Uranium is a key resource for the development of the nuclear industry, and extracting uranium from the natural seawater is one of the most promising ways to address the shortage of uranium resources. ...Herein, a semiconducting covalent organic framework (named NDA‐TN‐AO) with excellent photocatalytic and photoelectric activities was synthesized. The excellent photocatalytic effect endowed NDA‐TN‐AO with a high anti‐biofouling activity by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby increasing the uranium extraction capacity. Owing to the photoinduced effect, the adsorption capacity of NDA‐TN‐AO to uranium in seawater reaches 6.07 mg g−1, which is 1.33 times of that in dark. The NDA‐TN‐AO with enhanced adsorption capacity is a promising material for extracting uranium from the natural seawater.
Photoelectric and photocatalytic effects endow the covalent organic framework NDA‐TN‐AO with good anti‐biofouling activity. This occurs by generating biotoxic reactive oxygen species and promoting photoelectrons to reduce the adsorbed UVI to insoluble UIV, thereby improving the uranium adsorption capacity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ...ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons.
Methods
A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured.
Results
The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05).
Conclusions
High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the ...increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat‐treated residual HCC cells were cultured on tailorable 3D gel with different matrix stiffness, simulating the changed physical environment after thermal ablation, and then the mechanical alterations of matrix stiffness on cell phenotypes were explored. Increased stiffness was found to significantly promote the proliferation of the heat‐treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness‐dependent regulation of ERK phosphorylation. Heat‐exposed HCC cells cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness‐dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat‐treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerates HCC development. Vitamin K1 plus sorafenib can reverse this protumor effect.
Increased matrix stiffness after thermal ablation accelerates the progression of heat‐exposed residual HCC cells. Vitamin K1 and sorafenib disrupt the stiffness‐induced ERK activation to reverse the pro‐tumor effect as the potential therapeutic drugs. This new finding will help design strategy to treat the local tumor progression and prevent its rapid progression after RFA in the treatment of medium or large HCC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
During myocardial infarction (MI), cardiac fibroblasts (CFs) transform into myofibroblast (CMT). This study aimed to investigate the crosstalk of Notch1 and transforming growth factor‐β1 ...(TGF‐β1)/Smad3 signaling in the regulation of CMT and myocardial fibrosis.
Methods
Primary CFs were isolated from young rats and treated with TGF‐β1 or adenovirus to overexpress or knockdown Notch1 intracellular domain (N1ICD) or Smad3.
Results
TGF‐β1 decreased the expression of fibroblast markers but increased the expression of myofibroblast markers in rat CFs. TGF‐β1 increased the proliferation, invasion, and adhesion, and the secretion of collagen I of CFs, and these effects were inhibited by N1ICD overexpression. Moreover, endogenous Smad3 phosphorylation in CFs was enhanced by N1ICD knockdown, whereas TGF‐β1 induced Smad3 phosphorylation was antagonized by the N1ICD overexpression. Conversely, endogenous N1ICD activation in CFs was antagonized by Smad3, whereas TGF‐β1 induced N1ICD inactivation was antagonized by Smad3 knockdown. Coimmunoprecipitation showed that N1ICD interacted with Smad3 and immunostaining revealed the colocalization of N1ICD and Smad3 in the nuclei of CFs. Moreover, we demonstrated the functional antagonism of N1ICD and Smad3 on the phenotypes of CFs. Finally, TGF‐β1/Smad3 signaling promoted whereas Notch signaling inhibited myocardial fibrosis in rat MI model.
Conclusion
Notch signaling inhibits CMT by antagonizing TGF‐β1/Smad3 signaling. Notch signaling activators and TGF‐β1/Smad3 signaling inhibitors could be exploited for therapeutic intervention to inhibit myocardial fibrosis after MI.
N1ICD interacted with Smad3 and immunostaining revealed the colocalization of N1ICD and Smad3 in the nuclei of cardiac fibroblasts.
N1ICD and Smad3 antagonized each other to regulate the phenotypes of cardiac fibroblasts.
TGF‐β1/Smad3 signaling promoted but Notch signaling inhibited myocardial fibrosis in the rat model.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the ...myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad‐N1ICD and Ad‐shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.
Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the ...lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs,
. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure,
. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Biological soil crusts across the desert regions play a key role in regional ecological security and ecological health. They are vital biotic components of desert ecosystems that maintain soil ...stability, fix carbon and nitrogen, influence the establishment of vascular plants, and serve as habitats for a large number of arthropods and microorganisms, as well as influencing soil hydrological processes. Changes in temperature and precipitation are expected to influence the functioning of desert ecosystems by altering biotic components such as the species composition of biological soil crusts. However, it remains unclear how these important components will respond to the prolonged warming and reduced precipitation that is predicted to occur with climate change. To evaluate how the hydrological properties of these biological soil crusts respond to these alterations, we used open‐top chambers over a 10‐year period to simulate warming and reduced precipitation. Infiltration, dew entrapment, and evaporation were measured as surrogates of the hydrological functioning of biological soil crusts. It was found that the ongoing warming coupled with reduced precipitation will more strongly affect moss in crustal communities than lichens and cyanobacteria, which will lead to a direct alteration of the hydrological performance of biological soil crusts. Reductions in moss abundance, surface cover, and biomass resulted in a change in structure and function of crustal communities, decreased dew entrapment, and increased infiltration and evaporation of biological soil crusts in desert ecosystems, which further impacted on the desert soil water balance.
Warming coupled with reduced precipitation will more strongly affect moss in crustal communities than lichens and cyanobacteria. Reductions in moss abundance, surface cover, and biomass resulted in a change in structure and function of crustal communities, which will lead to a direct alteration of the hydrological performance of biological soil crusts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that ...the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Eosin Y, a well‐known economical alternative to metal catalysts in visible‐light‐driven single‐electron transfer‐based organic transformations, can behave as an effective direct hydrogen‐atom ...transfer catalyst for C−H activation. Using the alkylation of C−H bonds with electron‐deficient alkenes as a model study revealed an extremely broad substrate scope, enabling easy access to a variety of important synthons. This eosin Y‐based photocatalytic hydrogen‐atom transfer strategy is promising for diverse functionalization of a wide range of native C−H bonds in a green and sustainable manner.
Neutral eosin Y has been employed as an effective direct hydrogen‐atom transfer photocatalyst to activate a wide range of native C−H bonds in a green and sustainable fashion. This transformation is distinguished by its operational simplicity and amenability to large‐scale synthesis using continuous‐flow technology (EWG=aldehyde, ketone, ester, amide, imide, cyanide, sulfone, nitro, pyridine).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK