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Abstract Obesity has become a global concern because of increasing the risk of many diseases. Alterations in human gut microbiota have been proven to be associated with obesity, yet the mechanism of how the microbiota are altered by high salt diet (HSD) remains obscure. In this study, the changes of Small Intestinal Microbiota (SIM) in obesity-T2DM mice were investigated. High-throughput sequencing was applied for the jejunum microbiota analysis. Results revealed that high salt intake (HS) could suppress the body weight (B.W.) in some extent. In addition, significant T2DM pathological features were revealed in high salt-high fat diet (HS-HFD) group, despite of relatively lower food intake. High-throughput sequencing analysis indicated that the F/B ratio in HS intake groups increased significantly (P

Abstract The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid‐co‐glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid‐associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K‐AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

BackgroundRecent studies have shown that the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced under alkaline conditions. The purpose of this study is to assess the effect of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance among COVID-19 patients.Materials and methodsCOVID-19 patients were recruited and randomly divided into two group, i.e., the experimental group and the control group. The experimental group received regular care plus nasal irrigation and oral rinse with 5% sodium bicarbonate solution, while the control group only received regular care. Nasopharyngeal and oropharyngeal swab samples were collected daily for reverse transcription-polymerase chain reaction (RT-PCR) assays. The negative conversion time and hospitalization time of the patients were recorded, and the results were statistically analyzed.ResultsA total of 55 COVID-19 patients with mild or moderate symptoms were included in our study. There was no significant difference in gender, age and health status between the two groups. The average negative conversion time was 1.63 days after treatment with sodium bicarbonate, and the average hospitalization time of the control group and the experimental group were 12.53 and 7.7 days, respectively.ConclusionsNasal irrigation and oral rinse with 5% sodium bicarbonate solution is effective in virus clearance for COVID-19 patients.

High temperatures caused by climate warming severely affect the grain yield and quality of rice. In this study, the rice cultivars Longliangyou Huazhan (LLYHZ) and Quanliangyou 2118 (QLY2118) were selected as the experimental materials for investigation of an optimal cultivation system under high-temperature treatment. In addition, the heat-resistant cultivar Huanghuazhan (HHZ) and heat-sensitive cultivar Huiliangyou 858 (HLY858) were chosen as the experimental materials to study the effects of exogenous plant growth regulators on heat stress responses under high-temperature treatment. The results showed that mechanical transplanting of carpet seedlings and delayed sowing effectively increased the leaf area index and reduced the canopy temperature of LLYHZ and QLY2118. Furthermore, carpet seedling mechanical transplantation and delayed sowing improved grain yield and quality. Spray application of five plant growth regulators revealed that brassinolide and salicylic acid had the strongest effects on significantly improving antioxidant enzyme activities in the panicle, which would reduce the damage caused by the accumulation of reactive oxygen species and enhance plant tolerance of high-temperature stress. In addition, brassinolide and salicylic acid enhanced the percentage of anther dehiscence and percentage seed set. In this study, a set of simplified eco-friendly cultivation techniques for single-season indica rice adaptation to high-temperature stress was established. These results will be of great importance in alleviating the effects of high-temperature stress on rice production.

Bariatric surgery is a sustainable weight loss approach, including vertical sleeve gastrectomy (VSG). Obesity exacerbates tumor growth, while diet-induced weight loss impairs progression. It remains unknown how bariatric surgery-induced weight loss impacts cancer progression or alters response to therapy. Using a pre-clinical model of obesity followed by VSG or diet-induced weight loss, breast cancer progression and immune checkpoint blockade therapy were investigated. Weight loss by VSG or weight-matched dietary intervention before tumor engraftment protected against obesity-exacerbated tumor progression. However, VSG was not as effective as diet in reducing tumor burden despite achieving similar weight and adiposity loss. Leptin did not associate with changes in tumor burden; however, circulating IL-6 was elevated in VSG mice. Uniquely, VSG tumors displayed elevated inflammation and immune checkpoint ligand PD-L1+ myeloid and non-immune cells. VSG tumors also had reduced T lymphocytes and markers of cytolysis, suggesting an ineffective anti-tumor microenvironment which prompted investigation of immune checkpoint blockade. While obese mice were resistant to immune checkpoint blockade, anti-PD-L1 potently impaired tumor progression after VSG through improved anti-tumor immunity. Thus, in formerly obese mice, surgical weight loss followed by immunotherapy reduced breast cancer burden. Finally, we compared transcriptomic changes in adipose tissue after bariatric surgery from patients and mouse models. A conserved bariatric surgery-associated weight loss signature (BSAS) was identified which significantly associated with decreased tumor volume. Findings demonstrate conserved impacts of obesity and bariatric surgery-induced weight loss pathways associated with breast cancer progression.

In recent years, wave energy has gained attention for its sustainability and cleanliness. As one of the most important parameters of wave energy, significant wave height (SWH) is difficult to accurately predict due to complex ocean conditions and the ubiquitous chaotic phenomena in nature. Therefore, this paper proposes an integrated CEEMDAN-LSTM joint model. Traditional computational fluid dynamics (CFD) has a long calculation period and high capital consumption, but artificial intelligence methods have the advantage of high accuracy and fast convergence. CEEMDAN is a commonly used method for digital signal processing in mechanical engineering, but has not yet been used for SWH prediction. It has better performance than the EMD and EEMD and is more suitable for LSTM prediction. In addition, this paper also proposes a novel filter formulation for SWH outliers based on the improved violin-box plot. The final empirical results show that CEEMDAN-LSTM significantly outperforms LSTM for each forecast duration, significantly improving the prediction accuracy. In particular, for a forecast duration of 1 h, CEEMDAN-LSTM has the most significant improvement over LSTM, with 71.91% of RMSE, 68.46% of MAE and 6.80% of NSE, respectively. In summary, our model can improve the real-time scheduling capability for marine engineering maintenance and operations.

Late-stage nitrogen (N) fertilization is an important crop management for improving rice production and also affects the quality of rice, whereas information on the influence of late N on structural and functional properties of indica rice starch is lacking. In this study, effects of various N rates (0, 60, and 120 kg ha−1 referred to as N0, N60 and N120, respectively) on structural and functional properties of grain starches from two rice cultivars (OM052 and Chaoyou1000) were investigated. Comparison of different N treatments showed that late N application exhibited strong influence on starch properties, and the sensitivity to N application varied with rice genotypes. Compared to non N rate, higher input of N (N60 for OM052, and N120 for Chaoyou1000) significantly reduced apparent amylose content (AAC), relative crystallinity (RC), gelatinization enthalpy, swelling power, solubility and degree of hydrolysis, but significantly increased the proportion of short chains with degree of polymerization 6–12 in amylopectin and gelatinization onset temperature. Further comparison and principal component analyses revealed that the variations in the starch functional properties were due mainly to the changes in RC. The solubility was positively associated with AAC. The present results can provide important information for understanding the environmental regulation of starch biosynthesis in rice grain.

Rice growth is constantly challenged by severe environmental conditions, especially high-temperature stress, brought about by global warming. How to increase rice yields is a current issue in many countries. By analyzing the meteorological data from Anhui Province over the past 60 years, the frequency and level of high-temperature damage were comprehensively analyzed. On this basis, five indica rice varieties with strong high-temperature tolerance, relatively high yield and stable yield were selected by laboratory-simulated high-temperature and field high-temperature experiments: Longliangyou Huazan (LLYHZ), 9you-6 (9Y-6), Longliangyou-1988 (LLY-1988), Fengliangyou-4 (FLY-4) and Huanghuazan (HHZ). These are suitable for planting in the middle and lower reaches of the Yangtze River. This study provides a theoretical reference and scientific basis for the study of rice tolerance to high-temperature stress.

A set of 132 accessions of common millet, Panicum miliaceum L., from 12 provinces of China were assessed for endosperm starch type (waxy or non-waxy) using I2-KI staining, amylose and amylopectin contents using the dual-wavelength colorimetric method, and genotype of Waxy genes conditioning amylose content by gene sequencing. Endosperm starch content varied from 57.69% to 74.70%, while the amylose and amylopectin contents of the starch ranged from 0 to 23.29% and from 41.99% to 70.24%, respectively. Sequencing two Wx genes, including Wx-L (intron 5-exon 7 and intron 8–9) and Wx-S (exon 9–intron 10) revealed several polymorphisms (S0, S−15, LC, LF, LY). Marker M5-R11 linking to the Wx-S gene may be used to discriminate waxy common millet accessions from non-waxy ones. Among the 132 accessions, 68 with the S−15 allele had waxy endosperm starch with the amylose content range 0–2.58% and 64 accessions with the S0 allele had non-waxy endosperm starch with amylose content range 3.94%–23.29%. Five genotypes including S−15/LF (45% of the accessions), S0/LF (25%), S0/LY (12%), S0/LC (11%), and S−15/LY (7%) were identified. Six new SNPs were detected at the Wx-L locus. These results will facilitate common millet breeding, especially of cultivars free of amylose. Keywords: Common millet, Waxy gene, SNP, Starch

Allelic variation at the Wx locus plays a vital role in regulating apparent amylose content (AAC) as well as other important starch properties in rice grain. However, the extent of Wx allelic variation affecting amylopectin fine structure and enzymatic hydrolysis properties of rice starch remains unknown. In this paper, a series of rice single-segment substitution lines with five different Wx alleles (wx, Wxt, Wxg1, Wxg2 and Wxg3) were used for comparative studies. The results showed that the five Wx alleles exhibited a wide variation in amylopectin molecular structure, hydrolysis and in vitro digestion properties of rice starch. Amylopectin chain length distribution as evaluated by fluorophore-assisted capillary electrophoresis was significantly different for the five Wx alleles, which might result in different functional properties. The hydrolysis degree of the five Wx genotype starches by α-amylase or amyloglucocidase was in the order wx > Wxt > Wxg1 > Wxg3 > Wxg2. The rapidly digestible starch (RDS) content of the tested rice starches followed the order wx = Wxg3 > Wxt = Wxg1 > Wxg2. The extent decrease of slowly digestible starch (SDS) content was wx = Wxt > Wxg1 > Wxg2 > Wxg3, while the trend in resistant starch (RS) content was Wxg2 > Wxg3 > Wxg1 > Wxt > wx. Correlation analysis indicated that AAC was significantly positively correlated with RS but significantly negatively correlated with SDS and hydrolysis. The RDS showed a significant positive correlation with amylopectin short chains (DP 6–12) but no significant correlations with other structural properties. The present results could provide important information for the application of rice starches with different Wx genotypes.

The “ringing” response of a monopile foundation to focused wave groups was investigated in this study. Such responses are of practical interest in the context of offshore wind turbine foundations. Moderately steep transient focused wave groups were generated in a novel numerical wave tank, based on the high-order spectral method, which was verified and in good agreement with published laboratory data. The monopile was simplified into a slender linear elastic cantilever beam to measure the severity of the structural response. The resonant behavior was excited at the triple-wave frequency of the wave loads. The influence of the damping ratio on the ringing response was considered. Different incident wave models and hydrodynamic models were used to predict the wave loads and induced responses over different wave steepness. The wavelet transform was successfully applied to reveal the local characteristics of the wave loads and ringing response.

Maintenance of healthy bone quality and quantity requires a well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. Chemerin is a novel adipokine with known functions such as regulating immunity and energy homeostasis through activation of chemokine-like receptor 1 (CMKLR1). G protein-coupled receptor 1 (GPR1) is the second mammalian chemerin receptor with similar binding affinity as CMKLR1. In male GPR1–/– mice, a phenotype with significantly low bone mineral density was observed. We hypothesise that GPR1 might participate the process of bone remodelling. In this study, we investigated the role of GPR1 in regulating bone mass maintenance in male mice, and for the first time, revealed that GPR1–/– male mice manifested seriously trabecular bone loss and lower serum testosterone levels compared to the wild type animals. Accordingly, the mRNA expression of biomarkers related to both osteoblast [collagen type I alpha 2 (Col1A2), osteocalcin (OCN)] and osteoclast [tartrate-resistant acid phosphatase (TRAP), Cathepsin K, NFATc1] were significantly decreased or increased in GPR1–/– mice relative to the wild type, respectively. However, other osteogenic markers, Osterix and ALP levels, were increased. Microcomputed tomography scanning and histological analyses proved that there was a myriad of trabecular bone loss in GPR1–/– mice. In the meantime, GPR1–/– mice presented a significant decrease in serum testosterone level. Taken together, these findings suggested that chemerin–GPR1 signalling might be directly or indirectly communicated with testosterone synthesis on bone turnover regulation. Further detailed studies are required to unveil how chemerin–GPR1 participates in bone metabolism. The translational potential of this article: More studies and knowledge about GPR1 regulating function in bone turnover might supply a novel therapeutic target for osteoporosis in the future.

Abstract Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

TREK-1 deficient alveolar epithelial cells (AECs) secrete less IL-6, more MCP-1, and contain less F-actin. Whether these alterations in cytokine secretion and F-actin content are related remains unknown. We now hypothesized that cytokine secretion from TREK-1-deficient AECs was regulated by cytoskeletal rearrangements.We determined F-actin and α-tubulin contents of control, TREK-1-deficient and TREK-1-overexpressing human A549 cells by confocal microscopy and western blotting, and measured IL-6 and MCP-1 levels using real-time PCR and ELISA.Cytochalasin D decreased the F-actin content of control cells. Jasplakinolide increased the F-actin content of TREK-1 deficient cells, similar to the effect of TREK-1 overexpression in control cells. Treatment of control and TREK-1 deficient cells with TNF-α, a strong stimulus for IL-6 and MCP-1 secretion, had no effect on F-actin structures. The combination of TNF-α+cytochalasin D or TNF-α+jasplakinolide had no additional effect on the F-actin content or architecture when compared to cytochalasin D or jasplakinolide alone. Although TREK-1 deficient AECs contained less F-actin at baseline, quantified biochemically, they contained more α-tubulin. Exposure to nocodazole disrupted α-tubulin filaments in control and TREK-1 deficient cells, but left the overall amount of α-tubulin unchanged. Although TNF-α had no effect on the F-actin or α-tubulin contents, it increased IL-6 and MCP-1 production and secretion from control and TREK-1 deficient cells. IL-6 and MCP-1 secretions from control and TREK-1 deficient cells after TNF-α+jasplakinolide or TNF-α+nocodazole treatment was similar to the effect of TNF-α alone. Interestingly, cytochalasin D decreased TNF-α-induced IL-6 but not MCP-1 secretion from control but not TREK-1 deficient cells.Although cytochalasin D, jasplakinolide and nocodazole altered the F-actin and α-tubulin structures of control and TREK-1 deficient AEC, the changes in cytokine secretion from TREK-1 deficient cells cannot be explained by cytoskeletal rearrangements in these cells.

Acute Respiratory Distress Syndrome remains challenging partially because the underlying mechanisms are poorly understood. While inflammation and loss of barrier function are associated with disease progression, our understanding of the biophysical mechanisms associated with ventilator-associated lung injury is incomplete. In this line of thinking, we recently showed that changes in the F-actin content and deformability of AECs lead to cell detachment with mechanical stretch. Elsewhere, we discovered that cytokine secretion and proliferation were regulated in part by the stretch-activated 2-pore domain K(+) (K2P) channel TREK-1 in alveolar epithelial cells (AECs). As such, the aim of the current study was to determine whether TREK-1 regulated the mechanobiology of AECs through cytoskeletal remodeling and cell detachment. Using a TREK-1-deficient human AEC line (A549), we examined the cytoskeleton by confocal microscopy and quantified differences in the F-actin content. We used nano-indentation with an atomic force microscope to measure the deformability of cells and detachment assays to quantify the level of injury in our monolayers. We found a decrease in F-actin and an increase in deformability in TREK-1 deficient cells compared to control cells. Although total vinculin and focal adhesion kinase (FAK) levels remained unchanged, focal adhesions appeared to be less prominent and phosphorylation of FAK at the Tyr(925) residue was greater in TREK-1 deficient cells. TREK-1 deficient cells have less F-actin and are more deformable making them more resistant to stretch-induced injury.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters in the coastal region, etc. A higher-order scheme is used to discretize geometry of the structure as well as the physical wave potentials. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss–Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve its computation efficiency, an analytical solution is derived for a fast evaluation of the Green function that needs to be implemented thousands of times. In addition, the OpenMP parallelization technique is applied to the formation of the influence coefficient matrix, significantly reducing the running CPU time. Computations are performed on wave-exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates a good performance of the present method.

Numerical simulations were performed in this paper to investigate an elastically mounted circular cylinder subjected to vortex-induced vibration (VIV). A three-step finite element method (FEM) is introduced for solving the incompressible fluid flow equations in two dimensions. The computational procedure is coupled with a mesh movement scheme by use of the arbitrary Lagrangian-Eulerian (ALE) formulation on account of the body motion in the flow field. On running the numerical simulations, the Reynolds number was kept constant of Re = 100 and the reduced velocity U r = U /( f n D ) was varied from 3.0 to 10.2 by changing the natural frequency f n of the cylinder. The mass ratio m * = 4m/ρπD 2 and damping ratio ξ are set to be 10.0 and 0.01, respectively, where U is free-stream velocity, D the diameter of the circular cylinder, m the mass of the cylinder per unit length, and ρ the density of the fluid. Numerical results are examined for the response amplitude of transverse direction as well as the phase angle, φ, between the lift force and the transverse displacement of the cylinder. The numerical results reveal that the transverse amplitudes present only two branches, namely, initial branch and lower branch, rather than three branches as the results obtained from high-Re experiments with low m ∗ ξ. On the other hand, the phase angles present almost linear increase with the reduced velocity in the synchronization region. However, experiments concerned with high Re exhibit a sudden jump in phase angle of approximate 180 ∘ . The difference between the present study and the high-Re experiment is attributed to no substantial vortex shedding mode transition at the present numerical results of laminar flow.

Sloshing flows in a two-dimensional rigid rectangular tank under specified excitations in the coupled horizontal and vertical modes are simulated by using a higher-order boundary element method (BEM). The liquid sloshing is formulated as an initial-boundary-value problem based on the fully nonlinear potential flow theory. And a semi-mixed Eulerian-Lagrangian technique combined with the 4th-order Runge-Kutta scheme is employed to advance the solutions in the time marching process. A smoothing technique is applied to the free surface at every several time steps to avoid the possible numerical instabilities. Numerical results obtained are compared with the available solutions to validate the developed model. The parametric studies are carried out to show the liquid sloshing effects in terms of the slosh frequencies and excitation amplitudes in horizontal and vertical modes, the second-order resonance frequency, a bottom-mounted vertical rigid baffle, free surface displacement, and hydrodynamic forces acting on the tank.

Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow-derived macrophages (BMDMs) from wild-type (wt) and TREK-1–/– mice, we measured responses to inflammasome priming [using lipopolysaccharide (LPS)] and activation (LPS + ATP). We measured IL-1β, caspase-1, and NLRP3 via ELISA and Western blot. A membrane-permeable potassium indicator was used to measure potassium efflux during ATP exposure, and a fluorescencebased assay was used to assess changes in membrane potential. Inflammasome activation induced by LPS + ATP increased IL-1β secretion in wt AMs, whereas activation was significantly reduced in TREK-1–/– AMs. Priming of BMDMs using LPS was not affected by either genetic deficiency or pharmacological inhibition of TREK-1 with Spadin. Cleavage of caspase-1 following LPS + ATP treatment was significantly reduced in TREK-1–/– BMDMs. The intracellular potassium concentration in LPS-primed wt BMDMs was significant[ly lower compared with TREK-1–/– BMDMs or wt BMDMs treated with Spadin. Conversely, activation of TREK-1 with BL1249 caused a decrease in intracellular potassium in wt BMDMs. Treatment of LPS-primed BMDMs with ATP caused a rapid reduction in intracellular potassium levels, with the largest change observed in TREK-1–/– BMDMs. Intracellular K+ changes were associated with changes in the plasma membrane potential (Em), as evidenced by a more depolarized Em in TREK-1–/– BMDMs compared with wt, and Em hyperpolarization upon TREK-1 channel opening with BL1249. These results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages. NEW & NOTEWORTHY Because of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages and bone marrow-derived macrophages from wild-type and TREK-1–/– mice, we measured responses to inflammasome priming (using LPS) and activation (LPS + ATP). Our results suggest that TREK-1 is an important regulator of NLRP3 inflammasome activation in macrophages. [ABSTRACT FROM AUTHOR]