Circulating lymphocyte subsets are prognostic factors in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a geographically and racially variable disease that has a high incidence in Southeast China. According to previous studies on tumor immunity, we compared multiple clinical parameters and blood indexes with outcomes regarding to Epstein-Barr virus (EBV) status in NPC patients. METHODS: According to the EBV load at diagnosis, 220 NPC patients who received concurrent chemoradiotherapy (CRT) were divided into two groups: EBV DNA ≥ 1500 copies/mL and EBV DNA < 1500 copies/mL, respectively. We compared clinical parameters with peripheral blood mononuclear cells, lymphocyte subsets and biochemical indexes. We also analyzed distant metastases and the overall survival rate regarding to these characteristics. RESULTS: In most cases, the two groups showed the same trends. Most blood indexes were decreased during CRT and the decrease of the absolute count was more significant than the percentage. Patients with younger age showed the higher CD3+ and CD3 + CD8+ percentages. Patients whose EBV DNA ≥ 1500 copies/mL showed a higher N classification than those with EBV DNA < 1500 copies/mL at first diagnosis. Within patients with EBV DNA ≥ 1500 copies/mL, a higher CD3 + CD8+ percentage or lower CD3-CD56+ percentage had better OS rates, and the CD3 + CD8+ percentage was an independent prognostic factor by multivariate survival analyses. CONCLUSIONS: CRT caused an overall decrease of blood cells in NPC patients. Among all the blood indexes, the CD3 + CD8+ percentage showed a correlation with age and was an independent prognostic factor in patients with EBV DNA ≥ 1500 copies/mL at first diagnosis, which is worthy for further large cohort study.

Cancer patient management strategy in a Cancer Center of Zhejiang, China during the COVID-19 pandemic.

BACKGROUND: Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff. METHODS: Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment. RESULTS: A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital's infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital. CONCLUSION: This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.

Comprehensive mutation detection of BRCA1/2 genes reveals large genomic rearrangements contribute to hereditary breast and ovarian cancer in Chinese women.

BACKGROUND: Mutated BRCA1/2 genes are associated with hereditary breast and ovarian cancer (HBOC). So far most of the identified BRCA1/2 pathogenic variants are single nucleotide variants (SNVs) or insertions/deletions (Indels). However, large genomic rearrangements (LGRs) such as copy number variants (CNVs) are also playing an important role in HBOC predisposition. Their frequency and spectrum have been well studied in western populations but remain largely unknown for Chinese population. METHODS: Peripheral blood samples were collected from 218 unrelated familial breast and/or ovarian cancer (FBOC) patients living in Eastern China. PCR-based Sanger sequencing and panel-based next-generation sequencing (NGS) were performed to detect pathogenic SNVs and Indels in BRCA1/2 genes. For the patients lacking small pathogenic variants, multiplex ligation dependent probe amplification (MLPA) assay was conducted to screen for LGRs. RESULTS: In total, we identified 44 samples (20.1%) carrying small pathogenic variants (26 in BRCA1 and 18 in BRCA2, respectively). Among the rest of 174 samples, five were found carrying novel deleterious LGRs in BRCA1 which are exon5-7dup (1 patient), exon13-14dup (2 patients), and exon1-22del (2 patients). No LGR was found in BRCA2. Overall, LGRs accounted for 16.1% (5/31) of BRCA1 pathogenic variants, and were detected in 2.3% (5/218) of all FBOC patients. , CONCLUSIONS: LGR variants in BRCA1 gene play a significant role in Chinese HBOC patients. MLPA or other similar LGR-detecting methods should be recommended along with nucleotide sequencing as the initial screening approach for Chinese HBOC women.

ARHGEF19 interacts with BRAF to activate MAPK signaling during the tumorigenesis of non-small cell lung cancer.

