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The Great Unconformity marks a major gap in the continental geological record, separating Precambrian basement from Phanerozoic sedimentary rocks. However, the timing, magnitude, spatial heterogeneity, and causes of the erosional event(s) and/or depositional hiatus that lead to its development are unknown. We present field relationships from the 1.07-Ga Pikes Peak batholith in Colorado that constrain the position of Cryogenian and Cambrian paleosurfaces below the Great Unconformity. Tavakaiv sandstone injectites with an age of ≥676 ± 26 Ma cut Pikes Peak granite. Injection of quartzose sediment in bulbous bodies indicates near-surface conditions during emplacement. Fractured, weathered wall rock around Tavakaiv bodies and intensely altered basement fragments within unweathered injectites imply still earlier regolith development. These observations provide evidence that the granite was exhumed and resided at the surface prior to sand injection, likely before the 717-Ma Sturtian glaciation for the climate appropriate for regolith formation over an extensive region of the paleolandscape. The 510-Ma Sawatch sandstone directly overlies Tavakaiv-injected Pikes granite and drapes over core stones in Pikes regolith, consistent with limited erosion between 717 and 510 Ma. Zircon (U-Th)/He dates for basement below the Great Unconformity are 975 to 46 Ma and are consistent with exhumation by 717 Ma. Our results provide evidence that most erosion below the Great Unconformity in Colorado occurred before the first Neoproterozoic Snowball Earth and therefore cannot be a product of glacial erosion. We propose that multiple Great Unconformities developed diachronously and represent regional tectonic features rather than a synchronous global phenomenon., Competing Interests: Competing interest statement: P.F.H. and F.A.M. are coauthors on three papers, most recently in 2017.

Water molecules in vapor can exchange with gaseous water molecules sticking to surfaces of sampling tubing, and exchange rates are unique for each water isotopologue and tubing material. Therefore, water molecules on tubing walls take some time to reach isotopic equilibrium with a new vapor isotopic signal. This creates a memory effect that is observed as attenuation time for signal propagation in continuous stable water vapor isotope measurement systems. Tubing memory effects in δ D and δ18 O measurements can limit the ability to observe fast changes, and because δD and δ18 O memory are not identical, this introduces transient deuterium excess (D-excess, defined as δD-8×δ18O) artifacts in time-varying observations. To our knowledge, a comprehensive performance comparison of commonly used tubing material water exchange properties in laser-based measurement systems has not been published. We compared how a large isotopic step change propagated through five commonly used tubing materials for water isotopic studies – perfluoroalkoxy (PFA), fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), high-density polyethylene (HDPE), and copper – at two different temperatures and an airflow rate of 0.635 L min−1 through approximately 100 ft (30.5 m) of 1/4 in. (6.4 mm) outer diameter (o.d.) tubing. All commonly used tubing materials performed similarly to each other in terms of attenuation times, reaching δ18 O-location-adjusted δD and δ18 O 95 % completion in less than 45 s, with slight variations based on temperature. PFA does appear to perform slightly better than the other materials, although memory metric differences are small. A tubing material commonly used in the early 2000s but reported to have memory effects on δD , Dekabon, was also tested at ambient temperature and changing humidities. The Dekabon isotopic equilibrium was not reached until nearly an hour after source transition, much later than H2O mixing ratios equilibrated. Bev-A-Line XX (used in some soil O2 and CO2 gas studies) was also tested at ambient temperature, but it did not approach isotopic equilibrium until after nearly 6 h of testing. Therefore, we cannot recommend the use of Bev-A-Line XX or Dekabon in water vapor isotope applications. Source transition from heavy to light or from light to heavy affected isotopic transition speed only in experiments where H2O ppmv was changing. While a shorter tubing lengths and smaller inner diameters shorten the delay of signal propagation through the tubing, they did not greatly change the attenuation curves under these conditions for the current commonly used tubing materials tested. However, in Dekabon, attenuation curves were greatly extended with increased tubing length. Our results show that the commonly used plastic tubing materials tested were not inferior to copper in terms of isotopic memory under these conditions, and they are easier to work with and are less expensive than copper. [ABSTRACT FROM AUTHOR]

The conventional zircon (U–Th) / He (ZHe) method typically uses microscopy measurements of the dated grain together with the assumption that the zircon can be appropriately modeled as a geometrically perfect tetragonal or ellipsoidal prism in the calculation of volume (V), alpha-ejection correction (FT), equivalent spherical radius (RFT), effective uranium concentration (eU), and corrected (U–Th) / He date. Here, we develop a set of corrections for systematic error and determine uncertainties to be used in the calculation of the above parameters for zircon, using the same methodology as Zeigler et al. (2023) for apatite. Our approach involved acquiring both "2D" microscopy measurements and high-resolution "3D" nano-computed tomography (CT) data for a suite of 223 zircon grains from nine samples showcasing a wide range of morphology, size, age, and lithological source, calculating the V , FT , and RFT values for the 2D and 3D measurements and comparing the 2D vs. 3D results. We find that the values derived from the 2D microscopy data overestimate the true 3D V , FT , and RFT values for zircon, with one exception (V of ellipsoidal grains). Correction factors for this misestimation determined by regressing the 3D vs. 2D data range from 0.81–1.04 for V , 0.97–1.0 for FT , and 0.92–0.98 for RFT , depending on zircon geometry. Uncertainties (1 σ) derived from the scatter of data around the regression line are 13 %–21 % for V , 5 %–1 % for FT , and 8 % for RFT , again depending on zircon morphologies. Like for apatite, the main control on the magnitude of the corrections and uncertainties is grain geometry, with grain size being a secondary control on FT uncertainty. Propagating these uncertainties into a real dataset (N=28 ZHe analyses) generates 1 σ uncertainties of 12 %–21 % in eU and 3 %–7 % in the corrected ZHe date when both analytical and geometric uncertainties are included. Accounting for the geometric corrections and uncertainties is important for appropriately reporting, plotting, and interpreting ZHe data. For both zircon and apatite, the Geometric Correction Method is a practical and straightforward approach for calculating more accurate (U–Th) / He data and for including geometric uncertainty in eU and date uncertainties. [ABSTRACT FROM AUTHOR]

Background: No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis, which is characterized by insulin resistance, steatosis, and necroinflammation with or without centrilobular fibrosis. Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus., Methods: We randomly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet (a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight) plus pioglitazone (45 mg daily) or a hypocaloric diet plus placebo. Before and after treatment, we assessed hepatic histologic features, hepatic fat content by means of magnetic resonance spectroscopy, and glucose turnover during an oral glucose tolerance test ([14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion)., Results: Diet plus pioglitazone, as compared with diet plus placebo, improved glycemic control and glucose tolerance (P<0.001), normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels (by 40% vs. 21%, P=0.04), decreased alanine aminotransferase levels (by 58% vs. 34%, P<0.001), decreased hepatic fat content (by 54% vs. 0%, P<0.001), and increased hepatic insulin sensitivity (by 48% vs. 14%, P=0.008). Administration of pioglitazone, as compared with placebo, was associated with improvement in histologic findings with regard to steatosis (P=0.003), ballooning necrosis (P=0.02), and inflammation (P=0.008). Subjects in the pioglitazone group had a greater reduction in necroinflammation (85% vs. 38%, P=0.001), but the reduction in fibrosis did not differ significantly from that in the placebo group (P=0.08). Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone; no other adverse events were observed., Conclusions: In this proof-of-concept study, the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone. (ClinicalTrials.gov number, NCT00227110 [ClinicalTrials.gov] .)., (Copyright 2006 Massachusetts Medical Society.)

