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Dairy cows with mastitis are frequently treated with antibiotics. The potential effect of antibiotics on the milk microbiome is still not clear. Therefore, the objective of this research was to investigate the effect of 2 commonly used cephalosporins on the milk microbiota of dairy cows and the antibiotic resistance genes in the milk. The milk samples were collected from 7 dairy cows at the period before medication (d 0), medication (d 1, 2, 3), withdrawal period (d 4, 6, 8), and the period after withdrawal (d 9, 11, 13, 15). We applied 16S rRNA sequencing to explore the microbiota changes, and antibiotic resistance patterns were investigated by quantitative PCR. The microbiota richness and diversity in each sample were calculated using the Chao 1 (richness), Shannon (diversity), and Simpson (diversity) indices. The cephalosporins treatment lowered the Simpson diversity value at the period of withdrawal. Members of the Enterobacter genera were the most affected bacteria associated with mastitis. Meanwhile, antibiotic resistance genes in the milk were also influenced by antibiotic treatment. The cephalosporins treatment raised the proportion of bla TEM in milk samples at the period of withdrawal. Therefore, the treatment of cephalosporins led to change in the milk microbiota and increase of β-lactam resistance gene in the milk at the time of withdrawal period. [ABSTRACT FROM AUTHOR]

• More citations. • Clarified research question and hypotheses. • Reorganized methods section for improved clarity. • Added more experimental results for findings not included in original manuscript. • Improved overall writing style and grammar. Mild Cognitive Impairment (MCI) is an early stage of Alzheimer's Disease (AD), often mistaken for natural aging. Early detection and treatment of MCI are crucial for effective treatment, but the condition can be difficult to diagnose. In recent years, multi-modal data and deep learning methods have shown promise in this field. The objective of this study is to develop a computer-aided MCI diagnosis system that effectively processes multi-modal data using deep learning methods. We proposed a Dual Fusion Cluster Graph Convolution Network (DFCGCN) model, which combines two channels of feature extraction, one adjacency matrix, and the Cluster GCN in series. Brain imaging is downsampled using graph pooling and flattened into sparse vectors, from which advanced features are extracted. Similarity between connectivity matrices is calculated using the Gaussian kernel function and combined with non-imaging details to construct a population graph that better represents inter-subject variability. Finally, features are assigned to subjects in the population graph, and node embeddings are learned using Cluster GCN to output diagnostic results. We tested the proposed algorithm on the public Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, achieving an accuracy, sensitivity, and specificity of 90.7%, 91.1%, and 94.0%, respectively. The DFCGCN model presented in this study enhances the diagnosis of MCI and outperforms other state-of-the-art algorithms. This approach has potential to be a valuable tool for early detection and treatment of MCI. [ABSTRACT FROM AUTHOR]

The mechanisms leading to self-assembly of misfolded proteins into amyloid aggregates have been studied extensively in the test tube under well-controlled conditions. However, to what extent these processes are representative of those in the cellular environment remains unclear. Using super-resolution imaging of live cells, we show here that an amyloidogenic polyglutamine-containing protein first forms small, amorphous aggregate clusters in the cytosol, chiefly by diffusion. Dynamic interactions among these clusters limited their elongation and led to structures with a branched morphology, differing from the predominantly linear fibrils observed in vitro. Some of these clusters then assembled via active transport at the microtubule-organizing center and thereby initiated the formation of perinuclear aggresomes. Although it is widely believed that aggresome formation is entirely governed by active transport along microtubules, here we demonstrate, using a combined approach of advanced imaging and mathematical modeling, that diffusion is the principal mechanism driving aggresome expansion. We found that the increasing surface area of the expanding aggresome increases the rate of accretion caused by diffusion of cytosolic aggregates and that this pathway soon dominates aggresome assembly. Our findings lead to a different view of aggresome formation than that proposed previously. We also show that aggresomes mature over time, becoming more compacted as the structure grows. The presence of large perinuclear aggregates profoundly affects the behavior and health of the cell, and our super-resolution imaging results indicate that aggresome formation and development are governed by highly dynamic processes that could be important for the design of potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The morphology of PLA microspheres could be varied through the formation of PLA stereocomplex. • By simply changing the ratio of PLLA and PDLA in solution, the porosity of the microspheres could be varied. • The drug release rate of the PLLA/PDLA microspheres can be easily tuned from slow to fast with slight initial burst. Abstract The applications of Polylactide (PLA) microspheres in biomedical areas are greatly determined by the size, morphology and internal structure. Taking advantage of the formation of stereocomplex (SC) crystallites between poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), we propose a facile strategy to prepare PLA microspheres with tunable morphology and crystalline structure by compounding PLLA and PDLA. With increasing PDLA content, the crystallinity of SC-PLA rose gradually until the ratio of PLLA and PDLA reached 1:1 and then fell. Correspondingly, the morphology of the microspheres were varied (smooth, porous, golf-ball like, guava like) and higher crystallinity of SC-PLA would lead to a more coarse and porous structure. Finally, three typical kinds of Rifampicin-loaded microspheres with different ratio of PLLA and PDLA (7:3, 3:7, 10:0, sorted by porosity from high to low) were prepared and the release behavior was compared. At 30 h, the cumulative release of 7:3, 3:7 and 10:0 microspheres were 32.6%, 17.8% and 6.0% respectively, indicating that the release profiles were generally determined by the porosity of the microspheres. Our findings not only provide a new strategy to prepare PLA microspheres with controllable morphology but offer additional possibilities for the applications of SC-PLA products in biomedical area. [ABSTRACT FROM AUTHOR]

Background: The worsening problems of antibiotic resistance prompt the need for alternative strategies. Baicalin, which is isolated from Scutellaria baicalensisi, has been demonstrated to exhibit anti-inflammatory, anti-virulence and antimicrobial effects. Salmonella typhimurium is an important foodborne pathogenic bacteriaum that causes gastrointestinal disease in humans and many animals.Purpose: The aim of this study was to investigate the effects of baicalin on S. typhimurium infection in mice and its possible mechanism in vitro.Study Design: To evaluate the effect of baicalin in vivo, mice were orally administered of baicalin, and then were infected by an intragastric administration of S. typhimurium. The minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of baicalin, baicalein, and oroxylin A against S. typhimurium were detected under the guides of the Clinical and Laboratory Standards Institute. In vitro, Caco-2 cells were infected with S. typhimurium in the presence or absence of baicalin, baicalein, and oroxylin A at sub-MICs.Methods: In the in vivo experiment, the body weight loss, the serum levels of TNFα,  IL-6, and lactic dehydrogenase (LDH), the pathological changes of the caecum and the caecum bacterial burdens were examined. The MICs and MBCs of baicalin, baicalein, and oroxylin A against S. typhimurium were detected by two-fold serial dilutions. In vitro, Caco-2 cells were infected with S. typhimurium, and the invasion capacity, TNFα, nitrate, and LDH were analysed. The transcription levels of Salmonella pathogenicity island 1 virulence associated genes (sopB, sopE, sopE2) of S. typhimurium in the presence of baicalin, baicalein, and oroxylin A were detected by qRT-PCR.Results: Our results showed that baicalin significantly decreased the body weight loss, the serum levels of TNFα,  IL-6, and LDH, and the caecum bacterial burdens of mice challenged with S. typhimurium. Histological examination showed that baicalin decreased the lesion in the caecum of S. typhimurium-infected mice. MICs and MBCs of baicalin, and oroxylin A. against S. typhimurium were > 128 µg/ml. MICs and MBCs of baicalein against S. typhimurium were 64 µg/ml, and > 128 µg/ml, respectively. Pretreatment of Caco-2 cells or S. typhimurium with baicalin, baicalein, and oroxylin A significantly inhibited the invasion of Caco-2 cells by S. typhimurium in a dose-dependent manner. Sub-MICs of baicalin, baicalein, and oroxylin A also significantly decreased the levels of TNFα, nitrate, and LDH from S. typhimurium-infected Caco-2 cells. Moreover, the transcription levels of sopB, sopE, and sopE2 were significantly suppressed by baicalin, baicalein, and oroxylin A.Conclusions: These results demonstrated that baicalin is a promising agent for the prevention of S. typhimurium infection via the modulation of both bacterial virulence and host response. [ABSTRACT FROM AUTHOR]

