Biomarker Parameters Research Articles

Usefulness of Antigen Carbohydrate 125 and N-Terminal Pro-B-Type Natriuretic Peptide for Assessing Congestion in Chronic Heart Failure: Insights from the CARDIOREN Registry

Introduction: A comprehensive assessment of congestion, including circulating biomarkers, is recommended in patients with acute heart failure. The circulating biomarkers natriuretic peptides (NPs) and carbohydrate antigen-125 (CA125) could be useful for congestion assessment in ambulatory chronic heart failure (CHF), but there is only limited information about their applicability in this context. Therefore, this study aimed to examine the association of plasma CA125 and NP levels with clinical and ultrasound congestion parameters in CHF. Methods: This is a cross-sectional substudy of the Cardioren Spanish Registry, which enrolled 1,107 patients with CHF from 13 tertiary hospitals in Spain between October 2021 and February 2022. Through ambulatory visits, we performed a comprehensive assessment of congestion-related parameters, including clinical variables (orthopnea, peripheral edema, and jugular engorgement, represented by the composite congestion score [CCS]), echocardiography variables (lung B-lines and inferior vena cava [IVC] diameter), and circulating biomarkers (CA125 and NPs). The association of the NP and CA125 levels with the clinical and echocardiographic congestion parameters was examined by multiple linear and logistic regression analyses. Results: This substudy included 802 patients for whom all the biomarker parameters were available {median age, 74 (interquartile range [IQR], 63–81) years; 65% male}. The proportion of patients with left ventricular ejection fraction ≥50% and estimated glomerular filtration rate <60 was 34% and 58%, respectively. The median CCS was 0 (IQR: 0–1), with 45% of the sample exhibiting a median CCS of ≥1. The jugular engorgement, peripheral edema, and orthopnea rates were 32%, 21%, and 21%, respectively. A total of 35% of patients who underwent ultrasound examination showed lung B-lines, and the median IVC diameter was 16 mm. The median CA125 and NTproBNP levels were 14 U/mL (IQR: 9–28) and 1,382 pg/mL (IQR: 563–3,219), respectively. Multivariate analysis showed that higher CA125 levels were independently associated with higher odds of peripheral edema (p = 0.023) and lung B-lines (p < 0.001). Further, NTproBNP was positively associated with jugular engorgement (p < 0.001), orthopnea (p = 0.034), and enlarged IVC diameter (p = 0.031). Conclusions: Clinical signs of congestion are frequent in CHF. In the ambulatory setting, NTproBNP was associated with parameters linked to intravascular congestion such as orthopnea, jugular engorgement, and IVC diameter, whereas CA125 was associated with extravascular volume overload parameters (peripheral edema and lung B-lines).

Deceased donor kidney function and branched chain amino acid metabolism during ex vivo normothermic perfusion

Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12- hour ex vivo normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during ex vivo normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience.

The origin and migration laws of hydrocarbons in uranium‐bearing Luohe Formation, Pengyang area, SW Ordos Basin

The hydrocarbon activity in Pengyang area, situated in the southwestern Ordos Basin, is notably prominent. Investigation on the migration laws of hydrocarbons is imperative for comprehending the involvement in uranium mineralization. Based on the analysis of spatial distribution of hydrocarbon containing fluid and hydrocarbon generation conditions of sandstone in the Luohe Formation, the organic geochemical characteristics including hydrocarbon components, carbon isotopes and biomarker compounds were analysed. The research results indicate that: (1) hydrocarbon fluid activities in the Luohe Formation are predominantly observed in layers exhibiting higher uranium mineralization. The mudstone of the Luohe Formation had low organic matter content and low thermal maturity, which was not conducive to hydrocarbon generation. (2) Hydrocarbon‐containing fluid in the sandstone of Luohe Formation not only contained reducing gases such as methane and hydrogen but also chloroform asphalt components. The carbon isotopes of hydrocarbon in sandstone inform Luohe Formation resemble oil and gas in the Mesozoic. The biomarker parameter inferred that the parent rock of hydrocarbons in the Luohe Formation was formed under reducing and freshwater conditions, and hydrocarbon generation occurred at the mature stage. As above mentioned, a comparison was carried out between the affinity of hydrocarbon‐containing fluid in the Luohe Formation and different layers of hydrocarbon source rocks. The migration behaviour of hydrocarbon‐containing fluid in the Pengyang area has been summarized, and the involvement of hydrocarbon‐containing fluid in uranium mineralization has been discussed. The main concepts are as follows: the sedimentary environment and thermal evolution conditions of hydrocarbons in the sandstone of Luohe Formation resemble those of the primary hydrocarbon source rocks in the Yanchang Formation. The main hydrocarbon charging events in the Luohe Formation occurred before the Late Cretaceous period, which is primarily related to two hydrocarbon generation events from 130 to 100 Ma in the Yanchang Formation and fault conduits connecting the Triassic to the Cretaceous Strata. The hydrocarbon‐containing fluid released from Yanchang Formation migrating to the Luohe Formation provides reducing conditions for the precipitation of uranium in oxygen‐bearing water bodies.

