CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

PURPOSE: Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. METHODS: A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. RESULTS: During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. CONCLUSIONS: PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

Association between glyphosate exposure and osteoarthritis in US adults: Especially in people who are obese and inactive in leisure time physical activity.

OBJECTIVE: Little has been known on the effect of chronic glyphosate exposure on osteoarthritis (OA). The aim of this study was to investigate the association between glyphosate exposure and OA and to further investigate the different moderating effects of leisure time physical activity (LTPA) and body mass index (BMI) types on the association between glyphosate exposure and OA. METHODS: Cross-sectional data from 2540 participants in the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were used to explore the association between glyphosate exposure and OA. Multivariate logistic regression models and restricted cubic spline models were used to investigate the association between glyphosate exposure and OA, and further analyses were conducted to determine the association between glyphosate exposure and OA under different LTPA and BMI types. RESULTS: Of the 2540 participants, 346 had OA. Participants with the highest glyphosate concentration (Q4) had a higher incidence of OA compared to participants with the lowest glyphosate concentration (Q1) (OR, 1.88; 95 % confidence interval [CI]: 1.13, 3.13), there was no nonlinear association between glyphosate and OA (non-linear P = 0.343). In the no LTPA group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.65; 95%CI: 1.27, 5.51). In the obese group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.74; 95 % CI: 1.48, 5.07). Among people with high BMI and inactive in LTPA, glyphosate concentrations in Q4 were associated with OA (OR, 2.19; 95 % CI: 1.07, 4.48). CONCLUSIONS: Glyphosate is associated with OA odd, and physical activity and moderate weight loss can mitigate this association to some degree. This study provides a scientific basis for rational prevention of OA by regulation of LTPA and BMI under glyphosate exposure.

AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

Association between pyrethroid exposure and osteoarthritis: a national population-based cross-sectional study in the US.

BACKGROUND: With the restriction of organophosphorus and other insecticides, pyrethroids are currently the second most-used group of insecticides worldwide due to their advantages such as effectiveness and low toxicity for mammalian. Animal studies and clinical case reports have documented associations between adverse health outcomesand exposure to pyrethroids. At present, the association between chronic pyrethroid exposure and osteoarthritis (OA) remains elusive. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 and 2007-2014 were used to explore the associations of pyrethroid exposure and OA. Urinary level of 3-phenoxybenzoic acid (3-PBA) in urine samples was used to evaluate the exposure of pyrethroid, and OA was determined on the basis of self-reported physician diagnoses. Multivariable logistic regression models were used to investigate the association between pyrethroid exposure and OA. RESULTS: Among the 6528 participants, 650 had OA. The weighted geometric mean of urinary volume-based 3-PBA concentration were 0.45 µg/L. With adjustments for major confounders, compared to participants in the lowest quartile of urinary volume-based 3-PBA, those in the highest quartilehad higher odds of OA (odds ratio, 1.39; 95% confidence interval: 1.01, 1.92). There was no nonlinear relationship between urinary volume-based 3-PBA and OA (P for non-linearity = 0.89). CONCLUSION: High urinary 3-PBA concentration was associated with increased OA odds in the US adults. Pyrethroid exposure in the population should be monitored regularly.

Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.

Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.

Construction and Evaluation of a Nomogram to Predict Gallstone Disease Based on Body Composition.

Purpose: We aimed to analyze the body composition characteristics of gallstone disease (GD) patients with bioelectrical impedance analysis (BIA) and to construct a nomogram to predict GD based on body composition. Methods: Patients with or without symptomatic cholecystolithiasis or choledocholithiasis diagnosed in Inner Mongolia People's Hospital from July 2020 to December 2021 were selected as the case group, and healthy subjects during the same period were selected as the control group. The body composition of the two groups was determined by BIA. The risk predictors for GD were extracted to construct a nomogram based on regression analysis. ROC curves were used to evaluate the predictive power of the nomogram, and calibration curves were drawn to evaluate the consistency of the model. The bootstrap method was used to verify the model and evaluate the generalizability of the model. Results: A total of 1000 individuals were recruited for the study, including 500 GD cases and 500 controls, to evaluate body composition. Multivariate logistic regression analysis showed that sex (OR = 2.292, 95% CI: 1.436-3.660), BMI (OR = 1.828, 95% CI: 1.738-1.929), body fat percentage (BFP) (OR = 1.904, 95% CI: 1.811-2.205) and waist circumference (WC) (OR = 1.934, 95% CI: 1.899-1.972) were risk predictors of GD. The AUC was 0.770 (95% CI: 0.741-0.799). The calibration curve showed that the C-index was 0.767. The prediction model was validated internally with 1000 bootstrap resamples. The accurate value was 0.72, and the kappa value was 0.43. All of the indices indicated that the model was well constructed and could be used to predict the incidence of GD. Conclusion: A nomogram model of gallstone disease based on sex, BMI, BFP and WC was constructed with good discrimination, calibration and generalizability and can be used for the noninvasive and convenient prediction of gallstone disease in the general population.

Dynamic characteristics and synergistic effects of ecosystem services under climate change scenarios on the Qinghai-Tibet Plateau.

The Qinghai-Tibet Plateau (QTP) supplies many ecosystem services (ESs) that maintain local and global pan-Asian populations and ecosystems. The effects of climate change on ES provision in the QTP will have far-reaching impacts on the region and the many downstream ecosystems and countries that depend on ESs from the "Third Pole". This study undertook a systematic assessment of ES provision, trade-offs and synergies between four ESs (raw material provision, water yield, soil retention, and carbon storage) under future climate scenarios (representative concentration pathway). The results show that: (1) the total amount of the four ESs on the QTP is predicted to increase from 1980 to 2100 for three climate change scenarios. (2) The spatial pattern of ESs on the QTP will not change significantly in the future, and the grassland and forest ESs in the central and southern regions are predicted to increase significantly. (3) The synergistic interactions among ESs were generally consistent at three spatial scales (10 km (pixel), county and watershed scales), but with more significant synergistic effects at the watershed scale. This demonstrates the necessity for the examination of scale-dependent ES dynamics and interactions. This study will supply a reference for further research on long-term ES assessments, especially the dynamic ES changes and the spatial scale dependency of the ES interactions, and provide evidence-based strategies for formulating ecosystem management on the QTP under climate change.

A Comparison Study of Precipitation in the Poyang and the Dongting Lake Basins from 1960-2015.

The Dongting Lake Basin and the Poyang Lake Basin, both located in the middle reaches of the Yangtze River, provide 30% of the total water volume for the Yangtze River. Under global climate change, precipitation patterns have undergone varying degrees of changes in different regions. Analysing temporal and spatial rainfall variations is important for understanding the variations in capacity of the two lake basins and the water intake variations by the Yangtze River. This study analyses the temporal and spatial variations of the two basins based on 33 rain-gauge data series from 1960-2015, using statistical methods, GIS spatial analysis and the M-K trend test. Our results showed that the annual precipitation generally increased in the Poyang Lake Basin and we found no obvious changes in the Dongting Lake Basin from 1960 to 2015. Seasonal precipitation levels at interannual scales were roughly consistent, but exhibited variability larger by an order of magnitude in the Poyang Lake Basin than in the Dongting Lake Basin. In general, an increasing trend dominated in spring and autumn while a decreasing trend was observed in summer and winter. The increasing trend was significant from the 1990s in the Poyang Lake Basin and from the late 1990s in the Dongting Lake Basin. It was found that annual precipitation with relatively larger anomalies appeared in ENSO (El Niño and Southern Oscillation) years in most cases, such as in 1963, 1997/1998 and 2002, while a few anomalies appeared in the previous or next year around an ENSO year, such as 1971 and 1978. All monthly precipitation periods with relatively larger or smaller anomalies coincided with ENSO events. In addition, El Niño and SOI (Southern Oscillation) events had significant relationships with negative monthly precipitation anomalies. El Niño and the SOI exerted more significant impacts on the Poyang Lake Basin than on the Dongting Lake Basin, which explains the conclusions regarding seasonal precipitation trends as mentioned above.

LncRNA LINC00974 Upregulates CDK6 to Promote Cell Cycle Progression in Gastric Carcinoma.

Background: It is known that LINC00974 is an oncogenic long noncoding RNA in liver cancer. Results: The authors observed in this study that LINC00974 was upregulated in gastric cancer (GC) and positively correlated with CDK6. Survival analysis showed that high levels of LINC00974 and CDK6 predicted poor survival. In GC tissues, LINC00974 and CDK6 were positively correlated. In GC cells, LINC00974 overexpression led to upregulated, whereas LINC00974 siRNA silencing led to downregulated CDK6. Analysis of cell cycle progression and proliferation showed that LINC00974 and CDK6 overexpression promoted and siRNA silencing inhibited G1-S transition and cell proliferation. Conclusion: Therefore, LINC00974 upregulates CDK6 to promote cell cycle progression in GC.

