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Water quality criteria (WQC) serve as a scientific foundation for pollutant risk assessment and control in aquatic ecosystems. The development of regionally differentiated WQC tailored to specific regional characteristics has become an emerging trend. However, the current WQC is constrained by a lack of regional species toxicity data. To address these limitations, this study proposes the biological toxicity effect ratio (BER) method, which indirectly reflects the toxicity sensitivity of the overall aquatic ecosystem through the toxicity information on a limited number of species, enabling rapid WQC prediction. Using the established WQC in China and the USA as a case study, we combined mathematical derivation and data validation to evaluate the BER method. Among various species-taxon groups of freshwater organisms, planktonic crustaceans demonstrated the highest predictive accuracy. Our analysis further revealed that species toxicity sensitivity and regional variability jointly influence the prediction accuracy. Regardless of the evaluation indexes, planktonic crustaceans emerged as the most suitable species-taxon group for the BER method. Additionally, the BER method is particularly applicable to pollutants with conserved mechanisms across species. This study systematically explores the feasibility of using the BER method and offers new insights for deriving regionally differentiated WQC.
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Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50 values of 10.53 µM and 7.47 µM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.
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Antidepressivos , Autofagia , Neoplasias Colorretais , Sinergismo Farmacológico , Paclitaxel , Sertralina , Sertralina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Autofagia/efeitos dos fármacos , Paclitaxel/farmacologia , Humanos , Linhagem Celular Tumoral , Antidepressivos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , AnimaisRESUMO
This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.
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Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.
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Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.
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Apoptose , Proliferação de Células , Conotoxinas , NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Transdução de Sinais , Serina-Treonina Quinases TOR , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , NF-kappa B/metabolismo , Feminino , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Proliferação de Células/efeitos dos fármacos , Conotoxinas/farmacologia , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Humanos , Antineoplásicos/farmacologiaRESUMO
Animal-derived venom, like snake venom, has been proven to be valuable natural resources for the drug development. Previously, snake venom was mainly investigated in its pharmacological activities in regulating coagulation, vasodilation, and cardiovascular function, and several marketed cardiovascular drugs were successfully developed from snake venom. In recent years, snake venom fractions have been demonstrated with anticancer properties of inducing apoptotic and autophagic cell death, restraining proliferation, suppressing angiogenesis, inhibiting cell adhesion and migration, improving immunity, and so on. A number of active anticancer enzymes and peptides have been identified from snake venom toxins, such as L-amino acid oxidases (LAAOs), phospholipase A2 (PLA2), metalloproteinases (MPs), three-finger toxins (3FTxs), serine proteinases (SPs), disintegrins, C-type lectin-like proteins (CTLPs), cell-penetrating peptides, cysteine-rich secretory proteins (CRISPs). In this review, we focus on summarizing these snake venom-derived anticancer components on their anticancer activities and underlying mechanisms. We will also discuss their potential to be developed as anticancer drugs in the future.
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Antineoplásicos , Venenos de Serpentes , Humanos , Venenos de Serpentes/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Animais , Neoplasias/tratamento farmacológico , L-Aminoácido Oxidase/química , L-Aminoácido Oxidase/farmacologia , Apoptose/efeitos dos fármacos , Fosfolipases A2/metabolismo , Fosfolipases A2/química , Toxinas Biológicas/química , Toxinas Biológicas/farmacologiaRESUMO
The spread of multidrug-resistant organisms (MDROs) has resulted in a corresponding increase in the incidence of urinary tract infections (UTIs). The risk factors and hospitalization burden for community-acquired MDRO-associated UTIs are discussed herein. This retrospective study included 278 patients with community-based MDRO-associated UTIs from January 2020 to January 2022. The MDRO (nâ =â 139) and non-MDRO groups (nâ =â 139) were separated based on drug susceptibility results. Community-based MDRO-associated UTIs mainly occurred in the elderly and frail patients with a history of invasive urinary tract procedures. The MDRO group imposed a greater economic burden compared to the non-MDRO group. Independent risk factors for community-based MDRO-associated UTIs were as follows: white blood cell (WBC) countâ >â 10.0â ×â 109/L (ORâ =â 2.316, 95% CIâ =â 1.316-3.252; Pâ =â .018); ≥3 kinds of urinary tract obstructive diseases (ORâ =â 1.720, 95% CIâ =â 1.004-2.947; Pâ =â .048); use of 3rd generation cephalosporins (ORâ =â 2.316, 95% CIâ =â 1.316-4.076; Pâ =â .004); and a history of invasive urologic procedures (ORâ =â 2.652, 95% CIâ =â 1.567-4.487; Pâ <â .001). Days of hospitalization, antibiotic use, and bladder catheter use were significantly greater in the MDRO group than the non-MDRO group (Pâ <â .05).
