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1.
J Environ Sci (China) ; 149: 394-405, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181652

RESUMO

Heterogeneous crystallization is a common occurrence during the formation of solid wastes. It leads to the encapsulation of valuable/hazardous metals within the primary phase, presenting significant challenges for waste treatment and metal recovery. Herein, we proposed a novel method involving the in-situ formation of a competitive substrate during the precipitation of jarosite waste, which is an essential process for removing iron in zinc hydrometallurgy. We observed that the in-situ-formed competitive substrate effectively inhibits the heterogeneous crystallization of jarosite on the surface of anglesite, a lead-rich phase present in the jarosite waste. As a result, the iron content on the anglesite surface decreases from 34.8% to 1.65%. The competitive substrate was identified as schwertmannite, characterized by its loose structure and large surface area. Furthermore, we have elucidated a novel mechanism underlying this inhibition of heterogeneous crystallization, which involves the local supersaturation of jarosite caused by the release of ferric and sulfate ions from the competitive substrate. The local supersaturation promotes the preferential heterogeneous crystallization of jarosite on the competitive substrate. Interestingly, during the formation of jarosite, the competitive substrate gradually vanished through a dissolution-recrystallization process following the Ostwald rule, where a metastable phase slowly transitions to a stable phase. This effectively precluded the introduction of impurities and reduced waste volume. The goal of this study is to provide fresh insights into the mechanism of heterogeneous crystallization control, and to offer practical crystallization strategies conducive to metal separation and recovery from solid waste in industries.


Assuntos
Cristalização , Compostos Férricos , Compostos Férricos/química , Sulfatos/química , Compostos de Ferro/química , Ferro/química , Eliminação de Resíduos/métodos
2.
J Environ Sci (China) ; 147: 230-243, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003043

RESUMO

Enhancing soil organic matter characteristics, ameliorating physical structure, mitigating heavy metal toxicity, and hastening mineral weathering processes are crucial approaches to accomplish the transition of tailings substrate to a soil-like substrate. The incorporation of biomass co-pyrolysis and plant colonization has been established to be a significant factor in soil substrate formation and soil pollutant remediation. Despite this, there is presently an absence of research efforts aimed at synergistically utilizing these two technologies to expedite the process of mining tailings soil substrate formation. The current study aimed to investigate the underlying mechanism of geochemical changes and rapid mineral weathering during the process of transforming tailings substrate into a soil-like substrate, under the combined effects of biomass co-smoldering pyrolysis and plant colonization. The findings of this study suggest that the incorporation of smoldering pyrolysis and plant colonization induces a high-temperature effect and biological effects, which enhance the physical and chemical properties of tailings, while simultaneously accelerating the rate of mineral weathering. Notable improvements include the amelioration of extreme pH levels, nutrient enrichment, the formation of aggregates, and an increase in enzyme activity, all of which collectively demonstrate the successful attainment of tailings substrate reconstruction. Evidence of the accelerated weathering was verified by phase and surface morphology analysis using X-ray diffraction and scanning electron microscopy. Discovered corrosion and fragmentation on the surface of minerals. The weathering resulted in corrosion and fragmentation of the surface of the treated mineral. This study confirms that co-smoldering pyrolysis of biomass, combined with plant colonization, can effectively promote the transformation of tailings into soil-like substrates. This method has can effectively address the key challenges that have previously hindered sustainable development of the mining industry and provides a novel approach for ecological restoration of tailings deposits.


Assuntos
Biomassa , Mineração , Poluentes do Solo , Solo , Solo/química , Pirólise , Plantas , Biodegradação Ambiental
3.
Talanta ; 280: 126789, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39217706

RESUMO

The stability, reproducibility and engineering of SERS substrate faces a great challenge in melamine SERS assay. In this work, a simple, highly sensitive, stable and cost-efficient SERS detection platform for melamine was established based on its Raman fingerprints spectrum. The Ag@ porous silicon photonic crystal (Ag@PPC) was prepared as the 3D SERS substrate by electrochemical etching and magnetron sputter technology. The main influence factors for the preparation of SERS substrate were investigated in detail. The analytical enhancement factor of the 3D SERS substrate can reach to 2.6 × 108. The 3D SERS detection platform showed a wide linear detection range of 10-4∼10 mg L-1 and a low limit of detection of 0.1 µg L-1 for melamine. Moreover, such detection platform showed good stability, high reproducibility and high recovery rates for melamine. The 3D Ag@PPC SERS substrate can be easily prepared and engineered, displaying a great potential application in food safety field.

