Time series bioaccumulation of rare earth elements （REEs） in field-grown wheat with and without a dressing of extraneous REE fertilizer at different growth stages and fractionation of REEs during their transport in ...Time series bioaccumulation of rare earth elements （REEs） in field-grown wheat with and without a dressing of extraneous REE fertilizer at different growth stages and fractionation of REEs during their transport in a soil-wheat system were determined. Time-dependent accumulation of extraneous REEs was found in different parts of wheat. An upward transport of extraneous REEs from roots to shoots under a soil dressing and a downward transport from leaves to roots with a foliar dressing were also observed. Moreover, fractionation of REEs occurred in the soil-wheat system. Compared to the host soil a positive Eu anomaly in the stems and grains as well as heavy REE enrichment in the grains were found. The ability of the different wheat organs to fractionate Eu from the REE series was ranked in the order of sterns 〉 grains 〉 leaves 〉 roots.展开更多
The geochemical behaviors of hydrogen and oxygen isotopes in the hydrothermal system and their inher-ent relationship with the water / rock exchange are discussed in this paper In addition to the temperature con-ditio...The geochemical behaviors of hydrogen and oxygen isotopes in the hydrothermal system and their inher-ent relationship with the water / rock exchange are discussed in this paper In addition to the temperature con-ditions, the effective W / R ratio is another factor controlling the changes in H and O isotope compositions ofthe altered rock and hydrothermal water. Besides, the application and geological significance of the water-rockexchange theory are also discussed in the light of the H and O isotope compositions and their variation charac-teristics of the mineralizing hydrothermal water and altered rocks from several mineral deposits. Finally, abrief evolutional model of H and O istotope compositions of meteoric and magmatic hydrothermal waters in ahydrothermal system is given.展开更多
Developing a cost-effective and environmentally friendly process for the production of valuable chemicals from abundant herbal biomass receives great attentions in recent years.Herein,taking advantage of the“lignin f...Developing a cost-effective and environmentally friendly process for the production of valuable chemicals from abundant herbal biomass receives great attentions in recent years.Herein,taking advantage of the“lignin first”strategy,corn straw is converted to valuable chemicals including lignin monomers,furfural and 5-methoxymethylfurfural via a two steps process.The key of this research lies in the development of a green and low-cost catalytic process utilizing magnetic Raney Ni catalyst and high boiling point ethylene glycol.The utilization of neat ethylene glycol as the sole slovent under atmospheric conditions obviates the need for additional additives,thereby facilitating the entire process to be conducted in glass flasks and rendering it highly convenient for scaling up.In the initial step,depolymerization of corn straw lignin resulted in a monomer yield of 18.1 wt%.Subsequently,in a dimethyl carbonate system,the carbohydrate component underwent complete conversion in a one-pot process,yielding furfural and 5-methoxymethylfurfural as the primary products with an impressive yield of 47.7%.展开更多
Gypsum from the wet flue gas desulfurization system of the lignite fired thermal power plant Sostanj, Slovenia, can efficiently retain mercury (Hg), of which most is contained in finer gypsum fractions, with concentra...Gypsum from the wet flue gas desulfurization system of the lignite fired thermal power plant Sostanj, Slovenia, can efficiently retain mercury (Hg), of which most is contained in finer gypsum fractions, with concentrations above 10 kg-1. The aim of this work was to identify and study the temperature stability of Hg species in gypsum by a temperature fractionation (TF) method. A self-constructed apparatus was used that consisted of an electrical furnace for controlled heating up to 700°C, with a heating rate of 2.2°C·min-1, and an AAS detector with Zeeman background correction. The pattern of Hg release during temperature increase depends highly on the matrix/substrate in which it is contained. Based on spiking gypsum with known Hg compounds we concluded that the largest proportion of Hg in gypsum belongs to Hg-Cl and Hg-Br compounds appearing at 160°C to 200°C, followed by smaller amounts of HgO, HgS and Hg sulfates appearing at 300°C and 450°C. Further development of methodology for identifying Hg species would require identification of the decomposition fragments of Hg and other compounds, complemented by a better understanding of Hg reactivity at higher temperatures.展开更多
This study aimed to characterize constituents of phosphorus （P） fractionation as wel as reciprocities among factors in sediments of a freshwater shal ow lake. [Method] Surface sediment was discretely sampled at 24 s...This study aimed to characterize constituents of phosphorus （P） fractionation as wel as reciprocities among factors in sediments of a freshwater shal ow lake. [Method] Surface sediment was discretely sampled at 24 sites through Van Veen grabs. Based on a modified sequential extraction scheme, P fractionation was determined as Fe/Al bound P （Fe/Al-P）, Ca bound P （Ca-P）, solute and re-ductive P （S/R-P） and organic P （OP）. Curve estimation and Pearson product-mo-ment correlation were employed for statistical analysis. [Result] Total P （TP） content ranged from 443 to 774 mg/kg. Inorganic P （IP） was the major component of TP, of which Ca-P was dominated with an average of 51%±9.7%. Average contents of P fractionation were in the fol owing order： Ca-P（51%） 〉 OP（29%） 〉 S/R-P（8%） 〉Fe/Al-P（7%）. The molar ratio of Fe to P was 11 - 20, close to the threshold value of P leaching. [Conclusion] In freshwater shal ow lakes, IP and Ca-P were prone to be relatively high, whereas Fe/Al-P was low compared with deep lakes. Occurrence of spatial y monotonic gradient indicated the primary causation of anthropogenic sources. Imminent sediment P liberation was also expected. Close associations a-mong TP, Fe/Al-P and Ca-P, implying that anthropogenic P was mainly bound to metals in particulates. Significant correlations of TOC and P fractionation highlighted endogenous mechanism and authigenic origin in sediments.展开更多
This paper presents a model of isotopic fractionation by freezing under near equilibrium conditions in an open system and uses the model to predict the fractionation curve and slope gradient of δ 18 O versus δ...This paper presents a model of isotopic fractionation by freezing under near equilibrium conditions in an open system and uses the model to predict the fractionation curve and slope gradient of δ 18 O versus δD. The simulation results show that 1) the fractionation curve and slope gradient are determined by the ratio of freezing rate to input rate, 2) the isotopic value in the initial stage of freezing is determined by the isotopic value of initial water; 3) in the latter half of freezing in an open system, the isotopic value converges to a certain value determined by that of input water. These results suggest that the shape of the fractionation curve is the method to distinguish whether freezing occurred in a closed or open system. This analysis is applied to an isotopic curve observed in basal ice of Hamna Glacier, Sya drainage, East Antarctica. The isotopic curve indicates formation by regelation in an open system with a ratio of freezing/input rates of about 10/4.展开更多
