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Bovine mastitis harms milk quality and cattle health. Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are well-known milk-derived bioactive peptides with anti-inflammatory activity. However, the impact of VPP and IPP on mastitis remain unknown. This study aimed to investigate the anti-inflammatory effects and the underlying mechanisms of VPP and IPP in lipopolysaccharide (LPS)-induced inflammation. When cells were treated with LPS (1 µg/mL) for 24 h, the protein levels of pro-inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin(IL)-1β and IL-6)) and chemokine (monocyte chemotactic protein-1 (MCP-1)) were markedly increased, and the protein level of anti-inflammatory cytokine (IL-10) was reduced. Both VPP and IPP with concentrations of 50 and 100 µM reversed these phenomena and further inhibited the protein expression of β-casein induced by LPS. In a mouse mastitis model, different concentrations of VPP and IPP (300, 600 µM/kg) pretreatment alleviated histopathological lesions in the mammary gland and suppressed the mRNA expression of TNFα, IL1β, and IL6 induced by LPS. VPP and IPP also maintained the integrity of the blood–milk barrier in mice. RNA-seq analyses indicated that enriched phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways likely contribute to the changes observed (P < 0.05 and |log2 fold change (FC)| ≥ 1). Notably, fibronectin was identified as an important hub by protein–protein interaction (PPI) analysis and molecular docking combined with molecular dynamics simulation. In summary, VPP and IPP exerted a protective effect on LPS-induced inflammation by regulating PI3K/AKT signaling pathway via fibronectin.
This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.
Deep reinforcement learning (DRL) is employed to develop control strategies for drag reduction in direct numerical simulations of turbulent channel flows at high Reynolds numbers. The DRL agent uses near-wall streamwise velocity fluctuations as input to modulate wall blowing and suction velocities. These DRL-based strategies achieve significant drag reduction, with maximum rates $35.6\,\%$ at $Re_{\tau }\thickapprox 180$, $30.4\,\%$ at $Re_{\tau }\thickapprox 550$, and $27.7\,\%$ at $Re_{\tau }\thickapprox 1000$, outperforming traditional opposition control methods. An expanded range of wall actions further enhances drag reduction, although effectiveness decreases at higher Reynolds numbers. The DRL models elevate the virtual wall through blowing and suction, aiding in drag reduction. However, at higher Reynolds numbers, the amplitude modulation of large-scale structures significantly increases the residual Reynolds stress on the virtual wall, diminishing the drag reduction. Analysis of budget equations provides a systematic understanding of the underlying drag reduction dynamics. The DRL models reduce skin friction by inhibiting the redistribution of wall-normal turbulent kinetic energy. This further suppresses the wall-normal velocity fluctuations, reducing the production of Reynolds stress, thereby decreasing skin friction. This study showcases the successful application of DRL in turbulence control at high Reynolds numbers, and elucidates the nonlinear control mechanisms underlying the observed drag reduction.
The multi-robot path planning problem is an NP-hard problem. The coati optimization algorithm (COA) is a novel metaheuristic algorithm and has been successfully applied in many fields. To solve multi-robot path planning optimization problems, we embed two differential evolution (DE) strategies into COA, a self-adaptive differential evolution-based coati optimization algorithm (SDECOA) is proposed. Among these strategies, the proposed algorithm adaptively selects more suitable strategies for different problems, effectively balancing global and local search capabilities. To validate the algorithm’s effectiveness, we tested it on CEC2020 benchmark functions and 48 CEC2020 real-world constrained optimization problems. In the latter’s experiments, the algorithm proposed in this paper achieved the best overall results compared to the top five algorithms that won in the CEC2020 competition. Finally, we applied SDECOA to optimization multi-robot online path planning problem. Facing extreme environments with multiple static and dynamic obstacles of varying sizes, the SDECOA algorithm consistently outperformed some classical and state-of-the-art algorithms. Compared to DE and COA, the proposed algorithm achieved an average improvement of 46% and 50%, respectively. Through extensive experimental testing, it was confirmed that our proposed algorithm is highly competitive. The source code of the algorithm is accessible at: https://ww2.mathworks.cn/matlabcentral/fileexchange/164876-HDECOA.
An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.
Aims
To assess the bidirectional causal relationship between frailty and nine mental disorders.
Method
We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's Q-test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.
Results
Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36–2.53, P = 8.1 × 10−5), anxiety (odds ratio 2.76, 95% CI 1.56–4.90, P = 5.0 × 10−4), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69–3.87, P = 9.9 × 10−6), neuroticism (β = 0.25, 95% CI 0.11–0.38, P = 3.3 × 10−4) and insomnia (β = 0.50, 95% CI 0.25–0.75, P = 1.1 × 10−4). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: β = 0.071, 95% CI 0.033–0.110, P = 2.8 × 10−4; neuroticism: β = 0.269, 95% CI 0.173–0.365, P = 3.4 × 10−8; insomnia: β = 0.160, 95% CI 0.141–0.179, P = 3.2 × 10−61; suicide attempt: β = 0.056, 95% CI 0.029–0.084, P = 3.4 × 10−5). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.
Conclusions
Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.
Attention-deficit/hyperactivity disorder (ADHD) patients exhibit characteristics of impaired working memory (WM) and diminished sensory processing function. This study aimed to identify the neurophysiologic basis underlying the association between visual WM and auditory processing function in children with ADHD.
Methods
The participants included 86 children with ADHD (aged 6–15 years, mean age 9.66 years, 70 boys, and 16 girls) and 90 typically developing (TD) children (aged 7–16 years, mean age 10.30 years, 66 boys, and 24 girls). Electroencephalograms were recorded from all participants while they performed an auditory discrimination task (oddball task). The visual WM capacity and ADHD symptom severity were measured for all participants.
Results
Compared with TD children, children with ADHD presented a poorer visual WM capacity and a smaller mismatch negativity (MMN) amplitude. Notably, the smaller MMN amplitude in children with ADHD predicted a less impaired WM capacity and milder inattention symptom severity. In contrast, the larger MMN amplitude in TD children predicted a better visual WM capacity.
Conclusions
Our results suggest an intimate relationship and potential shared mechanism between visual WM and auditory processing function. We liken this shared mechanism to a total cognitive resource limit that varies between groups of children, which could drive correlated individual differences in auditory processing function and visual WM. Our findings provide a neurophysiological correlate for reports of WM deficits in ADHD patients and indicate potential effective markers for clinical intervention.
Biped wall-climbing robots (BWCRs) serve as viable alternatives to human workers for inspection and maintenance tasks within three-dimensional (3D) curtain wall environments. However, autonomous climbing in such environments presents significant challenges, particularly related to localization and navigation. This paper presents a pioneering navigation framework tailored for BWCRs to navigate through 3D curtain wall environments. The framework comprises three essential stages: Building Information Model (BIM)-based map extraction, 3D climbing path planning (based on our previous work), and path tracking. An algorithm is developed to extract a detailed 3D map from the BIM, including structural elements such as walls, frames, and ArUco markers. This generated map is input into a proposed path planner to compute a viable climbing motion. For path tracking during actual climbing, an ArUco marker-based global localization method is introduced to estimate the pose of the robot, enabling adjustments to the target foothold by comparing desired and actual poses. The conducted experiments validate the feasibility and efficacy of the proposed navigation framework and associated algorithms, aiming to enhance the autonomous climbing capability of BWCRs.
Neuroimaging studies have documented brain structural changes in schizophrenia at different stages of the illness, including clinical high-risk (cHR), genetic high-risk (gHR), first-episode schizophrenia (FES), and chronic schizophrenia (ChS). There is growing awareness that neuropathological processes associated with a disease fail to map to a specific brain region but do map to a specific brain network. We sought to investigate brain structural damage networks across different stages of schizophrenia.
Methods
We initially identified gray matter alterations in 523 cHR, 855 gHR, 2162 FES, and 2640 ChS individuals relative to 6963 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to four specific networks.
Results
Brain structural damage networks of cHR and gHR had limited and non-overlapping spatial distributions, with the former mainly involving the frontoparietal network and the latter principally implicating the subcortical network, indicative of distinct neuropathological mechanisms underlying cHR and gHR. By contrast, brain structural damage networks of FES and ChS manifested as similar patterns of widespread brain areas predominantly involving the somatomotor, ventral attention, and subcortical networks, suggesting an emergence of more prominent brain structural abnormalities with illness onset that have trait-like stability over time.
Conclusions
Our findings may not only provide a refined picture of schizophrenia neuropathology from a network perspective, but also potentially contribute to more targeted and effective intervention strategies for individuals at different schizophrenia stages.
This paper presents a numerical study on the flow around two tandem circular cylinders beneath a free surface at a Reynolds number of $180$. The free-surface effects on the wake dynamics and hydrodynamic forces are investigated through a parametric study, covering a parameter space of gap ratios from $0.20$ to $2.00$, spacing ratios from $1.50$ to $4.00$ and Froude numbers from $0.2$ to $0.8$. A jet-like flow accompanied by a shear layer of positive vorticity separating from the free surface is formed in the wake at small gap ratios, which significantly alters the wake pattern through its dynamic behaviours. At shallow submergence depths, the three-dimensional wake transitions from mode B to mode A as the distance between the cylinders increases. As submergence depth increases, the wavy deformation of the primary vortex cores disappears in the wake, and the flow transitions to a two-dimensional state. Higher Froude numbers can extend the effect of the free surface to deeper submergence depths. The critical spacing ratio tends to be larger at higher Froude numbers. Furthermore, the free-surface deformation is examined. The free-surface profile typically comprises a hydraulic jump immediately ahead of the upstream cylinder, trapped waves in the vicinity of the two tandem cylinders and well-defined travelling waves on the downstream side. The frequencies of the waves cluster around the vortex shedding frequency, indicating a close association between the generation of waves and the vortex shedding process.
Precise and efficient grasping detection is vital for robotic arms to execute stable grasping tasks in industrial and household applications. However, existing methods fail to consider refining different scale features and detecting critical regions, resulting in coarse grasping rectangles. To address these issues, we propose a real-time coarse and fine granularity residual attention (CFRA) grasping detection network. First, to enable the network to detect different sizes of objects, we extract and fuse the coarse and fine granularity features. Then, we refine these fused features by introducing a feature refinement module, which enables the network to distinguish between object and background features effectively. Finally, we introduce a residual attention module that handles different shapes of objects adaptively, achieving refined grasping detection. We complete training and testing on both Cornell and Jacquard datasets, achieving detection accuracy of 98.7% and 94.2%, respectively. Moreover, the grasping success rate on the real-world UR3e robot achieves 98%. These results demonstrate the effectiveness and superiority of CFRA.
The seminal Bolgiano–Obukhov (BO) theory established the fundamental framework for turbulent mixing and energy transfer in stably stratified fluids. However, the presence of BO scalings remains debatable despite their being observed in stably stratified atmospheric layers and convective turbulence. In this study, we performed precise temperature measurements with 51 high-resolution loggers above the seafloor for 46 h on the continental shelf of the northern South China Sea. The temperature observation exhibits three layers with increasing distance from the seafloor: the bottom mixed layer (BML), the mixing zone and the internal wave zone. A BO-like scaling $\alpha =-1.34\pm 0.10$ is observed in the temperature spectrum when the BML is in a weakly stable stratified ($N\sim 0.0018$ rad s$^{-1}$) and strongly sheared ($Ri\sim 0.0027$) condition, whereas in the unstably stratified convective turbulence of the BML, the scaling $\alpha =-1.76\pm 0.10$ clearly deviated from the BO theory but approached the classical $-$5/3 scaling in isotropic turbulence. This suggests that the convective turbulence is not the promise of BO scaling. In the mixing zone, where internal waves alternately interact with the BML, the scaling follows the Kolmogorov scaling. In the internal wave zone, the scaling $\alpha =-2.12 \pm 0.15$ is observed in the turbulence range and possible mechanisms are provided.
Predicting epidemic trends of coronavirus disease 2019 (COVID-19) remains a key public health concern globally today. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rate in previous studies of the transmission dynamics model was mostly a fixed value. Therefore, we proposed a meta-Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model by adding a time-varying SARS-CoV-2 reinfection rate to the transmission dynamics model to more accurately characterize the changes in the number of infected persons. The time-varying reinfection rate was estimated using random-effect multivariate meta-regression based on published literature reports of SARS-CoV-2 reinfection rates. The meta-SEIRS model was constructed to predict the epidemic trend of COVID-19 from February to December 2023 in Sichuan province. Finally, according to the online questionnaire survey, the SARS-CoV-2 infection rate at the end of December 2022 in Sichuan province was 82.45%. The time-varying effective reproduction number in Sichuan province had two peaks from July to December 2022, with a maximum peak value of about 15. The prediction results based on the meta-SEIRS model showed that the highest peak of the second wave of COVID-19 in Sichuan province would be in late May 2023. The number of new infections per day at the peak would be up to 2.6 million. We constructed a meta-SEIRS model to predict the epidemic trend of COVID-19 in Sichuan province, which was consistent with the trend of SARS-CoV-2 positivity in China. Therefore, a meta-SEIRS model parameterized based on evidence-based data can be more relevant to the actual situation and thus more accurately predict future trends in the number of infections.
Oncomelania hupensis (O. hupensis), the sole intermediate host of Schistosoma japonicum, greatly influence the prevalence and distribution of schistosomiasis japonica. The distribution area of O. hupensis has remained extensive for numerous years. This study aimed to establish a valid agent-based model of snail density and further explore the environmental conditions suitable for snail breeding. A marshland with O. hupensis was selected as a study site in Dongting Lake Region, and snail surveys were monthly conducted from 2007 to 2016. Combined with the data from historical literature, an agent-based model of snail density was constructed in NetLogo 6.2.0 and validated with the collected survey data. BehaviorSpace was used to identify the optimal ranges of soil temperature, pH, soil water content, and vegetation coverage for snail growth, development and reproduction. An agent-based model of snail density was constructed and showed a strong agreement with the monthly average snail density from the field surveys. As soil temperature increased, the snail density initially rose before declining, reaching its peak at around 21°C. There were similar variation patterns for other environmental factors. The findings from the model suggested that the optimum ranges of soil temperature, pH, soil water content and vegetation coverage were 19°C to 23 °C, 6.4 to 7.6, 42% to 75%, and 70% to 93%, respectively. A valid agent-based model of snail density was constructed, providing more objective information about the optimum ranges of environmental factors for snail growth, development and reproduction.
Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
Tea can improve the progression of some metabolic diseases through anti-inflammatory and antioxidant effects, but its impact on non-alcoholic fatty liver disease (NAFLD) is still controversial. The aim of this paper is to identify the relationship between tea and NAFLD by Mendelian randomisation (MR) and complete clinical validation using National Health and Nutrition Examination Survey (NHANES) database. MR used data from Genome Wide Association Study, with inverse-variance weighted (IVW) as principal analytical methods. The reliability of the results was verified by a series of sensitivity and heterogeneity tests. Subsequently, clinical validation was conducted using NHANES (2005–2018), involving 22 257 participants, grouped by the type of tea. Green tea drinkers were categorised into four groups (Q1–Q4) by quartiles of green tea intake, from lowest to highest (similar for black tea drinkers and other tea drinkers). Models were constructed by logistic regression to estimate the role of tea consumption (Q1–4) on NAFLD. Finally, using fibrosis-4 index (FIB-4) to evaluate the severity of hepatic fibrosis, the effect of tea consumption (Q1–4) on the degree of hepatic fibrosis was investigated by linear regression. IVW method (OR = 0·43, 95 % CI: 0·21, 0·85, P = 0·01) and weighted median method (OR = 0·35, 95 % CI: 0·14, 0·91, P = 0·03) revealed there was a causal relationship between tea and NAFLD. An array of sensitivity analyses validated the reliability of results. Analysis of NHANES indicated tea drinker present a slightly lower prevalence of NAFLD than non-tea drinker (green tea drinkers: 47·6 %, black tea drinkers: 46·3 %, other tea drinker: 43·2 %, non-tea drinkers: 48·1 %, P < 0·05). After adjusting for confounders, compared with the lowest black tea consumption (Q1), the population with the highest black tea consumption (Q4) was independently related to lower presence of NAFLD (Q4: OR = 0·69, 95 % CI: 0·50, 0·93, P < 0·05), such association remained stable in the overweight subgroup. As further analysed, Q4 also displayed a significant negative correlation with the level of hepatic fibrosis in patients with NAFLD (β = –0·073, 95 % CI: –0·126, −0·020, P < 0·01).Tea reduces the morbidity of NAFLD and ameliorates hepatic fibrosis degree in those already suffering from the disease.
Female crabs enter a stage of rapid ovarian development after mating, and cholesterol is a substrate for steroid hormone synthesis. Therefore, in this experiment, an 8-week feeding trial was conducted to investigate the effects of mating treatments (mated crab and unmated crab) and three dietary cholesterol levels (0·09 %, 0·79 % and 1·40 %) on ovarian development, cholesterol metabolism and steroid hormones metabolism of adult female swimming crab (Portunus trituberculatus). The results indicated that crabs fed the diet with 0·79 % cholesterol significantly increased gonadosomatic index (GSI) and vitellogenin (VTG) content than other treatments in the same mating status. Moreover, mated crabs had markedly increased GSI and VTG content in the ovary and hepatopancreas than unmated crabs. The histological observation found that exogenous vitellogenic oocytes appeared in the mated crabs, while previtellogenic oocytes and endogenous vitellogenic oocytes were the primary oocytes in unmated crabs. The transmission electron microscopy analysis showed that when fed diet with 0·79 % cholesterol, the unmated crabs contained more rough endoplasmic reticulum and mated crabs had higher yolk content than other treatments. Furthermore, mating treatment and dietary 0·79 % cholesterol level both promoted cholesterol deposition by up-regulation of the mRNA and protein expression levels of class B scavenger receptors 1 (Srb1), while stimulating the secretion of steroid hormones by up-regulation of the mRNA and protein expression of steroidogenic acute regulatory protein (Star). Overall, the present results indicated that mating behaviour plays a leading role in promoting ovarian development, and dietary 0·79 % cholesterol level can further promote ovarian development after mating.
China is still among the 30 high-burden tuberculosis (TB) countries in the world. Few studies have described the spatial epidemiological characteristics of pulmonary TB (PTB) in Jiangsu Province. The registered incidence data of PTB patients in 95 counties of Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System. Three-dimensional spatial trends, spatial autocorrelation, and spatial–temporal scan analysis were conducted to explore the spatial clustering pattern of PTB. From 2011 to 2021, a total of 347,495 newly diagnosed PTB cases were registered. The registered incidence rate of PTB decreased from 49.78/100,000 in 2011 to 26.49/100,000 in 2021, exhibiting a steady downward trend (χ2 = 414.22, P < 0.001). The average annual registered incidence rate of PTB was higher in the central and northern regions. Moran’s I indices of the registered incidence of PTB were all >0 (P< 0.05) except in 2016, indicating a positive spatial correlation overall. Local autocorrelation analysis showed that ‘high–high’ clusters were mainly distributed in northern Jiangsu, and ‘low–low’ clusters were mainly concentrated in southern Jiangsu. The results of this study assist in identifying settings and locations of high TB risk and inform policy-making for PTB control and prevention.
Shock waves are of great interest in many fields of science and engineering, but the mechanisms of their formation, maintenance and dissipation are still not well understood. While all transport processes existing in a shock wave contribute to its compression and irreversibility, they are not of equal importance. To figure out the roles of viscosity and heat conduction in shock transition, the existence of smooth shock solutions and the counter-intuitive entropy overshoot phenomenon (the specific entropy is not monotonically increasing and exhibits a peak inside the shock front) are theoretically and numerically investigated, with emphasis on the effects of viscosity and heat conduction. Instead of higher-order hydrodynamics, the Navier–Stokes formalism is employed for its stability and simplicity. Supplemented with nonlinear thermodynamically consistent constitutive relations, the Navier–Stokes equations are adequate to demonstrate the general nature of shock profiles. It is found that heat conduction cannot sustain strong shocks without the presence of viscosity, while viscosity can maintain smooth shock transition at all strengths, regardless of heat conduction. Hence, the critical role in shock compression is played by viscosity rather than heat conduction. Nevertheless, the dispensability of heat conduction would not compromise its essential role in the emergence of an entropy peak. It is the entropy flux resulting from heat conduction that neutralises the positive entropy production and thus prevents the decreasing entropy from violating the second law of thermodynamics. This mechanism of entropy overshoot has not been addressed previously in the literature and is revealed using the entropy balance equation.