A framework for validating watershed ecosystem service models in the United States using long-term water quality data: Applications with the InVEST Nutrient Delivery (NDR) model in Puerto Rico.

Modeling of watershed Ecosystem Services (ES) processes has increased greatly in recent years, potentially improving environmental management and decision-making by describing the value of nature. ES models may be sensitive to different conditions and, therefore, should ideally be validated against observed data for their use as a decision-support instrument. However, outcomes from such ES modeling are barely validated, making it difficult to assess uncertainties associated with the modeling and justify their actual usefulness to develop generalizable management recommendations. This study proposes a framework for the systematic validation of one of such tools, the InVEST Nutrient Delivery Model (NDR) for nutrient retention estimates. The framework is divided into three stages: 1) running the NDR model inputs, processes, and outputs; 2) building a long-term reference dataset from open access water quality observations; and 3) using the reference data for model calibration and validation. We applied this framework to twenty watersheds in the Commonwealth of Puerto Rico, where data availability resembles thar of watersheds across the United States. Long-term water quality data from monitoring stations facilitated model calibration and validation. Our framework provided a reproducible method to linking the vast monitoring network in the U.S. and its territories for evaluating the InVEST's NDR model performance. Beyond the framework development, this study found that the InVEST NDR model explained 62.7 % and 79.3 % of the variance in the total nitrogen and total phosphorus between 2000 and 2022, respectively, supporting the suitability of the model for watershed scale ecosystem services assessment. The findings can also serve as a reference to support the use of InVEST for other locations in the tropics without publically available monitoring data.

Identification of a novel immune prognostic model in gastric cancer.

PURPOSE: The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients. METHODS: Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset. RESULTS: Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores. CONCLUSION: This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.

Is there a role for chemotherapy and radiation in the treatment of patients with low-grade myofibroblastic sarcoma?

PURPOSE: Low-grade myofibroblastic sarcoma (LGMS) is a rare entity with a predilection for the head and neck. There are still no optimal treatment strategies for patients with LGMS. We retrospectively investigated the efficacies of chemotherapy and radiation treatment for patients with LGMS. METHODS/PATIENTS: We obtained data from the Surveillance, Epidemiology, and End Result (SEER) database for 96 patients diagnosed with LGMS between 2001 and 2015. We used Kaplan-Meier curves and log-rank tests to estimate overall survival (OS) and Cox proportional hazard regression to identify prognostic factors. RESULTS: The median age of the patients was 55.0 years. Twenty-two of the patients had LGMS in the head and neck region. Of the 96 patients, 86 (89.6%) received surgical treatment, 28 (29.2%) received radiation treatment, and 20 (10.4%) received chemotherapy. The mean OS was 125.2 [95% confidence interval (CI) 106.3-144.2] months. The 1, 3, 5, and 10-year OS rates were 88%, 77%, 70%, and 59%, respectively. Age greater than 60 years, positive nodal status, and no surgical treatment were independent prognostic factors for patients with LGMS, whereas chemotherapy and radiation treatment were not. CONCLUSIONS: Surgical resection is the most effective therapy for LGMS. Chemotherapy and radiation had limited effects on survival improvement for patients with LGMS. Therefore, chemotherapy and/or radiation therapy should not be routinely performed in LGMS, especially for those with negative margins after surgery.

Effect of oviposition by Bactrocera dorsalis on the antioxidant activity of orange juice / Efeito da oviposição de Bactrocera dorsalis na atividade antioxidante do suco de laranja

Abstract Among fruits and fruit products, oranges and orange juice are the most widely consumed worldwide. However, the effects of pest infestation of oranges on the quality of orange juice are not yet known. To evaluate the effect of the oriental fruit fly Bactrocera dorsalis on the antioxidant activity of orange juice, we measured changes in the vitamin C (Vc) concentration, total phenol content, and antioxidant activity of orange juice after the introduction of fruit fly eggs. Ten days after the eggs were introduced (larvae removed), the concentration of Vc in orange juice was 18.65 µg/mL, which was 9.16 µg/mL lower than that measured in healthy orange juice. In addition, the total phenol content decreased by 46.519 mg Gallic Acid Equivalents (GAE)/g to 9.748 mg GAE/g. Furthermore, the free-radical scavenging activity decreased from 22.297% to 5.393%. Correlation analysis indicated significant correlations between Vc concentration, total phenol content, and antioxidant activity of orange juice after B. dorsalis infestation. The decrease in Vc concentration, total phenol content and free-radical scavenging activity indicated that B. dorsalis changed the quality of orange juice by affecting the antioxidant activity of the juice after the oranges were infested.

Resumo Entre frutas e produtos de frutas, as laranjas e suco de laranja são os mais consumidos em todo o mundo. No entanto, os efeitos da infestação de laranjas sobre a qualidade do suco de laranja ainda não são conhecidos. Para avaliar o efeito da mosca-das-frutas oriental, Bactrocera dorsalis, sobre a atividade antioxidante do suco de laranja, foram medidas as mudanças na concentração de vitamina C (Vc), no teor de fenol total e na atividade antioxidante do suco de laranja após a introdução de ovos da mosca-das-frutas oriental. Dez dias após a introdução dos ovos (larvas removidas), a concentração de Vc no suco de laranja foi de 18,65 µg/mL, que foi 9,16 µg/mL menor do que a medida em suco de laranja saudável. Além disso, o teor total de fenol diminuiu de 46,519 mg em equivalente de ácido gípico (GAE)/g para 9,748 mg de GAE/g. Ademais, a atividade de eliminação de radicais livres diminuiu de 22,297% para 5,393%. A análise de correlação indicou correlações significativas dentre a concentração de Vc, o conteúdo total de fenol e a atividade antioxidante do suco de laranja após a infestação por B. dorsalis. A diminuição na concentração de Vc, o conteúdo total de fenol e a atividade sequestradora de radicais livres indicaram que B. dorsalis alterou a qualidade do suco de laranja, afetando a atividade antioxidante do suco após a infestação das laranjas.

Effect of oviposition by Bactrocera dorsalis on the antioxidant activity of orange juice.

Among fruits and fruit products, oranges and orange juice are the most widely consumed worldwide. However, the effects of pest infestation of oranges on the quality of orange juice are not yet known. To evaluate the effect of the oriental fruit fly Bactrocera dorsalis on the antioxidant activity of orange juice, we measured changes in the vitamin C (Vc) concentration, total phenol content, and antioxidant activity of orange juice after the introduction of fruit fly eggs. Ten days after the eggs were introduced (larvae removed), the concentration of Vc in orange juice was 18.65 µg/mL, which was 9.16 µg/mL lower than that measured in healthy orange juice. In addition, the total phenol content decreased by 46.519 mg Gallic Acid Equivalents (GAE)/g to 9.748 mg GAE/g. Furthermore, the free-radical scavenging activity decreased from 22.297% to 5.393%. Correlation analysis indicated significant correlations between Vc concentration, total phenol content, and antioxidant activity of orange juice after B. dorsalis infestation. The decrease in Vc concentration, total phenol content and free-radical scavenging activity indicated that B. dorsalis changed the quality of orange juice by affecting the antioxidant activity of the juice after the oranges were infested.

Novel exosomal miR-46146 transfer oxaliplatin chemoresistance in colorectal cancer.

