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In the past 10 years, extreme weather phenomena have increased, and global warming has markedly advanced; moreover, the intensity of human activity has gradually increased. These have an impact on the growth of global vegetation. Related studies have focused on the Tibetan Plateau and some northern provinces of China to estimate grassland AGB at a large scale but a low resolution. Hulunbuir Grassland is an important supplier of livestock products, and therefore, it is important to precisely map AGB and explore the response of Hulunbuir Grassland AGB to climate change and human activities at a high resolution to identify complex spatial details. In this study, we selected vegetation indices from Landsat 8 OLI and topographic indices and used multiple linear regression and machine learning algorithms to estimate the spatial distribution of AGB from 2013 to 2022. Then, we analyzed the correlations between AGB and cumulative precipitation and daily average temperature in summer and between population density and livestock density at the pixel level. Our results demonstrated that the RF model performed well, with an RMSE of 28.23 and R2 value of 0.74; the AGB was positively correlated with the cumulative precipitation in summer in 94.45 % of the area and negatively correlated with the daily average temperature in summer in 96.32 % of the area. We suggest that it is necessary to reduce grazing activities in future warm and drought years and to adjust sources of income to adapt to the decrease in AGB under global warming conditions. This study will provide reference for the countries or regions that depend on temperate grasslands for husbandry.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Marine Predators Algorithm (MPA) is a newly nature-inspired meta-heuristic algorithm, which is proposed based on the Lévy flight and Brownian motion of ocean predators. Since the MPA was proposed, it has been successfully applied in many fields. However, it includes several shortcomings, such as falling into local optimum easily and precocious convergence. To balance the exploitation and exploration ability of MPA, a modified marine predators algorithm hybridized with teaching-learning mechanism is proposed in this paper, namely MTLMPA. Compared with MPA, the proposed MTLMPA has two highlights. Firstly, a kind of teaching mechanism is introduced in the first phase of MPA to improve the global searching ability. Secondly, a novel learning mechanism is introduced in the third phase of MPA to enhance the chance encounter rate between predator and prey and to avoid premature convergence. MTLMPA is verified by 23 benchmark numerical testing functions and 29 CEC-2017 testing functions. Experimental results reveal that the MTLMPA is more competitive compared with several state-of-the-art heuristic optimization algorithms.

Underwater wireless optical communication (UWOC) in harbor waters can facilitate real-time monitoring underwater instruments for environmental monitoring, underwater inspection, and maintenance tasks. This study delves into the complex dynamics of UWOC in four distinct harbor waters. The research employs Monte Carlo method incorporated with Fournier–Forand scattering phase function for simulating photon transmission. Key parameters such as the Transmitted full divergence angle, received aperture, and Field of View (FOV) are meticulously evaluated for their impact on power loss and time delay spread. Notably, the normalized power loss and time delay spread are found to be more significantly affected by communication distance than water quality, and the traditional Beer–Lambert law is ineffective in harbor water. The power loss of Harbor II, III, and IV are found to be 14.00 dB, 31.59 dB, and 41.59 dB lower than that of Harbor I, and the time delay spread of Harbor II, III, and IV is 30.56%, 9.67%, and 0.49% times that of the Harbor I under certain conditions. In addition, increasing the received aperture and FOV, particularly over longer distance, make little contribution to reduce the power loss and mitigate the time delay spread. Based on the fixed transmitted full divergence angle, the most applicable received FOV range is 1–3.2 rad, and the most ideal received aperture is 0.15–0.4 m. Under these conditions, the variation in normalized power loss is less than 2 dB. Additionally, the time delay spread remains within the same order of magnitude with the attenuation length (AL) held constant. These conclusions hold substantial technical relevance for the engineering design of UWOC systems in harbor waters.