Background: Despite years of intervention, few studies describe the extent to which recommended tobacco use prevention and cessation activities occur in community-based family practices. This study was designed to discover current practice patterns in these areas and to describe physician outcome and efficacy expectations., Methods: An exploratory comparative case study of 11 family practices used direct observation of practices and clinical encounters, chart reviews, and in-depth interviews. Qualitative and quantitative information was gathered on (1) intensity of tobacco use prevention and cessation; (2) physicians' attitudes and beliefs regarding outcome expectations; and (3) physicians' perceptions of their ability to counsel. Qualitative content analysis and descriptive statistics were used to construct case studies for comparisons., Results: Themes common to most practices included the "provision of little prevention" and "a lack of perceived need to address smokeless tobacco." Responsibility for tobacco activities fell almost solely to physicians. Although physicians felt confident in their counseling skills, the skills they identified were fairly basic. Most physicians were pessimistic about the positive effects of these activities. None of the practices was using any specifically developed "package," and pharmaceutical companies provided almost all patient education material. There was considerable variation in intensity of activities because of differences in attitudes, expectation, and background., Conclusions: To increase tobacco control activities, practice systems need to be individually evaluated to identify what is needed, how it will fit within the practice culture, and how it can best be implemented in this specific practice. One-size-fits-all interventions probably will not be widely implemented.

Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more efficiently than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to those of NTV. A crucial feature of ML2006a4 is a derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Last, ML2006a4 was found to be less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory design can preemptively address potential resistance mechanisms to expand future treatment options against coronavirus variants. Editor's summary: The toolkit for preventing and treating patients with COVID-19 has expanded greatly since the pandemic began. Some of the most effective therapeutics for COVID-19 and, potentially, other coronavirus infections are antivirals that inhibit the SARS-CoV-2 main protease (Mpro). Mpro inhibitors include nirmatrelvir, a component of the oral treatment Paxlovid. However, second-generation drugs are needed, because there is a risk that new SARS-CoV-2 variants could become resistant to nirmatrelvir and other antivirals in clinical use. Here, Westberg et al. used the hepatitis C virus protease inhibitor boceprevir as a starting point to make such a next-generation Mpro inhibitor. Their optimized lead candidate, ML2006a4, exhibited robust antiviral activity in vitro and in mice infected with SARS-CoV-2 and could be administered orally. ML2006a4 appeared less sensitive to mutations in the SARS-CoV-2 Mpro, suggesting that the virus would be less likely to become resistant to ML2006a4 in the real world. —Courtney Malo [ABSTRACT FROM AUTHOR]

Synthesizing uniform and high concentrations of 3He within minerals via high‐energy proton irradiation is paramount for 4He/3He thermochronology and helium diffusion kinetic studies. Proton irradiations of geological material have hitherto exclusively been routinely conducted at the Francis H. Burr Proton Therapy Center (FHB); we thus explored alternative irradiation protocols at two European‐based facilities with the intention to improve the accessibility and efficiency in obtaining 4He/3He data. We conducted a single irradiation at the Paul Scherrer Institute (PSI) using an approach most similar to that used at FHB (wide, high‐energy beam), and four irradiations at the Helmholtz Zentrum Berlin (HZB) using a newly developed in‐vacuum irradiation protocol in a narrow, lower‐energy but high‐intensity beam. Internal shards of Durango apatite were irradiated in all experiments; 4He/3He release spectra and bulk 3He concentrations of PSI and HZB‐irradiated Durango shards were compared to those from FHB to assess the quality of each experiment in terms of the quantity and uniformity of synthesized 3He. While 3He was uniformly synthesized in PSI‐irradiated Durango shards, the bulk 3He concentration was below the required threshold due to limitations on the maximum allotted proton flux. Over the course of four irradiation experiments at HZB, the protocol evolved to ensure that uniform and high concentrations of 3He can be consistently induced. Furthermore, we demonstrate how HZB irradiations can be replicated using computer simulations, permitting the use of simulations to inform future modifications of the irradiation protocol in order to optimize the uniformity of the 3He distribution across all irradiated samples. Key Points: 4He/3He Thermochronology requires the synthesis of uniform and high concentrations of 3He within minerals via proton irradiationDurango apatite was irradiated at three proton irradiation facilities for quality assessment and comparisonA new in‐vacuum and high‐intensity irradiation protocol was established that has potential to improve the throughput of 4He/3He analyses [ABSTRACT FROM AUTHOR]

Macrostrat is a platform for deep‐time geoscientific research that integrates stratigraphic columns and geologic maps into a digital description of the crust. The database and supporting software track crustal evolution and provide location‐based geological information to geoscience end users. Macrostrat houses multiple scales of mapping and stratigraphic data, from continent‐ and basin level summaries to single quadrangles and measured sections. Currently, Macrostrat's primary data holdings consist of regional stratigraphic columns with a spatial footprint weighted heavily to North America. While the data are of sufficient scale and resolution to generate insights about Earth evolution, increasing resolution and expanding spatial coverage will allow a new generation of scientific and interpretive uses. The next phase of Macrostrat's development will increase the detail and complexity of Macrostrat's multiscale data holdings, largely by engaging a wider range of geoscientists in entering stratigraphic data. To support broad collaboration, we are building new web‐based software to assemble and visualize regional stratigraphic sequences, refine multiple working age models, and compose regional records from measured stratigraphic sections. These tools will allow Macrostrat to draw on the expertise of a wide range of geoscience workers and grow a dataset with global relevance and a variety of end uses. New capabilities will pave the way to processes for submission, review, coordination, and assimilation of community‐contributed stratigraphic datasets. Digital compilation of geological maps and columns requires substantial effort, and well‐designed systems for distributing this work in the geoscience community will allow Macrostrat to build more adaptable and scientifically relevant products. [ABSTRACT FROM AUTHOR]