4.
Sci Total Environ ; : 176159, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260490

RESUMO

Fine particulate matter (PM2.5) constituents are greatly affected by site-specific emission sources and are one of the main reasons for oxidative stress that leads to cardiovascular ailments. This study investigated the temporal, seasonal, and episodic variations in the oxidative potential (OP) of PM2.5 and its association with chemical components. Additionally, we have also examined the effect of filter substrates on OP. Dithiothreitol (DTT) and ascorbic acid (AA) acellular assays were used to estimate the formation of reactive oxygen species (ROS) in PM2.5 samples collected over a year from a regional site in India. PM2.5 morphology and functional groups were also analyzed. Results showed that OPDTTv was at the highest in winter (2.56 ±â€¯0.84 nmol min-1 m-3) and at the lowest during monsoon (0.79 ±â€¯0.65 nmol min-1 m-3). OPAAv exhibited the highest activity in post-monsoon (0.09 ±â€¯0.04 nmol min-1 m-3) and least in summer (0.05 ±â€¯0.04 nmol min-1 m-3). Biomass burning (BB) and open-field burning of crop residue during the rabi and kharif harvesting seasons were associated with significantly elevated PM2.5 toxicity, which is indicative of the contribution of combustion-derived particles. OPDTTv and OPAAv levels from BB in post-monsoon were 21 % and 67 % higher than the levels observed during BB in summer. Flaky irregular agglomerates and porous structures were observed during the BB period. Fourier-transformed infrared spectroscopy revealed that traffic-emitted organic hydrocarbons CH functional group was dominant across the season. Further, chemical species such as organics (OC and EC fractions) and ions (SO42-, NH4+, Cl-, NO3-) were found to be significantly associated with OP. Among the three filter substrates, the Teflon showed higher OP variability for both assays. This study emphasizes the impact of regional toxic aerosols across seasons and during episodic events. It contributes to our understanding of the toxicity of ambient PM2.5, which is crucial for developing targeted air-quality management strategies.

5.
J Biol Chem ; : 107755, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260691

RESUMO

Formycin A (FOR) and Pyrazofurin A (PYR) are nucleoside analogues with antiviral and antitumor properties. They are known to interfere with nucleic acid metabolism, but their direct effect on transcription is less understood. We explored how RNA polymerases (RNAPs) from bacteria, mitochondria, and viruses utilize FOR, PYR, and oxidized purine nucleotides. All tested polymerases incorporated FOR in place of adenine and PYR in place of uridine. FOR also exhibited surprising dual-coding behavior, functioning as a cytosine substitute, particularly for viral RNAP. In contrast, 8-oxoadenine and 8-oxoguanine were incorporated in place of uridine in addition to their canonical Watson-Crick codings. Our data suggest that the interconversion of canonical anti- and alternative syn-conformers underlies dual-coding abilities of FOR and oxidized purines. Structurally distinct RNAPs displayed varying abilities to utilize syn-conformers during transcription. By examining base pairings that led to substrate incorporation and the entire spectrum of geometrically compatible pairings, we have gained new insights into the nucleobase selection processes employed by structurally diverse RNAPs. These insights may pave the way for advancements in antiviral therapies.

