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The prediction of bathymetry has advanced significantly with the development of satellite altimetry. However, the majority of its data originate from marine gravity anomaly. In this study, based on the expression of vertical gravity gradient (VGG) of a rectangular prism, the governing equations for determining sea depths to invert bathymetry. The governing equation is solved by linearization through an iterative process, and numerical simulations verify its algorithm and its stability. We also study the processing methods of different interference errors. The regularization method improves the stability of the inversion process for errors. A piecewise bilinear interpolation function roughly replaces the low-frequency error, and numerical simulations show that the accuracy can be improved by 41.2 % after this treatment. For variable ocean crust density, simulation simulations verify that the root-mean-square (RMS) error of prediction is approximately 5 m for the sea depth of 6 km if density is chosen as the average one. Finally, two test regions in the South China Sea are predicted and compared with ship soundings data, RMS errors of predictions are 71.1 m and 91.4 m, respectively.

Study region: The Laochang Karst watershed (LCKW) is located in eastern Yunnan Province, southwestern China. It is the representative karst area affected by coal-mining activities in southwestern China. Study focus: Identifying hydrological processes of multi-layered aquifers in karst watersheds is challenging due to complex natural and anthropogenic processes. This study attempts to clarify the hydrological conceptual model of the LCKW using hydrochemistry and D, O, Sr, S, and C isotopes. New hydrological insights for the region: Surface water and multi-layered groundwater have the hydrochemical types of SO4-Ca·Mg, HCO3·SO4-Ca, and HCO3-Ca. Meteoric water and condensate were the major recharge sources. The main processes dominating hydrochemical compositions consist of sulfide oxidative dissolution, carbonate dissolution, positive cation exchange, and agricultural activities. Elevated SO42− concentration in the mine water, river water and shallow coalbed water mainly originated from the oxidation of pyrite in the coal-bearing strata of the Longtan Formation. whereas the deeper layers and groundwater away from the mines were hardly contaminated by SO42− due to the presence of aquiclude. HCO3− concentrations of surface water and multi-layered groundwater were mainly derived from carbonate dissolution and soil CO2, and mine water was also influenced by atmospheric CO2. Positive cation exchange contributed to increasing Na+ concentration. Agricultural activities contributed NO3−, Cl−, and K+ ions in aquifers, especially near large karst fallout caves. A hydrological model of multi-layered aquifers in the LCKW was built based on the above results. These findings will provide valuable guidance for understanding the hydrological processes of complex karst watersheds worldwide.

Intestinal organoids are a three-dimensional cell culture model derived from colon or pluripotent stem cells. Intestinal organoids constructed in vitro strongly mimic the colon epithelium in cell composition, tissue architecture, and specific functions, replicating the colon epithelium in an in vitro culture environment. As an emerging biomedical technology, organoid technology has unique advantages over traditional two-dimensional culture in preserving parental gene expression and mutation, cell function, and biological characteristics. It has shown great potential in the research and treatment of colorectal diseases. Organoid technology has been widely applied in research on colorectal topics, including intestinal tumors, inflammatory bowel disease, infectious diarrhea, and intestinal injury regeneration. This review focuses on the application of organoid technology in colorectal diseases, including the basic principles and preparation methods of organoids, and explores the pathogenesis of and personalized treatment plans for various colorectal diseases to provide a valuable reference for organoid technology development and application.

ABSTRACT: Lipopolysaccharide (LPS) from Gram-negative bacteria initially induces liver inflammation with proinflammatory cytokines expressions. However, the underlying hepatoprotective mechanism of quercetin on LPS-induced hepatic inflammation remains unclear. Specific pathogen-free chicken embryos (n = 120) were allocated control vehicle, PBS with or without ethanol vehicle, LPS (125 ng/egg) with or without quercetin treatment (10, 20, or 40 nmol/egg, respectively), quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated abovementioned solutions via the allantoic cavity. At embryonic d 19, the livers of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, and immunohistochemistry investigation. We found that the liver presented inflammatory response (heterophils infiltration) after LPS induction. The LPS-induced mRNA expressions of inflammation-related factors (TLR4, TNFα, IL-1β, IL-10, IL-6, MYD88, NF-κB1, p38, and MMP3) were upregulated after LPS induction when compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. Quercetin significantly decreased the immunopositivity to TLR4 and MMP3 in the treatment group when compared with the LPS group. Quercetin could significantly downregulate the mRNA expressions of autophagy-related genes (ATG5, ATG7, Beclin-1, LC3A, and LC3B) and necroptosis-related genes (Fas, Bcl-2, Drp1, and RIPK1) after LPS induction. Quercetin significantly decreased the immunopositivity to LC3 in the treatment group when compared with the LPS group; meanwhile, quercetin significantly decreased the protein expressions of LC3-I, LC3-II, and the rate of LC3-II/LC3-I. In conclusions, quercetin can alleviate hepatic inflammation induced by LPS through modulating autophagy and necroptosis.