Commercial milk products worldwide come not only from cows, but also from goats, buffaloes, camels, and yaks. Milk from non-bovine animals is important culturally and economically. Pseudomonas spp. are frequently linked to milk spoilage under storage temperatures. The objectives of this study were to identify Pseudomonas spp. isolated from goat, buffalo, camel, and yak milks, and to measure proteolytic activity of Pseudomonas spp. under different storage temperatures. Raw milk samples of goat (n = 50), buffalo (n = 25), camel (n = 25), and yak (n = 25) were collected from 5 provinces in China. Pseudomonas spp. were analyzed by Pseudomonas-specific 16S, universal 16S rRNA, and rpoB gene sequence analyses. Proteolytic activity on milk agar, quantification via the trinitrobenzenesulfonic acid assay at 2°C, 4°C, 7°C, 10°C and 25°C, as well as alkaline peptidase gene (aprX) identification were performed to ascertain the proteolytic activity of these isolates. Pseudomonas spp. were found in 46 samples out of total 125 samples. A total of 67 Pseudomonas spp. were identified. Of Pseudomonas isolates, we obtained extracellular peptidase activity in 7 (10.4%) at 2°C, 17 (25.4%) at 4°C, 24 (35.8%) at 7°C, 39 (58.2%) at 10°C, and 41 (61.2%) at 25°C. The results revealed that a wide diversity of Pseudomonas spp. were present in different non-bovine raw milks, with the ability to produce peptidases at storage temperatures. However, proteolytic activity varied widely among the peptidase-positive isolates. A majority of isolates from yak milk had high proteolytic activity. [ABSTRACT FROM AUTHOR]

Either arbuscular mycorrhizal (AM) fungi or earthworms as soil organisms promote plant growth, while their interaction on nitrogen (N) content in plants, soil, and glomalin-related soil protein (GRSP) is not known. In this study, an AM fungus (Funneliformis mosseae) and an earthworm (Pheretima guillelmi), either in single or in combination, were introduced into soil growing white clover to analyze their effects on plant growth, chlorophyll, soluble protein, N contents in leaves, roots, GRSP, and soil, and the contribution of N in purified GRSP to soil total N. The four-week introduction of earthworms significantly increased root mycorrhizal colonization rate, and accelerated an improved AM effect on chlorophyll and plant growth. The single introduction of earthworms significantly increased root N and soil total N contents, while the single introduction of AM fungi distinctly elevated N contents in leaves, roots, easily extractable GRSP, and soil (nitrate N and total N). The N in total GRSP was 5.78–7.70 mg g−1, accounting for 3.46 %–5.45 % of the soil total N, of which the contribution of N from easily extractable GRSP and difficult-to-extract GRSP was 1.84 %–3.07 % and 1.34 %–2.39 %, respectively. AM fungi, but not earthworms, significantly increased the contribution of N in GRSP to soil total N, and the introduction of earthworms further accelerated the increased effect of mycorrhizas on the contribution of N in easily extractable and total GRSP to soil total N. These results demonstrated that the introduction of earthworms into mycorrhizosphere can facilitate N storage in GRSP and thus a contribution to soil total N. • Effects of earthworms and AMF on N content of soil and plants were studied. • Dual earthworms and AMF addition recorded higher plant growth and chlorophyll than single addition. • Earthworms increased root N and soil total N, while AMF elevated N in plants, EE-GRSP, and soil NO 3 −−N and total N. • Dual addition recorded higher N contents in GRSPs than single addition. • Earthworm accelerated the AMF effect on the contribution of N in EE-GRSP and T-GRSP to soil total N. [ABSTRACT FROM AUTHOR]

Electrical status epilepticus during sleep (ESES) is an epileptic syndrome in which neurons in the brain continue to discharge during the sleep phase and is common in mid-childhood. Affected patients often experience a decline in cognition, learning ability, memory, and expressive language skills. Therefore, timely and accurate diagnosis can effectively protect the health of a patient. Currently, the identification and analysis of ESES activities mainly rely on manual detection or traditional matching learning algorithms, such as morphology and template matching. These algorithms are time-consuming or have low accuracy. Therefore, in this paper, we propose a graph convolutional neural network that can automatically and accurately identify ESES activity from non-ESES activity. We divide the whole EEG signal into small segments, each of which covers one second of the EEG data. Then, we construct a graph according to each segment of the EEG data and train a graph convolutional neural network to classify the graph into two categories: ESES or non-ESES. Compared with other state-of-the-art algorithms, for the proposed algorithm, the accuracy, F1-Score, Area Under Curve(AUC) and sensitivity reaches 91.2%, 95.0%, 96.5%, and 91.3%, respectively, and outperforms the other algorithms. [ABSTRACT FROM AUTHOR]

