Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular vesicles originating from autophagy mediate an antibody-resistant spread of classical swine fever virus in cell culture

ABSTRACT Free spread is a classical mode for mammalian virus transmission. However, the efficiency of this transmission approach is generally low as there are structural barriers or immunological surveillances in the extracellular environment under physiological conditions. In this study, we systematically analyzed the spreading of classical swine fever virus (CSFV) using multiple viral replication analysis in combination with antibody neutralization, transwell assay, and electron microscopy, and identified an extracellular vesicle (EV)-mediated spreading of CSFV in cell cultures. In this approach, intact CSFV virions are enclosed within EVs and transferred into uninfected cells with the movement of EVs, leading to an antibody-resistant infection of the virus. Using fractionation assays, immunostaining, and electron microscopy, we characterized the CSFV-containing EVs and demonstrated that the EVs originated from macroautophagy/autophagy. Taken together, our results showed a new spreading mechanism for CSFV and demonstrated that the EVs in CSFV spreading are closely related to autophagy. These findings shed light on the immune evasion mechanisms of CSFV transmission, as well as new functions of cellular vesicles in virus lifecycles. Abbreviations: 3-MA: 3-methyladenine; CCK-8: Cell Counting Kit-8; CSF: classical swine fever; CQ: chloroquine; CSFV: classical swine fever virus; DAPI, 4-,6-diamidino-2-phenylindole; EVs: extracellular vesicles; hpi: h post infection; IEM: immunoelectron microscopy; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MOI: multiplicity of infection; MVs: microvesicles; ND50: half neutralizing dose; PCR: polymerase chain reaction; PBS: phosphate-buffered saline; SEC: size-exclusion chromatography; siRNA: small interfering RNA; TEM: transmission electron microscopy.
Predictive Value of Insulin Resistance as Determined by Homeostasis Model Assessment in Acute Ischemic Stroke Patients: A Systematic Review and Meta-Analysis

Abstract Studies on association between homeostasis model assessment of insulin resistance (HOMA-IR) and adverse outcomes have yielded conflicting results in patients with acute ischemic stroke (AIS). This meta-analysis aimed to assess the predictive value of HOMA-IR in AIS patients. Two authors comprehensively searched PubMed and Embase databases until February 28, 2021. All observational studies investigating the association between HOMA-IR and adverse outcomes in AIS patients were included. Outcome measures were poor functional outcome (Modified Rankin Scale≥3), all-cause mortality, stroke recurrence, and neurologic worsening. Seven studies (eight articles) involving 8330 AIS patients were identified. For the highest versus lowest HOMA-IR, the pooled risk ratio (RR) of poor functional outcome was 2.55 (95% CI 1.76–3.70) after adjustment of conventional confounding factors. In addition, elevated HOMA-IR was associated with higher risk of neurologic worsening (RR 1.93; 95% CI 1.15–3.26). However, there were conflicting findings on the association of HOMA-IR with stroke recurrence and all-cause mortality. This meta-analysis confirms that HOMA-IR is significantly associated with an increased risk of poor functional outcome in patients with AIS. However, interpretation of the results of mortality, stroke recurrence, and neurologic worsening should be done with caution due to small number of studies available.
Choices in manufacturing strategy decision areas in batch production system – six case studies

The configuration of a production system can be described by the choices a firm makes in its manufacturing decision areas. Manufacturing strategy literature lacks empirical research in manufacturing decision areas. The current paper is an exploratory study using six case companies on alternative configurations that can exist in a batch production system. Choices made in decisions such as layout, shop floor control, etc., were found to be similar for all six companies that use batch process. However, there were a number of decisions that were found to be non-process specific and are influenced by product complexity, important competitive priorities, strategic orientation of manufacturing, top management decisions and the size of the company. The paper concludes with managerial implications and future research directions.
Diverging responses of water and carbon relations during and after heat and hot drought stress in Pinus sylvestris

