Synthesis, characterization and in vitro antiproliferative effects of isosteviol derivatives.

Nineteen isosteviol derivatives were designed and synthesized by C-16, C-19 and D-ring modifications of isosteviol. These compounds were screened for their cytotoxic activities against Hela and A549 cells in vitro. Among them, the inhibitory effect of compounds 3b and 16 on Hela cells was comparable to that of the positive control gefitinib, and the compounds 3b (IC50=7.84 ± 0.84 µM) and 7a (IC50=6.89 ± 0.33 µM) exhibited significant cytotoxicity superior to gefitinib (IC50=11.02 ± 3.27 µM) against A549 cells.

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aß generation.

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

[Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue].

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

[Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II].

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 µmol/L) with or without Ang II (0.4 µmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Arm locking using laser frequency comb.

The space-borne gravitational wave (GW) detectors, e.g., LISA, TaiJi, and TianQin, will open the window in the low-frequency regime (0.1 mHz to 1 Hz) to study the highly energetic cosmic events, such as coalescences and mergers of binary black holes and neutron stars. For the sake of successful observatory of GWs, the required strain sensitivity of the detector is approximately 10-21/Hz1/2 in the science band, 7 orders of magnitude better than the state of the art of the ultra-stable laser. Arm locking is therefore proposed to reduce the laser phase noise by a few orders of magnitude to relax the burden of time delay interferometry. During the past two decades, various schemes have been demonstrated by using single or dual arms between the spacecraft, with consideration of the gain, the nulls in the science band, and the frequency pulling characteristics, etc. In this work, we describe an updated version of single arm locking, and the noise amplification due to the nulls can be flexibly restricted with the help of optical frequency comb. We show that the laser phase noise can be divided by a specific factor with optical frequency comb as the bridge. The analytical results indicate that, the peaks in the science band have been greatly reduced. The performance of the noise suppression shows that the total noise after arm locking can well satisfy the requirement of time delay interferometry, even with the free-running laser source. When the laser source is pre-stabilized to a Fabry-Perot cavity or a Mach-Zehnder interferometer, the noise can reach the floor determined by the clock noise, the spacecraft motion, and the shot noise. We also estimate the frequency pulling characteristics of the updated single arm locking, and the results suggest that the pulling rate can be tolerated, without the risk of mode hopping. Arm locking will be a valuable solution for the noise reduction in the space-borne GW detectors. We demonstrate that, with the precise control of the returned laser phase noise, the noise amplification in the science band can be efficiently suppressed based on the updated single arm locking. Not only does our method allow the suppression of the peaks, the high gain, and low pulling rate, it can also serve for full year, without the potential risk of locking failure due to the arm length mismatch. We then discuss the unified demonstration of the updated single arm locking, where both the local and the returned laser phase noises can be tuned to generate the expected arm-locking sensor actually. Finally, the time-series simulations in Simulink have been carried out, and the results indicate a good agreement with the theory, showing that the presented method is reasonable and feasible. Our work could provide a back-up strategy for the arm locking in the future space-borne GW detectors.

Post-traumatic growth and influencing factors among frontline nurses fighting against COVID-19.

OBJECTIVE: To explore the level and influencing factors of frontline nurses' post-traumatic growth (PTG) during COVID-19 epidemic. METHODS: A cross-sectional survey was conducted in February 2020 in three hospitals in China. The Post-traumatic Growth Inventory (PTGI) was used to investigate the PTG of frontline nurses. Data on related factors, including demographic characteristics and subjective variables, were collected. The Event-Related Rumination Inventory was used to assess rumination. Pearson's or Spearman's correlation was calculated for bivariate analysis. Independent sample t-tests or one-way analysis of variance and multiple linear regression analysis were used to examine the related factors. RESULTS: A total of 179 frontline nurses were recruited, and 167 were included in the analyses. The mean PTG score was 70.53±17.26. The bivariate analyses showed that deliberate rumination was modestly positively correlated with PTG (r=0.557, p<0.01), while intrusive rumination had a modest negative correlation with PTG (r=-0.413, p<0.01). Multiple linear regression demonstrated that working years, self-confidence in frontline work, awareness of risk, psychological intervention or training during the epidemic and deliberate rumination were the main influencing factors of PTG among frontline nurses and accounted for 42.5% of the variance (F=31.626, p<0.001). CONCLUSIONS: The PTG of frontline nurses was at a medium to high level and was influenced by working years, self-confidence in frontline work, awareness of risk, psychological intervention or training and deliberate rumination. It is necessary to strengthen psychological guidance and training for frontline nurses and promote their deliberate rumination on epidemic events to improve their PTG.

NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. METHODS: We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. RESULTS: After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. CONCLUSIONS: NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

Revisiting the Stokes-Einstein relation for glass-forming melts.

Molecular dynamics simulations of Ni36Zr64, Cu65Zr35 and Ni80Al20 were carried out over a broad range of temperature (900-3000 K) to investigate the Stokes-Einstein (SE) relation for glass-forming melts. Our results reproduce experimental structural and transport properties. Results show that the breakdown temperature of the SE relation (TSE) equals the dynamical crossover temperature (TA) and both are roughly twice the glass-transition temperature (Tg) for the three glass-forming melts (TSE = TA ≈ 2.0Tg). The product of the individual component self-diffusion coefficient and viscosity Dαη can be roughly regarded as a constant at the transition zone (a small temperature range around TSE) in which the temperature behaviors of self-diffusion coefficient and viscosity switch from high-temperature Arrhenius to a low-temperature VFT behavior. Below TSE, the decoupling of component diffusion coefficients was found. In particular, the decoupling of component diffusion coefficients can be ascribed to the decoupling of the partial pair structural correlation of components, which can be clearly reflected by the intersection of the high-temperature and low-temperature behaviors of the ratio between the partial pair correlation entropy of components (Sß2/Sα2). Furthermore, the ratio between the partial pair correlation entropy of components may be used to predict the validity of the SE relation, in the absence of both transport coefficients and atomic coordinates.

Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement.

DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin-Sca1+cKit+ cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage. Consistent with leukemic cell accumulation in G2/M phase, CDK1 was up-regulated due to mTOR activation associated with DNA hypomethylation. Overexpressed CDK1-mediated EZH2 phosphorylation resulted in an abnormal trimethylation of H3K27 profile. The mTOR inhibitor rapamycin elicited a significant therapeutic response in Dnmt3aR878H/WT mice.

Trends in cognitive function assessed by a battery of neuropsychological tests after mild acute ischemic stroke.

OBJECTIVE: The aim of this study is to investigate the domain-specific trends of cognitive function up to 12 months after mild acute ischemic stroke. METHODS: Enrolment of consecutive cohort of patients with mild acute ischemic stroke with recorded clinical characteristics and extensive neuropsychological assessments, including five cognitive domains. The Montreal cognitive assessment of the Beijing version (MoCA-Bj) was used to assess overall cognition. All patients completed all domain-specific examinations were categorised into three groups according to the time between the stroke onset and neuropsychological profiling, the time duration including less than one month (n = 174), one month to six months (n = 65) and over six months (n = 39). RESULTS: The final cohort consisted of 278 patients. The executive (χ2 = 6.95, P<0.05) and memory dysfunctions (χ2 = 9.6, P<0.01) showed strong improvement, especially in executive function, which prevalence was 48.85% at <1- month group and 25.64% at >6 months group. The prevalence of attention and information processing also had a declining trend, the differences, however, were not statistically significant (χ2 = 0.23 and 2.25, respectively, P>0.05). There was no significant change in language function (χ2 = 0.46, P>0.05) and the MoCA (χ2 = 0.59, P>0.05) at 3-time point groups. In 195 first-ever stroke patients, the results of memory (χ2 = 6.94 P<0.05) and executive dysfunctions (χ2 = 6.25 P<0.05) also showed significant improvement. CONCLUSION: There is varying degree of improvement tendency in executive and memory dysfunctions after mild acute ischemic stroke. Early cognitive assessments after mild acute ischemic stroke do not reflect the cognitive level of stable period.

Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming.

Fecal microbiota transplantation (FMT) is gaining attention for the treatment of ulcerative colitis (UC). Data from individual case studies have suggested that FMT may be beneficial for UC, but the detailed microbial and molecular basis remains unknown. Here, we employ 16S rRNA gene sequencing and metabolomics to investigate the influence of FMT on gut microbial community composition and host metabolism in the dextran sulfate sodium-induced UC rat model. The findings from this pilot study suggest that FMT from normal donors to UC recipients could alleviate UC symptoms without close resemblance of donor's gut microbial and metabolic pattern. Meanwhile, FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption. Gut microbiota under normal conditions could maintain stable species richness and diversity upon FMT intervention, but the disturbed gut microbiota under UC conditions could not maintain such homeostasis. Significant correlations between altered bacterial composition and host metabolism could be assigned to the pathological effects of UC (accounting for 8.0 to 16.2% of total variance) and/or the FMT intervention effects (3.9 to 7.0% of total variance). Overall, our study reveals diverse gut microbial shifts in UC related FMT and their association with host metabolic reprogramming.IMPORTANCE This study combined clinical symptoms measurement, 16S rRNA gene microbial profiling and metabolomics to comprehensively investigate the gut bacterial and host metabolic association and reprogramming in FMT-treated experimental UC. These data can advance our understanding of the effect of FMT on UC and the involvement of gut microbial dysbiosis in the development of UC.

Characteristics and molecular determinants of a highly selective and efficient glycyrrhizin-hydrolyzing ß-glucuronidase from Staphylococcus pasteuri 3I10.

Glycyrrhizin (GL), the principal sweet-tasting bioactive ingredient of licorice (root of Glycyrrhiza glabra), shows poor oral absorption and gut microbial transformation of GL to glycyrrhetinic acid (GA) plays a major role for its multiple pharmacological effects. Co-administration of GL-hydrolyzing bacteria appears to be a feasible strategy to enhance GA exposure. This study reported a gut bacterial strain Staphylococcus pasteuri 3I10 which exhibited moderate p-nitrophenyl-ß-D-glucuronide (PNPG)-hydrolyzing activity but low GL deglucuronidation activity in its crude lysate. The gus gene encoding S. pasteuri 3I10 ß-glucuronidase was successfully cloned and overexpressed in Escherichia coli BL21(DE3). The purified ß-glucuronidase (SpasGUS) was 71 kDa and showed optimal pH and temperature at 6.0 and 50 °C, respectively. Comparing to E. coli ß-glucuronidase (EcoGUS), SpasGUS displayed lower velocity and affinity to PNPG hydrolysis (Vmax 16.1 ± 0.9 vs 140.0 ± 4.1 µmolmin-1 mg-1; Km 469.4 ± 73.4 vs 268.0 ± 25.8 µM), but could selectively convert GL to GA at much higher efficiency (Vmax 0.41 ± 0.011 vs 0.005 ± 0.002 µmolmin-1 mg-1; Km 116.9 ± 15.4 vs 53.4 ± 34.8 µM). Molecular docking studies suggested SpasGUS formed hydrogen bond interactions with the glucuronic acids at Asn414, Glu415 and Leu450, and Val159, Tyr475, Ala368, and Phe367 provided a hydrophobic environment for enhanced activity. Two special substrate interaction loops near the binding pocket of SpasGUS (loop 1 ß-glucuronidase) may account for the selective and efficient bioconversion of GL to GA, predicting that loop 1 ß-glucuronidases show high possibility in processing GL than mini-loop 1 and loop 2 ß-glucuronidases. These findings support potential applications of SpasGUS in cleaving GL to facilitate GA production in vivo or in pharmaceutical industry.

Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance.

BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1. RESULTS: Certain gene expression levels were associated with the cytogenetic aberration of the disease, especially for MECOM, MEIS1 and BAALC. FLT3, C-KIT and NRAS mutations contained conversed expression profile regarding MEIS1, WT1, GATA2 and BAALC expression, respectively. FLT3, DNMT3A, NPM1 and biallelic CEBPA represented the mutations associated with the prognosis of AML in our group. Higher MECOM and MEIS1 gene expression levels showed a significant impact on complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) both in univariate and multivariate analysis, respectively; and an additive effect could be observed. By systematically integrating gene mutational status results and gene expression profile, we could establish a more refined system to precisely subdivide AML patients into distinct prognostic groups. CONCLUSIONS: Gene expression abnormalities contained important biological and clinical informations, and could be integrated into current AML stratification system.

[Association of Insulin Resistance and ß Cell Function with Lipid Metabolism in Middle-aged and Elderly Hui and Han Populations].

OBJECTIVE: To explore the association of insulin resistance and ß cell function with lipid metabolism in middle-aged and elderly Hui and Han populations. METHODS: A total of 1000 subjects age over 40 years were recruited from five urban communities in Yinchuan and Wuzhong cities of Ningxia. The composition ratio between Hui and Han nationality was 1:2. A questionnaire-based survey was performed. Physical examinations were carried out to measure the height, body mass, waistline, and hipline. The levels of triglyceride (TG), total cholesterol (TC), blood uric acid (BUA), fasting blood glucose and insulin were measured. The boby mass index (BMI), waist-hip ratio (WHR), and secretion related index including insulin resistance index (IR), insulin sensitivity index (IAI), and beta cell function index (HBCI) were calculated. RESULTS: The BMI, WHR, IAI, HBCI, and the prevalence rate of diabetes in Hui nationality were significantly higher than those in Han nationality (P<0.01). The levels of BUA, fasting blood glucose, TC, and IR in Han nationality were significantly lower than those in Hui nationality (P<0.01). In Hui populations, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.234, r=0.193, r=0.143, and r=0.129, respectively; P<0.01) and were negatively correlated with IAI (r=-0.234, r=-0.193, r=-0.143, r=-0.129, respectively; P<0.01), whereas TC was negatively correlated with HBCI (r=-0.169, P<0.01). In Han populations, TC, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.140, r=0.257, r=0.288, r=0.163, r=0.104, P<0.01) and negatively correlated with IAI (r=-0.140, r=-0.257, r=-0.288, r=-0.163, and r=-0.104, P<0.01), whereas BMI was negatively correlated with HBCI (r=-0.111, P<0.01). After the influential factors such as gender, nationality, and age were adjusted, the TC, TG, BMI, WHR, BUA levels were positively correlated with IR (r=0.109, r=0.256, r=0.253, r=0.139, and r=0.142, P<0.01) and negatively correlated with IAI (r=-0.109, r=-0.256, r=-0.253, r=-0.139, and r=-0.142, P<0.01). TC and BMI were negatively correlated with HBCI (r=-0.113, r=-0.086, P<0.01). TG and BMI were independently associated with IR and IAI (r=0.218, r=0.182, r=-0.218, r=-0.182), while TC and BMI were independently associated with HBCI (r=-0.113, r=-0.086). CONCLUSIONS: The distributions of TC, TG, BMI, WHR, BUA, IR, IAI, and HBCI differ between Han and Hui populations. The development of insulin resistance is closely related with the increased levels of TC, TG, BMI, WHR, and BUA. However, the HBCI increases with the increased level of TC and BMI. TG and BMI may be related with insulin resistance. Also, TC and BMI may affect the secretion function of ß cells.

[Variation Characteristics of Tropospheric NO2 Vertical Column Densities over Large and Small Cities of Xinjiang in Summer].

