A high-sensitivity lab-on-a-chip analyzer for online monitoring of nitrite and nitrate in seawater based on liquid waveguide capillary cells.

Optical detection is an indispensable part of microfluidic systems for nutrient determination in seawater. Coupling total internal reflection capillaries with microfluidic chips is a practical alternative to increase the optical path length for high-sensitivity and a low detection limit in colorimetric assays, which has not been applied in microfluidic devices for seawater nutrients. Here, we present an online microfluidic system which integrated a total internal reflection capillary made of Teflon AF 2400 for the high-sensitivity detection of nitrite and nitrate in seawater. The off-chip capillary lengthens the optical path without changing the internal flow path of the microfluidic chip, enhancing the sensitivity, reducing the detection limit and widening the dynamic range of the system, which significantly improves the performance of the microfluidic system based on wet-chemistry. The detection limit for nitrite is 0.0150 µM using an external 20 cm capillary and 0.0936 µM using an internal 5 cm absorption cell, providing an over 6-fold improvement. Laboratory analysis of surface seawater samples collected from the South China Sea with this system and a one-month online deployment of an autonomous analyzer developed based on this system at a station revealed correlations between the nitrite and nitrate with tide, salinity and chlorophyll over slight variations and narrow ranges, demonstrating the high-sensitivity of this method.

Shortcut barcoding and early pooling for scalable multiplex single-cell reduced-representation CpG methylation sequencing at single nucleotide resolution.

DNA methylation is essential for a wide variety of biological processes, yet the development of a highly efficient and robust technology remains a challenge for routine single-cell analysis. We developed a multiplex scalable single-cell reduced representation bisulfite sequencing (msRRBS) technology. It allows cell-specific barcoded DNA fragments of individual cells to be pooled before bisulfite conversion, free of enzymatic modification or physical capture of the DNA ends, and achieves read mapping rates of 62.5 ± 3.9%, covering 60.0 ± 1.4% of CpG islands and 71.6 ± 1.6% of promoters in K562 cells. Its reproducibility is shown in duplicates of bulk cells with close to perfect correlation (R = 0.97-0.99). At a low 1 Mb of clean reads, msRRBS provides highly consistent coverage of CpG islands and promoters, outperforming the conventional methods with orders of magnitude reduction in cost. Here, we use this method to characterize the distinct methylation patterns and cellular heterogeneity of six cell lines, plus leukemia and hepatocellular carcinoma models. Taking 4 h of hands-on time, msRRBS offers a unique, highly efficient approach for dissecting methylation heterogeneity in a variety of multicellular systems.

Circular RNA circ_0000119 promotes cervical cancer cell growth and migration via miR-433-3p/PAK2 axis.

The purpose of this study was to investigate the role of circ_0000119 on CC progression and its molecular mechanism. The expression levels of circ_0000119, miR-433-3p, and p21-activated kinase 2 (PAK2) in CC tissues and cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Cell cycle and apoptosis were assessed by flow cytometry. Cell migration and invasive ability were examined by Transwell assays. Downstream binding targets of circ_0000119 were predicted by online bioinformatics tools and confirmed by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. The role of circ_0000119/miR-433-3p/PAK2 axis in regulating the CC process was explored by rescue experiments. A xenograft model was constructed to further determine the effect of circ_0000119 on CC tumor growth in vivo. Immunohistochemistry (IHC) assay was conducted for Ki67 expression. Circ_0000119 was aberrantly upregulated in CC tissues and cell lines. Knockdown of circ_0000119 inhibited CC cell proliferation, cell cycle progress, migration, invasion, and promoted apoptosis of CC cells. MiR-433-3p was a binding target of circ_0000119, and PAK2 was a downstream gene of miR-433-3p. MiR-433-3p inhibition reversed the inhibitory effect of silencing circ_0000119 on CC progression. In addition, PAK2 overexpression reversed the effect of miR-433-3p on CC progression. PAK2 expression was regulated by circ_0000119 and miR-433-3p. Moreover, circ_0000119 knockdown reduced tumor growth of CC in vivo. Circ_0000119 was upregulated in CC, and circ_0000119 knockdown suppressed CC malignant development through the miR-433-3p/PAK2 axis.

A frameshift variant in the SIRPB1 gene confers susceptibility to Crohn's disease in a Chinese population.