Rho guanine nucleotide exchange factors (RhoGEFs) are proteins that activate Rho GTPases in response to extracellular stimuli and regulate various biologic processes. ARHGEF19, one of RhoGEFs, was reported to activate RhoA in the Wnt-PCP pathway controlling convergent extension in Xenopus gastrulation. The goal of our study was to identify the role and molecular mechanisms of ARHGEF19 in the tumorigenesis of non-small cell lung cancer (NSCLC). ARHGEF19 expression was significantly elevated in NSCLC tissues, and ARHGEF19 levels were significantly associated with lymph node status, distant metastasis and TNM stage; Patients with high ARHGEF19 levels had poor overall survival (OS) and progression-free survival (PFS). Our investigations revealed that ARHGEF19 overexpression promoted the cell proliferation, invasion and metastasis of lung cancer cells, whereas knockdown of this gene inhibited these processes. Mechanistically, ARHGEF19 activated the mitogen-activated protein kinase (MAPK) pathway in a RhoA-independent manner: ARHGEF19 interacted with BRAF and facilitated the phosphorylation of its downstream kinase MEK1/2; both the Dbl homology (DH) and Pleckstrin homology (PH) domains of ARHGEF19 were indispensable for the phosphorylation of MEK1/2. Furthermore, downregulation of miR-29b was likely responsible for the increased expression of ARHGEF19 in lung cancer tissues and, consequently, the abnormal activation of MAPK signaling. These findings suggest that ARHGEF19 upregulation, due to the low expression of miR-29 in NSCLC tissues, may play a crucial role in NSCLC tumorigenesis by activating MAPK signaling. ARHGEF19 could serve as a negative prognostic marker as well as a therapeutic target for NSCLC patients.

Novel germline mutations and unclassified variants of BRCA1 and BRCA2 genes in Chinese women with familial breast/ovarian cancer.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes greatly increase a woman's risk of developing breast and/or ovarian cancer. The prevalence and distribution of such mutations differ across races/ethnicities. Several studies have investigated Chinese women with high-risk breast cancer, but the full spectrum of the mutations in these two genes remains unclear. METHODS: In this study, 133 unrelated Chinese women with familial breast/ovarian cancer living in Zhejiang, eastern China, were enrolled between the years 2008 and 2014. The complete coding regions and exon-intron boundaries of BRCA1 and BRCA2 were screened by PCR-sequencing assay. Haplotype analysis was performed to confirm BRCA1 and BRCA2 founder mutations. In silico predictions were performed to identify the non-synonymous amino acid changes that were likely to disrupt the functions of BRCA1 and BRCA2. RESULTS: A total of 23 deleterious mutations were detected in the two genes in 31 familial breast/ovarian cancer patients with a total mutation frequency of 23.3% (31/133). The highest frequency of 50.0% (8/16) was found in breast cancer patients with a history of ovarian cancer. The frequencies of BRCA1 and BRCA2 mutations were 13.5 % (18/133) and 9.8% (13/133), respectively. We identified five novel deleterious mutations (c.3295delC, c.3780_3781delAG, c.4063_4066delAATC, c.5161 > T and c.5173insA) in BRCA1 and seven (c.1-40delGA, c.4487delC, c.469_473delAAGTC, c.5495delC, c.6141T > A, c.6359C > G and c.7588C > T) in BRCA2, which accounted for 52.2% (12/23) of the total mutations. Six recurrent mutations were found, including four (c.3780_3781delAG, c.5154G > A, c.5468-1del8 and c.5470_5477del8) in BRCA1 and two (c.3109C > T and c.5682C > G) in BRCA2. Two recurrent BRCA1 mutations (c.5154G > A and c.5468-1del8) were identified as putative founder mutations. We also found 11 unclassified variants, and nine of these are novel. The possibility was that each of the non-synonymous amino acid changes would disrupt the function of BRCA1 and BRCA2 varied according to the different algorithms used. CONCLUSIONS: BRCA1 and BRCA2 mutations accounted for a considerable proportion of hereditary breast/ovarian cancer patients from eastern China and the spectrum of the mutations of these two genes exhibited some unique features. The two BRCA1 putative founder mutations may provide a cost-effective option to screen Chinese population, while founder effects of the two mutations should be investigated in a lager sample size of patients.