Cyr61 overexpression induced by interleukin 8 via NF-kB signaling pathway and its role in tumorigenesis of gastric carcinoma in vitro.

Cyr61 (CCN1) is a multifunctional matricellular protein in bridging inflammation and cancer, involved in many biological functions such as tumorigenesis and carcinogenesis. The role of Cyr61 in gastric cancer (GC) has not been fully understood and needs to be investigated and clarified. We examined Cyr61 expression in 6 GC cell lines and stable transfection of recombinants in to BGC823 specifically down regulated the Cyr61 mRNA and protein expression shown by the analysis with western blot, RT-PCR, western blot and immunofluorescence assay. The cells treated with siRNA shown markedly reduced activity in growth, migration and invasion compared with parental BGC823 cells as well as mock transfectants. The Cyr61 deficient cells demonstrated significantly inhibited colony formation in soft agar and reduced tumorigenicity was showed in nude mice, NF-kB pathway evidently inactivated respectively. However, under the stimulation of IL-8, the siRNA-treated cells can restore the capacity of proliferation and invasion. IL-8 can induce the high expression of Cyr61 and MMP11 through NF-kB signal pathway. Silencing of Cyr61 can inhibit or minimize the proliferation and invasiveness of gastric cancer cell. The results imply that Cyr61 enhance the proliferation and invasion of gastric cancer cells and this process is partially modulated by the IL-8 up-regulation. Cyr61 may mediate the proliferation and development of gastric carcinoma.

HSP90 interacts with HMGCR and promotes the progression of hepatocellular carcinoma.

Heat shock protein 90 (HSP90) has been reported to promote the growth and inhibit apoptosis of hepatocellular carcinoma (HCC) cells. However, the underlying mechanisms are not fully understood. Immunostaining of the tissue array demonstrated that HSP90 was upregulated in HCC clinical samples and was associated with clinical features. HSP90 interacted with 3­hydroxy­3­methylglutaryl­CoA reductase (HMGCR), the rate­limiting enzyme of mevalonate pathway, in the immunoprecipitation assay and regulated its protein expression level by inhibiting protein degradation. In addition, lovastatin, an inhibitor of HMGCR, impaired the oncogenic functions of HSP90 in the cell growth, migration and colony formation assays. Taken together, this study demonstrated that HSP90 promoted the progression of HCC by positively regulating the mevalonate pathway and indicated that HSP90 may be a promising therapeutic target.

Copper chelators promote nonamyloidogenic processing of AßPP via MT1/2 /CREB-dependent signaling pathways in AßPP/PS1 transgenic mice.

Copper is essential for the generation of reactive oxygen species (ROS), which are induced by amyloid-ß (Aß) aggregation; thus, the homeostasis of copper is believed to be a therapeutic target for Alzheimer's disease (AD). Although clinical trials of copper chelators show promise when applied in AD, the underlying mechanism is not fully understood. Here, we reported that copper chelators promoted nonamyloidogenic processing of AßPP through MT1/2 /CREB-dependent signaling pathways. First, we found that the formation of Aß plaques in the cortex was significantly reduced, and learning deficits were significantly improved in AßPP/PS1 transgenic mice by copper chelator tetrathiomolybdate (TM) administration. Second, TM and another copper chelator, bathocuproine sulfonate (BCS), promoted nonamyloidogenic processing of AßPP via inducing the expression of ADAM10 and the secretion of sAßPPα. Third, the inducible ADAM10 production caused by copper chelators can be blocked by a melatonin receptor (MT1/2 ) antagonist (luzindole) and a MT2 inhibitor (4-P-PDOT), suggesting that the expression of ADAM10 depends on the activation of MT1/2 signaling pathways. Fourth, three of the MT1/2 -downstream signaling pathways, Gq/PLC/MEK/ERK/CREB, Gs/cAMP/PKA/ERK/CREB and Gs/cAMP/PKA/CREB, were responsible for copper chelator-induced ADAM10 production. Based on these results, we conclude that copper chelators regulate the balance between amyloidogenic and nonamyloidogenic processing of AßPP via promoting ADAM10 expression through MT1/2 /CREB-dependent signaling pathways.