Oxygen isotope fractionation is studied during the synthesis of kaolinite under controlled conditions of temperature and time. Equilibrium conditions have been established and its relationship with temperature has bee...Oxygen isotope fractionation is studied during the synthesis of kaolinite under controlled conditions of temperature and time. Equilibrium conditions have been established and its relationship with temperature has been studied. Kaolinite was hydrothermally precipitated starting from non-crystalline aluminosilicate gels. The amount of kaolinite obtained increases up to a limited constant value and in all cases coexists with the amorphous starting gels. It can be seen that the data obtained at 48 hours of synthesis can be considered as quasi-equilibrium, since the total isotopic equilibrium has not been reached, only the sample obtained at 24 hours should be discarded for studies in equilibrium. This would allow us, with the samples obtained at 720 hours, to try to establish a relationship between isotopic fractionation and temperature, provided that we know the water in equilibrium with the synthesized kaolinite. Two equations have been obtained that show correlation coefficients with a high statistical significance.展开更多
Prediction of production decline and evaluation of the adsorbed/free gas ratio are critical for determining the lifespan and production status of shale gas wells.Traditional production prediction methods have some sho...Prediction of production decline and evaluation of the adsorbed/free gas ratio are critical for determining the lifespan and production status of shale gas wells.Traditional production prediction methods have some shortcomings because of the low permeability and tightness of shale,complex gas flow behavior of multi-scale gas transport regions and multiple gas transport mechanism superpositions,and complex and variable production regimes of shale gas wells.Recent research has demonstrated the existence of a multi-stage isotope fractionation phenomenon during shale gas production,with the fractionation characteristics of each stage associated with the pore structure,gas in place(GIP),adsorption/desorption,and gas production process.This study presents a new approach for estimating shale gas well production and evaluating the adsorbed/free gas ratio throughout production using isotope fractionation techniques.A reservoir-scale carbon isotope fractionation(CIF)model applicable to the production process of shale gas wells was developed for the first time in this research.In contrast to the traditional model,this model improves production prediction accuracy by simultaneously fitting the gas production rate and δ^(13)C_(1) data and provides a new evaluation method of the adsorbed/free gas ratio during shale gas production.The results indicate that the diffusion and adsorption/desorption properties of rock,bottom-hole flowing pressure(BHP)of gas well,and multi-scale gas transport regions of the reservoir all affect isotope fractionation,with the diffusion and adsorption/desorption parameters of rock having the greatest effect on isotope fractionation being D∗/D,PL,VL,α,and others in that order.We effectively tested the universality of the four-stage isotope fractionation feature and revealed a unique isotope fractionation mechanism caused by the superimposed coupling of multi-scale gas transport regions during shale gas well production.Finally,we applied the established CIF model to a shale gas well in the Sichuan Basin,China,and calculated the estimated ultimate recovery(EUR)of the well to be 3.33×10^(8) m^(3);the adsorbed gas ratio during shale gas production was 1.65%,10.03%,and 23.44%in the first,fifth,and tenth years,respectively.The findings are significant for understanding the isotope fractionation mechanism during natural gas transport in complex systems and for formulating and optimizing unconventional natural gas development strategies.展开更多
This article studies the existence and uniqueness of the mild solution of a family of control systems with a delay that are governed by the nonlinear fractional evolution differential equations in Banach spaces.Moreov...This article studies the existence and uniqueness of the mild solution of a family of control systems with a delay that are governed by the nonlinear fractional evolution differential equations in Banach spaces.Moreover,we establish the controllability of the considered system.To do so,first,we investigate the approximate controllability of the corresponding linear system.Subsequently,we prove the nonlinear system is approximately controllable if the corresponding linear system is approximately controllable.To reach the conclusions,the theory of resolvent operators,the Banach contraction mapping principle,and fixed point theorems are used.While concluding,some examples are given to demonstrate the efficacy of the proposed results.展开更多
In this paper,we study the existence of least energy solutions for the following nonlinear fractional Schrodinger–Poisson system{(−∆)^(s)u+V(x)u+φu=f(u)in R^(3),(−∆)^(t)φ=u^(2)in R^(3),where s∈(3/4,1),t∈(0,1).Und...In this paper,we study the existence of least energy solutions for the following nonlinear fractional Schrodinger–Poisson system{(−∆)^(s)u+V(x)u+φu=f(u)in R^(3),(−∆)^(t)φ=u^(2)in R^(3),where s∈(3/4,1),t∈(0,1).Under some assumptions on V(x)and f,using Nehari–Pohozaev identity and the arguments of Brezis–Nirenberg,the monotonic trick and global compactness lemma,we prove the existence of a nontrivial least energy solution.展开更多