Reaction mechanisms between ozone and extracellular polymeric substances (EPS) can be the key of understanding the improvements in microbial aggregates properties by low-concentration ozonation. In this study, EPS are extracted from activated sludge and treated continuously by ozone gas at 270 ± 41 ppm. The reaction between ozone and EPS was investigated by observation of EPS component concentrations, functional groups and molecular weight distributions using UV–Vis spectrometry, excitation-emission matrix fluorescence spectroscopy (EEM), high performance size-exclusion chromatography (HPSEC) and gas chromatography-mass spectrometry (GC–MS). In a 12-hour-ozonation experiment, significant ozone consumption was observed in the first 4 h and protein concentration in EPS solution was reduced by 30 ± 12%. However, the polysaccharides concentration only had a slightly decrease at the end of the ozonation process. UV–Vis spectra and EEM spectra results suggest that ozone removed protein and fluorescent matters (SMP and tryptophan-like aromatic protein) rapidly by attacking specific amino acid residues on polypeptide chain. After ozonation, the molecular weight of polysaccharide and protein dropped by 4 orders of magnitude according to HPSEC results. TOC concentration of EPS solution was reduced by 13 ± 2% after ozonation. The loss in TOC could be explained by the observation of volatile organic compounds such as carboxylic acids, aldehydes and ketones in the off-gas detected by GC–MS. The results in this study can provide a better understanding towards the mechanisms of improvements in activated sludge properties by ozonation. [ABSTRACT FROM AUTHOR]

Juxtanuclear aggresomes form in cells when levels of aggregation- prone proteins exceed the capacity of the proteasome to degrade them. It is widely believed that aggresomes have a protective function, sequestering potentially damaging aggregates until these can be removed by autophagy. However, most in-cell studies have been carried out over a few days at most, and there is little information on the long term effects of aggresomes. To examine these long term effects, we created inducible, singlecopy cell lines that expressed aggregation-prone polyglutamine proteins over several months. We present evidence that, as perinuclear aggresomes accumulate, they are associated with abnormal nuclear morphology and DNA double-strand breaks, resulting in cell cycle arrest via the phosphorylated p53 (Ser-15)- dependent pathway. Further analysis reveals that aggresomes can have a detrimental effect on mitosis by steric interference with chromosome alignment, centrosome positioning, and spindle formation. The incidence of apoptosis also increased in aggresome-containing cells. These severe defects developed gradually after juxtanuclear aggresome formation and were not associated with small cytoplasmic aggregates alone. Thus, our findings demonstrate that, in dividing cells, aggresomes are detrimental over the long term, rather than protective. This suggests a novel mechanism for polyglutamine-associated developmental and cell biological abnormalities, particularly those with early onset and non-neuronal pathologies. [ABSTRACT FROM AUTHOR]

Earthworms and arbuscular mycorrhizal fungi (AMF) are beneficial organisms in the soil and play an important role in improving soil fertility and plant growth. The objective of this study was to analyze the response of single versus dual inoculation of earthworms (Pheretima guillelmi) and AMF (Funneliformis mosseae) on mycorrhizal growth, root morphology, and rhizosphere properties of white clover (Trifolium repens). Addition of earthworms significantly increased the degree of root AMF colonization, while decreased hyphal length and spore number in the soil. Single or dual inoculation of F. mosseae and P. guillelmi significantly increased root traits (total length, area, volume, and average diameter), soil phosphatase activities (acid, neutral, and alkaline), easily extractable and total glomalin-related soil protein content, the percentage of soil water-stable aggregates at the size of 2–4 mm, 1–2 mm and 0.5–1 mm, aggregate stability, Bray-P, and soil organic carbon (SOC) contents. Among them, the dual inoculation further amplified the effect on glomalin production, phosphatase activity, and aggregate stability, but did not show a superposition effect on root improvement, Bray-P, and SOC. Our study, hence, suggested that AMF and earthworms have synergistic roles in elevating rhizosphere properties vis-à-vis agronomic responses of white clover. • Effects of earthworm-AMF (singly and in combination) on rhizosphere environment and crop response were studied. • Earthworms increased root AMF colonization, but reduced hyphae and spores in soils. • AMF or earthworms singly improved root traits, Bray-P, and soil organic carbon contents, but dual application of AMF and earthworms did not show a major effect than single application. • Single AMF or earthworms increased aggregation, phosphatase, GRSP, and dual addition amplified these responses. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dietary fructose promotes diethylnitrosamine-induced liver tumor initiation. • Excessive dietary fructose induces steatotic hepatitis. • Dietary fructose promotes the hepatic progenitor cell proliferation. • Fructose enhances the tumor initiating capability of hepatic progenitor cells. • Dietary fructose promotes the malignant transformation of hepatic progenitor cells. The incidence of nonalcoholic fatty liver disease (NAFLD)-associated liver cancer is rising particularly in western societies. Dietary fructose has been increasingly reported as a significant contributor for the onset of NAFLD. However, the association between a high-fructose diet and liver cancer incidence is not fully understood. In this study, we investigated the effect of dietary fructose on liver tumorigenesis. In a mouse model of diethylnitrosamine (DEN)-induced liver tumor initiation, high-fructose diet was found to significantly increased hepatic lipid deposition and expression of inflammatory cytokines in mouse livers. Besides, DEN administration induced the malignant transformation of hepatic progenitor cells (HPCs) into malignant tumor initiating cells, while DEN + Fructose mice had significantly enriched HPCs with enhanced proliferation, invasion, chemoresistance, and tumorigenic capabilities. This study for the first time demonstrates that fructose promotes liver carcinogenesis via increasing tumorigenic HPCs and inflammatory microenvironment, which warrants precautionary control of the excessive intake of dietary fructose. [ABSTRACT FROM AUTHOR]