Purpose: Non-alcoholic fatty liver disease (NAFLD) has become a leading cause of liver disease, affecting 30% of the global population. NAFLD prevalence is particularly high in obese individuals and patients with type 2 diabetes mellitus (T2DM). NAFLD ranges from simple fat deposition in the liver to necroinflammation and fibrosis (non-alcoholic steatohepatitis (NASH)), NASH-cirrhosis, and/or hepatocellular carcinoma. Insulin resistance plays a key role in NAFLD pathogenesis, alongside dysregulation of adipocytes, mitochondrial dysfunction, genetic factors, and changes in gut microbiota. Since insulin resistance is also a major predisposing factor of T2DM, the administration of anti-diabetic drugs for the management of NAFLD seems reasonable. Methods: In this review we provide the NAFLD-associated mechanisms of action of some of the most widely used anti-diabetic drugs, namely metformin, pioglitazone, sodium-glucose transport protein-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor analogs (GLP1 RAs), and dipeptyl-peptidase-4 inhibitors (DPP4i) and present available data regarding their use in patients with NAFLD, with and without T2DM. Results: Both metformin and DPP4i have shown rather contradictory results, while pioglitazone seems to benefit patients with NASH and is thus the only drug approved for NASH with concomitant significant liver fibrosis by all major liver societies. On the other hand, SGLT2i and GLP1 RAs seem to be beneficiary in patients with NAFLD, showing both remarkable results, with SGLT2i proving to be more efficient in the only head-to-head study so far. Conclusion: In patients with NAFLD and diabetes, pioglitazone, GLP1 RAs, and SGLT2i seem to be logical treatment options. Larger studies are needed before these drugs can be recommended for non-diabetic individuals. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide that poses a significant threat to human health. Cardiovascular disease (CVD) is the leading cause of mortality in NAFLD patients. NAFLD and CVD share risk factors such as obesity, insulin resistance, and type 2 diabetes. However, whether NAFLD is a causal risk factor for CVD remains a matter of debate. This review summarizes the evidence from prospective clinical and Mendelian randomization studies that underscore the potential causal relationship between NAFLD and CVD. The mechanisms of NAFLD contributing to the development of CVD and the necessity of addressing CVD risk while managing NAFLD in clinical practice are also discussed. [ABSTRACT FROM AUTHOR]

Methodological advancements have been made in in situ observations of water stable isotopes that have provided valuable insights into ecohydrological processes. The continuous measurement capabilities of laser-based analyzers allow for high temporal resolutions and non-destructive minimally invasive study designs of such in situ approaches. However, isotope analyzers are expensive, heavy, and require shelter and access to electrical power, which impedes many in situ assays. Therefore, we developed a new inexpensive technique to collect discrete water vapor samples in the field via diffusion-tight inflatable bags that can later be analyzed in the lab. In a series of structured experiments, we tested different procedural settings, bag materials, and closure types for diffusion tightness during storage as well as for practical handling during filling and extraction. To facilitate reuse of sampling bags, we present a conditioning procedure using ambient air as primer. In order to validate our method, direct measurements through hydrophobic in situ probes were compared to repeated measurements of vapor sampled with our bags from the same source. All steps are summarized in a detailed standard operating procedure (SOP). This procedure represents the preparation and measurement of calibration and validation vapor standards necessary for processing of unknown field-collected vapor samples in the foreseen application. By performing pertinent calibration procedures, accuracy was better than 0.4 ‰ for δ18 O and 1.9 ‰ for δ2 H after 1 d of storage. Our technique is particularly suitable when used in combination with minimally invasive water vapor sampling in situ probes that have already been employed for soils and tree xylem. It is an important step towards minimally invasive monitoring of stable isotope distributions and also time series in virtually undisturbed soils and trees without the need to have an analyzer in the field. It is therefore a promising tool for many applications in ecohydrology and meteorology. [ABSTRACT FROM AUTHOR]

Ancient magnetization(s), often recorded by hematite (Fe2O3), provide key paleomagnetic constraints on plate interactions through time. Primary remanent magnetizations may be modified or overprinted by secondary processes that complicate interpretations of paleomagnetic data. Hematite (U‐Th)/He (hematite He) dating has the potential to resolve when secondary magnetizations were acquired. Here, we compare hematite He data and paleomagnetic results in Paleoproterozoic crystalline rocks, meters below a major nonconformity in the Colorado Front Range, USA. Prior work and new rock magnetic data indicate that pervasive hematite alteration records a secondary chemical remanent magnetization (CRM) during the Permo‐Carboniferous Reverse Superchron, coincident with the Ancestral Rocky Mountain orogeny. We target minor hematite‐coated faults cutting basement for (U‐Th)/He analyses because they are of sufficient hematite purity to yield geologically meaningful dates. Two samples yield overlapping and scattered individual hematite He dates ranging from ∼138 to 27 Ma (n = 33), significantly younger than the age of the late Paleozoic CRM. Scanning electron microscopy, electron probe microanalysis, and Raman spectroscopy indicate that aliquots have variable grain size distributions and fluorocarbonate impurities. Thermal history models support hematite on fault surfaces mineralized coeval with CRM acquisition during the late Paleozoic, and hematite He data scatter reflects variable He loss during Mesozoic burial owing to differences in grain size distribution from fault slip comminution and in chemistry among aliquots. Our results underscore the differences in temperature sensitivity and sampling requirements between paleomagnetic and hematite He investigations and illustrate that hematite He dates will usually be younger than preserved remanent magnetizations. Plain Language Summary: Minerals such as hematite are capable of recording the direction of the Earth's magnetic field during formation and this paleomagnetic information helps geoscientists estimate the age of rocks and the past motions of tectonic plates. During geologic events like mountain‐building, primary paleomagnetic signatures in rocks may be modified or replaced by new, secondary paleomagnetic recordings. Such secondary magnetizations can be challenging to interpret, especially if the age of these magnetizations is unknown. (U‐Th)/He analysis, a form of radiometric dating, may aid paleomagnetic studies by revealing the age of minerals that carry secondary magnetizations. In this study, we compare hematite (U‐Th)/He data and a secondary magnetization carried by hematite from Colorado's Front Range and find that (U‐Th)/He dates are scattered and considerably younger than the reported age of the secondary magnetization. We interpret the variability of hematite (U‐Th)/He dates to reflect differences between aliquots relating to crystal size and the presence of non‐hematite minerals. Our results suggest that the (U‐Th)/He system was partially to fully reset by a more recent phase of burial and associated reheating that was not hot enough to fully reset the paleomagnetic system. We conclude that (U‐Th)/He and paleomagnetic investigations in hematite may not record the same geologic events. Key Points: We compare new hematite (U‐Th)/He dates with previously published paleomagnetic data from the same exposure of crystalline basement rockHematite (U‐Th)/He dates are younger than the inferred timing of magnetization and imply partial He loss since magnetization acquisition(U‐Th)/He dates may not relate to remanence acquisition because of differences in sampling requirements and temperature sensitivity [ABSTRACT FROM AUTHOR]