Water-soluble organic matter(WSOM)significantly influences the transport of metals and organic contaminants in soils,yet the interaction specifics with antimony(Sb)remain largely unexplored.Antimony is of particular e...Water-soluble organic matter(WSOM)significantly influences the transport of metals and organic contaminants in soils,yet the interaction specifics with antimony(Sb)remain largely unexplored.Antimony is of particular environmental concern due to its toxic properties and harmful effects on ecosystems and human health.Employing a three-step fractionation method with polyvinylpyrrolidone(PVP),this study aimed to isolate and analyze humic acids(HA),PVP-non adsorbed fulvic acids(FAA),and PVP-adsorbed fulvic acids(FAB)from WSOM in soil spiked with Sb and incubated for 18 months.These fractions underwent chemical analysis for carbon(C),nitrogen(N),total organic carbon(TOC),and Sb,complemented by FTIR and 1H NMR spectroscopic characterization.The study revealed that HA wasmore aliphatic,with Sb predominantly associating with the fulvic acid(FA)fraction,accounting for 97%of Sb in extracts.Specifically,the FAA subfraction held substantial portions of total carbon(TC),total nitrogen(TN),total organic carbon(TOC),and Sb.Correlations between Sb concentrations and TN,TC,and TOC were significant.Extraction methods showed NaOH and Na_(4)P_(2)O_(7) outperformed HCl and deionised water in extracting TC,TN,and TOC,with higher Sb concentrations found in Na_(4)P_(2)O_(7) and NaOH extracts.This underscores the role of Fe/Al-SOM complexes in Sb soil availability.The results revealed that FAA subfraction accounted for 76%,64%and 94%of TN,TOC and Sb,respectively.Therefore,this research highlights the FAA fraction’s central role,predominantly comprising non-humic substances like amines,in the availability of C,N,and Sb in Sb-impacted soils.The findings offer insights for environmental management and remediation strategies.展开更多
Based on geochemical data from natural gas samples across spring water systems and sedimentary basins,including Songliao,Bohai Bay,Sanshui,Sichuan,Ordos,Tarim and Ying-Qiong,this paper systematically compares the geoc...Based on geochemical data from natural gas samples across spring water systems and sedimentary basins,including Songliao,Bohai Bay,Sanshui,Sichuan,Ordos,Tarim and Ying-Qiong,this paper systematically compares the geochemical compositions of abiogenic versus biogenic gases.Emphasis is placed on the diagnostic signatures of abiogenic gases in terms of gas composition,and carbon,hydrogen and helium isotopes.The main findings are as follows.(1)In hydrothermal spring systems,abiogenic alkane gases are extremely scarce.Methane concentrations are typically less than 1%,with almost no detectable C^(2+)hydrocarbons.The gas is dominantly composed of CO_(2),while N_(2)is the major component in a few samples.(2)Abiogenic alkane gases display distinct isotopic signatures,including enriched methane carbon isotopic compositions(δ^(13)C_(1)>-25‰generally),complete carbon isotopic reversal(δ^(13)C_(1)>δ^(13)C_(2)>δ^(13)C_(3)>δ^(13)C_(4)),and enriched helium isotope(R/Ra>0.5,CH_(4)/^(3)He≤10^(6)generally).(3)The hydrogen isotopic composition of abiogenic alkane gases may be characterized by a positive sequence(δD_(1)<δD_(2)<δD_(3)),or a complete reversal(δD_(1)>δD_(2)>δD_(3)),or a V-shaped distribution(δD_(1)>δD_(2),δD_(2)<δD_(3)).The hydrogen isotopic compositions of methane generally show limited variation(about 9‰),possibly due to hydrogen isotopic exchange with connate water.(4)In terms of identifying gas origin,CH_(4)/^(3)He-R/Ra andδ^(13)CCO_(2)-R/Ra charts are more effective than CO_(2)/^(3)He-R/Ra chart.These new geological insights provide theoretical clues and diagnostic charts for the genetic identification of natural gas and further research on abiogenic gases.展开更多
Microbial vanadate(V(V))reduction is a key process for environmental geochemistry and detoxification of vanadium(V).However,the electron transfer pathways and V isotope fractionation involved in this process are not y...Microbial vanadate(V(V))reduction is a key process for environmental geochemistry and detoxification of vanadium(V).However,the electron transfer pathways and V isotope fractionation involved in this process are not yet fully understood.In this study,the V(V)reduction mechanisms with concomitant V isotope fractionation by the Gram-positive bacterium Bacillus subtilis(B.subtilis)and the Gramnegative bacterium Thauera humireducens(T.humireducens)were investigated.Both strains could effectively reduce V(V),removing(90.5%±1.6%)and(93.0%±1.8%)of V(V)respectively from an initial concentration of 50 mg L^(-1) during a 10-day incubation period.V(V)was bioreduced to insoluble vanadium(IV),which was distributed both inside and outside the cells.Electron transfer via cytochrome C,nicotinamide adenine dinucleotide,and glutathione played critical roles in V(V)reduction.Metabolomic analysis showed that differentially enriched metabolites(quinone,biotin,and riboflavin)mediated electron transfer in both strains.The aqueous V in the remaining solution became isotopically heavier as V(V)bioreduction proceeded.The obtained V isotope composition dynamics followed a Rayleigh fractionation model,and the isotope enrichment factor(e)was(–0.54‰±0.04‰)for B.subtilis and(–0.32‰±0.03‰)for T.humireducens,with an insignificant difference.This study provides molecular insights into electron transfer for V(V)bioreduction and reveals V isotope fractionation during this bioprocess,which is helpful for understanding V biogeochemistry and developing novel strategies for V remediation.展开更多
Taking deep coal-rock gas in the Yulin and Daning-Jixian areas of the Ordos Basin,NW China,as the research object,full-diameter coal rock samples with different cleat/fracture development degrees from the Carboniferou...Taking deep coal-rock gas in the Yulin and Daning-Jixian areas of the Ordos Basin,NW China,as the research object,full-diameter coal rock samples with different cleat/fracture development degrees from the Carboniferous Benxi Formation were selected to conduct physical simulation and isotope monitoring experiments of the full-life-cycle depletion development of coal-rock gas.Based on the experimental results,a dual-medium carbon isotope fractionation(CIF)model coupling cleats/fractures and matrix pores was constructed,and an evaluation method for free gas production patterns was established to elucidate the carbon isotope fractionation mechanism and adsorbed/free gas production characteristics during deep coal-rock gas development.The results show that the deep coal-rock gas development process exhibits a three-stage carbon isotope fractionation pattern:“Stable(Ⅰ)→Decrease(Ⅱ)→Increase(Ⅲ)”.A rapid decline in boundary pressure in stageⅢleads to fluctuations in isotope value,characterized by a“rapid decrease followed by continued increase”,with free gas being produced first and long-term supply of adsorbed gas.The CIF model can effectively match measured gas pressure,cumulative gas production,and δ^(13)C_(1) value of produced gas.During the first two stages of isotope fractionation,free gas dominated cumulative production.During the mid-late stages of slow depletion production,the staged pressure control development method can effectively increase the gas recovery.The production of adsorbed gas is primarily controlled by the rock's adsorption capacity and the presence of secondary flow channels.Effectively enhancing the recovery of adsorbed gas during the late stage remains crucial for maintaining stable production and improving the ultimate recovery factor of deep coal-rock gas.展开更多
