Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues

It is commonly known that different macrophage phenotypes play specific roles in different pathophysiological processes. In recent years, many studies have linked the phenotypes of macrophages to their characteristics in different metabolic pathways, suggesting that macrophages can perform different functions through metabolic reprogramming. It is now gradually recognized that lactate, previously overlooked as a byproduct of glycolytic metabolism, acts as a signaling molecule in regulating multiple biological processes, including immunological responses and metabolism. Recently, lactate has been found to mediate epigenetic changes in macrophages through a newfound lactylation modification, thereby regulating their phenotypic transformation. This novel finding highlights the significant role of lactate metabolism in macrophage function. In this review, we summarize the features of relevant metabolic reprogramming in macrophages and the role of lactate metabolism therein. We also review the progress of research on the regulation of macrophage metabolic reprogramming by lactylation through epigenetic mechanisms

MAC3A and MAC3B, Two Core Subunits of the MOS4-Associated Complex, Positively Influence miRNA biogenesis

MAC3A and MAC3B are conserved U-box containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis. However, their functional mechanisms remain elusive. Here we show that Arabidopsis thaliana MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result together with the fact that MAC3A associates with pri-miRNAs in vivo indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing and stability. Supplemental data and figures attached

MAC3A and MAC3B, Two Core Subunits of the MOS4-Associated Complex, Positively Influence miRNA biogenesis

MAC3A and MAC3B are conserved U-box containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis. However, their functional mechanisms remain elusive. Here we show that Arabidopsis thaliana MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result together with the fact that MAC3A associates with pri-miRNAs in vivo indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing and stability. 4 supplemental files attached (below)

Comprehensive Study of Liptinite-Rich Coal from the Pliocene Jinsuo Basin and the Eocene Shenbei Basin (China)

Considering the significance of liptinite maceral group to the hydrocarbon generative potential, a comprehensive petrographical, biomarker and isotopic study is performed on liptinite-rich coal to determine the origin of organic matter (OM), depositional conditions and maturity. The samples were collected from the Pliocene Jinsuo Basin (samples YNP and YND) and Eocene Shenbei Basin (sample SB) in China. The obtained results indicate mixed gymnosperm (Pinacea) and angiosperm sources of OM in the sporinite dominated YNP sample. The immature OM (Rr=0.25%) was deposited under oxidizing conditions with pronounced microbial activity. The OM of the resinite-rich YND sample was mostly derived from woody parts of plants and deposited under reducing conditions. The presence of polycyclic aromatic hydrocarbons at low maturity level (Rr=0.23%) is indicative for certain post-depositional events and/or palaeo-wildfires, that may be responsible for the observation of two kinds of resinite in this sample. The main sources of OM in the resinite-rich sample SB (Rr = 0.46%) were species of the conifer families Cupressaceae and Pinaceae. The OM was deposited under reducing conditions, with a very limited microbial activity. The δ2D values of all extracted liptinite-rich coal are lower than that of coal/kerogen, and falls in the range of lipids and resins

Occurrence and genetic mechanism of pyrite in the No. 9 coal seam in magmatic erosion area of the Handan coalfield