Soil water isotope datasets are useful for understanding connections between the hydrosphere, atmosphere, biosphere, and geosphere. However, they have been underproduced because of the technical challenges associated with collecting those datasets. Here, we present the results of testing and automation of the Soil Water Isotope Storage System (SWISS). The unique innovation of the SWISS is that we are able to automatically collect water vapor from the critical zone at a regular time interval and then store that water vapor until it can be measured back in a laboratory setting. Through a series of quality assurance and quality control tests, we tested whether the SWISS is resistant to both atmospheric intrusion and leaking in both laboratory and field settings. We assessed the accuracy and precision of the SWISS through a series of experiments in which water vapor of known composition was introduced into the flasks, stored for 14 d, and then measured. From these experiments, after applying an offset correction to report our values relative to Vienna Standard Mean Ocean Water (VSMOW), we assess the precision of the SWISS to be ±0.9 ‰ and ±3.7 ‰ for δ18 O and δ2 H, respectively. We deployed three SWISS units at three different field sites to demonstrate that the SWISS stores water vapor reliably enough that we are able to differentiate dynamics both between the sites as well within a single soil column. Overall, we demonstrate that the SWISS retains the stable isotope composition of soil water vapor for long enough to allow researchers to address a wide range of ecohydrologic questions. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is among the most widespread metabolic disease globally, and its associated complications including insulin resistance and diabetes have become threatening conditions for human health. Previous studies on non-alcoholic fatty liver disease (NAFLD) were focused on the liver's lipid metabolism. However, growing evidence suggests that mitochondrial metabolism is involved in the pathogenesis of NAFLD to varying degrees in several ways, for instance in cellular division, oxidative stress, autophagy, and mitochondrial quality control. Ultimately, liver function gradually declines as a result of mitochondrial dysfunction. The liver is unable to transfer the excess lipid droplets outside the liver. Therefore, how to regulate hepatic mitochondrial function to treat NAFLD has become the focus of current research. This review provides details about the intrinsic link of NAFLD with mitochondrial metabolism and the mechanisms by which mitochondrial dysfunctions contribute to NAFLD progression. Given the crucial role of mitochondrial metabolism in NAFLD progression, the application potential of multiple mitochondrial function improvement modalities (including physical exercise, diabetic medications, small molecule agonists targeting Sirt3, and mitochondria-specific antioxidants) in the treatment of NAFLD was evaluated hoping to provide new insights into NAFLD treatment. [ABSTRACT FROM AUTHOR]

Objective. The aim of study was to evaluate the effect and safety of pioglitazone-metformin combined treatment in the newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease. Methods. A total of 120 newly diagnosed type 2 diabetes patients with nonalcoholic fatty liver disease from 8 centers were randomly divided into the control group (metformin hydrochloride) and the test group (pioglitazone hydrochloride and metformin hydrochloride). Results. Compared to the control group, after treatment, the proportion of people with mild and moderate fatty liver increased, and the proportion of people with severe fatty liver decreased, and this change was more obvious in the population with moderate and severe fatty liver. The level of γ-GT decreased in both groups before and after treatment, which was statistically significant, and there was also a statistically significant difference in the level of γ-GT between the two groups after 24 weeks. There were no significant statistically differences in blood lipid, body weight, and waist circumference between the test group and the control group. Logistic regression analysis found that BMI is one of the risk factors for fatty liver. There was also no significant difference in the incidence of serious adverse events between the two groups (control group: 10.00% and test group: 6.67%, P = 0.74). Conclusion. Combined treatment with pioglitazone-metformin can effectively reduce liver fat content and gamma-GT level in newly diagnosed diabetic patients with nonalcoholic fatty liver disease, and adverse events do not increase compared with the control group, showing good safety and tolerance. This trial is registered with ClinicalTrials.gov NCT03796975. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic cardiomyopathy (DCM) is defined as a cardiac dysfunction derived from DM without the presence of coronary artery diseases and hypertension. Patients with either type 1 or type 2 DM are at high risk of developing DCM and even heart failure. Metabolic disorders of obesity and insulin resistance in type 2 diabetic environments result in dyslipidaemia and subsequent lipid‐induced toxicity (lipotoxicity) in organs including the heart. Although various mechanisms have been proposed underlying DCM, it remains incompletely understood how lipotoxicity alters cardiac function and how DM induces clinical heart syndrome. With recent progress, we here summarize the latest discoveries on lipid‐induced cardiac toxicity in diabetic hearts and discuss the underlying therapies and controversies in clinical DCM. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, associated with a high risk of progression to NASH, liver cirrhosis and hepatocarcinoma. Its prevalence is closely related to obesity (understood as adipose-based disease and insulin resistance), which makes that at present NAFLD can be considered a metabolic dysfunction hallmark, regardless of the body mass index. Despite being such a prevalent condition, with such severe consequences, at present there are no reliable biomarkers for its diagnosis or specific treatment. Significant and sustained weight loss, as well as some antidiabetic treatments, has shown promising results for NAFLD but data needs confirmation in larger clinical trials and longer follow-up. Efforts should be made for a better and more accurate baseline diagnosis (including large-scale genetics), identification of patients at higher risk for progression to NASH as well as adequate treatment, to allow us to offer a personalized approach in NAFLD in the context of precision medicine. [ABSTRACT FROM AUTHOR]

Archean rocks exposed in the Beartooth Mountains, Montana and Wyoming, have experienced a complex >2.5 Gyr thermal history related to the long‐term geodynamic evolution of Laurentia. We constrain this history using "deep‐time" thermochronology, reporting zircon U‐Pb, biotite 40Ar/39Ar, and zircon and apatite [U‐Th(‐Sm)]/He results from three transects across the basement‐core of the range. Our central transect yielded a zircon U‐Pb concordia age of 2,805.6 ± 6.4 Ma. Biotite 40Ar/39Ar plateau ages from western samples are ≤1,775 ± 27 Ma, while those from samples further east are ≥2,263 ± 76 Ma. Zircon (U‐Th)/He dates span 686.4 ± 11.9 to 13.5 ± 0.3 Ma and show a negative relationship with effective uranium—a proxy for radiation damage. Apatite (U‐Th)/He dates are 109.2 ± 23.9 to 43.6 ± 1.9 Ma and correlate with sample elevation. Multi‐chronometer Bayesian time‐temperature inversions suggest: (a) Cooling between ∼1.90 and ∼1.80 Ga, likely related to Big Sky orogeny thermal effects; (b) Reheating between ∼1.80 Ga and ∼1.35 Ga consistent with Mesoproterozoic burial; (c) Cooling to ≤100°C between Mesoproterozoic and early Paleozoic time, likely reflecting continental erosion; (d) Variable Paleozoic–Jurassic cooling, possibly related to Paleozoic tectonism and/or low eustatic sea level; (e) Rapid Cretaceous–Paleocene cooling, preceding accepted proxies for flat‐slab subduction; (f) Eocene–Miocene reheating consistent with reburial by Cenozoic volcanics and/or sediments; (g) Post‐20 Ma cooling consistent with Neogene development of topographic relief. Our results emphasize the utility of multi‐chronometer thermochronology in recovering complex, non‐monotonic multi‐billion‐year thermal histories. Plain Language Summary: The Beartooth Mountains in southern Montana and northern Wyoming consist of some of the oldest rocks in North America. These rocks have been exhumed to Earth's surface and reburied numerous times. However, sedimentary rocks recording many of these events have been eroded, erasing much of the primary record of the geologic history of this region. To recover this history, we use minerals within existing rocks that act as heat‐sensitive clocks. These "clocks" record a cooling date, reflecting the last time the rock was within a specific temperature range. We measure cooling dates for several different types of minerals and model the history of temperature fluctuations they record, corresponding to burial and erosion events. We interpret the results of these models by comparing them with the geologic history recorded in nearby preserved sedimentary rocks. We find that the Beartooth Mountains were involved in mountain‐building events not previously recognized and cooling associated with building of the modern Rocky Mountains began earlier, and is more complex, than is generally recognized. The ability to recover such long histories of temperature fluctuations is important, suggesting we may be able to learn about events far in Earth's past even when the rock record is missing. Key Points: Multi‐chronometer time‐temperature inversions resolve key aspects of the >2.5 Gyr thermal history of the Beartooth Mountains40Ar/39Ar and [U‐Th(‐Sm)]/He data constrain newly recognized Proterozoic and Paleozoic thermal eventsModels suggest complex, spatially variable cooling associated with basement‐involved thrusting initiating >90 Ma [ABSTRACT FROM AUTHOR]

