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The worldwide proliferation of marine jellyfish has become a crucial ecological and social issue, and as a cosmopolitan species, Aureliaspp. have received increasing scientific attentions. In the present study, the responses of strobilation in Aureliasp.1 to decreasing temperature were illuminated through the expression levels of the retinoid x receptor (RxR) gene and the gene encoding a secreted protein, CL390. We observed that a higher final temperature decreased the strobilation prophase and strobilation interphase periods, and the growth rate of the strobilae ratio increased with increasing CL390 gene expression. The ratio of strobilae at 12°C was highest, and the strobilae showed the higher releasing ratios at both 12°C and 16°C compared with those at 4°C and 8°C. Furthermore, more ephyrae were released at the higher final temperature. Additionally, up-regulation and down-regulation of the CL390 gene were observed in response to the four decreasing temperatures. Although the four CL390 gene transcript levels increased more significantly than the transcript levels of the RxR gene, similar trends were observed in both genes.

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Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (Ktrans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (>92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39–0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer.

The sediment mixed layer (SML) in the deep ocean is an important interface with a rich diversity of benthic organisms. With increasing ocean mineral exploration, and eventual mining, the effect of sediment mixing on deep ocean ecosystems has raised considerable concern. We evaluate the distribution patterns and driving factors of SML depth in deep ocean nodule fields using naturally occurring 210Pb–226Ra isotopes. Results show that average SML depth has increased in Mn‐nodule fields since the end of the last century. SML processes are associated with significant desorption of 226Ra from sediments, resulting in a departure from radioactive equilibrium. By estimating possible driving factors, we conclude that anthropogenic exploration activities, rather than natural physical and/or biological drivers, are the most likely mechanism for intensified sediment mixing. 210Pb–226Ra disequilibria may be a potential tracer for quantifying the impact of human exploration on deep‐ocean sediment mixing and associated biological and geochemical effects. The surface sediment mixed layer (SML) in the deep ocean is essential to benthic community structure and the biogeochemical cycling of many elements. The typical depth of mixed layers in the global deep ocean is <15 cm, which is mainly driven by natural biological and/or physical forces. By mapping sediment excess 210Pb profiles throughout the ocean, we found the depth of the SML in manganese nodule fields has increased significantly since the end of the twentieth century (reaching to >40 cm). The determine that the deepened mixed sediment layer is related to human exploration activities rather than other previously recognized natural drivers like bioturbation, internal solitary waves, and submarine storms. Keen attentions should be paid to the deepening and associated effects of sediment mixing in the deep ocean as human demand for critical materials continues to increase in the Anthropocene. Exploration approaches that involve low or negligible disturbance to deep‐ocean sediment should be encouraged. Human exploration is the main reason for deepening of the sediment mixed layer in the manganese nodule areaSediment mixed processes are associated with significant desorption of 226Ra from sediments210Pb–226Ra disequilibria is a potential tracer for quantifying the impact of human drivers on deep‐ocean sediment mixing Human exploration is the main reason for deepening of the sediment mixed layer in the manganese nodule area Sediment mixed processes are associated with significant desorption of 226Ra from sediments 210Pb–226Ra disequilibria is a potential tracer for quantifying the impact of human drivers on deep‐ocean sediment mixing

As a significant source of nutrients and other components into the coastal ocean, submarine groundwater discharge (SGD) is a combination of multiple spatial‐temporal scale processes, including fresh terrestrial groundwater (FSGD), recirculating seawater (RSGD), and porewater exchange (PEX). Quantifying the different types of SGD is extremely important for understanding the coastal biogeochemical cycles of various materials. The green tide bloom in the southern Yellow Sea (China) has attracted increasing attention during the past decade. Haizhou Bay is thought to be an important green tide proliferating area, but the source of an apparent high supply of nutrients has not been identified yet. We report here on our investigations of the distribution patterns of Ra and Rn isotopes in groundwater and seawater in Haizhou Bay. By solving a combined mass balance for 224Ra, 223Ra, 226Ra, and 222Rn, we estimated that the bay's water residence time is 28.8 days, FSGD is highest at 3.6 cm d−1, RSGD is 2.7 cm d−1, and PEX is lowest at 0.6 cm d−1. The total SGD into Haizhou Bay is estimated at 9.40 × 107m3d−1(6.9 cm d−1), about 12 times that of the local river discharge into the bay. SGD‐derived nutrients are shown to play an important role when considered among all known nutrient sources. Our results suggest that dissolved inorganic nitrogen (DIN) and silicate (DSi) are transported by SGD mainly via FSGD. We also note that the phosphorus (DIP) budget is heavily influenced by RSGD. Submarine groundwater discharge (SGD) has been drawing attention as an important benthic boundary exchange pathway in the global marginal seas. As any water flow entering the sea, SGD may happen on small scales (centimeters, minutes to hours) as porewater exchange (PEX), and/or large scales (>meters, days to seasons) as fresh groundwater discharge (FSGD) and seawater recirculation (RSGD) in the subterranean estuary. To better understand its significance, it is necessary to interpret multi‐scale SGD processes and quantify associated nutrients fluxes accordingly. In this study, different types of SGD and associated nutrient fluxes were quantified based on multiple radium and radon isotopes in Haizhou Bay, China, which is one of the world's largest green tide proliferating areas. The FSGD and RSGD were found to be the main processes, accounting for more than 90% of the total SGD fluxes. SGD was recognized as a key nutrient source in Haizhou Bay, which is more than one order of magnitude higher than that of the local river discharge. This study highlights the crucial role of benthic boundary exchange for the health of marine ecosystem and sustainability of the future ocean. Multi‐scale submarine groundwater discharge processes were differentiated and quantified via a multi‐isotope mass balance approachThe flux of fresh groundwater was about 30% higher than recirculated saline groundwater, and about 6 times higher than porewater exchangeFresh groundwater is a main nutrient source to Haizhou Bay, but recirculated saline groundwater makes a larger contribution to DIP inputs Multi‐scale submarine groundwater discharge processes were differentiated and quantified via a multi‐isotope mass balance approach The flux of fresh groundwater was about 30% higher than recirculated saline groundwater, and about 6 times higher than porewater exchange Fresh groundwater is a main nutrient source to Haizhou Bay, but recirculated saline groundwater makes a larger contribution to DIP inputs

Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyiADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilisand mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.

Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyiADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilisand mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.

The bacterial infection that involves antimicrobial resistance is a rising global threat to public health. Chlorine-based water disinfection processes can inactivate antibiotic resistant bacteria. However, at the same time, these processes may cause the release of antibiotic resistance genes into the water as free DNA, and consequently increase the risk to disseminate antibiotic resistance via natural transformation. Presently, little is known about the contribution of residual chlorine affecting the transformation of extracellular antibiotic resistance genes (ARGs). This study investigates whether chloramine and free chlorine promote the transformation of ARGs and how this may occur. We reveal that both chloramine and free chlorine, at practically relevant concentrations, significantly stimulated the transformation of plasmid-encoded ARGs by the recipient Acinetobacter baylyiADP1, by up to a 10-fold increase. The underlying mechanisms underpinning the increased transformations were revealed. Disinfectant exposure induced a series of cell responses, including increased levels of reactive oxygen species (ROS), bacterial membrane damage, ROS-mediated DNA damage, and increased stress response. These effects thus culminated in the enhanced transformation of ARGs. This promoted transformation was observed when exposing disinfectant-pretreated A. baylyito free plasmid. In contrast, after pretreating free plasmid with disinfectants, the transformation of ARGs decreased due to the damage of plasmid integrity. These findings provide important insight on the roles of disinfectants affecting the horizontal transfer of ARGs, which could be crucial in the management of antibiotic resistance in our water systems.