Geochemical evaluation of Sarvak oil reservoir using biomarkers, carbon isotope and trace element: A case study from Southwest Iran

The crude oils of the Sarvak reservoir were studied by integrated geochemical, inorganic and isotopic analyses to evaluate the origin, depositional conditions, geological age, thermal maturity of the source rocks and possible facies from which these oils were sourced. This study provides new insights into the Middle-Jurassic age source rock in the Azar Oilfield. This is the first geochemical study in Azar Oilfield where non-biomarker parameters and biomarker parameters were utilized to achieve the objectives. The n-alkane distribution pattern along with their standard ratios, including CPI (0.83–1.03), TAR (0.18–0.29) and isoprenoids (Pr/Ph, 0.52–0.65) as well as pristane/n-C17 versus phytane/n-C18 cross-plot indicate a marine source of the organic matter deposited in an anoxic condition. The sterane parameters such as C27 and C29 are characterized by the predominance of C27ααα-20R steranes (41%–49%) and also depict the algal source of organic matter. The organic input and facies of the source units were also determined by terpanes C29/C30H, Ts/Tm, C35/C34-HH, and DBT/Phen. The relatively high ratio of C29/C30H along with the ratios of Ts/Tm (<0.5) and C35/C34 (>0.8) reflect the carbonate marine facies of the source rocks. Furthermore, the higher values of the homohopane index (>0.1) along with the low ratio of the gammacerane/C30-H (0.06–0.22) as well as the high ratio of V/Ni (>1) further indicate anoxic environments. The dibenzothiophene/phenanthrene ratios of the oil samples (from 2.43 to 3.25) indicate the marine carbonates/marl zone. This genetic classification is also supported by stable carbon isotopic compositions (δ1³C). Most of the maturity-related biomarkers and non-biomarker parameters such as CPI, steranes-C29S/(S + R), ββ/(αα+ββ), moretane to hopane (M29/C30H), pentacyclic terpanes C27Ts/(Ts + Tm), C32-S/(S + R) hopanes, and methyl phenanthrene index agree that the analyzed oils have originated from mature source rocks. Ultimately, this study has demonstrated that analyses of biomarkers and their stable isotope compositions (δ13C and δ34S) complemented with trace element data provide an excellent novel tool for better understanding the basic concepts in petroleum basins and for solving a wide range of problems during petroleum exploration.

Biological origin and depositional environment of crude oils in the Qiongdongnan Basin: Insights from molecular biomarkers and whole oil carbon isotope