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Infecções Comunitárias Adquiridas , Farmacorresistência Bacteriana Múltipla , Infecções Urinárias , Humanos , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/economia , Estudos Retrospectivos , Masculino , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/economia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Fatores de Risco , Idoso , Pessoa de Meia-Idade , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , AdultoRESUMO
Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.
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OBJECTIVE: This study explored the pharmacological mechanism of Tanshinone IIA (TAN IIA) in the treatment of Osteoarthritis (OA), which provided a certain reference for further research and clinical application of Tan IIA in OA. METHODS: CHON-001 cells were stimulated with 10 µg/mL IL-1ß for 48 h and treated with 10 µM TAN IIA for 48 h. Cellular viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, and Cleaved caspase-3 was measured by Immunoblot assay and RT-qPCR. TNF-α, IL-6, and iNOS in CHON-001 cells were determined by RT-qPCR and ELISA. To further verify the effect of TAN IIA on OA, a rat model of OA in vivo was established by right anterior cruciate ligament transection. TAN IIA was administered at 50 mg/kg or 150 mg/kg for 7 weeks. The degree of cartilage destruction in OA rats was observed by TUNEL and HE staining. Cleaved caspase-3 and FBXO11 were measured by immunohistochemical staining, RT-qPCR, and Immunoblot. TNF-α, IL-6, and iNOS in chondrocytes of OA rats were detected by ELISA. RESULTS: IL-1ß stimulated CHON-001 cell apoptosis and inflammation, and TAN IIA had anti-apoptosis and anti-inflammatory effects on IL-1ß-regulated CHON-001 cells. TAN IIA down-regulated FBXO11 and inhibited PI3K/AKT and NF-κB pathways, thereby alleviating apoptotic and inflammatory reactions in CHON-001 cells under IL-1ß treatment. Moreover, TAN IIA treatment improved chondrocyte apoptosis and inflammations in OA rats. CONCLUSION: TAN IIA inhibits PI3K/Akt and NF-κB pathways by down-regulating FBXO11 expression, alleviates chondrocyte apoptosis and inflammation, and delays the progression of OA.
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Abietanos , Apoptose , Condrócitos , Interleucina-1beta , Osteoartrite , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Animais , Abietanos/farmacologia , Apoptose/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/metabolismo , Masculino , Proteínas F-Box/metabolismo , Ratos Sprague-Dawley , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Caspase 3/metabolismoRESUMO
Neurovascular unit mural cells called 'pericytes' maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer's disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25-40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 ± 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection.