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.

The short-range order (SRO) structure in high-entropy alloys (HEAs) is closely associated with many properties, which can be studied through density functional theory (DFT) calculations. Atomic-scale modeling and calculations require substantial computational resources, and machine learning can provide rapid estimations of DFT results. To describe SRO information in HEAs, a new descriptor based on Voronoi Analysis and Shannon Entropy (VASE) is proposed. Based on Voronoi analysis, the Shannon entropy is introduced to directly characterize atomic spatial arrangement information except for composition and atomic interactions, which is necessary for describing the disorder atomic occupancy in HEAs. The new descriptor is used for predicting the formation energy of FeCoNiAlTiCu system based on machine learning model, which is more accurate than other descriptors (Coulomb matrices, partial radial distribution functions, and Voronoi analysis). Moreover, the model trained based on VASE descriptors exhibits the best predictive performance for unrelaxed structures (24.06 meV/atom). The introduction of Shannon entropy provides an effective representation of atomic arrangement information in HEAs, which is a powerful tool for investigating the SRO phenomena.

This article presents the control synthesis of robotic manipulators with an unknown constant payload. A novel nonlinear disturbance observer with an adaptive scheme is designed to estimate the external force induced by the unknown constant payload. A general design procedure for designing the gain of the nonlinear observer is developed rather than the time-consuming trials and error to choose proper gain. The nonlinear observer gain is designed using an adaptive technique to extend the applicability of the disturbance observer. The stability of the proposed observer is established using Lyapunov method under certain conditions. The proposed nonlinear disturbance observer will be integrated with the sliding mode control to substantially alleviate the chattering problem. Also, simulation results are presented to verify the effectiveness of the proposed methods.

The bacterial infection that involves antimicrobial resistance is a rising global threat to public health. Chlorine-based water disinfection processes can inactivate antibiotic resistant bacteria. However, at the same time, these processes may cause the release of antibiotic resistance genes into the water as free DNA, and consequently increase the risk to disseminate antibiotic resistance via natural transformation. Presently, little is known about the contribution of residual chlorine affecting the transformation of extracellular antibiotic resistance genes (ARGs). This study investigates whether chloramine and free chlorine promote the transformation of ARGs and how this may occur. We reveal that both chloramine and free chlorine, at practically relevant concentrations, significantly stimulated the transformation of plasmid-encoded ARGs by the recipient Acinetobacter baylyiADP1, by up to a 10-fold increase. The underlying mechanisms underpinning the increased transformations were revealed. Disinfectant exposure induced a series of cell responses, including increased levels of reactive oxygen species (ROS), bacterial membrane damage, ROS-mediated DNA damage, and increased stress response. These effects thus culminated in the enhanced transformation of ARGs. This promoted transformation was observed when exposing disinfectant-pretreated A. baylyito free plasmid. In contrast, after pretreating free plasmid with disinfectants, the transformation of ARGs decreased due to the damage of plasmid integrity. These findings provide important insight on the roles of disinfectants affecting the horizontal transfer of ARGs, which could be crucial in the management of antibiotic resistance in our water systems.

In this study, we constructed a highly sensitive and selective electrochemical sensing strategy for l-ascorbic acid (AA) based on a covalent organic framework (COF)-loading non-noble transition metal Co ion and macrocyclic cationic pillar[6]arene (CP6) nanocomposite (CP6-COF-Co). The COF plays a crucial role in anchoring the Co ion according to its crystalline porous and multiple coordination sites and has an outstanding performance for building an electrochemical sensing platform based on a unique two-dimensional structure. Accordingly, the transition-metal Co ion can be successfully anchored on the framework of COF and shows strong catalytic activity for the determination of AA. Moreover, introduction of host–guest recognition based on CP6 and AA can bring new properties for enhancing selectivity, sensitivity, and practical application in real environment. Host–guest interactions between CP6 and AA were evaluated by the 1H NMR spectrum. When compared with other literatures, our method displayed a lower determination limit and broader linear range. To the best of our knowledge, this is the first study carried out for the non-noble transition-metal Co ion, COF, and pillar[6]arene hybrid material in sensing field, which has a potential value in sensing, catalysis, and preparation of advanced multifunction materials.

Deoxygenation is a global problem in open oceans and coastal regions and has led to the expansion of oxygen minimum zones and coastal hypoxia. Here, using time series observations in the northern Yellow Sea, we illustrate the seasonality of deoxygenation and associated mechanisms in this semienclosed shelf ecosystem and explore the linkage of dissolved oxygen (DO) declines with seawater warming and anthropogenic eutrophication. Our results show that the DO concentration displayed a decreasing trend in winter, with rates of ~0.76 and ~0.78 μmol kg−1yr−1in the surface and bottom waters, respectively. The rapid decline in DO was also observed in the bottom water in summer, with a decreasing rate of ~1.43 μmol kg−1yr−1. In winter, when the water column is vertically homogeneous, the near saturation of DO indicates that physical mixing overwhelmed biological activities, and the estimated results and a linear correlation between DO concentration and temperature suggest that ocean warming is the most plausible driver of deoxygenation in this region in winter. In the stratified water column during summer, increased nutrient availability at the surface and consequently enhanced productivity are responsible for the drawdown of DO in the bottom layer, and the stoichiometric pattern between DO and nitrate also suggests a cascading linkage between the exacerbation of eutrophic conditions and bottom deoxygenation. Our results provide strong evidence that a rapid, semienclosed shelf‐scale decline in DO is underway and highlight the necessity of nutrient reduction strategies in the future. Studying the deoxygenation and its drivers is important to understand the changing marine ecosystem. As an important semienclosed marginal shelf sea in the Northwest Pacific, the Yellow Sea (YS) is one of the world's 64 Large Marine Ecosystems. Due to the natural and anthropogenic stressors, the YS ecosystem has undergone drastic changes over the past decades. In this study, using the long‐term monitoring data set in the northern YS (NYS), the deoxygenation and associated mechanisms in this semienclosed shelf ecosystem are examined in seasonality, and the linkage of dissolved oxygen declines with seawater warming and anthropogenic eutrophication is explored. The results imply that a rapid, semienclosed shelf‐scale declining of dissolved oxygen is ongoing in the continental margin area, reflecting an alarming symptom of coastal environment degradation in the NYS. This work also offers a viewpoint of deoxygenation mechanisms in terms of seasonality in the multiple pressures‐influenced margins, improving our understanding of the marine environmental responses to anthropogenic and natural perturbations. Deoxygenation and its associated mechanisms in the semienclosed northern Yellow Sea were illustrated in terms of seasonalityDecreases in dissolved oxygen (DO) were observed in winter and in the bottom layer in summerLinkage of DO declines with seawater warming and anthropogenic eutrophication was explored