6.
Environ Res ; : 119967, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260718

RESUMO

PER: and polyfluoroalkyl substances (PFASs), typical persistent organic pollutants detected in various water environments, have attracted widespread attention due to their undesirable effects on ecology and human health. Constructed wetlands (CWs) have emerged as a promising, cost-effective, and nature-based solution for removing persistent organic pollutants. This review summarizes the removal performance of PFASs in CWs, underlying PFASs removal mechanisms, and influencing factors are also discussed comprehensively. Furthermore, the environmental risks of PFASs-enriched plants and substrates in CWs are analyzed. The results show that removal efficiencies of total PFASs in various CWs ranged from 21.3% to 98%. Plant uptake, substrate absorption and biotransformation are critical pathways in CWs for removing PFASs, which can be influenced by the physiochemical properties of PFASs, operation parameters, environmental factors, and other pollutants. Increasing dissolved oxygen supply and replacing traditional substrates in CWs, and combining CWs with other technologies could significantly improve PFASs removal. Further, CWs pose relatively lower ecological and environmental risks in removing PFASs, which indicates CWs could be an alternative solution for controlling PFASs in aquatic environments.

7.
Bioresour Technol ; : 131471, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260727

RESUMO

To achieve industrial-scale putrescine production, a high efficient bio-synthesis of putrescine involving arginase (ARG, EC 3.5.3.1) and L-ornithine decarboxylase was evaluated here. Among the four arginases tested, ARGBT from Bos Taurus showed the highest activity (1966 U/mg). Compared to the L-arginine decarboxylase (ADC) pathway, the strain expressing ARGBT and L-ornithine decarboxylase (SpeC) produced 28.7 g/L putrescine, a 38.6 % increase. Two pyridoxal phosphate (PLP) salvage pathways were evaluated, and the strain BL-PTac-PdxK co-expressed pyridoxal kinase (PdxK) performed better. D-Glucose was used as the co-substrate to improve the putrescine titer further. Under optimal conditions, 43.6 g/L putrescine was produced from 87.1 g/L L-arginine, and 76 g/L putrescine was synthesized on a 0.5 L scale. Using L-arginine fermentation broth (60 g/L) as the substrate, a titer of 30 g/L putrescine was achieved. This efficient biotransformation process presented here enables feasible industrial-scale putrescine production.

8.
Nano Lett ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225502

RESUMO

The anode-free lithium metal battery (AF-LMB) demonstrates the emerging battery chemistry, exhibiting higher energy density than the existing lithium-ion battery and conventional LMB empirically. A systematic step-by-step while bottom-up calculation system is first developed to quantitatively depict the energy gap from theory to practice. The attainable high energy of AF-LMB necessitates a homogeneous Li+ flux on the anode side to achieve an improved Li reversibility against inventory loss. On such basis, a lithiophilic Cu3P-decorated 3D copper foil to promote dendrite-free lithium deposition is further reported. The phosphorized surface of high affinity toward Li+ incorporating the nanostructure of abundant nucleation sites synergistically regulates the Li nucleation/growth behavior, extending the cycling lifespan of high-loading AF-LMBs. The processed foil featuring lightweight and ultrathin merits further increases the energy density, both gravimetrically and volumetrically. This study provides a novel scheme for simultaneously realizing the uniform deposition of lithium and increasing the energy density of future AF-LMBs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39243255

RESUMO

BACKGROUND: Although targeting atrial fibrillation (AF) drivers and substrates has been used as an effective adjunctive ablation strategy for patients with persistent AF (PsAF), it can result in iatrogenic scar-related atrial tachycardia (iAT) requiring additional ablation. Personalized atrial digital twins (DTs) have been used preprocedurally to devise ablation targeting that eliminate the fibrotic substrate arrhythmogenic propensity and could potentially be used to predict and prevent postablation iAT. OBJECTIVES: In this study, the authors sought to explore possible alternative configurations of ablation lesions that could prevent iAT occurrence with the use of biatrial DTs of prospectively enrolled PsAF patients. METHODS: Biatrial DTs were generated from late gadolinium enhancement-magnetic resonance images of 37 consecutive PsAF patients, and the fibrotic substrate locations in the DT capable of sustaining reentries were determined. These locations were ablated in DTs by representing a single compound region of ablation with normal power (SSA), and postablation iAT occurrence was determined. At locations of iAT, ablation at the same DT target was repeated, but applying multiple lesions of reduced-strength (MRA) instead of SSA. RESULTS: Eighty-three locations in the fibrotic substrates of 28 personalized biatrial DTs were capable of sustaining reentries and were thus targeted for SSA ablation. Of these ablations, 45 resulted in iAT. Repeating the ablation at these targets with MRA instead of SSA resulted in the prevention of iAT occurrence at 15 locations (18% reduction in the rate of iAT occurrence). CONCLUSIONS: Personalized atrial DTs enable preprocedure prediction of iAT occurrence after ablation in the fibrotic substrate. It also suggests MRA could be a potential strategy for preventing postablation AT.