Association of dietary zinc consumption with periodontitis in diabetes mellitus patients: A cross-sectional study of national health and nutrition examination surveys database (2009-2014).

Background/purpose: Periodontitis is an independent risk factor for diabetes mellitus (DM), and DM patients had an increased risk in susceptibility to periodontitis. And serum zinc (Zn) levels were low in patients with periodontitis combined with DM. Herein, this study aimed to explore the association between dietary Zn intake and the risk of periodontitis in DM patients, in order to provide some scientific references for the prevention and treatment for periodontitis clinically. Materials and methods: Demographic and clinical data of DM patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2009-2014 in this cross-sectional study. Weighted univariate logistic regression and backward regression analyses were used for covariates screening. Weighted univariate and multivariate logistic regression analyses were used to explore the association between Zn and periodontitis with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age and gender were also performed. Results: Of the eligible participants, 1281 had moderate or severe periodontitis. After adjusting for the covariates, we found that comparing to DM patients who had not reach the recommended Zn intake level, those who reached had low odds for periodontitis [OR = 0.76, 95% CI: (0.58-0.99)]. In patients who aged ≥65 years old [OR = 0.59, 95% CI: (0.36-0.97)] and were female [OR = 0.71, 95% CI: (0.51-0.99)], reaching the recommended level of Zn intake was related to low odds of periodontitis. Conclusion: Sufficient dietary Zn intake antagonized the risk of periodontitis, which may provide some references for diet management in DM patients to reduce the risk of periodontitis.

Clinical performance and utility of a noninvasive urine-based methylation biomarker: TWIST1/Vimentin to detect urothelial carcinoma of the bladder.

Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.

A rapid on-site visualization platform based on RPA coupled with CRISPR-Cas12a for the detection of genetically modified papaya 'Huanong No.1'.

The Papaya ringspot virus (PRSV)-resistant genetically modified (GM) papaya 'Huanong No.1' has been certified as safe for consumption and widely planted in China for about 18 years. To protect consumers' rights and facilitate government supervision and monitoring, it is necessary to establish a simple, rapid, and specific detection method for 'Huanong No.1'. Herein, we developed a platform based on recombinase polymerase amplification (RPA) coupled with CRISPR-Cas12a for the detection of 'Huanong No.1'. The RPA-CRISPR-Cas12a platform was found to have high specificity, with amplification signals only present in 'Huanong No.1'. Additionally, the platform was highly sensitive, with a limit of detection (LOD) of approximately 20 copies. The detection process was fast and could be completed in less than 1 h. This novel platform enables the rapid on-site visualization detection of 'Huanong No.1', eliminating dependence on laboratory conditions and specialized instruments, and can serve as a technical reference for the rapid detection of other GM plants.

Genome Mining in Glass Chemistry Using Linear Component Analysis of Ion Conductivity Data.

Understanding the multivariate origin of physical properties is particularly complex for polyionic glasses. As a concept, the term genome has been used to describe the entirety of structure-property relations in solid materials, based on functional genes acting as descriptors for a particular property, for example, for input in regression analysis or other machine-learning tools. Here, the genes of ionic conductivity in polyionic sodium-conducting glasses are presented as fictive chemical entities with a characteristic stoichiometry, derived from strong linear component analysis (SLCA) of a uniquely consistent dataset. SLCA is based on a twofold optimization problem that maximizes the quality of linear regression between a property (here: ionic conductivity) and champion candidates from all possible combinations of elements. Family trees and matrix rotation analysis are subsequently used to filter for essential elemental combinations, and from their characteristic mean composition, the essential genes. These genes reveal the intrinsic relationships within the multivariate input data. While they do not require a structural representation in real space, how possible structural interpretations agree with intuitive understanding of structural entities known from spectroscopic experiments is finally demonstrated.