PURPOSE: Oxaliplatin (OX) is widely used for patients with advanced colorectal cancer (CRC). However, most of them will turn out to be OX resistant. Therefore, it is necessary to uncover the causes underlying this phenomenon. METHODS: Emerging works have reported that exosomal miRNAs are linked to chemoresistance in many types of cancer. Hence, we separated exosomes from OX sensitive (Exo-S) and resistant CRC cells (Exo-R) by ultracentrifugation and characterized those exosomes by transmission electron microscope and Nanosight NS300. The differentiated miRNAs between Exo-S and Exo-R were identified by small RNA deep sequencing. The expression of miRNA was examined by quantitative real-time PCR (qRT-PCR). The effect of Exo-R and exosomal miR-46146 was determined by CCK-8 assay and flow cytometry (FCM). The target gene of miR-46146 was predicted by computational algorithms and validated by dual luciferase assay. RESULTS: We found that parental OX sensitive CRC cell acquired increased resistance to the cytotoxicity of OX when they were cocultured with exosomes secreted by OX-resistant CRC. Notably, a novel miRNA miR-46146 was identified and proved to be upregulated in the Exo-R which was internalized by its recipient cells and contributes to the chemoresistance transfer. Furthermore, we demonstrated that PDCD10 was the direct functional target of miR46146 and augmentation of the PDCD10 expression might reverse the effect of Exo-miR-46146-driven chemoresistance. CONCLUSIONS: These results indicate that exosomal miR-46146 functions as a vital mediator of OX resistance by targeting PDCD10 and could be a potential target to re-sensitize CRC cell to OX.

Effect of oviposition by Bactrocera dorsalis on the antioxidant activity of orange juice

Among fruits and fruit products, oranges and orange juice are the most widely consumed worldwide. However, the effects of pest infestation of oranges on the quality of orange juice are not yet known. To evaluate the effect of the oriental fruit fly Bactrocera dorsalis on the antioxidant activity of orange juice, we measured changes in the vitamin C (Vc) concentration, total phenol content, and antioxidant activity of orange juice after the introduction of fruit fly eggs. Ten days after the eggs were introduced (larvae removed), the concentration of Vc in orange juice was 18.65 µg/mL, which was 9.16 µg/mL lower than that measured in healthy orange juice. In addition, the total phenol content decreased by 46.519 mg Gallic Acid Equivalents (GAE)/g to 9.748 mg GAE/g. Furthermore, the free-radical scavenging activity decreased from 22.297% to 5.393%. Correlation analysis indicated significant correlations between Vc concentration, total phenol content, and antioxidant activity of orange juice after B. dorsalis infestation. The decrease in Vc concentration, total phenol content and free-radical scavenging activity indicated that B. dorsalis changed the quality of orange juice by affecting the antioxidant activity of the juice after the oranges were infested.(AU)

Entre frutas e produtos de frutas, as laranjas e suco de laranja são os mais consumidos em todo o mundo. No entanto, os efeitos da infestação de laranjas sobre a qualidade do suco de laranja ainda não são conhecidos. Para avaliar o efeito da mosca-das-frutas oriental, Bactrocera dorsalis, sobre a atividade antioxidante do suco de laranja, foram medidas as mudanças na concentração de vitamina C (Vc), no teor de fenol total e na atividade antioxidante do suco de laranja após a introdução de ovos da mosca-das-frutas oriental. Dez dias após a introdução dos ovos (larvas removidas), a concentração de Vc no suco de laranja foi de 18,65 µg/mL, que foi 9,16 µg/mL menor do que a medida em suco de laranja saudável. Além disso, o teor total de fenol diminuiu de 46,519 mg em equivalente de ácido gípico (GAE)/g para 9,748 mg de GAE/g. Ademais, a atividade de eliminação de radicais livres diminuiu de 22,297% para 5,393%. A análise de correlação indicou correlações significativas dentre a concentração de Vc, o conteúdo total de fenol e a atividade antioxidante do suco de laranja após a infestação por B. dorsalis. A diminuição na concentração de Vc, o conteúdo total de fenol e a atividade sequestradora de radicais livres indicaram que B. dorsalis alterou a qualidade do suco de laranja, afetando a atividade antioxidante do suco após a infestação das laranjas.(AU)

A new genus and species, Barbaropus flatus, from Ecuador with notes on Empoascini (Hemiptera: Cicadellidae: Typhlocybinae).