The design of vertical and lateral PIN Ge-on-Si photodetectors was motivated by the disparity in electron and hole mobilities. In the case of vertical PIN junction detectors, configuring the slab region as n-type doping leads to a notable increase in the bandwidth of approximately 20 GHz compared to utilizing p-type doping for the slab. For lateral PIN junction detectors, we determined that setting the length of the n-type slab region to be 2.8 times that of the p-type slab region, based on the carrier saturation drift rate ratio, does not compromise the bandwidth. This configuration enhances the bandwidth while minimizing light absorption loss from the electrode. The proposed design in this study enhances the performance of Ge-on-Si photodetectors without adding complexity to the fabrication process. The principles applied in this study serve as instructive references for the conceptualization of other photonic or electronic devices, reinforcing the widespread applicability of these design strategies.

This paper presents an adjoint method for locating potential leakage in a single-phase fluid pipeline based on the analytic solution of inversion modeling. By studying the mechanism of pipeline leakage pressure, the adjoint equation based on the governing equation of transient flow is established in the single-liquid phase aspect using inverse adjoint theory and sensitivity analysis method. The inverse transient adjoint equation is primarily derived from the single linear fluid pipeline in the semi-infinite domain. The Laplace method is then used to obtain an analytical solution that determines the location of pipeline leakage. The experimental results indicate that the analytic solution can quickly and accurately judge the leakage location of the pipeline. Furthermore, it presents a new approach to engineering applications, such as gas-liquid two-phase flow complex pipe networks, etc.

The middle segment of the Xiaojiang fault zone consists of strike-slip faults with frequent strong and medium–strong earthquakes under the joint influence of NE-trending faults and deep structural characteristics. The distribution characteristics of the deep subfaults of each branch need to be revealed. Two short-period dense array survey lines are deployed in the area. Shear wave velocity structures are obtained using ambient noise tomography. The results reveal that the faults in each branch dip nearly eastward, with strike-slip characteristics in the north‒south direction. Strong velocity lateral variation infer imply that the deformation characteristics of the upper crust may be brittle. NE faults are observed, which are characterized by typical compression. The high-velocity zone in the Songming Basin may be related to the deeper upwelling of high-velocity strata in the upper crustal flow.

Xanthine oxidase (XO) activity is critical to modulate uric acid and hyperuricemia. Hemoglobin was hydrolyzed by bromelain and the protease from Geobacillus stearothermophilus (GsProS8) to express excellent protein recovery rate (54.87%) and XO inhibitory activity (IC50 of 0.744 mg/mL), resulting from higher contents of tryptophan, glutamic acid and glycine. The hydrolysate was fractionated and identified three novel XO inhibitory peptides IVYPW, YPWTQ, and LITGLW (IC50 of 0.63–1.09 mM). Unlike allopurinol, IVYPW and YPWTQ were mixed-type inhibitors, whereas LITGLW was a non-competitive inhibitor. In addition to the well-recognized contribution of tryptophan, molecular docking studies revealed tyrosine residue in IVYPW and YPWTQ importantly enhanced XO inhibitory activities via hydrogen-bond and Pi-Sigma interactions with Thr1010 and His875, respectively. The total number of Pi-related interactions positively determined XO inhibition as comparing IVYPW, YPWTQ and LITGLW. This study provided a promising strategy to prepare anti-hyperuricemic peptides and understand inhibition mechanisms for the management of hyperuricemia.

Fires greatly threaten the grassland ecosystem, human life, and economic development. However, since limited research focuses on grassland fire prediction, it is necessary to find a better method to predict the probability of grassland-fire occurrence. Multiple environmental variables impact fire occurrence. After selecting natural variables based on remote sensing data and anthropogenic variables, we built regression models of grassland fire probability, taking into account historical fire points and variables in Inner Mongolia. We arrived at three methods to identify grassland fire drivers and predict fire probability: global logistic regression, geographically weighted logistic regression, and random forest. According to the results, the random forest model had the best predictive effect. Nine variables selected by a geographically weighted logistic regression model exercised a spatially unbalanced influence on grassland fires. The three models all showed that meteorological factors and a normalized difference vegetation index (NDVI) were of great importance to grassland fire occurrence. In Inner Mongolia, grassland fires occurring in different areas indicated varying responses to the influencing drivers, and areas that differed in their natural and geographical conditions had different fire-prevention periods. Thus, a grassland fire management strategy based on local conditions should be advocated, and existing fire-monitoring systems based on original meteorological factors should be improved by adding remote sensing data of grassland fuels to increase accuracy.

