ABSTRACT
Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking1,2. The molecular mechanism that underlies this temporal pattern is unclear. Here we show that the nuclear receptors REV-ERB-α and REV-ERB-ß (referred to here as 'REV-ERB') in the GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviours during regular light-dark cycles. REV-ERB regulates the rhythmic expression of genes that are involved in neurotransmission in the SCN, and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at waking leads to glucose intolerance, whereas restoration of the temporal pattern of either SCNGABA neuron firing or REV-ERB expression rescues the time-dependent glucose metabolic phenotype caused by REV-ERB depletion. In individuals with diabetes, an increased level of blood glucose after waking is a defining feature of the 'extended dawn phenomenon'3,4. Patients with type 2 diabetes with the extended dawn phenomenon exhibit a differential temporal pattern of expression of REV-ERB genes compared to patients with type 2 diabetes who do not have the extended dawn phenomenon. These findings provide mechanistic insights into how the central circadian clock regulates the diurnal rhythm of hepatic insulin sensitivity, with implications for our understanding of the extended dawn phenomenon in type 2 diabetes.
Subject(s)
Circadian Rhythm , GABAergic Neurons/physiology , Insulin Resistance , Liver/physiology , Nuclear Receptor Subfamily 1, Group D, Member 1/physiology , Animals , Blood Glucose , Circadian Clocks , Diabetes Mellitus, Type 2 , Female , Glucose/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Photoperiod , Suprachiasmatic Nucleus/cytology , Synaptic TransmissionABSTRACT
Multiple facets of global change affect the earth system interactively, with complex consequences for ecosystem functioning and stability. Simultaneous climate and biodiversity change are of particular concern, because biodiversity may contribute to ecosystem resistance and resilience and may mitigate climate change impacts. Yet, the extent and generality of how climate and biodiversity change interact remain insufficiently understood, especially for the decomposition of organic matter, a major determinant of the biosphere-atmosphere carbon feedbacks. With an inter-biome field experiment using large rainfall exclusion facilities, we tested how drought, a common prediction of climate change models for many parts of the world, and biodiversity in the decomposer system drive decomposition in forest ecosystems interactively. Decomposing leaf litter lost less carbon (C) and especially nitrogen (N) in five different forest biomes following partial rainfall exclusion compared to conditions without rainfall exclusion. An increasing complexity of the decomposer community alleviated drought effects, with full compensation when large-bodied invertebrates were present. Leaf litter mixing increased diversity effects, with increasing litter species richness, which contributed to counteracting drought effects on C and N loss, although to a much smaller degree than decomposer community complexity. Our results show at a relevant spatial scale covering distinct climate zones that both, the diversity of decomposer communities and plant litter in forest floors have a strong potential to mitigate drought effects on C and N dynamics during decomposition. Preserving biodiversity at multiple trophic levels contributes to ecosystem resistance and appears critical to maintain ecosystem processes under ongoing climate change.
Subject(s)
Droughts , Ecosystem , Biodiversity , Forests , Plant Leaves , CarbonABSTRACT
Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such as divergent selection and local recombination rate variation, can influence the formation of these genomic islands. Examination of the genomic landscapes of species pairs that are still in the early stages of speciation provides an insight into this conundrum. In this study, population genomic analyses were undertaken using a wide range of sampling and whole-genome resequencing data from 96 unrelated individuals of Kentish plover (Charadrius alexandrinus) and white-faced plover (Charadrius dealbatus). We suggest that the two species exhibit varying levels of population admixture along the Chinese coast and on the Taiwan Island. Genome-wide analyses for introgression indicate that ancient introgression had occurred in Taiwan population, and gene flow is still ongoing in mainland coastal populations. Furthermore, we identified a few genomic regions with significant levels of interspecific differentiation and local recombination suppression, which contain several genes potentially associated with disease resistance, coloration, and regulation of plumage molting and thus may be relevant to the phenotypic and ecological divergence of the two nascent species. Overall, our findings suggest that divergent selection in low recombination regions may be a main force in shaping the genomic islands in two incipient shorebird species.
Subject(s)
Genome-Wide Association Study , Genomic Islands , Humans , Genetic Speciation , Genome , Gene Flow , Recombination, Genetic , Selection, GeneticABSTRACT
A protocol for selective and efficient synthesis of symmetrical and unsymmetrical m-terphenyls is presented among aryl acetylene and DMSO in the presence of KOH and methanol. In this reaction, two molecules of aryl acetylene contribute four carbons, and DMSO, as a dual carbon donor, provides two carbons to a new aromatic ring. This protocol can be tolerated for the electron-donating or disubstituted phenylacetylenes as well as the heterocyclic acetylene derivatives.