Molecular biomarker and whole oil carbon isotope (δ13Coil) analyses were conducted on eleven typical crude oils from the Qiongdongnan Basin to investigate their biological sources and depositional environments. Saturated hydrocarbon biomarkers in most samples are characterized by angiosperm-derived compounds, with aromatic compounds dominated by the naphthalene, phenanthrene, biphenyl, and fluorene series. The related source rocks of these oils were mainly deposited under oxic condition, but a subanoxic–suboxic and enclosed water column condition in the Central Depression during Oligocene. The identification of simonellite and related compounds in the aromatic fractions provides reliable evidence for the input of coniferous gymnosperms. Cadalene may also have a potential association with gymnosperms since it shows a strong positive correlation with simonellite. Evidence from density, n-alkanes, short-chain alkylbenzenes and secondary brine inclusions indicates that the unique crude oil B13–1 may have suffered from thermal alteration. These crude oils (excluding B13-1) can be classified into four types based on the δ13Coil values and molecular biomarkers. Type A oil (solely S34-3) is characterized by non-angiosperm plants, with minor dinoflagellates and increasing contribution from conifer gymnosperms than others. Type B oils (L17–2, L18–1, L25-1, and L25-1W) show heavy δ13Coil (−24 ‰ to −25 ‰) and mixed contributions from both angiosperms and marine algae, with the marine algae contribution increasing. Type C oils (L13–2 and B21-1) share similar biological sources with Type B, but the moderately δ13Coil (−25‰ to −26‰) and high level of terrestrial biomarkers suggesting a predominant contribution of angiosperms. Type D oils (sample Y13-1a, Y13-1b, and Y13-4) possess the lightest δ13Coil (mainly below −26‰) and are primarily derived from angiosperms, with mangrove vegetation playing an important role. Spearman correlation analysis among 14 source biomarker parameters with δ13Coil and geological setting of related source rocks implied that the marine algae should be responsible for the heavy δ13Coil in the Type B. The contribution of marine algae in the Central Depression may have been neglected in the past, as it is usually covered by remarkable angiosperm biomarkers.

A new method to quantify the source contribution of mixed biodegraded oil based on pareto-optimized nonnegative matrix factorization and chord diagram visualization

The biogenic information of different components in crude oils with varying degrees of biodegradation is partially obscured, making traditional molecular indicators ineffective in determining the contributions of mixed sources. Previous studies have mainly focused on calculating mixed source proportion for normal oils, with few investigations involving biodegraded mixed oils. Developing a quantitative method for the mixed source contribution of biodegraded oils using machine learning (ML) algorithms is a significant attempt both to the exploration practice and theoretical progress. Taking the biomarker parameters resistant to biodegradation of 150 oil samples as input datasets, a new method called Pareto-Optimized NMF (PONMF) was proposed in this study, which combines multi-objective optimization (Pareto optimization) with non-negative matrix factorization (NMF) to analyze the relationship between biodegraded oils in the absence of source rock samples or original end-member (EM) oils while satisfying non-negativity constraints and additional constraint conditions. This method decomposes the matrix of crude oil samples into multiple end-members, each representing a possible input from a hydrocarbon source rock. Analysis of the end-member characteristics facilitates the deduction of potential hydrocarbon source layers and the traits of their depositional environments. This examination is supported by data derived from 15 prospective hydrocarbon source rock samples, which were employed to ascertain the actual geological significance of the end-members. The chord diagram depicts the visualization results of the overall relative contribution of source rock end members to crude oil in each area after the PONMF calculation results. The relative contribution of source rocks in different areas to the investigated crude oil samples is proportionate, and the arc length can reflect the contribution of the three sets of source rocks to a certain area. The findings indicate that the oils extracted from the stratified reservoirs in Eastern Chepaizi are primarily derived from the Permian source strata within the Shawan Depression, with a significant contribution ranging from 30% to 90% (EM2), and a lesser extent from the Carboniferous sources, contributing between 5% and 30% (EM1). Conversely, the provenance of oil in Western Chepaizi is overwhelmingly attributed to the Jurassic source interval located in the Sikeshu Depression, where EM3 accounts for over 85% of the source. Meanwhile, the oils in the Central Zone exhibit a composite origin, intermingling contributions from both EM1 and EM3. The advantage of this method is that it does not require direct access to hydrocarbon source rock samples or end-member oils but infers potential hydrocarbon source layers through the existing mixed-source oil samples. The PONMF method provides an effective tool for identifying the sources of biodegraded oils and can be used to study potential hydrocarbon source rock analysis for oils that have undergone biodegradation after hydrocarbon accumulation.