IMPORTANCE: Survival differences between male and female patients with breast cancer have been reported, but the underlying factors associated with the disparity have not been fully studied. This understanding is fundamental to developing strategies for cancer treatment and survivorship care. OBJECTIVE: To compare mortality between male and female patients with breast cancer and quantitatively evaluate the factors associated with sex-based disparity in mortality. DESIGN, SETTING, AND PARTICIPANTS: This large, nationwide, registry-based cohort study used the National Cancer Database to identify and obtain data on patients who received a breast cancer diagnosis between January 1, 2004, and December 31, 2014. After exclusions, the final study population comprised 1 816 733 patients. Statistical analyses were conducted from September 1, 2018, to January 15, 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival. Secondary outcomes were 3-year and 5-year mortality. Mortality differences were evaluated by Kaplan-Meier analysis. The roles of race/ethnicity, clinical characteristics, treatments, and access-to-care factors in the association between sex and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age. RESULTS: In total, 16 025 male (mean [SD] age, 63.3 [13.0] years) and 1 800 708 female (mean [SD] age, 59.9 [13.3] years) patients with breast cancer were included in the study. Compared with female patients, male patients had higher mortality across all stages. For men, the overall survival rate was 45.8% (95% CI, 49.5-54.0; P &lt; .001), the 3-year rate was 86.4% (95% CI, 85.9-87.0; P &lt; .001), and the 5-year rate was 77.6% (95% CI, 76.8-78.3; P &lt; .001). For women, the overall survival rate was 60.4% (95% CI, 58.7-62.0; P &lt; .001), the 3-year rate was 91.7% (95% CI, 91.7-91.8; P &lt; .001), and the 5-year rate was 86.4% (95% CI, 86.4-86.5; P &lt; .001). Overall, clinical characteristics and undertreatments were associated with a 63.3% excess mortality rate for male patients. A higher proportion of excess deaths in men were explained by these factors in the first 3 years after breast cancer diagnosis (66.0%) and in all patients with early-stage cancer (30.5% for stage I and 13.6% for stage II). However, sex remained a significant factor associated with overall mortality (adjusted hazard ratio [HR], 1.19; 95% CI, 1.16-1.23) as well as mortality at 3-year (adjusted HR, 1.15; 95% CI, 1.10-1.21) and 5-year (adjusted HR, 1.19; 95% CI, 1.14-1.23) analyses, even after adjustment for clinical characteristics, treatment factors, age, race/ethnicity, and access to care. CONCLUSIONS AND RELEVANCE: This study found that mortality after cancer diagnosis was higher among male patients with breast cancer compared with their female counterparts. Such disparity appeared to persist after accounting for clinical characteristics, treatment factors, and access to care, suggesting that other factors (particularly additional biological attributes, treatment compliance, and lifestyle factors) should be identified to help in eliminating this disparity.

ABSTRACTNon-caloric artificial sweeteners have been widely permitted as table sugar substitutes with high intensities of sweetness. They can pass through the intestinal tract without significant metabolization and frequently encounter the gut microbiome, which is composed of diverse bacterial species and is a pool of antibiotic resistance genes (ARGs). However, little is known about whether these sweeteners could accelerate the spread of ARGs in the gut microbiome. Here, we established an in vitroconjugation model by using Escherichia colithat carries chromosome-inserted Tn7 lacIq-pLpp-mCherryand plasmid-encoded gfpmut3bgene as the donor and murine fecal bacteria as the recipient. We found that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) can increase reactive oxygen species (ROS) production and promote plasmid-mediated conjugative transfer to the gut microbiome. Cell sorting and 16S rRNA gene amplicon sequencing analysis of fecal samples reveal that the tested sweeteners can promote the broad-host-range plasmid permissiveness to both Gram-negative and Gram-positive gut bacteria. The increased plasmid permissiveness was also validated with a human pathogen Klebsiella pneumoniae. Collectively, our study demonstrates that non-caloric artificial sweeteners can induce oxidative stress and boost the plasmid-mediated conjugative transfer of ARGs among the gut microbiota and a human pathogen. Considering the soaring consumption of these sweeteners and the abundance of mobile ARGs in the human gut, our results highlight the necessity of performing a thorough risk assessment of antibiotic resistance associated with the usage of artificial sweeteners as food additives.

As China's only continental sea, the Bohai Sea is a relatively closed environment and is vulnerable to natural changes and human activities. In this paper, the long‐term variations in nutrients in the Bohai Sea and the potential influencing factors were analyzed based on historical summer and winter data from 1978 to 2016. The results showed that the concentrations of dissolved inorganic nitrogen (DIN) in the Bohai Sea continuously increased from 1990 and rapidly increased after 2002, the phosphate (PO4‐P) concentration exhibited a decreasing trend, and the silicate (SiO3‐Si) concentration decreased from 1978 to 1987 and increased from 1987 to 2008. The nutrient concentrations were lower in summer than in winter, and the bottom concentrations were higher than the surface concentrations in summer, whereas the vertical differences were insignificant in winter. The dominant factor determining the long‐term variations in DIN were atmospheric deposition and nonpoint sources due to various human activities; the primary factors affecting PO4‐P were riverine inputs and nonpoint sources related to natural changes and human activities; the primary factors afftecting SiO3‐Si were riverine inputs. The N/P ratio followed the DIN variation, the Si/P ratio followed the SiO3‐Si variation, and the Si/N ratio decreased. The nutrient ratios were lower at the bottom than at the surface and were lower in winter than in summer. The nutrient limitation changed from nitrogen limitation to phosphorus and silicon limitations. The long‐term nutrient variations in the Bohai Sea have potential ecological impacts on the local red tide features. Nutrients are important to primary productivity and thus important to marine ecosystems. Nutrient variations in coastal oceans may potentially impact the occurrence of ecological disasters. As the only continental sea in China, the Bohai Sea is a relatively closed environment and is vulnerable to natural and anthropogenic impacts. We found that the concentration of dissolved inorganic nitrogen in the Bohai Sea increased from 1990 to 2006; the phosphate concentration decreased from 1978 to 2016, and the silicate concentration decreased before 1987 and increased after 1987. We also found that N/P increased and Si/N decreased. The nutrient concentrations were higher, whereas the nutrient ratios were lower in winter than in summer. In summer, the bottom nutrient concentrations were higher than the surface concentrations, whereas the bottom ratios were lower than the surface ratios; in winter, the vertical differences were insignificant. The primary factors driving the silicate variations were riverine inputs related to natural changes and human activities; the primary factors in the phosphate variations could be riverine inputs and nonpoint sources related to natural changes and human activities; the dominant factor in the dissolved inorganic nitrogen variations could be atmospheric deposition and nonpoint sources due to various human activities. The red tide features in the Bohai Sea seemed to be potentially related to the long‐term nutrient variations. DIN increased; PO4‐P decreased; SiO3‐Si decreased before 1987 and increased after 1987 in the Bohai Sea; winter concentrations are higherN/P increased, Si/N decreased, and Si/P slightly increased in the Bohai Sea; ratios are higher in winter than in summerVariations in Si/N ratios may have ecological impacts on the red tide features in the Bohai Sea

The dynagraph card is an important tool for diagnosing work conditions in rod pump systems. However, a key problem is that actual dynagraph cards may have different working conditions yet exhibit similar graphs. This reduces the classification performance of existing models and leads to poor diagnostic accuracy. To solve this problem, we propose a novel method based on transfer learning and ViT models for diagnosing the working conditions of rod pumping systems. Specifically, we first pre-trained the ViT model using the ImageNet-1k dataset, and then fine-tuned the weights of the model using the actual dynagraph card dataset. This transfer learning way not only significantly reduce the training time of the model, but also effectively improve the accuracy of the working condition diagnosis. To evaluate the performance of the proposed method, we compare it with ResNet, DenseNet, and RegNet models. Our experimental results demonstrate that our method achieves a work condition diagnosis accuracy of 0.9060, which is higher than other methods by 0.2–0.3. Moreover, our method performs well on the problem of different work conditions but graphically similar dynagraph cards. Therefore, our transfer learning and ViT model-based method can better solve the practical problems of dynagraph cards and meet the needs of oilfield sites.

