Expression and immunogenicity of hepatitis E virus-like particles based on recombinant truncated ORF2 capsid protein.

Hepatitis E is an emerging zoonotic disease, posing a severe threat to public health in the world. Since there are no specific treatments available for HEV infection, it is crucial to develop vaccine to prevent this infection. In this study, the truncated ORF2 encoded protein of 439aa∼617aa (HEV3-179) from HEV CCJD-517 isolates was expressed as VLPs in E. coli with diameters of approximate 20 nm. HEV3-179 protein was immunized with mice, and the results showed that a higher titre of antibody was induced in NIH mice in comparison with that of KM mice (P < 0.01) and BALB/c mice (P < 0.01). The induced antibody titer is much higher in subcutaneous immunization mice than that in the mice inoculated via abdominal immunization (P < 0.05) and muscles immunization (P < 0.01). Mice immunized with 12 µg and 6 µg candidate vaccine induced higher level of antibody titer than that of 3 µg dosage group (P < 0.01, P < 0.05). Antibody change curve showed that HEV IgG antibody titer increased from 14 days post immunization (dpi) to 1:262144 and reached the peak level on 42 dpi before gradually retreated with the same level antibody titer with 1:131072 until 84 dpi. Mice inoculated with HEV3-179 produced higher titer of cytokines than the mock group, and the concentration of IL-1ß (P < 0.01) and IFN-γ (P < 0.01) further increased after stimulated by candidate vaccine. The result indicated that HEV3-179 possesses good immunogenicity, which could be used as a potential candidate for future HEV vaccine development.

Intergenerational toxic effects of parental exposure to [Cn mim]NO3 (n = 2,4,6) on nervous and skeletal development in zebrafish offspring.

Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.

Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study.

BACKGROUND: The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients. METHODS: We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018. RESULTS: The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30-40 (P = 0.047). CONCLUSIONS: AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.

Predictive power of a body shape index and traditional anthropometric indicators for cardiovascular disease: a cohort study in rural Xinjiang, China.

BACKGROUND: A body shape index (ABSI) has been proven to be related to a population's CVD incidence. However, the application of this indicator has produced different results. AIM: This study aimed to evaluate the applicability of the ABSI in predicting the incidence of CVD in rural Xinjiang, China, and compare it with waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI). SUBJECTS AND METHODS: 5375 people aged 18 years or older were included in the study. We used the Cox proportional hazard model to evaluate the relationship between WC, WHR, WHtR, BMI, and ABSI and the incidence of CVD, the area under the curve (AUC) to evaluate the predictive power of each anthropometric index for the incidence of CVD, and restricted cubic splines are used to analyse the trend relationship between anthropometric indicators and the incidence of CVD. RESULTS: After multivariate adjustment, standardised WC, WHR, WHtR, BMI, and ABSI all positively correlated with the incidence of CVD. WC had the highest HR (95% CI) value, 1.64 (1.51-1.78), and AUC (95% CI) value, 0.7743 (0.7537-0.7949). ABSI had the lowest HR (95% CI) value, 1.21(1.10-1.32), and AUC (95% CI) value, 0.7419 (0.7208-0.7630). In the sex-specific sensitivity analysis, the predictive ability of traditional anthropometric indicators for the incidence of CVD is higher than that of ABSI. CONCLUSIONS: In the rural areas of Xinjiang, the traditional anthropometric indicators of WC had better ability to predict the incidence of CVD than ABSI.

Metabolically healthy obesity and unhealthy normal weight rural adults in Xinjiang: prevalence and the associated factors.

