Plasma and milk metabolomics profiles in dairy cows with subclinical and clinical ketosis.

Ketosis, a commonly observed energy metabolism disorder in dairy cows during the peripartal period, is distinguished by increased concentrations of ß-hydroxybutyrate (BHB) in blood. This condition has a negative impact on milk production and quality, causing financial losses. An untargeted metabolomics approach was performed on plasma samples from cows between 5 and 7 DIM diagnosed as controls (CON, BHB <1.2 mM, n = 30), subclinically ketotic (SCK, 1.2 < BHB <3.0 mM, n = 30), or clinically ketotic (CK, BHB >3.0 mM, n = 30). Cows were selected from a commercial farm of 214 Holstein cows (average 305-d yield in the previous lactation of 35.42 ± 7.23 kg/d; parity, 2.41 ± 1.12; body condition score, 3.1 ± 0.45). All plasma and milk samples (n = 90) were subjected to Liquid Chromatography-Mass Spectrometry (LC-MS)-based metabolomic analysis. Statistical analyses was performed using the Graph Pad Prism 8.0, MetaboAnalyst 4.0 and R packages (version 4.1.3). Compared with the CON group, both SCK and CK groups had greater milk fat, freezing point, and fat-to-protein ratio and lower milk protein, lactose, solids-nonfat, and milk density. Within 21 d after calving, compared with CON, the SCK group experienced a reduction of 2.65 kg/d in milk yield, while the CK group experienced a decrease of 7.7 kg/d. Untargeted metabolomics analysis facilitated the annotation of a total of 5,259 and 8,423 metabolites in plasma and milk. Differentially affected metabolites were screened in CON vs. SCK, CON vs. CK, and SCK vs. CK (unpaired t-test, False discovery rate <0.05; and absolute value of log(2)-fold change >1.5). A total of 1,544 and 1,888 differentially affected metabolites were detected in plasma and milk. In plasma, glycerophospholipid metabolism, pyrimidine metabolism, tryptophan metabolism, sphingolipid metabolism, amino sugar and nucleotide sugar metabolism, phenylalanine metabolism, steroid hormone biosynthesis were identified as significant pathways. Weighted gene co-expression network analysis (WGCNA) indicated that tryptophan metabolism is a key pathway associated with the occurrence and development of ketosis. Increases in 5-Hydroxytryptophan and decreases in kynurenine and 3-indoleacetic acid in SCK and CK were suggestive of an impact at the gut level. The decrease of most glycerophospholipids indicated that ketosis is associated with disordered lipid metabolism. For milk, pyrimidine metabolism, purine metabolism, pantothenate and CoA biosynthesis, amino sugar and nucleotide sugar metabolism, nicotinate and nicotinamide metabolism, sphingolipid metabolism, fatty acid degradation were identified as significant pathways. The WGCNA indicated that purine and pyrimidine metabolism in plasma was highly correlated with milk yield during the peripartal period. Alterations in purine and pyrimidine metabolism characterized ketosis, with lower levels of these metabolites in both milk and blood underscoring reduced efficiency in nitrogen metabolism. Our results may help to establish a foundation for future research investigating mechanisms responsible for the occurrence and development of ketosis in peripartal cows.

Fabrication and Characterization of a Lead-Free Cesium Bismuth Iodide Perovskite through Antisolvent-Assisted Crystallization.

Cesium bismuth iodide perovskite material offers good stability toward ambient conditions and has potential optoelectronic characteristics. However, wide bandgap, absorber surface roughness, and poor surface coverage with pinholes are among the key impediments to its adoption as a photovoltaic absorber material. Herein, bandgap modification and the tailoring of surface morphology have been performed through molar ratio variation and antisolvent treatment, whereby type III antisolvent (toluene) based on Hansen space has been utilized. XRD and Raman spectroscopy analyses confirm the formation of a 0D/2D mixed dimensional structure with improved optoelectronic properties when the molar ratio of CsI/BiI3 was adjusted from 1.5:1 to 1:1.5. The absorption results and Tauc plot determination show that the fabricated film has a lower bandgap of 1.80 eV. TRPL analysis reveals that the film possesses a very low charge carrier lifetime of 0.94 ns, suggesting deep defects. Toluene improves the charge carrier lifetime to 1.89 ns. The average grain size also increases from 323.26 nm to 444.3 nm upon toluene addition. Additionally, the inclusion of toluene results in a modest improvement in PCE, from 0.23% to 0.33%.