Chemometric analysis on concentrations and ratios of terpanes and steranes and implications for oils from the cratonic region of the Tarim Basin, NW China

More than 2 × 109 tonnes of proved oils have been found in the cratonic region of the Tarim Basin. The source rocks for these oils remain unresolved although the source rocks are marine facies within the Cambrian and Ordovician strata with total thickness over 5 km. So far, there is no systematic classification of these oils on the basis of source facies. In this study, a practical approach was presented to select effective and sensitive biomarker parameters for source facies and maturity assessments for the studied oils on the basis of biomarker classification by hierarchical cluster analysis (HCA). Twenty-one terpanes and steranes in oils from both the Tabei (Northern Tarim) and Tazhong (Central Tarim) uplifts were classified into three groups using HCA on the basis of terpane and sterane concentrations. The result of biomarker grouping mainly reflects the differences in thermal stabilities among biomarkers for the 45 Tabei oils, providing a general thermal stability sequence for terpanes and steranes that helps the selection of effective maturity parameters. However, biomarker grouping suggests that both source facies and thermal stability have major influences on relative biomarker concentrations for the 75 Tazhong oils. The Tabei oils are mainly derived from a single source with relatively homogeneous facies while the Tazhong oils are derived from multiple sources or a single source with more heterogeneous facies. Based on the HCA results, twelve terpane and sterane ratios were selected as source facies parameters for the Tabei and Tazhong oils. These studied oils were consequently classified into four families by HCA and principle component analysis (PCA) integrating the twelve selected facies parameters of terpanes and steranes along with Pr/n-C17 and Ph/n-C18 ratios. Family 1 and 2 oils are mainly in the Tabei uplift while Family 3 and 4 oils are almost in the Tazhong uplift. Family 1 and 2 oils are derived from source rocks located at the northern, central and southern areas of the Northern Depression and the Tabei Uplift with marine mudstone facies. Family 3 and 4 oils are derived from source rocks located mainly at the southern area of the Northern Depression and the Tazhong Uplift with carbonate and evaporite facies. This study provides a practical approach to trace oil origins for oil and condensate reservoirs in the Tarim Basin and elsewhere.

A Correlation Study on Serum Biomarker and Biochemical Parameters in Acute Heart Failure with Duration of Hospital Stay among Patients with Acute Heart Failure

A Correlation Study on Serum Biomarker and Biochemical Parameters in Acute Heart Failure with Duration of Hospital Stay among Patients with Acute Heart Failure

Accumulation and Quantitative Assessment of Terrigenous Organic Matter in Upper Oligocene to Lower Miocene Marine Source Rocks of the Qiongdongnan Basin.

The intense collision between marine and terrestrial agents results in the dual-source (marine and terrigenous) characteristics of marine source rocks. Our research quantitatively assessed terrestrial organic matter and revealed the crucial role of terrestrial organic materials in the organic matter enrichment of lower Miocene to upper Oligocene marine source rocks in the Qiongdognnan Basin. The quantitative assessment was achieved using partial least-squares analysis with eight biomarker parameters associated with n-alkanes, isoprenoids, bicadinanes, taraxerane, tricyclic terpanes, and gammacerane. Differential unloading of terrestrial organic materials based on sedimentary facies of the delta-marginal sea system were observed through oleanane and bicadinane contents. It should be noted that the diagnostic ratio of oleanane was excluded from the quantitative analysis due to the dual influence from differential unloading and contact with seawater of the terrestrial organic materials. Calculation results show that the terrestrial organic matter was highest in the delta front at 70%, followed by prodelta at 59% and inner shallow marine at 57%. From the late Oligocene to the early Miocene, the proportion of terrestrial organic matter in marine source rocks continuously increased, with the highest average value observed in the second member of the Sanya Formation at 69% and the lowest occurring in the third member of the Lingshui Formation at 46%. Increasing terrestrial organic material inputs and preservation driven by the East Asian summer monsoon provided first-order control of the accumulation of organic carbon in the Qiongdongnan Basin during late Oligocene to early Miocene, rather than the bioproductivity of marine algae. The redox conditions of the water column determine the enrichment extent of organic matter.