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Doença de Alzheimer , Isquemia Encefálica , Demência Vascular , Acidente Vascular Cerebral , Humanos , Camundongos , Animais , Doença de Alzheimer/patologia , Demência Vascular/patologia , Pericitos/patologia , Hipocampo/patologia , Encéfalo/patologia , Acidente Vascular Cerebral/patologia , Isquemia Encefálica/patologiaRESUMO
The scientific advancement of water quality criteria (WQC) stands as one of the paramount challenges in ensuring the security of aquatic ecosystem. The region-dependent species distribution and water quality characteristics would impact the toxicity of pollutant, which would further affect the derivation of WQC across regions. Presently, however, numerous countries adhere to singular WQC values. The "One-size-fits-all" WQC value for a given pollutant may lead to either "over-protection" or "under-protection" of organisms in specific region. In this study, we used cadmium(Cd) pollution in surface waters of China as a case study to shed light on this issue. This study evaluated critical water quality parameters and species distribution characteristics to modify WQC for Cd across distinct regions, thus unveiling the geographical variations in ecological risk for Cd throughout China. Notably, regional disparities in ecological risk emerged a substantial correlation with water hardness, while species-related distinctions magnified these regional variations. After considering the aforementioned factors, the variation in long-term WQC among different areas reached 84-fold, while the divergence in risk quotient extended to 280-fold. This study delineated zones of both heightened and diminished ecological susceptibility of Cd, thereby establishing a foundation for regionally differentiated management strategies.
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Poluentes Ambientais , Poluentes Químicos da Água , Cádmio/análise , Ecossistema , Organismos Aquáticos , Poluentes Químicos da Água/análise , Qualidade da Água , China , Medição de RiscoRESUMO
Abstract Objective This study explored the pharmacological mechanism of Tanshinone IIA (TAN IIA) in the treatment of Osteoarthritis (OA), which provided a certain reference for further research and clinical application of Tan IIA in OA. Methods CHON-001 cells were stimulated with 10 μg/mL IL-1β for 48 h and treated with 10 μM TAN IIA for 48 h. Cellular viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, and Cleaved caspase-3 was measured by Immunoblot assay and RT-qPCR. TNF-α, IL-6, and iNOS in CHON-001 cells were determined by RT-qPCR and ELISA. To further verify the effect of TAN IIA on OA, a rat model of OA in vivo was established by right anterior cruciate ligament transection. TAN IIA was administered at 50 mg/kg or 150 mg/kg for 7 weeks. The degree of cartilage destruction in OA rats was observed by TUNEL and HE staining. Cleaved caspase-3 and FBXO11 were measured by immunohistochemical staining, RT-qPCR, and Immunoblot. TNF-α, IL-6, and iNOS in chondrocytes of OA rats were detected by ELISA. Results IL-1β stimulated CHON-001 cell apoptosis and inflammation, and TAN IIA had anti-apoptosis and anti-inflammatory effects on IL-1β-regulated CHON-001 cells. TAN IIA down-regulated FBXO11 and inhibited PI3K/AKT and NF-κB pathways, thereby alleviating apoptotic and inflammatory reactions in CHON-001 cells under IL-1β treatment. Moreover, TAN IIA treatment improved chondrocyte apoptosis and inflammations in OA rats. Conclusion TAN IIA inhibits PI3K/Akt and NF-κB pathways by down-regulating FBXO11 expression, alleviates chondrocyte apoptosis and inflammation, and delays the progression of OA.
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Cancer is a major global public health problem with high morbidity. Depression is known to be a high-frequency complication of cancer diseases that decreases patients' life quality and increases the mortality rate. Therefore, antidepressants are often used as a complementary treatment during cancer therapy. During recent decades, various studies have shown that the combination of antidepressants and anticancer drugs increases treatment efficiency. In recent years, further emerging evidence has suggested that the modulation of autophagy serves as one of the primary anticancer mechanisms for antidepressants to suppress tumor growth. In this review, we introduce the anticancer potential of antidepressants, including tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In particular, we focus on their autophagy-modulating mechanisms for regulating autophagosome formation and lysosomal degradation. We also discuss the prospect of repurposing antidepressants as anticancer agents. It is promising to repurpose antidepressants for cancer therapy in the future.