Occupying an area of about 1,020,000 km2 with the sparse vegetation and the Taklimakan Desert(TD), The Tarim Basin (TB) is isolated by the surrounding mountains and plateaus, especially to the north of the Tibetan Plateau (TP) with a large drop in elevation. An intense dust storm occurring over TB, Northwest China from April 27 to May 1, 2015 was simulated by using the Weather Research and Forecasting model with chemistry (WRF-Chem v3.8.1). The sources of dust emissions were centered over the northeastern TB with the high dust emission flux reaching 24μgm−2 s−1 injected by strong near-surface northeasterly winds from basin mouth invading the TD. A large amount of dust aerosols accumulated in the windward northern slope of the TP. Dry deposition is the dominant removal process of dust aerosols from the atmosphere over the arid TB. The spatial distribution of dust dry deposition in the TB was similar to the columnar dust loading pattern during this dust storm event. With the impacts of the TB deep terrain structures on atmospheric circulation, the high column loading of dust aerosols was concentrated over the southeastern TB, where dust aerosols mainly accumulated at the lower troposphere below 3000 m. Once dust aerosols were lifted at a high elevation (>3500 m), they were exported from the TB driven by the westerlies in the free troposphere, and the zonal transport flux of dust aerosols (>3000 μgm−2 s−1) peaked at an elevation of approximately 4000 m along 41° N over the TB. The eastern border of TB was found to be the largest contributors to dust export from the TB. It was estimated for this intense dust storm that among the dust aerosols emitted from the dust emission sources over the TD, about 22.28% of dust aerosols were relatively inefficiently exported for the downwind dust regional transport from the TB compared to about 27.17% dust aerosols deposited on the basin surface, and a high fraction of about 50.54% dust aerosols suspending in the atmosphere over the TB, implying a significant implication of dust aerosols from the TD for climate and environment over the central Asian region. The Taklimakan Desert (TD) is located in the Tarim Basin (TB) isolated by the surrounding mountains and plateaus with the only an open in the northeastern TB edge. The effect of topography especially the Tibetan Plateau on dust aerosol distribution over the TB. Once dust aerosols were lifted at a high elevation (>3500 m), they were exported from the TB driven by the westerlies in the free troposphere, and the zonal transport flux of dust aerosols (>3000 μgm−2 s−1) peaked at an elevation of approximately 4000 m along 41° N over the TB. The eastern border of TB was found to be the largest contributor to dust export from the TB. The high fraction of 50.54% dust aerosols suspending in the atmosphere over the TB potentially exerted a large impact on regional changes of climate and environment over the TB for this dust storm event. Unlabelled Image • A strong effect of the Tibetan Plateau on the dust aerosol distribution over the Tarim Basin. • The zonal transport flux of dust aerosols peaked at an elevation of approximately 4000 m over the Tarim Basin. • The eastern border of Tarim Basin was found to be largest contributor to the downwind regional transport of dust aerosols. • A high fraction of about 50.54% dust aerosols suspending in the atmosphere over the Tarim Basin. [ABSTRACT FROM AUTHOR]