The Identification of the Banana Endogenous Reference Gene MaSPS1 and the Construction of Qualitative and Quantitative PCR Detection Methods.

Endogenous reference genes play a crucial role in the qualitative and quantitative PCR detection of genetically modified crops. Currently, there are no systematic studies on the banana endogenous reference gene. In this study, the MaSPS1 gene was identified as a candidate gene through bioinformatics analysis. The conservation of this gene in different genotypes of banana was tested using PCR, and its specificity in various crops and fruits was also examined. Southern blot analysis showed that there is only one copy of MaSPS1 in banana. The limit of detection (LOD) test showed that the LOD of the conventional PCR method is approximately 20 copies. The real-time fluorescence quantitative PCR (qPCR) method also exhibited high specificity, with a LOD of approximately 10 copies. The standard curve of the qPCR method met the quantitative requirements, with a limit of quantification (LOQ) of 1.14 × 10-2 ng-about 20 copies. Also, the qPCR method demonstrated good repeatability and stability. Hence, the above results indicate that the detection method established in this study has strong specificity, a low detection limit, and good stability. It provides a reliable qualitative and quantitative detection system for banana.

Quantitative analysis of microbiota in saliva, supragingival, and subgingival plaque of Chinese adults with chronic periodontitis.

OBJECTIVE: The aim of this study was to determine the profiles of periodontopathogenic bacteria in a Chinese population using quantitative real-time polymerase chain reaction (qRT-PCR). MATERIALS AND METHODS: Twenty-four periodontally healthy Chinese subjects and 60 patients with chronic periodontitis (CP) were enrolled in this cross-sectional study. qRT-PCR was used to quantify Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia as well as total bacterial counts from 252 samples collected from the saliva, supragingival plaque, and subgingival plaque of all 84 subjects. RESULTS: The detection frequency of A. actinomycetemcomitans was less than 50%. F. nucleatum was detected in all subjects and CP patients had higher bacterial loads than healthy subjects. The median proportion of F. nucleatum was significantly higher in subgingival plaque than in supragingival plaque and saliva. P. gingivalis and P. intermedia had higher detection frequencies and bacterial loads in CP patients than in healthy subjects. The median proportion of P. gingivalis was significantly different among the three intraoral locations in the CP group and its proportion in subgingival plaque was 9.01%. Moreover, strong positive Spearman's correlations were found in A. actinomycetemcomitans, P. gingivalis, and P. intermedia counts across the three intraoral locations. CONCLUSION: The presence and bacteria loads of these four bacteria in this Chinese population are similar to those from other populations. CLINICAL RELEVANCE: Examination of bacterial detection frequency and loads in Chinese adults may assist microbial studies of periodontal disease and will shed light on periodontal disease diagnosis and treatment using antibiotics in the Chinese population.

CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer.

PURPOSE: Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC) and have been identified in multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese patients with HDGC, and their frequency remains unclear. Here, we aimed to examine the frequency of CDH1 germline mutations in Chinese patients with HDGC. In total, 285 patients who met the International Gastric Cancer Linkage Consortium 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. METHODS: All 16 CDH1 exons, including neighboring intronic sequences, were amplified using polymerase chain reaction and screened using Sanger sequencing. Variants were analyzed using Mutation Surveyor V4.0, SIFT, and PolyPhen-2 software. RESULTS: Three nonsense and nine missense CDH1 germline mutations were identified in 21 of 285 index cases (7.4%). Two CDH1 germline mutations, N405Y (Asn405Tyr) and W409X (Trp409Ter), were identified as new variants. In addition, up to 28.6% of CDH1 mutations in the 21 indicated patients were identified as c.1775G>C (E551Q). The frequency of CDH1 mutations was 6.5% (7/108) in HDGC and 7.9% (14/177) in early onset diffuse gastric cancer (EODGC). The mutation detection rates of CDH1 in males and females were 6.7% (4/60) and 8.5% (10/117) in EODGC and 4.6% (3/65) and 9.3% (4/43) in HDGC, respectively. CONCLUSION: These data reveal, for the first time, the type and frequency of CDH1 germline mutations in Chinese HDGC and demonstrate that germline CDH1 mutations are a noteworthy contributor to the high frequency of HDGC in Chinese.