Differences in Glutamate Dehydrogenase (GLDH) and Other Liver Biochemistry Levels before and after Remdesivir Treatment in COVID-19

Background: Remdesivir (RDV) is a broad-spectrum antiviral approved by the Food and Drug Administration (FDA) for the treatment of Covid-19 patients, known to have the potential to cause toxic effects on the liver. Routine monitoring of liver biochemical parameters such as AST, ALT, bilirubin, ALP and GGT, can help detect liver injury. Drug-induced liver injury, according to Hy's law, is characterized by an increase in ALT &gt; 5x ULN, or ALP &gt; 2x ULN, or an increase in ALT &gt; 3x and total bilirubin &gt; 2x ULN, simultaneously. Glutamate dehydrogenase (GLDH) is a sensitive and specific hepatic marker, which can detect liver injury and loss of mitochondrial integrity earlier than other liver biochemical parameters. This study aimed to analyze GLDH levels and liver biochemical parameters before and after RDV therapy in patients with Covid-19. We also analyze several factors that affect liver function and suggest renal function. Methods: This study used an observational analytical with a prospective cohort design, in a population of Covid-19 patients receiving RDV therapy at the infectious emergency department and isolation ward Dr. Soetomo Surabaya for September-November. Consecutive sampling was taken. The subject had drawn blood twice; once before therapy and 5 days after receiving intravenous RDV. GLDH examination is using sandwich ELISA method, while ALT, AST, ALP, GGT, direct and total bilirubin were determined spectrophotometrically. Mann-whitney, the Wilcoxon rank test and Spearman correlation test were used to analyze the data. Results: The number of samples was 34 participants with an average age of 52.47+15.21 years. Concomitant medications were dominated by n-acetylcysteine (94.1%), antioxidants (91.2%) and immunomodulators (82.4%). None of the subjects suffered liver injury induced by RDV according to Hy’s Law. Median GLDH serum levels before RDV treatment 1,14 U/L and after 5 days RDV administration 0,85 U/L (p=0,945), AST (36,4 U/L; 34, 00U/L; p=0,140), ALT (30,43 U/L; 30,20 U/L; p=0,301), DBI (0,15mg/dL; 0,24mg/dL; p=0,090), TBI (0,49mg/dL; 0,50mg/dL; p=0,567), ALP (85,0U/L; 87, 5 U/L; p=0,313) dan GGT (64,5U/L; 71,0U/L; p=0,871). The use of concomitant medication was thought to have protective properties against hepatocytes. Conclusion: After 5 days of RDV treatment, there is no evidence of liver injury. There are no significant differences in GLDH levels and other liver biomarker parameters compared to baseline. There is no difference in delta GLDH levels between groups with and without renal impairment.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Investigation on the thermal maturity, organic matter sources and depositional environment of lacustrine source rocks in the Dongying Formation of the Bozhong Sag, Bohai Bay Basin, China

The unclear understanding of the source rock characteristics for the Paleogene Dongying Formation in the Bozhong Sag leads to the lack of cognition in oil and gas exploration. This research systematically evaluated the discrepancy in geochemical characteristics of source rock intervals in the Dongying Formation based on detailed analysis using Rock‐Eval pyrolysis, total organic carbon (TOC), vitrinite reflectance (Ro), maceral components, stable carbon isotopes and biomarker parameters. It discusses the organic matter sources, depositional environment, thermal maturity and hydrocarbon generation potential in the source rock intervals of the Dongying Formation. The organic matter abundance in the third member (E3d3) and lower sub‐member of the second member (E3d2L) of the Dongying Formation is higher, with an average TOC of 2.08% and 1.03%, respectively, indicating that these source rock intervals could have good and excellent quality. The source rocks of the Dongying Formation predominately contain exinite maceral group and type II1 and II2 kerogen. The thermal evolution is mainly in the low‐mature and mature stages. The organic matter sources in the Dongying Formation are mainly dominated by mixed origin (the carbon isotope reversal of aromatics also provides a potential explanation). However, the values of 1,2,5−/1,3,6‐trimethylnaphthalene, (1,2,5,6 + 1,2,3,5)‐tetramethylnaphthalene/tetramethylnaphthalenes, methyldibenzofuran/methylphenanthrene (MDBF/MP) and dibenzofuran/phenanthrene (DBF/PHEN) parameters in the E3d3 and some samples in E3d2L decipher relatively smaller values than other source rock intervals, proving the enhancement of the contribution of lower organisms. Moreover, the terrestrial input in the bottom‐up deposition process of the Dongying Formation gradually increases. The depositional environment reveals the Dongying Formation source rocks mainly developed freshwater sulphur‐poor lacustrine facies and shallow lake‐fluvial delta facies in an open clay‐rich sedimentary environment with poor water column stratification, belonging to the typical weak oxidation–reduction depositional conditions. The comprehensive geochemical evaluation concludes that the favourable supply of lower organisms and stable clay‐rich depositional environment in the E3d3 interval of the Dongying Formation are potential explanations for the formation of lacustrine source rocks with high organic matter abundance, intermediate thermal evolution and excellent hydrocarbon generation potential, providing a good foundation for the exploration and development prospects of hydrocarbons.

