Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary Crude Protein Levels Affect Milk Production,Nitrogen Utilization and Blood Hormones of Chinese Holstein Dairy Cows

This experiment was conducted to investigate the effects of dietary crude protein levels on milk production,nitrogen utilization and blood hormones of Chinese Holstein dairy cows.Eight multiparous Chinese Holstein cows were used in a replicated 4×4 Latin square design and the crude protein(CP) levels of four diets were 12.56%,13.96%,15.53% and 16.93%,respectively.Each lactating cow had 4 experimental periods and each period had a 14-d adaptation,following by a 4-d total faecal and urine collection period.Milk yield,milk composition and dry matter intake(DMI) were measured in the 4 d.Blood samples were taken in the last day of the collection period.The results showed that milk and energy-corrected milk(ECM) production of cows fed 12.56% CP diet were much lower than those of cows fed the other three diets(P0.05). Milk and ECM production of cows fed 13.96% CP diet and 16.93% CP diet were similar,and their milk production were 28.18 and 28.72 kg/d and ECM were 32.64 and 32.04 kg/d(P0.05). Milk protein percentage was improved with dietary CP content increased(P0.05),but the other milk components were not affected(P0.05). Milk nitrogen efficiency of cows fed 12.56% CP diet and 13.96% CP diet was higher than that of cows fed 15.53% CP diet and 16.93% CP diet(P0.05,P0.01). The higher dietary CP levels increased urinary nitrogen excretion,milk nitrogen secretion and nitrogen retention(P0.05,P0.01),and only 16.93% CP diet increased fecal nitrogen excretion(P0.05). The blood leptin concentration of 12.56% CP diet was highest(P0.05),and 12.56% CP diet had higher concentrations of prolactin(PRL),growth hormone(GH),insulin-like growth factor(IGF-1),glucose,non-esterified fatty acids(NEFA) and β-hydroxybutyrate(BHBA) numerically.On the contrary,the plasma urea nitrogen(PUN) concentration of 16.93% CP diet was the highest(P0.01),and the concentrations of insulin,GH were increased and the IGF-1 concentration was decreased.It is concluded that the diet containing 13.96% CP is sufficient for the milk performance,nitrogen utilization and endocrine regulation in Chinese Holstein cows producing 28 kg/d milk or 32 kg/d ECM.
Induction of IFN-β through TLR-3– and RIG-I–Mediated Signaling Pathways in Canine Respiratory Epithelial Cells Infected with H3N2 Canine Influenza Virus

Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-β in a canine respiratory epithelial cell line (KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-β induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (p < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-β significantly (p < 0.001) decreased, and the protein expression of IFN-β also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I significantly reduced IRF3 (p < 0.001) and IFN-β (p < 0.001) mRNA levels. Moreover, the protein concentration of IFN-β was significantly (p < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIGI alone. Also, the antiviral protein MX1 was only expressed in KU-CBE cells infected with CIV or treated with IFN-β or IFN-α. Thus, we speculate that IFN-β further induces MX1 expression, which might suppress CIV replication. Taken together, these data indicate that TLR3 and RIG-I synergistically induce IFN-β expression via the activation of IRF3, and the produced IFN-β further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.
Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons

Plexin-B2 deletion leads to aberrant lamination of cerebellar granule neurons (CGNs) and Purkinje cells. Although in the cerebellum Plexin-B2 is only expressed by proliferating CGN precursors in the outer external granule layer (oEGL), its function in CGN development is still elusive. Here, we used 3D imaging, in vivo electroporation and live-imaging techniques to study CGN development in novel cerebellum-specific Plxnb2 conditional knockout mice. We show that proliferating CGNs in Plxnb2 mutants not only escape the oEGL and mix with newborn postmitotic CGNs. Furthermore, motility of mitotic precursors and early postmitotic CGNs is altered. Together, this leads to the formation of ectopic patches of CGNs at the cerebellar surface and an intermingling of normally time-stamped parallel fibers in the molecular layer (ML), and aberrant arborization of Purkinje cell dendrites. There results suggest that Plexin-B2 restricts CGN motility and might have a function in cytokinesis.
Essential and toxic elements in sardines and tuna on the Colombian market

ABSTRACT The presence of metals in canned fish has been associated with adverse effects on human health. The aim of this study was to evaluate risk-based fish consumption limits based on the concentrations of eight essential elements and four elements of toxicological concern in sardines and tuna brands commercially available in the Latin American canned goods market. One brand of canned sardines and six of canned tuna were collected and evaluated by ICP-MS and direct mercury analysis. The Hg content was much higher than that previously observed in scientific literature. According to the calculated hazard quotients, all brands may present some risk in terms of this element, especially brand F in which levels up to 3.1 µg/g were measured. Sardine samples surpassed the maximum limits of Mn and As. Stricter quality control in retail chains and industries should be implemented in order to guarantee safe levels in fishery products.
Aromatase and the three little paralogs

The rapid progress of scientific knowledge is continuously built on established earlier findings. Integrating previous observations with more recent data can be challenging and occasionally well-established data is unfortunately overlooked. This may lead to unnecessary redundancy in research and, in the worst-case scenario, to misinterpretation of data. In the present contribution we would like to draw attention to such a circumstance, which has crept into several recent papers on expression and functional relevance of the porcine CYP19 gene cluster that encodes functionally distinct isoforms of aromatase cytochrome P450 (aromatase) in pigs.
Aspergillus versicolor Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes

Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated Aspergillus versicolor (3 × 105 spores), or viable A. versicolor (3 × 105 spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable A. versicolor spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory (Tnf and Il1b) and glial activity (Gdnf and Cxc3r1) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of A. versicolor exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of Drd1, Penk, and Pdyn mRNA expression was confirmed in the 4-week A. versicolor exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated A. versicolor inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to A. versicolor inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.
Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response

Significance Renal cell carcinomas (RCCs) are heterogeneous malignancies thought to arise from kidney tubular epithelial cells, and clear cell RCC is the most common entity. This study demonstrates that cell atlases generated from benign kidney and two common RCCs using single-cell RNA sequencing can predict putative cells of origin for more than 10 RCC subtypes. A focused analysis of distinct cell-type compartments reveals the potential role of tumor epithelia in promoting immune infiltration and other molecular attributes of the tumor microenvironment. Finally, an observed association between the lack of immunotherapy response and endothelial cell fraction has important clinical implications. The current study, therefore, significantly contributes toward understanding disease ontogenies and the molecular dynamics of tumor epithelia and the microenvironment. Diverse subtypes of renal cell carcinomas (RCCs) display a wide spectrum of histomorphologies, proteogenomic alterations, immune cell infiltration patterns, and clinical behavior. Delineating the cells of origin for different RCC subtypes will provide mechanistic insights into their diverse pathobiology. Here, we employed single-cell RNA sequencing (scRNA-seq) to develop benign and malignant renal cell atlases. Using a random forest model trained on this cell atlas, we predicted the putative cell of origin for more than 10 RCC subtypes. scRNA-seq also revealed several attributes of the tumor microenvironment in the most common subtype of kidney cancer, clear cell RCC (ccRCC). We elucidated an active role for tumor epithelia in promoting immune cell infiltration, potentially explaining why ccRCC responds to immune checkpoint inhibitors, despite having a low neoantigen burden. In addition, we characterized an association between high endothelial cell types and lack of response to immunotherapy in ccRCC. Taken together, these single-cell analyses of benign kidney and RCC provide insight into the putative cell of origin for RCC subtypes and highlight the important role of the tumor microenvironment in influencing ccRCC biology and response to therapy.
TC10 as an essential molecule in axon regeneration through membrane supply and microtubule stabilization