Background: Crohn's disease (CD), a chronic gastrointestinal inflammatory disease, is increasing in China. With a focus on Han Chinese families with CD, the aim of this study was to find genetic variations that increase CD susceptibility by genome sequencing, genetic association, expression, and functional research. Materials and methods: We performed family-based genome sequencing (WGS) analysis on 24 patients with CD from 12 families and then filtered shared potential causal variants by incorporating association results from meta-analyses of CD GWAS and immunology genes and in silico variant effect prediction algorithms. Replication analyses were performed in an independent cohort including 381 patients with CD and 381 control subjects. Results: There were 92 genetic variants significantly associated with CD in Chinese individuals. Among them, 61 candidate loci were validated in replication analyses. As a result, patients carrying a rare frameshift variant (c.1143_1144insG; p. Leu381_Leu382fs) in gene SIRPB1 had significantly higher risk to develop CD (p = 0.03, OR 4.59, 95% CI 0.98-21.36, 81.82% vs. 49.53%). The frameshift variation induced tyrosine phosphorylation of Syk, Akt, and Jak2, elevated the expression of SIRPB1 at the mRNA and protein levels, activated DAP12, and controlled the activation of NF-κB in macrophages. Additionally, it promoted the synthesis of the pro-inflammatory cytokines IL-1, TNF-, and IL-6. Conclusion: Our results suggest that the rare gain-of-function frameshift variant in SIRPB1 is associated in Han Chinese patients with CD. The functional mechanism of SIRPB1 and its downstream inflammatory pathways was preliminarily explored in CD.

Glomerular deposition of fibrinogen predicts good prognosis of IgA nephropathy: a single-center cohort study.

PURPOSE: It has been proven that fibrinogen deposition exists in IgA nephropathy (IgAN), but its clinical significance has not been identified. We aim to investigate the clinical implication of fibrinogen deposition in evaluating the activity and prognosis of IgA nephropathy. METHODS: In this cohort, 935 adult IgAN patients were divided into 3 groups according to the intensity of glomerular fibrinogen deposition. Primary outcome refers to a composite event of either a ≥ 50% reduction in eGFR or ESRD (eGFR < 15 ml/min/1.73m2, dialysis, or renal transplantation). Factors associated with fibrinogen deposition and prognosis were identified. RESULTS: The results showed that the intensity of fibrinogen deposition was positively correlated with eGFR (P < 0.001), serum albumin (P = 0.041), and hemoglobin levels (P < 0.05), but negatively correlated with age (P = 0.04), serum fibrinogen levels (P < 0.001), serum C4 (P = 0.023), the proportion of patients with hypertension (P = 0.003), and the percentage of glomeruli sclerosis (P < 0.001). The prognostic analyses identified that fibrinogen deposition was an independent predictor for the progression of IgAN (P = 0.033). CONCLUSION: Our study indicated that the deposition of renal fibrinogen can predict the prognosis of IgAN with high reliability.

Temporal dynamics of lateral carbon export from an onshore aquaculture farm.

Many coastal areas are hotspots of aquaculture expansion, where the overuse of artificial feeds results in the accumulation of organic carbon in nearshore aquaculture ponds. In rural areas, wastewater from the aquaculture ponds is discharged to the nearshore waters through artificial ditches causing lateral carbon export from the land to the ocean. Such flux may be meaningful in coastal carbon budgets since aquaculture is the hotspot of carbon sequestration and storage. To quantify the magnitude and temporal dynamics of lateral carbon export from aquaculture ponds, we used high-frequency in-situ monitoring of turbidity, fluorescent dissolved organic matter, etc. across different temporal scales. We measured water levels and velocity profiles in a ditch cross-section to obtain year-round water exchange. Carbon export was integrated from water fluxes and organic carbon concentrations. Our results suggested that aquaculture ponds were a source of particular organic carbon (POC) and dissolved organic carbon (DOC). The net lateral flux of POC and DOC was 148 ± 38 kg yr-1 and 296 ± 18 kg yr-1. Temporally, the export of POC and DOC is influenced by both tides and wastewater discharge. Under the disturbance with aquaculture wastewater discharge, the mean DOC export in the ditch increased by 497 kg, which was 1.5 times that of the undisturbed; the mean POC export increased by 190 kg, which was 1.8 times that of the undisturbed. Thus, aquaculture activities can considerably disturb the coastal carbon balance by facilitating carbon-rich fluid exchange from onshore farms to nearshore estuaries. As aquaculture expands across Asia and the globe, this study provides important insights into the impacts of aquaculture on coastal carbon budgets.

Two-year longitudinal change in choroidal and retinal thickness in school-aged myopic children: exploratory analysis of clinical trials for myopia progression.

BACKGROUND: With increasing axial length and myopia progression, the micro-structure of the retina and choroid gradually changes. Our study describes the longitudinal changes in retinal and choroidal thickness in school-aged children with myopia and explores the relationship between changes in choroidal thickness and myopia progression. METHODS: An exploratory analysis of a randomized trial was performed. Children (n = 168, aged 7 to 12 years) with myopia from - 0.75 dioptre (D) to - 4.00 D were enrolled in this prospective longitudinal study. Cycloplegic refraction, axial length (AL), retinal and choroidal thicknesses were measured at baseline and at 1- and 2-year follow-ups. "Rapid progression myopia" was defined as increasing in myopia > 1.00 D and "stable progression myopia" was ≤ 1.00 D during the 2-year follow-up. Factors affecting the changes in choroidal thickness were analysed using linear mixed models. RESULTS: AL significantly increased by 0.67 ± 0.24 mm with a myopic shift of - 1.50 ± 0.64 D over the 2 years. The overall retinal thickness increased from 251.12 ± 15.91 µm at baseline to 253.47 ± 15.74 µm at the 2-year follow-up (F = 23.785, P < 0.001). The subfoveal choroidal thickness decreased from 231.03 ± 54.04 µm at baseline to 206.53 ± 59.71 µm at the 2-year follow-up (F = 73.358, P < 0.001). Choroidal thinning was significantly associated with AL elongation (ß = - 43.579 µm/mm, P = 0.002) and sex (ß = - 17.258, P = 0.001). Choroidal thickness continued to decrease in subjects with rapid progression (F = 92.06, P < 0.001) but not in those with steady progression (F = 2.23, P = 0.119). CONCLUSION: Significant choroidal thinning was observed and was associated with rapid progression and sex. These findings indicate a need to understand the role of the choroid in eye growth and myopia development. SYNOPSIS/PRECIS: The macular choroidal thickness of myopic children is relevant to different degrees of myopic progression in this 2-year longitudinal study. These findings suggest that control of choroidal thickness might work to regulate human ocular growth. Trial registration Chinese Clinical Trial Register (ChiCTR): ChiCTR-INR-16007722.

Effect of Lactobacillus fermentum HFY03 on the Antifatigue and Antioxidation Ability of Running Exhausted Mice.

Yak yogurt is mainly produced in Qinghai-Tibet Plateau. It is a kind of naturally fermented dairy product. It contains abundant microorganisms. Lactobacillus fermentum (LF) HFY03 is a lactic acid bacteria derived from it. Our main research content is to study the influence of LF-HFY03 on the antifatigue and antioxidation ability of running exhausted mice. We gave different doses of LF-HFY03 to mice by gavage for 4 weeks. We selected vitamin C as the positive control group, mainly to study the relationship between antioxidant capacity and fatigue resistance and LF-HFY03 in mice with running exhaustion. The results showed that LF-HFY03 and vitamin C could significantly improve the running time of mice. And with the increase in LF-HFY03 concentration, the exhaustion time of mice was also extended. LF-HFY03 can reduce the content of urea nitrogen and lactic acid and also can increase the content of free fatty acids and liver glycogen. The levels of alanine aminotransferase, serum creatine kinase, and aspartate aminotransferase in mice decreased gradually as the antioxidant peptide level of walnut albumin increased. LF-HFY03 can reduce malondialdehyde (MDA) levels in a quantification-dependent manner and can also increase catalase (CAT) and superoxide dismutase (SOD) levels. LF-HFY03 can also increase the expressions of CAT mRNA, Cu/Zn-SOD, and Mn-SOD in the liver of mice. At the same time, LF-HFY03 can also increase the expression of protein of threonine transporter 1 (AST1)/alanine/cysteine/serine, mRNA, nNOS, and eNOS. At the same time, the solution could reduce the expression of TNF-α, syncytin-1, and inducible nitric oxide synthase (iNOS). The results showed that LF-HFY03 has a high development and application prospect as an antifatigue probiotic nutritional supplement.