Tetrathiomolybdate Treatment Leads to the Suppression of Inflammatory Responses through the TRAF6/NFκB Pathway in LPS-Stimulated BV-2 Microglia.

Although the positive relationship between copper and Alzheimer's disease (AD) was reported by a lot of epidemiological data, the mechanism is not completely known. Copper is a redox metal and serves as a mediator of inflammation. Because the homeostasis of copper is altered in Aß precursor protein (APP) and presenilin 1 (PS1) transgenic (Tg) mice, the using of copper chelators is a potential therapeutic strategy for AD. Here we report that a copper chelator, tetrathiomolybdate (TM), is a potential therapeutic drug of AD. We investigated whether TM treatment led to a decrease of pro-inflammatory cytokines in vivo and in vitro, and found that TM treatment reduced the expression of iNOS and TNF-α in APP/PS1 Tg mice through up-regulating superoxide dismutase 1 (SOD1) activity. In vitro, once stimulated, microglia secretes a variety of proinflammatory cytokines, so we utilized LPS-stimulated BV-2 cells as the inflammatory cell model to detect the anti-inflammatory effects of TM. Our results indicated that TM-pretreatment suppressed the ubiquitination of TRAF6 and the activation of NFκB without affecting the expression of TLR4 and Myd88 in vitro. By detecting the activity of SOD1 and the production of reactive oxygen species (ROS), we found that the anti-inflammatory effects of TM could be attributed to its ability to reduce the amount of intracellular bioavailable copper, and the production of ROS which is an activator of the TRAF6 auto-ubiquitination. Hence, our results revealed that TM-treatment could reduce the production of inflammatory cytokines by the suppression of ROS/TRAF6/AKT/NFκB signaling pathway.

DIAPH3 promoted the growth, migration and metastasis of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling.

The enhanced ability of cancer cell migration and metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Diaphanous-related formin 3 (DIAPH3) has been reported to regulate the motility of cells by remodeling the cytoskeleton. However, the mechanism through which DIAPH3 regulated the motility of cancer cells remains largely unknown. In this study, we have shown that the expression of DIAPH3 was up-regulated in HCC. DIAPH3 positively regulated the growth, migration, colony formation, epithelia mesenchymal transition, and metastasis of HCC cells. Mechanically, DIAPH3 activated the beta-catenin/TCF signaling by binding HSP90 and disrupting the interaction between GSK3beta and HSP90. Taken together, our study demonstrated the oncogenic activity of DIAPH3 in the progression of HCC and suggested that PDIAPH3 might be a therapeutic target.

Assessing winter oilseed rape freeze injury based on Chinese HJ remote sensing data.

The winter oilseed rape (Brassica napus L.) accounts for about 90% of the total acreage of oilseed rape in China. However, it suffers the risk of freeze injury during the winter. In this study, we used Chinese HJ-1A/1B CCD sensors, which have a revisit frequency of 2 d as well as 30 m spatial resolution, to monitor the freeze injury of oilseed rape. Mahalanobis distance-derived growing regions in a normal year were taken as the benchmark, and a mask method was applied to obtain the growing regions in the 2010-2011 growing season. The normalized difference vegetation index (NDVI) was chosen as the indicator of the degree of damage. The amount of crop damage was determined from the difference in the NDVI before and after the freeze. There was spatial variability in the amount of crop damage, so we examined three factors that may affect the degree of freeze injury: terrain, soil moisture, and crop growth before the freeze. The results showed that all these factors were significantly correlated with freeze injury degree (P<0.01, two-tailed). The damage was generally more serious in low-lying and drought-prone areas; in addition, oilseed rape planted on south- and west-oriented facing slopes and those with luxuriant growth status tended to be more susceptible to freeze injury. Furthermore, land surface temperature (LST) of the coldest day, soil moisture, pre-freeze growth and altitude were in descending order of importance in determining the degree of damage. The findings proposed in this paper would be helpful in understanding the occurrence and severity distribution of oilseed rape freeze injury under certain natural or vegetation conditions, and thus help in mitigation of this kind of meteorological disaster in southern China.

Identification of differentially-expressed genes in intestinal gastric cancer by microarray analysis.