BACKGROUND: This study aimed to describe the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW) rural adults in Xinjiang and to explore their influencing factors. METHODS: We selected 13,525 Uyghur, Kazakh and Han participants in Kashi, Yili and Shihezi areas in Xinjiang from 2009 to 2010. Weight status was classified according to body mass index. Metabolic phenotype was further defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The prevalence of normal weight, overweight, and obesity were 51.6, 30.2, and 14.4%, respectively. The mean age of the population was 45.04 years. The prevalence of MHO was 5.5% overall and was 38.5% among obese participants. The prevalence of MUNW was 15.5% overall and was 30.1% among normal weight participants. A metabolically healthy phenotype among obese individuals was positively associated with females and vegetable consumption ≥4 plates per week. However, this was inversely associated with higher age, red meat consumption ≥2 kg per week, and larger waist circumference (WC). Conversely, a metabolically unhealthy phenotype among normal-weight individuals was positively associated with higher age, red meat consumption ≥2 kg per week, and larger WC; this was however inversely associated with vegetable consumption ≥4 plates per week. CONCLUSIONS: The prevalence of MHO among obese adults in Xinjiang is higher than that of Han adults, while the prevalence of MUNW among normal weight adults is lower than that among Han adults. In obese and normal weight participants, higher age, more red meat consumption, and larger WC increase the risk of metabolic abnormality, and more vegetable consumption reduces the risk of metabolic abnormality.

Association of total bilirubin and indirect bilirubin content with metabolic syndrome among Kazakhs in Xinjiang.

BACKGROUND: Some studies have shown that a high level of bilirubin is a protective factor against metabolic syndrome (MS), while a high level of transaminase is a risk factor for MS. However, the existing results are inconsistent and few cohort studies have been published. METHODS: Using an ambispective cohort study, 565 Kazakhs from Xinjiang, China were selected as the study subjects. The baseline serum bilirubin and transaminase levels of the subjects were divided into quartiles and the relationship between these values and the incidence of MS was analyzed. The definition of MS was based on the Joint Interim Statement (JIS) diagnostic criteria. RESULTS: The average follow-up time for the subjects was 5.72 years. The cumulative incidence of MS was 36.11% (204 of the 565 subjects), and the incidence density was 63.10/1000 person-years. Multivariate Cox regression analysis showed that the levels of total bilirubin (TBIL) and indirect bilirubin (IBIL) were negatively correlated with the occurrence of MS, Compared to the lowest quartile level (Q1), the hazard ratios of MS the TBIL levels at the Q2-Q4 quartiles were: 0.47 (0.31-0.71), 0.53 (0.35-0.79), and 0.48 (0.32-0.72), respectively, while IBIL levels at the Q2-Q4 quartiles showed an MS hazard ratio of 0.48 (0.32-0.72), 0.54(0.36-0.81), and 0.52 (0.35-0.77), respectively, all at a 95% confidence level. However, no relationship was found between transaminase levels and the incidence of MS. CONCLUSION: Serum TBIL and IBIL levels were negatively correlated with the incidence of MS in a Kazakh population in China.

Probabilistic model predicts dynamics of vegetation biomass in a desert ecosystem in NW China.

The temporal dynamics of vegetation biomass are of key importance for evaluating the sustainability of arid and semiarid ecosystems. In these ecosystems, biomass and soil moisture are coupled stochastic variables externally driven, mainly, by the rainfall dynamics. Based on long-term field observations in northwestern (NW) China, we test a recently developed analytical scheme for the description of the leaf biomass dynamics undergoing seasonal cycles with different rainfall characteristics. The probabilistic characterization of such dynamics agrees remarkably well with the field measurements, providing a tool to forecast the changes to be expected in biomass for arid and semiarid ecosystems under climate change conditions. These changes will depend-for each season-on the forecasted rate of rainy days, mean depth of rain in a rainy day, and duration of the season. For the site in NW China, the current scenario of an increase of 10% in rate of rainy days, 10% in mean rain depth in a rainy day, and no change in the season duration leads to forecasted increases in mean leaf biomass near 25% in both seasons.

Sesamolin exerts anti-proliferative and apoptotic effect on human colorectal cancer cells via inhibition of JAK2/STAT3 signaling pathway.