Selecting the representative large and small towns which were Urumqi, Korla, Bole cities in Xinjiang, the ground-based mini MAX-DOAS measurement was carried out to observe the tropospheric NO2 vertical column density at town, industrial districts and farmland area in different grade cities from Jul to Aug 2014. It turned out(1) In the diurnal variation of the concentration of tropospheric NO2 vertical column density have peaks and troughs, the difference between its peak in the large and small towns, Urumqi(7.590×1015molec·cm-2)>Korla(7.559×1015molec·cm-2)>Bole(3.578×1015molec·cm-2); (2)During summer the tropospheric NO2 vertical column density has relationship with urban surface condition. Especially it has close relationship with the number of cars in the observational area, town(4.643×1015molec·cm-2)>industrial districts (4.469×1015molec·cm-2)>farmland area(2.425×1015molec·cm-2); (3)Under different weather conditions the tropospheric NO2 vertical column density : the minimum density appeared on a rainy day(3.082×1015molec·cm-2), it turned out the precipitation has an important influence on NO2.

[Intervention of berberine on lipid deposition in liver cells of non-alcoholic fatty liver disease rats induced by high fat diet].

OBJECTIVE: To explore the effect of berberine on lipid metabolism disorder and lipid deposition in liver cells of non-alcoholic fatty liver disease (NAFLD) rats induced by high fat diet. METHODS: After one week adaptable feeding, 45 SPF level male SD rats were randomly divided into 3 groups, the normal control group, the model group, and the berberine group, 15 in each group. Except those in the normal control group, all rats were fed with high fat diet to prepare NAFLD model. As for rats in the berberine group, Berberine Hydrochloride was administered by gastrogavage. HE staining and oil red O staining were performed to identify the model after 8 weeks. Hepatocytes were isolated, and their activities and purities were tested by Typan blue staining and flow cytometry (FCM). Serum levels of TC, TG, HDL-C, and LDL-C were detected using automatic biochemical analyzer. mRNA expression levels of LXRα and FAS in liver cells were analyzed by Real-time quantitative polymerase chain reaction (PCR). Protein levels of LXRα and FAS in liver cells were examined by Western blot. RESULTS: The NAFLD rat model was successfully established by high fat diet. The yields of purified liver cells in each rat were (6.0-7.5) x 10(8). The viability of isolated liver cells with purity over 90% (tested by FCM analysis) was higher than 95%. Compared with the normal control group,the expression of LXRα and FAS at mRNA and protein levels was higher in the model group (P < 0.01). Compared with the model group, the expression of LXRα and FAS at mRNA and protein levels was obviously down-regulated in the berberine group (P < 0.01). CONCLUSIONS: LXRα/FAS signaling pathway was one of important signaling pathways of NAFLD lipid metabolism disorders. Berberine could recover hepatocyte fatty deposits in NAFLD rats by adjusting the LXR/FAS signaling pathway of hepatocytes, which might be one of important mechanisms for fighting against NAFLD.

Transport coefficients and entropy-scaling law in liquid iron up to Earth-core pressures.

Molecular dynamics simulations were applied to study the structural and transport properties, including the pair distribution function, the structure factor, the pair correlation entropy, self-diffusion coefficient, and viscosity, of liquid iron under high temperature and high pressure conditions. Our calculated results reproduced experimentally determined structure factors of liquid iron, and the calculated self-diffusion coefficients and viscosity agree well with previous simulation results. We show that there is a moderate increase of self-diffusion coefficients and viscosity along the melting curve up to the Earth-core pressure. Furthermore, the temperature dependencies of the pair correlation entropy, self-diffusion, and viscosity under high pressure condition have been investigated. Our results suggest that the temperature dependence of the pair correlation entropy is well described by T(-1) scaling, while the Arrhenius law well describes the temperature dependencies of self-diffusion coefficients and viscosity under high pressure. In particular, we find that the entropy-scaling laws, proposed by Rosenfeld [Phys. Rev. A 15, 2545 (1977)] and Dzugutov [Nature (London) 381, 137 (1996)] for self-diffusion coefficients and viscosity in liquid metals under ambient pressure, still hold well for liquid iron under high temperature and high pressure conditions. Using the entropy-scaling laws, we can obtain transport properties from structural properties under high pressure and high temperature conditions. The results provide a useful ingredient in understanding transport properties of planet's cores.

In silico genome-wide analysis of homeodomain-leucine zipper transcription factors in Cannabis sativa L.

HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.