Flux Analysis Research Articles

Fumarate Restrains Alveolar Bone Restoration via Regulating H3K9 Methylation.

Nonresolving inflammation causes irreversible damage to periodontal ligament stem cells (PDLSCs) and impedes alveolar bone restoration. The impaired tissue regeneration ability of stem cells is associated with abnormal mitochondrial metabolism. However, the impact of specific metabolic alterations on the differentiation process of PDLSCs remains to be understood. In this study, we found that inflammation altered the metabolic flux of the tricarboxylic acid cycle and induced the accumulation of fumarate through metabolic testing and metabolic flux analysis. Transcriptome sequencing revealed the potential of fumarate in modulating epigenetics. Specifically, histone methylation typically suppresses the expression of genes related to osteogenesis. Fumarate was found to impede the osteogenic differentiation of PDLSCs that exhibited high levels of H3K9me3. Various techniques, including assay for transposase-accessible chromatin with high-throughput sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing, were used to identify the target genes regulated by H3K9me3. Mechanistically, accumulated fumarate inhibited lysine-specific demethylase 4B (KDM4B) activity and increased H3K9 methylation, thus silencing asporin gene transcription. Preventing fumarate from binding to the histone demethylase KDM4B with α-ketoglutarate effectively restored the impaired osteogenic capacity of PDLSCs and improved alveolar bone recovery. Collectively, our research has revealed the significant impact of accumulated fumarate on the regulation of osteogenesis in stem cells, suggesting that inhibiting fumarate production could be a viable therapeutic approach for treating periodontal diseases.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

Effects of Different Nitrogen Application Measures on N2O Emissions in Wheat-maize Rotation System

To investigate the response of N2O emissions from farmland soil to different nitrogen application measures and the factors affecting it in the wheat and jade rotation system in North China, we analyzed the results of the one-time application of fertilizer in the following six treatments： without fertilization （CK）, conventional nitrogen application （urea, one instance of follow-up fertilization, U1）, optimized nitrogen application （20% nitrogen reduction, one instance of follow-up fertilization, U2）, one-time fertilization of controlled-release doped fertilizers （50% urea + controlled-release urea 50%, nitrogen reduction 20%, SRU1）, controlled-release fertilizer one-time fertilization （nitrogen reduction 20%, SRU2）, and inhibitor-type controlled-release fertilizer one-time fertilization （nitrogen reduction 20%, ISRU）, and the differences in N2O emission fluxes and soil physicochemical properties were determined. The results showed that soil N2O emission fluxes were dynamic during the wheat and jade crop rotation, and the N2O emission peaks of the CK, U1, and U2 treatments appeared in the corn season at 4-7d of basal fertilizer and 6-10d of fertilizer, and out of the wheat season its emission peaks appeared in the basal fertilizer at 4-8 d and 6-9 d of fertilizer. The emission peaks of SRU1, SRU2, and ISRU appeared in the basal fertilizer at 10-21 d, 12-20 d, and 12-20 d of fertilizer, respectively, in the corn season and the wheat season. At 21 d and 12-20 d, the application of controlled-release fertilizer significantly reduced the peak and frequency of N2O emission. Compared with those in U1, the N2O emission fluxes of the U2, SRU1, SRU2, and ISRU treatments were significantly reduced by 8.5%, 20.0%, 33.8%, and 43.6%, respectively, and the N2O emission fluxes were higher in the corn season than in the wheat season, which accounted for 58.1%-65.1% of the whole crop rotation cycle. Yield was reduced by 5.9% and 1.9% for the U2 and SRU1 treatments and increased by 1.7% and 7.0% for the SRU2 and ISRU treatments, respectively, compared to that in U1. In the maize season, the ISRU yield increased by 14.6%, the environmental benefit was $581, and the net economic benefit increased by up to 18.6% compared to that in U1, whereas the wheat season showed a decrease in yield and net economic benefit, which resulted in a one-time application of the inhibitor controlled-release fertilizers being more suitable for the maize season. Correlation analysis of N2O emission fluxes with the physicochemical indices of soil properties revealed that N2O was correlated with moisture, ammonium N, nitrate N, and microbial carbon and nitrate N and nitrogen. N2O and moisture, ammonium N, nitrate N, and microbial amount of carbon and nitrogen were significantly positively correlated. Thus, the one-time application of inhibitor-type controlled-release fertilizers played a positive role in reducing labor inputs and environmental benefits, and it could be an effective method of N fertilizer management for maize cultivation in North China.