Anti-Solvent-Free Fabrication of Stable FA0.9Cs0.1PbI3 Perovskite Solar Cells with Efficiency Exceeding 24.0% through a Naphthalene-Based Passivator.

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

Genetic variations in ZmEREB179 are associated with waterlogging tolerance in maize.

Maize (Zea mays) is highly susceptible to waterlogging stress, which reduces both the yield and quality of this important crop. However, the molecular mechanism governing waterlogging tolerance is poorly understood. In this study, we identify a waterlogging- and ethylene-inducible gene ZmEREB179 that encodes an ethylene responsive factor (ERF) localized in the nucleus. Overexpression of ZmEREB179 in maize increases the sensitivity to waterlogging stress. Conversely, the zmereb179 knockout mutants are more tolerant to waterlogging, suggesting that ZmEREB179 functions as a negative regulator of waterlogging tolerance. A transcriptome analysis of the ZmEREB179-overexpressing plants reveals that the ERF-type transcription factor modulates the expression of various stress-related genes, including ZmEREB180. We find that ZmEREB179 directly targets the ZmEREB180 promoter and represses its expression. Notably, the analysis of a panel of 220 maize inbred lines reveals that genetic variations in the ZmEREB179 promoter (Hap2) are significantly associated with waterlogging resistance. The functional association of Hap2 with waterlogging resistance is tightly co-segretated in two F2 segregating populations, highlighting its potential applications in breeding programs. Our findings shed light on the involvement of the transcriptional cascade of ERFs in regulating plant waterlogging tolerance.

Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells.

BACKGROUND: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent. RESULTS: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR. CONCLUSIONS: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.

Exploring Aeromonas dhakensis in Aldabra giant tortoises: a debut report and genetic characterization.

Aeromonas dhakensis (A. dhakensis) is becoming an emerging pathogen worldwide, with an increasingly significant role in animals and human health. It is a ubiquitous bacteria found in terrestrial and aquatic milieus. However, there have been few reports of reptile infections. In this study, a bacterial strain isolated from a dead Aldabra giant tortoise was identified as A. dhakensis HN-1 through clinical observation, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS), and gene sequencing analysis. Subsequently, to evaluate its pathogenicity, the detection of virulence genes and mice infection experiments were performed. A. dhakensis HN-1 was found to contain seven virulence genes, including alt, ela, lip, act, aerA, fla, and hlyA. Mice infected with A. dhakensis HN-1 exhibited hemorrhage of varying degrees in multiple organs. The half-maximal lethal dose (LD50) value of A. dhakensis HN-1 for mice was estimated to be 2.05 × 107 colony forming units (CFU)/mL. The antimicrobial susceptibility test revealed that A. dhakensis HN-1 was resistant to amoxicillin, penicillin, ampicillin and erythromycin. This is the first report of A. dhakensis in Aldabra giant tortoises, expanding the currently known host spectrum. Our findings emphasize the need for One Health surveillance and extensive research to reduce the spread of A. dhakensis across the environment, humans, and animals.

Trappc1 intrinsically prevents ferroptosis of naive T cells to avoid spontaneous autoinflammatory disease in mice.