A Novel Approach for Investigating the Paleo-Oil Filling Orientations: Constraints by Biodegradation Evaluation Proxies and Recovered Biomarker Parameters

A Novel Approach for Investigating the Paleo-Oil Filling Orientations: Constraints by Biodegradation Evaluation Proxies and Recovered Biomarker Parameters

Geochemical investigation and hydrocarbon generation–potential of the Chia Gara (Tithonian–Berriasian) source rocks at Hamrin and Kirkuk fields, Northwestern Zagros Basin, Iraq

This study investigates the geochemical characteristics and hydrocarbon generation potential of the Chia Gara Formation (Tithonian–Berriasian) in the Northwestern (NW) Zagros Basin, Iraq. A comprehensive analysis of forty–seven extract samples and seven crude oil samples was conducted to evaluate the formation’s petroleum potential. The total organic carbon (TOC) content of the analyzed samples ranged from 0.68% to 3.95%, indicating fair to excellent source rock quality. Rock–Eval parameters revealed thermal maturity, suggesting an environment favorable for both oil and gas generation.Integrated analysis of TOC/Rock–Eval data, stable carbon isotope data, and biomarker parameters confirmed the existence of kerogen Type–II and mixed–II/III constituents, along with carbonate–rich deposits. These findings suggest deposition within an algal–dominant anoxic-marine environment.Characterization of crude oils from these fields revealed paraffinic types, further supporting the interpretation of the Chia Gara interval as the primary source rock in the NW Zagros Basin. The oil–source correlation strengthens the evidence, consolidating the formation’s significance in the region’s petroleum system.

Geochemical Characteristics of Mesoproterozoic Source Rocks in North China: Insights for Organic Matter Enrichment and Thermal Evolution

In recent years, the exploration of oil and gas in China’s Precambrian strata has garnered significant attention, leading to notable advancements in exploration play assessment. However, there is a dearth of published literature on Proterozoic source rocks’ organic sources, sedimentary environments, marine hydrochemistry, and other attributes. This study focuses on investigating potential source rocks within the Hongshuizhuang and Xiamaling Formations in the Jibei Depression of North China. A comprehensive analysis was conducted to evaluate hydrocarbon generation characteristics, using hydrocarbon biomarkers and polar compounds as geochemical indicators for precursor biota and maturity levels. The results indicate high organic matter abundance with predominantly type I-II1 organic matter composition in the studied source rocks. These samples are at an immature–low mature stage, with the potential for primarily generating aromatic crude oil. The parent material is mainly attributed to lower aquatic organisms, such as bacteria and algae. The sedimentary environment exhibits marine facies, characterized by high evaporation rates, salinity levels, and strong euxinic conditions, that led to sulfur incorporation into the organic matter matrix. It should be noted that correlations between biomarker parameters and maturity may not be fully applicable to ancient source rocks; however, the methyldibenzothiophene ratio (MDR) demonstrates a strong correlation with Tmax. The compounds and their total monoisotope ions abundance (TMIA) were primarily identified and analyzed using FT–ICR MS. It was observed that these compounds were influenced by the depositional environment and organic matter maturity. Importantly, it was clearly demonstrated that the DBE and carbon number range of CH compounds gradually increased with maturity, due to the removal of N, S, and O functional groups. Specifically, N1 compounds predominantly consisted of carbazoles with short alkyl side chains which readily converted into N1Ox compounds. On the other hand, O1 compounds mainly comprised benzofurans with low abundance, indicating a reducing sedimentary environment, as suggested by their low TMIA values. Furthermore, S1 compounds were primarily thiophenes whose DBE range and carbon number increased with maturity, possibly suggesting an abiotic input of inorganic sulfur. Notably, the maturity indices (MAT) proved suitable for Mesoproterozoic source rocks while exhibiting strong linear relationships.

Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double-blind clinical trial.

Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced Clostridium clostridioforme (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating Bacteroides caccae and Bacteroides uniformis (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.

Impact of aerobic reworking of biomass on steroid and hopanoid biomarker parameters recording ecological conditions and thermal maturity

Steranes and hopanes are the biomarkers of eukaryotic sterols and bacterial hopanols. Extracted from sedimentary rock, they are widely used to assess burial temperatures and palaeoecological conditions. The relative proportion of steranes and hopanes is commonly applied as a measure of the flux of eukaryotic versus bacterial biomass into sediments, and the relative abundances of C27, C28 and C29 steranes are proxies for shifts in eukaryote ecology. In Recent sediments, intact sterols provide additional information about particular eukaryotic origins. However, biological lipid distributions are not always recorded faithfully in sediments. Based on observations on modern algae and plants, and on 558 million year old fossil macroalgae from the Ediacaran of the White Sea, we suggest that these biomarker proxies can be severely altered by aerobic microbial reworking, to the extent that a complete loss of primary ecological information may occur. Network analysis on the biomarker data suggests that oxic degradation also affects isomer and homolog distributions of saturated and aromatic steroids, hopanes, cheilanthanes and n-alkanes, generating anomalies in apparent thermal maturity indicators and other proxies. In our dataset, between Ediacaran macroalgae that experienced the least and the most oxic degradation, the absolute concentration of biomarkers decreases 80-fold, and at the same time the proportion of steranes over hopanes decreases by a factor of 82, while the proportion of C29 steranes among total steranes decreases from 91% to 47%. Such redox dependent offsets may explain the recurrently erratic behaviour of numerous biomarker parameters. While these results impart constraints on the interpretation of biomarker distributions, they do provide a tool for evaluating the effects of oxygen exposure and microbial degradation on organic matter preservation in recent and ancient environments and may point towards a solution for the correction of such effects.

Intelligent geochemical interpretation of mass chromatograms: Based on convolution neural network

Gas chromatography-mass spectrometry (GC-MS) is an extremely important analytical technique that is widely used in organic geochemistry. It is the only approach to capture biomarker features of organic matter and provides the key evidence for oil-source correlation and thermal maturity determination. However, the conventional way of processing and interpreting the mass chromatogram is both time-consuming and labor-intensive, which increases the research cost and restrains extensive applications of this method. To overcome this limitation, a correlation model is developed based on the convolution neural network (CNN) to link the mass chromatogram and biomarker features of samples from the Triassic Yanchang Formation, Ordos Basin, China. In this way, the mass chromatogram can be automatically interpreted. This research first performs dimensionality reduction for 15 biomarker parameters via the factor analysis and then quantifies the biomarker features using two indexes (i.e. MI and PMI) that represent the organic matter thermal maturity and parent material type, respectively. Subsequently, training, interpretation, and validation are performed multiple times using different CNN models to optimize the model structure and hyper-parameter setting, with the mass chromatogram used as the input and the obtained MI and PMI values for supervision (label). The optimized model presents high accuracy in automatically interpreting the mass chromatogram, with R2 values typically above 0.85 and 0.80 for the thermal maturity and parent material interpretation results, respectively. The significance of this research is twofold: (i) developing an efficient technique for geochemical research; (ii) more importantly, demonstrating the potential of artificial intelligence in organic geochemistry and providing vital references for future related studies.

Evaluation of disease progression in patients with ATTR amyloidosis with cardiomyopathy following treatment with patisiran: post-hoc analysis of the APOLLO-B study