Colorectal cancer (CRC) is a common malignant tumor that seriously threatens human health and quality of life. At present, the search for safe and more effective treatment for CRC has become necessary. The present study investigated the anti-proliferative and apoptotic effects of sesamolin on human colorectal cancer (HCT116) cells, and the underlying mechanism. Cell proliferation was determined using MTT assay, while the expressions of JAK2, STAT3 and p-STA3 were determined using Western blotting. The levels of expression of matrix metalloproteinases-1, 2 and 9 (MMP1, MMP2 and MMP9) were determined using real-time quantitative polymerase chain reaction (qRT-PCR). The degree of migration and invasion of the cells was assessed using wound healing assay. The results of MTT assay showed that sesamolin significantly and time- and dose-dependently inhibited the proliferation of HCT116 cells (p < 0.05). Treatment of HCT116 cells with sesamolin significantly inhibited their migratory ability (p < 0.05). The expressions of p-JAK2 and p-STAT3 were significantly down-regulated 48 h after 20 µM of JAK2 specific inhibitor (AG490) was added to HCT116 cells (p < 0.05). The expression of p-STAT3 was also significantly and dose-dependently down-regulated 6 h after treatment of HCT116 cells with sesamolin (p < 0.05). Sesamolin and AG490 had synergistic effect and their combination significantly down-regulated the expression of p-STAT3, when compared with sesamolin alone (p < 0.05). Treatment of HCT116 cells with sesamolin significantly and dose-dependently reduced the levels of IL-6-induced expressions of MMP-1, MMP-2 and MMP-9 (p < 0.05). These results suggest that sesamolin induces apoptosis in HCT116 cells and prevents cell invasion via inhibition of the JAK2/STAT3 signaling pathway.

Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study.

OBJECTIVE: This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. METHODS: Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. RESULTS: Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. CONCLUSION: BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.

Effect of Antigen Retrieval Methods on Nonspecific Binding of Antibody-Metal Nanoparticle Conjugates on Formalin-Fixed Paraffin-Embedded Tissue.

Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissues provides important diagnostic and prognostic information in pathology. Metal nanoparticles (NPs) and, in particular, surface-enhanced Raman scattering (SERS) nanotags as a new class of labeling reagents are promising to be used for multiplexed protein profiling on tissue sections. However, nonspecific binding of NPs onto the tissue specimens greatly hampers their clinical applications. In this study, we found that the antigen retrieval method strongly influences the extent of nonspecific binding of the antibody-SERS NP conjugates to the tissue. Our SERS labels comprised ca. 70 nm Au nanostars coated with ethylene glycol-modified Raman reporter molecules for hydrophilic stabilization and subsequent covalent bioconjugation to antibodies. We systematically investigated the influence of heat- and protease-induced epitope retrieval (HIER and PIER, respectively) on the immunostaining quality of prostate-specific antigen (PSA) on human prostate tissue sections. The best staining results were obtained with PIER. Pretreatment of the tissue sections by HIER led to selective but nonspecific adsorption of the antibody-Au nanostar conjugates onto epithelial cells, while enzymatic treatment within PIER did not. In addition to gold nanostars, also other types of metal NPs with different shapes and sizes (including ca. 20 nm quasi-spherical Au NPs and ca. 60 nm quasi-spherical Au/Ag nanoshells) as well as tissue sections from different organs (including prostate and breast) were tested; in each case the same tendency was observed, i.e., PIER yielded better results than HIER. Therefore, we recommend PIER for future NP-based tissue immunostaining such as immuno-SERS microscopy. Alternatively, for antigens that can only be unmasked by heating, PEGylation of the NPs is recommended to avoid nonspecific binding.

Fast and reproducible iSERS microscopy of single HER2-positive breast cancer cells using gold nanostars as SERS nanotags.

Speed is often a bottleneck in conventional Raman microscopy on biological specimens. In immuno-Raman microspectroscopy, or for short iSERS microscopy, the acquisition times per pixel have been reduced by more than one order of magnitude over the past decade since its proof of concept. Typically rather high laser power densities are employed with the intention of compensating for the shorter acquisition times, without checking the reproducibility of the results in repeated experiments on the same sample. Here, we systematically analyze this aspect at the single-cell level since it forms the basis of quantification and is very important for reinspection of the same specimen. Specifically, we investigate experimentally the role of the laser power density in conjunction with the acquisition times per pixel in a series of repeated iSERS experiments on the same single cell overexpressing the breast cancer tumor marker human epidermal growth factor receptor 2 (HER2). Confocal iSERS mapping experiments were guided by wide-field fluorescence microscopy for selecting the regions of interest. We demonstrate that the combination of ca. a 1-2 mW laser power (40× objective, NA 0.6), 50 ms acquisition time per pixel and a high EM-CCD signal gain yields highly reproducible iSERS images in a series of four repeated experiments on the same single cell. In contrast, longer acquisition times (0.8 s, no EM gain) and in particular higher laser power (4 mW up to 18 mW) densities lead to non-reproducible iSERS results due to signal degradation.