Using water-stable isotopes to track plant water uptake or soil water processes has become an invaluable tool in ecohydrology and physiological ecology. Recent studies have shown that laser absorption spectroscopy can measure equilibrated water vapour well enough to support inference of liquid-stable isotope composition of plant or soil water, on-site and in real-time. However, current in situ systems require the presence of an instrument in the field. Here we tested, first in the lab and then in the field, a method for equilibrating, collecting, storing, and finally analysing water vapour for its isotopic composition that does not require an instrument in the field. We developed a vapour storage vial system (VSVS) that relies on in situ sampling into crimp neck vials with a double-coated cap using a pump and a flow metre powered through a small battery and measuring the samples in a laboratory. All components are inexpensive and commercially available. We tested the system's ability to store the isotopic composition of its contents by sampling a range of water vapour of known isotopic compositions (from -95 ‰ to +1700 ‰ for δ2H) and measuring the isotopic composition after different storage periods. Samples for the field trial were taken in a boreal forest in northern Sweden. The isotopic composition was maintained to within 0.6 ‰ to 4.4 ‰ for δ2H and 0.6 ‰ to 0.8 ‰ for δ18O for natural-abundance samples. Although 2H -enriched samples showed greater uncertainty, they were sufficient to quantify label amounts. We detected a small change in the isotopic composition of the sample after a long storage period, but it was correctable by linear regression models. We observed the same trend for the samples obtained in the field trial for δ18O but observed higher variation in δ2H than in the lab trial. Our method combines the best of two worlds, sampling many trees in situ while measuring at high precision in the laboratory. This provides the ecohydrology community with a tool that is not only cost efficient but also easy to use. [ABSTRACT FROM AUTHOR]

The Precambrian–Cambrian unconformity boundary is ubiquitous and globally documented, which is of great significance to studying major global scientific issues such as environmental transition, positions of the supercontinent, Cambrian explosion, and global geochemical cycle. However, few studies have been on the palaeogeographic features and provenance changes of the Precambrian–Cambrian unconformity boundary at the southern margin of North China Craton (NCC). This uncertainty hampers us from further understanding the early climate change and plate evolutionary history of the NCC. To improve the knowledge of the palaeogeographic features and provenance changes of the Precambrian–Cambrian unconformity boundary on the southern margin of the NCC, the Luoquan and Xinji formations at the southern margin of the NCC were selected as the research object integrated with sedimentary petrology, trace elements, and detrital zircon geochronology investigation. The results suggest a depositional gap between the Luoquan and Xinji formations. The former is glacial to deglaciation deposits, while the latter is shallow to coastal sediments. Compared with the sedimentary stratum of the South China Craton, the Luoquan Formation lacks at least one transgression and regression cycle. The Xinji Formation has detrital zircon age peaks of 1200, 1100, and 950 Ma, unavailable in the Luoquan Formation. The provenance areas of the Luoquan and Xinji formations have changed, indicating that the provenances of the Luoquan Formation belong to the NCC and part of the provenances of the Xinji Formation belong to the North Qinling Terrane (NQT). The trace element data indicate that the tectonic setting of the Luoquan and Xinji formations has changed from a continental island arc to a passive continental margin. It is suggested that the NCC be involved in the evolution of Rodinia supercontinent, which leads to the change of the provenance and tectonic setting. This research provides an explanation for the Precambrian–Cambrian tectonic history, basin development, stratigraphic correlation, and palaeogeographic reconstruction of NCC. [ABSTRACT FROM AUTHOR]

Rocks in Earth's crust are formed, modified, and destroyed in response to myriad interactions between the solid Earth (tectonics, geodynamics), the fluid Earth (ocean-atmosphere, cryosphere), and the living Earth (evolution, biochemistry). As such, the geological record is an integrator of geological, biological, and climatological processes and their histories. Here we review contrasting perceptions of the processes that govern the formation and destruction of the geological record, beginning with the relationship between macroevolutionary patterns in the fossil and sedimentary rock records and culminating with contrasting models of rock cycling. Using the approach of macrostratigraphy, we present an integrated summary of the quantity-age properties of rocks in continental and oceanic crust. The predominant process signal in the rock quantity-age distribution in continental crust is one of episodic growth, whereas in oceanic crust it is one of continual destruction. Relatively abrupt shifts in the dominant locus of sediment deposition, from fast-cycling oceanic crust to long-term continental reservoirs, and attendant expansions and contractions in the area of crust that is emergent, are correlated in timing and magnitude with shifts in the concentration of oxygen in the atmosphere and major macroevolutionary transitions in the biosphere. The most recent of possibly two such first-ordertransitions occurred at the start of the Phanerozoic and is marked by a prominent preserved geomorphic surface known as the Great Unconformity. Macrostratigraphy uses the bulk characteristics of the rock record to probe the evolution of the Earth system. Quantifying the creation and destruction of rock units can illuminate the long-term evolution of continents and the life that inhabits them. [ABSTRACT FROM AUTHOR]