Abstract Forests are increasingly affected by heatwaves, often co-occurring with drought, with consequences for water and carbon (C) cycling. However, our ability to project tree resilience to more intense hot droughts remains limited. Here, we used single tree chambers (n = 18) to investigate transpiration (E), net assimilation (Anet), root respiration (Rroot) and stem diameter change in Scots pine seedlings in a control treatment and during gradually intensifying heat or drought-heat stress (max. 42 °C), including recovery. Alongside this, we assessed indicators of stress impacts and recovery capacities. In the heat treatment, excessive leaf heating was mitigated via increased E, while under drought-heat, E ceased and leaf temperatures reached 46 °C. However, leaf electrolyte leakage was negligible, while light-adapted quantum yield of photosystem II (F′v/F′m) declined alongside Anet moderately in heat, but strongly in drought-heat seedlings, in which respiration exceeded C uptake. Drought-heat largely affected the hydraulic system as apparent in stem diameter shrinkage, declining relative needle water content (RWCNeedle) and water potential (ΨNeedle) reaching −2.7 MPa, alongside a 90% decline of leaf hydraulic conductance (KLeaf). Heat alone resulted in low functional impairment and all measured parameters recovered quickly. Contrary, following drought-heat, the recovery of KLeaf was incomplete and stem hydraulic conductivity (KS) was 25% lower than the control. However, F′v/F′m recovered and the tree net C balance reached control values 2 days post-stress, with stem increment rates accelerating during the second recovery week. This indicates a new equilibrium of C uptake and release in drought-heat seedlings independent of hydraulic impairment, which may slowly contribute to the repair of damaged tissues. In summary, Scots pine recovered rapidly following moderate heat stress, while combined with drought, hydraulic and thermal stress intensified, resulting in functional damage and slow recovery of hydraulic conductance. This incomplete hydraulic recovery could critically limit evaporative cooling capacities and C uptake under repeated heatwaves.
Reliability of 3 Radiologic Classifications for the Severity of the Developmental Dysplasia of the Hip in Children Older Than 4 Years

Background: Tonnis, International Hip Dysplasia Institute (IHDI), and lateral metaphyseal height (LMH) are commonly used classifications for grading the severity of the developmental dysplasia of the hip. The reliability of these classifications is not widely studied in older children. The aim of the study was to evaluate the reliability of these 3 radiologic classifications in children older than 4 years and compared with children younger than 4 years and evaluate the cases with varied inter-rater reliability. Methods: A purposeful sample of 40 children with untreated developmental dysplasia of the hip with ages between 6 months to 8 years was studied for the assessment of the severity grading according to all 3 classifications. Six pediatric orthopaedic surgeons classified all hips for all 3 categorical classifications as per the original description. Inter-rater and intrarater reliability was calculated according to the intraclass correlation coefficient. The cases with different ratings were assessed in detail to evaluate the reasons for the varied rating. Results: The interobserver and intraobserver reliability of all 3 classifications were excellent [intraclass correlation coefficient (ICC): 0.935, 0.820, and 0.935 for IHDI, Tonnis, and LMH classification, respectively]. The excellent reliability was also observed in younger and older children. Interobserver reliability of only dysplastic hips (52 hips) was good for Tonnis (ICC: 0.741) and excellent for IHDI (ICC: 0.911) and LMH classification (ICC-0.9). The main reason for the varied rating was because of the varied perception of the superolateral margin of the acetabulum in few hips. Conclusion: The inter-rater and intrarater reliability of all 3 classifications (IHDI, Tonnis, and LMH) is excellent. All classifications can be used till the age of 8 years. The difficulty in selecting the superolateral margin of the acetabulum is a major cause of inter-rater variability. Level of Study: Level III.
Effects of exogenous sucrose and selenium on plant growth, quality, and sugar metabolism of pea sprouts