Radioactive tracer techniques may be useful for assessing water transport and the overall effects of concurrent biogeochemical processes in river‐reservoir systems. In this study, we show that radium isotopes can assess the hydrodynamics and sediment/nutrient retention in the Xiaolangdi Reservoir, the largest impoundment along the Yellow River, China. Activity ratios of 224Ra/226Ra and 223Ra/226Ra were used for water mass agecalculations in the riverine, transition, and lentic reaches of the reservoir. Water ages were combined with the length scale of three river‐reservoir zones to determine water transport rates of 3.6 ± 1.2, 1.3 ± 0.3, and 0.16 ± 0.14 km/day, respectively. Radium ages were also used to quantify the net retention of sediment and nutrients in different parts of the river‐reservoir system. Suspended sediment was removed at a rate of 1.4 ± 0.6 g/m3/day, mainly in the riverine zone. Nutrient dynamics were more complicated, with addition or removal at different rates within the three zones. This paper should be of interest to fluvial aquatic scientists and resource managers. Typically, numerical models have been used to estimate reservoir hydrodynamics, and associated biogeochemical processes are investigated separately. Here for the first time, we explore the validity of using radium isotope tracers to assess water age distributions in the Xiaolangdi Reservoir, the largest impoundment along the Yellow River (China). Radium ages were then used to quantitatively evaluate the net retentions of suspended sediments and nutrients within the reservoir. The technique is easy to conduct at relatively low cost and allows one to assess the overall effect of synchronized biogeochemical processes. Ra‐age technique is suitable for hydrodynamic assessments in river‐reservoir systems where model assumptions are metSediment and nutrient retentions may be quantified using Ra water agesNutrients are added and/or removed at different rates within three identified zones of the reservoir

Ecological small towns can attract a large number of rural surplus labors and ease the population pressure, how to carry out the planning and construction ecological town becomes a hotspot of research. Based on this, planning and construction of ecological small towns absorbing surplus rural labor based on fuzzy evaluation method were proposed. First of all, planning and construction of small towns under the concept of ecology were elaborated; and then the planning and construction strategies of small towns integrating ecological concepts were put forward, including the utilization of water resources, ecological the landscape and transportation planning; at the same time, a project for ecological small town in Hebei Province was taken as an example for the planning and design; in addition, the planning objectives and layout planning were analyzed and evaluated by fuzzy evaluation method, and the results confirmed the success of planning and design.

ABSTRACTRecent studies have shown that long non-coding RNAs (lncRNAs) are involved in a number of biological processes; however, further study is still warranted to comprehensively reveal their functions. In this study, we showed that the lncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) was related to breast cancer cell proliferation, metastasis and chemoresistance. Loss- and gain-of function studies were used to assess the role of LINP1 in promoting breast cancer progression. LINP1 knockdown mitigated breast cancer cell growth by inducing G1-phase cell cycle arrest and apoptosis. LINP1 also promoted breast cancer cell metastasis and influenced the expression of epithelial-mesenchymal transition-related markers. We identified p53 as a regulator of LINP1, and LINP1 overexpression could restore the metastatic effects of p53. Furthermore, LINP1 was upregulated in doxorubicin- and 5-fluorouracil-resistant cells and induced chemoresistance. We also observed that LINP1 enrichment played a critical functional role in chemoresistance by inhibiting chemotherapeutics-induced apoptosis. Moreover, LINP1 in tumors was associated with lower overall survival and disease-free survival. In conclusion, LINP1 may serve as a potential oncogene and chemoresistance-related regulator of breast cancer cells, suggesting that LINP1 might be a potent therapeutic target and might reduce chemoresistance in breast cancer.

Arsenic (As) released from As-loaded nano zero-valent iron (nZVI) after As(v) remediation could become an environmental hazard, thus deserving in-depth investigations. This study investigated As release from As-loaded nZVI under different geochemical conditions (i.e., pH, Ca2+, and humic acid (HA) concentrations), as well as the effects of nZVI surface modification (chitosan and polyaniline) and As loadings (low and high) on As release. Alkaline condition (pH = 9) and the presence of humic acid were found to enhance As release from all the types of nZVI samples. Ca2+had no effect on As release for all the types of nZVI at both As loadings, except for chitosan- and polyaniline-modified nZVI at high As loading when Ca2+concentrations increased up to 16 mg L−1. At low As loading, surface modification had a limited impact on As release from As-loaded nZVI. When As loading was high, a higher percentage of As was released from pristine nZVI than those from both the types of modified nZVI. This is because pristine nZVI either formed only monodentate complexes or had a higher ratio of As(iii)/As(v). Under the same geochemical conditions, As released from all the types of As-loaded nZVI at high As loadings was lower than that at low As loadings. This is due to the formation of bidentate complexes with stronger bindings and lower ratios of As(iii)/As(v) for high As loadings. These findings provide a fundamental understanding regarding the environmental behaviors of As-loaded nZVI under natural conditions and the risk associated with the release of As from As-loaded nZVI.

Bottom water breakthrough, which is posed by the failure in an initial water control during acid treatment, is a complex problem in fractured-vuggy dolomite reservoirs with bottom water. To analyze the feasibility of upper stimulation during foamed acid treatment, various experiments were performed, including the analysis of acid flow and etching exclusively in fractures and that in fractures between caves (or reservoirs). The results confirm the abilities of the retarding and upper stimulation of foamed acid. Foamed acid penetrates into the upper fractures and replaces the oil in this part of the reservoir, whereas thickened acid invariably displaces into fractures present in the lower part. During treatment with foamed acid, the displacement rate of oil increases with an increase in the upper fracture connectivity. Furthermore, upper stimulation is suitable for reservoirs with developed upper and undeveloped lower fractures. For field applications, the flow rate should not be extremely high when using foamed acid for upper stimulation of fractured-vuggy dolomite reservoirs with bottom water, and should be maintained at the minimum while ensuring construction efficiency; otherwise, it might result in bottom water breakthrough.

Dam construction in river systems affects the biogeochemistry of nitrogen (N), yet most studies on N cycling in reservoirs do not consider the transformations and retention of the different N species. This study addresses the N inputs, transport, transformations, and retention in the Three Gorges Reservoir (TGR) in the Changjiang River, the world largest water storage project, during its filling phase in 2004–2007. The results indicate that dissolved inorganic nitrogen (DIN) was the most abundant N form in the TGR and particulate N was only 2% to the total N flow and retention. About 34% of the dissolved organic nitrogen (DON), 64% of nitrite, and 44% of ammonia were retained by transformation within the TGR in 2007. Time‐series data show that about 8% of inflowing total dissolved N was lost by denitrification and sedimentation. Transformations of DON, nitrite and ammonia caused an increase of the nitrate load by 6%; and at the same time the DIN flux increased by 4% while the water moved through the TGR, which is the balance between formation and retention of DIN. The large contribution of biogeochemical transformations to nitrate loading in the TGR indicates the importance of internal processing for the river N species composition.

