Nebivolol (NEB) is widely used for the treatment of hypertension and chronic heart failure and has become an ubiquitous emerging organic pollutant. It has been shown to undergo direct photolysis, but ...the role of DOM in its degradation kinetics and mechanism is not well understood. In this study, we studied the photochemical behavior of NEB in the presence of seawater DOM (SW-DOM) and freshwater DOM (SRNOM) under simulated sunlight irradiation. SW-DOM had a promotion effect on NEB photodegradation, whereas SRNOM retarded its photolytic transformation. After eliminating the influence of light screening, we found that the indirect photodegradation rate of NEB in the presence of SRNOM was lower than that in the presence of SW-DOM. Results show that the indirect photodegradation pathway occurred by reaction with triplet-excited DOM (3DOM*). The second-order rate constants for 3SW-DOM* and 3SRNOM* reaction with NEB are 3.7 × 109 M−1 s−1 and 3.7 × 108 M−1 s−1, respectively. The electron donating capacity of SRNOM is higher than that of SW-DOM, indicating that SRNOM may contain more activated phenolic moieties. SRNOM may thus have higher antioxidant activity, leading a higher inhibitory effect on NEB photodegradation. A total of six degradation products were identified in the absence and presence of DOM by HPLC-ESI-MS/MS. The substitution of F by OH-groups and further oxidation a OH-group in the lateral chain to a ketone, and cleavage of N–C bond by the attack of 3DOM* are here proposed as the main degradation pathways.
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•Seawater DOM promotes NEB photodegradation under simulated sunlight irradiation.•Freshwater DOM retards the photodegradation of NEB.•3DOM* contributes to the indirect photodegradation of NEB.•Photoreactivity of seawater 3DOM* to NEB is higher than that of freshwater 3DOM*.•Three new photoproducts are identified in DOM solutions compared to pure water.
Oncogenic KRAS is a major driver in lung adenocarcinoma (LUAD) that has yet to be therapeutically conquered. Here we report that the SLC7A11/glutathione axis displays metabolic synthetic lethality ...with oncogenic KRAS. Through metabolomics approaches, we found that mutationally activated KRAS strikingly increased intracellular cystine levels and glutathione biosynthesis. SLC7A11, a cystine/glutamate antiporter conferring specificity for cystine uptake, was overexpressed in patients with KRAS-mutant LUAD and showed positive association with tumor progression. Furthermore, SLC7A11 inhibition by either genetic depletion or pharmacological inhibition with sulfasalazine resulted in selective killing across a panel of KRAS-mutant cancer cells in vitro and tumor growth inhibition in vivo, suggesting the functionality and specificity of SLC7A11 as a therapeutic target. Importantly, we further identified a potent SLC7A11 inhibitor, HG106, that markedly decreased cystine uptake and intracellular glutathione biosynthesis. Furthermore, HG106 exhibited selective cytotoxicity toward KRAS-mutant cells by increasing oxidative stress- and ER stress-mediated cell apoptosis. Of note, treatment of KRAS-mutant LUAD with HG106 in several preclinical lung cancer mouse models led to marked tumor suppression and prolonged survival. Overall, our findings reveal that KRAS-mutant LUAD cells are vulnerable to SLC7A11 inhibition, offering potential therapeutic approaches for this currently incurable disease.
Novel brominated flame retardants (NBFRs) have become ubiquitous emerging organic pollutants. However, little is known about their transformation in natural waters. In this study, aquatic ...photochemical behavior of a representative NBFR, 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE), was investigated by simulated sunlight irradiation experiment. Results show that DPTE can undergo direct photolysis (apparent quantum yield 0.008 ± 0.001) and hydroxyl radical (·OH) initiated oxidation (second order reaction rate constant 2.4 × 109 M–1·s–1). Dissolved organic matter (DOM) promotes the photodegradation due to generation of excited triplet DOM and ·OH. Two chlorinated intermediates were identified in the photodegradation of DPTE in seawaters. Density functional theory calculation showed that ·Cl or ·Cl2 – addition reactions on C–Br sites of the phenyl group and H-abstraction reactions from the propyl group are main reaction pathways of DPTE with the chlorine radicals. The ·Cl or ·Cl2 – addition proceeds via a replacement mechanism to form chlorinated intermediates. Environmental half-lives of DPTE relevant with photodegradation are estimated to be 6.5–1153.9 days in waters of the Yellow River estuarine region. This study provides valuable insights into the phototransformation behavior of DPTE in natural waters, which is helpful for persistence assessment of the NBFRs.
ACE2 Shedding and the Role in COVID-19 Wang, Jieqiong; Zhao, Huiying; An, Youzhong
Frontiers in cellular and infection microbiology,
01/2022, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe ...acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.
Exploiting the valley degree of freedom to store and manipulate information provides a novel paradigm for future electronics. A monolayer transition-metal dichalcogenide (TMDC) with a broken ...inversion symmetry possesses two degenerate yet inequivalent valleys, which offers unique opportunities for valley control through the helicity of light. Lifting the valley degeneracy by Zeeman splitting has been demonstrated recently, which may enable valley control by a magnetic field. However, the realized valley splitting is modest (∼0.2 meV T-1 ). Here we show greatly enhanced valley spitting in monolayer WSe2 , utilizing the interfacial magnetic exchange field (MEF) from a ferromagnetic EuS substrate. A valley splitting of 2.5 meV is demonstrated at 1 T by magnetoreflectance measurements and corresponds to an effective exchange field of ∼12 T. Moreover, the splitting follows the magnetization of EuS, a hallmark of the MEF. Utilizing the MEF of a magnetic insulator can induce magnetic order and valley and spin polarization in TMDCs, which may enable valleytronic and quantum-computing applications.
•Seawater DOM facilitates but freshwater DOM slightly retards SCP photodegradation.•3DOM* photogenerated by S-DOM is low in concentration but high in quantum yields.•High sensitization reactivity of ...3S-DOM* to SCP is owed to less phenolic antioxidant.•Mariculture activity enhances formation of Hi-3DOM* from seawater DOM.•Predicted photolytic rates of SCP are within big error using DOM analogs instead of real DOM.
Coastal seawater constitutes an important ecosystem receiving inputs of organic micropollutants (OMPs) such as sulfa antibiotics from land-based sources or mariculture activities. It is necessary to investigate photodegradation of OMPs in coastal seawaters for assessing their environmental fate and risks. However, effects of coastal seawater dissolved organic matter (S-DOM) on OMPs photodegradation are largely unknown, given that chemical compositions of S-DOM are different from those of freshwater DOM. Herein, photochemical characteristics of S-DOM extracted from Dalian coastal seawaters were investigated by simulating photochemical experiment adopting sulfachloropyridazine as a case. Results show that S-DOM accelerates the photodegradation mainly through excited triplet-state DOM (3DOM*) with an apparent rate constant (4.43 × 108 M−1 s−1) ten folds of that of freshwater DOM, which is mainly due to much lower phenol contents detected in the S-DOM (0.022 mg-Gallic acid mg-C−1). The S-DOM impacted by mariculture can photogenerate more high-energy 3DOM* than those less impacted by mariculture, further contributing to the high 3DOM* reactivity. The study shows that to accurately predict photolytic persistence of OMPs in field water bodies, it is of significance to determine the second-order reaction rate constants between 3DOM* and target OMPs using DOM extracted from relevant water bodies.
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•Importance of photodegradation in removal of OMPs in waters was discussed.•Processes of OMPs’ photodegradation was compared to biodegradation.•Understanding on roles of DOM on photodegradation is ...concisely updated.•Major knowledge gaps in environmental photochemistry are identified.
Photochemical reactions widely occur in the aquatic environment and play fundamental roles in aquatic ecosystems. In particular, solar-induced photodegradation is efficient for many organic micropollutants (OMPs), especially those that cannot undergo hydrolysis or biodegradation, and thus can mitigate chemical pollution. Recent reports indicate that photodegradation may play a more important role than biodegradation in many OMP transformations in the aquatic environment. Photodegradation can be influenced by the water matrix such as pH, inorganic ions, and dissolved organic matter (DOM). The effect of the water matrix such as DOM on photodegradation is complex, and new insights concerning the disparate effects of DOM have recently been reported. In addition, the photodegradation process is also influenced by physical factors such as latitude, water depth, and temporal variations in sunlight as these factors determine the light conditions. However, it remains challenging to gain an overview of the importance of photodegradation in the aquatic environment because the reactions involved are diverse and complex. Therefore, this review provides a concise summary of the importance of photodegradation and the major processes related to the photodegradation of OMPs, with particular attention given to recent progress on the major reactions of DOM. In addition, major knowledge gaps in this field of environmental photochemistry are highlighted.
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A large number of opportunities for biomedical hydrogel design and functionality through photo-processing have stretched the limits of innovation. As both photochemical understanding and engineering ...technologies continue to develop, more complicated geometries and spatiotemporal manipulations can be realized through photo-exposure, producing multifunctional hydrogels with specific chemical, biological and physical characteristics for the achievement of biomedical goals. This report describes the role that light has recently played in the synthesis and functionalization of biomedical hydrogels and primarily the design of photoresponsive hydrogels via different chemical reactions (photo crosslinking and photo degradation) and conventional light curing processes (micropatterning, stereolithography and two/multiphoton techniques) as well as typical biomedical applications of the hydrogels (cell culture, differentiation and in vivo vascularization) and their promising future.
Mariculture activities and river inputs lead to coastal seawaters with DOM levels that are comparable to or even higher than those in terrestrial water bodies. However, effects of seawater DOM, and ...especially of DOM occurring in areas impacted by mariculture, on photodegradation of organic micropollutants, are largely unknown. In this study, simulated sunlight irradiation experiments were performed to probe the effects of DOM extracted from mariculture impacted seawaters and from offshore areas, on photodegradation of three sulfonamide antibiotics (SAs). Results show that the SAs are transformed mainly by indirect photodegradation induced by triplet excited DOM (3DOM*). Compared with DOM from the more pristine coastal waters, the DOM from mariculture impacted areas undergoes less photobleaching, contains higher percentage of humic-like materials and higher proportions of aromatic and carbonyl structures. Thus, the DOM from mariculture areas exhibits higher rates of light absorption, higher formation quantum yields of 3DOM*, higher 3DOM* steady-state concentrations and higher reactivity on photodegradation of the SAs. Photochemistry of the seawater DOM is different from that reported for freshwater lake DOM. This study highlights the importance of probing the effects of DOM from coastal seawaters on photodegradation of organic micropollutants since coastal seawaters are sinks of many aquatic pollutants.
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•DOM were isolated from mariculture ponds, tidal creek waters and offshore waters.•Effects of DOM in coastal waters on photodegradation of pollutants were unveiled.•DOM from mariculture areas has higher aromaticity than those from offshore waters.•DOM from mariculture areas exhibits high reactivity on degradation of sulfonamides.
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