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ZIF-8 membranes have emerged as the most promising candidate for propylene/propane (C3 H6 /C3 H8 ) separation through its precise molecular sieving characteristics. The poor reproducibility and durability, and high cost, thus far hinder the scalable synthesis and industrial application of ZIF-8 membranes. Herein, we report a semi-solid process featuring ultrafast and high-yield synthesis, and outstanding scalability for reproducible fabrication of ZIF-8 membranes. The membranes show excellent C3 H6 /C3 H8 separation performance in a wide temperature and pressure range, and remarkable stability over 6â months. The ZIF-8 membrane features dimethylacetamide entrapped ZIF-8 crystals retaining the same diffusion characteristics but offering enhanced adsorptive selectivity for C3 H6 /C3 H8 . The ZIF-8 membrane was prepared on a commercial flat-sheet ceramic substrate. A prototypical plate-and-frame membrane module with an effective membrane area of about 300â cm2 was used for efficient C3 H6 /C3 H8 separation.
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UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva is likely the major vehicle for KSHV transmission, we studied in vitro KSHV infection of oral epithelial cells. Through infection of two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV can undergo robust lytic replication in oral epithelial cells. By employing de novo lytic infection of HOK16B cells, we studied the functions of two previously uncharacterized genes, ORF18 and ORF30, during the KSHV lytic cycle. For this purpose, an ORF18-deficient virus and an ORF30-deficient virus were generated using a mutagenesis strategy based on bacterial artificial chromosome (BAC) technology. We found that neither ORF18 nor ORF30 is required for immediately early or early gene expression or viral DNA replication, but each is essential for late gene expression during both de novo lytic replication and reactivation. This critical role of ORF18 and ORF30 in late gene expression was also observed during KSHV reactivation. In addition, global analysis of viral transcripts by RNA sequencing indicated that ORF18 and ORF30 control the same set of viral genes. Therefore, we suggest that these two viral ORFs are involved in the same mechanism or pathway that coregulates the viral late genes as a group. IMPORTANCE: While KSHV can infect multiple cell types in vitro, only a few can support a full lytic replication cycle with progeny virions produced. Consequently, KSHV lytic replication is mostly studied through reactivation, which requires chemicals to induce the lytic cycle or overexpression of the viral transcriptional activator, RTA. In this study, we present a robust de novo lytic infection system based on oral epithelial cells. Using this system, we demonstrate the role of two viral ORFs, ORF18 and ORF30, in regulating viral gene expression during KSHV lytic replication. As the major route of KSHV transmission is thought to be via saliva, this new KSHV lytic replication system will have important utility in the field.
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Regulação Viral da Expressão Gênica , Herpesvirus Humano 8/genética , Queratinócitos/virologia , Fases de Leitura Aberta , Proteínas Virais/genética , Sequência de Bases , Linhagem Celular , Cromossomos Artificiais Bacterianos , Herpesvirus Humano 8/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Queratinócitos/patologia , Dados de Sequência Molecular , Mucosa Bucal/patologia , Mucosa Bucal/virologia , Deleção de Sequência , Transdução de Sinais , Proteínas Virais/metabolismo , Ativação Viral , Replicação ViralRESUMO
In this study, microalgae Chlorella vulgaris (C. vulgaris) were simultaneously exposed to environmental concentrations of amino-functionalized polystyrene nanoplastics (PS-NH2; 0.05, 0.1, 0.2, 0.3 and 0.4 mg/L) and the world's second most used pesticide, the herbicide atrazine (ATZ; 10 µg/L), in the absence and presence of humic acid (HA; 1 mg/L) for 21 days. Due to the low concentrations of PS-NH2, the majority of them could not cause a significant difference in the end-points of biomass, chlorophylls a and b, total antioxidant, total protein, and superoxide dismutase and malondialdehyde compared to the control group (p > 0.05). On the other hand, by adding ATZ to the PS-NH2, all the mentioned end-point values showed a considerable difference from the control (p < 0.05). The exposure of PS-NH2+ATZ treatments to the HA could remarkably reduce their toxicity, additionally, HA was able to decrease the changes in the expression of genes related to oxidative stress (e.g., superoxide dismutase, glutathione reductase, and catalase) in the C. vulgaris in the most toxic treatment group (e.g., PS-NH2+ATZ). The synergistic toxicity of the PS-NH2+ATZ group could be due to their enhanced bioavailability for algal cells. Nevertheless, the toxicity alleviation in the PS-NH2+ATZ treatment group after the addition of HA could be due to the eco-corona formation, and changes in their zeta potential from positive to negative value, which would increase their electrostatic repulsion with the C. vulgaris cells, in such a way that HA also caused a decrease in the formation of C. vulgaris-NPs hetero-aggregates. This research underscores the complex interplay between PS-NH2, ATZ, and HA in aquatic environments and their collective impact on microalgal communities.
