three-generation Chinese family with MYH9-related syndrome (11 individuals, including 3 patients) and 100 healthy individuals. Polymerase chain reaction (PCR) amplification and direct sequencing of DNA were performed to analyze mutations of MYH9 gene. RESULTS: Thrombocytopenia, increased volume of platelet, and granulocyte inclusion bodies were found in the patients with MYH9-related syndrome via a peripheral blood test. A missense mutation of a base pair (G-A) in exon 30 was revealed by PCR amplification and direct sequencing of MYH9 of the proband. That lead to Asp-Asn substitution at position 1424 (D1424N mutation). The mutation was the same as in other patients with MYH9-related syndrome. It was not found in healthy people from the Chinese family or in the other 100 healthy individuals. CONCLUSIONS: Patients with MYH9-related syndrome show diverse symptoms. Mutation of MYH9 gene may be the molecular mechanism of MYH9-related syndrome, and D1424N mutation of MYH9 has not been reported in Chinese people. Early diagnosis of MYH9-related syndrome can be carried out by investigating family history and making early examinations.

SCS: signal, context, and structure features for genome-wide human promoter recognition.

This paper integrates the signal, context, and structure features for genome-wide human promoter recognition, which is important in improving genome annotation and analyzing transcriptional regulation without experimental supports of ESTs, cDNAs, or mRNAs. First, CpG islands are salient biological signals associated with approximately 50 percent of mammalian promoters. Second, the genomic context of promoters may have biological significance, which is based on n-mers (sequences of n bases long) and their statistics estimated from training samples. Third, sequence-dependent DNA flexibility originates from DNA 3D structures and plays an important role in guiding transcription factors to the target site in promoters. Employing decision trees, we combine above signal, context, and structure features to build a hierarchical promoter recognition system called SCS. Experimental results on controlled data sets and the entire human genome demonstrate that SCS is significantly superior in terms of sensitivity and specificity as compared to other state-of-the-art methods. The SCS promoter recognition system is available online as supplemental materials for academic use and can be found on the Computer Society Digital Library at http://doi.ieeecomputersociety.org/10.1109/TCBB.2008.95.

Finding human promoter groups based on DNA physical properties.

DNA rigidity is an important physical property originating from the DNA three-dimensional structure. Although the general DNA rigidity patterns in human promoters have been investigated, their distinct roles in transcription are largely unknown. In this paper, we discover four highly distinct human promoter groups based on similarity of their rigidity profiles. First, we find that all promoter groups conserve relatively rigid DNAs at the canonical TATA box [a consensus TATA(A/T)A(A/T) sequence] position, which are important physical signals in binding transcription factors. Second, we find that the genes activated by each group of promoters share significant biological functions based on their gene ontology annotations. Finally, we find that these human promoter groups correlate with the tissue-specific gene expression.

Physical signals for protein-DNA recognition.

This paper discovers consensus physical signals around eukaryotic splice sites, transcription start sites, and replication origin start and end sites on a genome-wide scale based on their DNA flexibility profiles calculated by three different flexibility models. These salient physical signals are localized highly rigid and flexible DNAs, which may play important roles in protein-DNA recognition by the sliding search mechanism. The found physical signals lead us to a detailed hypothetical view of the search process in which a DNA-binding protein first finds a genomic region close to the target site from an arbitrary starting location by three-dimensional (3D) hopping and intersegment transfer mechanisms for long distances, and subsequently uses the one-dimensional (1D) sliding mechanism facilitated by the localized highly rigid DNAs to accurately locate the target flexible binding site within 30 bp (base pair) short distances. Guided by these physical signals, DNA-binding proteins rapidly search the entire genome to recognize a specific target site from the 3D to 1D pathway. Our findings also show that current promoter prediction programs (PPPs) based on DNA physical properties may suffer from lots of false positives because other functional sites such as splice sites and replication origins have similar physical signals as promoters do.

Structural properties of replication origins in yeast DNA sequences.

Sequence-dependent DNA flexibility is an important structural property originating from the DNA 3D structure. In this paper, we investigate the DNA flexibility of the budding yeast (S. Cerevisiae) replication origins on a genome-wide scale using flexibility parameters from two different models, the trinucleotide and the tetranucleotide models. Based on analyzing average flexibility profiles of 270 replication origins, we find that yeast replication origins are significantly rigid compared with their surrounding genomic regions. To further understand the highly distinctive property of replication origins, we compare the flexibility patterns between yeast replication origins and promoters, and find that they both contain significantly rigid DNAs. Our results suggest that DNA flexibility is an important factor that helps proteins recognize and bind the target sites in order to initiate DNA replication. Inspired by the role of the rigid region in promoters, we speculate that the rigid replication origins may facilitate binding of proteins, including the origin recognition complex (ORC), Cdc6, Cdt1 and the MCM2-7 complex.

Structural property of regulatory elements in human promoters.

The capacity of transcription factors to activate gene expression is encoded in the promoter sequences, which are composed of short regulatory motifs that function as transcription factor binding sites (TFBSs) for specific proteins. To the best of our knowledge, the structural property of TFBSs that controls transcription is still poorly understood. Rigidity is one of the important structural properties of DNA, and plays an important role in guiding DNA-binding proteins to the target sites efficiently. After analyzing the rigidity of 2897 TFBSs in 1871 human promoters, we show that TFBSs are generally more flexible than other genomic regions such as exons, introns, 3' untranslated regions, and TFBS-poor promoter regions. Furthermore, we find that the density of TFBSs is consistent with the average rigidity profile of human promoters upstream of the transcription start site, which implies that TFBSs directly influence the promoter structure. We also examine the local rigid regions probably caused by specific TFBSs such as the DNA sequence TATA(A/T)A(A/T) box, which may inhibit nucleosomes and thereby facilitate the access of transcription factors bound nearby. Our results suggest that the structural property of TFBSs accounts for the promoter structure as well as promoter activity.