Analysis of radiative heat flux using ASTER thermal images: Climatological and volcanological factors on Java Island, Indonesia

This study focuses on analysing natural Radiative Heat Flux (RHF) anomalies to map out the heat distribution across the Java Island. Leveraging remote sensing techniques, we calculated natural RHF anomalies using Land Surface Temperature (LST) and Land Surface Emissivity (LSE) data obtained from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) imagery. A key aspect of our approach was distinguishing between natural and anthropogenic heat sources by cross-referencing the LST Map with the Land Use Land Cover (LULC) map of Java Island. The study interprets natural RHF anomalies by examining regional trends in non-volcanic areas and local trends within volcanic regions, considering climatological and volcanological factors. Relation with climatological factors involves assessing soil moisture parameters from Soil Moisture Active Passive (SMAP) data, precipitation from monthly Global Precipitation Measurement (GPM) data, and classifications according to the Köppen-Geiger climate schema. Our regional analysis reveals high natural RHF anomalies in the northern regions of West Java, parts of Central Java, and most of East Java, attributed to low soil moisture and low precipitation in savanna and monsoon climates. On a more localised scale, RHF values are significantly high in volcanic areas, particularly around Central and East Java's volcanoes, such as Mt. Merapi, Mt. Slamet, Mt. Semeru, the Sidoarjo Mud Volcano, and Mt. Ijen. The Natural RHF anomalies at volcanoes in West Java were identified as not being high except at Mt Patuha. These areas exhibit average natural RHF anomalies ranging between 32.22 W/m2 and 115.13 W/m2, indicating strong and intense volcanic activity. The insights obtained from these findings explain the overall thermal characteristics of Java Island and highlight the presence of subsurface thermal zones associated with volcanic activity and geothermal potential.

Mechanism of Wind and Buoyancy Driving on Ventilation and Pollutant Transport in an Idealized Urban Street Canyon

The mechanisms underlying the effects of wind and buoyancy on ventilation in urban street canyons are unclear. This study investigated the effects of facade heating on ventilation and pollutant transport in an idealized street canyon with a 1.67 aspect ratio through computational fluid dynamics simulations. The dispersion pattern of discharged hot pollutants was also studied. A primary recirculation was observed when facade heating was not applied; this recirculation was promoted in leeward-wall and ground heating cases. However, the recirculation was bifurcated into two recirculations in windward-wall heating cases, restricting ventilation. Enhanced recirculation increased the ventilation and decreased the pollution level; by contrast, air pollution increased considerably when the recirculation was bifurcated and ventilation was restricted. In the hot-pollutant case, similar results to those in the ground-heating case were observed. The hot discharged pollutant enhanced ventilation, reducing pollution. The pollutant transport mechanism was determined through an analysis of pollutant fluxes. For the one-recirculation pattern, air convection transported the pollutant from the ground level to the top boundary, and turbulent diffusion then caused pollutant removal. For the two-recirculation pattern, turbulent diffusion contributed substantially to pollutant transport both in the junction between the recirculations and through the top boundary of the street canyon.