T lymphocytes are pivotal in adaptive immunity. The role of the trafficking protein particle complex (TRAPPC) in regulating T-cell development and homeostasis is unknown. Using CD4cre -Trappc1flox/flox (Trappc1 cKO) mice, we found that Trappc1 deficiency in T cells significantly decreased cell number of naive T cells in the periphery, whereas thymic T-cell development in Trappc1 cKO mice was identical as WT mice. In the culture assays and mouse models with adoptive transfer of the sorted WT (CD45.1+ CD45.2+ ) and Trappc1 cKO naive T cells (CD45.2+ ) to CD45.1+ syngeneic mice, Trappc1-deficient naive T cells showed significantly reduced survival ability compared with WT cells. RNA-seq and molecular studies showed that Trappc1 deficiency in naive T cells reduced protein transport from the endoplasmic reticulum to the Golgi apparatus, enhanced unfolded protein responses, increased P53 transcription, intracellular Ca2+ , Atf4-CHOP, oxidative phosphorylation, and lipid peroxide accumulation, and subsequently led to ferroptosis. Trappc1 deficiency in naive T cells increased ferroptosis-related damage-associated molecular pattern molecules like high mobility group box 1 or lipid oxidation products like prostaglandin E2, leukotriene B4, leukotriene C4, and leukotriene D4. Functionally, the culture supernatant of Trappc1 cKO naive T cells significantly promoted neutrophils to express inflammatory cytokines like TNFα and IL-6, which was rescued by lipid peroxidation inhibitor Acetylcysteine. Importantly, Trappc1 cKO mice spontaneously developed severe autoinflammatory disease 4 weeks after birth. Thus, intrinsic expression of Trappc1 in naive T cells plays an integral role in maintaining T-cell homeostasis to avoid proinflammatory naive T-cell death-caused autoinflammatory syndrome in mice. This study highlights the importance of the TRAPPC in T-cell biology.

Basigin Deficiency Induces Spontaneous Polycystic Kidney in Mice.

BACKGROUND: Polycystic kidney disease is the most common hereditary kidney disorder with early and frequent hypertension symptoms. The mechanisms of cyst progression in polycystic kidney disease remain incompletely understood. METHODS: Bsg (basigin) heterozygous and homozygous knockout mice were generated using cas9 system, and Bsg overexpression was achieved by adeno-associated virus serotype 9 injection. Renal morphology was investigated through histological and imaging analysis. Molecular analysis was performed through transcriptomic profiling and biochemical approaches. RESULTS: Bsg-deficient mice exhibited significantly elevated arterial blood pressure. Further investigation demonstrated that Bsg deficiency triggers spontaneous cystic formation in mouse kidneys, which shares similar cyst pathological features and common transcriptional regulatory pathways with human polycystic kidney disease. Moreover, Bsg disruption promoted polycystin-1 ubiquitination and degradation, leading to activation of polycystic kidney disease associated cAMP and AMPK signaling pathways in Bsg knockout mouse kidneys. Finally, adeno-associated virus serotype 9 mediated Bsg reexpression reversed cystic progression in Bsg knockout mice in vivo, and Bsg overexpression inhibited the expansion of Madin-Darby canine kidney cysts in vitro. CONCLUSIONS: Our findings show that Bsg deficiency leads to an early-onset spontaneous polycystic kidney phenotype, suggesting that dysregulated Bsg signaling may be a contributing factor in cystogenesis.

Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.

The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections.

Strontium Attenuates LPS-Induced Inflammation via TLR4/MyD88/NF-κB Pathway in Bovine Ruminal Epithelial Cells.