Abstract BACKGROUND Pea sprouts are considered a healthy food. Sucrose is a key nutritional factor affecting taste and flavor. Meanwhile, selenium (Se) is an essential micronutrient that plays multiple roles in wide variety of physiological processes and improves crop quality and nutritional value. Nonetheless, the effects of the combination of sucrose and Se treatment on growth, quality, and sugar metabolism of pea sprouts have not been explored. RESULTS The results revealed that sucrose at 10 mg L−1 obviously increased fresh weight, vitamin C, soluble protein, soluble sugar, fructose, glucose, and sucrose contents. Se treatments also improved nutritional quality, but higher Se (2.5 mg L−1) significantly inhibited the growth of seedlings. Interestingly, the combined application of sucrose (10 mg L−1) and Se (1.25 mg L−1) could effectively promote vitamin C, sucrose, and fructose contents, especially the Se content, compared with Se application alone. Additionally, there were significant differences in the regulation of sugar metabolism between Se alone and combined application of sucrose and Se. Acid invertase and neutral invertase play a pivotal role in the accumulation of soluble sugar under Se treatments alone, and acid invertase might be the key enzyme to limit sugar accumulation under combined application of sucrose and Se. CONCLUSION The moderate combined application of sucrose (10 mg L−1) and Se (1.25 mg L−1) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Novel experimental model of brain arteriovenous malformations using conditional Alk1 gene deletion in transgenic mice.

OBJECTIVE Hereditary hemorrhagic telangiectasia is the only condition associated with multiple inherited brain arteriovenous malformations (AVMs). Therefore, a mouse model was developed with a genetics-based approach that conditionally deleted the causative activin receptor-like kinase 1 (Acvrl1 or Alk1) gene. Radiographic and histopathological findings were correlated, and AVM stability and hemorrhagic behavior over time were examined. METHODS Alk1-floxed mice were crossed with deleter mice to generate offspring in which both copies of the Alk1 gene were deleted by Tagln-Cre to form brain AVMs in the mice. AVMs were characterized using MRI, MRA, and DSA. Brain AVMs were characterized histopathologically with latex dye perfusion, immunofluorescence, and Prussian blue staining. RESULTS Brains of 55 Tagln-Cre+;Alk12f/2f mutant mice were categorized into three groups: no detectable vascular lesions (group 1; 23 of 55, 42%), arteriovenous fistulas (AVFs) with no nidus (group 2; 10 of 55, 18%), and nidal AVMs (group 3; 22 of 55, 40%). Microhemorrhage was observed on MRI or MRA in 11 AVMs (50%). AVMs had the angiographic hallmarks of early nidus opacification, a tangle of arteries and dilated draining veins, and rapid shunting of blood flow. Latex dye perfusion confirmed arteriovenous shunting in all AVMs and AVFs. Microhemorrhages were detected adjacent to AVFs and AVMs, visualized by iron deposition, Prussian blue staining, and macrophage infiltration using CD68 immunostaining. Brain AVMs were stable on serial MRI and MRA in group 3 mice (mean age at initial imaging 2.9 months; mean age at last imaging 9.5 months). CONCLUSIONS Approximately 40% of transgenic mice satisfied the requirements of a stable experimental AVM model by replicating nidal anatomy, arteriovenous hemodynamics, and microhemorrhagic behavior. Transgenic mice with AVFs had a recognizable phenotype of hereditary hemorrhagic telangiectasia but were less suitable for experimental modeling. AVM pathogenesis can be understood as the combination of conditional Alk1 gene deletion during embryogenesis and angiogenesis that is hyperactive in developing and newborn mice, which translates to a congenital origin in most patients but an acquired condition in patients with a confluence of genetic and angiogenic events later in life. This study offers a novel experimental brain AVM model for future studies of AVM pathophysiology, growth, rupture, and therapeutic regression.
Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics

Androgenetic alopecia (AGA) is the most common form of hair loss consisting of a characteristic receding frontal hairline in men and diffuse hair thinning in women, with frontal hairline retention, and can impact an individual's quality of life. The condition is primarily mediated by 5‐alpha‐reductase and dihydrotestosterone (DHT) which causes hair follicles to undergo miniaturization and shortening of successive anagen cycles. Although a variety of medical, surgical, light‐based and nutraceutical treatment options are available to slow or reverse the progression of AGA, it can be challenging to select appropriate therapies for this chronic condition.
A near-infrared AIE fluorescent probe for myelin imaging: From sciatic nerve to the optically cleared brain tissue in 3D