High-capacity, long-distance underwater wireless optical communication (UWOC) technology is an important component in building fast, flexible underwater sensing networks. Underwater communication with light as a carrier has a large communication capacity, but channel loss induced by light attenuation and scattering largely limits the underwater wireless optical communication distance. To improve the communication distance, a low-power 450 nm blue continuous wave (CW) laser diode (LD)-based UWOC system was proposed and experimentally demonstrated. A communication link was designed and constructed with a BER of 3.6 × 10−3 in a total link loss of 80.72 dB in c = 0.51 m−1 water with a scintillation index (S.I.) equal to 0.02 by combining with 32-pulse-position modulation (32-PPM) at a bandwidth of 12.5 MHz and single photon counting reception techniques. The allowable underwater communication distance in Jerlov II (c = 0.528 m−1) water was estimated to be 35.64 m. The attenuation lengths were 18.82, which were equal at link distances of 855.36 m in Jerlov I (c = 0.022 m−1) water. A receiving sensitivity of 0.34 photons/bit was achieved. To our knowledge, this is the lowest receiving sensitivity ever reported under 0.1 dB of signal-to-noise ratio (SNR) in the field of UWOC.

Purpose: A multi-field optimization (MFO) technique that uses beam-specific spot placement volumes (SPVs) and spot avoidance volumes (SAVs) is introduced for bilateral head and neck (H&N) cancers. These beam-specific volumes are used to guide the optimizer to consistently achieve optimal organ-at-risk (OAR) sparing with target coverage and plan robustness. Materials and Methods: Implementation of this technique using a 4-beam, 5-beam, and variant 5-beam arrangement is discussed. The generation of beam-specific SPVs and SAVs derived from target and OARs are shown. The SPVs for select fields are further partitioned into optimization volumes for uniform dose distributions that resemble those of single-field optimization (SFO). A conventional MFO plan that does not use beam-specific spot placement guidance (MFOcon) and an MFO plan that uses only beam-specific SPV (MFOspv) are compared with current technique (MFOspv/sav), using both simulated scenarios and forward-calculated plans on weekly verification computed tomography (VFCT) scans. Results: Dose distribution characteristics of the 4-beam, 5-beam, and variant 5-beam technique are demonstrated with discussion on OAR sparing. When comparing the MFOcon, MFOspv, and MFOspv/sav, the MFOspv/sav is shown to have superior OAR sparing in 9 of the 14 OARs examined. It also shows clinical plan robustness when evaluated by using both simulated uncertainty scenarios and forward-calculated weekly VFCTs throughout the 7-week treatment course. Conclusion: The MFOspv/sav technique is a systematic approach using SPVs and SAVs to guide the optimizer to consistently reach desired OAR dose values and plan robustness.

Abstract Background Proteases are important for hydrolysis of proteins to generate peptides with many bioactivities. Thus, the development of novel proteases with high activities is meaningful to discover bioactive peptides. Because natural isolation from animal, plant and microbial sources is impractical to produce large quantities of proteases, gene cloning and expression of target protease are preferred. Results In this study, an alkaline serine protease gene (GsProS8) from Geobacillus stearothermophilus was successfully cloned and expressed in Bacillus subtilis. The recombinant GsProS8 was produced with high protease activity of 3807 U/mL after high cell density fermentation. GsProS8 was then purified through ammonium sulfate precipitation and a two-step chromatographic method to obtain the homogeneous protease. The molecular mass of GsProS8 was estimated to be 27.2 kDa by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and 28.3 kDa by gel filtration. The optimal activity of GsProS8 was found to be pH 8.5 and 50 °C, respectively. The protease exhibited a broad substrate specificity and different kinetic parameters to casein and whey protein. Furthermore, the hydrolysis of whey protein using GsProS8 resulted in a large amount of peptides with high angiotensin-I-converting enzyme (ACE) inhibitory activity (IC50 of 0.129 mg/mL). Conclusions GsProS8 could be a potential candidate for industrial applications, especially the preparation of antihypertensive peptides.