Seafloor topography prediction can fill in sea areas without ship sounding data. However, the dependence of various topographic prediction algorithms on ship soundings varies significantly. Hence, this study explores the impact of the number and distributions of ship soundings on topographic prediction using the gravity–geologic method (GGM) and an analytical algorithm. Firstly, this study investigates the influence of ship sounding coverage on the two algorithms. The simulation results demonstrate that increasing coverage from 5.40% to 31.80%, coupled with more uniform distributions across the study area, substantially reduces the RMS error of the GGM. Specifically, the RMS error decreases from 238.68 m to 42.90 m, an improvement of 82.03%. The analytical algorithm maintains a consistent RMS error of 40.39 m because it does not depend on ship soundings. Furthermore, we select a 1° × 1° sea area (134.8°–135.8°E, 30.0°–31.0°N), and the ship soundings are divided into two control groups, Part I and Part II, with coverages of 8.19% and 33.19%, respectively. When Part II is used for calculation, the RMS error of the GGM decreases from 204.17 m to 126.95 m compared to when Part I is used, while the analytical algorithm exhibits an RMS error of 167.94 m. The findings indicate that the prediction accuracy of the GGM is significantly affected by ship soundings, whereas the analytical algorithm is more stable and independent of ship soundings. Based on simulation experiments and realistic examples, when the effective ship soundings coverage exceeds 30%, the GGM may have more advantages. Conversely, the analytical algorithm may be better. This suggests that effectively combining and utilizing different algorithms based on the ship sounding coverage can improve the accuracy of topographic prediction. This will provide a basis for integrating multiple algorithms to construct a global seafloor topography model.

BackgroundThyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that has a significant impact on individuals and society. The etiology of TAO is complicated and poorly understood. Thus, the goal of this study was to use bioinformatics to look into the pathogenesis of TAO and to identify the optimum feature genes (OFGs) and immune infiltration patterns of TAO.MethodsFirstly, the GSE58331 microarray data set was utilized to find 366 differentially expressed genes (DEGs). To find important modular genes, the dataset was evaluated using weighted gene coexpression network analysis (WGCNA). Then, the overlap genes of major module genes and DEGs were further assessed by applying three machine learning techniques to find the OFGs. The CIBERSORT approach was utilized to examine immune cell infiltration in normal and TAO samples, as well as the link between optimum characteristic genes and immune cells. Finally, the related pathways of the OFGs were predicted using single gene set enrichment analysis (ssGSEA).ResultsKLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 were the six best feature genes that were employed to create a nomogram with high predictive performance. The immune cell infiltration investigation revealed that the development of TAO may include memory B cells, T cell follicular helper cells, resting NK cells, macrophages of type M0, macrophages of type M1, resting dendritic cells, active mast cells, and neutrophils. In addition, ssGSEA results found that these characteristic genes were closely associated with lipid metabolism pathways.ConclusionIn this research, we found that KLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 are intimately associated with the development and progression of TAO, as well as with lipid metabolism pathways.

Forest roads are a common land use feature with a significant impact on sediment yield and the water sediment transport processes within a watershed, seriously disrupting the safety and stability of the watershed. Previous studies have focused on the sediment production processes within the road prism. However, there has been limited attention given to the transport processes of road-eroded sediment at various scales, which is crucial for understanding the off-site effects of road erosion. This paper reviews research conducted on forest road erosion over the past two decades. It summarizes the mechanisms of sediment production from road erosion and provides a detailed analysis of the transport mechanisms of eroded sediments from roads to streams at the watershed scale. The paper also examines the ecological and hydrological effects, research methods, and control measures related to sediment transport caused by forest road erosion. It identifies current research limitations and outlines future research directions. The findings of this review highlight several key points: (1) Most research on forest road erosion tends to be specific and unilateral, often neglecting the broader interaction between roads and the watershed in terms of water–sediment dynamics. (2) Various research methods are employed in the study of forest road erosion, including field monitoring, artificial simulation experiments, and road erosion prediction models. Each method has its advantages and disadvantages, but the integration of emerging technologies like laser scanning and fingerprint recognition remains underutilized, hindering the simultaneous achievement of convenience and accuracy. (3) The transport processes of forest road-eroded sediment, particularly on road–stream slopes, are influenced by numerous factors, including terrain, soil, and vegetation. These processes exhibit significant spatial and temporal variability, and the precise quantification of sediment transport efficiency to the stream remains challenging due to a lack of long-term and stable investigation and monitoring methods. The establishment and operation of runoff plots and sedimentation basins may help offer a solution to this challenge. (4) Both biological and engineering measures have proven effective in reducing and limiting sediment erosion and transport. However, the costs and economic benefits associated with these regulation measures require further investigation. This review provides a comprehensive summary of relevant research on sediment erosion and transport processes on unpaved forest roads, enhancing our understanding of sediment yield in watersheds and offering valuable insights for reducing sediment production and transport to streams.