12614 Induction Of Gpt2 During Metabolic Stress Is Associated With Reduced Incretin Responsiveness And Decreased β-cell Resilience To Metabolic Stress

Abstract Disclosure: S. Sen: None. A.V. Rozo: None. M. Haemmerle: None. J. Roman: None. A.V. Scota: None. J.A. Christine: None. E.M. Morrow: None. S.A. Tersey: None. C.B. Newgard: None. N.M. Doliba: None. D.A. Stoffers: None. Elevated blood glucose and lipids compromise pancreatic β-cell survival and function, but the underlying molecular mechanisms are ill-understood. We previously found that mitochondrial glutamate-pyruvate transaminase 2 (GPT2) is induced by ER and glucolipotoxic (GLT) stress. Here, we find that islets from type 2 diabetic donors exhibited markedly elevated levels of GPT2 compared to those of non-diabetic donors. GLT stress induced GPT2 in MIN6 cells, primary murine, and human non-diabetic islets. We generated β-cell specific Gpt2-deficient (Gpt2βKO) and Gpt2 floxed control (Gpt2f/f) mice to study the in vivo role of Gpt2 in β-cells. Intraperitoneal (IP) glucose tolerance (GTT) of Gpt2βKO mice was minimally affected on chow diet; therefore, we placed Gpt2f/f and Gpt2βKO mice on 45 kcal% high-fat and matched control diets. At 1 week, HFD-fed Gpt2βKO mice exhibited reduced β-cell death, measured by droplet digital PCR of circulating unmethylated preproinsulin DNA and by TUNEL analysis. Over 37 weeks, HFD-fed Gpt2βKO mice showed lower random blood glucose similar to Gpt2f/f mice under a control diet. While IPGTT was modestly improved in HFD-fed Gpt2βKO compared to HFD-fed Gpt2f/f mice, insulin secretion was not enhanced. Remarkably, oral glucose administration markedly improved glucose tolerance and enhanced insulin secretion of control- and HFD-fed Gpt2βKO mice compared to Gpt2f/f mice, while GLP-1 and GIP levels were unaltered, suggesting enhanced incretin action on the β-cell. Indeed, Gpt2βKO mice (under both control and high-fat diets) were more responsive to administration of GLP1R agonist Exendin-4 (Ex4) than Gpt2f/f mice. Isolated Gpt2βKO islets secreted more insulin when stimulated by Ex4 and GIP but not acetylcholine. Perifusion assay revealed markedly enhanced insulin secretion of Gpt2βKO islets in response to a stepwise exposure to increasing Ex4 doses, indicating enhanced incretin sensitivity. Metabolic flux analysis of Gpt2βKO and Gpt2f/f islets exposed to uniformly labeled glucose (U-13C glucose) under low (2.8mM), high (12mM) glucose, and high glucose with Ex4 conditions revealed elevated levels of key TCA cycle intermediates in Gpt2βKO islets under high glucose and high glucose+Ex4 conditions, indicating increased TCA cycle flux that likely enhances insulin secretion. Gpt2βKO mice had higher β cell mass than Gpt2f/f littermates under control diet and HFD feeding. Bulk islet RNA-seq from Gpt2f/f and Gpt2βKO mice exposed to GLT revealed upregulation of genes responsible for cell cycle and division pathways and downregulation of apoptosis and ER stress genes, consistent with enhanced survival of Gpt2βKO islets under stress conditions. In summary, β-cell GPT2 is increased during metabolic stress and T2D. Its deficiency induces a metabolic reprogramming that improves incretin sensitivity and protects pancreatic β-cells from metabolic stress. Presentation: 6/2/2024

The intricacies of mitochondrial calcium and enzyme regulation in liver metabolism

Mitochondrial Ca2+ plays a positive role in regulating pyruvate dehydrogenase, as well as the TCA cycle enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. This regulation boosts the production of reducing equivalents that fuel the electron transport chain, ultimately driving ATP production. The Mitochondrial Calcium Uniporter (MCU) is the highly selective channel responsible for mitochondrial Ca2+ uptake when local Ca2+ levels reach the threshold for channel activation. In a recent study, LaMoia et al. used an innovative [13C5]glutamine-based metabolic flux analysis method (Q-flux) to measure in vivo hepatic metabolic fluxes in liver-specific MCU-/- mice. Surprisingly, they observed increased flux through isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Metabolic pathways are continuously reorganized in response to intrinsic cellular signals, as well as hormonal and nutritional inputs. Integrating metabolic flux analysis into complex systems can provide deeper insights into how metabolic adaptations occur under different conditions.