Co-MOFs as Emerging Pulse Modulators for Femtosecond Ultrafast Fiber Laser.

The metal organic framework (MOF) has attracted more and more attention due to its unique morphology, functional linkers, and orderly network structure. Zeolitio imidazolata frameworks (ZIFs), which are formed by bivalent transition metals (Zn, Co, etc.) and nitrogen-containing heterocyclic imidazole or purine organic ligands, are a very attractive subclass of MOFs. ZIF-67, obtained by the nucleation growth of dimethylimidazole and Co 2p, has been developed as a precursor for porous nanostructured cobalt-based metal oxides. During material preparation we add rGO because it can be used as a basic element to construct macroscopic three-dimensional carbon structural materials, which self-assemble into a 3D network structure with ZIF-67 through simple van der Waals forces or hydrogen bonds, and some samples contain specific functional groups that are added to the precursor. In this paper, we employ liquid-phase synthesis to generate rGO-ZIF-67 and calcine it at the temperature of 350 °C to obtain rGO-Co3O4. Then we fabricate rGO-Co3O4 and rGO-ZIF-67 modulators based on microfibers and test their nonlinear optical absorption in 1.5 µm range. The modulation depths of rGO-Co3O4 and rGO-ZIF-67 are measured as 10.41% and 6.61%, respectively. By using microfiber-based rGO-Co3O4 modulator, we have obtained a conventional soliton and a soliton molecule in Er3+-doped fiber lasers. The conventional soliton has a pulse width of 793.4 fs and a spectral width of 3.3 at 1558.9 nm, respectively. The obtained soliton molecule has a spectral modulation period of 1.65 nm and temporal separation of 4.94 ps at 1563.2 nm. By employing a microfiber-based rGO-ZIF-67 modulator, we obtain conventional solitons with a spectral width of 1.9 nm at the central wavelength of 1529.8 nm. Our research may expand the MOF-based materials for ultrafast photonics, blazing a new path for fiber laser, optical communications, and optoelectronics, etc.

The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+ follicular regulatory T cells in breast cancer.

BACKGROUND: Follicular regulatory T cells (Tfr) are a subset of regulatory T cells (Tregs) that suppress the humoral immune response in the germinal center. They are associated with increased rates of disease stabilization and decreased autoantibody levels in a variety of tumor and autoimmune diseases. The binding of T-cell immunoglobulin mucin 3 (TIM-3) and its ligand on the surface of Tfr cells could result in the depletion of T lymphocytes and the termination of the immune response mediated by helper T cell 1. However, the role of Tfr cells in breast cancer (BC) remains unclear. METHODS: In this study, we detected the expression of CD4+CXCR5+Foxp3+Tfr cells in the peripheral blood of 35 BC patients and 30 healthy control patients by flow cytometry, and analyzed the relationship between Tfr cells and the clinical characteristics of patients. In addition, the expression of TIM-3 on the surface of Tfr cells in 6 triple-negative BC (TNBC) patients was further investigated using mass spectrometry. RESULTS: We found a significant increase in Tfr cells in BC patients compared to healthy control patients (23.47%±9.70% vs. 10.99%±4.68%; P=0.001). Notably, the increase was more significant in early stage than advanced stage TNBC patients (28.52%±10.75% vs. 18.69%±5.19%; P=0.006), and there was a negative correlation between Tfr cells and serum lactate dehydrogenase (LDH) in early stage TNBC patients (r=-0.585; P=0.008). Additionally, we found that the expression of Tfr cells was higher in TNBC patients than luminal BC patients (28.25%±10.11% vs. 18.5%±8.15%; P=0.028); however, there was no significant difference in expression in hormone receptor positive (HR+) BC and hormone receptor negative (HR-) BC (P=0.141) patients. Notably, the surface of Tfr cells of TNBC patients had higher levels of TIM-3 expression than those of healthy control patients (3.93±0.92 vs. 2.65±0.15, respectively; t=-3.02; P<0.05), which the mass spectrometry showed were positively correlated with the intracellular Foxp3 expression of Tfr cells (r=0.82; P=0.036). CONCLUSIONS: Our results suggest that circulating Tfr cells and the expression of TIM-3 were significantly increased in BC patients, which were related to stage and histological type, and may be involved in the pathogenesis of BC.