10.
Harmful Algae ; 138: 102700, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39244235

RESUMO

The ecological dynamics of particle-attached bacteria (PAB) were observed through changes in the core phytoplankton phycosphere, and were associated with the dynamics of free-living bacteria (FLB) using metabarcoding and microscopic analyses over 210 days (with weekly sampling intervals) in the Jangmok coastal ecosystem, South Korea. Cluster analysis and non-metric multidimensional scaling classified the phytoplankton community into six groups comprising core phytoplankton species, including the harmful algal species Akashiwo sanguinea (dinoflagellate) in late autumn, Teleaulax amphioxeia (cryptomonads) in early winter and spring, Skeletonema marinoi-dohrnii complex (diatom) in winter, Pseudo-nitzschia delicatissima (diatom) in early spring, and diatom complexes such as Chaetoceros curvisetus and Leptocylindrus danicus in late spring. We identified 59 and 32 indicators in PAB and FLB, respectively, which rapidly changed with the succession of the six core phytoplankton species. The characteristics of PAB were mainly divided into "Random encounters" or "Attraction of motivation by chemotaxis." When Akashiwo sanguinea bloomed, bacteria of the genera Kordiimonas and Polaribacter, which are commonly observed in PAB and FLB, indicated "Random encounter" characteristics. In addition, Sedimenticola of PAB was uniquely presented in Akashiwo sanguinea, exhibiting characteristics of "Attraction of motivation by chemotaxis." In contrast, FLB followed the strategy of "Random encounters" because it was not affected by specific habitats and energy sources. Thus, many common bacteria were PAB and FLB, thereby dictating the bacteria's strategy of "Random encounters." "Attraction of motivation by chemotaxis" has characteristics of the species-specific interactions between PAB and specific harmful algal species, and is potentially influenced by organic matter of core phytoplankton cell surface and/or EPS released from phytoplankton.


Assuntos
Bactérias , Ecossistema , Fitoplâncton , Bactérias/classificação , Fitoplâncton/fisiologia , República da Coreia , Proliferação Nociva de Algas , Dinoflagellida/fisiologia
11.
J Appl Glycosci (1999) ; 71(3): 91-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234032

RESUMO

We recently found two α-L-glucosidases, which can hydrolyze p-nitrophenyl α-L-glucopyranoside (PNP L-Glc) rather than p-nitrophenyl α-L-fucopyranoside, in glycoside hydrolase family 29. This study evaluated their substrate specificity for p-nitrophenyl α-L-rhamnopyranoside (PNP L-Rha), α-L-quinovopyranoside (PNP L-Qui), and α-L-xylopyranoside (PNP L-Xyl), of which structure is similar to PNP L-Glc. The two α-L-glucosidases had little activity toward PNP L-Rha. They exhibited higher k cat/K m values for PNP L-Qui but smaller for PNP L-Xyl than for PNP L-Glc. The molecular docking studies indicated that these specificities were correlated well with the active-site structure of the α-L-glucosidases. The finding that α-L-quinovoside, which has been suggested to occur in nature, is also a substrate for α-L-glucosidases indicates that this enzyme are not solely dedicated to α-L-glucoside hydrolysis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39248315