Mammalian central nervous system (CNS) neurons lose axon regenerative ability as they mature. This failure to regenerate shows a clear contrast to a remarkable potential of axon growth during embryonic development and after an injury in the peripheral nervous system (PNS) (Hilton and Bradke, 2017). The absence of regeneration in the mature CNS neurons is caused by an inhibitory influence of the environment of the injured axons and the deficit of intrinsic factors that enable regeneration in the PNS (He and Jin, 2016). In the last two decades, gene manipulation strategies and compound screening have identified several neuron-intrinsic players involved in axon regeneration (Ribas and Costa, 2017). The central players are the PTEN/mTOR pathway, which contributes to protein synthesis, and transcription factors (such as SOCS3, KLF family, and SOX11) which control the cell differentiation/de-differentiation status. In addition, cytoskeletal dynamics at growth cones and material transport in axons are essential for axon regrowth; however, it is unclear how the components that regulate these functions are modulated in injured CNS neurons. In this study, we have discussed our recent discovery of an indispensable role of TC10 in CNS and PNS axon regeneration (Koinuma et al., 2020).
PtrMYB120 functions as a positive regulator of both anthocyanin and lignin biosynthetic pathway in a hybrid poplar.

Both anthocyanins and lignins are essential secondary metabolites in plant growth and development. Their biosynthesis is metabolically interconnected and diverges in the central metabolite 4-coumaroyl CoA of the phenylpropanoid pathway. Considerable progress has been made in understanding transcriptional regulation of genes involved in lignin and anthocyanin synthesis pathways, but the concerted regulation of these pathways is not yet fully understood. Here, we functionally characterized PtrMYB120, a R2R3-MYB transcription factor from Populus trichocarpa. Overexpression of PtrMYB120 in a hybrid poplar (i.e., 35S::PtrMYB120) was associated with increased anthocyanin (i.e., cyanidin 3-O-glucoside) accumulation and upregulation of anthocyanin biosynthetic genes. However, transgenic poplars with dominant-suppression of PtrMYB120 function achieved by fusing the ERF-associated Amphiphilic Repression motif to PtrMYB120 (i.e., 35S::PtrMYB120-SRDX) had a dramatic decrease in not only anthocyanin but also Klason lignin content with downregulation of both anthocyanin and lignin biosynthetic genes. Indeed, 35S::PtrMYB120-SRDX poplars had irregularly-shaped xylem vessels with reduced S-lignin content in stems, which was proportionally related to the level of the introduced PtrMYB120-SRDX gene. Furthermore, protoplast-based transcriptional activation assay using the PtrMYB120-GR system suggested that PtrMYB120 directly regulates genes involved in both anthocyanin and lignin biosynthesis, including chalcone synthase and ferulate-5 hydroxylase. Interestingly, the saccharification efficiency of line #6 of 35S::PtrMYB120-SRDX poplars, which had slightly reduced lignin content with a normal growth phenotype, was dramatically enhanced (> 45%) by NaOH treatment. Taken together, our results suggest that PtrMYB120 functions as a positive regulator of both anthocyanin and lignin biosynthetic pathways, and can be targeted to enhance saccharification efficiency in woody perennials.
Mediational Pathways From Genetic Risk to Alcohol Use Disorder in Swedish Men and Women.

OBJECTIVE The purpose of this study was to clarify the mediational pathways from genetic risk for alcohol use disorder (AUD) to AUD itself. METHOD Using information on AUD status from first- through fourth-degree relatives obtained from national registries, we created a genetic risk score for AUD for the Swedish population. We first tested a simple mediational path model in males and females separately, with early onset externalizing psychopathology (EPP), internalizing psychopathology (IPP), and poor educational attainment (EA). We then tested a more complex model in a smaller, older sample of males that contained additional self-report measures from late adolescence. RESULTS In our basic model, the largest mediational pathway from AUD genetic risk to AUD in both sexes was via high EPP followed by low EA and high IPP. The EPP pathway was considerably stronger in males, the low EA pathway was modestly stronger in females, and the IPP pathway was identical in both sexes. Our more complex model replicated the strong externalizing pathway to AUD, showing that it connected to key downstream risk factors such as early drug and alcohol use and low resilience. CONCLUSIONS Our models concurred in showing that the strongest mediational pathway for genetic risk to AUD includes externalizing symptoms and disorders, which in turn predict further key downstream risk factors. Pathways through lower EA and IPP had smaller effects. IPP had mixed effects (partly predisposing and partly protective) on downstream risk factors. The largest sex difference was a stronger externalizing pathway to genetic risk to AUD in males than in females.
Heavy Metals (Cd, Ni and Pb) Contamination of Soils, Plants and Watersin Madina Town of Faisalabad Metropolitan and Preparation of Gis BasedMaps