The No. 9 coal of Yunjialing Coal Mine in Handan Coalfield, which is subject to obvious magmatic intrusion, is taken as the research object. Optical microscope observation, electron probe energy spectrometry (EPMA-EDS), X-ray diffractometer (XRD), X-ray fluorescence spectrometry (XRF) and other analytical tests were used to analyze the enrichment characteristics of whole sulfur, sulfur forms and minerals, to study the occurrence of sulfur and pyrite in the coals, and to explore the sources of different types of pyrite. The results show that the No. 9 coal of Yunjialing Coal Mine in Handan Coalfield is a high-sulfur coal (0.61%～7.12%), sulfide sulfur is the main form of sulfur in the coal (1.18%～4.90%), followed by organic sulfur (0.56%～2.16%) with a little sulphate sulfur (0.01%～0.06%). The No. 9 coal of Yunhailing coal mine was deposited in the transitional environment of sea and land phases, and seawater intrusion provided abundant sulfur source for the No. 9 coal seam, the gas-liquid materials brought about by neutral magmatism during the Yanshan period elevate the total sulfur content in the No. 9 coal of the Yunjialing Caol Mine, especially the total sulfur content of the upper coal plies are significantly higher than the total sulfur content of the whole coal seam. The microscopic occurrence of pyrite in the No. 9 coal mainly includes massive pyrite, disseminated pyrite and fissure-filled pyrite, and is characterized by multi-stage evolution. Massive pyrite is mainly formed in the early diagenetic stage, the high temperature and gas-liquid materials brought about by neutral magmatism during the Yanshan period modified the morphology of pyrite in the coal, resulting in the activation and recrystallization of pyrite in the coal into a massive fraction. Inorganic sulfur from the high-temperature-affected portion of the pyrite diffused into the surrounding coal body and sequestered as organic sulfur, increasing the organic sulfur content of the upper coal plies

FTIR characteristics of charcoal with different combustion degrees as an indication of the genesis by and their significances for formation of fusinite in coal

Fourier transform infrared spectroscopy (FTIR), as a non-destructive method, is widely used for the identification of compounds and the characterization of molecular structures. In order to characterize the changes in the chemical structure of charcoal under different combustion temperatures, and thus to provide a theoretical basis for the formation of fusinite in coal, plant samples (charcoal) from modern wildfires with different degrees of combustion were selected to quantify their chemical structures using FTIR. The results shown that the sample reflectance was positively proportional to the combustion temperature. The sample No. 1 with maximum combustion temperature had the highest degree of combustion, which was measured to reach 518 ℃. The aromatic structure was dominated by tri-substituted benzene rings in all samples except the highest combustion sample No. 1, but dehydrocondensation occurred with increasing combustion temperature, resulting in a reduction of tri-substituted content of benzene rings to 20.5%. The tetra-substituted content was elevated due to dehydroaromatization of the naphthenic structure, while the change in the penta-substituted content was related to the cyclization of aliphatic chain and the decarboxylation of benzene ring. With the increase of combustion temperature, the CC content gradually increased due to the formation of aromatic hydrocarbons or the shedding of molecular side chains after dehydrogenation of cycloalkanes, reached 32% in the sample No. 1. The content of C－O first decreased and then increased. In the sample No. 1, the content of alkyl ether and aryl ether was the lowest, and the content of phenolic hydroxyl group was the highest, which may be the generation of phenolic substances by thermal breakage of ether bond under high temperature combustion. The CO content increased and then decreased to as low as 5.6% in the sample No. 1, which was due to the poor stability of the bond. Due to the influence of combustion temperature, the content of fatty substances varied greatly, with an overall gradual increase in methylene content, a decrease in methyl group, and an increase in branching degree. There were five types of hydrogen bonds in the samples, with ether-oxygen hydrogen bonds predominating in samples affected by low temperature (>55%). Cyclic hydrogen bonds and hydroxyl-N hydrogen bonds appeared in sample No. 1, while the content of ether-oxygen hydrogen bonds decreased significantly to 13.2%, which was attributed to the reduction of oxygen-containing functional groups caused by the increasing temperature. Comparison of reflectance and FTIR characteristics of fusinite in coal revealed that the characteristics of fusinite (semifusinite) in coal were very similar to those of charcoal, which might be produced mainly by wildfires. These changes indicated the effect of combustion temperature on the chemical structure in charcoal, reflecting the process of organic molecular structure changed with temperature in charcoal, and providing a theoretical basis for the evolution of organic matter and the formation of fusinite in coal