Gastric cancer (GC) is one of the most frequent malignant tumors. In order to systematically characterize the cellular and molecular mechanisms of intestinal GC development, in this study, we used 22K oligonucleotide microarrays and bioinformatics analysis to evaluate the gene expression profiles of GC in 45 tissue samples, including 20 intestinal GC tissue samples, 20 normal appearing tissues (NATs) adjacent to tumors and 5 noncancerous gastric mucosa tissue samples. These profiles allowed us to explore the transcriptional characteristics of GC and determine the change patterns in gene expression that may be of clinical significance. 1519 and 1255 differentially-expressed genes (DEGs) were identified in intestinal GC tissues and NATs, respectively, as determined by Bayesian analysis (P<0.001). These genes were associated with diverse functions such as mucosa secretion, metabolism, proliferation, signaling and development, which occur at different stages of GC development.

Spatio-temporal reconstruction of air temperature maps and their application to estimate rice growing season heat accumulation using multi-temporal MODIS data.

The accumulation of thermal time usually represents the local heat resources to drive crop growth. Maps of temperature-based agro-meteorological indices are commonly generated by the spatial interpolation of data collected from meteorological stations with coarse geographic continuity. To solve the critical problems of estimating air temperature (T(a)) and filling in missing pixels due to cloudy and low-quality images in growing degree days (GDDs) calculation from remotely sensed data, a novel spatio-temporal algorithm for T(a) estimation from Terra and Aqua moderate resolution imaging spectroradiometer (MODIS) data was proposed. This is a preliminary study to calculate heat accumulation, expressed in accumulative growing degree days (AGDDs) above 10 °C, from reconstructed T(a) based on MODIS land surface temperature (LST) data. The verification results of maximum T(a), minimum T(a), GDD, and AGDD from MODIS-derived data to meteorological calculation were all satisfied with high correlations over 0.01 significant levels. Overall, MODIS-derived AGDD was slightly underestimated with almost 10% relative error. However, the feasibility of employing AGDD anomaly maps to characterize the 2001-2010 spatio-temporal variability of heat accumulation and estimating the 2011 heat accumulation distribution using only MODIS data was finally demonstrated in the current paper. Our study may supply a novel way to calculate AGDD in heat-related study concerning crop growth monitoring, agricultural climatic regionalization, and agro-meteorological disaster detection at the regional scale.

Nimesulide inhibits the proliferation of HepG2 by up-regulation of Smad4.

OBJECTIVES: Hepatocellular carcinoma (HCC) is receiving increased attention. This study was designed to investigate the effect of selective Cyclooxygenase-2 (COX-2) inhibitor, nimesulide, on the expression of Smad4 in human hepatocellular carcinoma HepG2. MATERIALS AND METHODS: HepG2 cells were incubated in various concentrations of nimesulide (25, 50, 100, 200, 400 µmol/L) to detect the effect of proliferation by MTS. The apoptosis of HepG2 was determined by TUNEL; fluorescence microscope was used to observe the expression of Smad4. RESULTS: The result showed that nimesulide inhibited the proliferation of HepG2 cell in a concentrations-dependent manner, and promoted the karyopyknosis and fragmentation of HepG2 cell nucleus, induced its apoptosis, the number of fluorescence labeling of Smad4 in Nimesulide group was higher than control group (P<0.05). CONCLUSIONS: Nimesulide inhibits the proliferation and promotes apoptosis of HepG2 by up-regulation of Smad4 in HepG2.

Top-down modulations from dorsal stream in lexical recognition: an effective connectivity FMRI study.

Both the ventral and dorsal visual streams in the human brain are known to be involved in reading. However, the interaction of these two pathways and their responses to different cognitive demands remains unclear. In this study, activation of neural pathways during Chinese character reading was acquired by using a functional magnetic resonance imaging (fMRI) technique. Visual-spatial analysis (mediated by the dorsal pathway) was disassociated from lexical recognition (mediated by the ventral pathway) via a spatial-based lexical decision task and effective connectivity analysis. Connectivity results revealed that, during spatial processing, the left superior parietal lobule (SPL) positively modulated the left fusiform gyrus (FG), while during lexical processing, the left SPL received positive modulatory input from the left inferior frontal gyrus (IFG) and sent negative modulatory output to the left FG. These findings suggest that the dorsal stream is highly involved in lexical recognition and acts as a top-down modulator for lexical processing.