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OBJECTIVE: The survival benefit of first-line treatment with bevacizumab in advanced ovarian cancer patients are multifaceted. In our study, we aimed to identify potential markers of bevacizumab efficacy to help predict which patients would experience survival benefits. METHODS: This was a retrospective analysis of 114 patients examined from January 1, 2015, to March 1, 2023, and data on clinical, biological, and imaging variables, such as ascites, serum LDH, and CA125, were extracted from electronic medical records. We performed a correlation analysis and principal component analysis to investigate correlations among variables and reduce their dimensionality. Then, univariate and multivariate Cox proportional hazards regression analyses were used to identify the predictors of progression-free survival. RESULTS: Favorable KELIM score (≥ 1, HR 0.376, 95% CI [0.202-0.700], p = 0.002), which indicated better chemosensitivity, and lower LDH levels (≤ 210 U/L, HR 38.73, 95% CI [6.108-245.6], p < 0.001) were found to be independent predictors of a treatment benefit with bevacizumab in patients with advanced ovarian cancer. Regardless of LDH level, patients with favorable KELIM scores had a higher progression-free survival (PFS) benefit (p = 0.18). Among patients with unfavorable KELIM scores, those with higher LDH levels had the lowest PFS benefit (median: 11.5 months, p = 0.0059). CONCLUSION: Patients with poor chemosensitivity and low LDH levels are more likely to benefit from first-line bevacizumab treatment. The combination of the two markers can be a helpful predictor of patients who are most likely to benefit from treatment and a guide for treatment decisions-making. Retrospectively registered: 2020-MD-371, 2020.10.12.
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We report on the growth, polarized spectroscopy and first laser operation of an orthorhombic (space group Pnma) Tm3+,Ho3+-codoped gadolinium orthoscandate (GdScO3) perovskite-type crystal. A single crystal of 3.76 at.% Tm, 0.35 at.% Ho:GdScO3 was grown by the Czochralski method. Its polarized absorption and fluorescence properties were studied revealing a broadband emission around 2â µm. The parameters of the Tm3+ â Ho3+ energy transfer was quantified, P28 = 1.30 × 10-22 cm3µs-1, and P71 = 0.99 × 10-23 cm3µs-1, and the thermal equilibrium lifetime was measured to be 3.5â ms. The crystal-field splitting of Tm3+ and Ho3+ multiplets in Cs symmetry sites of the perovskite structure was determined by low-temperature spectroscopy and the mechanism of spectral line broadening is discussed. The continuous-wave Tm,Ho:GdScO3 laser generated 1.16 W at â¼2.1â µm with a slope efficiency of 50.5%, a laser threshold of 184â mW, a linear laser polarization (E || c) and a spatially single-mode output. The Tm,Ho:GdScO3 crystal is promising for broadly tunable and femtosecond mode-locked lasers emitting above 2â µm.
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Percarbonate encompasses sodium percarbonate (SPC) and composite in-situ generated peroxymonocarbonate (PMC). SPC emerges as a promising alternative to hydrogen peroxide (H2O2), hailed for its superior transportation safety, stability, cost-effectiveness, and eco-friendliness, thereby becoming a staple in advanced oxidation processes for mitigating water pollution. Yet, scholarly literature scarcely explores the deployment of percarbonate-AOPs in eradicating organic contaminants from aquatic systems. Consequently, this review endeavors to demystify the formation mechanisms and challenges associated with reactive oxygen species (ROS) in percarbonate-AOPs, alongside highlighting directions for future inquiry and development. The genesis of ROS encompasses the in situ chemical oxidation of activated SPC (including iron-based activation, discharge plasma, ozone activation, photon activation, and metal-free materials activation) and composite in situ chemical oxidation via PMC (namely, H2O2/NaHCO3/Na2CO3, peroxymonosulfate/NaHCO3/Na2CO3 systems). Moreover, the ROS generated by percarbonate-AOPs, such as â¢OH, O2â¢-, CO3â¢-, HO2â¢-, 1O2, and HCO4-, can work individually or synergistically to disintegrate target pollutants. Concurrently, this review systematically addresses conceivable obstacles posing percarbonate-AOPs in real-world application from the angle of environmental conditions (pH, temperature, coexisting substances), and potential ecological toxicity. Considering the outlined challenges and advantages, we posit future research directions to amplify the applicability and efficacy of percarbonate-AOPs in tangible settings. It is anticipated that the insights provided in this review will catalyze the progression of percarbonate-AOPs in water purification endeavors and bridge the existing knowledge void.
Subject(s)
Carbonates , Oxidation-Reduction , Wastewater , Carbonates/chemistry , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Hydrogen Peroxide/chemistry , Reactive Oxygen SpeciesABSTRACT
Cancer cells are characterized by increased glycolysis, known as the Warburg effect, which leads to increased production of cytotoxic methylglyoxal (MGO) and apoptotic cell death. Cancer cells often activate the protective nuclear factor erythroid 2related factor2 (Nrf2)/glyoxalase1 (Glo1) system to detoxify MGO. The effects of sodium butyrate (NaB), a product of gut microbiota, on Nrf2/Glos/MGO pathway and the underlying mechanisms in prostate cancer (PCa) cells were investigated in the present study. Treatment with NaB induced the cell death and reduced the proliferation of PCa cells (DU145 and LNCap). Moreover, the protein kinase RNA-like endoplasmic reticulum kinase/Nrf2/Glo1 pathway was greatly inhibited by NaB, thereby accumulating MGO-derived adduct hydroimidazolone (MG-H1). In response to a high amount of MGO, the expression of Nrf2 and Glo1 was attenuated, coinciding with an increased cellular death. NaB also markedly inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (Stat3) pathway. Conversely, cotreatment with Colivelin, a Stat3 activator, significantly reversed the effects of NaB on Glo1 expression, MG-H1 production, and the cell migration and viability. As expected, overexpression of Stat3 or Glo1 reduced NaBinduced cell death. The activation of calcium/calmodulin dependent protein kinase II gamma and reactive oxygen species production also contributed to the anticancer effect of NaB. The present study, for the first time, demonstrated that NaB greatly increases MGO production through suppression of the JAK2/Stat3/Nrf2/Glo1 pathway in DU145 cells, a cell line mimicking castrationresistant PCa (CRPC), suggesting that NaB may be a potential agent for PCa therapy.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Humans , Male , Butyric Acid/pharmacology , Janus Kinase 2/metabolism , Magnesium Oxide/metabolism , NF-E2-Related Factor 2/metabolism , Pyruvaldehyde/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Low-cost, low-energy extraction of heavy metal(loid)s (HMs) from hazardous gypsum cake is the goal of the metallurgical industry to mitigate environmental risks and carbon emissions. However, current extracting routes of hydrometallurgy often suffer from great energy inputs and substantial chemical inputs. Here, we report a novel solid-like approach with low energy consumption and chemical input to extract HMs by thin films under ambient conditions. Through constructing a nanoscale sulfuric acid film (NSF) of â¼50 nm thickness on the surface of arsenic-bearing gypsum (ABG), 99.6% of arsenic can be removed, surpassing the 50.3% removal in bulk solution. In-situ X-ray diffraction, infrared spectral, and ab initio molecular dynamics (AIMD) simulations demonstrate that NSF plays a dual role in promoting the phase transformation from gypsum to anhydrite and in changing the ionic species to prevent re-doping in anhydrite, which is not occurred in bulk solutions. The potential of the NSF is further validated in extracting other heavy metal(loid)s (e.g., Cu, Zn, and Cr) from synthetic and actual gypsum cake. With energy consumption and costs at 1/200 and 1/10 of traditional hydrometallurgy separately, this method offers an efficient and economical pathway for extracting HMs from heavy metal-bearing waste and recycling industrial solid waste.