iSERS microscopy guided by wide field immunofluorescence: analysis of HER2 expression on normal and breast cancer FFPE tissue sections.

Surface-enhanced Raman scattering (SERS) microscopy is an emerging imaging technique for tissue-based cancer diagnostics. Specifically, immuno-SERS (iSERS) microscopy employs antibodies labelled by molecularly functionalized noble metal colloids for antigen localization on tissue specimen. Spectrally resolved iSERS acquisition schemes are typically rather time-consuming when large tissue areas must be scanned. Here, we demonstrate the application of iSERS imaging guided by wide field immunofluorescence (IF) for localization of the human epidermal growth factor receptor 2 (HER2) on breast tissue sections. The addition of unlabelled anti-HER2 primary antibodies to the tissue is followed by the incubation with secondary antibodies labelled with both Alexa-647 (for IF) and hydrophilically stabilized gold nanostars coated with aromatic thiols (for iSERS). False-color iSERS images clearly reveal the different HER2 expression levels on normal and breast cancer tissue, respectively. A series of negative controls confirms that the binding specificity of the secondary antibody is maintained after conjugation to the SERS nanoparticles.

Stabilizing radical cation and dication of a tetrathiafulvalene derivative by a weakly coordinating anion.

After the chemical oxidation of the neutral tetrakis(methylthio)tetrathiafulvalene (TMT-TTF, 1) by specific oxidation agents with weakly coordinating anion, [Al(ORF)4](-) [ORF = OC(CF3)3], the radical cation TMT-TTF(•+) (1(•+)) and dication TMT-TTF(2+) (1(2+)) were successfully stabilized and isolated. All the compounds are well-soluble in some solvents and have been systematically investigated by absorption spectra, (1)H NMR, electron paramagnetic resonance (EPR) measurements. Their crystal structures and electronic properties have been studied in conjunction with theoretical calculation. The synthetic approach for chemical oxidation by specific salts of weakly coordinating anions is useful for stable radical cations of tetrathiafulvalene (TTF) and its derivatives in both solution and solid state, which will extend the further research, including structure-property relations on stable radicals for TTF derivatives and new functional materials based on them.

Diurnal and seasonal variations of surface albedo in a spring wheat field of arid lands of Northwestern China.

Surface albedo greatly affects the radiation energy balance of croplands and is a significant factor in crop growth monitoring and yield estimation. Precise determination of surface albedo is thus important. This study aimed to examine the influence of growth stages (tillering, jointing, heading, filling and maturity) on albedo and its diurnal asymmetry by measuring diurnal albedo variations. Results indicated that the daily mean surface albedo generally exhibited an increased tendency during tillering to heading but decreased after heading. Surface albedos were much higher in the morning than the corresponding values of the same solar elevation angles in the afternoon when the solar elevation angle was less than 40°, indicating a diurnal asymmetry in surface albedo. However, less difference was found in surface albedos between forenoon and afternoon when the solar elevation angle was greater than 40°. Dew droplets on the leaf surface in the morning were assumed to be the main factor resulting in the diurnal asymmetry in albedo of spring wheat.

SCF-FBXL8 contributes to liver metastasis and stem-cell-like features in colorectal cancer cells by mediating ubiquitination and degradation of TP53.