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Atrazina , Chlorella vulgaris , Herbicidas , Substâncias Húmicas , Microplásticos , Estresse Oxidativo , Poliestirenos , Superóxido Dismutase , Poluentes Químicos da Água , Chlorella vulgaris/efeitos dos fármacos , Atrazina/toxicidade , Poliestirenos/toxicidade , Poliestirenos/química , Superóxido Dismutase/metabolismo , Herbicidas/toxicidade , Herbicidas/química , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Clorofila/metabolismo , Malondialdeído/metabolismo , Antioxidantes/metabolismo , Biomassa , Clorofila A/metabolismoRESUMO
Concurrent infection in breast cancer patients is the direct cause of the high mortality rate of the disease. However, there is no available method to increase the survival rate until now. To address the problem, we propose one drug with two target strategy to treat the refractory disease. A small chemical, ph-ph+, was attempted to be used in the study to explore the feasibility of the approach in anticancer and antifungus at the same time. The results showed that ph-ph+ could prevent the proliferation and metastasis of breast cancer cells, and kill C. albicans simultaneously. The molecular mechanism was associated with the activation of an evolutionarily conserved protease CLpP in the cancer and C. albicans cells. Also, the signaling pathway mediated by PLAGL2 that highly expressed in cancer cells participated in preventing cell metastasis and inducing apoptosis of ph-ph+. The one drug with dual targets inhibited the growth and metastasis of the cancer cells, and meanwhile eliminated C. albicans in tissues in the experimental animals. The results suggested that ph-ph+ with dual targets of CLpP and PLAGL2 would be a feasible approach to prolong the survival rate in patients with metastatic breast cancer and pathogenic infection.
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Neoplasias da Mama , Candida albicans , Candidíase , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Animais , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Camundongos , Linhagem Celular Tumoral , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Endopeptidase Clp/metabolismo , Endopeptidase Clp/antagonistas & inibidores , Endopeptidase Clp/genética , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Camundongos Nus , Proliferação de Células/efeitos dos fármacosRESUMO
Increasing amounts of amino-functionalized polystyrene nanoplastics (PS-NH2) are entering aquatic ecosystems, raising concerns. Hence, this study investigated 96-h acute toxicity of PS-NH2 and its combination with the pesticide atrazine (ATZ) in the absence/presence of humic acid (HA) on the microalgae Chlorella vulgaris (C. vulgaris). Results showed that both PS-NH2 and PS-NH2+ATZ reduced algal growth, photosynthetic pigments, protein content, and antioxidant capacity, while increasing enzymatic activities. Gene expression related to oxidative stress was altered in C. vulgaris exposed to these treatments. Morphological and intracellular changes were also observed. The combined toxicity of PS-NH2+ATZ demonstrated a synergistic effect, but the addition of environmentally relevant concentration of HA significantly alleviated its toxicity to C. vulgaris, indicating an antagonistic effect due to the emergence of an eco-corona, and entrapment and sedimentation of PS-NH2+ATZ particles by HA. This study firstly highlights the role of HA in mitigating the toxicity of PS-NH2 when combined with other harmful compounds, enhancing our understanding of HA's presence in the environment.
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Atrazina , Chlorella vulgaris , Herbicidas , Substâncias Húmicas , Microplásticos , Poliestirenos , Poluentes Químicos da Água , Chlorella vulgaris/efeitos dos fármacos , Atrazina/toxicidade , Herbicidas/toxicidade , Poliestirenos/toxicidade , Poliestirenos/química , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Antioxidantes/metabolismo , Testes de Toxicidade Aguda , Fotossíntese/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVE: Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. METHODS: A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) and the maximum observed concentration (Cmax). RESULTS: A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0-t and Cmax of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80-125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. CONCLUSIONS: Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. CLINICAL TRIALS REGISTRATION: This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.
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Cápsulas , Estudos Cross-Over , Preparações de Ação Retardada , Voluntários Saudáveis , Equivalência Terapêutica , Cloridrato de Venlafaxina , Humanos , Cloridrato de Venlafaxina/farmacocinética , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos , Masculino , Adulto , Preparações de Ação Retardada/farmacocinética , Feminino , Adulto Jovem , Área Sob a Curva , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/efeitos adversos , Povo Asiático , China , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open-label, single-dose, 2-sequence, and 2-period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography-tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%-125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers.
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Candesartan is an antihypertensive agent that acts on an angiotensin II receptor. Candesartan cilexetil is a prodrug that is converted into the active form of candesartan during intestinal absorption. This study aimed to assess the pharmacokinetics and bioequivalence of a reference and a test formulation of candesartan cilexetil tablets in healthy Chinese volunteers. A randomized, open-label, single-dose, crossover study was conducted with two treatment periods. Forty-eight healthy Chinese volunteers participated under fasted conditions. Qualified subjects were randomly divided into two groups (1:1 ratio) to receive either the test or reference formulation first. A washout period of 14 days separated the administration of the two formulations. Blood samples were collected at specific time points and analyzed for candesartan concentration using Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). The maximum concentration (Cmax), the AUC from time zero to the last measured time point (AUC0-t) and the AUC from time zero to infinity (AUC0-∞) fell within the bioequivalence range of 80% to 125%. These results suggest that the test and reference formulations of candesartan cilexetil tablets are bioequivalent, meaning they have similar rates and extents of absorption in healthy Chinese volunteers. No serious adverse events or side effects were reported throughout the study.
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Liquid electrolyte systems of aluminum-ion batteries (AIBs) have restrictive issues, such as high moisture sensitivity, strong corrosiveness, and battery leakage, so researchers have turned their attention to developing high safety, leak-free polymer electrolytes. However, the stability of the active factor of AIB systems is difficult to maintain with most of polymeric frameworks due to the special Al complex ion balance in chloroaluminate salts. Based on this, this work clarified the feasibility and specific mechanism of using polymers containing functional groups with lone pair electrons as frameworks of solid-state electrolytes for AIBs. As for the polymers reacting unfavorably with AlCl3, they cannot be used as the frameworks directly due to the decrease or even disappearance of chloroaluminate complex ions. In contrast, a class of polymers represented by polyacrylamide (PAM) can interact with AlCl3 and provide ligands, which not only have no effect on the activity of Al species but also provide chloroaluminate complex ions through complexation reactions. According to DFT calculations, amide groups tend to coordinates with AlCl2 + via O atoms to form [AlCl2(AM)2]+ cations, while disassociating chloroaluminate anions. Furthermore, the PAM-based solid-state and quasi-solid-state gel polymer electrolytes were also prepared to investigate their electrochemical properties. This work is expected to provide new theoretical and practical directions for the further development of polymer electrolytes for AIBs.
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Sulfur-containing compounds are essential for plant development and environmental adaptation, and closely related to the flavor and nutrition of the agricultural products. Cysteine, the first organic sulfur-containing molecule generated in plants, is the precursor for most of these active substances. Serine acetyltransferase (SERAT) catalyzes the rate-limiting step of its formation. However, despite their importance, systematic analyses of these enzymes in individual species, especially in economically important crops, are still limited. Here, The SERAT members (SlSERATs, four in total) were identified and characterized in tomato. Phylogenetically, the four SlSERAT proteins were classified into three subgroups with distinct genomic structures and subcellular localizations. On the function, it was interesting to find that SlSERAT3;1, possessed a high ability to catalyze the formation of OAS, even though it contained a long C-terminus. However, it retained the essential C-terminal Ile, which seems to be a characteristic feature of SERAT3 subfamily members in Solanaceae. Besides, SlSERAT1;1 and SlSERAT2;2 also had high activity levels and their catalyzing abilities were significantly improved by the addition of an OAS-(thiol)-lyase protein. At the transcriptional level, the four SlSERAT genes had distinct expression patterns during tomato plant development. Under abiotic stress conditions, the chloroplast-localized SlSERATs were the main responders, and the SlSERATs adopted different strategies to cope with osmotic, ion toxicity and other stresses. Finally, analyses in the loss-of-function and overexpression lines of SlSERAT1;1 suggested that function redundancy existed in the tomato SERAT members, and the tomato SERAT member was ideal target for S-assimilation manipulating in molecular breeding.
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Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication.