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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.
Brown dwarfs are failed stars with very low mass (13 to 75 Jupiter mass), and an effective temperature lower than 2500 K. Their mass range is between Jupiter and red dwarfs. Thus, they play a key role in understanding the gap in the mass function between stars and planets. However, due to their faint nature, previous searches are inevitably limited to the solar neighbourhood (20 pc). To improve our knowledge of the low mass part of the initial stellar mass function and the star formation history of the MilkyWay, it is crucial to find more distant brown dwarfs. Using JamesWebb Space Telescope (JWST) COSMOS-Web data, this study seeks to enhance our comprehension of the physical characteristics of brown dwarfs situated at a distance of kpc scale. The exceptional sensitivity of the JWST enables the detection of brown dwarfs that are up to 100 times more distant than those discovered in the earlier all-sky infrared surveys. The large area coverage of the JWST COSMOS-Web survey allows us to find more distant brown dwarfs than earlier JWST studies with smaller area coverages. To capture prominent water absorption features around 2.7 μm, we apply two colour criteria, F115W – F277W + 1 < F277W – F444W and F277W – F444W > 0.9. We then select point sources by CLASS_STAR, FLUX_RADIUS, and SPREAD_MODEL criteria. Faint sources are visually checked to exclude possibly extended sources. We conduct SED fitting and MCMC simulations to determine their physical properties and associated uncertainties. Our search reveals 25 T-dwarf candidates and 2 Y-dwarf candidates, more than any previous JWST brown dwarf searches. They are located from 0.3 kpc to 4 kpc away from the Earth. The spatial number density of 900-1050 K dwarf is (2.0 ± 0.9) × 10–6 pc–3, 1050–1200 K dwarf is (1.2 ± 0.7) × 10–6 pc–3, and 1200–1350 K dwarf is (4.4 ± 1.3) × 10–6 pc–3. The cumulative number count of our brown dwarf candidates is consistent with the prediction from a standard double exponential model. Three of our brown dwarf candidates were detected by HST, with transverse velocities 12 ± 5 km s–1, 12 ± 4 km s–1, and 17 ± 6 km s–1. Along with earlier studies, the JWST has opened a new window of brown dwarf research in the MilkyWay thick disk and halo.
The hydrodynamic behaviours of finite-size microorganisms in turbulent channel flows are investigated using a direct-forcing fictitious domain method. The classical ‘squirmer’ model, characterized by self-propulsion through tangential surface waves at its boundaries, is employed to mimic the swimming microorganisms. We adopt various simulation parameters, including a friction Reynolds number Reτ = 180, two squirmer volume fractions 𝜑0 = 12.7 % and 2.54 % and a blocking ratio (squirmer radius/half-channel width) κ = 0.125. Results show that pushers (propelled from the rear) induce a more pronounced decrease in the velocity profile than neutral squirmers and pullers (propelled from the front). This hindrance and the induced particle inner stress τpI positively correlate with the quantity of squirmers accumulated in the near-wall region. Notably, the increase in τpI primarily occurs at the expense of diminishing the fluid Reynolds stress τfR. Compared with passive spheres, a low volume fraction (𝜑0 = 2.54 %) of pullers results in a slightly enhanced velocity profile across the channel. In the near-wall region, the swimming direction of the squirmers shows no significant tendency with respect to the flow direction. In the bulk-flow region, pushers and neutral squirmers tend to align their axes more along the flow direction, whereas pullers exhibit a slight preference for alignment with the normal direction.
Despite being almost 4000m above sea level, cereal crops have been grown in the Ngari Prefecture on the Tibetan Plateau for thousands of years. Where and when domestic crop species adapted to high-altitude growing conditions is a matter of ongoing debate. Here, the authors present a new radiocarbon date from the Gepa serul cemetery, providing the earliest evidence of naked six-rowed barley in Tibet (c. 3500 BP). Evaluating the available evidence for barley cultivation and interregional connections in central Asia at this time, two hypotheses are considered—a generational advance with farmers migrating up river valleys or rapid, long-distance trade through mountain corridors.
A transverse ledge climbing robot inspired by athletic locomotion is a customized robot aiming to travel through horizontal ledges in vertical walls. Due to the safety issue and complex configurations in graspable ledges such as horizontal, inclined ledges, and gaps between ledges, existing well-known vision-based navigation methods suffering from occlusion problems may not be applicable to this special kind of application. This study develops a force feedback-based motion planning strategy for the robot to explore and make feasible grasping actions as it continuously travels through reachable ledges. A contact force detection algorithm developed using a momentum observer approach is implemented to estimate the contact force between the robot’s exploring hand and the ledge. Then, to minimize the detection errors due to dynamic model uncertainties and noises, a time-varying threshold is integrated. When the estimated contact force exceeds the threshold value, the robot control system feeds the estimated force into the admittance controller to revise the joint motion trajectories for a smooth transition. To handle the scenario of gaps between ledges, several ledge-searching algorithms are developed to allow the robot to grasp the next target ledge and safely overcome the gap transition. The effectiveness of the proposed motion planning and searching strategy has been justified by simulation, where the four-link transverse climbing robot successfully navigates through a set of obstacle scenarios modeled to approximate the actual environment. The performance of the developed grasping ledge searching methods for various obstacle characteristics has been evaluated.
In this study, a single specimen of Pacific black scabbardfish Aphanopus arigato Parin, 1994 was collected at a depth of ~500 m near Dongsha Island in southwestern Taiwan (18°49′ to 20°45′N and 112°46′ to 116°15′E), on 14 March 2023. This is the southernmost record of A. arigato, with a significantly wide range extension from northern Japan, and southern Kuril Islands to the South China Sea. We also provide comparisons of the morphological measurements, first description of sagittae otoliths, and a partial sequence of the cytochrome oxidase subunit I gene for the specimen studied in this study.
Galaxy morphology in stellar light can be described by a series of ‘non-parametric’ or ‘morphometric’ parameters, such as concentration-asymmetry-smoothness, Gini, $M_{20}$, and Sérsic fit. These parameters can be applied to column density maps of atomic hydrogen (H 1). The H 1 distribution is susceptible to perturbations by environmental effects, for example, intergalactic medium pressure and tidal interactions. Therefore, H 1 morphology can potentially identify galaxies undergoing ram-pressure stripping or tidal interactions. We explore three fields in the WALLABY Pilot H 1 survey and identify perturbed galaxies based on a k-nearest neighbour (kNN) algorithm using an H 1 morphometric feature space. For training, we used labelled galaxies in the combined NGC 4808 and NGC 4636 fields with six H 1 morphometrics to train and test a kNN classifier. The kNN classification is proficient in classifying perturbed galaxies with all metrics – accuracy, precision, and recall – at 70–80%. By using the kNN method to identify perturbed galaxies in the deployment field, the NGC 5044 mosaic, we find that in most regards, the scaling relations of perturbed and unperturbed galaxies have similar distribution in the scaling relations of stellar mass versus star formation rate and the Baryonic Tully–Fisher relation, but the H 1 and stellar mass relation flatter than of the unperturbed galaxies. Our results for NGC 5044 provide a prediction for future studies on the fraction of galaxies undergoing interaction in this catalogue and to build a training sample to classify such galaxies in the full WALLABY survey.
The exploration of molecular characteristics has emerged as a prominent trend to advance precision medicine. The utilization of genetic testing to guide therapy is integral to precision medicine. This study aims to investigate the potential patient populations for the reimbursement of next-generation sequencing (NGS) and assess the budget impact from the perspective of Taiwan’s single insurer, the National Health Insurance Administration.
Methods
To comprehend the scope for medicines with companion diagnostics (CDx) involved, we analyze the U.S. Food and Drug Administration-approved/cleared diagnostic tests, conduct a literature review to identify medicines approved by the European Medicines Agency that require a CDx, and identify the medicines with CDx involved covered by the National Health Insurance (NHI) in Taiwan. Subsequently, we explore the potential reimbursement indications for NGS testing and conduct a budget impact analysis to evaluate the expected financial impact for the NHI over a five-year period. Furthermore, sensitivity analyses are conducted to deal with uncertainty.
Results
We have compiled 13 cancer types for which NGS can serve as a companion diagnostic. These encompass non-small-cell lung cancer, colorectal cancer, breast cancer, ovarian cancer, biliary tract cancer, acute myeloid leukemia, acute lymphoblastic leukemia, melanoma, cholangiocarcinoma, prostate cancer, pancreatic cancer, gastrointestinal stromal tumor, and thyroid cancer/medullary thyroid cancer. The implementation of NGS reimbursement in NHI will benefit 25,000 to 30,000 patients undergoing targeted therapies. The projected incremental budget impact ranges from TWD570 million to TWD650 million (USD19 million to USD22 million) over five years.