Stable Sr isotopic composition(δ^(88/86)Sr)can be used to study magmatic processes,but their fractionation mechanism during magmatic evolution remains unclear.To understand the fractionation behaviors of the stable S...Stable Sr isotopic composition(δ^(88/86)Sr)can be used to study magmatic processes,but their fractionation mechanism during magmatic evolution remains unclear.To understand the fractionation behaviors of the stable Sr isotopes during magmatism,we report theδ^(88/86)Sr values of the Huili granitic pluton,which was subjected to intensive crystal-melt separation.The Huili pluton consists of K-feldspar granite and more evolved albite granite,and the albite granite exhibits significantly higherδ^(88/86)Sr values(+0.36‰to+0.52‰)than that of K-feldspar granite(+0.11‰to+0.25‰).K-feldspar,which contributes most of the Sr budget of the K-feldspar granite,has slightly lowerδ^(88/86)Sr values(−0.01‰to+0.17‰)than the whole rock.Theδ^(88/86)Sr variation of the Huili granites can be explained by separation of melt from K-feldspar-dominated crystals,because crystallization of K-feldspar can result in heavy Sr isotopic composition of the extracted interstitial melt.Stable Sr and Ba isotopic ratios in the Huili granites are highly coupled toward the heavy direction,refl ecting their similar element partitioning and isotope fractionation behaviors between the crystalline K-feldspar and melt.This study indicates that melt extraction plays a key role in granitic magma evolution.展开更多
Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing fac...Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.展开更多
The Precambrian Homrit-Waggat granite is a post-orogenic batholithic intrusion located in the northern region of the Nubian Shield,characterized by a typical annular morphology and significant secondary alteration.Thi...The Precambrian Homrit-Waggat granite is a post-orogenic batholithic intrusion located in the northern region of the Nubian Shield,characterized by a typical annular morphology and significant secondary alteration.This study aims to elucidate the processes that have shaped the intrusion in both macroscopic and microscopic perspectives,employing a combination of field observation and petrographic analysis alongside major and trace element compositions of minerals.Within the central region of the pluton,biotite and amphibole are observed sporadically,while the predominant crystallization of anhydrous oligoclase in the outer regions has led to a progressive increase in volatile components within the residual melt,ultimately resulting in a volatile-saturated aluminosilicate melt.The exsolved fluids subsequently interacted with the previously crystallized mineral assemblage,producing metasomatic overprinting.As the cooling and crystallization continued,the water pressure within the magma chamber gradually escalated until it equaled or surpassed the confining pressure,leading to the formation of fractures and veins filled with minerals that crystallized from the residual aqueous fluids.The ongoing degassing and expulsion of aqueous fluids from the magma chamber’s interior ultimately contributed to the collapse of the chamber’s roof,resulting in the annular ring-dike morphology observed in the Homrit Waggat pluton.展开更多
In this paper, we study the stability of a class of conformable fractional-order systems using the Lyapunov function. We assume that the nonlinear part of the system satisfies the one-sided Lipschitz condition and the...In this paper, we study the stability of a class of conformable fractional-order systems using the Lyapunov function. We assume that the nonlinear part of the system satisfies the one-sided Lipschitz condition and the quadratic inner-bounded condition. We provide some sufficient conditions that ensure the asymptotic stability of the system. Furthermore, we present the construction of a feedback stabilizing controller for conformable fractional bilinear systems.展开更多
In this paper,we investigate the following fractional Schrödinger-Poisson system with concave-convex nonlinearities and a steep potential well{(-Δ)^(s)u+V_(λ)(x)u+ϕu=f(x)|u|^(q-2)u+|u|^(p-2)u,in R^(3),(-Δ)^(t)...In this paper,we investigate the following fractional Schrödinger-Poisson system with concave-convex nonlinearities and a steep potential well{(-Δ)^(s)u+V_(λ)(x)u+ϕu=f(x)|u|^(q-2)u+|u|^(p-2)u,in R^(3),(-Δ)^(t)ϕ=u^(2),in R^(3),where s∈(3/4,1),t∈(0,1),q∈(1,2),p∈(4,2_(s)^(*)),2_(s)^(*):=6/3-2s is the fractional critical exponent in dimension 3,V_(λ)(x)=λV(x)+1 withλ>0.Under the case of steep potential well,we obtain the existence of the sign-changing solutions for the above system by using the constraint variational method and the quantitative deformation lemma.Furthermore,we prove that the energy of ground state sign-changing solution is strictly more than twice of the energy of the ground state solution.Our results improve the recent results in the literature.展开更多
BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic d...BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic dysfunction-associated steatohepatitis(MASH)in phase 2 clinical trials.AIM To summarize the safety and effectiveness of EFX in managing MASH.METHODS Electronic databases and registries were systematically searched from their inception to May 15,2025,for randomized-controlled trials(RCTs)that included EFX in the intervention arm and placebo in the control arm in individuals with MASH.The primary outcome was the safety of EFX,while additional outcomes included its efficacy in altering hepatic and metabolic parameters.Meta-analyses were conducted using the RevMan web computer program with the random-effects model.RESULTS Four phase 2 RCTs(five reports),mostly with low risk of bias,involving 450 subjects,were analyzed.Compared to the placebo,EFX 50 mg was associated with higher risks of treatment-emergent adverse events(TEAEs)[risk ratio(RR)=1.05],TEAEs leading to discontinuation(RR=3.05),nausea(RR=1.78),and diarrhea(RR=1.9).EFX 28 mg increased risks of vomiting(RR=2.17)and frequent bowel movements(RR=8.98).Both doses of EFX were associated with higher risks of drug-related TEAEs(28 mg:RR=1.45;50 mg:RR=1.67)and increased appetite(28 mg:RR=3.16;50 mg:RR=5.66).EFX(28 and 50 mg)and placebo exhibited identical risks for severe TEAEs,serious AEs,abdominal pain,fatigue,headache,injection site erythema,and injection site reactions.EFX(28 and 50 mg)was associated with improvements in hepatic safety outcomes,including liver enzymes and urate levels.EFX outperformed the placebo in both relative and absolute reductions in hepatic fat fraction.Reductions in enhanced liver fibrosis score,Pro-C3,and liver stiffness were also more robust with EFX.EFX was superior in terms of MASH resolution and improvement in fibrosis stage,MASH resolution and no worsening of the fibrosis stage,and fibrosis regression by≥1 stage and no worsening in steatohepatitis.Furthermore,EFX also improved metabolic parameters,including reductions in HbA1c and insulin resistance,as well as improvements in adiponectin and lipid parameters.CONCLUSION EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH.However,gastrointestinal side effects and the need for parenteral administration require caution.Long-term data are still necessary to fully evaluate safety and long-term effectiveness.展开更多
基金Project supported by the National Natural Science Foundation of China (Nos. 40232022 and 40571146).