Significance The high spatial resolution of three-dimensional (3D) fluorescence imaging of myelinated fibers will greatly facilitate the understanding of 3D neural networks and the pathophysiology of demyelinating diseases. However, existing myelin probes are far from satisfactory because of their low–signal-to-background ratio and poor tissue permeability. We herein developed a near-infrared aggregation-induced emission-active probe, PM-ML, for high-performance myelin imaging. PM-ML could specifically image myelinated fibers in teased sciatic nerves and mouse brain tissues with high contrast, good photostability, and deep penetration depth. PM-ML staining is compatible with several tissue-clearing methods. Its application in assessing myelination for neuropathological studies was also demonstrated using a multiple sclerosis mouse model. Myelin, the structure that surrounds and insulates neuronal axons, is an important component of the central nervous system. The visualization of the myelinated fibers in brain tissues can largely facilitate the diagnosis of myelin-related diseases and understand how the brain functions. However, the most widely used fluorescent probes for myelin visualization, such as Vybrant DiD and FluoroMyelin, have strong background staining, low-staining contrast, and low brightness. These drawbacks may originate from their self-quenching properties and greatly limit their applications in three-dimensional (3D) imaging and myelin tracing. Chemical probes for the fluorescence imaging of myelin in 3D, especially in optically cleared tissue, are highly desirable but rarely reported. We herein developed a near-infrared aggregation-induced emission (AIE)-active probe, PM-ML, for high-performance myelin imaging. PM-ML is plasma membrane targeting with good photostability. It could specifically label myelinated fibers in teased sciatic nerves and mouse brain tissues with a high–signal-to-background ratio. PM-ML could be used for 3D visualization of myelin sheaths, myelinated fibers, and fascicles with high-penetration depth. The staining is compatible with different brain tissue–clearing methods, such as ClearT and ClearT2. The utility of PM-ML staining in demyelinating disease studies was demonstrated using the mouse model of multiple sclerosis. Together, this work provides an important tool for high-quality myelin visualization across scales, which may greatly contribute to the study of myelin-related diseases.
Chryseobacterium endalhagicum sp. nov., isolated from seed of leguminous plant

A Gram-stain-negative, yellow-pigmented bacterium, designated as L7T, was isolated from seeds of Alhagi sparsifolia Shap. , a leguminous plant that grows in northwest PR China. Strain L7T was found to be non-flagellated, non-spore forming rods which can grow at 10–37 °C, pH 6.0–8.5 and in 0–3 % (v/w) NaCl concentration. The 16S rRNA gene sequence analysis showed that strain L7T belongs to the genus Chryseobacterium with sequence similarities to Chryseobacterium vietnamense GIMN1.005T (98.1%), C. bernardetii NCCTC13530T (98.0%), C. vrystaatense LMG 22846T (97.9%), C. nakagawai NCTC13529T (97.7%), C. shigense DSM 17126T (97.6%) and C. rhizosphaerae RSB3-1T (97.5%). The average nucleotide identity of strain L7T to 31 reference strains were 78.6–85.6 %, lower than the species delineation threshold of 95 %. MK-6 was the only respiratory quinone of L7T and major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1 ω7c and/or C16 : 1 ω6c, isoC17 : 1 ω9c and/or C16 : 0 10-methyl. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, two unidentified aminolipids, three unidentified glycolipids and two unidentified lipids. The G+C content of the genome was 38.58 mol%. On the basis of polyphasic taxonomy analyses in this study, strain L7T is considered to represent a novel species in the genus Chryseobacterium , for which the name Chryseobacterium endalhagicum sp. nov. is proposed. The type strain is L7T (=MCCC 1K05687T=JCM 34506T)
Applying lean thinking to new product introduction