Owing to the dependence of algorithms on the measurement of ship soundings and geophysical parameters, the accuracy and coverage of topography still need to be improved. Previous studies have mostly predicted topography using gravity or gravity gradient, However, there is a relative lack of integrated research combining or comparing gravity and gravity gradient. In this study, we develop observation equations to predict topography based on vertical gravity anomalies (VG; also called gravity anomalies) and vertical gravity gradient (VGG) anomalies generated by a rectangular prism. The sources of interference are divided into medium- to high-frequency errors and low-frequency errors, and these new methods reduce these errors through regularization and error equations. We also use numerical simulations to test the efficiency of the algorithm and error-reduction method. Statistics show that VGG anomalies are more sensitive to topographic fluctuations; however, the linear correlation between VG anomalies and topography is stronger. Additionally, we use the EIGEN-6C4 model of VG and VGG anomalies to predict topography in shallow and deep-sea areas, with maximum depths of 2 km and 5 km, respectively. In the shallow and deep-sea areas, the root mean square (RMS) errors of VGG anomalies prediction are 93.8 m and 233.8 m, and the corresponding accuracies improved by 7.3% and 2.3% compared with those of VG anomaly prediction, respectively. Furthermore, we use cubic spline interpolation to fuse ship soundings and improve the accuracy of the final topography results. We develop a novel analytical algorithm by constructing an observation equation system applicable to VG and VGG anomalies. This will provide new insights and directions to refine topography prediction based on VG and VGG anomalies.

Abstract Background Previous studies have primarily implemented problem-based learning (PBL) or flipped classroom (FC) teaching models in different majors; however, research on the combined PBL-FC teaching method in clinical medicine is scarce. Therefore, we investigated the combined PBL-FC teaching method in teaching ocular trauma on students’ competencies. Method About 75 ophthalmology postgraduates were randomly divided into PBL-FC and traditional teaching groups. Students completed pre-and post-class theoretical examinations, skills evaluation, learning ability scales, and feedback questionnaires. Results Both groups showed significantly higher theoretical scores and improved learning ability. Feedback questionnaire scores of the PBL-FC group’s postgraduates without clinical experience were significantly higher than the traditional group’s for some items; there was no difference between groups in postgraduates with clinical experience. PBL-FC group’s pre-class preparation time was significantly longer than the traditional group’s, but the post-class review time was significantly shorter. PBL-FC group’s post-class theoretical performance was significantly higher than the traditional group’s. There was no statistical difference between the groups regarding skill operation. Among postgraduates without clinical experience, the PBL-FC group’s skill operation performance was significantly higher than the traditional group’s; for postgraduates with clinical experience, the traditional group’s skill operation performance was significantly higher than the PBL-FC group’s. Conclusions PBL-FC teaching is better for students without clinical experience or knowledge of ophthalmic diseases. Meanwhile, traditional teaching is a good choice for students with clinical experience who need more relevant knowledge.