Subacute ruminal acidosis (SARA) is a common nutritional metabolic disease in ruminants that causes significant economic losses to dairy farming. Strontium (Sr) is known to be involved in bone metabolism and exhibits potent anti-inflammatory effects. To evaluate the effect of Sr on inflammation in bovine ruminal epithelial cells, a model of LPS-induced inflammation was established in this study, and the cell viability of bovine ruminal epithelial cells was measured using CCK-8. The production of pro-inflammatory cytokines was measured by ELISA and real-time PCR, respectively. The related proteins of the TLR4/MyD88/NF-κB pathway were assayed through Western blotting, and the fluorescence of p-p65 and p-IκB were assayed by immunofluorescence. Molecular docking of Sr and TLR4/MyD88/NF-κB pathway-related proteins was performed using MIB2 ( http://bioinfo.cmu.edu.tw/MIB2/ ). Results showed that after treatment for 24 h, the cell viability was decreased at the high concentration of Sr (≥ 10 mmol/L). Sr significantly decreased the production of TNF-α, IL-1ß, and IL-6, downregulated the related proteins expression of the TLR4/MyD88/NF-κB pathway, and reduced the fluorescence levels of p-p65 and p-IκB. The NF-κB pathway inhibitor PDTC and molecular docking further revealed that Sr reduced LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway. These results suggest that Sr reduces LPS-induced pro-inflammatory cytokines production via the TLR4/MyD88/NF-κB pathway, thereby exerting an anti-inflammatory effect in bovine ruminal epithelial cells, providing a basis for Sr in the treatment of bovine rumen acidosis disease.

Influence of Corrosion on the Bond-Slip Behaviour between Corroded Bars and Concrete.

Pull-out tests were conducted to investigate the effects of corrosion of both the longitudinal bars and stirrups on the bond slip behaviour of reinforced concrete specimens. The main experimental variables include concrete strength (26.7 MPa, 37.7 MPa and 45.2 MPa) and expected corrosion loss (0%, 4%, 8% and 12%), with a total of 63 specimens fabricated. The results show that the relative bonding strength of specimens under different concrete strengths gradually decreases with increasing corrosion loss, but the higher the concrete strength is, the faster its degradation rate. The influence of stirrup corrosion on the peak slip can be ignored, but it will further aggravate the degradation of the bonding strength of the specimens. This reduction in bonding strength is linearly related to the stirrup corrosion loss. Based on the experimental results of this work and the achievements of other scholars, a modified relative bonding strength degradation model and a bond-slipbond-slip constitutive model of corroded reinforced concrete are presented by accounting for the influence coefficient of concrete strength. The results show that the constitutive model is in good agreement with the relevant experimental results.

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

BACKGROUND: Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients. METHODS: Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic biomarkers were measured at 3-year follow-up. We used linear and multinomial logistic regression models to test the association between cardiometabolic biomarkers and clinical trajectories and performed mediation analyzes, while adjusting for clinical and demographic confounders. RESULTS: Cognitive performance was inversely associated with increased body mass index (mean difference [ß], ßhigh = -1.24, 95% CI = -2.28 to 0.20, P = 0.02) and systolic blood pressure (ßmild = 2.74, 95% CI = 0.11 to 5.37, P = 0.04). The severity of positive symptoms was associated with increased glycated hemoglobin (HbA1c) levels (ßlow = -2.01, 95% CI = -3.21 to -0.82, P = 0.001). Increased diastolic blood pressure (ORhigh-decreased = 1.04, 95% CI = 1.01 to 1.08, P = 0.02; ORhigh-increased = 1.04, 95% CI = 1.00 to 1.08, P = 0.048) and decreased high-density lipoprotein (OR high-increased = 6.25, 95% CI = 1.81 to 21.59, P = 0.004) were associated with more severe negative symptoms. Increased HbA1c (ORmoderate = 1.05, 95% CI = 1.01 to 1.10, P = 0.024; ORhigh = 1.08, 95% CI = 1.02 to 1.14, P = 0.006) was associated with more severe positive symptoms. These associations were not mediated by antipsychotics. CONCLUSIONS: We showed an association between cardiometabolic dysregulations and clinical and cognitive symptoms in SSD patients. The observed associations underscore the need for early identification of patients at risk of cardiometabolic outcomes.

Structures, principles, and properties of metamaterial perfect absorbers.