RESUMO

BACKGROUND: Low voltage areas (LVA) are pivotal in atrial fibrillation (AF) pathogenesis, influencing local left atrial LA excitation and perpetuating AF occurrences. While pulmonary vein isolation (PVI) with cryo-balloon (CB) ablation is effective for AF, it doesn't provide insights into the LA substrate or detect LVA, which affects ablation success rates. This study examines whether LA voltage and LVAs can be anticipated by analyzing the voltage signal amplitude at the coronary sinus (CS) catheter, which is standard in CB and radiofrequency ablation procedures. METHODS: A retrospective analysis of 284 patients with recurrent AF undergoing RF catheter ablation was conducted at a high-volume EP center in Germany. The correlation between LA voltage and LVA with the CS signal was explored. RESULTS: The signal amplitude in the CS significantly correlated with voltage in LA walls, particularly in the proximal CS (correlation coefficient ρ = 0.81, p < 0.001). A CS signal cut-off of 1.155 mV effectively predicted severe atrial LVAs (>40%) with a sensitivity of 90.7% and a specificity of 100%. While a threshold of 1.945 mV identified patients with no significant atrial LVAs (<5%) with a sensitivity of 88% and a specificity of 50% (AUC: 0.81, 95% CI: 0.71-0.89, p < 0.001). CONCLUSION: The CS signal amplitude is associated with the LA voltage. Due to its potential as a diagnostic tool for atrial LVAs, the signal amplitude in the CS could provide valuable information about the LA substrate, especially when 3D mapping is not feasible.

13.
Sci Rep ; 14(1): 21192, 2024 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261563

RESUMO

A key player in energy metabolism is phosphofructokinase-1 (PFK1) whose activity and behavior strongly influence glycolysis and thus have implications in many areas. In this research, PFK1 assays were performed to convert F6P and ATP into F-1,6-P and ADP for varied pH and ATP concentrations. PFK1 activity was assessed by evaluating F-1,6-P generation velocity in two ways: (1) directly calculating the time slope from the first two or more datapoints of measured product concentration (the initial-velocity method), and (2) by fitting all the datapoints with a differential equation explicitly representing the effects of ATP and pH (the modeling method). Similar general trends of inhibition were shown by both methods, but the former gives only a qualitative picture while the modeling method yields the degree of inhibition because the model can separate the two simultaneous roles of ATP as both a substrate of reaction and an inhibitor of PFK1. Analysis based on the model suggests that the ATP affinity is much greater to the PFK1 catalytic site than to the inhibitory site, but the inhibited ATP-PFK1-ATP complex is much slower than the uninhibited PFK1-ATP complex in product generation, leading to reduced overall reaction velocity when ATP concentration increases. The initial-velocity method is simple and useful for general observation of enzyme activity while the modeling method has advantages in quantifying the inhibition effects and providing insights into the process.


Assuntos
Trifosfato de Adenosina , Fosfofrutoquinase-1 , Trifosfato de Adenosina/metabolismo , Fosfofrutoquinase-1/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Frutosefosfatos/metabolismo , Difosfato de Adenosina/metabolismo , Glicólise
14.
Front Genet ; 15: 1469011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262420

RESUMO

N7-Methylguanosine (m7G) is important RNA modification at internal and the cap structure of five terminal end of message RNA. It is essential for RNA stability of RNA, the efficiency of translation, and various intracellular RNA processing pathways. Given the significance of the m7G modification, numerous studies have been conducted to predict m7G sites. To further elucidate the regulatory mechanisms surrounding m7G, we introduce a novel bioinformatics framework, m7GRegpred, designed to forecast the targets of the m7G methyltransferases METTL1 and WDR4, and m7G readers QKI5, QKI6, and QKI7 for the first time. We integrated different features to build predictors, with AUROC scores of 0.856, 0.857, 0.780, 0.776, 0.818 for METTL1, WDR4, QKI5, QKI6, and QKI7, respectively. In addition, the effect of window lengths and algorism were systemically evaluated in this work. The finial model was summarized in a user-friendly webserver: http://modinfor.com/m7GRegpred/. Our research indicates that the substrates of m7G regulators can be identified and may potentially advance the study of m7G regulators under unique conditions.