A new microleafhopper genus, Barbaropus gen. nov., is described based on a new species, Barbaropus flatus sp. nov. from Ecuador. Male habitus photos and illustrations of male genitalia are provided and differences between the new genus and closely related Neotropical genera are discussed. The relationship and the status of this new genus within the tribe are also discussed.

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin.

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic ß-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Identification a novel set of 6 differential expressed genes in prostate cancer that can potentially predict biochemical recurrence after curative surgery.

PURPOSE: Approximately, 30% patients after radical prostatectomy (RP) will undergo post-operative biochemical recurrence (BCR). Present stratification method by TNM staging and Gleason score was not adequate to screen high-risk patients. In this study, we intended to identify a novel set of differentially expressed gene (DEG) signature that can predict BCR after RP. MATERIALS/PATIENTS: 358 patients after RP with follow-up data were extracted from The Cancer Genome Atlas (TCGA), among which 61 patients had undergone BCR. Key DEGs were confirmed by the intersection of GSE35988 and TCGA_PCa dataset, and their gene expression data were also extracted from TCGA_PCa dataset. Kaplan-Meier plot and Cox proportion hazard regression model were applied to assess the relationship between risk score and survival outcome (BCR). RESULTS: 310 DEGs were confirmed in two prostate cancer dataset. 6 DEGs (SMIM22, NINL, NRG2, TOP2A, REPS2, and TPCN2) were selected to construct a risk score formula. The risk score was a powerful predictive factor independent of TNM stage (HR 3.045, 95% CI 1.655-5.602, p < 0.001). CONCLUSION: In this study, a novel 6-gene signature with robust predictive ability on post-operative BCR was constructed and 4 genes (SMIM22, NRG2, NINL and TPCN2) in the 6-gene signature were not reported to be associated with prostate cancer.

Effect of oviposition by Bactrocera dorsalis on the antioxidant activity of orange juice

Abstract Among fruits and fruit products, oranges and orange juice are the most widely consumed worldwide. However, the effects of pest infestation of oranges on the quality of orange juice are not yet known. To evaluate the effect of the oriental fruit fly Bactrocera dorsalis on the antioxidant activity of orange juice, we measured changes in the vitamin C (Vc) concentration, total phenol content, and antioxidant activity of orange juice after the introduction of fruit fly eggs. Ten days after the eggs were introduced (larvae removed), the concentration of Vc in orange juice was 18.65 µg/mL, which was 9.16 µg/mL lower than that measured in healthy orange juice. In addition, the total phenol content decreased by 46.519 mg Gallic Acid Equivalents (GAE)/g to 9.748 mg GAE/g. Furthermore, the free-radical scavenging activity decreased from 22.297% to 5.393%. Correlation analysis indicated significant correlations between Vc concentration, total phenol content, and antioxidant activity of orange juice after B. dorsalis infestation. The decrease in Vc concentration, total phenol content and free-radical scavenging activity indicated that B. dorsalis changed the quality of orange juice by affecting the antioxidant activity of the juice after the oranges were infested.

Resumo Entre frutas e produtos de frutas, as laranjas e suco de laranja são os mais consumidos em todo o mundo. No entanto, os efeitos da infestação de laranjas sobre a qualidade do suco de laranja ainda não são conhecidos. Para avaliar o efeito da mosca-das-frutas oriental, Bactrocera dorsalis, sobre a atividade antioxidante do suco de laranja, foram medidas as mudanças na concentração de vitamina C (Vc), no teor de fenol total e na atividade antioxidante do suco de laranja após a introdução de ovos da mosca-das-frutas oriental. Dez dias após a introdução dos ovos (larvas removidas), a concentração de Vc no suco de laranja foi de 18,65 µg/mL, que foi 9,16 µg/mL menor do que a medida em suco de laranja saudável. Além disso, o teor total de fenol diminuiu de 46,519 mg em equivalente de ácido gípico (GAE)/g para 9,748 mg de GAE/g. Ademais, a atividade de eliminação de radicais livres diminuiu de 22,297% para 5,393%. A análise de correlação indicou correlações significativas dentre a concentração de Vc, o conteúdo total de fenol e a atividade antioxidante do suco de laranja após a infestação por B. dorsalis. A diminuição na concentração de Vc, o conteúdo total de fenol e a atividade sequestradora de radicais livres indicaram que B. dorsalis alterou a qualidade do suco de laranja, afetando a atividade antioxidante do suco após a infestação das laranjas.