Based on literature data and shipboard observations, this study investigated the main environmental characteristics of the seafloor topography, current field, front, and upwelling that are closely related to hypoxia occurrence off the Changjiang estuary. The physical processes of the plume front and upwelling off the Changjiang estuary in summer were coupled. The vertical distribution pattern of the plume front was closely related to the upwelling. By reviewing and analyzing the historical summer hypoxia events off the Changjiang estuary, we statistically demonstrated the spatial structure of the horizontal distribution of the hypoxic zone and investigated the location of occurrence zone of the hypoxia. We found that the dissolved oxygen (DO) concentration on the inner continental shelf off the estuary showed a “V” shape in relation to station depth. Therefore, we noted that the hypoxic water on the inner continental shelf mostly occurred on the slopes with steep seafloor topography. Base on the current understanding of the hypoxic mechanisms off the Changjiang estuary, we analyzed the biogeochemical mechanisms that could cause the steep terrain off the Changjiang estuary to become the main areas prone to summer hypoxia and explained the internal relations between the location of the hypoxic zone on the slopes and the plume front and upwelling. The plume front and upwelling off the Changjiang estuary and their coupling were important driving forces of summer hypoxia. The continuous supply of nutrients affected by the interaction of the plume front extension of the Changjiang Diluted Water (CDW) and upwelling and the favorable light conditions were important mechanisms causing the phytoplankton blooms and benthic hypoxia off the Changjiang estuary in summer. By analyzing oxygen utilization, organic carbon mineralization, and nutrient regeneration in the hypoxic zone, we observed that the significant oxygen utilization process off the Changjiang estuary in summer also mainly occurred near the steep slopes with front and upwelling features and confirmed the apparent nutrient loss in the benthic hypoxic zone. Meanwhile, our analysis revealed that the sediment resuspension in the benthic boundary layer in the mud areas off the Changjiang estuary could also affect the oxygen utilization and mineralization of organic carbon and nutrient recycling and regeneration. This study also demonstrated that the steep terrain off the Changjiang estuary was the main location for summer acidification, and the coupling between the plume front and upwelling on the steep slopes was an important physical driving force inducing summer benthic acidification. Finally, we discussed issues to address in future studies of the hypoxic zone and water acidification off the Changjiang estuary.

Ferromanganese nodules (Fe‐Mn nodules) are considered as potential sources of in‐demand metals (such as manganese, cobalt, nickel, copper, and rare‐earth elements) that are used in high‐technology industries. The resource potential of Mn nodules in the world ocean remains uncertain due to technological and financial challenges. Here we propose an effective tracer: the natural radioactive radon isotope (222Rn) to assess the abundance of Fe‐Mn nodules on the sea floor. Significant linear relationships were observed between benthic excess 222Rn fluxes and concentrations with Fe‐Mn nodule occurrence and coverage on the global seafloor. Benthic excess 222Rn flux >107dpm/m2/yr or bottom water 222Rn concentrations >2,000 dpm/m3indicate the possibility of Fe‐Mn nodules occurrence at >80% and seabed coverage of >25%. Our results indicate radon, relatively easy to measure, could serve as a novel and efficient tool for targeting Fe‐Mn nodule resources in the global abyssal ocean. Ferromanganese nodules (Fe‐Mn nodules) are source of critical and rare metal for high technology industries. They are found on the abyssal plains of the deep oceans, but their abundance distributions are not well known. Here we proposed a more efficient method to locate Fe‐Mn nodule deposits and asses abundance of Fe‐Mn nodule field by measuring bottom water 222Rn. Bottom water 222Rn was mapped globally and found to overlap well with the distribution of the Fe‐Mn nodules. Benthic excess 222Rn flux and concentration were linearly increased with the probability and ocean floor coverage of Fe‐Mn nodules occurrence. Other processes, including molecular diffusion, biological activity, and deep ocean currents are not sufficient to support the measured near bottom 222Rn. This method is time‐saving and cost‐effective, most importantly, occurrence and abundance of the Fe‐Mn nodules can be quantitatively estimated via benthic ex222Rn flux or bottom water 222Rn activity. A significant positive linear relationship was found between the probability of Mn nodule occurrence and the benthic ex222Rn flux (r= 0.95)Benthic ex222Rn flux was linearly correlated with the percentage of the ocean floor coverage by Fe‐Mn nodules (r= 0.93)Surplus of ex222Rn flux can be a robust monitor to pinpoint locations and assess abundance of Fe‐Mn fields in the global deep ocean A significant positive linear relationship was found between the probability of Mn nodule occurrence and the benthic ex222Rn flux (r= 0.95) Benthic ex222Rn flux was linearly correlated with the percentage of the ocean floor coverage by Fe‐Mn nodules (r= 0.93) Surplus of ex222Rn flux can be a robust monitor to pinpoint locations and assess abundance of Fe‐Mn fields in the global deep ocean

Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

Using gas chromatography-mass spectrometry (GC-MS) as a means of separation and identification, a solvent extraction (SE) method was first developed and used for isolating and concentrating the volatile components from Syringaflowers. Its performance was assessed by comparing it with headspace solid-phase microextraction (HS-SPME) technology, which is generally recognized as an effective means for trapping volatile substances. Four main influencing parameters, the solvent, solvent volume, extraction time and heating temperature, were optimized in order to achieve high extraction efficiency. The experimental results show that both methods exhibit their own extraction performance for Syringa emodiWall. Among a total of 21 substances that were separated, 17 substances were identified using these two methods. Of these, 15 were identified by SE and 12 by HS-SPME. Among these 17 substances, 10 were identified by both methods and seven only by one method: five by SE and two by HS-SPME. Both methods also give different relative contents of the substances involved. These comparative results show that SE has an ability to trap the volatile components that is even better than that of HS-SPME in this case. Moreover, this method was also applied to 15 other varieties of Syringaflowers.

Objective To investigate breast cancer risk factors in Chinese women residing in urban and rural areas of eastern China using a large-scale cross-sectional survey.Methods In this multistage, stratified cluster sampling epidemiological survey, information on demographic characteristics, diet and lifestyle variables were gathered using a carefully designed questionnaire. Multivariate logistic regression analysis and subgroup analyses of the data were performed, including separate analyses of data from women residing in urban and rural areas.Results A total of 122 058 women were included in the survey. Age, body mass index, number of miscarriages, family history of breast cancer and menopausal status were found to be risk factors for breast cancer, while the consumption of soya bean products was a protective factor. Among women residing in urban areas, high or moderate intake of soya bean products and red meat were protective factors. Among women residing in rural areas, obesity and a high intake of milk were identified as risk factors for breast cancer, while a moderate intake of soya bean products was a protective factor.Conclusions This type of data is crucial for understanding the risk factors for breast cancer and could facilitate the development and targeting of effective intervention strategies, with the ultimate aim of breast cancer prevention.