Cancer cachexia (CC), a wasting syndrome of muscle and adipose tissue resulting in weight loss, is observed in 50% of patients with solid tumors. Management of CC is limited by the absence of biomarkers and knowledge of molecules that drive its phenotype. To identify such molecules, we injected 54 human non–small cell lung cancer (NSCLC) lines into immunodeficient mice, 17 of which produced an unambiguous phenotype of cachexia or non-cachexia. Whole-exome sequencing revealed that 8 of 10 cachexia lines, but none of the non-cachexia lines, possessed mutations in serine/threonine kinase 11 (STK11/LKB1), a regulator of nutrient sensor AMPK. Silencing of STK11/LKB1 in human NSCLC and murine colorectal carcinoma lines conferred a cachexia phenotype after cell transplantation into immunodeficient (human NSCLC) and immunocompetent (murine colorectal carcinoma) models. This host wasting was associated with an alteration in the immune cell repertoire of the tumor microenvironments that led to increases in local mRNA expression and serum levels of CC-associated cytokines. Mutational analysis of circulating tumor DNA from patients with NSCLC identified 89% concordance between STK11/LKB1 mutations and weight loss at cancer diagnosis. The current data provide evidence that tumor STK11/LKB1 loss of function is a driver of CC, simultaneously serving as a genetic biomarker for this wasting syndrome.

A deep ice core was drilled at Dome A, Antarctic Plateau, East Antarctica, which started with the installation of a casing in January 2012 and reached 800.8 m in January 2017. To date, a total of 337 successful ice-core drilling runs have been conducted, including 118 runs to drill the pilot hole. The total drilling time was 52 days, of which eight days were required for drilling down and reaming the pilot hole, and 44 days for deep ice coring. The average penetration depths of individual runs were 1 and 3.1 m for the pilot hole drilling and deep ice coring, respectively. The quality of the ice cores was imperfect in the brittle zone (650−800 m). Some of the troubles encountered are discussed for reference, such as armoured cable knotting, screws falling into the hole bottom, and damaged parts, among others.

Energy deficiency causes multiple organ dysfunctions after LPS induction. Quercetin is a phenolic compound found in herbal medicines. However, the effects of quercetin in alleviating LPS-induced energy deficiency remain unclear. In the present study, an in vivo LPS-induced inflammation model was established in chicken embryos. Specific pathogen-free chicken embryos (n = 120) were allocated to control, PBS with or without ethanol, quercetin (10, 20, or 40 nmol, respectively), and LPS (125 ng/egg) with or without quercetin groups. Fifteen day old embryonated eggs were injected with the abovementioned solutions via the allantoic cavity. On embryonic day 19, the tissues of the embryos were collected for histopathological examination using frozen oil red O staining, RNA extraction, real-time quantitative polymerase chain reaction, and immunohistochemical investigations. The glycogen and lipid contents in the liver increased after LPS stimulation as compared with the PBS group, whereas quercetin decreased the accumulation as compared with the LPS group. The mRNA expressions of AMPKα1 and AMPKα2 in the duodena, ceca, and livers were upregulated after LPS induction as compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. The immunopositivity of AMPKα2 in the villus, crypt, lamina propria, tunica muscularis, and myenteric plexus in the duodena and in the cytoplasms of hepatocytes significantly increased after LPS induction when compared with the PBS group (p < 0.01), whereas the immunopositivity to AMPKα2 in the quercetin treatment group significantly decreased when compared with the LPS group (p < 0.01 or p < 0.05). The LPS-induced high expressions of transcription factor PPARα and glucose transporter (SGLT1) were blocked by quercetin in the duodena, ceca, and livers. Quercetin treatment improved the LPS-induced decrease in APOA4 in the duodena, ceca, and livers. The mRNA expression of PEPT1 in the duodena and ceca increased after LPS challenge, whereas quercetin could downregulate PEPT1 gene expression. These data demonstrate that quercetin improved the energy deficiency induced by LPS in chicken embryos. The LPS-induced inflammation model was established to avoid the effect of LPS exposure from the environment and intestinal flora. The results form the basis the administration of quercetin pretreatment (in ovo infection) to improve the energy state of chicken embryos and improve the inflammation response.

Adipose tissue inflammation is observed in multiple metabolically-altered states including cancer-associated cachexia and obesity. Although cachexia is a syndrome of adipose loss and obesity is a disease of adipose excess, both pathologies demonstrate increases in circulating levels of IL-6 family cytokines, β-adrenergic signaling, and adipocyte lipolysis. While β-adrenergic-stimulated adipocyte lipolysis is well described, there is limited mechanistic insight into how cancer cachexia-associated inflammatory cytokines contribute to adipocyte lipolysis under pathologic conditions. Here, we set out to compare adipocyte lipolysis signaling by cancer cachexia-associated IL-6 family cytokines (IL-6 and LIF) to that of the β-adrenergic agonist isoproterenol. Unlike isoproterenol, the IL-6 family of cytokines required JAK/STAT3-dependent transcriptional changes to induce adipocyte lipolysis. Furthermore, cachexia-associated cytokines that used STAT3 to induce lipolysis were primarily dependent on the lipase ATGL and its cofactor CGI-58 rather than lipases HSL and MAGL. Finally, administration of JAK but not β-adrenergic inhibitors suppressed adipose STAT3 phosphorylation and associated adipose wasting in a murine model of cancer cachexia characterized by increased systemic IL-6 family cytokine levels. Combined, our results demonstrate how the IL-6 family of cytokines diverge from β-adrenergic signals by employing JAK/STAT3-driven transcriptional changes to promote adipocyte ATGL/CGI-58-dependent lipolysis contributing to adipose wasting in cancer cachexia.