Escherichia coli has been frequently reported as a major foodborne bacterium contaminating raw milk or pasteurized milk. Therefore, the aim of this study was to explore a quantitative real-time PCR (qPCR) technique combined with sodium dodecyl sulfate (SDS) and propidium monoazide (PMA) to detect culturable E. coli in milk. An internal amplification control was also added into this reaction system as an indicator of false-negative results. The inclusivity and exclusivity of the primers were tested using DNA from 7 E. coli and 14 other bacterial strains. The concentrations of SDS and PMA were determined according to plate counts and quantitative cycle values of qPCR, respectively. A standard curve was established using series diluted E. coli DNA. The reliability and specificity of this method were further determined by the detection of E. coli in spiked milk. The results showed that the optimal concentrations of SDS and PMA were 100 µg/mL and 40 μ M , respectively. A standard curve with a good linear relationship (coefficient of determination = 0.997; amplification efficiency = 100.5%) was obtained. Compared with conventional PCR and PMA-qPCR, the SDS-PMA-qPCR assay was more specific and sensitive in culturable E. coli detection. Therefore, we evaluated and improved the SDS-PMA-qPCR method for detecting culturable E. coli in milk. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common degenerative disease among the elderly population. In addition to cognitive impairment, AD is often accompanied by behavioral manifestations. However, little attention has been paid to changes in bone metabolism and related mechanisms in patients with AD. We found that AD mice (APPswe/PS1dE9) had reduced bone density, weakened bone strength, and amyloid beta (Aβ) deposition in the bone tissue. It was further found that targeting autophagy receptors Optineurin (OPTN) and Sequestosome 1 (SQSTM1) increased bone density and bone strength in AD mice, promoted the clearance of Aβ in the bone tissue, and maintained bone homeostasis. Our study suggests that abnormal Aβ deposition may be the co-pathogenesis of AD and osteoporosis (OP). Targeting OPTN and SQSTM1 has a dual-functional effect of alleviating both AD and OP through selective autophagy that specifically targets Aβ for clearance. Therapeutic strategies targeting autophagy may help guide the treatment of patients with AD complicated with OP. • Alzheimer's disease is often accompanied by behavioral manifestations. • Aβ deposition may be the co-pathogenesis of Alzheimer's disease and osteoporosis. • Selective autophagy contributes to the clearance of abnormally deposited Aβ. • Targeting autophagy is beneficial for Alzheimer's disease and osteoporosis. [ABSTRACT FROM AUTHOR]

Conventional quantitative PCR (qPCR) are unable to differentiate DNA of viable Staphylococcus aureus cells from dead ones. The aim of this study was to use sodium dodecyl sulfate (SDS) and propidium monoazide (PMA) coupled with lysostaphin to detect viable Staph. aureus. The cell suspensions were treated with SDS and PMA before DNA extraction. The SDS is an anionic surfactant, which can increase the permeability of dead cells to PMA without compromising the viability of live cells. The lysostaphin was applied to improve the effectiveness of DNA extraction. The reliability and specificity of this method were further determined by the detection of Staph. aureus in spiked milk. The results showed that there were significant differences between the SDS-PMA-qPCR and qPCR when a final concentration of 200 μg/mL of lysostaphin was added in DNA extraction. The viable Staph. aureus could be effectively detected when SDS and PMA concentrations were 100 µg/mL and 40 μM, respectively. Compared with conventional qPCR, the SDS-PMA-qPCR assay coupled with lysostaphin was more specific and sensitive. Therefore, this method could accurately detect the number of viable Staph. aureus cells. [ABSTRACT FROM AUTHOR]

The cell wall lipids phthiocerol dimycocerosates (PDIMs) and its structurally-related compound, phenolic glycolipids (PGLs) are major virulence factors of mycobacterium, as shown by the reduced growth of PDIMs/PGLs deficient mutants in various animal models. PDIMs/PGLs play active roles in modulating host immune responses. However, the cellular and molecular mechanisms of how PDIMs/PGLs deficient mutant was eliminated in vivo are still elusive. Our aim was to investigate what host immune responses have effect on mycobacterium elimination in vivo. Using microarray, we find PDIMs/PGLs modulate divergent host responses, including chemotaxis and focal adhesion's downstream pathway and apoptosis. We examine these two host responses by Diff-Quik stain, coupled with transmission electron microscopy and TUNEL stain respectively. The ultrastructure observation showed that eosinophils appeared in WT-infected zebrafish at day 1, however eosinophils arrived was delayed to day 7 in PDIMs/PGLs-deficient mutant-infected animals. More intriguingly, apoptosis was markedly increased in PDIMs/PGLs-mutant infected zebrafish at day 1 after infection, compared to WT-infected fishes at this time. However, apoptosis trend was fully reversed by day 7, with increased apoptosis were detected in WT-infected zebrafish compared with the PDIMs/PGLs-deficient mutant, especially more apoptosis within the granuloma. This study shows that the anti-apoptotic effects of PDIMs/PGLs and the recruitment of eosinophils in tissue during the early infection in zebrafish might promote bacterium growth in vivo. [ABSTRACT FROM AUTHOR]