Heavy metal pollution is a great threat to the environment. These metals are enters to the soil-plant environment through anthropogenic sources. A survey study was conducted to assess the heavy metals contamination of soils, plants and waters of Madina town of Faisalabad, Metropolitan area in 2010. Soil, plant and water samples were collected in the vicinity of Faisalabad following 4 × 4 Km grids. Soil samples were taken from 0-15 cm and 15-30 cm depths and prepared for the determination of metals (Cd, Pb and Ni). Plant samples were also taken from the same location and dried and digested in HClO4:HNO3 in the ratio of 1:3. AB-DTPA extract of soil, plants extract and water samples was analyzed on Atomic Absorption Spectrophotometer (Model Thermo S series). The results of the study showed the concentration of metals in Soils ranged from Cd (0.00-0.111 ppm), Pb (0.87-8.97 ppm) and Ni (0.017-1.72 ppm) at 0-15 cm while Cd (0.00-0.88 ppm), Pb (0.43-6.77 ppm) and Ni (0.055-0.852 ppm) at 15-30 cm respectively. Cd, Pb and Ni concentration in the plants ranged from 0.00-2.25 ppm 1.11-5.29 ppm and 1.51-4.96 respectively. Concentration of metal in the ground water ranged from Cd (0.00-0.06 ppm), Pb (0.10-11.10 ppm) and Ni (0.03-0.05). The concentration Pb and Ni was below the permissible limits while concentration of Cd in waters and plants above the permissible limits. Finally it was concluded that soil, plant and water of Madina town were in the safe limits with respect to metals. The use of city effluent is increasing the level of metals into the soils that ultimately contaminate the soils, plants and waters. So, it is suggested that city effluent must be treated for the detoxification of metals before use in irrigation purposes for crops.
Optogenetic modulation of cardiac action potential properties may prevent arrhythmogenesis in short and long QT syndromes

Abnormal action potential (AP) properties, as occurs in long or short QT syndromes (LQTS and SQTS, respectively), can cause life-threatening arrhythmias. Optogenetics strategies, utilizing light-sensitive proteins, have emerged as experimental platforms for cardiac pacing, resynchronization, and defibrillation. We tested the hypothesis that similar optogenetic tools can modulate the cardiomyocyte’s AP properties, as a potentially novel antiarrhythmic strategy. Healthy control and LQTS/SQTS patient–specific human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) were transduced to express the light-sensitive cationic channel channelrhodopsin-2 (ChR2) or the anionic-selective opsin, ACR2. Detailed patch-clamp, confocal-microscopy, and optical mapping studies evaluated the ability of spatiotemporally defined optogenetic protocols to modulate AP properties and prevent arrhythmogenesis in the hiPSC-CMs cell/tissue models. Depending on illumination timing, light-induced ChR2 activation induced robust prolongation or mild shortening of AP duration (APD), while ACR2 activation allowed effective APD shortening. Fine-tuning these approaches allowed for the normalization of pathological AP properties and suppression of arrhythmogenicity in the LQTS/SQTS hiPSC-CM cellular models. We next established a SQTS–hiPSC-CMs–based tissue model of reentrant-arrhythmias using optogenetic cross-field stimulation. An APD-modulating optogenetic protocol was then designed to dynamically prolong APD of the propagating wavefront, completely preventing arrhythmogenesis in this model. This work highlights the potential of optogenetics in studying repolarization abnormalities and in developing novel antiarrhythmic therapies.
Phytochemical characterisation of Phlomis linearis Boiss. & Bal and screening for anticholinesterase, antiamylase, antimicrobial, and cytotoxic properties