Although satellite gravity gradient data plays a great role in determining short-wavelength part of static gravity field model, accuracy of the long-wavelength part of gravity field model recovered by them are poor, which leads to only a few applications in time-variable gravity investigation. The reason is that some factors limit the accuracy of the gravity field recovered using gradient data, including accuracy of the gravity gradient observations, measurement bandwidth (MBW) of gradiometer, satellite inclination, etc. This paper aims at analyzing the influence of these limitations on gravity field recovery and discusses the possibility of time-variable gravity field detection by using gravity gradient observations. Firstly, for arbitrary satellite orbit inclination, we give the frequency distributions of all the components of gravity gradients (i.e. Txx,Tyy,Tzz,Txy,TxzandTyz, ). The results show that the maximum frequency of each component of the gravity gradients is the same, i.e. l/Ts (l is degree of the gravity field model, Ts is the orbital periods), and it is not influenced by the inclination of the satellite orbits. Secondly, the paper gives a theory proof to explain why only the low orders of the coefficients are influenced by polar gaps. Big polar gaps are experimented by a numerical test with inclination of 45°. Finally, considering that the measurement bandwidth can be expanded and accuracy of gradient observations can be improved by superconducting gravity gradiometer (SGG) compared to gradiometer used in Gravity field and steady-state Ocean Circulation Explorer (GOCE), the possibility of detecting time-variable gravity using gravity gradient observations is discussed. The results show that the SGG creates errors in MBW with magnitude of 0.014 mE, which is smaller than the magnitude of the time-variable gravity gradient signals (i.e., 0.02 mE) derived from Gravity Recovery and Climate Experiment (GRACE) gravity field models. This indicates the potential of SGG in time-variable gravity detection.

As high-resolution global coverage cannot easily be achieved by direct bathymetry, the use of gravity data is an alternative method to predict seafloor topography. Currently, the commonly used algorithms for predicting seafloor topography are mainly based on the approximate linear relationship between topography and gravity anomaly. In actual application, it is also necessary to process the corresponding data according to some empirical methods, which can cause uncertainty in predicting topography. In this paper, we established analytical observation equations between the gravity anomaly and topography, and obtained the corresponding iterative solving method based on the least square method after linearizing the equations. Furthermore, the regularization method and piecewise bilinear interpolation function are introduced into the observation equations to effectively suppress the high-frequency effect of the boundary sea region and the low-frequency effect of the far sea region. Finally, the seafloor topography beneath a sea region (117.25°–118.25°E, 13.85°–14.85°N) in the South China Sea is predicted as an actual application, where gravity anomaly data of the study area with a resolution of 1′ × 1′ are from the DTU17 model. Comparing the prediction results with the data of ship soundings from the National Geophysical Data Center (NGDC), the root-mean-square (RMS) error and relative error can be up to 127.4 m and approximately 3.4%, respectively.