文摘Time series bioaccumulation of rare earth elements （REEs） in field-grown wheat with and without a dressing of extraneous REE fertilizer at different growth stages and fractionation of REEs during their transport in a soil-wheat system were determined. Time-dependent accumulation of extraneous REEs was found in different parts of wheat. An upward transport of extraneous REEs from roots to shoots under a soil dressing and a downward transport from leaves to roots with a foliar dressing were also observed. Moreover, fractionation of REEs occurred in the soil-wheat system. Compared to the host soil a positive Eu anomaly in the stems and grains as well as heavy REE enrichment in the grains were found. The ability of the different wheat organs to fractionate Eu from the REE series was ranked in the order of sterns 〉 grains 〉 leaves 〉 roots.
文摘The geochemical behaviors of hydrogen and oxygen isotopes in the hydrothermal system and their inher-ent relationship with the water / rock exchange are discussed in this paper In addition to the temperature con-ditions, the effective W / R ratio is another factor controlling the changes in H and O isotope compositions ofthe altered rock and hydrothermal water. Besides, the application and geological significance of the water-rockexchange theory are also discussed in the light of the H and O isotope compositions and their variation charac-teristics of the mineralizing hydrothermal water and altered rocks from several mineral deposits. Finally, abrief evolutional model of H and O istotope compositions of meteoric and magmatic hydrothermal waters in ahydrothermal system is given.
基金supported by the Fundamental Research Funds for the Central Universities(QNTD202302)National Natural Science Foundation of China(22378024)the Foreign expert program(G2022109001L).
文摘Developing a cost-effective and environmentally friendly process for the production of valuable chemicals from abundant herbal biomass receives great attentions in recent years.Herein,taking advantage of the“lignin first”strategy,corn straw is converted to valuable chemicals including lignin monomers,furfural and 5-methoxymethylfurfural via a two steps process.The key of this research lies in the development of a green and low-cost catalytic process utilizing magnetic Raney Ni catalyst and high boiling point ethylene glycol.The utilization of neat ethylene glycol as the sole slovent under atmospheric conditions obviates the need for additional additives,thereby facilitating the entire process to be conducted in glass flasks and rendering it highly convenient for scaling up.In the initial step,depolymerization of corn straw lignin resulted in a monomer yield of 18.1 wt%.Subsequently,in a dimethyl carbonate system,the carbohydrate component underwent complete conversion in a one-pot process,yielding furfural and 5-methoxymethylfurfural as the primary products with an impressive yield of 47.7%.
基金supported by the ARRS program P1-0143,a project J1-4288 and the ARRS young researcher program as well as the program“Young researchers from Industry 2010”partly financed by the European Union,European Social Fundfinancial support from the state budget by the Slovenian Research Agency.
文摘Gypsum from the wet flue gas desulfurization system of the lignite fired thermal power plant Sostanj, Slovenia, can efficiently retain mercury (Hg), of which most is contained in finer gypsum fractions, with concentrations above 10 kg-1. The aim of this work was to identify and study the temperature stability of Hg species in gypsum by a temperature fractionation (TF) method. A self-constructed apparatus was used that consisted of an electrical furnace for controlled heating up to 700°C, with a heating rate of 2.2°C·min-1, and an AAS detector with Zeeman background correction. The pattern of Hg release during temperature increase depends highly on the matrix/substrate in which it is contained. Based on spiking gypsum with known Hg compounds we concluded that the largest proportion of Hg in gypsum belongs to Hg-Cl and Hg-Br compounds appearing at 160°C to 200°C, followed by smaller amounts of HgO, HgS and Hg sulfates appearing at 300°C and 450°C. Further development of methodology for identifying Hg species would require identification of the decomposition fragments of Hg and other compounds, complemented by a better understanding of Hg reactivity at higher temperatures.
基金Supported by the National Natural Science Foundation of China(grant No.41171384,41271414 and 41301529)
文摘This study aimed to characterize constituents of phosphorus （P） fractionation as wel as reciprocities among factors in sediments of a freshwater shal ow lake. [Method] Surface sediment was discretely sampled at 24 sites through Van Veen grabs. Based on a modified sequential extraction scheme, P fractionation was determined as Fe/Al bound P （Fe/Al-P）, Ca bound P （Ca-P）, solute and re-ductive P （S/R-P） and organic P （OP）. Curve estimation and Pearson product-mo-ment correlation were employed for statistical analysis. [Result] Total P （TP） content ranged from 443 to 774 mg/kg. Inorganic P （IP） was the major component of TP, of which Ca-P was dominated with an average of 51%±9.7%. Average contents of P fractionation were in the fol owing order： Ca-P（51%） 〉 OP（29%） 〉 S/R-P（8%） 〉Fe/Al-P（7%）. The molar ratio of Fe to P was 11 - 20, close to the threshold value of P leaching. [Conclusion] In freshwater shal ow lakes, IP and Ca-P were prone to be relatively high, whereas Fe/Al-P was low compared with deep lakes. Occurrence of spatial y monotonic gradient indicated the primary causation of anthropogenic sources. Imminent sediment P liberation was also expected. Close associations a-mong TP, Fe/Al-P and Ca-P, implying that anthropogenic P was mainly bound to metals in particulates. Significant correlations of TOC and P fractionation highlighted endogenous mechanism and authigenic origin in sediments.