BACKGROUND: FBXL8 is a conserved F-box protein, belonging to the ubiquitin ligase complex, which promotes the development and progression of tumours. However, the regulation function and mechanism of FBXL8's involvement in colorectal cancer (CRC) remain unclear. METHODS: RT-PCR is used to detect gene expression levels. Protein levels were determined by western blotting and flow cytometry. The bindings of FBXL8 and p53 and ubiquitination levels were detected by cell transfection and immunoprecipitation. The transwell assay was used to measure the ability of cells to migrate and invade. Animal studies were used to verify the function of FBXL8 in vivo. RESULTS: The expression of FBXL8 was up-regulated in CRC tissues, and its overexpression was associated with poor prognosis in CRC patients. The up-regulation of FBXL8 promoted the proliferation, invasion and migration of CRC tumour cells and maintained the stem-cell characteristics of colorectal tumour cells. Further analysis demonstrated that FBXL8 targeted p53 and reduced its stability through ubiquitination. Knockout of FBXL8 down-regulated the proliferation, migration and stem-like properties of tumour cells. CRC mouse xenograft tumour model confirmed that FBXL8 gene knockout inhibited tumour formation and liver metastasis. CONCLUSION: FBXL8 was highly expressed in CRC. Mechanism studies have shown that FBXL8 degraded tumour suppressor gene p53 by ubiquitination. FBXL8 knockout inhibited the proliferation and stem characteristics of CRC cells, so SCF-FBXL8-TP53 has potential to be used as a therapeutic target for CRC in subsequent studies.

Community plant height modulated by aridity promotes spatial vegetation patterns in Alxa plateau in Northwest China.

Spatial vegetation patterns are associated with ecosystem stability and multifunctionality in drylands. Changes in patch size distributions (PSDs) are generally driven by both environmental and biological factors. However, the relationships between these factors in driving PSDs are not fully understood. We investigated 80 vegetation plots along an aridity gradient in the Alxa plateau, Northwest China. The sizes of vegetation patches were obtained from aerial images, and the heights of patch-forming species were measured in the field. Soil samples were collected on the bare ground between patches for determination of physiochemical properties. Point pattern analysis was used to infer plant-plant interactions. A model selection procedure was employed to select the best predictors for the shape of PSDs and biological factors (vegetation total cover, community plant height, and plant-plant interactions). We then used structural equation modeling to evaluate the direct and indirect effects of environmental and biological factors on the shape of PSDs. In our study area, two types of PSDs coexisted, namely those that best fit to power law distributions and those that best fit to lognormal distributions. Aridity was the main environmental factor, while community mean height and competition between plants were the main biological factors for the shape of PSDs. As aridity and community mean height increased, power law-like PSDs were exhibited, whereas competition led to deviations of PSDs from power laws. Aridity affected the shape of PSDs indirectly through changes in community mean height. Community mean height was correlated with competition, thereby indirectly affecting the shape of PSDs. Our results suggest the use of community functional traits as a link between the environment and plant-plant interactions, which may improve the understanding of the underlying mechanisms of PSD dynamics.

LITAF inhibits colorectal cancer stemness and metastatic behavior by regulating FOXO1-mediated SIRT1 expression.

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis.

Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety.

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.

The E3 ubiquitin ligase SCF (FBXW10)-mediated LATS2 degradation regulates angiogenesis and liver metastasis in colorectal cancer.

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.

Analysis of lymph node spread and its prognostic significance in ampullary adenocarcinoma: A retrospective study.

Background: Nodal status is a vital prognostic factor for ampullary adenocarcinoma. This study was designed to evaluate the clinical significance of the positive nodes in this disease. Methods: Data from 110 patients who underwent curative pancreatoduodenectomy for ampullary adenocarcinoma between January 2007 and December 2018 were retrospectively collected and analyzed. Results: The median number of lymph nodes per patient was 32 (20-46). Metastatic lymph nodes were found in 84 (76.4%) patients. In patients with positive nodules, the most commonly involved nodes were the #13 (80.1%) and #17 (78.6%) nodes, followed by #12 (69.0%) and #8 nodes (57.1%). Patients with 3-4 positive nodes among #13, #17, #12, and #8 had lower survival rates than those with 0 or 1-2 nodes. Conclusion: Ampullary adenocarcinoma commonly spreads to #13, #17, #12, and #8 lymph nodes. These nodes affected the patients' survival rates dramatically.