Lean Thinking and its principles as prescribed by Womack and Jones have been successfully applied to manufacturing and operations environments, and associated case studies and research literature have been published extensively. The same cannot be said for Lean application to the new product introduction (NPI) or development processes. The aim of this paper is to describe the application of the Womack and Jones principles of Lean Thinking to the NPI process (from concept development to detailed design through to customer delivery). While techniques such as concurrent engineering (or concurrent product development) have been implemented and have been quite successful in improving NPI, there is still a shortfall in the expected or desired improvements to NPI. This shortfall we believe can be bridged through the application of Lean Thinking to NPI; in particular, the five lean principles proposed by Womack and Jones. The five Lean principles are briefly ‘specify value’, ‘identify the value stream and eliminate waste’, ‘make the value flow’, ‘let the customer pull the process’, and ‘pursue perfection’. In this paper each principle is defined and characterized within the context of NPI. The work presented was developed on the Society of British Aerospace Companies' UK Lean Aerospace Initiative involving 40 aerospace companies of all sizes from across the UK. Two case studies from the industry are also presented to demonstrate aspects of Lean application in NPI (in particular, in product design and development). The paper concludes by summarizing the key methods and tools that enable Lean in NPI, and by discussing the key adjustments required to the manufacturing/operations definitions of waste and value to accommodate the demands of effective and efficient NPI.
CIFDock: A novel CHARMM‐based flexible receptor–flexible ligand docking protocol

Docking studies play a critical role in the current workflow of drug discovery. However, limitations may often arise through factors including inadequate ligand sampling, a lack of protein flexibility, scoring function inadequacies (e.g., due to metals, co‐factors, etc.), and difficulty in retaining explicit water molecules. Herein, we present a novel CHARMM‐based induced fit docking (CIFDock) workflow that can circumvent these limitations by employing all‐atom force fields coupled to enhanced sampling molecular dynamics procedures. Self‐guided Langevin dynamics simulations are used to effectively sample relevant ligand conformations, side chain orientations, crystal water positions, and active site residue motion. Protein flexibility is further enhanced by dynamic sampling of side chain orientations using an expandable rotamer library. Steps in the procedure consisting of fixing individual components (e.g., the ligand) while sampling the other components (e.g., the residues in the active site of the protein) allow for the complex to adapt to conformational changes. Ultimately, all components of the complex—the protein, ligand, and waters—are sampled simultaneously and unrestrained with SGLD to capture any induced fit effects. This modular flexible docking procedure is automated using CHARMM scripting, interfaced with SLURM array processing, and parallelized to use the desired number of processors. We validated the CIFDock procedure by performing cross‐docking studies using a data set comprised of 21 pharmaceutically relevant proteins. Five variants of the CHARMM‐based SWISSDOCK scoring functions were created to quantify the results of the final generated poses. Results obtained were comparable to, or in some cases improved upon, commercial docking program data.
Spatial-Temporal Variability of Northern Hemisphere Sea Ice Concentrations and Concurrent Atmospheric Teleconnections

Because the Arctic is so integrally connected with the Earth's climate system, there is concern that the recent era of global warming has irreversibly altered the polar sea ice cover. This can have global consequences. However, we need to improve our knowledge of sea ice-atmosphere teleconnections if we are to increase our confidence in such climate change scenarios. In this paper, we apply the method of principal components analysis to twenty years of pentad-averaged Arctic sea ice concentration anomaly data derived from satellite observations to retrieve the most significant spatial and temporal patterns. We then linked these patterns to coincident 500 mb geopotential height (500Z) data. The strongest spatial-temporal ice concentration anomaly pattern over the 1980-1999 period was the phase-shifted anomalies between the Greenland and Barents Seas and the Labrador Sea and in Davis Strait. We found this pattern to be associated with strong low pressure anomalies over the North Atlantic and is significantly correlated with the large-scale atmospheric patterns of the North Atlantic Oscillation and El Nino. Other regions where spatially and temporally consistent patterns of anomalous ice concentrations were identified include the Beaufort Sea, on the Siberian side of the Arctic Basin, and the Sea of Okhotsk. We identify the atmospheric patterns coincident with these anomalies. We conclude that our approach of link- ing PCA results of ice anomaly data with highly loading 500Z patterns is an effective analysis method. We recommend that this study be extended to link full atmospheric PCA results with the sea ice pentads used here.