The Central Asian Orogenic Belt (CAOB) is a globally magnificent accretionary orogenic belt that has been formed since the Phanerozoic as a result of the Paleozoic closing of the Paleo-Asian Ocean (PAO). The transition zone between the North China Craton (NCC) and the Siberia Plate is located in the eastern CAOB and has been thoroughly investigated by various seismic investigations. However, other types of geophysical approaches lag behind, especially integrated magnetic-gravity surveying, which could provide regional continent-scale constraints on the deep crustal structure. Here, the high-resolution ground gravity and airborne magnetic data covering the study region are newly processed by upward continuation, an improved potential field normalization differential algorithm, an analytical signal approach, and correlation analysis. The processed gravity and magnetic anomalies reveal dominant differences between the CAOB and the northern margin of the NCC; these regions are tectonically divided by the upper crustal Chifeng-Baiyan Obo fault, which is expressed by an important geological boundary. In the middle and lower crust, this tectonic boundary extends northward to the Xar Moron fault. Unexposed Mesozoic granites may be distributed extensively in the mid-lower crust along the Solonker suture zone. The local negative correlation characteristics of gravity and magnetic anomalies may be related to the structural fabrics derived from the convergence of the two terrains.

Underwater wireless optical communication is facing absorption, scattering problems, which, in principle, can be greatly resolved by underwater photon-counting communication (UPCC) technology that exhibits high-sensitivity communication characteristics in long-range underwater wireless optical communication. Recent studies on UPCC are mainly focused on a single intensity modulation such as on–off keying (OOK) and pulse position modulation (PPM) technologies, and the comprehensive analysis of communication performance combing OOK modulation and digital pulse modulations remains a lack. To this, by using a UPCC system based on a single-photon avalanche diode, we reveal the communication performances of OOK, PPM, differential pulse interval modulation (DPIM), differential pulse position modulation (DPPM), and dual-header pulse interval modulation, and find that (1) the PPM has the longest transmission distance at the same bit error ratio when M > 2, but the lowest communication rate under identical modulation bandwidth and average transmit power; and (2) the DPPM and DPIM perform the optimum communication performance at the fixed communication rate when M = 8. We thus conclude that the DPPM and DPIM have advantages of low modulation bandwidth and long time slot time compared with PPM, indicating the significance of reducing the difficulty of signal synchronization and the complexity of the underwater photon-counting system accordingly.

BACKGROUND: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired. PURPOSE: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions. METHODS: The patients external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patients orientation and each beams gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the frameworks analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm. RESULTS: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps. CONCLUSION: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry.

Biomass fuel production has a variety of methods, and the use of biomass cracking to produce biofuels is an advanced technology used in many countries. In the control of the biofuel production process, how to get the motion law of the heat carrier in the cone relative to the cone becomes a problem that must be solved. This study uses the basic theory of dynamics and computer simulation calculation function to carry out dynamic analysis of each of the above contents, and analyses the response problem of comprehensive factors, and obtains the simulation results in accordance with the experimental results. This analysis provides a detailed design rationale for the optimal design of biomass cone pyrolysis equipment.

Plasmonic sensors have attracted intensive attention due to their high sensitivity. However, due to intrinsic metallic loss, plasmonic sensors usually have a large full width at half maximum (FWHM) that limits the wavelength resolution. In this paper, we numerically investigate and propose a dielectric grating-assisted plasmonic device, leveraging the bound states in the continuum (BIC) effect to suppress the FWHM of the resonance. We initiate quasi-SP-BIC modes at 1559 nm and 1905 nm wavelengths by slightly tilting the incident angle at 2° to break the symmetry, featuring a narrow linewidth of 1.8 nm and 0.18 nm at these two wavelengths, respectively. Refractive index sensing has also been investigated, showing high sensitivity of 938 nm/RIU and figure of merit (FOM) of 521/RIU at 1559 nm and even higher sensitivity of 1264 nm/RIU and FOM of 7022/RIU at 1905 nm.

Identifying waterfowl habitat suitability under changing environments, especially land-use change, is crucial to make waterfowl habitat conservation planning. We took Wetland Nature Reserve of Liaohe Estuary, the largest breeding area of Saunders’s Gulls (Larus saundersi) in the world, as our study area, generated land-use-type maps through interpretation of satellite images from four different years (1988, 2000, 2009, 2017), and predicted the potential breeding habitat of Saunders’s Gulls by MaxEnt model based on the land-use map, along with other environmental variables (NDVI, distance to roads and artificial facilities, distance to rivers and water bodies, DEM and distance to shoreline) for the four years, respectively. The models were evaluated using the area under the curve (AUC). We analyzed the changes of the breeding habitat from 1988 to 2017 and utilized RDA to explore the relationships among the changes of suitable habitat of Larus saundersi and the dynamics of land uses. Our results showed that the most suitable habitat decreased by 1286.46 ha during 1988-2009 and increased by 363.51 ha from 2009 to 2017. The suitable habitat decreased by 582.48 ha from 1988 to 2009 and then increased to 1848.96 ha in 2017, while the unsuitable habitat increased by 2793.87 ha during 1988–2009 and then decreased by 178.83 ha from 2009 to 2017. We also found that land use, distance to the coastline, distance to artificial facilities, distance to rivers, distance to roads, and NDVI had certain degrees of impact on the Larus saundersi distribution. The contribution of land use ranged from 16.4% to 40.3%, distance to coastline from 34.7% to 48.0%, distance to artificial facilities from 5.9% to 11.1%, distance to rivers from 5.5% to 11.0%, distance to roads from 3.9% to 12.5%, and NDVI from 0.3% to 6.3%. The change in suitable habitat of Larus saundersi has a positive relationship with the change of seepweed marsh. Human-induced changes in seepweed marsh and coastline position are the main factors influencing the potential breeding habitat of Saunders’s Gulls. We suggest strict conservation of seepweed marsh and implementation of habitat management practices to better protect Saunders’ Gull’s breeding habitat.

The feasibility of a protease of Pseudomonas aeruginosa (PaproA) to prepare angiotensin I-converting enzyme (ACE) inhibitory peptides from wheat gluten was evaluated according to physiochemical and antihypertensive performances. The wheat gluten hydrolyzed by Alcalase plus PaproA (WGH_APae) to produce small fragments (

Background/Aims: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. Methods: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. Results: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. Conclusion: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

This comparative study aimed to investigate the effects of an Augmented-Reality Game-Based Learning application, "StemUp," on the English learning performance and motivation of distinct rural and urban groups of young EFL (English as a Foreign Language) learners. Multiple sources of data collection were employed, including pre- and post-tests, Keller's (1987) ARCS pre- and post-survey, and semi-structured interviews of the fifty participants. Quantitative findings confirmed that the study's AR game-based intervention resulted in a significant improvement in English performance and motivation for both groups, with the students from the rural area improving more in both English performance and motivation compared to those from the urban area. Motivation and enjoyment, gamification, and learning effectiveness were three important qualitative interview themes. Overall, this mixed-methods study found that the learning design employing "StemUp," with its unique 3D AR features/affordances, not only improved participant language gains in vocabulary, speaking, and listening, but also enabled participants to be more engaged and motivated in their English learning. The conclusion is that StemUP is a promising tool for assisting EFL learners in both rural and urban areas in their English language development as well as motivation improvement by facilitating an immersive language learning environment for EFL young learners.