ABSTRACT
BACKGROUND: Improving the job engagement of health professionals can effectively enhance the quality of their medical services. However, few studies have investigated whether and how perceived professional benefits affect job engagement. Based on resource conservation theory, this study explored the effect of the influence of perceived professional benefits on job engagement, and also examined the mediating role of psychological availability and the moderating role of future perceived professional benefits. METHODS: A cross-sectional study was conducted in six tertiary hospitals and seven secondary hospitals in Liu Panshui, a city in western China. A total of 1,406 valid questionnaires were obtained and analysed by using correlation analysis, hierarchical regression analysis, and bootstrap tests. RESULT: The study found a significant positive association between health professionals' perceived professional benefits and their job engagement. Additionally, psychological availability was found to mediate this relationship. Future perceived professional benefits not only positively moderate this relationship between perceived professional benefits on health professionals' psychological availability but also positively moderate the mediating role of psychological availability between perceived professional benefits and job engagement. CONCLUSION: Improving health professionals' perceived professional benefits can enhance their job engagement by increasing their psychological availability. However, for health professionals with low future perceived professional benefits, this improvement may disappear. Therefore, it is important to enhance both their current and future perceived professional benefits to improve their job engagement.
Subject(s)
Burnout, Professional , Job Satisfaction , Humans , Cross-Sectional Studies , Health Personnel/psychology , Surveys and Questionnaires , Tertiary Care CentersABSTRACT
Passenger thermal comfort in high-speed train (HST) carriages presents unique challenges due to factors such as extensive operational areas, longer travel durations, larger spaces, and higher passenger capacities. This study aims to propose a new prediction model to better understand and address thermal comfort in HST carriages. The proposed prediction model incorporates skin wettedness, vertical skin temperature difference (ΔTd), and skin temperature as parameters to predict the thermal sensation vote (TSV) of HST passengers. The experiments were conducted with 65 subjects, evenly distributed throughout the HST compartment. Thermal environmental conditions and physiological signals were measured to capture the subjects' thermal responses. The study also investigated regional and overall thermal sensations experienced by the subjects. Results revealed significant regional differences in skin temperature between upper and lower body parts. By analyzing data from 45 subjects, We analyzed the effect of 25 variables on TSV by partial least squares (PLS), from which we singled out 3 key factors. And the optimal multiple regression equation was derived to predict the TSV of HST occupants. Validation with an additional 20 subjects demonstrated a strong linear correlation (0.965) between the actual TSV and the predicted values, confirming the feasibility and accuracy of the developed prediction model. By integrating skin wettedness and ΔTd with skin temperature, the model provides a comprehensive approach to predicting thermal comfort in HST environments. This research contributes to advancing thermal comfort analysis in HST and offers valuable insights for optimizing HST system design and operation to meet passengers' comfort requirements.
Subject(s)
Air Conditioning , Skin Temperature , Humans , Air Conditioning/methods , Thermosensing/physiology , TemperatureABSTRACT
Acoustic imaging technology has the advantages of non-contact and intuitive positioning. It is suitable for the rapid positioning of defects such as the mechanical loosening, discharge, and DC bias of power equipment. However, the existing research lacks the optimization design of microphone array topology. The acoustic frequency domain characteristics of typical power equipment are elaborately sorted out. After that, the cut-off frequencies of acoustic imaging instruments are determined, to meet the needs of the full bandwidth test requirements. Through a simulation calculation, the circular array is demonstrated to be the optimal shape. And the design parameters affect the imaging performance of the array to varying degrees, indicating that it is difficult to obtain the optimal array topology by an exhaustive method. Aimed at the complex working conditions of power equipment, a topology optimization design method of an acoustic imaging array for power equipment is proposed, and the global optimal solution of microphone array topology is obtained. Compared with the original array, the imaging performance of the improved LF and HF array is promoted by 54% and 49%, respectively. Combined with the simulation analysis and laboratory test, it is verified that the improved array can not only accurately locate the single sound source but also accurately identify the main sound source from the interference of the contiguous sound source.