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We report on the investigation of continuous-wave (CW) and SEmiconductor Saturable Absorber Mirror (SESAM) mode-locked operation of a Yb:GdScO3 laser. Using a single-transverse-mode, fiber-coupled InGaAs laser diode at 976â nm as a pump source, the Yb:GdScO3 laser delivers 343â mW output power at 1062â nm in the CW regime, which corresponds to a slope efficiency of 52%. Continuous tuning is possible across a wavelength range of 84â nm (1027-1111â nm). Using a commercial SESAM to initiate mode-locking and stabilize soliton-type pulse shaping, the Yb:GdScO3 laser produces pulses as short as 42 fs at 1065.9â nm, with an average output power of 40â mW at 66.89â MHz. To the best of our knowledge, this is the first demonstration of passively mode-locking with Yb:GdScO3 crystal.
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The solid-liquid separation is an indispensable and primary link in the process of sludge treatment and disposal. The past research was focused primarily on the technique explorations of sludge dewatering and always disregarded the internal pore structure and water migration behavior in sludge. In this work, the real three-dimensional pore structure of sludge was obtained by Nano-CT. Based on this, a pore-scale heterogeneous sludge micromodel was firstly presented, and the water flooding experiment was carried out to visualize the water migration behavior. The results showed that the sludge structure transformed from sheet-like floc to microsphere particles, and then agglomerated into large globular granules during anaerobic ammonia oxidation. And the equivalent pore size increases from 342 µm to 617 µm, improving the sludge dewaterability characterized by capillary suction time (CST). The most significant implication of this work was revealing the critical role of invalid connected pore in sludge dewatering. Such pore was not contributed to fluid flow but the circulating vortex in it even induced energy dissipation, thus deteriorated the sludge dewaterability. This work may be helpful to understand the critical role of pore characteristic in water migration and shed light on the new dewatering techniques from the perspective of regulating sludge structure.
Subject(s)
Sewage , Waste Disposal, Fluid , Sewage/chemistry , Waste Disposal, Fluid/methods , Water/chemistryABSTRACT
We present the growth, spectroscopy, continuous-wave (CW) and passively mode-locked (ML) operation of a novel "mixed" tetragonal calcium rare-earth aluminate crystal, Yb3+:Ca(Gd,Y)AlO4. The absorption, stimulated-emission, and gain cross-sections are derived for π and σ polarizations. The laser performance of a c-cut Yb:Ca(Gd,Y)AlO4 crystal is studied using a spatially single-mode, 976-nm fiber-coupled laser diode as a pump source. A maximum output power of 347â mW is obtained in the CW regime with a slope efficiency of 48.9%. The emission wavelength is continuously tunable across 90â nm (1010 - 1100â nm) using a quartz-based Lyot filter. With a commercial SEmiconductor Saturable Absorber Mirror to initiate and maintain ML operation, soliton pulses as short as 35 fs are generated at 1059.8â nm with an average output power of 51â mW at â¼65.95â MHz. The average output power can be scaled to 105â mW for slightly longer pulses of 42 fs at 1063.5â nm.
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We report on the continuous-wave (CW) and, for what we believe to be the first time, passively mode-locked (ML) laser operation of an Yb3+-doped YSr3(PO4)3 crystal. Utilizing a 976-nm spatially single-mode, fiber-coupled laser diode as pump source, the Yb:YSr3(PO4)3 laser delivers a maximum CW output power of 333â mW at 1045.8â nm with an optical efficiency of 55.7% and a slope efficiency of 60.9%. Employing a quartz-based Lyot filter, an impressive wavelength tuning range of 97â nm at the zero level was achieved in the CW regime, spanning from 1007â nm to 1104â nm. In the ML regime, incorporating a commercially available semiconductor saturable absorber mirror (SESAM) to initiate and maintain soliton-like pulse shaping, the Yb:YSr3(PO4)3 laser generated pulses as short as 61 fs at 1062.7â nm, with an average output power of 38â mW at a repetition rate of â¼66.7â MHz.