8603 Sex Steroids Have Opposing Impacts on Female Gonadotrope Metabolism and LH Secretion via GLUT1

Abstract Disclosure: C. Garcia: None. C. Nguyen: None. S. Wang: None. D. Trinh: None. U. Le: None. R. Kapadia: None. J. De La Torre: None. C.K. De La Cruz: None. D. Nicholas: None. Gonadotropes of the anterior pituitary regulate reproductive hormone synthesis and secretion not only through GnRH signaling from the hypothalamus, but by also determining if glucose availability, via GLUT1, meets the current requirements to support reproduction. GLUT1 facilitates glucose uptake and in gonadotropes its expression increases during the LH surge which indicates its necessity in the maximal secretion of LH through glycolysis. However, the mechanisms underlying the feedback from sex steroids that also mediate female reproduction have not been completely elucidated. By manipulating GLUT1 expression and sex steroid levels using cell lines and a conditional knockout of GLUT1 in mouse gonadotrope we show that sex steroids alter GLUT1 expression and translocation effecting gonadotrope glycolysis and subsequent gonadotropin secretion. Tamoxifen treated iGricCre +/+ GLUT1 fl/fl mice display disrupted estrous cycles and changes in serum gonadotropins. Dihydrotestosterone (DHT) or estradiol (E2) replacement in gonadectomized male and female, respectively, surprisingly result in increased (by DHT) or reduced (by E2) pituitary GLUT1 protein as measured by western blot despite both inhibiting serum LH. Using extracellular flux analysis and imaging flow cytometry, we show that LβT2 cells treated with DHT increase while E2 decreases glycolysis and translocation of GLUT1 to the cellular surface. We conclude that sex steroids regulate gonadotropin secretion and reproduction through direct impacts on gonadotrope metabolism through GLUT1. Presentation: 6/1/2024

Evaluation of thermal and epithermal neutron flux using the ko­NAA method with Gold and Zirconium monitors

Neutron flux analysis plays a crucial role in various nuclear research studies and sample analysis in research reactors. Accurate knowledge of the neutron flux spectrum and the ratio of thermal to epithermal neutrons is essential in these applications. In recent years, the newly k₀ method has been utilized to determine thermal and epithermal neutron flux. This method involves the irradiation of two monitors, typically gold and zirconium, followed by the counting of emitted gamma rays using suitable detectors like HpGe. By analyzing the photonic peak area of the collected gamma-ray spectrum from the monitors, the thermal and epithermal neutron flux at the irradiation site can be calculated. In this study, the k₀ method was employed to determine the thermal and epithermal neutron flux of Miniature Neutron Source Reactors (MNSRs).The method involved the irradiation of gold and zirconium monitors, followed by the measurement of emitted gamma rays. The photonic peak area of the gamma-ray spectrum obtained from the monitors was utilized to calculate the thermal and epithermal neutron flux. The research achieved a calculated error of 4 percent in determining the neutron flux. The k₀ method, using gold and zirconium monitors, proved to be an effective approach for determining the thermal and epithermal neutron flux in the Isfahan's MNSR. The use of zirconium, with its suitable neutron absorption cross-sections, along with cadmium calculations, contributed to the accuracy of the flux determination. It is recommended to apply the k₀ method in neutron and boron therapies and perform simulations using popular computational codes alongside the dual metal (gold and zirconium) measurement. This would enhance the accuracy of dosimetry calculations for absorbed doses resulting from neutron therapy.

NMR-Based Analysis of Cellular Central Energy Metabolism and Exchange Rates.