Longitudinal Rehabilitation of Binocular Function in Adolescent Intermittent Exotropia After Successful Corrective Surgery.

PURPOSE: To study the longitudinal rehabilitation of binocular visual function in adolescent intermittent exotropia (IXT) after successful surgery and compare the results with those of a normal population. The role of binocular function in ocular alignment stability was also evaluated postoperatively. METHODS: In this prospective study, 30 adolescents with IXT successfully corrected after 1 month were followed for 12 months, and 30 children with normal vision were enrolled as controls. Stereopsis, the fusional vergence amplitude, sensory fusion, and accommodative flexibility were measured to assess binocular function at baseline and 6 and 12 months postoperatively. The controls were tested once when they were enrolled in the study. RESULTS: The deviation was -32.00 ± 8.60 prism diopters (PD) at distance fixation and -36.0 ± 9.10 PD at near fixation preoperatively with an average correction of 28.53 ± 3.79 PD and 30.67 ± 1.34 PD at 1 month postoperatively. Distance stereoacuity and near stereoacuity improved from 1 to 12 months postoperatively (p = 0.025 and p = 0.041, respectively). Compared with the controls, the fusional convergence reserve at distance (p = 0.025) and near (p = 0.033) fixations and fusion reserve ratio at distance (p = 0.000) and near (p = 0.000) fixations remained subnormal, whereas sensory fusion (p = 0.237), distance stereopsis (p = 0.120), and the fusional divergence amplitude at a distance (p = 0.168) were normal. However, no significant correlations were found between binocular functions at 1 month postoperatively and the postoperative drift. CONCLUSION: Binocular function significantly improved from before to after successful corrective surgery and continued to improve from 1 to 12 months postoperatively in adolescents with IXT. No significant correlations were found between binocular functions at 1 month postoperatively and ocular alignment stability.

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest.

[This retracts the article DOI: 10.3892/etm.2018.5710.].

Can Clinical Measures of Postoperative Binocular Function Predict the Long-Term Stability of Postoperative Alignment in Intermittent Exotropia?

PURPOSE: To evaluate whether clinical measures of postoperative binocular functions could predict the long-term stability of postoperative ocular alignment in children with intermittent exotropia. METHODS: A retrospective study was performed in thirty-nine children (median: 7 years) who have been surgically treated from intermittent exotropia without overcorrection (less than 10 prism diopters [pd] of exodeviation at 1 month postoperatively). Angles of deviation and binocular functions were measured preoperatively and at 1 month, 6 months, and the final follow-up visit (≥24 months) postoperatively. We examined the relationships between postoperative drift (change of ocular alignment) and binocular functions (sensory fusion, fusional convergence amplitude, and stereoacuity). RESULTS: The surgical success rate (esophoria/tropia ≤5 pd to exophoria/tropia ≤10 pd) dropped to 76.9% at 6 months after surgery and to 53.8% at individuals' last visit (mean: 37 months). The mean exodrift was 7.7 ± 9.2 pd from the postoperative month 1 to the final visit (p < 0.001) on distance fixation. Distance stereoacuity, central fusion, and fusional convergence amplitude significantly improved following surgery (p < 0.05). However, no significant correlation was found between their binocular functions measured at the beginning of each follow-up period and the postoperative drift (all p > 0.13). CONCLUSION: Our findings suggest that the clinical measures of sensory fusion, fusional convergence amplitude, and stereoacuity cannot serve as a robust predictor for the long-term stability of postoperative ocular alignment in patients who underwent successful surgery without overcorrection at 1 month postoperatively.

Serum complement C4 is an important prognostic factor for IgA nephropathy: a retrospective study.

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and is an important cause of end-stage renal disease (ESRD). Exploring novel biomarkers is necessary for predicting the disease activity and progression of IgAN patients. The present study sought to investigate the value of serum C4 for predicting the prognosis of IgAN patients. METHODS: The primary endpoint of this retrospective study was a composite event of either a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. The associations between serum C4 and clinicopathological parameters and prognosis of this cohort of IgAN patients were evaluated. RESULTS: The present study included 1356 IgAN patients. Serum C4 levels correlated significantly with clinical prognostic factors. Serum C4 levels correlated positively with urinary protein excretion (r = 0.307, P < 0.001), and negatively correlated with estimated glomerular filtration rate (r = - 0.281, P < 0.001). Furthermore, serum C4 levels increased with aggravation of tubulointerstitial injury, crescents and ratios of global sclerosis (all P < 0.05). Prognostic analyses with the Cox proportional hazards regression model and Kaplan-Meier survival curves further identified serum C4 as an independent risk factor for the prognosis of IgAN. CONCLUSIONS: The present study identified serum C4 as a useful predictor for the prognosis of IgAN patients. The mechanism of the trend of serum C4 in IgAN needs to be illustrated in further research.