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Heavy metals raise a global concern and can be easily retained by ubiquitous iron (oxyhydr)oxides in natural and engineered systems. The complex interaction between iron (oxyhydr)oxides and heavy metals results in various mineral-metal binding configurations, such as outer-sphere complexes and edge-sharing inner-sphere complexes, which determine the accumulation and release of heavy metals in the environment. However, traditional experimental approaches are time-consuming and inadequate to elucidate the complex binding relationships and configurations between iron (oxyhydr)oxides and heavy metals. Herein, a workflow that integrates the binding configuration data of 11 heavy metals on 7 iron (oxyhydr)oxides and then trains machine learning models to predict unknown binding configurations was proposed. The well-trained multi-grained cascade forest models exhibited high accuracy (> 90%) and predictive performance (R2 â¼ 0.75). The underlying effects of mineral properties, metal ion species, and environmental conditions on mineral-metal binding configurations were fully interpreted with data mining. Moreover, the metal release rate was further successfully predicted based on mineral-metal binding configurations. This work provides a method to accurately and quickly predict the binding configuration of heavy metals on iron (oxyhydr)oxides, which would provide guidance for estimating the potential release behavior of heavy metals and remediating heavy metal pollution in natural and engineered environments.
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The Li3MX6 compounds (M=Sc, Y, In; X=Cl, Br) are known as promising ionic conductors due to their compatibility with typical metal oxide cathode materials. In this study, we have successfully synthesized γ-Li3ScCl6 using high pressure for the first time in this family. Structural analysis revealed that the high-pressure polymorph crystallizes in the polar and chiral space group P63mc with hexagonal close-packing (hcp) of anions, unlike the ambient-pressure α-Li3ScCl6 and its spinel analog with cubic closed packing (ccp) of anions. Investigation of the known Li3MX6 family further revealed that the cation/anion radius ratio, rM/rX, is the factor that determines which anion sublattice is formed and that in γ-Li3ScCl6, the difference in compressibility between Sc and Cl exceeds the ccp rM/rX threshold under pressure, enabling the ccp-to-hcp conversion. Electrochemical tests of γ-Li3ScCl6 demonstrate improved electrochemical reduction stability. These findings open up new avenues and design principles for lithium solid electrolytes, enabling routes for materials exploration and tuning electrochemical stability without compositional changes or the use of coatings.
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OBJECTIVE: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia. METHODS: We analyzed summary data of epilepsy, memory loss, and dementia from the genome-wide association study (GWAS) using the two-sample Mendelian randomization (MR) method. We used the estimated odds ratio of memory loss and dementia associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: all epilepsy, focal epilepsy (including focal epilepsy with hippocampal sclerosis, lesion-negative focal epilepsy, and focal epilepsy with other lesions), and genetic generalized epilepsy (including childhood absence epilepsy, generalized tonic-clonic seizures alone, Juvenile absence epilepsy, and Juvenile myoclonic epilepsy). RESULTS: According to the result of MR using the inverse variance weighted method (IVW), we found that genetically predicted epilepsy did not causally increase the risk of memory loss and dementia (p > 0.05). Results of the MR-Egger and weighted median method were consistent with the IVW method. CONCLUSIONS: No evidence has been found to support the notion that epilepsy can result in memory loss and dementia. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.
Subject(s)
Dementia , Epilepsies, Partial , Epilepsy, Absence , Humans , Child , Mendelian Randomization Analysis , Genome-Wide Association Study , Epilepsy, Absence/complications , Epilepsy, Absence/epidemiology , Epilepsy, Absence/genetics , Amnesia , Dementia/complications , Dementia/epidemiology , Dementia/geneticsABSTRACT
Due to the difference between the system of weights and measures, and the dosage of clinical prescriptions of traditional Chinese medicine in various historical periods, the dosage and conversion standard of prescriptions in past dynasties are different. Therefore, when discounting the dosage of famous classical formulas, the principles of inheriting the essence, making the past serve the present, linking the past and the present, and forming a consensus should be followed, firstly, the dosage of the prescription was converted according to the weights and measures system of the past dynasties. If the converted dosage significantly exceeds the provisions of the 2020 edition of Chinese Pharmacopoeia, then on the premise of ensuring that the proportion of the original prescription drug dosage remains unchanged, the conversion shall be based on expert consensus and drug safety evaluation. For drugs measured in non-standard units, a conversion range is provided based on comprehensive literature analysis and physical measurements. For the conversion of service volume, the original text was used as the basis for the conversion with reference to the measurement standards of different eras. If the original dosage is not clear, the converted dosage will be determined based on the historical evolution of the formula, referring to relevant ancient books, and combining modern applications. Eventually, the converting standard for famous classical formulas was determined as follows:during the Han and Tang dynasties, one Liang(两) was equivalent to 13.8 g and one Sheng(升) was equivalent to 200 mL, in the Tang dynasty, one Fen(分) was equivalent to 3.45 g, during the Song, Jin and Yuan dynasties, one Qian(钱) was equivalent to 4.13 g and one Zhan(盏) was equivalent to 300 mL, during the Ming and Qing dynasties, one Qian(钱) was equivalent to 3.73 g, and one Bei(杯) and one Zhong(盅) were equivalent to 200 mL. For drugs recorded in non-standard units of measurement, it is necessary to conduct actual measurements to determine their conversion standards based on comprehensive analysis to determine their origin. If necessary, different records of the dosage of drugs with the same or similar efficacy and indications in medical books of similar ages can be used to assist in determining the conversion standards. The analysis of the principle of dosage conversion for Chinese medicine is helpful for the clinical application and development of famous classical formulas.
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Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE
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ObjectiveTo observe the clinical course and explore the risk factors for SARS-CoV-2 RNA negative conversion duration (NCD) in asymptomatic and mild-symptomatic patients infected with the SARS-CoV-2 Omicron variant. MethodsClinical data were collected from 244 confirmed cases of corona virus disease (COVID-19) with Omicron variant infection admitted to a temporal makeshift hospital in Shanghai from April 9, 2022 to May 20, 2022. Demographic and clinical data were analyzed, with a primary focus on the time of COVID-19 nucleic acid conversion. Univariate and multivariate Cox regression analysis were used to determine identify risk factors associated with NCD. ResultsThe median duration of negative RNA conversion was 9 days (ranged 7‒12 days). The percentage of patients with positive nucleic acid results on the 5th, 7th, 10th, and 14th days after confirmed infection was 68.4%, 47.1%, 20.1%, and 5.7%, respectively. Kaplan-Meier curves indicated a median nucleic acid conversion time of 12 days (ranged 10‒14 days) for patients with hypertension, 9 days (ranged 7‒11 days) in patients without hypertension, and 11 days (ranged 9‒13 days) for patients aged ≥60 years, and 9 days (ranged 7‒11 days) for patients aged <60 years. Multivariate Cox regression analysis showed that only hypertension was an independent risk factor of NCD (RR=1.60; 95% CI: 1.03‒2.49, P=0.036). ConclusionIn asymptomatic or mildly symptomatic patients infected with the Omicron variant, 20.1% patients continue to exhibit positive viral nucleic acid on the 10th days of infection. The independent risk factor associated with the conversion of SARS-CoV-2 nucleic acid to negative is hypertension.
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In order to provide a reference basis for the development of relevant compound preparations, this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives, and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics, decoction methods, administration and dosage, and combining conversion methods of weights and measures by ancient medical practitioners, along with the dosage and administration of the listed Han dynasty famous classical formulas, it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents[13.8 g per Liang(两)], ensuring the safe and effective medication of these formulas. After combing, it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty, the administration is flexible. The crude drug amount per administration serves as the foundational dose, with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study, it is recommended that when developing compound formulations of famous classical formulas in Han dynasty, the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose, with the frequency of administration described within a range(1 to N times per day, where N is the maximum number of administrations as per the original text). The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies, where the dosage per administration serves as the basis for toxicity research, and the toxicity profile at the maximum administration frequency should be observed, providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.