Radium isotopes are powerful proxies in oceanography and hydrology. Radium mass balance models, including assessments of submarine groundwater discharge (SGD), often overlook particle scavenging (PS) as a pathway for dissolved radium removal from the world ocean. Here, we build a global ocean 226Ra mass balance model and reevaluate the potential importance of PS. We find that PS is the major 226Ra sink for the upper ocean, removing about 96% of the total input from various sources. Aside from vertical exchange with the lower ocean, SGD is the largest 226Ra source into the upper ocean. The biological pump transfers particles to the deep ocean, resulting in a major but often overlooked impact on the global 226Ra marine budget. Our findings suggest that radium mass balance models should consider PS in systems with high siliceous algae production and export fluxes and long water residence times to prevent underestimation of large‐scale SGD fluxes. Radium is a very powerful tracer for many oceanographic processes. A common assumption in radium investigations is that incorporation into particles plays a negligible role in mass balances. Contrary to this assumption, we found that particle scavenging related to the so‐called “biological pump” is the largest sink for 226Ra in the global ocean, and that submarine groundwater discharge is the largest terrestrial input. Particle scavenging can be even more important in highly productive coastal systems with long water residence times and high particle burial efficiencies. Particle scavenging, which has been overlooked in many mass balance calculations, may be important for 226Ra and 228Ra budgets from local to global scales. Particle scavenging is the major 226Ra sink for the upper ocean, removing about 96% of the total input from various sourcesSubmarine groundwater discharge (SGD) is the largest terrestrial 226Ra source into the upper ocean, followed by river input and sediment diffusionParticle scavenging can be important in coastal oceans with high primary production and particle burial efficiencies Particle scavenging is the major 226Ra sink for the upper ocean, removing about 96% of the total input from various sources Submarine groundwater discharge (SGD) is the largest terrestrial 226Ra source into the upper ocean, followed by river input and sediment diffusion Particle scavenging can be important in coastal oceans with high primary production and particle burial efficiencies

Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed by both lower motor neurons and skeletal muscle. Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC) transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients.

The concentrations of phosphate (PO43−), ammonium, nitrite, nitrate, silicate, dissolved organic nitrogen (DON), dissolved organic phosphorus (DOP), particulate phosphorus (PP) and particulate nitrogen (PN) along the salinity gradient were measured in the Changjiang Estuary in April 2007. The behavior of nutrient species along the continuum from the freshwater to the coastal zone is discussed. In the mixing zone between the riverine and marine waters, nitrate and phosphate behave non-conservatively, while silicate behaves conservatively. Nutrient import was quantified from the river load. Nutrient export to the sea was quantified from river discharge and from the salinity-nutrient gradient in the outer estuary. Using these data, a nitrogen and phosphorus budget was made. The internal estuarine fluxes played an important role in the nutrient estuarine fluxes, which accounted for approximately 41% of the nitrogen flux and 45% of the phosphorus flux. The mixing experiments in the laboratory generally reproduced well the inorganic process affecting nutrient dynamics in the Changjiang Estuary, indicating that the primary P and N transformation processes were phosphate and nitrate desorption along the salinity gradient.

Free nitrous acid (FNA, i.e., HNO2) has been recently applied to biofilm control in wastewater management. The mechanism triggering biofilm detachment upon exposure to FNA still remains largely unknown. In this work, we aim to prove that FNA induces biofilm dispersal via extracellular polymeric matrix breakdown and cell lysis. Biofilms formed by a model organism, Pseudomonas aeruginosaPAO1, were treated with FNA at concentrations ranging from 0.2 to 15 mg N/L for 24 h (conditions typically used in applications). The biofilms and suspended biomass were monitored both before and after FNA treatment using a range of methods including optical density measurements, viability assays, confocal laser scanning microscopy, and atomic force microscopy. It was revealed that FNA treatment caused substantial and concentration-dependent biofilm detachment. The addition of a reactive nitrogen species (RNS) scavenger, that is, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, substantially reduced biofilm dispersal, suggesting that the nitrosative decomposition species of HNO2(i.e., RNS, e.g., •NO + •NO2) were mainly responsible for the effects. The study provides insight into and support for the use of FNA for biofilm control in wastewater treatment.

Although triclosan, as a widely used antiseptic chemical, is known to promote the transmission of antibiotic resistance to diverse hosts in pure culture, it is still unclear whether and how triclosan could affect the transmission of broad-host-range plasmids among complex microbial communities. Here, bacterial culturing, fluorescence-based cell sorting, and high-throughput 16S rRNA gene amplicon sequencing were combined to investigate contributions of triclosan on the transfer rate and range of an IncP-type plasmid from a proteobacterial donor to an activated sludge microbiome. Our results demonstrate that triclosan significantly enhances the conjugative transfer of the RP4 plasmid among activated sludge communities at environmentally relevant concentrations. High-throughput 16S rRNA gene sequencing on sorted transconjugants demonstrates that triclosan not only promoted the intergenera transfer but also the intragenera transfer of the RP4 plasmid among activated sludge communities. Moreover, triclosan mediated the transfer of the RP4 plasmid to opportunistic human pathogens, for example, Legionellaspp. The mechanism of triclosan-mediated conjugative transfer is primarily associated with excessive oxidative stress, followed by increased membrane permeability and provoked SOS response. Our findings offer insights into the impacts of triclosan on the dissemination of antibiotic resistance in the aquatic environmental microbiome.

Objectives MicroRNA-206 (miR-206) is downregulated in many human malignancies, which correlates with tumour progression. This study characterized the contribution of miR-206 to the initiation and progression of human breast cancer.Methods Consecutive primary breast cancer patients who received radical resection were enrolled. Breast cancer tissue samples were obtained during surgery. MiR-206 levels in matched pairs of cancer tissue and normal adjacent tissue (NAT) samples were examined using quantitative reverse transcription–polymerase chain reaction. The relationship between miR-206 levels and clinicopathological characteristics and overall survival was also investigated.Results In 128 patients with breast cancer, miR-206 was downregulated in 119 (93%) tumour tissue compared with their matched NAT samples. Decreased miR-206 was significantly associated with advanced clinical stage and lymph node metastasis. Univariate and multivariate Cox proportional hazard regression analysis revealed that a low miR-206 level was an unfavourable prognostic factor for overall survival, in patients with breast cancer.Conclusions This study indicated that miR-206 may be a good candidate as a novel prognostic indicator in breast cancer patients.

AbstractThe interconnect architecture is essential to the performance of the interconnection network, so it is very significant to design a new cost-effective interconnect architecture. 2D meshes are the most popular interconnect architecture for parallel processing. However, the diameter and average distance of a 2D mesh are large enough to greatly influence performance of the network. This paper presents a novel interconnect architecture called TM, which combines the advantages of both a 2D torus and a 2D mesh. For an n× nnetwork, number of links of a TM is the same as that of a mesh, while the diameter of a TM is close to that of a torus. Besides, the average distance of a TM is at the middle of that of a torus and a mesh. To prevent deadlocks in TMs, a novel deadlock avoidance scheme, called proxy policy, is proposed. Moreover, both the deterministic and fully adaptive routing techniques in TMs are proposed using proxy policy to prevent deadlocks. Sufficient simulation results are presented to show the effectiveness of the TM network and the new routing schemes.

Abstract: Relationships between phytoplankton community composition and environmental variables in the East China Sea (ECS) and Yellow Sea (YS) were investigated using geochemical and molecular microbiology methods. The diversity of phytoplankton was characterized using cultivation-independent PCR-based denaturing gradient gel electrophoresis (DGGE). Groups resulting from unweighted pair-group method with arithmetic averages clustering of the DGGE profiles showed good consistency with the eco-environmental characteristics of the sea area they belonged to. Additionally, the clustering results based on DGGE fingerprinting and those based on morphological compositions were practically identical. The relationship of phytoplankton diversity to environmental factors was statistically analyzed. Temperature, dissolved inorganic nitrogen (DIN), and silicate-Si were found significantly related to the phytoplankton community composition. Canonical correspondence analysis (CCA) was performed to reveal the relationship between community composition and these three environmental factors. Generally, values of the ECS are clearly separated from those of the YS in the CCA biplot, due to mainly the effect of temperature and DIN.