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Metals geochemistry and mass export from the Mississippi-Atchafalaya River system to the Northern Gulf of Mexico.

Discharging 680 km3 of freshwater annually to the Northern Gulf of Mexico (NGOM), the Mississippi-Atchafalaya River System (MARS) plays a significant role in transporting major and trace elements to the ocean. In this study, we analyzed total recoverable concentrations of thirty-one metals from water samples collected at five locations along the MARS during 2013-2016 to quantify their seasonal mass exports. The Atchafalaya River flows through a large swamp floodplain, allowing us to also test the hypothesis that floodplains function as a sink for metals. We found that the seven major elements (Ca, Na, Mg, Si, K, Al, and Fe) constituted 99% of the total annual mass load of metals (7.38 × 107 tons) from the MARS. Higher concentrations of Al, Ba, B, Ca, Fe, Mg, Mn, Ag, and Ti were found in the Mississippi River, while significantly higher Si and Na concentrations were found in the Atchafalaya River. Significant relationships were found between daily discharge and daily loads of Ba, Ca, Fe, K, Sr, and Ti in both rivers, while significant relationships were also found for Al, Mg, Mn, V, and Zn in the Atchafalaya River and B in the Mississippi River. Overall, the Mississippi River contributed 64-76% of the total annual loading of metals from the MARS to the NGOM. Daily loads of Al, Ba, B, Fe, Li, Mn, P, K, Si, Ag, Ti, V, and Zn regularly decreased upstream to downstream in the Atchafalaya River, partially accepting the initial hypothesis on metals transport in river floodplains.

Correction to: High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells.

n the original version of the article, Table 2 was incorrect. The corrected Table 2 is shown here. Therefore, in Results (page 3 of original version, right column, line 13), the OR of non-optimal debulking should read OR = 3.036 with 95% CI 1.452-6.348.

High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells.

PURPOSE: HO-1 has been proved to be associated with tumor aggressivity and poor prognosis in various cancers. Our study provides the first study to demonstrate the relationship of HO-1 expression and clinical characteristics in ovarian cancer patients. METHODS: Immunohistochemistry and western blotting were used to examine the expression of HO-1 in tissue species and fresh tissues. CCK-8 was used to investigate cell viability. Transwell chamber was performed to estimate migration and invasion capacities in A2780 and Skov-3 cells. RESULTS: Immunohistochemistry and western blotting showed that the expression of HO-1 was higher in ovarian cancer tissues than normal ovarian tissues. High expression of HO-1 was significantly associated with serous ovarian cancer, high FIGO stage, lymph node metastasis, and non-optimal debulking. Patients with high expression of HO-1 exhibited an unfavorable prognosis. In vitro inducing the expression of HO-1 promoted the proliferation and metastasis of A2780 and Skov-3 cells, with the increased expressions of mesenchymal marker (Vimentin), epithelial-mesenchymal transition-associated transcript factor (Zeb-1), anti-apoptotic protein (Bcl-2), and the decreased expressions of epithelial marker (Keratin) and pro-apoptotic protein (Bax). Meanwhile, after incubating A2780 and Skov-3 together with HO-1 inhibitor, above results could be reversed. CONCLUSION: HO-1 might be a potential marker for prediction of ovarian cancer prognosis and a target for ovarian cancer treatment.

