The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis.

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

Biofilm of petroleum-based and bio-based microplastics in seawater in response to Zn(II): Biofilm formation, community structure, and microbial function.

Microplastic biofilms are novel vectors for the transport and spread of pathogenic and drug-resistant bacteria. With the increasing use of bio-based plastics, there is an urgent need to investigate the microbial colonization characteristics of these materials in seawater, particularly in comparison with conventional petroleum-based plastics. Furthermore, the effect of co-occurring contaminants, such as heavy metals, on the formation of microplastic biofilms and bacterial communities remains unclear. In this study, we compared the biofilm bacterial community structure of petroleum-based polyethylene (PE) and bio-based polylactic acid (PLA) in seawater under the influence of zinc ions (Zn2+). Our findings indicate that the biofilm on PLA microplastics in the late stage was impeded by the formation of a mildly acidic microenvironment resulting from the hydrolysis of the ester group on PLA. The PE surface had higher bacterial abundance and diversity, with a more intricate symbiotic pattern. The bacterial structures on the two types of microplastics were different; PE was more conducive to the colonization of anaerobic bacteria, whereas PLA was more favorable for the colonization of aerobic and acid-tolerant species. Furthermore, Zn increased the proportion of the dominant genera that could utilize microplastics as a carbon source, such as Alcanivorax and Nitratireductor. PLA had a greater propensity to harbor and disseminate pathogenic and drug-resistant bacteria, and Zn promoted the enrichment and spread of harmful bacteria such as, Pseudomonas and Clostridioides. Therefore, further research is essential to fully understand the potential environmental effects of bio-based microplastics and the role of heavy metals in the dynamics of bacterial colonization.

Heat statistics in the relaxation process of the Edwards-Wilkinson elastic manifold.

The stochastic thermodynamics of systems with a few degrees of freedom has been studied extensively so far. We would like to extend the study to systems with more degrees of freedom and even further-continuous fields with infinite degrees of freedom. The simplest case for a continuous stochastic field is the Edwards-Wilkinson elastic manifold. It is an exactly solvable model of which the heat statistics in the relaxation process can be calculated analytically. The cumulants require a cutoff spacing to avoid ultraviolet divergence. The scaling behavior of the heat cumulants with time and the system size as well as the large deviation rate function of the heat statistics in the large size limit is obtained.

Full counting statistics and fluctuation theorem for the currents in the discrete model of Feynman's ratchet.

We provide a detailed investigation of the fluctuations of the currents in the discrete model of Feynman's ratchet proposed by Jarzynski and Mazonka in 1999. Two macroscopic currents are identified, with the corresponding affinities determined using Schnakenberg's graph analysis. We also investigate full counting statistics of the two currents and show that fluctuation theorem holds for their joint probability distribution. Moreover, fluctuation-dissipation relation, Onsager reciprocal relation and their nonlinear generalizations are numerically shown to be satisfied in this model.

Convergent and divergent gray matter volume abnormalities in unaffected first-degree relatives and ultra-high risk individuals of schizophrenia.

High-risk populations of schizophrenia can be mainly identified as genetic high-risk based on putative endophenotypes or ultra-high-risk (UHR) based on clinically manifested symptoms. Previous studies have consistently shown brain structural abnormalities in both genetic high-risk and UHR individuals. In this study, we aimed to disentangle the convergent and divergent pattern of gray matter alterations between UHR and unaffected first-degree relatives from genetic high-risk individuals. We used structural MRI scans and voxel-based morphometry method to examine gray matter volume (GMV) differences among 23 UHR subjects meeting the Structured Interview for Prodromal Syndromes (SIPS) criteria, 18 unaffected first-degree relatives (UFDR), 26 first-episode schizophrenia patients (FES) and 54 healthy controls (CN). We found that a number of brain regions exhibited a monotonically decreasing trend of GMV from CN to UFDR to UHR to FES. Compared with CN, the UHR subjects showed significant decreases of GMV similar to the patients in the inferior temporal gyrus, fusiform gyrus, middle occipital gyrus, insula, and limbic regions. Moreover, the UHR transformed subgroup had significantly lower GMV than UHR non-transformed subgroup in the right inferior temporal/fusiform gyrus. On the other hand, the UFDR subjects only showed significant GMV decreases in the inferior temporal gyrus and fusiform. Moreover, we found GMV in the occipital lobe was negatively correlated with the UHR subjects' composite positive symptom of SIPS, and GMV in the cerebellum was positively correlated with FES subjects' symptom severity. Our results suggest that GMV deficits and regional dysfunction are evident prior to the onset of psychosis and are more prominent in the UHR than the UFDR individuals.

Comparative transcriptome analysis reveals physiological responses in liver tissues of Epinephelus coioides under acute hypoxia stress.

Hypoxia is a common stressor for aquatic animals, including Epinephelus coioides, with a considerable impact on sustainable aquaculture. E. coioides is a widely consumed fish in China owing to its high nutritious value and taste. However, water hypoxia caused by high density culture process has become a great threat to E. coioides culture, and its response to hypoxia stress has not been discussed before. Therefore, the aim of this study was to examine the response of E. coioides to acute hypoxia using transcriptomic techniques. To this end, RNA sequencing was performed on the liver tissues of fish exposed to normoxic and hypoxic conditions for 1 h. The results presented 503 differentially expressed genes (DEGs) in the liver tissue of fish exposed to hypoxic condition compared with those in the normoxic group. Enrichment analysis using the Gene Ontology database showed that the DEGs were mainly enriched for functions related to cell apoptosis signaling pathways, insulin resistance, antioxidant enzymes, and glycolysis/gluconeogenesis signaling pathways. KEGG enrichment analysis showed that HIF-1, PI3K-AKT, IL-17, NF-kappa B, and MAPK signaling pathways were significantly enriched by the DEGs. The DEGs were mainly involved in immune response, inflammatory response, cell apoptosis regulation, energy metabolism, and substance metabolism. Additionally, the hypoxia response in E. coioides was mainly regulated via the PI3K-AKT-HIF-1 signaling axis. Overall, the findings of this study contribute to the understanding of hypoxia stress response in E. coioides, and provides target genes for breeding hypoxia-tolerant Epinephelus spp.

Mimicking DNA Periodic Docking Grooves for Adaptive Identification of l-/d-Tryptophan in a Biological Metal-Organic Framework.

Bioinspired metal-organic frameworks (MOFs) serve as suitable crystalline models for recognition and sensing of biomolecules mimicking natural processes, providing new ideas and concepts for cutting-edge biomedical applications. Here, we have successfully prepared a robust biological metal-organic framework with periodic docking grooves resembling the major and minor grooves in the DNA double helix structure, which can be used as unique recognition sites for selectively identifying l-/d-tryptophan (l-/d-Trp). Notably, successful encapsulation of Trp could be observed by single-crystal X-ray diffraction for the first time. Trp has matched size and shape to fit snugly into the major groove. Combined with isothermal titration calorimetry, it was found that ZnBTCHx could spontaneously capture l-/d-Trp through two different thermodynamic pathways: enthalpy-driven for encapsulating l-Trp and entropy-driven for uptaking d-Trp. Furthermore, molecular dynamics and density functional theory verified the role of hydrogen bonding and π-π/C-H···π interactions in the host-guest interface. This work provides unique insight for the construction of bionic models to mimic the natural binding properties, which is of great significance for the fields of pharmaceutical chemistry and biomedical science.

Development of a novel five-lncRNA prognostic signature for predicting overall survival in elderly patients with breast cancer.

BACKGROUND: Breast cancer (BC) is an age-related disease. Long noncoding RNAs (lncRNAs) have been proven to be crucial contributors in tumorigenesis. This study aims to develop a novel lncRNA-based signature to predict elderly BC patients' prognosis. METHODS: The RNA expression profiles and corresponding clinical information of 182 elderly BC patients were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) between BC and adjacent normal samples were used to construct the signature in the training set through univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the predictive performance. Besides, we developed the nomogram. Gene set enrichment analysis (GSEA) was performed to reveal the underlying molecular mechanisms. RESULTS: We constructed the five-lncRNA signature (including LEF1-AS1, MEF2C-AS1, ST8SIA6-AS1, LINC01224, and LINC02408) in the training set, which successfully divided the patients into low- and high-risk groups with significantly different prognosis (p = 0.000049), and the AUC at 3 and 5 years of the signature was 0.779 and 0.788, respectively. The predictive performance of this signature was validated in the test and entire set. The 5-lncRNA signature was an independent prognostic factor of OS (p = 0.007) and the nomogram constructed by independent prognostic factors was an accurate predictor of predicting overall survival probability. Besides, several pathways associated with tumorigenesis have been identified by GSEA. CONCLUSIONS: The 5-lncRNA signature and nomogram are reliable in predicting elderly BC patients' prognosis and provide clues for clinical decision-making.