Conclusions
This study focuses on evaluating the financial impact of incorporating NGS testing into NHI reimbursement for relevant cancer drug indications. The findings can serve as references for the planning of reimbursement policies. However, with the advancement of precision medicine, it is foreseeable that there will be a broader range of applications for NGS, and its cost will gradually decrease.
This paper introduces a novel fiber-based picosecond burst-mode laser system capable of operating at high power and high repetition rates. A pulse-circulating fiber ring was developed as a burst generator, achieving an intra-burst repetition rate of 469 MHz without the need for a high-repetition-rate seed source. This design also allows for flexible adjustment of the number of sub-pulses, burst repetition rate and burst shape. In addition, a master oscillator power amplifier was employed to analyze the amplification characteristics of bursts. The system demonstrated a maximum average power of 606 W, with a measured sub-pulse duration of 62 ps and the highest sub-pulse peak power of 980 kW. To the best of our knowledge, this marks the highest average power obtained in burst-mode ultrafast lasers. Such a laser system holds potential for applications in precision manufacturing, high-speed imaging, high-precision ranging and other diverse domains.
Bacterial infection risk in work environments has been extensively reported for healthcare workers, while this risk is rarely researched in other occupations. This study aimed to identify occupational environments in Taiwan’s agricultural and healthcare industries with elevated bacterial infection risks by comparing risks for general bacterial infections and pneumonia. Using labour and health insurance claim data from 3.3 million workers (January 2004–December 2020), a retrospective cohort was constructed to estimate occupational infection risks with Cox regression and the Anderson-Gill extension. Significantly elevated hazard ratios were found for workers in vegetable growing, crop cultivation service, mushroom growing, flower growing, and fruit growing, ranging from 1.13 to 1.39 for general bacterial infections and 1.68 to 3.06 for pneumonia infections. In afforestation and the inland fishing industry, pneumonia risk was significantly elevated with, respectively, 1.87 and 1.21. In the healthcare section, especially workers in residential care services and residential care services for elderly stand out regarding their pneumonia risk, with significant hazard ratios of 3.49 and 1.75. The methods used in this study were proven to be effective in identification of occupation environments at risk and can be used in other settings. These findings call for prioritization of bacterial infection prevention by occupation.
Introduction: Late-life depression (LLD) is associated with cognitive deficit with risk of future dementia. By examining the entropy of the spontaneous brain activity, we aimed to understand the neural mechanism pertaining to cognitive decline in LLD.
Methods: We collected MRI scans in older adults with LLD (n = 32), mild cognitive impairment [MCI (n = 25)] and normal cognitive function [NC, (n = 47)]. Multiscale entropy analysis (MSE) was applied to resting-state fMRI data. Under the scale factor (tau) 1 and 2, reliable separation of fMRI data and noise was achieved. We calculated the brain entropy in 90 brain regions based on automated anatomical atlas (AAL). Due to exploratory nature of this study, we presented data of group-wise comparison in brain entropy between LLD vs. NC, MCI vs. NC, and LLD and MCD with a p-value below 0.001.
Results: The mean Mini-Mental State Examination (MMSE) score of LLD and MCI was 27.9 and 25.6. Under tau 2, we found higher brain entropy of LLD in left globus pallidus than MCI (p = 0.002) and NC (p = 0,009). Higher brain entropy of LLD than NC was also found in left frontal superior gyrus, left middle superior gyrus, left amygdala and left inferior parietal gyrus. The only brain region with higher brain entropy in MCI than control was left posterior cingulum (p-value = 0.015). Under tau 1, higher brain entropy was also found in LLD than in MCI in right orbital part of medial frontal gyrus and left globus pallidus (p-value = 0.007 and 0.005).
Conclusions: Our result is consistent with prior hypothesis where higher brain entropy was found during early aging process as compensation. We found such phenomenon particular in left globus pallidus in LLD, which could be served as a discriminative brain region. Being a key region in reward system, we hypothesis such region may be associated with apathy and with unique pathway of cognitive decline in LLD. We will undertake subsequent analysis longitudinally in this cohort
The influence of the SNP rs174575 (C/G) within the fatty acid desaturase 2 gene on the levels of long-chain PUFA was determined through statistical meta-analysis. Six databases were searched to retrieve the relevant literature. Original data were analysed using Stata 17·0, encompassing summary statistics, tests for heterogeneity, assessment of publication bias, subgroup analysis and sensitivity analysis. A total of ten studies were identified and grouped into twelve trials. Our results showed that individuals who carried the minor G allele of rs174575 had significantly higher dihomo-γ-linolenic acid levels (P = 0·005) and lower arachidonic acid levels (P = 0·033) than individuals who were homozygous for the major allele. The subgroup analysis revealed that the G-allele carriers of rs174575 were significantly positively correlated with linoleic acid (P = 0·002) and dihomo-γ-linolenic acid (P < 0·001) and negatively correlated with arachidonic acid (P = 0·004) in the European populations group. This particular SNP showed a potential association with higher concentrations of dihomo-γ-linolenic acid (P = 0·050) and lower concentrations of arachidonic acid (P = 0·030) within the breast milk group. This meta-analysis has been registered in the PROSPERO database (ID: CRD42023470562).
Interface-resolved direct numerical simulations (DNS) of clustered settling suspensions in a periodic domain are performed to study the filtered drag force for clustered particle-laden flows. Our results show that, for the homogeneous system, the filtered drag is independent of the filter size, whereas for the clustered particle-laden flows, the averaged drag becomes smaller than the homogeneous drag at the filter size above 4 particle diameters. The drag reduction saturates at the filter size being comparable to the cluster size in the horizontal direction in our simulations. A new correlation is proposed to account for the mesoscale effect on the filtered drag force by using drift velocity and variance of the solid volume fraction, based on the modification of existing subgrid drag models for the inhomogeneous system. The existing models for the drift velocity and the variance of the solid volume fraction are assessed using our DNS data. A new model for the drift velocity and the variance of the solid volume fraction is proposed, based on the combination and modification of the previous models. All mesoscale models considered can predict well the filtered drag with comparable accuracy, and are superior to the homogeneous drag model for the clustered system. Our models with the same parameter values obtained from the large-scale system can also predict well the filtered drag for smaller computational domain sizes.
Purple nutsedge (Cyperus rotundus L.) is one of the world’s resilient upland weeds, primarily spreading through its tubers. Its emergence in rice (Oryza sativa L.) fields has been increasing, likely due to changing paddy-farming practices. This study aimed to investigate how C. rotundus, an upland weed, can withstand soil flooding and become a problematic weed in rice fields. The first comparative analysis focused on the survival and recovery characteristics of growing and mature tubers of C. rotundus exposed to soil-flooding conditions. Notably, mature tubers exhibited significant survival and recovery abilities in these environments. Based on this observation, further investigation was carried out to explore the morphological structure, nonstructural carbohydrates, and respiratory mechanisms of mature tubers in response to prolonged soil flooding. Over time, the mature tubers did not form aerenchyma but instead gradually accumulated lignified sclerenchymal fibers, with lignin content also increasing. After 90 d, the lignified sclerenchymal fibers and lignin contents were 4.0 and 1.1 times higher than those in the no soil-flooding treatment. Concurrently, soluble sugar content decreased while starch content increased, providing energy storage, and alcohol dehydrogenase activity rose to support anaerobic respiration via alcohol fermentation. These results indicated that mature tubers survived in soil-flooding conditions by adopting a low-oxygen quiescence strategy, which involves morphological adaptations through the development of lignified sclerenchymal fibers, increased starch reserves for energy storage, and enhanced anaerobic respiration. This mechanism likely underpins the flooding tolerance of mature C. rotundus tubers, allowing them to endure unfavorable conditions and subsequently germinate and grow once flooding subsides. This study provides a preliminary explanation of the mechanism by which mature tubers of C. rotundus from the upland areas confer flooding tolerance, shedding light on the reasons behind this weed’s increasing presence in rice fields.