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Electroreduction of nitric oxide (NO) to NH3 (NORR) has gained extensive attention for the sake of low carbon emission and air pollutant treatment. Unfortunately, NORR is greatly hindered by its sluggish kinetics, especially under low concentrations of NO. Herein, we developed a chlorine (Cl) vacancy strategy to overcome this limitation over FeOCl nanosheets (FeOCl-VCl ). Density functional theory (DFT) calculations revealed that the Cl vacancy resulted in defective Fe with sharp d-states characteristics in FeOCl-VCl to enhance the absorption and activation of NO. In situ X-ray absorption near-edge structure (XANES) and attenuated total reflection-infrared spectroscopy (ATR-IR) verified the lower average oxidation state of defective Fe to enhance the electron transfer for NO adsorption/activation and facilitate the generation of key NHO and NHx intermediates. As a result, the FeOCl-VCl exhibited superior NORR activities with the NH3 Faradaic efficiency up to 91.1 % while maintaining a high NH3 yield rate of 455.4â µg cm-2 h-1 under 1.0â vol % NO concentration, competitive with those of previously reported literatures under higher NO concentration. Further, the assembled Zn-NO battery utilizing FeOCl-VCl as cathode delivered a record peak power density of 6.2â mW cm-2 , offering a new route for simultaneous NO removal, NH3 production, and energy supply.
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The interactive effect of soil cooling and nitrogen (N) addition can accurately simulate climatic and anthropogenic effects on terrestrial and other land-based ecosystems, but direct empirical measurements on the effects of cooling and N addition on soil carbon (C) and N are lacking. Hence, transplanting soils into colder regions was used to evaluate the effects of cooling and N addition on soil C and N. We used PVCs of 30 cm in height and 8 cm in diameter to extract soil samples. Soil C and N were significantly (P < 0.05) increased by transplanting soils into colder regions. In contrast, cooling has insignificantly (P > 0.05) increased the soil dissolved organic C (DOC) and dissolved organic (DON), but the effect was negatively significant on soil pH compared to the C/N ratio. Similarly, N addition significantly increased the measured soil N stock. However, the effect was negatively significant on soil pH (P < 0.05) compared to the C/N ratio (P > 0.05). Nevertheless, the interaction of cooling and N addition did not affect the soil C and N storage. A similar effect was observed on the soil DOC and DON. The results presented here illustrate that transplanting soils into colder regions and N deposition has perfectly simulated the effects of climate-forcing factors on soil C and N storage in terrestrial and other land-based ecosystems. Accordingly, this study suggests that low temperatures have stimulated the accumulation of the measured soil organic and dissolved properties, but the effect is less consequential when low temperature interacts with N addition in high-elevation areas where ecosystem structures and functions are limited by temperature and may serve as a baseline for future research on land feedbacks to the climate system.
Subject(s)
Ecosystem , Soil , Soil/chemistry , Carbon , Forests , Nitrogen/analysisABSTRACT
Antimony (Sb) in natural water has long-term effects on both the ecological environment and human health. Iron mineral phase transformation (IMPT) is a prominent process for removing Sb(V) from natural water. However, the importance of IMPT in eliminating Sb remains uncertain. This study examined the various Sb-Fe binding mechanisms found in different IMPT pathways in natural water, shedding light on the underlying mechanisms. The study revealed that the presence of goethite (Goe), hematite (Hem), and magnetite (Mag) significantly affected the concentration of Sb(V) in natural water. Elevated pH levels facilitated higher Fe content in iron solids but impeded the process of removing Sb(V). To further our understanding, polluted natural water samples were collected from various locations surrounding Sb smelter sites. Results confirmed that converting ferrihydrite (Fhy) to Goe significantly reduced Sb levels (<5 µg/L) in natural water. The emergence of secondary iron phases resulted in greater electrostatic attraction and stabilized surface complexes, which was the most likely cause of the decline of Sb concentration in natural water. The comprehensive findings offer new insights into the factors governing IMPT as well as the Sb(V) behavior control.