Vibrational disorder and densification-induced homogenization of local elasticity in silicate glasses.

We report the effect of structural compaction on the statistics of elastic disorder in a silicate glass, using heterogeneous elasticity theory with the coherent potential approximation (HET-CPA) and a log-normal distribution of the spatial fluctuations of the shear modulus. The object of our study, a soda lime magnesia silicate glass, is compacted by hot-compression up to 2 GPa (corresponding to a permanent densification of ~ 5%). Using THz vibrational spectroscopic data and bulk mechanical properties as inputs, HET-CPA evaluates the degree of disorder in terms of the length-scale of elastic fluctuations and the non-affine part of the shear modulus. Permanent densification decreases the extent of non-affine elasticity, resulting in a more homogeneous distribution of strain energy, while also decreasing the correlation length of elastic heterogeneity. Complementary 29Si magic angle spinning NMR spectroscopic data provide a short-range rationale for the effect of compression on glass structure in terms of a narrowing of the Si-O-Si bond-angle and the Si-Si distance.

Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing.

Oral microbiota plays a vital role in maintaining the homeostasis of oral cavity. Dental caries are among the most common oral diseases in children and pathogenic bacteria contribute to the development of the disease. However, the overall structure of bacterial communities in the oral cavity from children with dental caries has not been explored deeply heretofore. We used high-throughput barcoded pyrosequencing and PCR-denaturing gradient gel electrophoresis (DGGE) to examine bacterial diversity of oral microbiota in saliva and supragingival plaques from 60 children aged 3 to 6 years old with and without dental caries from China. The multiplex barcoded pyrosequencing was performed in a single run, with multiple samples tagged uniquely by multiplex identifiers. As PCR-DGGE analysis is a conventional molecular ecological approach, this analysis was also performed on the same samples and the results of both approaches were compared. A total of 186,787 high-quality sequences were obtained for evaluating bacterial diversity and 41,905 unique sequences represented all phylotypes. We found that the oral microbiota in children was far more diverse than previous studies reported, and more than 200 genera belonging to ten phyla were found in the oral cavity. The phylotypes in saliva and supragingival plaques were significantly different and could be divided into two distinct clusters (p < 0.05). The bacterial diversity in oral microbiome analyzed by PCR-DGGE and barcoded pyrosequencing was employed to cross validate the data sets. The genera of Streptococcus, Veillonella, Actinomyces, Granulicatella, Leptotrichia, and Thiomonas in plaques were significantly associated with dental caries (p < 0.05). The results showed that there was no one specific pathogen but rather pathogenic populations in plaque that significantly correlated with dental caries. The enormous diversity of oral microbiota allowed for a better understanding of oral microecosystem, and these pathogenic populations in plaque provide new insights into the etiology of dental caries and suggest new targets for interventions of the disease.