15.
Heart Rhythm O2 ; 5(8): 561-572, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39263615

RESUMO

Ventricular tachycardia (VT) is a life-threatening heart rhythm and has long posed a complex challenge in the field of cardiology. Recent developments in advanced imaging modalities have aimed to improve comprehension of underlying arrhythmic substrate for VT. To this extent, high-resolution cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) have emerged as tools for accurately visualizing and characterizing scar tissue, fibrosis, and other critical structural abnormalities within the heart, providing novel insights into VT triggers and substrate. However, clinical implementation of knowledge derived from these advanced imaging techniques in improving VT treatment and guiding invasive therapeutic strategies continues to pose significant challenges. A pivotal concern lies in the absence of standardized imaging protocols and analysis methodologies, resulting in a large variance in data quality and consistency. Furthermore, the clinical significance and outcomes associated with VT substrate characterization through CMR and CCT remain dynamic and subject to ongoing evolution. This highlights the need for refinement of these techniques before their reliable integration into routine patient care can be realized. The primary objectives of this study are twofold: firstly, to provide a comprehensive overview of the studies conducted over the last 15 years, summarizing the current available literature on imaging-based assessment of VT substrate. Secondly, to critically analyze and evaluate the selected studies, with the aim of providing valuable insights that can inform current clinical practice and future research.

16.
Environ Sci Technol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226236

RESUMO

This study demonstrated that NiO and Ni(OH)2 as Ni(II) catalysts exhibited significant activity for organic oxidation in the presence of various oxyanions, such as hypochlorous acid (HOCl), peroxymonosulfate (PMS), and peroxydisulfate (PDS), which markedly contrasted with Co-based counterparts exclusively activating PMS to yield sulfate radicals. The oxidizing capacity of the Ni catalyst/oxyanion varied depending on the oxyanion type. Ni catalyst/PMS (or HOCl) degraded a broad spectrum of organics, whereas PDS enabled selective phenol oxidation. This stemmed from the differential reactivity of two high-valent Ni intermediates, Ni(III) and Ni(IV). A high similarity with Ni(III)OOH in a substrate-specific reactivity indicated the role of Ni(III) as the primary oxidant of Ni-activated PDS. With the minor progress of redox reactions with radical probes and multiple spectroscopic evidence on moderate Ni(III) accumulation, the significant elimination of non-phenolic contaminants by NiOOH/PMS (or HOCl) suggested the involvement of Ni(IV) in the substrate-insensitive treatment capability of Ni catalyst/PMS (or HOCl). Since the electron-transfer oxidation of organics by high-valent Ni species involved Ni(II) regeneration, the loss of the treatment efficiency of Ni/oxyanion was marginal over multiple catalytic cycles.