The vertical distribution and transport properties of dust aerosols play a key role in regional and even global climate and environmental changes. However, there are still gaps in understanding the optical properties, transport mechanisms, and topographic effects on dust in the dust-prone area-southern margin of the Tarim Basin. In this study, we use the Ground-Based Aerosol Lidar (GBQL-01) installed in Hotan and Minfeng in cooperation with the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) to synthesize and analyze the dust formation process at the southern margin of the basin once, and to test the reliability of the ground-based aerosol lidar. The variability characteristics of meteorological elements during this dust process will be discussed. Furthermore, the Weather Research and Forecasting Model with Chemistry (WRF-Chem) was used to reproduce this dust process. The results show that the vertical transport of dust particles reaches about 4 km and 3 km in Hotan and Minfeng, respectively, and the dust aerosol stratification intensity is obvious within 1 km height in both places, and there is a dust aerosol layer at 3 km height in both places. The high winds are blocked by the large topography of the Tianshan Mountains and the northern slopes of the Tibet Plateau, and they change to northeasterly winds, triggering dusty weather outbreaks at the southern margin of the Tarim Basin. When the dusty weather subsided, dust aerosols with concentrations of 300–400 μg m−3 were still present at an altitude of 4 km, and a clear suspended dust phenomenon was formed. Meanwhile, the increase of wind speed and relative humidity, as well as the decrease of temperature, easily contribute to the occurrence of dusty weather and the transport of particulate matter. This work provides a useful reference for the study of regional climate change, topographic effects and "suspended dust". • The evaluation of the ground-based aerosol lidar's performance was conducted in an integrated manner using CALIPSO and particulate matter data. This assessment is essential for future studies. • Data on the height of dust stratification in the southern margin of the Tarim Basin (Hotan and Minfeng) was collected, confirming the presence of a stable aerosol layer at an altitude of 3 km. • The analysis using the WRF-Chem model clearly demonstrates the influence of topographic effects on dust aerosols. Additionally, this study confirms the occurrence of a unique phenomenon known as "suspended dust.". [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and a-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in a-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates a-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect a-synuclein pathology. We further demonstrate that similar mechanisms are involved in amyloid-b 1-42 (Ab42) aggregation. Our results suggest that, in addition to other protein quality control pathways, such as the ubiq proteasome system, mitochondria per se can influence protein homeostasis of cytosolic aggregation-prone proteins. We propose that approaches that seek to maintain mitochondrial fitness, rather than target downstream mitochondrial dysfunction, may aid in the search for therapeutic strategies to manage PD and related neuropathologies. [ABSTRACT FROM AUTHOR]

Poor eating habits, especially high-fat and -glucose diets intake, can lead to endoplasmic reticulum (ER) stress in islet β-cells, insulin resistance, and islet β-cell dysfunction and cause islet β-cell apoptosis, which leads to type 2 diabetes mellitus (T2DM). Taurine is a crucial amino acid in the human body. In this study, we aimed to explore the mechanism through which taurine reduces glycolipid toxicity. INS-1 islet β-cell lines were cultured with a high concentration of fat and glucose. SD rats were fed a high-fat and -glucose diet. MTS, Transmission electron microscopy, Flow cytometry, Hematoxylin-eosin, TUNEL, Western blotting analysis and other methods were used to detect relevant indicators. The research found that taurine increases the cell activity, reduces the apoptosis rate, alleviates the structural changes of ER under high-fat and -glucose exposure models. In addition, taurine improves blood lipid content and islets pathological changes, regulates the relative protein expression in ER stress and apoptosis, increases the insulin sensitivity index (HOMA-IS), and reduces the insulin resistance index (HOMAC-IR) of SD rats fed with a high-fat and -glucose diet. • Taurine can prevent T2DM caused by excessive high-fat and -glucose diets. • Apoptosis induced by HFHG diets are alleviated by taurine through inhibiting ER stress signalling pathway in islet β-cells. • Taurine can reduce the weight gain, blood sugar and insulin resistance caused by glycolipid toxicity. [ABSTRACT FROM AUTHOR]