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Antidepressivos , Neoplasias , Humanos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina , Antidepressivos Tricíclicos , Norepinefrina , Autofagia , Neoplasias/tratamento farmacológicoRESUMO
Articular cartilage degeneration caused by chondrocyte damage is the primary pathological mechanism of osteoarthritis (OA). Oxidative stress is correlated with chondrocyte injury by potentiating ferroptosis, a newly identified form of cell death. Given the effects of Tanshinone IIA (Tan IIA) on alleviating oxidative stress, we further explored whether Tan IIA inhibited chondrocyte death and cartilage degeneration by decreasing ferroptosis. ATDC5 chondrocytes were treated with lipopolysaccharides (LPS) and Tan IIA, and cell viability was assessed using cell counting kit-8 (CCK-8) assays. Matrix metalloproteinase-13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS5), and type II collagen (Col II) levels were measured using quantitative real-time polymerase chain reaction (qRTâPCR), western blotting, and immunofluorescence (IF) analysis. We demonstrated that Tan IIA treatment prominently increased ATDC5 cell viability and decreased cell apoptosis in the presence of LPS-induced stress. MMP13 and ADAMTS5 expression was increased, and Col II expression was decreased in ATDC5 cells after LPS stimulation, whereas these changes were reversed by Tan IIA. Mechanistically, Tan IIA inhibited LPS-induced ferroptosis in ATDC5 cells, as indicated by decreased levels of iron, reactive oxygen species, and malondialdehyde and increased GSH levels. Importantly, a ferroptosis agonist partially abrogated the effect of Tan IIA on alleviating chondrocyte damage and death. Taken together, these results suggest that Tan IIA ameliorates chondrocyte apoptosis and cartilage degeneration by inhibiting ferroptosis and may be a potential therapeutic agent for OA.
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Cancer is a serious disease with high mortality and morbidity worldwide. Natural products have served as a major source for developing new anticancer drugs during recent decades. Magnolol, a representative natural phenolic lignan isolated from Magnolia officinali, has attracted considerable attention for its anticancer properties in recent years. Accumulating preclinical studies have demonstrated the tremendous therapeutic potential of magnolol via a wide range of pharmacological mechanisms against cancer. In this review, we summarized the latest advances in preclinical studies investigating anticancer properties of magnolol and described the important signaling pathways explaining its underlying mechanisms. Magnolol was capable of inhibiting cancer growth and metastasis against various cancer types. Magnolol exerted anticancer effects through inhibiting proliferation, inducing cell cycle arrest, provoking apoptosis, restraining migration and invasion, and suppressing angiogenesis. Multiple signaling pathways were also involved in the pharmacological actions of magnolol against cancer, such as PI3K/Akt/mTOR signaling, MAPK signaling and NF-κB signaling. Based on this existing evidence summarized in the review, we have conclusively confirmed magnolol had a multi-target anticancer effect against heterogeneous cancer disease. It is promising to develop magnolol as a drug candidate for cancer therapy in the future.
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Antineoplásicos , Produtos Biológicos , Lignanas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Produtos Biológicos/farmacologia , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Owing to many problems of the detriment by large amount of organic reagents, high cost and difficulty of industrialization, development of high-efficiency economical technologies for uranium extraction is an irresistible trend to support steady supply of nuclear energy. Herein, a novel fibrous adsorbent, named as AO-HPE fibers, was prepared by introduction of amidoxime groups using the green vapor-phase grafting polymerization (VPGP) technology of monomer acrylonitrile (AN). Gaseous AN was grafted onto the ultra high molecular weight polyethylene (UHMWPE) fibers at 80 °C in the enclosed evaporation and condensation reflux system. The innovative technology not only endowed synthetic process high monomer utilization ratio but also excellent environmental friendliness. The AO-HPE fibers exhibited an appreciable calculated maximum adsorption capacity (Q m) of 1144.94 mg·g-1 in uranium solution and an adsorption capacity of 14.11 mg·g-1 in simulated seawater. Meanwhile, the higher uranium selectivity than main competing ion vanadium (adsorption mass ratio was almost 5) was achieved. The adsorption process accorded closely with chemisorption mechanism. This work provided a novel idea for the synthetic method of adsorbents for uranium extraction, and inspired the sustainable technologies for grafting polymerization of monomer AN.