文摘This paper presents a model of isotopic fractionation by freezing under near equilibrium conditions in an open system and uses the model to predict the fractionation curve and slope gradient of δ 18 O versus δD. The simulation results show that 1) the fractionation curve and slope gradient are determined by the ratio of freezing rate to input rate, 2) the isotopic value in the initial stage of freezing is determined by the isotopic value of initial water; 3) in the latter half of freezing in an open system, the isotopic value converges to a certain value determined by that of input water. These results suggest that the shape of the fractionation curve is the method to distinguish whether freezing occurred in a closed or open system. This analysis is applied to an isotopic curve observed in basal ice of Hamna Glacier, Sya drainage, East Antarctica. The isotopic curve indicates formation by regelation in an open system with a ratio of freezing/input rates of about 10/4.
文摘Oxygen isotope fractionation is studied during the synthesis of kaolinite under controlled conditions of temperature and time. Equilibrium conditions have been established and its relationship with temperature has been studied. Kaolinite was hydrothermally precipitated starting from non-crystalline aluminosilicate gels. The amount of kaolinite obtained increases up to a limited constant value and in all cases coexists with the amorphous starting gels. It can be seen that the data obtained at 48 hours of synthesis can be considered as quasi-equilibrium, since the total isotopic equilibrium has not been reached, only the sample obtained at 24 hours should be discarded for studies in equilibrium. This would allow us, with the samples obtained at 720 hours, to try to establish a relationship between isotopic fractionation and temperature, provided that we know the water in equilibrium with the synthesized kaolinite. Two equations have been obtained that show correlation coefficients with a high statistical significance.
基金supported by the Natural Science Foundation of China(Grant No.42302170)National Postdoctoral Innovative Talent Support Program(Grant No.BX20220062)+3 种基金CNPC Innovation Found(Grant No.2022DQ02-0104)National Science Foundation of Heilongjiang Province of China(Grant No.YQ2023D001)Postdoctoral Science Foundation of Heilongjiang Province of China(Grant No.LBH-Z22091)the Natural Science Foundation of Shandong Province(Grant No.ZR2022YQ30).
文摘Prediction of production decline and evaluation of the adsorbed/free gas ratio are critical for determining the lifespan and production status of shale gas wells.Traditional production prediction methods have some shortcomings because of the low permeability and tightness of shale,complex gas flow behavior of multi-scale gas transport regions and multiple gas transport mechanism superpositions,and complex and variable production regimes of shale gas wells.Recent research has demonstrated the existence of a multi-stage isotope fractionation phenomenon during shale gas production,with the fractionation characteristics of each stage associated with the pore structure,gas in place(GIP),adsorption/desorption,and gas production process.This study presents a new approach for estimating shale gas well production and evaluating the adsorbed/free gas ratio throughout production using isotope fractionation techniques.A reservoir-scale carbon isotope fractionation(CIF)model applicable to the production process of shale gas wells was developed for the first time in this research.In contrast to the traditional model,this model improves production prediction accuracy by simultaneously fitting the gas production rate and δ^(13)C_(1) data and provides a new evaluation method of the adsorbed/free gas ratio during shale gas production.The results indicate that the diffusion and adsorption/desorption properties of rock,bottom-hole flowing pressure(BHP)of gas well,and multi-scale gas transport regions of the reservoir all affect isotope fractionation,with the diffusion and adsorption/desorption parameters of rock having the greatest effect on isotope fractionation being D∗/D,PL,VL,α,and others in that order.We effectively tested the universality of the four-stage isotope fractionation feature and revealed a unique isotope fractionation mechanism caused by the superimposed coupling of multi-scale gas transport regions during shale gas well production.Finally,we applied the established CIF model to a shale gas well in the Sichuan Basin,China,and calculated the estimated ultimate recovery(EUR)of the well to be 3.33×10^(8) m^(3);the adsorbed gas ratio during shale gas production was 1.65%,10.03%,and 23.44%in the first,fifth,and tenth years,respectively.The findings are significant for understanding the isotope fractionation mechanism during natural gas transport in complex systems and for formulating and optimizing unconventional natural gas development strategies.
文摘This article studies the existence and uniqueness of the mild solution of a family of control systems with a delay that are governed by the nonlinear fractional evolution differential equations in Banach spaces.Moreover,we establish the controllability of the considered system.To do so,first,we investigate the approximate controllability of the corresponding linear system.Subsequently,we prove the nonlinear system is approximately controllable if the corresponding linear system is approximately controllable.To reach the conclusions,the theory of resolvent operators,the Banach contraction mapping principle,and fixed point theorems are used.While concluding,some examples are given to demonstrate the efficacy of the proposed results.
基金Supported by NSFC(No.12561023)partly by the Provincial Natural Science Foundation of Jiangxi,China(Nos.20232BAB201001,20202BAB211004)。
文摘In this paper,we study the existence of least energy solutions for the following nonlinear fractional Schrodinger–Poisson system{(−∆)^(s)u+V(x)u+φu=f(u)in R^(3),(−∆)^(t)φ=u^(2)in R^(3),where s∈(3/4,1),t∈(0,1).Under some assumptions on V(x)and f,using Nehari–Pohozaev identity and the arguments of Brezis–Nirenberg,the monotonic trick and global compactness lemma,we prove the existence of a nontrivial least energy solution.
基金financial support provided by the University of New England,Australia for conducting this research。
文摘Water-soluble organic matter(WSOM)significantly influences the transport of metals and organic contaminants in soils,yet the interaction specifics with antimony(Sb)remain largely unexplored.Antimony is of particular environmental concern due to its toxic properties and harmful effects on ecosystems and human health.Employing a three-step fractionation method with polyvinylpyrrolidone(PVP),this study aimed to isolate and analyze humic acids(HA),PVP-non adsorbed fulvic acids(FAA),and PVP-adsorbed fulvic acids(FAB)from WSOM in soil spiked with Sb and incubated for 18 months.These fractions underwent chemical analysis for carbon(C),nitrogen(N),total organic carbon(TOC),and Sb,complemented by FTIR and 1H NMR spectroscopic characterization.The study revealed that HA wasmore aliphatic,with Sb predominantly associating with the fulvic acid(FA)fraction,accounting for 97%of Sb in extracts.Specifically,the FAA subfraction held substantial portions of total carbon(TC),total nitrogen(TN),total organic carbon(TOC),and Sb.Correlations between Sb concentrations and TN,TC,and TOC were significant.Extraction methods showed NaOH and Na_(4)P_(2)O_(7) outperformed HCl and deionised water in extracting TC,TN,and TOC,with higher Sb concentrations found in Na_(4)P_(2)O_(7) and NaOH extracts.This underscores the role of Fe/Al-SOM complexes in Sb soil availability.The results revealed that FAA subfraction accounted for 76%,64%and 94%of TN,TOC and Sb,respectively.Therefore,this research highlights the FAA fraction’s central role,predominantly comprising non-humic substances like amines,in the availability of C,N,and Sb in Sb-impacted soils.The findings offer insights for environmental management and remediation strategies.