Abstract Introduction Transthyretin-mediated (ATTR) amyloidosis is a progressive, fatal disease in which cardiac deposition of transthyretin (TTR) amyloid commonly manifests as cardiomyopathy. Patisiran, an RNA interference therapeutic that reduces TTR synthesis, is approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy. The Phase 3 APOLLO-B study (NCT03997383) evaluated the clinical efficacy and safety of patisiran in patients with ATTR amyloidosis with cardiomyopathy (CM). Purpose This post-hoc analysis evaluated disease progression in APOLLO-B patients following treatment with patisiran vs placebo, based on the European Society of Cardiology (ESC) expert consensus on monitoring patients with ATTR amyloidosis with CM every 6–12 months using three domains: Clinical/Functional, Laboratory Biomarker, and Imaging/Electrocardiography (ECG). Methods Patients with ATTR amyloidosis with CM were randomised (1:1) to intravenous patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. Disease progression was defined at Month 12 (M12) relative to baseline using Clinical/Functional criteria (≥1 heart failure-related hospitalisation, increased New York Heart Association class ≥1, decline in Kansas City Cardiomyopathy Questionnaire ≥5, or decline in 6-minute walk test ≥30 metres), Laboratory Biomarker criteria (increased N-terminal prohormone B-type natriuretic peptide ≥30% and absolute change ≥300 ng/L, troponin I ≥30%, or ATTR disease stage ≥1), and Imaging/ECG criteria (conduction disturbances or change in left ventricular wall thickness ≥2 mm, change in diastolic dysfunction grade ≥1, or change in systolic function measurements). One marker from each domain provides the minimum criteria for disease progression. Results At M12, the patisiran group (N = 180) had improved odds of no disease progression compared with the placebo group (N = 178; odds ratio [OR] 1.4; 95% confidence interval [CI] 0.77, 2.55) (Figure). The patisiran group had benefits in Clinical and Functional markers vs placebo at M12 (OR 1.58; 95% CI 1.03, 2.42). Patisiran also showed favourable changes in Laboratory Biomarkers vs placebo at M12 (OR 2.14; 95% CI 1.33, 3.43) and a favourable trend in Imaging assessments/ECG vs placebo at M12 (OR 1.31; 95% CI 0.80, 2.15). Conclusion In this post-hoc analysis of APOLLO-B, fewer patisiran-treated patients had disease progression with respect to clinical, functional, and biomarker parameters vs placebo. The risk of disease progression was lower by Clinical/Functional and Laboratory Biomarker composite criteria, and trended lower by individual criterion from the ESC consensus statement among patisiran-treated patients at 12 months vs placebo patients. Long-term follow-up will further assess the impact of patisiran in patients with ATTR amyloidosis with CM.Figure 1

Abstract 16840: A Novel Long-Acting CRF2 Receptor Agonist COR-1167 Improves Cardiac and Renal Function on Top of Furosemide in a Sheep Model of Pacing Induced Heart Failure

Urocortin-2 (UCN-2), a member of the corticotrophin releasing factor family, has cardiovascular protective effects mediated via activation of CRF2 receptors. Exploratory studies in ovine heart failure (HF) and in HF patients demonstrated that acute intravenous (IV) infusion of UCN-2 (1-4hrs), on top of standard of care, temporarily improved cardiac function. However, the short t 1/2 of recombinant UCN-2 (~15 min) limits its therapeutic utility. A stable CRF2 peptide agonist was developed, named COR-1167, that is potent and selective for CRF2 versus CRF1 receptors and it was tested chronically in vivo. Adult female sheep were anesthetized, and instrumented with 7F His bundle electrodes, arterial, venous and Swan-Ganz catheters, pressure transducers, and flow probes. After recovery, HF was induced by rapid cardiac pacing that was maintained during the study. COR-1167 (5 μg/kg/day SC) in combination with furosemide (0.35 mg/kg/day IV) versus furosemide alone was administered for 5 days and cardiorenal parameters were constantly monitored in conscious sheep. Furosemide had no effect on cardiac function while it increased urine Na + , when compared to pre-treatment measurements. Compared to furosemide, COR-1167 plus furosemide significantly enhanced cardiac and renal function parameters (Table). Mean + SEM for Days 1-5 (CV, biomarker and renal parameters), F (n=5-7), F + COR-1167 (n=6-7), Repeated Measures ANOVA; *BW Day 0 minus Day 5 = BW change, Unpaired t test. COR-1167 cardiorenal benefits occurred within 2 hours of the first dose and were sustained, without changing SBP. It increased natriuresis and decreased net fluid balance (water intake minus urine volume) and BW (reflecting a reduction in congestion). In conclusion, chronic CRF2 receptor activation by COR-1167 significantly improved both cardiac and renal function on top of furosemide in ovine HF and potentially is a unique therapy for HF patients.