OpenLane-V2: A Topology Reasoning Benchmark for Unified 3D HD Mapping

Accurately depicting the complex traffic scene is a vital component for autonomous vehicles to execute correct judgments. However, existing benchmarks tend to oversimplify the scene by solely focusing on lane perception tasks. Observing that human drivers rely on both lanes and traffic signals to operate their vehicles safely, we present OpenLane-V2, the first dataset on topology reasoning for traffic scene structure. The objective of the presented dataset is to advance research in understanding the structure of road scenes by examining the relationship between perceived entities, such as traffic elements and lanes. Leveraging existing datasets, OpenLane-V2 consists of 2,000 annotated road scenes that describe traffic elements and their correlation to the lanes. It comprises three primary sub-tasks, including the 3D lane detection inherited from OpenLane, accompanied by corresponding metrics to evaluate the model's performance. We evaluate various state-of-the-art methods, and present their quantitative and qualitative results on OpenLane-V2 to indicate future avenues for investigating topology reasoning in traffic scenes.Comment: Accepted by NeurIPS 2023 Track on Datasets and Benchmarks | OpenLane-V2 Dataset: https://github.com/OpenDriveLab/OpenLane-V

The origin of pale and dark layers in Pliocene Jinsuo lignite basin from Yunnan Province, Southwestern China

Cenozoic lignite deposits are widespread across Europe, Asia, America, Australia, and Indonesia. These deposits were the subject of numerous studies on changes in regional/global paleoclimates, paleobotany, paleoenvironment, and basin evolutions, which led to the formation of these lignites. In some of these Cenozoic lignite deposit basins, a succession of pale and dark lignite layers has been described in the Miocene Lower Rhine Basin in Germany, the Oligo-Miocene Gippsland Basin in southeastern Australia, and several Mio-Pliocene basins in southwestern China. Furthermore, pale and dark lithotypes in lignite seams also have been found in some Pliocene lignite deposit basins from Slovenia, Serbia, and Poland. The widespread cyclic occurrence of pale and dark layers in lignite basins might represent alternating depositional conditions related to the changes in plant communities, the regional/global climate, the tectonic setting, the Asian monsoon, and orbital periodicity during peat formation. ...Känozoische Braunkohlevorkommen sind in Europa, Asien, Amerika, Australien und Indonesien weit verbreitet. Diese Lagerstätten waren der Gegenstand umfangreicher Studien zur Rekonstruktion von Veränderungen des regionalen/globalen Paläoklimas, der Paläobotanik, der Paläoumwelt und der Beckenentwicklung, die zur Bildung dieser Braunkohle führten. Von einigen Känozoischen Lagerstätten von Braunkohlen wurde das Auftreten von Abfolgen mit hellen und dunklen Schichten beschrieben, z.B. aus den Miozänen Braunkohlen der Niederrheinischen Bucht in Deutschland, den Oligo-Miozänen Braunkohlen im Gippsland-Becken im Südosten Australiens und mehreren Mio-Pliozän-Braunkohlenbecken in Südwestchina. Darüber wurden helle und dunkle Lithotypen in Pliozänen Braunkohlen in Slowenien, Serbien und Polen gefunden. Das weite verbreitete zyklische Auftreten von hellen und dunklen Schichten in zahlreichen Braunkohlebecken könnte die Folge alternierender Depositionsbedingungen sein, die mit den Veränderungen der Pflanzengemeinschaft, des regionalen/globalen Klimas, der tektonischen Umgebung, der Intensität des asiatischen Monsuns und der Orbitalperiodizitäten während der Torfbildung zusammenhängen können. ..

Alteration in the Expression of Cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11) in the Liver of Mouse Induced by Microcystin-LR

Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR) on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11) at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice

MAC3A and MAC3B, Two Core Subunits of the MOS4-Associated Complex, Positively Influence miRNA biogenesis

MAC3A and MAC3B are conserved U-box containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis. However, their functional mechanisms remain elusive. Here we show that Arabidopsis thaliana MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result together with the fact that MAC3A associates with pri-miRNAs in vivo indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing and stability. 4 supplemental files attached (below)