During an earthquake, work done to overcome fault friction is dissipated as heat. Coseismic temperature rise, critical for identifying and constraining the magnitude of past earthquakes, is difficult to accurately quantify. To address this issue, we compare two temperature‐sensitive geochemical systems, zircon (U‐Th)/He (ZHe) thermochronometry and thermal maturity of organic matter (biomarkers), which respond to short‐duration, high temperatures. Models of prior biomarker data from the Punchbowl fault (PF), CA, indicate coseismic temperatures of ∼465–1,065°C in the principal slip zone (PSZ; Savage & Polissar, 2019, https://doi.org/10.1029/2019gc008225) depending on prescribed thickness of the deforming zone. We resampled two PF sample sites and acquired high‐spatial resolution ZHe data (n = 45 individual analyses) from the PSZ and fault core gouge, together with adjacent crystalline basement and Punchbowl Formation rocks. Results define a positive ZHe date‐effective U (eU) trend from ∼10 to 60 Ma and ∼20–700 ppm eU with a plateau at ∼65 Ma at >700 ppm eU. This pattern suggests the PSZ and fault core gouge share a similar thermal history to material outside the PF. Individual apatite (U‐Th)/He dates (n = 5) from an undeformed Punchbowl Formation sample are ∼4 Ma for grains with ∼30–150 ppm eU, implying rapid cooling and exhumation at that time due to PF activity. Zircon damage‐diffusivity relationships inform a suite of numerical models that collectively bracket coseismic temperatures on the PF to <725–800°C for 90% He loss. Results support general compatibility between ZHe and biomarker‐derived temperature rise estimates, and spatio‐temporal variability in coseismic temperatures along the PF. Plain Language Summary: Earthquakes produce heat along faults from friction created as blocks of rock slide past each other. Identifying evidence of and quantifying these temperatures can pinpoint past earthquakes along faults and help us understand the physics of earthquakes. It is difficult to measure temperatures of modern earthquakes because the fault may be hot for less than a minute far below Earth's surface. Here we compare data from two techniques, heat‐induced chemical changes in organic materials (biomarkers) and geochemical changes in minerals (zircon (U‐Th)/He analysis), which are sensitive to short‐lived, high temperatures. We apply zircon (U‐Th)/He analysis to samples within and away from the Punchbowl fault, a strike slip fault in southern California and an ancient strand of the San Andreas fault system, where prior biomarker data showed evidence of past earthquake temperature rise in material within the fault. Zircon (U‐Th)/He results, along with numerical models, reveal that earthquake temperatures were likely less than 725–800°C within the fault, similar to previous temperature estimates. Data also suggest earthquake temperatures may have been variable in space and time. Our work illustrates the agreement between these two geochemical methods and that this dual‐approach can quantify earthquake‐generated heat in other fault zones worldwide. Key Points: We directly compare zircon (U‐Th)/He data and thermal maturation of organic matter from within and outside the Punchbowl fault, CaliforniaZircon (U‐Th)/He dates are not completely reset and models indicate coseismic temperatures were likely ≤725–800°CTemperatures inferred from zircon (U‐Th)/He data are consistent with biomarker results and suggest temperature rise varied in space and time [ABSTRACT FROM AUTHOR]

Adiponectin is well established to mediate many beneficial metabolic effects, and this has stimulated great interest in development and validation of adiponectin receptor agonists as pharmaceutical tools. This study investigated the effects of ALY688, a peptide-based adiponectin receptor agonist, in rat L6 skeletal muscle cells. ALY688 significantly increased phosphorylation of several adiponectin downstream effectors, including AMPK, ACC, and p38MAPK, assessed by immunoblotting and immunofluorescence microscopy. Temporal analysis using cells expressing an Akt biosensor demonstrated that ALY688 enhanced insulin sensitivity. This effect was associated with increased insulin-stimulated Akt and IRS-1 phosphorylation. The functional metabolic significance of these signaling effects was examined by measuring glucose uptake in myoblasts stably overexpressing the glucose transporter GLUT4. ALY688 treatment increased basal glucose uptake and enhanced insulin-stimulated glucose uptake. In the model of high-glucose/high-insulin (HGHI)-induced insulin-resistant cells, both temporal studies using the Akt biosensor as well as immunoblotting to assess Akt and IRS-1 phosphorylation indicated that ALY688 significantly reduced insulin resistance. Importantly, we observed that ALY688 administration to high-fat high-sucrose-fed mice also improves glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects. [ABSTRACT FROM AUTHOR]

Obesity is a predisposing factor to diseases such as diabetes mellitus, hypertension, and coronary artery disease. Lemongrass essential oil (LEO), from Cymbopogon flexuosus, possesses numerous therapeutic properties including modulation of obesity in vivo. This experiment investigated the effect of LEO and its major components citral (3,7‐dimethyl‐2,6‐octadienal), citral dimethyl acetal (1,1‐dimethoxy‐3,7‐dimethylocta‐2,6‐diene), and citral diethyl acetal (1,1‐diethoxy‐3,7‐dimethylocta‐2,6‐diene) in modulation of adipogenesis and genetic expression in adipocytes. Adipogenesis was induced from murine 3T3‐L1 preadipocytes procured from ATCC and maintained in Dulbecco's modified Eagle's medium (DMEM) enriched with calf serum. Differentiation was conducted using DMEM enriched with 10% fetal bovine serum, Dexamethasone 0.25 µM, 3‐isobutyl‐methylxanthine 0.5 mM, and insulin 10 mg/ml for 2 days, followed by 5 days of insulin 10 mg/ml alone. Samples were subjected to experimental treatments at a concentration of 2.5 × 10−3. Intracellular triglycerides were quantified and photomicrographs were obtained following Oil red O (ORO) staining procedure. Total ribonucleic acid was extracted and expression of genes effecting in lipid metabolism were quantitated using real‐time polymerase chain reaction. ORO staining procedure and spectrophotometric analysis demonstrated decreased lipid accumulation following treatments. LEO and its major constituents significantly inhibited expression of sterol response binding protein 2, cluster of differentiation 36, fatty acid binding protein 4, and peripilin. These results indicate modulation of lipid accumulation through decreased lipid uptake, increased lipolysis, decreased differentiation, and downregulated lipid biosynthesis. This investigation suggests that LEO and its constituents exert effects on adipocyte metabolism and are important for understanding metabolic disease. Further investigation is required to elucidate the degree that each mechanism implicated contributes to the observed effect. [ABSTRACT FROM AUTHOR]

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Crystalline basement rocks of southwestern Montana have been subjected to multiple tectonothermal events since ~3.3 Ga: the Paleoproterozoic Big Sky/Great Falls orogeny, Mesoproterozoic extension associated with Belt-Purcell basin formation, Neoproterozoic extension related to Rodinia rifting, and the late Phanerozoic Sevier-Laramide orogeny. We investigated the long-term (>1 Ga), low-temperature (erosion/burial within 10 km of the surface) thermal histories of these tectonic events with zircon and apatite (U-Th)/He thermochronology. Data were collected across nine sample localities (n = 55 zircon and n = 26 apatite aliquots) in the northern and southern Madison ranges, the Blacktail-Snowcrest arch, and the Tobacco Root uplift. Our zircon (U-Th)/He data show negative trends between single aliquot date and effective uranium (a radiation damage proxy), which we interpreted with a thermal history model that considers the damage-He diffusivity relationship in zircon. Our model results for these basement ranges show substantial cooling from temperatures above 400°C to near surface conditions between 800 and 510 Ma. Subsequent Phanerozoic exhumation culminated by ~75 Ma. Late Phanerozoic cooling is coincident with along-strike Sevier belt thin-skinned thrusting in southeastern Idaho, and older than exhumation in basement-involved uplifts of the Wyoming Laramide province. Our long- term, low-temperature thermal record for these southwestern Montana basement ranges shows that: (a) these basement blocks have experienced multiple episodes of upper crustal exhumation and burial since Archean time, possibly influencing Phanerozoic thrust architecture and (b) the late Phanerozoic thick- skinned thrusting recorded by these rocks is among the earliest thermochronologic records of Laramide basement-involved shortening and was concomitant with Sevier belt thin-skinned thrusting. [ABSTRACT FROM AUTHOR]