Metamaterials are a kind of artificial material with special properties, showing huge potential for applications in fields such as infrared measurement, solar cells, optical sensors, and optical stealth. A metamaterial perfect absorber (MPA) is designed based on a metamaterial, featuring strong absorption, small volume, light weight, ultra-bandwidth, tunability and other characteristics. This paper introduces the absorption mechanism of MPAs from microwave to optical wave band, and four directions of absorber design are elaborated. Equivalent impedance matching, plasma resonance and interference effect are the main absorption mechanisms of MPA. Multiband perfect absorption, ultra-wideband and ultra-narrowband perfect absorption, polarization and angle insensitive absorption, and dynamically controllable tunable absorption are the main design aspects. Among them, the proposal of a dynamically tunable absorber realizes the dynamic absorption. Finally, the problems and challenges of metamaterial perfect absorber design are discussed.

Function and regulation of ubiquitin-like SUMO system in heart.

The small ubiquitin-related modifier (SUMOylation) system is a conserved, reversible, post-translational protein modification pathway covalently attached to the lysine residues of proteins in eukaryotic cells, and SUMOylation is catalyzed by SUMO-specific activating enzyme (E1), binding enzyme (E2) and ligase (E3). Sentrin-specific proteases (SENPs) can cleave the isopeptide bond of a SUMO conjugate and catalyze the deSUMOylation reaction. SUMOylation can regulate the activity of proteins in many important cellular processes, including transcriptional regulation, cell cycle progression, signal transduction, DNA damage repair and protein stability. Biological experiments in vivo and in vitro have confirmed the key role of the SUMO conjugation/deconjugation system in energy metabolism, Ca2+ cycle homeostasis and protein quality control in cardiomyocytes. In this review, we summarized the research progress of the SUMO conjugation/deconjugation system and SUMOylation-mediated cardiac actions based on related studies published in recent years, and highlighted the further research areas to clarify the role of the SUMO system in the heart by using emerging technologies.

MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Effects of perinatal stress on the metabolites and lipids in plasma of dairy goats.

Dairy goats experience metabolic stress during the peripartal period, and their ability to navigate this stage of lactation is related to the occurrence and development of metabolic diseases. Unlike dairy cows, there is a lack of comprehensive analysis of changes in the plasma profiles of peripartal dairy goats, particularly using high-throughput techniques. A subset of 9 clinically-healthy dairy goats were used from a cohort of 96 primiparous Guanzhong dairy goats (BCS, 2.75 ± 0.15). Blood samples were collected at seven time points around parturition (d 21, 14, 7 before parturition, the day of kidding, and d 7, 14, 21 postpartum), were analyzed using untargeted metabolomics and targeted lipidomics. The orthogonal partial least squares discriminant analysis model revealed a total of 31 differential metabolites including p-cresol sulfate, pyruvic acid, cholic acid, and oxoglutaric acid. The pathway enrichment analysis identified phenylalanine metabolism, aminoacyl-tRNA biosynthesis, and citrate cycle as the top three significantly-altered pathways. The Limma package identified a total of 123 differentially expressed lipids. Phosphatidylserine (PS), free fatty acids (FFA), and acylcarnitines (ACs) were significantly increased on the day of kidding, while diacylglycerols (DAG) and triacylglycerols (TAG) decreased. Ceramides (Cer) and lyso-phosphatidylinositols (LPI) were significantly increased during postpartum period, while PS, FFA, and ACs decreased postpartum and gradually returned to antepartum levels. Individual species of FFA and phosphatidylcholines (PC) were segregated based on the differences in the saturation and length of the carbon chain. Overall, this work generated the largest repository of the plasma lipidome and metabolome in dairy goats across the peripartal period, which contributed to our understanding of the multifaceted adaptations of transition dairy goats.

Evaluating anti-viral effect of Ivermectin on porcine epidemic diarrhea virus and analyzing the related genes and signaling pathway by RNA-seq in vitro.

Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig industry. However, there remains no effective drugs for PEDV infection. Ivermectin is an FDA-approved anthelmintic drug used to treat worm infections. In this study, we reported the broad-spectrum antiviral activity of Ivermectin in vitro. Ivermectin can inhibit PEDV infections of different genotypes. Avermectin derivatives can also inhibit PEDV infections. A time of addition assay showed that Ivermectin exhibited potent anti-PEDV activity when added simultaneously with or post virus infection. Furthermore, Ivermectin significantly inhibited the late stage of viral infection by affecting viral release. RNA sequencing indicates Ivermectin induces cell cycle arrest, which may be related to its ability to inhibit viral release. Interestingly, when combined with Niclosamide, Ivermectin demonstrated an enhanced anti-PEDV effect. These findings highlight Ivermectin as a novel antiviral agent with potential for the development of drugs against PEDV infection.

mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway.

Myeloid hematopoiesis is a finely controlled consecutive developmental process, which is essential to maintain peripheral innate immune homeostasis. Herein, we found that Rictor deletion caused the remarkable reduction of granulocyte-monocyte progenitors (GMPs), monocytes, and macrophages, while the levels of neutrophils were unaffected. Adoptive transfer of Rictor-deleted GMPs or common myeloid progenitors (CMPs) in syngeneic mice showed poor re-constitution of monocytes compared to wild-type GMPs or CMPs. In addition to decreasing the proliferation of CMPs/GMPs, Rictor deletion preferentially inhibited Ly6C+ monocyte differentiation, while enhancing neutrophil differentiation, as determined by colony formation assays. mTORC2 promotes monocyte development by downregulation of the AKT-Foxo4-activating transcription factor 5 (ATF5)-mitochondrial unfolded protein response (mtUPR) pathway. Genetic overexpression of ATF5 or exposure to ethidium bromide significantly rescued monocyte/macrophage differentiation defects of Rictor-deficient myeloid progenitors. Therefore, Rictor is required for CMP/GMP proliferation and acts as an important switch to balance monocytic and granulocytic lineage commitment in bone marrow.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Effects of Chromium Propionate and Calcium Propionate on Lactation Performance and Rumen Microbiota in Postpartum Heat-Stressed Holstein Dairy Cows.

Chromium propionate (Cr-Pro) and calcium propionate (Ca-Pro) are widely applied in dairy production, especially in the alleviation of heat stress (HS). HS can reduce the abundance of rumen microbiota and the lactation performance of dairy cows. The present work mainly focused on evaluating the effects of Cr-Pro and Ca-Pro on the performance, ruminal bacterial community, and stress of postpartum HS dairy cows as well as identifying the differences in their mechanisms. Fifteen multiparous postpartum Holstein cows with equivalent weights (694 ± 28 kg) and milk yields (41.2 ± 1.21 kg/day) were randomly divided into three groups: control (CON), Cr-Pro (CRPR), and Ca-Pro (CAPR). The control cows received the basal total mixed ration (TMR) diet, while the CRPR group received TMR with 3.13 g/day of Cr-Pro, and the CAPR group received TMR with 200 g/day of Ca-Pro. The rumen microbial 16S rRNA was sequenced using the Illumina NovaSeq platform along with the measurement of ruminal volatile fatty acids (VFAs) and milking performance. Cr-Pro and Ca-Pro improved lactation performance, increased the rumen VFA concentration, and altered the rumen microbiota of the HS dairy cows. Cr-Pro significantly improved the milk yield (p < 0.01). The richness and diversity of the microbial species significantly increased after feeding on Ca-Pro (p < 0.05). Gene function prediction revealed increased metabolic pathways and biological-synthesis-related function in the groups supplemented with Cr-Pro and Ca-Pro. Our results indicate that the application of Cr-Pro or Ca-Pro can provide relief for heat stress in dairy cows through different mechanisms, and a combination of both is recommended for optimal results in production.