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Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.
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Cerebral pericytes are an integral component of the neurovascular unit, which governs the blood-brain barrier. There is paucity of knowledge on cortical pericytes across different dementias. We quantified cortical pericytes in capillaries in 124 post-mortem brains from subjects with post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer's disease (AD) and AD-VaD (Mixed) and, post-stroke non-demented (PSND) stroke survivors as well as normal ageing controls. Collagen 4 (COL4)-positive nucleated pericyte soma were identified as protrusions on capillaries of the frontal cortex. The COL4-positive somata or nodule-like cell bodies were also verified by platelet derived growth factor receptor-ß (PDGFR-ß) immunohistochemistry. The mean (± SEM) pericyte somata in frontal cortical capillaries in normal young controls (46-65 years of age) was estimated as 5.2 ± 0.2 per mm capillary length. This number was reduced by 45% in older controls (> 78 years) to 2.9 ± 0.1 per mm capillary length (P < 0.001). We further found that the numbers of pericyte cell bodies per COL4 mm2 area or per mm capillary length were not decreased but rather preserved or increased in PSD, AD and Mixed dementia groups compared to similar age older controls (P < 0.01). Consistent with this, we noted that capillary length densities identified by the endothelial marker glucose transporter 1 or COL4 were not different across the dementias compared to older controls. There was a negative correlation with age (P < 0.001) suggesting fewer pericyte somata in older age, although the % COL4 immunoreactive capillary area was increased in older controls compared to young controls. Using a proven reliable method to quantify COL4-positive nucleated pericytes, our observations demonstrate ageing related loss but mostly preserved pericytes in the frontal cortex of vascular and AD dementias. We suggest there is differential regulation of capillary pericytes in the frontal lobe between the cortex and white matter in ageing-related dementias.
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Doença de Alzheimer/patologia , Capilares/patologia , Demência Vascular/patologia , Demência/patologia , Lobo Frontal/irrigação sanguínea , Pericitos/patologia , Idoso , Idoso de 80 Anos ou mais , Capilares/citologia , Estudos de Casos e Controles , Contagem de Células , Colágeno Tipo IV/metabolismo , Demência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericitos/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Acidente Vascular Cerebral/complicaçõesRESUMO
Phosphorus (P) extraction from human urine is a potential strategy to address global resource shortage, but few approaches are able to obtain high-quality liquid P products. In this study, we introduced an innovative flow-electrode capacitive deionization (FCDI) system, also called ion-capture electrochemical system (ICES), for selectively extracting P and N (i.e., urea) from fresh human urine simply by integrating a liquid membrane chamber (LMC) using a pair of anion exchange membrane (AEM). In the charging process, negatively charged P ions (i.e., HPO42- and H2PO4-) can be captured by acidic extraction solutions (e.g., solutions of HCl, HNO3 and H2SO4) on their way to the anode chamber, leading to the conversion of P ions to uncharged H3PO4, while other undesired ions such as Cl- and SO42- are expelled. Simultaneously, uncharged urea molecules remain in the urine effluent with the removal of salt. Thus, high-purity phosphoric acid and urea solutions can be obtained in the LMC and spacer chambers, respectively. The purification of P in an acidic environment is ascribed largely to the competitive migration and protonation of ions. The latter contributes ~27% for the selective capture of P. Under the optimal operating conditions (i.e., ratio of the urine volume to the HCl volume = 7:3, initial pH of the extraction solution = 1.43, current density = 20 A/m2 and threshold pH ~ 2.0), satisfactory recovery performance (811 mg/L P with 73.85% purity and 8.3 g/L urea-N with 81.4% extraction efficiency) and desalination efficiency (91.1%) were obtained after 37.5 h of continuous operation. Our results reveal a promising strategy for improving in selective separation and continuous operation via adjustments to the cell configuration, initiating a new research dimension toward selective ion separation and high-quality P recovery.