Combination of Endogenous Estradiol and Adipokine Leptin in Breast Cancer Risk and Prognosis Assessment in Postmenopausal Chinese Women.

Objective: Our study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women. Design: The serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher's exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset. Setting: The study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Patients: A total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis. Main Outcome Measure: Serum circulating estradiol and leptin level. Results: The level of estradiol was significantly higher (P<0.001) but the level of leptin had no significant difference (P = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P>0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038). Conclusion: Circulating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.

[Quantitative separation of evapotranspiration components of Platycladus orientalis ecosystem based on multiple isotope models]. / åŸºäºŽå¤šç§åŒä½ç´ æ¨¡åž‹çš„ä¾§æŸæž—ç”Ÿæ€ç³»ç»Ÿè’¸æ•£ç»„åˆ†å®šé‡æ‹†åˆ†.

To fully understand the changes in the evapotranspiration components in forest ecosystem and their contribution to evapotranspiration at daily scale, we used the hypothesis theory of isotopic steady state and non-steady state combined with the water isotope analyzer system to quantitatively split and compare the evapotranspiration components of Platycladus orientalis ecosystem during the growing season. Results showed that the 18O of water from different sources during the four mea-surement days (August 5, 8, 10, 11, 2016) all showed surface soil water and oxygen isotope composition (δS) > branch water and oxygen isotope composition (δX) > atmospheric water vapor oxygen isotopes composition (δV), with obvious differences due to the isotope fractionation. Oxygen isotopes composition of soil evaporated water vapor (δE) was between -26.89‰ï½ž-59.68‰ at the daily scale, showing a pattern of first rising and then decreasing. The oxygen isotopic composition of evapotranspiration water vapor in forest ecosystem (δET) was between -15.99‰ï½ž-10.04‰. The oxygen isotopic composition of transpired water vapor under steady state(δT-ISS) was between -12.10‰ï½ž-9.51‰. The oxygen isotopic composition of transpired water vapor under non-steady state (δT-NSS) was between -13.02‰ï½ž-7.23‰. δET and δT-NSS had the same changing trend throughout the day at the daily scale, while the trend of δET, δT-ISS and δT-NSS was approximately the same during 11:00-17:00. In general, the contribution rate of plant transpiration to total evapotranspiration showed that FT-ISS was between 79.1%-98.7%, and FT-NSS was between 88.7%-93.7%. Our results suggested that water consumption through soil evaporation was far less than that of vegetation transpiration in the study area, and that vegetation transpiration dominated forest evapotranspiration.

[Formation and changes of regulated trihalomethanes and haloacetic acids in raw water of Yangtze River, Huangpu River and different treatment processes and pipelines network].

OBJECTIVES: To investigate the pollutant levels of regulated disinfection by-products trihalomethanes (THMs) and haloacetic acids (HAAs) in raw water from the Huangpu River, the Yangtze River and different treatment processes and finished water, and to explore the changes tendency in transmission and distribution pipeline network. METHODS: A total of 65 ml water samples with two replicates were collected from different raw water, corresponding treatment processes, finished water and six national surveillance points in main network of transmission and distribution, water source for A water plant and B, C water plant was the Huangpu River and the Yangtze River, respectively. Regulated THMs and HAAs above water samples were detected by gas chromatography. RESULTS: The total trihalomethanes (THM(4)) concentration in different treatment processes of A water plant was ND-9.64 µg/L, dichlorobromomethane was the highest (6.43 µg/L). The THM(4) concentration in B and C water plant was ND to 38.06 µg/L, dibromochloromethane (12.24 µg/L) and bromoform (14.07 µg/L) were the highest in the B and the C water plant respectively. In addition to trichloroacetic acid in A water plant from the raw water, the other HAAs came from different treatment processes. The total haloacetic acids (HAA(6)) concentration of different treated processes in A water plant was 3.21 - 22.97 µg/L, mobromoacetic acid (10.40 µg/L) was the highest. Dibromoacetic acid was the highest both in B (8.25 µg/L) and C (8.84 µg/L) water plant, HAA(6) concentration was ND to 27.18 µg/L. The highest and the lowest concentration of THM(4) were found from the main distribution network of C and A water plant respectively, but the concentration of HAA(6) in the main water pipes network of A water plant was the highest, and the lowest in C water plant. The THMs concentration was 21.11 - 31.18 µg/L in C water plant and 6.72 - 8.51 µg/L in A water plant. The concentration of HAA(6) was 25.02 - 37.31 µg/L in A water plant and 18.69 - 23.32 µg/L in C water plant. The highest concentrations of brominated disinfection by-products in B and C water plant were 54.57 µg/L and 45.38 µg/L respectively, those were higher than A water plant (18.98 µg/L), and higher than the chlorinated disinfection by-products in B and C water plants (30.23 µg/L and 30.60 µg/L). CONCLUSIONS: The THM(4) concentrations of finished water treated from Huangpu River was lower than finished water from the Yangtze River, while the HAAs concentrations in finish water from Huangpu River was higher than the two water plants of Yangtze River. The fluctuations of THMs and HAAs concentration in distribution network were low during transmission and distribution process.