This study aimed to explore the combined association between the dietary antioxidant quality score (DAQS) and leisure-time physical activity on sleep patterns in cancer survivors. Data of cancer survivors were extracted from the National Health and Nutrition Examination Surveys database in 2007–2014 in this cross-sectional study. Weighted multivariable logistic regression models were used to estimate OR and 95 % CI for the association of DAQS and leisure-time physical activity on sleep patterns. The combined association was also assessed in subgroups of participants based on age and use of painkillers and antidepressants. Among the eligible participants, 1133 had unhealthy sleep patterns. After adjusting for covariates, compared with low DAQS level combined with leisure-time physical activity level < 600 MET·min/week, high DAQS level combined with leisure-time physical activity ≥ 600 MET·min/week was associated with lower odds of unhealthy sleep patterns (OR = 0·41, 95 % CI: 0·23, 0·72). Additionally, the association of high DAQS level combined with high leisure-time physical activity with low odds of unhealthy sleep patterns was also significant in < 65 years old (OR = 0·30, 95 % CI: 0·13, 0·70), non-painkiller (OR = 0·39, 95 % CI: 0·22, 0·71), non-antidepressant (OR = 0·49, 95 % CI: 0·26, 0·91) and antidepressant (OR = 0·11, 95 % CI: 0·02, 0·50) subgroups. DAQS and leisure-time physical activity had a combined association on sleep patterns in cancer survivors. However, the causal associations of dietary nutrient intake and physical activity with sleep patterns in cancer survivors need further clarification.
High-resolution simulations of gravity currents in the lock-exchange configuration are conducted to study the flow within the head. The simulations exhibit the geometric features of the head as reported in the laboratory experiments and numerical simulations, and provide more detailed information on the flow within the head of a gravity current. The flow in the lower part of the head, where the lobes and clefts are forming at the leading edge, is qualitatively different from but interconnected to the flow in the upper part of the head, where steepening bulges are protruding from the upright surface above the clefts. Interestingly, regions of positive and negative streamwise vorticity are observed not only in the lower part of the head but also in the upper part of the head at staggered spanwise locations. We have shown that both the streamwise vorticity at the leading edge of the lobes in the lower part of the head and the streamwise vorticity at the steepening bulges in the upper part of the head are contributed from the twisting of spanwise vorticity into the streamwise direction, due to the geometric features of the lobes and the steepening bulges, and contributed from the baroclinic production of vorticity. Our results from visualization using tracers indicate that the ambient fluid ingested in and rising from the clefts is being swept towards the leading edge of a gravity current before being carried upwards from the leading edge to the upright surface above the left and right neighbouring lobes. Furthermore, the heavy fluid inside a lobe may descend towards the bottom boundary, move forward towards the leading edge and outwards towards the neighbouring clefts, and ultimately be carried upwards to the upright surface above the left and right neighbouring lobes. With the knowledge that the erosive power of a gravity current is concentrated in the head region, it is plausible that the bed material, once resuspended by a gravity current, may be lifted up away from the bottom boundary and be dispersed in both the streamwise and spanwise directions. The present study complements existing findings in the literature and provides new insights into the three-dimensional flow field within the head of a gravity current.
The elasto-inertial focusing and rotating characteristics of spheroids in a square channel flow of Oldroyd-B viscoelastic fluids are studied by the direct forcing/fictitious domain method. The rotational behaviours, changes in the equilibrium positions and travel distances are explored to analyse the mechanisms of spheroid migration in viscoelastic fluids. Within the present simulated parameters (1 ≤ Re ≤ 100, 0 ≤ Wi ≤ 2, 0.4 ≤ α ≤3), the results show that there are four kinds of equilibrium positions and six (five) kinds of rotational behaviours for the elasto-inertial migration of prolate (oblate) spheroids. We are the first to identify a new rotational mode for the migration of prolate spheroids. Only when the particles are initially located at a corner and wall bisector, some special initial orientations of the spheroids have an impact on the final equilibrium position and rotational mode. In other general initial positions, the initial orientation of the spheroid has a negligible effect. A higher Weissenberg number means the faster the particles migrate to the equilibrium position. The spheroid gradually changes from the corner (CO), channel centreline (CC), diagonal line (DL) and cross-section midline (CSM) equilibrium positions as the elastic number decreases, depending on the aspect ratio, initial orientation and rotational behaviour of the particles and the elastic number of the fluid. When the elastic number is less than the critical value, the types of rotational modes of the spheroids are reduced. By controlling the elastic number near the critical value, spheroids with different aspect ratios can be efficiently separated.