Context: Chronic pain affects approximately 100 million Americans, but little is known about the factors associated with pain frequency.Objectives: This article examines participants' sociodemographics, medical history, health care access and utilization, self-management barriers, and social support associated with pain frequency among a sample of middle-aged and older adults with one or more chronic condition.Methods: Data were from the National Council on Aging Chronic Care Survey. An ordinal regression model was fitted to examine factors associated with self-reported pain frequency.Results: Having more chronic conditions (P < 0.001), taking more medication daily (P < 0.001), and visiting the physician five or more times a year (P = 0.011) were associated with more frequent pain. Always getting the help and support needed to manage their health problems was associated with less frequent pain (P < 0.001).Conclusion: More attention should be given to pain management during interactions with health care providers. Providing resources and support for disease self-management may help reduce pain frequency and self-management in middle-aged and older adults with chronic conditions. [ABSTRACT FROM AUTHOR]

Psoriasis is a type of chronic autoimmune-mediated inflammatory skin condition in which clinical manifestations are characterized by erythema and scaly changes, with complex pathogenesis and ease of relapse, and it is difficult to cure. Lenalidomide (Len) is a structural analog of thalidomide, which belongs to the second generation of immunomodulators and has the functions of tumor killing, immune regulation, anti-angiogenesis and regulation of the myeloma microenvironment. In the current experiment, we investigated the therapeutic effect of transdermal application of Len on the pathological changes of imiquimod (IMQ)-induced skin irritations and inflammation in psoriatic-like mice. The in vivo results revealed that Len nanoemulsion-based gels markedly reduced the IMQ-induced Psoriasis Area Severity Index (PASI) score, spleen-to-body weight index and CD4 protein expression in the derma of mice and improved IMQ-induced skin inflammatory cell infiltration. Transcriptome sequencing was intended to obtain the differentially expressed genes among the skin of Con mice and the skin of IMQ mice, and then, the GO enrichment classification and KEGG pathway analysis of the significant genes was executed to obtain major signaling pathways in the pathogenesis of the psoriasis mouse model. It was found that the PI3K/AKT signaling pathway was a major pathway in the pathogenesis of psoriasis in a mouse model induced by IMQ. The immunohistochemical results confirmed that Len could modulate the protein expression of AKT and NF-κB in skin. In conclusion, the protective effect of transdermal administration of Len may be related to the inhibition of the PI3K/AKT signaling pathway and its downstream NF-κB pathway against IMQ-induced psoriasis in mice. [Display omitted] • The network pharmacology is applied to predict the therapeutic effect of Len on psoriasis. • Transcriptomic is applied to analyse the differentially expressed genes between Con group and IMQ group. • The Len nanoemulsion-based gels were first prepared and it is effective for the psoriasis treatment. [ABSTRACT FROM AUTHOR]

The vertical distributions of sand-dust aerosols (SDAs) over the Taklimakan Desert (TD; 37°N–41°N, 78°E−88°E) that occurred during the spring are essential for both long-range transport and climate effects, apart from the living environment and health. In this study, we investigated the optical properties of SDAs and evaluated the correlation between optical properties and meteorological factors over the TD area located in the northwest of China. For this, we have utilized the A-train multiple-satellite remote sensing data provided quasi-synchronized observations by the Cloud-aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), CloudSat, and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments for the study period during 2007–2010. Besides, we have verified the meteorological factors observed from the CALIPSO to know the applicability and reliability with the Radiosonde sounding data. We found that the cloud–aerosol discrimination (CAD) algorithm can accurately identify clouds and SDAs over the TD area, especially during blowing dust/floating dust (BD/FD). Overall, it is revealed that the total depolarization ratio of SDAs is below 0.5. Besides, the temperature (T) and pressure (P) of CALIPSO satellite products data are in excellent agreement with the radiosonde sounding measured data over the TD area. Further, most data points during the DS (BD/FD) event spread towards lower (higher) relative humidity (RH) ranged between 0.0386 and 0.6306 (0.1079 and 1.00). Our analysis provides the observational evidence from the CALIOP that the optical properties of vertical dust particles and meteorological elements over the TD have distinct variability below and above 4 km height for DS and BD/FD events. The results obtained will provide not only reliable reference values for the improvement of the CAD algorithm used in the CALIPSO but also provide critical information for model evaluation and enhancement of CALIPSO products. Image 1 • We have investigated the optical properties of sand dust aerosols (SDAs) over the Taklimakan Desert from radiosonde and A-train satellite datasets. • We have evaluated the correlation between SDAs and meteorological factors during spring. • The meteorological factors observed from the CALIPSO are verified using the radiosonde data. [ABSTRACT FROM AUTHOR]