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest.

Cervical cancer is one of the primary causes of cancer-associated mortality worldwide. Due to the increasing incidence of cervical cancer, multiple treatment options are required. Initial responses to chemotherapy and surgical interventions are generally positive, however patients often experience relapse and tumor recurrence. Currently, the effects of cucurbitacins on different types of cancer are being investigated, as they exhibit a wide variety of bioactivities. The anticancer activity of the cucurbitacin 23,24-dihydrocucurbitacin B against a panel of human cervical cancer cell lines was investigated in the current study. Cell viability was determined using an MTT assay and apoptosis was detected using DAPI staining. The proportion of apoptotic cells, cell cycle distribution, mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were estimated using flow cytometry. Protein expression was determined using western blot analysis. The results of the current study indicated that 23,24-dihydrocucurbitacin B inhibited the viability of human cervical cancer cell lines and had an IC50 of 40-60 µM. However, its cytotoxic effects were much less pronounced in normal epithelial fr2 and HerEpiC cells, where it had an IC50 of 125 µM. The underlying mechanisms of this were further studied and the results demonstrated that 23,24-dihydrocucurbitacin B induced apoptosis in HeLa cells and caused ROS-mediated shifts in the ΔΨm. Additionally, it caused the cell cycle arrest of HeLa cells at the G2/M checkpoint. The phosphoinositide 3 kinase/protein kinase B/mechanistic target of rampamycin (PI3K/AKT/mTOR) cascade may serve an important role in cancer tumorigenesis, progression and resistance to chemotherapy. The results indicated that 23,24-dihydrocucurbitacin B significantly decreased the expression of important proteins in the PI3K/Akt/mTOR cascade. Taken together, these results suggest that 23,24-dihydrocucurbitacin B may be novel method of treating cervical cancer.

A molecular inversion probe-based next-generation sequencing panel to detect germline mutations in Chinese early-onset colorectal cancer patients.

The currently known Mendelian colorectal cancer (CRC) predisposition syndromes account for ~5-10% of all CRC cases, and are caused by inherited germline mutations in single CRC predisposing genes. Using molecular inversion probes (MIPs), we designed a targeted next-generation sequencing panel to identify mutations in seven CRC predisposing genes: APC, MLH1, MSH2, MSH6, PMS2, MUTYH and NTHL1. From a consecutive series of 2,371 Chinese CRC patients, 140 familial and non-familial cases were selected that were diagnosed with CRC at or below the age of 35 years. Through MIP-based sequencing we identified pathogenic variants in six genes in 16 out of the 140 (11.4%) patients selected. In 10 patients, known pathogenic mutations in APC (five patients), MLH1 (three patients), or MSH2 (two patients) were identified. Three additional patients were found to carry novel, likely pathogenic truncating (n = 2) and missense (n = 1) mutations in the MSH2 gene and a concomitant loss of expression of both the MSH2 and MSH6 proteins in their respective tumor tissues. From our data, we conclude that targeted MIP-based sequencing is a reliable and cost-efficient approach to identify patients with a Mendelian CRC syndrome.

Design, methodology, and baseline data of the Personalized Addition Lenses Clinical Trial (PACT).