ABSTRACT
Heating, Ventilation, and Air Conditioning (HVAC) systems in high-speed trains (HST) are responsible for consuming approximately 70% of non-operational energy sources, yet they frequently fail to ensure provide adequate thermal comfort for the majority of passengers. Recent advancements in portable wearable sensors have opened up new possibilities for real-time detection of occupant thermal comfort status and timely feedback to the HVAC system. However, since occupant thermal comfort is subjective and cannot be directly measured, it is generally inferred from thermal environment parameters or physiological signals of occupants within the HST compartment. This paper presents a field test conducted to assess the thermal comfort of occupants within HST compartments. Leveraging physiological signals, including skin temperature, galvanic skin reaction, heart rate, and ambient temperature, we propose a Predicted Thermal Comfort (PTC) model for HST cabin occupants and establish an intelligent regulation model for the HVAC system. Nine input factors, comprising physiological signals, individual physiological characteristics, compartment seating, and ambient temperature, were formulated for the PTS model. In order to obtain an efficient and accurate PTC prediction model for HST cabin occupants, we compared the accuracy of different subsets of features trained by Machine Learning (ML) models of Random Forest, Decision Tree, Vector Machine and K-neighbourhood. We divided all the predicted feature values into four subsets, and did hyperparameter optimisation for each ML model. The HST compartment occupant PTC prediction model trained by Random Forest model obtained 90.4% Accuracy (F1 macro = 0.889). Subsequent sensitivity analyses of the best predictive models were then performed using SHapley Additive explanation (SHAP) and data-based sensitivity analysis (DSA) methods. The development of a more accurate and operationally efficient thermal comfort prediction model for HST occupants allows for precise and detailed feedback to the HVAC system. Consequently, the HVAC system can make the most appropriate and effective air supply adjustments, leading to improved satisfaction rates for HST occupant thermal comfort and the avoidance of energy wastage caused by inaccurate and untimely predictive feedback.
Subject(s)
Machine Learning , Skin Temperature , Humans , Air Conditioning/instrumentation , Air Conditioning/methods , Heart Rate , Galvanic Skin Response , Thermosensing , Temperature , MaleABSTRACT
Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.
Subject(s)
Colitis, Ulcerative , Mesalamine , Humans , Mesalamine/therapeutic use , Mesalamine/adverse effects , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Bile Acids and Salts , Biomarkers , Anti-Inflammatory Agents, Non-Steroidal/therapeutic useABSTRACT
BACKGROUND: The nuclear receptor Rev-erbα/ß, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. METHODS: We generated mouse lines with cardiac-specific Rev-erbα/ß knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) analyses, and performed dietary and pharmacological rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. RESULTS: KO mice display progressive dilated cardiomyopathy and lethal heart failure. Inducible ablation of Rev-erbα/ß in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, in particular, in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, in particular, in the dark cycle. Increasing dietary lipid or sugar supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acid availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorate cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with dilated cardiomyopathy. CONCLUSIONS: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipid supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human dilated cardiomyopathy. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and dilated cardiomyopathy.
Subject(s)
Circadian Rhythm/physiology , Myocardium/pathology , Obesity/physiopathology , Animals , Circadian Clocks , Heart Diseases , Humans , Mice , Mice, KnockoutABSTRACT
The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting-state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN-related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R2 = .34; data set 2, R2 = .15) and anxiety symptoms (data set 1, R2 = .35; data set 2, R2 = .34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI-based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms.
Subject(s)
Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/diagnostic imaging , Brain Mapping/methods , Consciousness , Cerebellum , Magnetic Resonance Imaging/methods , Arousal , Brain/diagnostic imagingABSTRACT
In-situ monitoring of refractive index changes during a liquid-solid phase transition is achieved by measurement of the transmission spectrum from a single tilted fiber Bragg grating immersed in water. Differential wavelength shifts of multiple mode resonances are used to eliminate cross-talk from temperature, throughout the phase transition, and from strains occurring after solidification. The measured sudden shift of refractive index at the phase transition is shown to be consistent with the expected difference from water to ice, in spite of the observed onset of compressive strain on the fiber by the frozen water. Beyond the obvious application to research on the dynamics of liquid-solid phase transitions, this work demonstrates the multiparameter measurement capabilities of multiresonant gratings.