In the present work, essential oil and fatty acids and extracts obtained from aerial parts of Phlomis linearis Boiss. & Bal. were investigated for chemical composition and biological activities. The phytochemical analyses were conducted with gas chromatography-mass spectrometry/flame ionisation detector (GC-MS/FID) and liquid chromatography-mass spectromtetry (LC-MS/MS) techniques. The extracts and essential oil were studied for α-amylase and acetylcholinesterase activities with two different spectrophotometric methods. Antimicrobial activities of the extracts were investigated by microdilution. The extracts were evaluated in vitro for cytotoxic effects against cancer and normal cell lines by MTT assay. The essential oil (EO) contained α-pinene (12.5%) and β-caryophyllene (10.7%) as main compounds. Palmitic (26.5%) and nonadecanoic acids (26.6%) were determined as fatty acids. Phytochemical analysis of the extracts found phenolic acids, phlinosides, verbascoside, and flavonoids. The extracts and essential oil demonstrated poor α-amylase inhibitory activity. The best acetylcholinesterase inhibitory activity was obtained for diethly ether extract of P. linearis (67.2 ± 3.4%) at 10 mg /mL concentration. Ethyl acetate extract found to be effective against Staphlococcus aureus at a minimum inhibitory concentration (MIC) of 156.26 µg/mL. Diethyl ether extract of P. linearis was active on A549 cell lines with an IC50 = 316 ± 4.16 µg/mL when compared with cisplatin IC50 = 24.43 ± 0.14 µg/mL. To the best of our knowledge, the present work is the first comprehensive report on anti-acetylcholinesterase, anti-α-amylase, and antimicrobial activities, as well as cytotoxic effects of P. linearis.
Device for Controlling Stimulus Self-Application During Autonomic Nervous System Tests

Abstract Assessment of autonomic nervous system (ANS) functioning may be performed non-invasively using autonomic tests which are based on evaluation of response of cardiovascular system to the applied stimuli, such as increased air pressure during Valsalva maneuver, skeletal muscle contraction during static handgrip or deep slow breathing. The cardiovascular response depends, besides ANS reaction and test protocol, also on the way stimulus is self-applied by the test subject. We present a versatile device for controlling stimulus self-application during three ANS tests: Valsalva maneuver, static handgrip, and deep breathing. It integrates two different gauges and a pace setter for breathing into one device. The core of the device is a linear LED display which, using green, yellow, and red diodes, informs the subject about the correctness of self-application of respective stimulus. The settings of the device can be adjusted to the needs of the protocol chosen. The device can record the duration of mouth air pressure or the force produced by the subject during ANS tests, which assures correctness of the tests, thus allowing to track individual variability changes in the response to the test. The device was verified during ANS tests and its use was intuitive for patients, reducing the time needed for training before tests and decreasing the effort of the physician.
Current role of nanoparticles in the treatment of lung cancer

Background: Worldwide, lung cancer is one of the leading causes of cancer death. Nevertheless, new therapeutic agents have been developed to treat lung cancer that could change this mortality-rate. Interestingly, incredible advances have occurred in recent years in the development and application of nanotechnology in the detection, diagnosis, and treatment of lung cancer. Aim: Nanoparticles (NPs) have the ability to incorporate multiple drugs and targeting agents and therefore lead to an improved bioavailability, sustained delivery, solubility, and intestinal absorption. Relevance for patients: This review briefly summarizes the latest innovations in therapeutic nanomedicine in lung cancer with examples on magnetic, lipid, and polymer NP. Emphasis will be placed on future studies and ongoing clinical trials in this field.