BACKGROUND: The aim of this study was to describe the design, methods, and baseline characteristics of children enrolled in the Personalized Addition lenses Clinical Trial (PACT). PACT aims to test the myopia control efficacy of progressive addition lenses (PALs) with personalized addition values compared with standard (+2.00 D) addition PALs and single vision lenses (SVLs). METHODS: PACT is a randomized, controlled, double-masked clinical trial. Two hundred eleven myopic Chinese children (7-12 years) were enrolled and randomized into 1 of the 3 following groups: personalized addition PALs; +2.00 addition PALs; and SVLs. Personalized addition values were determined based on the highest addition that satisfied Sheard criterion. Axial length and other biometric data were also recorded. RESULTS: At baseline, no differences were found between the right and left eyes for any of the main parameters. The enrolled children were 9.7 ±â€Š1.1 years' old with cycloplegic autorefraction (right eye [OD]: -2.36 ±â€Š0.64 D), near phoria (1.0 ±â€Š5.0 prism diopter esophoria), lag of accommodation (1.40 ±â€Š0.50 D) and axial length (OD: 24.58 ±â€Š0.74 mm). The personalized addition values ranged from +0.75 to +3.00 (average ±â€ŠSD: 2.19 ±â€Š0.73 D). CONCLUSION: PACT is a clinical trial evaluating whether myopia progression in children can be slowed by wearing personalized addition PALs compared with fixed addition PALs and SVLs as measured by cycloplegic autorefraction and axial length. Baseline data were comparable with those of previous myopia control studies in children. Subjects will be followed up every 6 months for 2 years.

Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility.

Approximately 25-30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5-10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency ≤ 0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (≤30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC.

Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases.

AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer (CRC) predisposing genes in early-onset or familial CRC cases. METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with non-polyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 first-degree relative diagnosed with CRC at ≤ 55 years of age. Genomic DNA from blood was enriched for exome sequences using the SureSelect Human All Exon Kit, version 2 (Agilent Technologies) and sequencing was performed on an Illumina HiSeq 2000 platform. Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes. RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing. In 6 of the 21 families (29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1 (5 patients), MSH2 (1 patient), and MUTYH (biallelic, 1 patient), five of which were reported as pathogenic. In the remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations. One previously unreported variant identified in a conserved region of EIF2AK4 (p.Glu738_Asp739insArgArg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy (33.3% vs 7%, P < 0.001). CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes.

Perivascular epithelioid cell tumor of gastrointestinal tract: case report and review of the literature.

Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are exceedingly rare, with only a limited number of published reports worldwide. Given the scarcity of GI PEComas and their relatively short follow-up periods, our current knowledge of their biologic behavior, molecular genetic alterations, diagnostic criteria, and prognostic factors continues to be very limited.We present 2 cases of GI PEComas, one of which showed an aggressive histologic behavior that underwent multiple combined chemotherapies. We also review the available English-language medical literature on GI PEComas-not otherwise specified (PEComas-NOS) and discuss their clinicopathological and molecular genetic features.Pathologic analyses including histomorphologic, immunohistochemical, and ultrastructural studies were performed to evaluate the clinicopathological features of GI PEComas, their diagnosis, and differential diagnosis. Immunohistochemistry, semiquantitative reverse transcriptase polymerase chain reaction, and DNA sequencing assays were carried out to detect the potential molecular genetic alterations in our cases. Microscopically, the tumors showed distinctive histologic features of PEComas-NOS, including fascicular or nested architecture, epithelioid or spindled cell type, and clear to eosinophilic cytoplasm. The tumor cells were immunohistochemically positive for melanocytic markers. Molecular pathological assays confirmed a PSF-TFE3 gene fusion in one of our cases. Furthermore, in this case microphthalmia-associated transcription factor and its downstream genes were found to exhibit elevated transcript levels.Knowledge about the molecular genetic alterations in GI PEComas is still limited and warrants further study.

Visible-light driven degradation of ibuprofen using abundant metal-loaded BiVO4 photocatalysts.

An efficient method for the degradation of ibuprofen as an aqueous contaminant was developed under visible-light irradiation with as-prepared bismuth vanadate (BiVO4) catalysts. The metal-loaded catalysts Cu-BiVO4 and Ag-BiVO4 were synthesized using a hydrothermal process and then a wet-impregnation method. All of the materials were fully characterized by X-ray diffraction, scanning electron microscopy, UV-vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy and BET surface area. The results indicated that all of the prepared samples had monoclinic scheelite structures. In the metal-loaded catalysts, silver existed as a mixture of Ag and Ag2O on the surface of the catalysts. However, copper existed as Cu2O and CuO. Additionally, the band gap values of BiVO4, Ag-BiVO4, and Cu-BiVO4 were 2.38, 2.31, and 2.30eV, respectively. Compared to the BiVO4 catalyst, the metal-loaded BiVO4 catalysts showed superior photocatalytic properties for the degradation of ibuprofen.