Abstract: Suspended particulate matter (SPM) collected in the Changjiang (Yangtze River) estuary in June 2006 was separated into five fractions via water elutriation: clay-very fine silt (<8 µm), fine silt (8–16 µm), medium silt (16–32 µm), coarse silt (32-63 µm) and sand (>63 µm). The SPM and fractionated particles were sequentially analyzed by a modified SEDEX sequential extraction method to obtain six species of phosphorus: exchangeable or loosely-sorbed P, organic P, Fe-bound P, authigenic P, detrital P and refractory P. The results indicated that all particulate phosphorus species except for detrital P were negatively correlated to particle size; a high detrital P content was found in coarse silt and very coarse silt. From the inside of the river mouth to the gate of the river mouth, organic P, Fe-bound P and refractory P in the suspended particles decreased and a higher amount of exchangeable P appeared around the gate of the river mouth. From the gate of the river mouth to the sea, exchangeable P and organic P in suspended particles increased distinctly. The total particulate P flux into the estuary from the Changjiang River was about 45.45×108 µmol/s during sampling. Of this, about 8.27×108 µmol/s was associated with the “truly suspended” fraction. The bio-available particulate P flux was about 13.58×108 µmol/s. Of this, about 4.24×108 µmol/s was transported by “truly suspended” particles.

Here, we used a mouse model of Kennedy disease, a degenerative disorder caused by an expanded CAG repeat in the androgen receptor (AR) gene, to explore pathways leading to cellular dysfunction. We demonstrate that male mice containing a targeted Ar allele with 113 CAG repeats (AR113Q mice) exhibit hormone- and glutamine length-dependent missplicing of Clcn1 RNA in skeletal muscle. Changes in RNA splicing are associated with increased expression of the RNA-binding protein CUGBP1. Furthermore, we show that skeletal muscle denervation in the absence of a repeat expansion leads to increased CUGBP1 expression. However, this induction of CUGBP1 is not sufficient to alter Clcn1 RNA splicing, indicating that changes mediated by both denervation and AR113Q toxicity contribute to altered RNA processing. To test this notion directly, we exogenously expressed the AR in vitro and observed hormone-dependent changes in the splicing of pre-mRNAs from a human cardiac troponin T minigene. These effects were notably similar to changes mediated by RNA with expanded CUG tracts, but not CAG tracts, highlighting unanticipated similarities between CAG and CUG repeat diseases. The expanded glutamine AR also altered hormone-dependent splicing of a calcitonin/calcitonin gene-related peptide minigene, suggesting that toxicity of the mutant protein additionally affects RNA processing pathways that are distinct from those regulated by CUGBP1. Our studies demonstrate the occurrence of hormone-dependent alterations in RNA splicing in Kennedy disease models, and they indicate that these changes are mediated by both the cell-autonomous effects of the expanded glutamine AR protein and by alterations in skeletal muscle that are secondary to denervation.

The metabolism and disposition of [14C]apixaban, an orally bioavailable, highly selective, and direct acting/reversible factor Xa inhibitor, was investigated in 10 healthy male subjects without (group 1, n = 6) and with bile collection (group 2, n = 4) after a single 20-mg oral dose. Urine, blood, and feces samples were collected from all subjects. Bile samples were also collected for 3 to 8 h after dosing from group 2 subjects. There were no serious adverse events or discontinuations due to adverse effects. In plasma, apixaban was the major circulating component and O-demethyl apixaban sulfate, a stable and water-soluble metabolite, was the significant metabolite. The exposure of apixaban (Cmaxand area under the plasma concentration versus time curve) in subjects with bile collection was generally similar to that in subjects without bile collection. The administered dose was recovered in feces (group 1, 56.0%; group 2, 46.7%) and urine (group 1, 24.5%; group 2, 28.8%), with the parent drug representing approximately half of the recovered dose. Biliary excretion represented a minor elimination pathway (2.44% of the administered dose) from group 2 subjects within the limited collection period. Metabolic pathways identified for apixaban included O-demethylation, hydroxylation, and sulfation of hydroxylated O-demethyl apixaban. Thus, apixaban is an orally bioavailable inhibitor of factor Xa with elimination pathways that include metabolism and renal excretion.

An appropriate proxy could help to better understand dissolved oxygen variations in the past, helping to predict potential outcomes of future environmental changes. In the Changjiang Estuary (China), the foraminifer Cribrononion subincertum(C. subincertum) shows a distinct population maximum in the topmost sediment, an indication of an epifaunal species. Therefore, the geochemical composition of C. subincertumtests could record changes in the region’s bottom water chemistry. Our results showed that Mn/Ca ratios in tests of living (Rose‐Bengal stained) C. subincertumanalyzed by LA‐ICP‐MS were responsive to variations of bottom water dissolved oxygen concentrations, with average foraminiferal Mn/Ca ratios three times higher during low‐oxygen period than in winter. In the uppermost centimeters of sediment, wider ranges of foraminiferal Mn/Ca occurred in summer compared to winter ranges. Our results imply that this epifaunal benthic foraminiferal species could serve as a useful benthic monitor with the Mn/Ca ratios representing a reliable proxy of hypoxia in the past. We explored how different dissolved oxygen contents impacts the geochemical composition of benthic foraminiferal shells (tests) in a dynamic coastal setting. We collected sediment samples and identified living (Rose Bengal stained) foraminifera from the Changjiang (Yangtze) Estuary, one of the largest seasonally hypoxic (low oxygen) zones in the world. Sampling at 1‐cm intervals revealed Cribrononion subincertumpredominantly inhabits the surface sediments in this area. Mn/Ca ratios in living tests of this benthic foraminifer were measured via laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS). As expected, Mn/Ca ratios responded to changing Mn in the bottom waters which itself is correlated to DO levels. Our results imply that this epifaunal benthic foraminiferal species could serve as a useful benthic monitor with the Mn/Ca ratios representing a reliable proxy of hypoxia in the past. The microhabitat of Cribrononion subincertumwas found to be epifaunal in the Changjiang EstuaryCribrononion subincertumMn/Ca ratios were responsive to variations of bottom water dissolved oxygenEpifaunal benthic foraminifera can be a robust monitor for coastal hypoxia; more species need to be similarly studied The microhabitat of Cribrononion subincertumwas found to be epifaunal in the Changjiang Estuary Cribrononion subincertumMn/Ca ratios were responsive to variations of bottom water dissolved oxygen Epifaunal benthic foraminifera can be a robust monitor for coastal hypoxia; more species need to be similarly studied

The Changjiang (Yangtze River) Estuary (CE) and adjacent inner East China Sea (ECS) shelf are among the most well‐known hypoxic aquatic environments. However, the coupled effects of coastal upwelling and the river plume on hypoxic dynamics in this region are rarely examined. Based on observations off the CE and Zhejiang coast in the summer of 2018, the dynamic mechanisms were revealed by highlighting the combined role of the river plume and upwelling in regulating hypoxia. The bottom hypoxic water formed in the steep slope on the inner ECS shelf expands upward and seaward. Coastal upwelling and the river plume combine to regulate the primary production regime and hypoxia. The frontal regions in the upper layers are prone to phytoplankton blooms, while the convergent slope generally acts as a hot spot of bottom hypoxic center along cross‐shelf sections. The regional selectivity of hypoxia is responsible for the decoupling between locations of bottom‐water hypoxia and upper‐water phytoplankton patches. The upwelling transports oxygen‐deficient water to the upper layers, resulting in shoreward shoaling of the oxycline. Meanwhile, mainly forced by the seaward expansion of low‐oxygen water protruding from the bottom hypoxia in the sloping region, a pronounced midlayer hypoxic plume forms. Together, upwelling and offshore spreading potentially expand the spatial volume of the hypoxic zone. Vertical secondary circulation and subsequent physical–biogeochemical processes leading to hypoxia are indicated off the CE and Zhejiang coast. Our results demonstrate that the combination of upwelling and the river plume plays an important role in regulating the spatial distribution of coastal and estuarine hypoxia. The Changjiang Estuary (CE) has become one of the well‐known eutrophic hypoxic systems in summer. Exploring the mechanisms of hypoxia formation is of great significance for evaluating and predicting its effects on estuarine ecosystems. Here, specific attention was given to the hypoxic dynamics by highlighting the combined role of the river plume and coastal upwelling in the CE and adjacent inner East China Sea. We show that bottom hypoxic water spreads upward and seaward on the inner shelf. A pronounced intermediate‐layer hypoxic plume was observed, expanding offshore from the bank slope area. Vertical secondary circulation and associated physical–biogeochemical processes regulate hypoxia within the coupled river plume–upwelling region. Our results offer new insight into the spatial variations and mechanisms of hypoxia in estuarine ecosystems under coastal upwelling and river plume. Hypoxic water spreads upward and seaward under convergent upwelling on the inner East China Sea shelfA pronounced intermediate‐layer hypoxic plume was observed to expand offshore from the bank slope areaSecondary circulation and associated physical‐biogeochemical processes are suggested to regulate hypoxia in the coupled upwelling‐river plume region Hypoxic water spreads upward and seaward under convergent upwelling on the inner East China Sea shelf A pronounced intermediate‐layer hypoxic plume was observed to expand offshore from the bank slope area Secondary circulation and associated physical‐biogeochemical processes are suggested to regulate hypoxia in the coupled upwelling‐river plume region

Abstract: Underground brine samples were collected along the southern coast of the Laizhou Bay, Shangdong, China in two field investigations in 2003. The brines are confined in the Quaternary sediment and underwent a series of geochemical changes. The redox states of these brines were assessed qualitatively based on the measurements of Eh and redox-sensitive species such as DO, NO NO3−, Mn2+, Fe2+, SO42− in the brines. The redox condition of the underground brine is anoxic, and the redox reactions that controlled the redox potential of brines should be Fe(III) reduction and sulfate reduction.

Dietary gamma-linolenic acid (GLA), a omega-6 polyunsaturated fatty acid found in borage oil (BOR), lowers systolic blood pressure in spontaneously hypertensive rats (SHRs). GLA is converted into arachidonic acid (AA) by elongation and desaturation steps. Epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 (P450)-derived AA eicosanoids with important roles in regulating blood pressure. This study tested the hypothesis that the blood pressure-lowering effect of a GLA-enriched diet involves alteration of P450-catalyzed AA metabolism. Microsomes and RNA were isolated from the renal cortex of male SHRs fed a basal fat-free diet for 5 weeks to which 11% by weight of sesame oil (SES) or BOR was added. There was a 2.6- to 3.5-fold increase in P450 epoxygenase activity in renal microsomes isolated from the BOR-fed SHRs compared with the SES-fed rats. Epoxygenase activity accounted for 58% of the total AA metabolism in the BOR-treated kidney microsomes compared with 33% in the SES-treated rats. More importantly, renal 14,15- and 8,9-EET levels increased 1.6- to 2.5-fold after dietary BOR treatment. The increase in EET formation is consistent with increases in CYP2C23, CYP2C11, and CYP2J protein levels. There were no differences in the level of renal P450 epoxygenase mRNA between the SES- and BOR-treated rats. Enhanced synthesis of the vasodilatory EETs and decreased formation of the vasoconstrictive 20-HETE suggests that changes in P450-mediated AA metabolism may contribute, at least in part, to the blood pressure-lowering effect of a BOR-enriched diet.

An unresolved question in the study of the polyglutamine neurodegenerative disorders is the extent to which partial loss of normal function of the mutant protein contributes to the disease phenotype. To address this, we studied Kennedy disease, a degenerative disorder of lower motor neurons caused by a CAG/glutamine expansion in the androgen receptor(Ar) gene. Signs of partial androgen insensitivity, including testicular atrophy and decreased fertility, are common in affected males, although the underlying mechanisms are not well understood. Here, we describe a knock-in mouse model that reproduces the testicular atrophy, diminished fertility, and systemic signs of partial androgen insensitivity that occur in Kennedy disease patients. Using this model, we demonstrate that the testicular pathology in this disorder is distinct from that mediated by loss of AR function. Testes pathology in 113 CAG knock-in mice was characterized by morphological abnormalities of germ cell maturation, decreased solubility of the mutant AR protein, and alterations of the Sertoli cell cytoskeleton, changes that are distinct from those produced by AR loss-of-function mutation in testicular feminization mutantmice. Our data demonstrate that toxic effects of the mutant protein mediate aspects of the Kennedy disease phenotype previously attributed to a loss of AR function.

Epoxyeicosatrienoic acids are cytochrome P-450 metabolites of arachidonic acid with multiple biological functions, including the regulation of vascular tone, renal tubular transport, cellular proliferation, and inflammation. Epoxyeicosatrienoic acids are converted by soluble epoxide hydrolase into the corresponding dihydroxyeicosatrienoic acids, and epoxyeicosatrienoic acid hydration is regarded as one mechanism whereby their biological effects are eliminated. Previous animal studies indicate that soluble epoxide hydrolase plays an important role in the regulation of renal eicosanoid levels and systemic blood pressure. To begin to elucidate the mechanism of these effects, we determined the cellular localization of soluble epoxide hydrolase in human kidney by examining biopsies taken from patients with a variety of non-end-stage renal diseases, as well as those without known renal disease. Immunohistochemical staining of acetone-fixed kidney biopsy samples revealed that soluble epoxide hydrolase was preferentially expressed in the renal vasculature with relatively low levels in the surrounding tubules. Expression of soluble epoxide hydrolase was evident in renal arteries of varying diameter and was localized mostly in the smooth muscle layers of the arterial wall. Western blot analysis and functional assays confirmed the expression of soluble epoxide hydrolase in the human kidney. There were no obvious differences in soluble epoxide hydrolase expression between normal and diseased human kidney tissue in the samples examined. Our results indicate that soluble epoxide hydrolase is present in the human kidney, being preferentially expressed in the renal vasculature, and support an essential role for this enzyme in renal hemodynamic regulation and its potential utility as a target for therapeutic intervention.

A novel water‐diluted hybrid coating, consisting of fluorinated poly(urethane‐acrylate) (PUA) and colloidal silica, was prepared by introducing a small amount of fluorinated methacrylate units into the PUA chains. The surface composition and surface morphology of the hybrid film were studied extensively. Attenuated total reflectance spectra of infrared analyses showed an enrichment of fluorine‐containing polymer and silica particles on the surface. Using X‐ray photoelectron spectroscopy with Ar+etching, it was confirmed that a higher concentration than the calculated value of fluorine element was found on the surface of the fluorinated hybrid film, and the amount of silica increased from the very surface to the near surface. The fluorinated alkyl side chains of the fluorinated polymethacrylate were found to orient toward the surface. It is inferred that the silica particles prevent the migration of fluorine‐containing chains for some kind of effect. A comparison of surface topography between the fluorinated PUA film and the fluorinated PUA/SiO2hybrid film was carried out using atomic force microscopy. Finally, the surface property of the hybrid coating was also determined by contact angle measurement. © 2002 Wiley Periodicals, Inc. Adv Polym Techn 21: 268–274, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10030