Positive temperature coefficient (PTC) materials have many applications in self-regulating heating; however, they are generally used in the high temperature range, and their use in the room temperature range have rarely been reported. A new kind of PTC material with the Curie temperature of 37 °C was proposed in this study. The material was prepared by adding 6wt % carbon black (CB) and 5wt % dioctyl phthalate (DOP) into the copolymer of ethylene vinyl acetate (EVA) and lauric acid (LA) (1:3). The results showed that it had an exceptionally high PTC intensity of 5.5 and rationally low electrical resistivity of 600 Ω·cm. at room temperature. And this PTC material also shows a preferable repeatability in the PTC intensity after the thermal cycle of 4th. Moreover, the PTC material shows a great potential application in warming the human body in a cold environment.

The effects of sarcopenic obesity, the co-existence of sarcopenia and obesity, on mood disorders have not been studies extensively. Our objective was to examine the association of depressive symptoms with sarcopenia and obesity status in older Japanese adults. We analyzed data from 1731 functionally-independent, community-dwelling Japanese adults aged 65 years or older (875 men, 856 women) randomly selected from the resident register of Kashiwa city, Chiba, Japan in 2012. Sarcopenia was defined based on appendicular skeletal muscle mass, grip strength and usual gait speed. Obesity was defined as the highest sex-specific quintile of the percentage body fat. Depressive symptoms were defined as a Geriatric Depression Scale 15-item score ≥ 6. Multiple logistic regression was employed to examine the association of depressive symptoms with four groups defined by the presence/absence of sarcopenia and obesity. The prevalence of depressive symptoms was 10.1% and the proportions of sarcopenia/obesity, sarcopenia/non-obesity, non-sarcopenia/obesity, non-sarcopenia/non-obesity were 3.7%, 13.6%, 16.9% and 65.8%, respectively. After adjustment for potential confounders, sarcopenia/obesity was positively associated with depressive symptoms compared with non-sarcopenia/non-obesity, whereas either sarcopenia or obesity alone was not associated with depressive symptoms. The association was particularly pronounced in those aged 65 to 74 years in age-stratified analysis. We conclude that our findings suggest a synergistic impact exerted by sarcopenic obesity on the risk of depressive symptoms, particularly in those aged 65 to 74 years.

Heat-stable toxins (STs) produced by enterotoxigenic bacteria cause endemic and traveler’s diarrhea by binding to and activating the intestinal receptor guanylyl cyclase C (GC-C). Advances in understanding the biology of GC-C have extended ST from a diarrheagenic peptide to a novel therapeutic agent. Here, we summarize the physiological and pathophysiological role of GC-C in fluid-electrolyte regulation and intestinal crypt-villus homeostasis, as well as describe translational opportunities offered by STs, reflecting the unique characteristics of GC-C, in treating irritable bowel syndrome and chronic constipation, and in preventing and treating colorectal cancer.

DNA looping has emerged as a central paradigm of transcriptional regulation, as it is shared across many living systems. One core property of DNA looping-based regulation is its ability to greatly enhance repression or activation of genes with only a few copies of transcriptional regulators. However, this property based on a small number of proteins raises the question of the robustness of such a mechanism with respect to the large intracellular perturbations taking place during growth and division of the cell. Here we address the issue of sensitivity to variations of intracellular parameters of gene regulation by DNA looping. We use the lac system as a prototype to experimentally identify the key features of the robustness of DNA looping in growing Escherichia coli cells. Surprisingly, we observe time intervals of tight repression spanning across division events, which can sometimes exceed 10 generations. Remarkably, the distribution of such long time intervals exhibits memoryless statistics that is mostly insensitive to repressor concentration, cell division events, and the number of distinct loops accessible to the system. By contrast, gene regulation becomes highly sensitive to these perturbations when DNA looping is absent. Using stochastic simulations, we propose that the observed robustness to division emerges from the competition between fast, multiple rebinding events of repressors and slow initiation rate of the RNA polymerase. We argue that fast rebinding events are a direct consequence of DNA looping that ensures robust gene repression across a range of intracellular perturbations.