In situ zircon U-Pb and Hf isotopic data from ∼1.1 Ga intrusive igneous rocks in Mexico and from Grenvillian (0.9–1.3 Ga) detrital zircons in sandstones from the southern midcontinent of Laurentia were used to refine provenance determinations for the Grenvillian detrital zircons delivered to southwestern Laurentia from the Neoproterozoic to the Cambrian and to address the reduction in the Grenvillian detrital zircon abundances documented in Cambrian sandstones from this region. Igneous zircons from Mesoproterozoic anorthosites and granites in northern Sonora have low εHf(0) values (<−22) and could not have been sources of the higher-εHf(0) (>−22), ∼1.1 Ga detrital zircons characteristic of Ediacaran to Terreneuvian sandstones in southwestern Laurentia. Abundant Grenvillian detrital zircons in Cryogenian sandstone injectites from central Colorado have U-Pb ages and high εHf(0) values (>−22) similar to those of zircons in Ediacaran to Terreneuvian sandstones throughout southwestern Laurentia. These zircons were derived from Mesoproterozoic rocks in the Llano uplift and vicinity in Texas and were fluvially transported across southwestern Laurentia from the Cryogenian to the Terreneuvian. In contrast, Cambrian glauconitic sandstones in the subsurface of east-central Colorado and from the Sawatch Sandstone in central Colorado have low Grenvillian zircon abundances, as observed in Cambrian sandstones exposed farther west in Laurentia. The low abundances of Grenvillian detrital zircons in sandstones found both east (Colorado) and west of the strike of a proposed Cambrian "transcontinental arch" suggest that this feature did not disrupt the supply of Llano uplift–derived Grenvillian zircons to southwestern Laurentia. The low Grenvillian zircon abundances instead coincide with the development of marine conditions in south-central Laurentia, suggesting that the progressive encroachment of the Sauk Sea into the continental interior provided a sink for fluvial sediments derived from the Llano uplift that restricted their transport farther to the north and west in the continent. [ABSTRACT FROM AUTHOR]

The Great Unconformity between the Precambrian basement and the Phanerozoic successions marks a major gap in the stratigraphic records globally. However, previous studies on the time, magnitude, and the spatial distribution of this unconformity in the North China Craton (NCC) mainly focused on the south‐eastern margin and were seldom investigated in the central area. In this study, we report detrital zircon geochronological data of the Huoshan Formation, a siliciclastic stratigraphic unit between the Archean‐Palaeoproterozoic metamorphic basement and Cambrian successions in the central NCC. The youngest age peak of 685 Ma suggests that the Huoshan Formation was formed in the post‐Ediacaran rather than the counterpart of the lower Palaeo‐Mesoproterozoic Changcheng Group. The detrital zircons of the quartz sandstone from the Huoshan Formation show varied age populations of 2,700–2,600 Ma, 2,600–2,500 Ma, 2,200–2,000 Ma, 1,900–1,800 Ma, and 700–600 Ma, which correspond to typical tectono‐thermal events of the NCC. First, the widely developed Precambrian tectono‐thermal events in the NCC were archived in the detrital zircons in the Huoshan Formation, for instance, the crustal growth event at 2,600–2,500 Ma and the 1,850–1,800 Ma magmatic and metamorphic events. Second, the age peaks younger than 1,000 Ma are not distinct in the NCC and are possibly from other terranes. The Great Unconformity represented by the boundary between the Huoshan Formation and the underlying Archean‐Palaeoproterozoic basement suggested a high topography and long‐term denudation in the Lüliang area during the transition from the Proterozoic to the Phanerozoic. [ABSTRACT FROM AUTHOR]

Liver fibrosis resulting from chronic liver injury is a key factor to develop liver cirrhosis and risk of hepatocellular carcinoma (HCC) which are major health burden worldwide. Therefore, it is necessary for antifibrotic therapies to prevent chronic liver disease progression and HCC development. There has been tremendous progress in understanding the mechanisms of liver fibrosis in the last decade, which has created new opportunities for the treatment of this condition. In this review, we aim to make an overview on information of different potential therapies (drug treatment, cell therapy, and liver transplantation) for the liver fibrosis and hope to provide the therapeutic options available for the treatment of liver fibrosis and discuss novel approaches. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the effects of hydro-alcoholic extract of spinach (HES) on hepatic and serum measurements of NAFLD in a rat model. Methods: In the prevention phase, 18 Sprague–Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, or a chow diet for seven weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg/kg HES, a chow diet, or a chow diet plus 400 mg/kg HES for four weeks (n = 6). Results: Administration of HES combined with high-fat diet in rats was associated with decreased food intake (P < 0.01), weight loss (P = 0.01), and increased superoxide dismutase (SOD) (P = 0.02) enzyme activity in the liver, at the end of the prevention phase. hs-CRP (P < 0.05), PTX-3 (P < 0.05), and TNF-α (P < 0.05) gene expression in the liver were decreased and PPAR-γ (P < 0.05) gene expression in the liver was increased by spinach intake, both in the prevention and treatment phases. Furthermore, administration of spinach in the treatment phase increased serum TAC (P = 0.03) and hepatic GPX (P = 0.01) enzyme activity. Conclusion: Taking into account the potential beneficial effects of HES on prevention and treatment of NAFLD in the present study, to confirm these findings, we propose that further clinical trials be conducted on human subjects with NAFLD. [ABSTRACT FROM AUTHOR]

Zircon (U–Th)/He (zircon He) thermochronometry and visual radiation damage relationships reveal the timing and patterns of Orocopia Schist and North American basement exhumation in the Mecca Hills, CA. Zircon crystals from these units were selected to maximize the spectrum in visual metamictization and effective U (eU) concentrations, and thus He retentivity, in each sample. Zircon He dates (n = 31 analyses) from six of seven samples are ∼24 Ma regardless of eU, despite a large spread in eU (>2,800 ppm) across all grains. One sample (n = 7 analyses) yields a mean ∼65 Ma date. Uniform zircon He dates over a range of eU concentrations and their preserved visual metamictization indicate these grains experienced a thermal history that induced complete He loss, but did not anneal the damage. This is consistent with recent work that indicates zircon radiation damage anneals at higher temperatures than parameterized in current damage annealing models. The zircon He data patterns, together with new zircon U‐Pb results and thermal history modeling, reveal the two basement units in the Mecca Hills exhumed simultaneously at ∼24 Ma, likely by the Orocopia Mountains detachment fault. This requires both basement units lie in the footwall of the detachment, and implies the breakaway zone of the Orocopia Mountains detachment fault was west of the present‐day Mecca Hills basement exposures and has been translated by the San Andreas fault. Combined with prior work, our data suggest large‐magnitude late Oligocene–early Miocene extension in the southwestern Cordillera was more widespread than previously recognized. Key Points: Zircon (U‐Th)/He data record late Oligocene–early Miocene exhumation of basement in Mecca Hills along Orocopia Mountains detachment faultData support more extensive detachment system; breakaway zone lies west of the Mecca Hills, likely displaced by the San Andreas faultLarge‐magnitude ∼24 Ma extension in the southwestern Cordillera has a larger aerial extent than previously recognized [ABSTRACT FROM AUTHOR]