Cell cultures are widely used in studies to gain mechanistic insights of metabolic processes. The foundation of these studies lies on the quantification of intracellular and extracellular metabolites, and nuclear magnetic resonance (NMR) is one of the key analytical platforms used to this aim. Among the factors influencing the quality of the produced data are the sampling procedures as well as the acquisition and processing of spectroscopic data. Here we provide our workflow for obtaining quantitative metabolic data from adherent mammalian cells using NMR spectroscopy. The described protocol is compatible with other analytical methods like LC- or GC-MS-based lipidomics and untargeted metabolomics from the same sample. We also show how the collected extracellular data can be used to extract exchange flux rates, particularly useful for flux analysis studies and metabolic engineering of human-induced pluripotent stem cells.

TOI-3568 b: A super-Neptune in the sub-Jovian desert

The sub-Jovian desert is a region in the mass-period and radius-period parameter space that typically encompasses short-period ranges between super-Earths and hot Jupiters, and exhibits an intrinsic dearth of planets. This scarcity is likely shaped by photoevaporation caused by the stellar irradiation received by giant planets that have migrated inward. We report the detection and characterization of TOI-3568 b, a transiting super-Neptune with a mass of 26.4 ± 1.0 M⊕, a radius of 5.30 ± 0.27 R⊕, a bulk density of 0.98 ± 0.15 g cm−3, and an orbital period of 4.417965 (5) d situated in the vicinity of the sub-Jovian desert. This planet orbiting a K dwarf star with solar metallicity was identified photometrically by the Transiting Exoplanet Survey Satellite (TESS). It was characterized as a planet by our high-precision radial-velocity (RV) monitoring program using MAROON-X at Gemini North, supplemented with additional observations from the SPICE large program with SPIRou at CFHT. We performed a Bayesian MCMC joint analysis of the TESS and ground-based photometry, and MAROON-X and SPIRou RVs, to measure the orbit, radius, and mass of the planet, as well as a detailed analysis of the high-resolution flux and polarimetric spectra to determine the physical parameters and elemental abundances of the host star. Our results reveal TOI-3568 b to be a hot super-Neptune rich in hydrogen and helium, with a core of heavier elements of between 10 and 25 M⊕ in mass. We analyzed the photoevaporation status of TOI-3568 b and find that it experiences one of the highest extreme-ultraviolet (EUV) luminosities among planets with a mass of Mp < 2 MNep, yet it has an evaporation lifetime exceeding 5 Gyr. Positioned in the transition between two significant populations of exoplanets on the mass-period and energy diagrams, this planet presents an opportunity to test theories concerning the origin of the sub-Jovian desert.

A Method for Interpreting the Role of Parameterized Turbulence on Global Metrics in the Community Earth System Model

AbstractThe parameterization of subgrid‐scale processes such as boundary layer (PBL) turbulence introduces uncertainty in Earth System Model (ESM) results. This uncertainty can contribute to or exacerbate existing biases in representing key physical processes. This study analyzes the influence of tunable parameters in an experimental version of the Cloud Layers Unified by Binormals (CLUBBX) scheme. CLUBB is the operational PBL parameterization in the Community Atmosphere Model version 6 (CAM6), the atmospheric component of the Community ESM version 2 (CESM2). We perform the Morris one‐at‐a‐time (MOAT) parameter sensitivity analysis using short‐term (3‐day), initialized hindcasts of CAM6‐CLUBBX with 24 unique initial conditions. Several input parameters modulating vertical momentum flux appear most influential for various regionally‐averaged quantities, namely surface stress and shortwave cloud forcing (SWCF). These parameter sensitivities have a spatial dependence, with parameters governing momentum flux most influential in regions of high vertical wind shear (e.g., the mid‐latitude storm tracks). We next evaluate several experimental 20‐year simulations of CAM6‐CLUBBX with targeted parameter perturbations. We find that parameter perturbations produce similar physical mechanisms in both short‐term and long‐term simulations, but these physical responses can be muted due to nonlinear feedbacks manifesting over time scales longer than 3 days, thus causing differences in how output metrics respond in the long‐term simulations. Analysis of turbulent fluxes in CLUBBX indicates that the influential parameters affect vertical fluxes of heat, moisture, and momentum, providing physical pathways for the sensitivities identified in this study.