Abstract Background The use of gene signatures can potentially be of considerable value in the field of clinical diagnosis. However, gene signatures defined with different methods can be quite various even when applied the same disease and the same endpoint. Previous studies have shown that the correct selection of subsets of genes from microarray data is key for the accurate classification of disease phenotypes, and a number of methods have been proposed for the purpose. However, these methods refine the subsets by only considering each single feature, and they do not confirm the association between the genes identified in each gene signature and the phenotype of the disease. We proposed an innovative new method termed Minimize Feature's Size (MFS) based on multiple level similarity analyses and association between the genes and disease for breast cancer endpoints by comparing classifier models generated from the second phase of MicroArray Quality Control (MAQC-II), trying to develop effective meta-analysis strategies to transform the MAQC-II signatures into a robust and reliable set of biomarker for clinical applications. Results We analyzed the similarity of the multiple gene signatures in an endpoint and between the two endpoints of breast cancer at probe and gene levels, the results indicate that disease-related genes can be preferably selected as the components of gene signature, and that the gene signatures for the two endpoints could be interchangeable. The minimized signatures were built at probe level by using MFS for each endpoint. By applying the approach, we generated a much smaller set of gene signature with the similar predictive power compared with those gene signatures from MAQC-II. Conclusions Our results indicate that gene signatures of both large and small sizes could perform equally well in clinical applications. Besides, consistency and biological significances can be detected among different gene signatures, reflecting the studying endpoints. New classifiers built with MFS exhibit improved performance with both internal and external validation, suggesting that MFS method generally reduces redundancies for features within gene signatures and improves the performance of the model. Consequently, our strategy will be beneficial for the microarray-based clinical applications.

Many methods, including parametric, nonparametric, and Bayesian methods, have been used for detecting differentially expressed genes based on the assumption that biological systems are linear, which ignores the nonlinear characteristics of most biological systems. More importantly, those methods do not simultaneously consider means, variances, and high moments, resulting in relatively high false positive rate. To overcome the limitations, the SWang test is proposed to determine differentially expressed genes according to the equality of distributions between case and control. Our method not only latently incorporates functional relationships among genes to consider nonlinear biological system but also considers the mean, variance, skewness, and kurtosis of expression profiles simultaneously. To illustrate biological significance of high moments, we construct a nonlinear gene interaction model, demonstrating that skewness and kurtosis could contain useful information of function association among genes in microarrays. Simulations and real microarray results show that false positive rate of SWang is lower than currently popular methods (T-test, F-test, SAM, and Fold-change) with much higher statistical power. Additionally, SWang can uniquely detect significant genes in real microarray data with imperceptible differential expression but higher variety in kurtosis and skewness. Those identified genes were confirmed with previous published literature or RT-PCR experiments performed in our lab.

For microbiome biology to become a more predictive science, we must identify which descriptive features of microbial communities are reproducible and predictable, which are not, and why. We address this question by experimentally studying parallelism and convergence in microbial community assembly in replicate glucose-limited habitats. Here, we show that the previously observed family-level convergence in these habitats reflects a reproducible metabolic organization, where the ratio of the dominant metabolic groups can be explained from a simple resource-partitioning model. In turn, taxonomic divergence among replicate communities arises from multistability in population dynamics. Multistability can also lead to alternative functional states in closed ecosystems but not in metacommunities. Our findings empirically illustrate how the evolutionary conservation of quantitative metabolic traits, multistability, and the inherent stochasticity of population dynamics, may all conspire to generate the patterns of reproducibility and variability at different levels of organization that are commonplace in microbial community assembly.