基金Supported by PetroChina Science and Technology Research and Technology Development Project(2021DJ0502)Open Research Project of Key Laboratory of Shale Gas Resources Exploration,Ministry of Natural Resources(Chongqing Institute of Geology and Mineral Resources)(KLSGE-2023).
文摘Based on geochemical data from natural gas samples across spring water systems and sedimentary basins,including Songliao,Bohai Bay,Sanshui,Sichuan,Ordos,Tarim and Ying-Qiong,this paper systematically compares the geochemical compositions of abiogenic versus biogenic gases.Emphasis is placed on the diagnostic signatures of abiogenic gases in terms of gas composition,and carbon,hydrogen and helium isotopes.The main findings are as follows.(1)In hydrothermal spring systems,abiogenic alkane gases are extremely scarce.Methane concentrations are typically less than 1%,with almost no detectable C^(2+)hydrocarbons.The gas is dominantly composed of CO_(2),while N_(2)is the major component in a few samples.(2)Abiogenic alkane gases display distinct isotopic signatures,including enriched methane carbon isotopic compositions(δ^(13)C_(1)>-25‰generally),complete carbon isotopic reversal(δ^(13)C_(1)>δ^(13)C_(2)>δ^(13)C_(3)>δ^(13)C_(4)),and enriched helium isotope(R/Ra>0.5,CH_(4)/^(3)He≤10^(6)generally).(3)The hydrogen isotopic composition of abiogenic alkane gases may be characterized by a positive sequence(δD_(1)<δD_(2)<δD_(3)),or a complete reversal(δD_(1)>δD_(2)>δD_(3)),or a V-shaped distribution(δD_(1)>δD_(2),δD_(2)<δD_(3)).The hydrogen isotopic compositions of methane generally show limited variation(about 9‰),possibly due to hydrogen isotopic exchange with connate water.(4)In terms of identifying gas origin,CH_(4)/^(3)He-R/Ra andδ^(13)CCO_(2)-R/Ra charts are more effective than CO_(2)/^(3)He-R/Ra chart.These new geological insights provide theoretical clues and diagnostic charts for the genetic identification of natural gas and further research on abiogenic gases.
基金supported by the National Natural Science Foundation of China(U21A2033)the Fundamental Research Funds for the Central Universities(2652022103).
文摘Microbial vanadate(V(V))reduction is a key process for environmental geochemistry and detoxification of vanadium(V).However,the electron transfer pathways and V isotope fractionation involved in this process are not yet fully understood.In this study,the V(V)reduction mechanisms with concomitant V isotope fractionation by the Gram-positive bacterium Bacillus subtilis(B.subtilis)and the Gramnegative bacterium Thauera humireducens(T.humireducens)were investigated.Both strains could effectively reduce V(V),removing(90.5%±1.6%)and(93.0%±1.8%)of V(V)respectively from an initial concentration of 50 mg L^(-1) during a 10-day incubation period.V(V)was bioreduced to insoluble vanadium(IV),which was distributed both inside and outside the cells.Electron transfer via cytochrome C,nicotinamide adenine dinucleotide,and glutathione played critical roles in V(V)reduction.Metabolomic analysis showed that differentially enriched metabolites(quinone,biotin,and riboflavin)mediated electron transfer in both strains.The aqueous V in the remaining solution became isotopically heavier as V(V)bioreduction proceeded.The obtained V isotope composition dynamics followed a Rayleigh fractionation model,and the isotope enrichment factor(e)was(–0.54‰±0.04‰)for B.subtilis and(–0.32‰±0.03‰)for T.humireducens,with an insignificant difference.This study provides molecular insights into electron transfer for V(V)bioreduction and reveals V isotope fractionation during this bioprocess,which is helpful for understanding V biogeochemistry and developing novel strategies for V remediation.
基金Youth Fund of National Natural Science Foundation of China(42302170)CNPC Scientific and Technological Innovation Fund(2022DQ02-0104)RIPED Open Project Fund(2024-KFKT-31).
文摘Taking deep coal-rock gas in the Yulin and Daning-Jixian areas of the Ordos Basin,NW China,as the research object,full-diameter coal rock samples with different cleat/fracture development degrees from the Carboniferous Benxi Formation were selected to conduct physical simulation and isotope monitoring experiments of the full-life-cycle depletion development of coal-rock gas.Based on the experimental results,a dual-medium carbon isotope fractionation(CIF)model coupling cleats/fractures and matrix pores was constructed,and an evaluation method for free gas production patterns was established to elucidate the carbon isotope fractionation mechanism and adsorbed/free gas production characteristics during deep coal-rock gas development.The results show that the deep coal-rock gas development process exhibits a three-stage carbon isotope fractionation pattern:“Stable(Ⅰ)→Decrease(Ⅱ)→Increase(Ⅲ)”.A rapid decline in boundary pressure in stageⅢleads to fluctuations in isotope value,characterized by a“rapid decrease followed by continued increase”,with free gas being produced first and long-term supply of adsorbed gas.The CIF model can effectively match measured gas pressure,cumulative gas production,and δ^(13)C_(1) value of produced gas.During the first two stages of isotope fractionation,free gas dominated cumulative production.During the mid-late stages of slow depletion production,the staged pressure control development method can effectively increase the gas recovery.The production of adsorbed gas is primarily controlled by the rock's adsorption capacity and the presence of secondary flow channels.Effectively enhancing the recovery of adsorbed gas during the late stage remains crucial for maintaining stable production and improving the ultimate recovery factor of deep coal-rock gas.
基金supported by National Natural Science Foundation of China(42473009).
文摘Stable Sr isotopic composition(δ^(88/86)Sr)can be used to study magmatic processes,but their fractionation mechanism during magmatic evolution remains unclear.To understand the fractionation behaviors of the stable Sr isotopes during magmatism,we report theδ^(88/86)Sr values of the Huili granitic pluton,which was subjected to intensive crystal-melt separation.The Huili pluton consists of K-feldspar granite and more evolved albite granite,and the albite granite exhibits significantly higherδ^(88/86)Sr values(+0.36‰to+0.52‰)than that of K-feldspar granite(+0.11‰to+0.25‰).K-feldspar,which contributes most of the Sr budget of the K-feldspar granite,has slightly lowerδ^(88/86)Sr values(−0.01‰to+0.17‰)than the whole rock.Theδ^(88/86)Sr variation of the Huili granites can be explained by separation of melt from K-feldspar-dominated crystals,because crystallization of K-feldspar can result in heavy Sr isotopic composition of the extracted interstitial melt.Stable Sr and Ba isotopic ratios in the Huili granites are highly coupled toward the heavy direction,refl ecting their similar element partitioning and isotope fractionation behaviors between the crystalline K-feldspar and melt.This study indicates that melt extraction plays a key role in granitic magma evolution.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82304443,82030107,and 82373944).
文摘Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.
基金supported by Science and Technology Development Fund(STDF)of the Arab Republic of Egypt(No.23080)entitled―Rare Metal Ore Deposits in Egypt:A comparative survey in altered granites from selected areas in the Central Eastern Desert‖(to M.A.ABU EL-RUS)National Key Research and Development Program of China(No.2023YFF0804200).
文摘The Precambrian Homrit-Waggat granite is a post-orogenic batholithic intrusion located in the northern region of the Nubian Shield,characterized by a typical annular morphology and significant secondary alteration.This study aims to elucidate the processes that have shaped the intrusion in both macroscopic and microscopic perspectives,employing a combination of field observation and petrographic analysis alongside major and trace element compositions of minerals.Within the central region of the pluton,biotite and amphibole are observed sporadically,while the predominant crystallization of anhydrous oligoclase in the outer regions has led to a progressive increase in volatile components within the residual melt,ultimately resulting in a volatile-saturated aluminosilicate melt.The exsolved fluids subsequently interacted with the previously crystallized mineral assemblage,producing metasomatic overprinting.As the cooling and crystallization continued,the water pressure within the magma chamber gradually escalated until it equaled or surpassed the confining pressure,leading to the formation of fractures and veins filled with minerals that crystallized from the residual aqueous fluids.The ongoing degassing and expulsion of aqueous fluids from the magma chamber’s interior ultimately contributed to the collapse of the chamber’s roof,resulting in the annular ring-dike morphology observed in the Homrit Waggat pluton.
文摘In this paper, we study the stability of a class of conformable fractional-order systems using the Lyapunov function. We assume that the nonlinear part of the system satisfies the one-sided Lipschitz condition and the quadratic inner-bounded condition. We provide some sufficient conditions that ensure the asymptotic stability of the system. Furthermore, we present the construction of a feedback stabilizing controller for conformable fractional bilinear systems.
基金supported by the Natural Science Foundation of Sichuan(No.2023NSFSC0073)。
文摘In this paper,we investigate the following fractional Schrödinger-Poisson system with concave-convex nonlinearities and a steep potential well{(-Δ)^(s)u+V_(λ)(x)u+ϕu=f(x)|u|^(q-2)u+|u|^(p-2)u,in R^(3),(-Δ)^(t)ϕ=u^(2),in R^(3),where s∈(3/4,1),t∈(0,1),q∈(1,2),p∈(4,2_(s)^(*)),2_(s)^(*):=6/3-2s is the fractional critical exponent in dimension 3,V_(λ)(x)=λV(x)+1 withλ>0.Under the case of steep potential well,we obtain the existence of the sign-changing solutions for the above system by using the constraint variational method and the quantitative deformation lemma.Furthermore,we prove that the energy of ground state sign-changing solution is strictly more than twice of the energy of the ground state solution.Our results improve the recent results in the literature.
文摘BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic dysfunction-associated steatohepatitis(MASH)in phase 2 clinical trials.AIM To summarize the safety and effectiveness of EFX in managing MASH.METHODS Electronic databases and registries were systematically searched from their inception to May 15,2025,for randomized-controlled trials(RCTs)that included EFX in the intervention arm and placebo in the control arm in individuals with MASH.The primary outcome was the safety of EFX,while additional outcomes included its efficacy in altering hepatic and metabolic parameters.Meta-analyses were conducted using the RevMan web computer program with the random-effects model.RESULTS Four phase 2 RCTs(five reports),mostly with low risk of bias,involving 450 subjects,were analyzed.Compared to the placebo,EFX 50 mg was associated with higher risks of treatment-emergent adverse events(TEAEs)[risk ratio(RR)=1.05],TEAEs leading to discontinuation(RR=3.05),nausea(RR=1.78),and diarrhea(RR=1.9).EFX 28 mg increased risks of vomiting(RR=2.17)and frequent bowel movements(RR=8.98).Both doses of EFX were associated with higher risks of drug-related TEAEs(28 mg:RR=1.45;50 mg:RR=1.67)and increased appetite(28 mg:RR=3.16;50 mg:RR=5.66).EFX(28 and 50 mg)and placebo exhibited identical risks for severe TEAEs,serious AEs,abdominal pain,fatigue,headache,injection site erythema,and injection site reactions.EFX(28 and 50 mg)was associated with improvements in hepatic safety outcomes,including liver enzymes and urate levels.EFX outperformed the placebo in both relative and absolute reductions in hepatic fat fraction.Reductions in enhanced liver fibrosis score,Pro-C3,and liver stiffness were also more robust with EFX.EFX was superior in terms of MASH resolution and improvement in fibrosis stage,MASH resolution and no worsening of the fibrosis stage,and fibrosis regression by≥1 stage and no worsening in steatohepatitis.Furthermore,EFX also improved metabolic parameters,including reductions in HbA1c and insulin resistance,as well as improvements in adiponectin and lipid parameters.CONCLUSION EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH.However,gastrointestinal side effects and the need for parenteral administration require caution.Long-term data are still necessary to fully evaluate safety and long-term effectiveness.