[Total calvarial reconstruction for sagittal synostosis].

OBJECTIVE: To study the technique of total calvaria reconstruction for sagittal synostosis. METHODS: 11 children with sagittal synostosis were treated. The David II procedure was used to reconstruct the calvarial gap in 6 cases; Osteotomies with reversal change was performed on 2 cases; Plum-plasty of the calvaria was performed on 3 cases. RESULTS: The 11 cases were cured with satisfactory head shape. CONCLUSIONS: The David II procedure is applicable for patient of 1 approximately 3 months. The technique of floating skull flap plasty and plum-plasty of the calvaria can be performed on patients older than 3 months.

[Study on expression of Ki-67, early apoptotic protein M30 in endometrial carcinoma and their correlation with prognosis].

OBJECTIVE: To assess the correlation between expression of proliferation antigen Ki-67, early apoptotic protein M30 (M30CytoDEATH, CK18) and biologic characteristics in endometrial carcinoma. METHODS: SP immunohistochemical technique was used to detect the expression of Ki-67 and M30 in 79 cases of endometrial carcinoma respectively. RESULTS: The mean Ki-67 indices varied with histological grading and clinical stage of the tumor, being 20.48 +/- 14.86 in grade 1, 24.12 +/- 14.42 in grade 2 and 38.84 +/- 11.88 in grade 3; 20.65 +/- 13.56 in stage I; 26.92 +/- 14.71 in stage II; and: 35.14 +/- 14.70 in stage III. The mean M30 indices varied with the grading and stage of the tumor, being 1.03 +/- 1.42 in grade 1, 1.03 +/- 1.64 in grade 2 and 1.94 +/- 1.20 in grade 3; 0.30 +/- 0.58 in stage I; 1.66 +/- 1.74 in stage II; and 2.07 +/- 1.62 in stage III. CONCLUSIONS: Ki-67 and M30 indexes are significantly correlated with biologic behavior and prognosis in endometrial carcinoma. There is a positive relationship between Ki-67 and M30 indexes.

Induction of apoptosis by arsenic trioxide and hydroxy camptothecin in gastriccancer cells in vitro.

AIM:To study the effects of arsenic trioxide and HCPT on dif ferent degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28) with respect to both cytotoxicity and induction of apoptosis in vitro.METHODS:The cytotoxicity of As(2)O(3) and HCPT on gastric cancer cells was det ermined by MTT assay.Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As(2)O(3) we re investigated by TUNEL method and flow cytometry.RESULTS:As(2)O(3) and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC(50) of As(2)O(3) on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8.91 &mgr;mol/L, 10.57 &mgr;mol/L, and 11.65&mgr;mol/L, respectively. The IC(50) of HCP T on MKN-28, SGC-7901, and MKN-45 were 9.35 mg/L, 10.21 mg/L,and 12.63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, includ ing cell shrinkage,nuclear condensation, and formation of apoptotic bodies. A ty pical subdiploid peak before G(0)/G(1) phase was observed by flow cytometry. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 13.84%, 22.52%, and 9.68%, respectively after48 h exposure to 10&mgr;mol/L As(2)O(3). The apoptotic ra tes of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30.26%, resp ectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7%-15% a s assessed by TUNEL method. The effect of As(2)O(3) on SGC-7901 showed remarkab le cell cycle specificity, which induced cell death in G(1) phase, and blocked G(2)/M phase.HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G(1) phase and arrest of proliferation at Sphase.CONCLUSION:As(2)O(3) and HCPT exhibit significant cytotoxicity on gastric canc er cells by induction of apoptosis. As(2)O(3) and HCPT might have a promising pr ospect in the treatment of gastric cancer, which needs to be further studied.