MiR-596 down regulates SOX4 expression and is a potential novel biomarker for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most commonly diagnosed malignancies of the human digestive tract, and currently there is a dearth of effective biomarkers for this disease. METHODS: MiR-598 expression levels were analyzed by the cancer genome atlas (TCGA database) mining and verified in GC patient plasma using real-time reverse transcription polymerase chain reaction (RT-PCR) assay. We used the GEPIA and UALCAN databases and immunohistochemistry (IHC) to analyze SOX4 expression. The MTT assay assessed MNK28 and SGC7901 cell proliferation after transfection with miR-596 plasmids. The analytical tools, Functional Enrichment Analysis Tool (FunRich), Database of Immune Cell Expression (DICE) and Tumor IMmune Estimation Resource (TIMER) were used to analyze correlations between SOX4 and immune responses. Furthermore, a Kaplan Meier plotter database explored correlations between miR-596, SOX4 and overall patient survival. RESULTS: Data from TCGA and RT-PCR indicated that miR-598 was lowly expressed in GC patients. The miRWalk database showed that SOX4 was the target genes of miR-596 and also revealed that miR-596 bound directly to SOX4. MiR-596 over-expression further depressed GC cell proliferation. In addition, the FunRich database showed that SOX4 was involved in immune responses, and was further shown to be differentially expressed in CD4+ T cells by DICE. Specifically, TIMER indicated that high expression of SOX4 was negatively correlated with infiltrating CD4+ T cells in stomach adenocarcinoma (STAD). Moreover, high expression of miR-596 and low expression of SOX4 prolonged the overall survival (OS) of GC patients. CONCLUSIONS: Our study reveals a crucial role for miR-596 in tumor-associated immune infiltration and predicting prognoses in GC patients.

Deleterious Mutations in DNA Repair Gene FANCC Exist in BRCA1/2-Negative Chinese Familial Breast and/or Ovarian Cancer Patients.

Introduction: FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China. Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation. Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients. Conclusion: FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

Plasma metabolites Xanthine, 4-Pyridoxate, and d-glutamic acid as novel potential biomarkers for pulmonary tuberculosis.

BACKGROUND: The lack of rapid and efficient diagnostic methods has been one of the most frustrating challenges in controlling the pulmonary tuberculosis (TB) epidemic. This study was aimed to identify novel non-invasive biomarkers for pulmonary TB. METHODS: The subjects in this study were divided into four groups: the pulmonary TB group, the community-acquired pneumonia (CAP) group, the lung cancer (LC) group, and the normal control (NC) group. Plasma small molecule metabolites were investigated in each group by using ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry. Multivariate statistical methods and bioinformatics were used to analyze the data. RESULTS: We identified three differential plasma metabolites such as, Xanthine, 4-Pyridoxate and d-glutamic acid in the pulmonary TB group, compared to the other groups (CAP, LC and NC). The pathway enrichment analysis indicated that the energy source in pulmonary TB was multi-center, which might be involved in maintaining the reproductive ability and virulence of Mycobacterium tuberculosis. CONCLUSION: The results suggested that Xanthine, 4-Pyridoxate, and d-glutamic acid may serve as potential biomarkers for pulmonary TB. The present study provides experimental basis for developing potential biomarkers of pulmonary TB.

Light extraction from fundamental modes in modulated waveguides for homogeneous side-emission.

Dedicated control of axial light emission from light-guides enables a new generation of functional light sources for volumetric illumination. A primary challenge is to ensure homogeneous emission intensity across the full length of the device. Here, we introduce an approach towards homogeneously side-emitting waveguides which do not rely on imposing local scattering centers such as bubbles, micro-/nanoparticles, and rough or abrupt interfaces, but on modulated core radius. Previous quantitative studies of the relationship between structural parameters and radiation losses provide initial conditions for tailoring side-emission through core-diameter modulations, however, with strongly limited amplitude of modulation. We now employ and verify numerical simulation to overcome this limitation towards meter-long homogeneously side-emitting waveguides in which the amplitude of core-diameter modulation is of the same order of magnitude as the core diameter itself. Similar emission properties can be obtained through modulation of the core refractive index instead of the core diameter, or through a combination of both approaches. Using the present model, we deduce exemplary conditions for homogeneous side-emission in which the power flow within the waveguides decays linearly, what may present another interesting feature for applications beyond illumination.