ABSTRACT
Dual-atom catalysts (DACs) are promising candidates for various catalytic reactions, including electrocatalysis, chemical synthesis, and environmental remediation. However, the high-activity origin and mechanism underlying intrinsic activity enhancement remain elusive, especially for the Fenton-like reaction. Herein, we systematically compared the catalytic performance of dual-atom FeCo-N/C with its single-atom counterparts by activating peroxymonosulfate (PMS) for pollutant abatement. The unusual spin-state reconstruction on FeCo-N/C is demonstrated to effectively improve the electronic structure of Fe and Co in the d orbital and enhance the PMS activation efficiency. Accordingly, the dual-atom FeCo-N/C with an intermediate-spin state remarkably boosts the Fenton-like reaction by almost 1 order of magnitude compared with low-spin Co-N/C and high-spin Fe-N/C. Moreover, the established dual-atom-activated PMS system also exhibits excellent stability and robust resistance against harsh conditions. Combined theoretical calculations reveal that unlike unitary Co atom or Fe atom transferring electrons to the PMS molecule, the Fe atom of FeCo-N/C provides extra electrons to the neighboring Co atom and positively shifts the d band of the Co center, thereby optimizing the PMS adsorption and decomposition into a unique high-valent FeIV-O-CoIV species via a low-energy barrier pathway. This work advances a conceptually novel mechanistic understanding of the enhanced catalytic activity of DACs in Fenton-like reactions and helps to expand the application of DACs in various catalytic reactions.
Subject(s)
Electronics , Electrons , Adsorption , CatalysisABSTRACT
Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However, how AGS3 regulates the transport of Cdh1 to the plasma membrane remains undetermined. To investigate this, AGS3 was knocked out using the Cas9-sgRNA system. Both trans-Golgi network protein 46 (TGN46, also known as TGOLN2) and transmembrane p24-trafficking protein 7 (TMED7) were tracked in early mouse embryos by tagging these proteins with a fluorescent protein label. We observed that the majority of the AGS3-edited embryos were developmentally arrested and were fragmented after the four-cell stage, exhibiting decreased accumulation of Cdh1 at the membrane. The trans-Golgi network and TMED7-positive vesicles were also dispersed and were not polarized near the membrane. Additionally, increased Gαi1 (encoded by GNAI1) expression could rescue AGS3-overexpressed embryos. In conclusion, AGS3 reinforces the dynamics of the trans-Golgi network and the transport of TMED7-positive cargo containing Cdh1 to the cell-contact surface during early mouse embryo development.
Subject(s)
Guanine Nucleotide Dissociation Inhibitors/genetics , Protein Transport , trans-Golgi Network , Animals , Cell Membrane/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , GTP-Binding Proteins/metabolism , Gene Expression Regulation, Developmental , Mice , Signal Transduction , trans-Golgi Network/metabolismABSTRACT
In diffuse optics, quantitative assessment of the human brain is confounded by the skull and scalp. To better understand these superficial tissues, we advance interferometric near-infrared spectroscopy (iNIRS) to form images of the human superficial forehead blood flow index (BFI). We present a null source-collector (S-C) polarization splitting approach that enables galvanometer scanning and eliminates unwanted backscattered light. Images show an order-of-magnitude heterogeneity in superficial dynamics, implying an order-of-magnitude heterogeneity in brain specificity, depending on forehead location. Along the time-of-flight dimension, autocorrelation decay rates support a three-layer model with increasing BFI from the skull to the scalp to the brain. By accurately characterizing superficial tissues, this approach can help improve specificity for the human brain.
Subject(s)
Interferometry , Spectroscopy, Near-Infrared , Brain/diagnostic imaging , Hemodynamics , Humans , SkullABSTRACT
High value unsaturated fatty acids can be produced by de novo synthesis in microalgal cells, especially via heterotrophic cultivation. Unfortunately, the lipid accumulation of heterotrophic microalgae cannot be improved efficiently in conventional ways. Here we reported heterotrophic Tribonema minus, a promising resource for the production of palmitoleic acid which has increasing demands in health service for patients with metabolic syndrome, as whole-cell biocatalyst to develop a novel way of shifting low value exogenous saturated fatty acids to high value ones. Results showed that myristic acid is the best precursor for whole-cell catalysis; it elevated the lipid content of T. minus to 42.2%, the highest among the tried precursors. The influences of cultivation condition on the utilization of extrinsic myristic acid and lipid accumulation were also determined. Under the optimized condition, the lipid content reached as high as 48.9%. In addition, our findings showed that ~13.0% of C16:1 in T. minus is derived from extrinsic myristic acid, and 30.1% of metabolized precursor is converted into heterologous fatty acids. Thus, a feasible approach for both increasing the value of low value saturated fatty acid by bioconversion and enhancing the lipid accumulation in microalgae is proposed by supplementing extrinsic myristic acid.