A multiscale hybrid modelling methodology for cell cultures enabled by enzyme-constrained dynamic metabolic flux analysis under uncertainty

Mammalian cell cultures make a significant contribution to the pharmaceutical industry. They produce many of the biopharmaceuticals obtaining FDA-approval each year. Motivated by quality-by-design principles, various modelling methodologies are frequently trialled to gain insight into these bioprocesses. However, these systems are highly complex and uncertain, involving dynamics at different scales, both in time and space, making them challenging to model in a comprehensive and fully mechanistic manner. This study develops a machine-learning-supported multiscale modelling framework of cell cultures, linking the macroscale bioprocess dynamics to the microscale metabolic flux distribution. As a relevant biopharmaceutical case study, we consider the production of Trastuzumab by Chinese Hamster Ovary (CHO) cells in batch. A macroscale hybrid model is constructed by integrating macro-kinetic and machine-learning approaches. Enzyme-constrained Dynamic Metabolic Flux Analysis (ecDMFA) is adopted to calculate flux distributions based on the dynamic predictions of the hybrid model. Uncertainty estimation of the multiscale model is conducted through bootstrapping. Judging from experimental data, our hybrid model can reduce the modelling error of the macroscale dynamics to 8.0%; a 70% reduction from the purely mechanistic model. In addition, the predicted dynamic flux distribution aligns with observations seen in literature, highlighting important metabolic changes throughout the process. Model uncertainty is maintained at a low level, demonstrating the trustworthiness of the predictions. Overall, our comprehensive modelling framework has the potential to facilitate the development of digital twins in the biopharmaceutical industry.

The Synergistic Combination of Curcumin and Polydatin Improves Temozolomide Efficacy on Glioblastoma Cells.

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness.

A new framework for assessing carbon fluxes in alpine rivers

Riverine carbon dynamics connecting land and ocean carbon cycles play a crucial role in regulating global carbon turnover. Despite its importance, the impact of climate change and runoff components on riverine carbon dynamics, particularly in alpine regions, remains underexplored. In this study, we introduce a conceptual framework to assess the impact of climate change on riverine carbon fluxes across various runoff components. We use a distributed hydrological model and stable isotopes to identify key runoff components, then identify the dominant drivers of variability in runoff carbon concentrations. We establish component-specific relationships between carbon concentrations and dominant drivers, assessing the watershed carbon balance through a comparative analysis of carbon fluxes in various runoff components. The proposed framework was validated in a representative watershed on the Qinghai-Tibet Plateau, and it effectively captured the seasonal carbon dynamics and the impact of climate change and runoff components. Our results indicated that runoff and temperature dominate riverine carbon concentrations. The carbon fluxes associated with rainfall and groundwater showed higher sensitivity to runoff, while those in the snowmelt component were more sensitive to temperature. We found seasonal variability in carbon fluxes, with particulate organic carbon concentrations peaking at 4.80 mgC/L during the thawing period and other carbon components (i.e., dissolved organic carbon, dissolved inorganic carbon, particulate inorganic carbon) peaking during the freezing period. We quantified the total carbon input and output for the watershed as 15.12 tC/km2/yr and 12.19 tC/km2/yr, with 51.2% of the carbon influx attributed to rainfall, 10.9% to groundwater, and 37.9% to snowmelt. Our study enhances the understanding of riverine carbon dynamics and offers a promising approach for predicting carbon budgets under climate change.