17.
Circulation ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253856

RESUMO

BACKGROUND: The docking protein IRS2 (insulin receptor substrate protein-2) is an important mediator of insulin signaling and may also regulate other signaling pathways. Murine hearts with cardiomyocyte-restricted deletion of IRS2 (cIRS2-KO) are more susceptible to pressure overload-induced cardiac dysfunction, implying a critical protective role of IRS2 in cardiac adaptation to stress through mechanisms that are not fully understood. There is limited evidence regarding the function of IRS2 beyond metabolic homeostasis regulation, particularly in the context of cardiac disease. METHODS: A retrospective analysis of an electronic medical record database was conducted to identify patients with IRS2 variants and assess their risk of cardiac arrhythmias. Arrhythmia susceptibility was examined in cIRS2-KO mice. The underlying mechanisms were investigated using confocal calcium imaging of ex vivo whole hearts and isolated cardiomyocytes to assess calcium handling, Western blotting to analyze the involved signaling pathways, and pharmacological and genetic interventions to rescue arrhythmias in cIRS2-KO mice. RESULTS: The retrospective analysis identified patients with IRS2 variants of uncertain significance with a potential association to an increased risk of cardiac arrhythmias compared with matched controls. cIRS2-KO hearts were found to be prone to catecholamine-sensitive ventricular tachycardia and reperfusion ventricular tachycardia. Confocal calcium imaging of ex vivo whole hearts and single isolated cardiomyocytes from cIRS2-KO hearts revealed decreased Ca²+ transient amplitudes, increased spontaneous Ca²+ sparks, and reduced sarcoplasmic reticulum Ca²+ content during sympathetic stress, indicating sarcoplasmic reticulum dysfunction. We identified that overactivation of the AKT1/NOS3 (nitric oxide synthase 3)/CaMKII (Ca2+/calmodulin-dependent protein kinase II)/RyR2 (type 2 ryanodine receptor) signaling pathway led to calcium mishandling and catecholamine-sensitive ventricular tachycardia in cIRS2-KO hearts. Pharmacological AKT inhibition or genetic stabilization of RyR2 rescued catecholamine-sensitive ventricular tachycardia in cIRS2-KO mice. CONCLUSIONS: Cardiac IRS2 inhibits sympathetic stress-induced AKT/NOS3/CaMKII/RyR2 overactivation and calcium-dependent arrhythmogenesis. This novel IRS2 signaling axis, essential for maintaining cardiac calcium homeostasis under stress, presents a promising target for developing new antiarrhythmic therapies.

18.
Int J Biol Macromol ; 279(Pt 3): 135426, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251006

RESUMO

Recognizing the critical need to elucidate the molecular determinants of this selectivity offers a pathway to engineer enzymes with broader and more versatile catalytic capabilities. Through integrated methods including phylogenetic analysis, molecular docking, and structural analysis, we identified a pivotal amino acid residue, αTrp116, linking the substrate binding pocket and the active site of a NHase from Pseudonocardia thermophila JCM 3095 (PtNHase). This residue acts as a crucial determinant of substrate specificity within the NHase enzyme. The mutant αW116R modified the substrate specificity of PtNHase, significantly enhancing its catalytic efficiency towards aromatic substrates. The catalytic activity for aromatic compounds such as 3-Cyanopyridine was 14-fold that of the wild-type, whereas its activity for aliphatic substrates diminished to one-sixth. MD simulations revealed that replacing αTrp116 with Arg allowed aromatic nitrile substrates to achieve more favorable conformations within the active site. Based on the mutant αW116R, we further constructed a combinatorial variant Pt-4, tailored for aromatic substrates, which exhibited an enzyme activity 50 times that of the wild-type. These results highlight the critical influence of amino acid residues in the enzyme's active site on substrate specificity and offer fresh perspectives and approaches for the evolution of enzymes.

19.
Polymers (Basel) ; 16(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39274073

RESUMO

An electroactive polyazomethine was prepared directly on a transparent electrode by the polycondensation of bis(triphenylamine) dialdehyde and its complementary methoxytriphenylamine diamine. The spray-and-bake method of coating the electrode for preparing electrochromic layers could be upscaled to prepare working devices larger than standard test devices. The film prepared by thermally annealing the complementary monomers was both electroactive and switched its color with an applied potential. The yellow electrochromic polyazomethine could be electrochemically oxidized reversibly to obtain a blue film. The electrochromic test device fabricated from the polyazomethine was operated upwards of 1 h for performance assessment. The electrochromic response times of the electrochromic device were ca. 3.3 and 1.2 s for the coloration and bleaching, respectively. The upscaled device prepared by the straightforward coating approach had consistent metrics with the small-area test device.

20.
J Clin Med ; 13(17)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39274244

RESUMO

Despite advances in ablative therapies, outcomes remain less favorable for persistent atrial fibrillation often due to presence of non-pulmonary vein triggers and abnormal atrial substrates. This review highlights advances in ablation technologies and notable scientific literature on clinical outcomes associated with pursuing adjunctive ablation targets and substrate modification during persistent atrial fibrillation ablation, while also highlighting notable future directions.

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