Subject(s)
Microalgae , Stramenopiles , Biofuels , Biomass , Catalysis , Fatty Acids/metabolism , Humans , Microalgae/metabolism , Myristic Acids/metabolismABSTRACT
INTRODUCTION: Scleral hypoxia (HO) is present in myopic eyes, and interleukin (IL)-6 is increased in the aqueous humor of patients with high myopia. The aim of this study was to investigate the effects of IL-6 on scleral fibroblast proliferation, differentiation, and apoptosis under conditions of HO and the possible role of IL-6 in myopic scleral remodeling. METHODS: Primary human scleral fibroblasts (HSFs) were cultured using a tissue mass adherent method. First, cells were cultured under conditions of HO (2% O2) or normoxia (NO, 20% O2) for different times. A quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence were used to detect the expression of IL-6 in HSFs. Next, cells were divided into five groups: NO, HO, HO plus IL-6, HO plus IL-6 receptor inhibitor (IL6RI), and HO plus IL-6 and IL6RI. The groups were treated separately for 72 h. Cell counting kit-8 assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Western blotting and qRT-PCR were used to detect the expression of various genes in the transforming growth factor-ß1/Smad2/matrix metalloproteinase-2 pathway; these methods and immunofluorescence were also used to detect transdifferentiation of HSFs. RESULTS: HO resulted in upregulation of IL-6 expression in HSFs. Compared with NO, HO resulted in diminished cell proliferation and increased apoptosis and differentiation in HSFs; the above trend was further enhanced by the addition of IL6RI. Compared with the HO group, the addition of IL-6 led to a decrease in cell proliferation and an increase in apoptosis and differentiation of HSFs; the above trends showed opposite changes after the addition of both IL-6 and IL6RI. Additionally, IL-6 and IL6RI exerted opposite regulatory effects on the transforming growth factor-ß1/Smad2/matrix metalloproteinase-2 pathway under conditions of HO. CONCLUSION: HO caused HSFs to overexpress IL-6. IL-6 has a role in scleral remodeling in myopic eyes through affecting the proliferation, differentiation, and apoptosis of HSFs.
Subject(s)
Interleukin-6 , Myopia , Apoptosis , Cell Proliferation , Cells, Cultured , Fibroblasts , Humans , Interleukin-6/metabolism , Interleukin-6/pharmacology , Matrix Metalloproteinase 2/metabolism , Myopia/metabolism , Receptors, Interleukin-6/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
As COVID-19 swept over the world, people discussed facts, expressed opinions, and shared sentiments about the pandemic on social media. Since policies such as travel restriction and lockdown in reaction to COVID-19 were made at different levels of the society (e.g., schools and employers) and the government, we build a large geo-tagged Twitter dataset titled UsaGeoCov19 and perform an exploratory analysis by geographic location. Specifically, we collect 650,563 unique geo-tagged tweets across the United States covering the date range from January 25 to May 10, 2020. Tweet locations enable us to conduct region-specific studies such as tweeting volumes and sentiment, sometimes in response to local regulations and reported COVID-19 cases. During this period, many people started working from home. The gap between workdays and weekends in hourly tweet volumes inspire us to propose algorithms to estimate work engagement during the COVID-19 crisis. This paper also summarizes themes and topics of tweets in our dataset using both social media exclusive tools (i.e., #hashtags, @mentions) and the latent Dirichlet allocation model. We welcome requests for data sharing and conversations for more insights. UsaGeoCov19 link:http://yunhefeng.me/geo-tagged_twitter_datasets/.
ABSTRACT
ACSS1/2 converts acetate into acetyl-coenzyme A, which contributes to histone acetylation in the mitochondria and cytoplasm. Zygotic genome activation (ZGA) is critical for embryo development involving drastic histone modification. An efficient crRNAs-Cas13a targeting strategy was employed to investigate the ACSS1/2 function during ZGA. The results showed that nuclear accumulation of ACSS1 and ACSS2 occurs during ZGA. Knockdown of ACSS1/2 did not affect blastocyst formation when using a normal medium. On culturing embryos in a medium with acetate and no pyruvate (-P + Ace), knockdown of ACSS1 did not affect histone acetylation levels but significantly reduced ATP levels, whereas knockdown of ACSS2 significantly reduced histone acetylation levels in porcine embryos. Inhibition of fatty acid beta-oxidation by etomoxir significantly reduced ATP levels, which could be restored by acetate. The histone acetylation levels in the ACSS1 and ACSS2 knockdown groups both decreased considerably after etomoxir treatment. Moreover, acetate showed dose-dependent effects on SIRT1 and SIRT3 levels when under metabolic stress. The C-terminus of ACSS1 regulated the nuclear translocation. In conclusion, ACSS1/2 helps to maintain ATP and histone acetylation levels in porcine early embryos under metabolic stress during ZGA.