Diarrhea has been a global health problem for centuries, and the treatment has become increasingly difficult duo to the antibiotics overuse and resistance. Quercetin is a common flavonoid of extracts of vegetables, fruits, and traditional Chinese herbs, however, the mechanism of quercetin alleviating LPS-induced duodenal inflammation remains elusive. Specific pathogen-free chicken embryos (n = 120) were allocated to groups including control, PBS with or without alcohol, LPS (125 ng/egg) with or without quercetin (10, 20, or 40 nmol/egg, respectively), and quercetin groups (10, 20, or 40 nmol/egg). Fifteen day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the duodena of the embryos were collected for histopathological examination, RNA extraction and real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting. The results demonstrated quercetin enhanced the inflammatory cell infiltration in the Peyer’s patch of the intestinal mucosa after LPS induction. The LPS-induced expressions of these inflammation-related factors (TLR4, IL-1β, MMP3, MMP9, NFKB1, IFNγ, IL-8, IL-6) were completely blocked by quercetin. Quercetin also decreased the protein expression of TLR4, IL-1β, MMP3, and MMP9 after LPS induction. Quercetin could down-regulate autophagy gene expression (ATG5, LC3-1, LC3-2, and LKB1), and decreased the protein expression of ATG5, and LC3-1/LC3-2 after LPS induction. Quercetin treatment prevented LPS-induced increases of the gene expressions of programmed cell death factors (TNFα, Fas, CASP1, CASP3, CASP12, Drp1, and RIPK1); meanwhile, quercetin decreased the protein expression of CASP1 and CASP3 after LPS challenge. LPS reduced the gene expression of mucin 2, but upregulated the mRNA and protein expression of claudin 1, occludin, and ZO-1, and this was balanced by quercetin. This evidence suggests that quercetin can alleviate duodenal inflammation induced by LPS through modulating autophagy, programmed cell death, intestinal barrier function.

Forest roads often increase runoff and sediment loss, thus greatly impacting hydrological processes in mountainous watersheds. While there has been previous investigation on best management practices (BMPs) to reduce soil erosion from forest roads, few studies have attempted to optimize BMPs based on how much they can decrease sediment connectivity between forest roads and streams. To close this gap in knowledge, we analyzed the spatial relationship between forest roads and streams, presented the spatial distribution of sediment connectivity by integrating the forest roads into the calculation of the index of connectivity (IC), determined how sediment connectivity would respond to additional BMPs through simulating scenarios, and used these data to optimize the BMPs so they would intercept the greatest sediment loads. We found that forest roads and streams in the Xiangchagou watershed in the Dabie Mountain area of China tend to occur within 180 m of each other; however, within the same buffer zones, streams are more often accompanied by forest roads. IC was greatest near road–stream crossings but smaller near streams and forest roads, and it tended to decrease as the buffer distance increased. Furthermore, we found that sediment connectivity was decreased through running a variety of scenarios that used sediment basin and riparian buffers as BMPs between forest roads and streams. Specifically, within this watershed, riparian buffers should be 64 m wide, and there should be 30 sediment basins with a minimum upslope drainage area of 2 ha. At these quantities, the BMPs in this watershed would significantly affect sediment connectivity. By contrast, beyond these thresholds, increasing the width of riparian buffers or the number of sediment basins does not lead to meaningful sediment reductions. In this way, we were able to use the mean change point method to determine the optimal sediment basin quantity (30 with corresponding minimum upslope drainage area of 2 ha) and the optimal riparian buffer width (64 m) for the Xiangchagou watershed. While these results are a first approximation in a novel research area, they can guide forest managers and stakeholders to design and optimize BMPs that control the delivery of eroded sediments associated with forest roads.

Forest roads significantly affect sediment connectivity in mountainous catchments by contributing to the production of and disturbing the confluence of sediment-loaded runoff. This study considered forest roads as pathways and sinks of sediment-loaded runoff to understand the effects of forest roads on the confluence characteristics and sediment connectivity in mountainous a catchment using a scenario simulation. In order to determine the contribution and spatial relationship between sediment connectivity and influencing factors, this study utilized buffer analysis, an extremely randomized tree model, and multiscale geographically weighted regression. The results show that the presence of forest roads significantly changes the transport process and connectivity of runoff and sediment in the mountainous catchment. Specifically, flow length increases, but flow accumulation, upslope contributing area, and topographic index decrease with increasing distance from roads and streams. Meanwhile, the effects of roads on convergence characteristics and sediment connectivity are mainly manifested within a certain threshold that varies with different confluence characteristics. Moreover, sediment connectivity increases when considering roads as pathways and sinks of sediment-loaded runoff, especially on the upper hillslopes intercepted by roads and at the road–stream crossings. In addition, the closer the distance to the roads, the greater the impact of road on the confluence characteristics and sediment connectivity. Change in flow length is the most important factor affecting the sediment connectivity among all of the other convergence, terrain, and spatial distance characteristics. The longer the flow length, the lower the sediment connectivity. In conclusion, this study demonstrates that the altered confluence processes by roads increases the possibility that sediment-loaded runoff will be transported to the catchment outlet, which is of significance for the proper management of forest roads in mountainous catchments.