Is endobronchial ultrasound-guided transbronchial needle aspiration with a stylet necessary for lymph node screening in lung cancer patients?

During endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), a needle is commonly used with a stylet, although recently the stylet has been omitted. This prospective study aimed to compare the quality of specimens obtained by EBUS-TBNA performed with and without a stylet. Between November 2013 and November 2014, 131 patients with lung cancer underwent EBUS-TBNA, with a total of 148 mediastinal or hilar lymph nodes sampled both with and without an inner-stylet, yielding 296 cytological specimens. Specimens were scored cytologically using five parameters: background blood or clot, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and retention of appropriate architecture. The procedure with a stylet required significantly longer operation time than without a stylet (14.5±0.8 vs 12.7±1.1 min, P<0.001). Excellent specimens were obtained in 261/296 and 260/296 samples in the procedures with and without a stylet, respectively (P=0.9), while the remaining 35 and 36 samples, respectively, were adequate. The diagnosing and staging of lung cancer using EBUS-TBNA did not differ significantly between the groups. In conclusion, specimen collection by EBUS-TBNA without a stylet is easier and faster than the procedure using a stylet and absence of a stylet did not alter specimen quality or diagnostic accuracy.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method.

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Association between MFN2 gene polymorphisms and the risk and prognosis of acute liver failure: a case-control study in a Chinese population.

This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.

Novel endodontic sealers induce cell cytotoxicity and apoptosis in a dose-dependent behavior and favorable response in mice subcutaneous tissue.

OBJECTIVES: The objective of the present study is to evaluate the in vitro cytotoxicity and in vivo biocompatibility of two novel endodontic sealers: RealSeal XT1 and Sealapex Xpress on the subcutaneous connective tissue of mice. MATERIALS AND METHODS: The cytotoxicity was assessed by cell viability using the MTT assay (one-way ANOVA), trypan blue test (Mann-Whitney) and cell apoptosis by flow cytometer. For the subcutaneous study, polyethylene tubes filled with the sealers were implanted in 70 BALB/c mice: 6 experimental groups (n = 10/group) and 2 control groups with empty tubes (n = 5/group). At the end of experimental periods (7, 21, and 63 days), the tissue was removed and histotechnically processed. Angioblastic proliferation and edema (Fisher's exact test) were evaluated, besides thickness measurement (µm) of the reactionary granulomatous tissue and neutrophil counts (Kruskal-Wallis and Dunn's post test; Mann-Whitney) (α = 0.05). RESULTS: MTT assay, trypan blue, and analysis of apoptotic cells showed a dose-dependent direct effect: the more diluted the sealer, the less cytotoxic. Regarding the angioblastic proliferation and edema, difference between the sealers at 7 and 63 days occurred (p < 0.05). Both endodontic sealers initially promoted perimaterial tissue reaction as a foreign body granuloma and thus stimulated favorable tissue responses. CONCLUSIONS: Both sealers showed a dose-dependent effect and promoted satisfactory subcutaneous tissue response; the sealer Sealapex Xpress was less cytotoxic and more biocompatible than RealSeal XT. CLINICAL RELEVANCE: The step of root canal filling during endodontic treatment is highly important for the preservation of the periapical tissue integrity. Subcutaneous reaction to endodontic sealers enables scientific basis for clinical use.

Role of TIM-3 in ovarian cancer.

Evidences have suggested that immunotherapy for ovarian cancer is effective. Immune checkpoints have emerged in the field of cancer immunotherapy. Multiple studies have shown negative regulation of TIM-3 expression on CD4+ and CD8+ T cells and other immunocytes. Overexpression of TIM-3 in innate immune cells has been found in certain types of tumor. The blockade of TIM-3 leads to sustained anti-tumor reactions. TIM-3 plays an inhibitive role for immunity in ovarian cancer. TIM-3 is involved in the development of various subtypes of ovarian cancer and thus has the potential to be a therapeutic target for treatment of ovarian cancer.