A widespread provenance shift recorded by passive margin strata of western Laurentia, from predominant Stenian (1.2–1.0 Ga) detrital zircon age components to their absence, occurred during the Neoproterozoic–Cambrian Sauk transgression and is commonly used as a ca. 540 Ma chronostratigraphic marker throughout the west/south‐western United States. However, in Neoproterozoic–Cambrian strata of this region, we identify a probable shift from distal to more proximal Stenian‐age zircon sources before a diachronous loss of Stenian detrital zircon age components. We suggest these provenance patterns reflect progressive subsidence of the passive margins surrounding Laurentia and concomitant relative uplift of the Transcontinental Arch, a broad and segmented northeast–southwest trending topographic high across the Laurentian midcontinent possibly due to lithospheric flexure. The Transcontinental Arch segments align with transverse rift structures of the Neoproterozoic–Cambrian Iapetan margin and the Mesoproterozoic Midcontinent Rift, perhaps reflecting rejuvenation of midcontinent lithospheric weaknesses during the Sauk transgression and final Rodinia breakup. [ABSTRACT FROM AUTHOR]

Disentangling ecosystem evapotranspiration (ET) into evaporation (E) and transpiration (T) is of high relevance for a wide range of applications, from land surface modelling to policymaking. Identifying and analysing the determinants of the ratio of T to ET (T/ET) for various land covers and uses, especially in view of climate change with an increased frequency of extreme events (e.g. heatwaves and floods), is prerequisite for forecasting the hydroclimate of the future and tackling present issues, such as agricultural and irrigation practices. One partitioning method consists of determining the water stable isotopic compositions of ET , E , and T (δET , δE , and δE , respectively) from the water retrieved from the atmosphere, the soil, and the plant vascular tissues. The present work emphasizes the challenges this particular method faces (e.g. the spatial and temporal representativeness of the T/ET estimates, the limitations of the models used, and the sensitivities to their driving parameters) and the progress that needs to be made in light of the recent methodological developments. As our review is intended for a broader audience beyond the isotopic ecohydrological and micrometeorological communities, it also attempts to provide a thorough review of the ensemble of techniques used for determining δET , δE , and δE and solving the partitioning equation for T/ET. From the current state of research, we conclude that the most promising way forward to ET partitioning and capturing the subdaily dynamics of T/ET is by making use of non-destructive online monitoring techniques of the stable isotopic composition of soil and xylem water. Effort should continue towards the application of the eddy covariance technique for high-frequency determination of δET at the field scale as well as the concomitant determination of δET , δE , and δE at high vertical resolution with field-deployable lift systems. [ABSTRACT FROM AUTHOR]

The Great Unconformity is a widely distributed surface separating Precambrian rocks from overlying Phanerozoic sedimentary sequences. The causes and implications of this feature, and whether it represents a singular global event, are much debated. Here, we present new apatite (U-Th)/He (AHe) thermochronologic data from the central Canadian Shield that constrain when the Precambrian basement last cooled to near-surface temperatures, likely via exhumation, before deposition of overlying early Paleozoic sedimentary sequences that mark the Great Unconformity. AHe data from 11 samples (n = 57) across a broad region define a similar date-eU pattern, implying a common thermal history. Higher eU (>25 ppm) apatite form distinct flat profiles of reproducible dates at ∼510 ± 49 Ma (mean and 1σ standard deviation), while lower eU (<25 ppm) apatite define a positive date-eU trend with younger dates. The data patterns, geologic context, and thermal history modeling point toward >3 km of erosion across the entire ∼450,000 km2 study area between 650 and 440 Ma, followed by modest reheating during later burial. Plume activity associated with intracratonic basin formation or continental rifting/breakup may have caused this erosion event. The post-650 Ma timing of the last major sub-Great Unconformity exhumation phase in this region implies a late Great Unconformity that is younger than inferred elsewhere in North America. This suggests that this feature is likely the result of multiple temporally distinct erosion events with differing footprints and mechanisms. [ABSTRACT FROM AUTHOR]

The article presents the discussion on exploring the history of subcrustal topographic support of Madagascar. Topics include Madagascar underlain by thinned lithospheric mantle and thermal anomaly lies within an asthenospheric layer beneath northern Madagascar; and subsequent Mesozoic tectonic history being characterized by a combination of regional extension and magmatism.

Radiation damage exerts a fundamental control on He diffusion in zircon, which manifests as correlations between (U‐Th)/He date and effective uranium concentration. These correlations can be exploited with modeling to explore long‐term thermal histories. This manuscript focuses on one such model, the zircon radiation damage accumulation and annealing model (ZRDAAM) of Guenthner et al. (2013), https://doi.org/10.2475/03.2013.01, by integrating newly defined alpha damage annealing kinetics measured by Ginster et al. (2019), https://doi.org/10.1016/j.gca.2019.01.033, into ZRDAAM. I explore several consequences of this alpha damage annealing model as it relates to (U‐Th)/He date‐effective uranium (eU) correlations, using representative time‐temperature paths and previously published results. Comparison between the current version of ZRDAAM, which uses fission track annealing, and the new annealing model demonstrates that, for thermal histories with prolonged periods at low temperatures (<50°C), alpha dose annealing kinetics yield slightly younger model dates at low to moderate eU concentrations, older dates at moderate to high eU, and substantially younger dates at the highest eU concentrations. The absolute eU concentrations over which the differences are observed varies for a given thermal history, so these ranges should be interpreted as relative or proportional. Younger model dates at high eU in most thermal histories result from lower amounts of annealing that occur with the Ginster et al. (2019) alpha dose annealing kinetics. This annealing model comparison illustrates that the choice of annealing kinetics has the greatest influence over model output for thermal histories involving either prolonged time periods in the 200–300°C temperature window, or a late‐stage reheating event. Key Points: A new modeling scheme is provided for radiation damage annealing in zirconThe new annealing model has implications for thermal history model results for zircon (U‐Th)/He date‐effective uranium trendsLarge discrepancies in output between the previous and latest model version manifest for thermal histories with late‐stage reheating events [ABSTRACT FROM AUTHOR]