Summary: The role of chronic adipose inflammation in diet-induced obesity (DIO) and its sequelae including fatty liver disease remains unclear. Leukemia inhibitory factor (LIF) induces JAK-dependent adipocyte lipolysis and altered adipo/cytokine expression, suppressing in vivo adipose expansion in normal and obese mouse models. To characterize LIF receptor (LIFR-α)-dependent cytokine signaling in DIO, we created an adipocyte-specific LIFR knockout mouse model (Adipoq-Cre;LIFRfl/fl). Differentiated adipocytes derived from this model blocked LIF-induced triacylglycerol lipolysis. Adipoq-Cre;LIFRfl/fl mice on a high-fat diet (HFD) displayed reduced adipose STAT3 activation, 50% expansion in adipose, 20% body weight increase, and a 75% reduction in total hepatic triacylglycerides compared with controls. To demonstrate that LIFR-α signals adipocytes through STAT3, we also created an Adipoq-Cre;STAT3fl/fl model that showed similar findings when fed a HFD as Adipoq-Cre;LIFRfl/fl mice. These findings establish the importance of obesity-associated LIFR-α/JAK/STAT3 inflammatory signaling in adipocytes, blocking further adipose expansion in DIO contributing to ectopic liver triacylglyceride accumulation.

Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG45–PLV19) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG45–PLV19 shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.

The boundary value problem of deflections of vertical with ellipsoid boundary is studied in the paper. Based on spherical harmonic series, the ellipsoidal corrections for the boundary value problem are derived so that it can be well solved. In addition, an imitation arithmetic is given for examining the accuracies of solutions for the boundary value problem as well as its spherical approximation problem, and the computational results illustrate that the boundary value problem has higher accuracy than its spherical approximation problem if deflection of the vertical are measured on geoid.

When using the dynamic approach to recover the time-variable gravity field, the reference orbit generated by the perturbation model and the non-conservative force observed from the accelerometer should be introduced at first, and then the observation equations of the residual orbit and the residual range rate are established. This introduces a perturbation model error and instrument noise. Thus, there are low-frequency errors in the residual orbit and the residual range rate. Currently, most studies only focus on the low-frequency error of the residual range rate, neglecting the influence of the low-frequency error in the residual orbit. Therefore, under the condition of the perturbation model error and instrument noise including the constant term and 1CPR term, the low-frequency error formulas of the residual orbit and residual range rate are derived according to the characteristics of the solution of the Hill equation. Then, the influence of the low-frequency error on the residuals is analyzed by using the simulation and the real data processing respectively. In the simulation and real data processing, the accuracy of the recovered gravity field can maintain a good consistency for different arc lengths by removing the low-frequency error in the residual orbit. Finally, the time-variable gravity field model UCAS-IGG (University of Chinese Academy of Sciences-Institute of Geodesy and Geophysics) was solved from January 2005 to February 2010 by removing the low-frequency error of the residual orbit and residual range rate. Compared with the official institutions, the UCAS-IGG presents a good consistency in the estimating time-variable gravity field signal. This study demonstrates how the effect of the low-frequency error of the residual orbit should be taken into consideration when the longer arc length is used to recover a time-variable gravity field. Using a long arc length can reduce the variables of the initial state and recover the influence of the small force.

Understanding the distribution and transport of Uranium is important because it can lead to both chemical and radiological toxicity. This study presents the Uranium concentrations time series from 1964 to 2009 obtained from a 3 m deep snow pit at Dome Argus, East Antarctic Plateau. The data shows that Uranium concentrations vary from 0.0067 pg g-1 to 0.12 pg g-1, with a mean concentration of 0.044 pg g-1. Its mean concentration is 2-3 folds lower than at West Antarctica study sites, such as the Antarctic Peninsula (mean 0.12 pg g-1), IC-6 (Ice Core-6) (mean 0.11 pg g-1) and a suite of ice cores from the US ITASE traverse. Before the mid-1980s, the varieties of Uranium concentrations are relatively stable, with a very low mean concentration of 0.016 pg g-1and its main source is sea salt deposition, while a small number of anthropogenic sources are likely to be caused by Uranium mining operations in South Africa. A remarkable increase of Uranium concentrations has occurred since the mid-1980s (by a factor of ~ 9) compared with the amount before the mid-1980s. This increase coincides with the Uranium records at IC-6 and Antarctic Peninsula (DP-07-01) during the same period, and are mostly attributed to Uranium mining operations in Australia as a potential primary anthropogenic Uranium source. Our observations suggest that Uranium pollution in the atmosphere might have already become a global phenomenon.