Investigating sediment dynamics on a continental shelf mud patch under the influence of a macrotidal estuary: A numerical modeling analysis

Shelf mud patches represent major sinks for fine-grained particles on continental shelves, as well as for carbon and contaminants of continental origin. The West Gironde Mud Patch (WGMP) is an interesting example of such offshore marine systems as it is an active mud deposition area located offshore the Gironde estuarine mouth (France) at depths between 30 and 70 m. It is known to be the trap of fine particles coming from the estuary, but the contribution of this material to the total mass of the depocenter is poorly quantified. In addition, despite the economic and ecological issues at stake, the response of such subtidal sedimentary structure to the combination of tidal currents, waves, and river supply remain poorly understood. Thus, using a realistic 3-D hydrodynamic and mixed (mud/sand) sediment transport model, this study aims at investigating the sediment dynamics of the WGMP under different hydrometeorological conditions. The analysis of the residual fluxes at the estuarine mouth exhibited large discrepancies between the different sediment classes as well as for contrasted hydro-and meteorological conditions induced by different dominant transport mechanisms. During winter, the reinforced density gradients drive strong up-estuary baroclinic circulation at the bottom that dominates the sediment dynamics over the barotropic export of mud particles. The model also reproduced the signature of a subtidal mud accumulation area over the continental shelf around 30–40 m water depth, on the proximal side of the observed WGMP. On average over two years, 26% of the mud mass accumulating on the simulated subtidal mudflat comes from the estuary. The trapping efficiency of this mud patch is negatively correlated with the significant wave height. Moreover, due to the estuarine turbid plume being more concentrated and developed at the surface during high river discharge, the trapping efficiency of the mud body is enhanced compared to lower discharge. This study highlights the sensitivity of mud and sand fluxes to vertical and horizontal residual circulation, and points out the uncertainties associated with the simulation of short-term (i.e., years) fine particle deposits compared to long-term (i.e., centuries) sediment accumulation trends. In addition, these results show the primordial effects of both wave action and riverine sediment supply on the dynamics of such subtidal muddy structures, which raises concern about their fate facing climate change and human activities in the future.

Comment on, "Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat".

Wu et al. (2021) investigated the neuroprotective effects of hypoxia preconditioning (HPC) in a rat model of traumatic brain injury (TBI). The study demonstrated that HPC enhances brain resilience to TBI by upregulating glucose transporters GLUT1 and GLUT3 through the HIF-1α signaling pathway. Comprehensive molecular and histological analyses confirmed increased expression of these transporters, correlating with reduced neuronal apoptosis and cerebral edema. The robust methodology, including rigorous statistical validation and time-course assessments, underscores HPC's potential therapeutic role in mitigating neuronal loss and improving glucose transport post-injury. However, the study could be strengthened by incorporating additional preconditioning controls, comparative analyses with other neuroprotective strategies, and exploring downstream metabolic effects in greater detail. Furthermore, expanding the research to include diverse animal models and examining sex-dependent responses would enhance the generalizability and translational relevance of the findings. Future studies should also integrate metabolic flux analysis and advanced imaging techniques to further elucidate HPC's mechanisms of action.

Performance analysis of various fluxes in different variants of the TIG welding process on the quality of welding

The tungsten inert gas (TIG) welding process is widely used in various industries for its ability to produce high-quality welds at a low cost. However, TIG welding struggles with welding thick stainless steel in a single pass, reducing production efficiency. To address this, new TIG variants such as activated TIG (A-TIG), flux bound TIG (FB-TIG), and flux zone TIG (FZ-TIG) have been developed to enhance penetration in austenitic stainless steel. This study investigates the effects of TiO2 and Fe2O3 flux on 304 stainless steels welded using A-TIG, FB-TIG, and FZ-TIG processes. Results show a slight increase in the depth-to-width (d/w) ratio for A-TIG and FB-TIG, while FZ-TIG achieved a 59% higher d/w ratio compared to autogenous TIG welding. The increased penetration is attributed to the reversal Marangoni convection and arc constriction. Microstructural analysis reveals a higher delta ferrite content in A-TIG and FZ-TIG welds due to increased heat input. Additionally, FZ-TIG welds exhibited an 11.5% higher microhardness compared to autogenous TIG welds. FZ-TIG welding enhances penetration and mechanical properties effectively.

Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites

ObjectivesHistone acetylation is an important epigenetic modification that regulates various biological processes and cell homeostasis. Acetyl-CoA, a hub molecule of metabolism, is the substrate for histone acetylation, thus linking metabolism with epigenetic regulation. However, still relatively little is known about the dynamics of histone acetylation and its dependence on metabolic processes, due to the lack of integrated methods that can capture site-specific histone acetylation and deacetylation reactions together with the dynamics of acetyl-CoA synthesis. MethodsIn this study, we present a novel proteo-metabo-flux approach that combines mass spectrometry-based metabolic flux analysis of acetyl-CoA and histone acetylation with computational modelling. We developed a mathematical model to describe metabolic label incorporation into acetyl-CoA and histone acetylation based on experimentally measured relative abundances. ResultsWe demonstrate that our approach is able to determine acetyl-CoA synthesis dynamics and site-specific histone acetylation and deacetylation reaction rate constants, and that consideration of the metabolically labelled acetyl-CoA fraction is essential for accurate determination of histone acetylation dynamics. Furthermore, we show that without correction, changes in metabolic fluxes would be misinterpreted as changes in histone acetylation dynamics, whereas our proteo-metabo-flux approach allows to distinguish between the two processes. ConclusionsOur proteo-metabo-flux approach expands the repertoire of metabolic flux analysis and cross-omics and represents a valuable approach to study the regulatory interplay between metabolism and epigenetic regulation by histone acetylation.

Anatomy of a fumarole field: drone remote-sensing and petrological approaches reveal the degassing and alteration structure at La Fossa cone, Vulcano, Italy

Abstract. Hydrothermal alteration and mineralization processes can affect the physical and chemical properties of volcanic rocks. Aggressive acidic degassing and fluid flow often also lead to changes in the appearance of a rock, such as changes in surface coloration or intense bleaching. Although hydrothermal alteration can have far-reaching consequences for rock stability and permeability, limited knowledge exists on the detailed structures, extent, and dynamic changes that take place near the surface of hydrothermal venting systems. By integrating drone-based photogrammetry with mineralogical and chemical analyses of rock samples and surface gas flux, we investigate the structure of the evolving volcanic degassing and alteration system at the La Fossa cone on the island of Vulcano, Italy. Our image analysis combines principal component analysis (PCA) with image classification and thermal analysis through which we identify an area of approximately 70 000 m2 that outlines the maximum extent of hydrothermal alteration effects at the surface, represented by a shift in rock color from reddish to gray. Within this area, we identify distinct gradients of surface coloration and temperature that indicate a local variability in the degassing and alteration intensity and define several structural units within the fumarole field. At least seven such larger units of increased activity could be constrained. Through mineralogical and geochemical analysis of samples from the different alteration units, we define a relationship between surface appearance in drone imagery and the mineralogical and chemical composition. Gradients in surface color from reddish to gray correlate with a reduction in Fe2O3 from up to 3.2 % in the unaltered regime to 0.3 % in the altered regime, and the latter coincides with the area of increased diffuse acid gas flux. As the pixel brightness increases towards higher alteration gradients, we note a loss of the initial (igneous) mineral fraction and a change in the bulk chemical composition with a concomitant increase in sulfur content from close to 0 % in the unaltered samples to up to 60 % in samples from the altered domains. Using this approach of combined remote-sensing and in situ analyses, we define and spatially constrain several alteration units and compare them to the present-day thermally active surface and degassing pattern over the main crater area. The combined results permit us to present a detailed anatomy of the La Fossa fumarole field, including high-temperature fumaroles and seven larger units of increased alteration intensity, surface temperature, and variably intense surface degassing. Importantly, we also identify apparently sealed surface domains that prevent degassing, likely as a consequence of mineral precipitation from degassing and alteration processes. By assessing the thermal energy release of the identified spatial units quantitatively, we show that thermal radiation of high-temperature fumaroles accounts for &lt; 50 % of the total thermal energy release only and that the larger part is emitted by diffuse degassing units. The integrated use of methods presented here has proven to be a useful combination for a detailed characterization of alteration and activity patterns of volcanic degassing sites and has the potential for application in alteration research and for the monitoring of volcanic degassing systems.