The present study describes an AuPPh3Cl/AgSbF6-catalyzed cascade reaction between amine nucleophiles and alkynoic acids in water. This process proceeds in high step economy with water as the sole coproduct, and leads to the generation of two rings, together with the formation of three new bonds in a single operation. This green cascade process exhibits valuable features such as low catalyst loading, good to excellent yields, high efficiency in bond formation, excellent selectivity, great tolerance of functional groups, and extraordinarily broad substrate scope. In addition, this is the first example of the generation of an indole/thiophene/pyrrole/pyridine/naphthalene/benzene-fused N-heterocycle library through gold catalysis in water from readily available materials. Notably, the discovery of antibacterial molecules from this library demonstrates its high quality and potential for the identification of active pharmaceutical ingredients.

Lipid droplets are cellular organelles that consists of a neutral lipid core covered by a monolayer of phospholipids and many proteins. They are thought to function in the storage, transport, and metabolism of lipids, in signaling, and as a specialized microenvironment for metabolism in most types of cells from prokaryotic to eukaryotic organisms. Lipid droplets have received a lot of attention in the last 10 years as they are linked to the progression of many metabolic diseases and hold great potential for the development of neutral lipid-derived products, such as biofuels, food supplements, hormones, and medicines. Proteomic analysis of lipid droplets has yielded a comprehensive catalog of lipid droplet proteins, shedding light on the function of this organelle and providing evidence that its function is conserved from bacteria to man. This review summarizes many of the proteomic studies on lipid droplets from a wide range of organisms, providing an evolutionary perspective on this organelle.

Storage of cellular triacylglycerols (TAGs) in lipid droplets (LDs) has been linked to the progression of many metabolic diseases in humans, and to the development of biofuels from plants and microorganisms. However, the biogenesis and dynamics of LDs are poorly understood. Compared with other organisms, bacteria seem to be a better model system for studying LD biology, because they are relatively simple and are highly efficient in converting biomass to TAG. We obtained highly purified LDs from Rhodococcus sp. RHA1, a bacterium that can produce TAG from many carbon sources, and then comprehensively characterized the LD proteome. Of the 228 LD-associated proteins identified, two major proteins, ro02104 and PspA, constituted about 15% of the total LD protein. The structure predicted for ro02104 resembles that of apolipoproteins, the structural proteins of plasma lipoproteins in mammals. Deletion of ro02104 resulted in the formation of supersized LDs, indicating that ro02104 plays a critical role in cellular LD dynamics. The putative α helix of the ro02104 LD-targeting domain (amino acids 83–146) is also similar to that of apolipoproteins. We report the identification of 228 proteins in the proteome of prokaryotic LDs, identify a putative structural protein of this organelle, and suggest that apolipoproteins may have an evolutionarily conserved role in the storage and trafficking of neutral lipids.

BACKGROUND: Glioma is a type of tumor that develops in the central nerve system, mainly the brain. Alterations of genomic sequence and sequence segments (such as copy number variations or CNV and copy neutral loss of heterozygosities or cnLOH) are thought to be a major determinant of the tumor grade. METHODS: We mapped genomic variations between low-grade and high-grade gliomas (LGG and HGG) in Chinese population based on Illumina's Beadchip and validated the results using real-time qPCR. RESULTS: AT THE CYTOBAND LEVEL, WE DISCOVERED: (1) unique losses in LGG on 5q, 8p and 11q, and in HGG on 6q, 11p, 13q and 19q; (2) unique gains in the LGG on 1p and in HGG at 5p, 7p, 7q and 20q; and (3) cnLOH in HGG only on 3q, 8q, 10p, 14q, 15q, 17p, 17q, 18q and 21q. Subsequently, we confirmed well-characterized oncogenes among tumor-related loci (such as EGFR and KIT) and detected novel genes that gained chromosome sequences (such as AASS, HYAL4, NDUFA5 and SPAM1) in both LGG and HGG. In addition, we found gains, losses, and cnLOH in several genes, including VN1R2, VN1R4, and ZNF677, in multiple samples. Mapping grade-associated pathways and their related gene ontology (GO) terms, we classified LGG-associated functions as "arachidonic acid metabolism", "DNA binding" and "regulation of DNA-dependent transcription" and the HGG-associated as "neuroactive ligand-receptor interaction", "neuronal cell body" and "defense response to bacterium". CONCLUSION: LGG and HGG appear to have different molecular signatures in genomic variations and our results provide invaluable information for the diagnosis and treatment of gliomas in patients with variable duration or diverse tumor differentiation.