RESUMO
BACKGROUND AND AIM: The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. METHODS: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed. RESULTS: There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. CONCLUSIONS: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.
Assuntos
Inibidores da Bomba de Prótons , Rabdomiólise , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Inibidores da Bomba de Prótons/efeitos adversos , Pantoprazol , Rabeprazol , Farmacovigilância , Teorema de Bayes , Omeprazol/efeitos adversos , Lansoprazol , Rabdomiólise/induzido quimicamente , Rabdomiólise/epidemiologiaRESUMO
Hydroxypropyl chitosan-Cs3Bi2Cl9 perovskite quantum dots (HPCS-PQDs) were synthesized by a simple ligand-assisted reprecipitation method via green hydroxypropyl chitosan as the ligand and used as the specific signal of a fluorescence probe to achieve the highly sensitive detection of hexavalent chromium (Cr(VI)) and compared with chitosan-Cs3Bi2Cl9 QDs (CS-PQDs). HPCS-PQDs with multiple active hydroxyl passivations were found to enhance the photoluminescence quantum yield (PLQY) by 90%. After being placed in aqueous solution and irradiated with ultraviolet light for 96 h the fluorescence intensity of HPCS-PQDs remained above 60%. The blue emission of HPCS-PQDs has a good selectivity and short response time (30 s) for Cr(VI). A good linear relationship is established between the fluorescence quenching rate of the HPCS-PQDs and concentration of Cr(VI) from 0.8 to 400 µM, with a limit of detection (LOD) of 0.27 µM. The fluorescence quenching mechanism is the static quenching and internal filtration effect caused by HPCS-PQDs forming a non-fluorescent ground-state complex with Cr(VI). The sensor can not only be used to detect Cr(VI) in water samples with high accuracy but can also be prepared as a test paper for the detection for Cr(VI).
RESUMO
BACKGROUND: Gout pain seriously affects the quality of patients' life. There is still no effective treatment. The inflammatory response is the main mechanism of gout. Here, we found that ozone can reduce the inflammatory reaction in the joints of gouty mice and relieve gout pain, and we further explore its protective mechanism. METHODS: MSU was used to establish the gouty mice model. Nociception was assessed by Von Frey hairs. Cell signaling assays were performed by western blotting and immunohistochemistry. The mouse leukemia cells of monocyte macrophage line RAW264.7 were cultured to investigate the effects of ozone administration on macrophage. RESULTS: Ozone reduced inflammation, relieved gout pain and improved the paw mean intensity and duty cycle of the gouty mice. Ozone increased the phosphorylation of AMP-activated protein kinase (AMPK), induced suppressor of cytokine signaling 3 (SOCS3) expression and inhibited metallopeptidase 9 (MMP9) expression. In vivo, ozone activated AMPK to induce Gas6 release, and upregulated MerTK/SOCS3 signaling pathway to reduce inflammation in mouse macrophage line RAW264.7. Inhibitors of AMPK and MerTK, respectively abolished the analgesic and anti-inflammatory effects of ozone in vivo and in vitro. Gas6 knockout cancelled the protectively effects of ozone on gout pain and the paw mean intensity and duty cycle of gouty mice. Additionally, the level of Gas6 and protein S in plasma of patients with hyperuricemia was significantly higher than that of healthy contrast group. CONCLUSION: Ozone reduces inflammation and alleviates gout pain by activating AMPK to up-regulate Gas6/MerTK/SOCS3 signaling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP , Artralgia , Gota , Ozônio , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , c-Mer Tirosina Quinase/metabolismo , Gota/terapia , Inflamação/complicações , Inflamação/terapia , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Ozônio/uso terapêutico , Artralgia/terapia , Modelos Animais de DoençasRESUMO
Electrochemical nitrite (NO2-) reduction is recognized as a promising strategy for synthesizing valuable ammonia (NH3) and degrading NO2- pollutants in wastewater. The six-electron process for the NO2- reduction reaction is complex and necessitates a highly selective and stable electrocatalyst for efficient conversion of NO2- to NH3. Herein, a FeP nanoparticle-decorated TiO2 nanoribbon array on a titanium plate (FeP@TiO2/TP) is proposed as an efficient catalyst for NH3 production under ambient conditions. In 0.1 M NaOH with 0.1 M NO2-, such a FeP@TiO2/TP affords a large NH3 yield of 346.6 µmol h-1 cm-2 and a high Faradaic efficiency of 97.1%. Additionally, it demonstrates excellent stability and durability during long-term cycling tests and electrolysis experiments.
RESUMO
BACKGROUND: To reconstruct massive bone defects of the femoral diaphysis and proximal end with limited bilateral cortical bone after joint-preserving musculoskeletal tumor resections, two novel 3D-printed customized intercalary femoral prostheses were applied. METHODS: A series of nine patients with malignancies who received these novel 3D-printed prostheses were retrospectively studied between July 2018 and November 2021. The proximal and diaphyseal femur was divided into three regions of interest (ROIs) according to anatomic landmarks, and anatomic measurements were conducted on 50 computed tomography images showing normal femurs. Based on the individual implant-involved ROIs, osteotomy level, and anatomical and biomechanical features, two alternative 3D-printed prostheses were designed. In each patient, Hounsfield Unit (HU) value thresholding and finite element analysis were conducted to identify the bone trabecula and calcar femorale and to determine the stress distribution, respectively. We described the characteristics of each prosthesis and surgical procedure and recorded the intraoperative data. All patients underwent regular postoperative follow-up, in which the clinical, functional and radiographical outcomes were evaluated. RESULTS: With the ROI division and radiographic measurements, insufficient bilateral cortical bones for anchoring the traditional stem were verified in the normal proximal femur. Therefore, two 3D-printed intercalary endoprostheses, a Type A prosthesis with a proximal curved stem and a Type B prosthesis with a proximal anchorage-slot and corresponding locking screws, were designed. Based on HU value thresholding and finite element analysis, the 3D-printed proximal stems in all prostheses maximally preserved the trabecular bone and calcar femorale and optimized the biomechanical distribution, as did the proximal screws. With the 3D-printed osteotomy guide plates and reaming guide plates, all patients underwent the operation uneventfully with a satisfactory duration (325.00 ± 62.60 min) and bleeding volume (922.22 ± 222.36 ml). In the follow-up, Harris Hip and Musculoskeletal Tumor Society scores were ameliorated after surgery (P < 0.001 and P < 0.001, respectively), reliable bone ingrowth was observed, and no major complications occurred. CONCLUSIONS: Two novel 3D-printed femoral intercalary prostheses, which achieved acceptable overall postoperative outcomes, were used as appropriate alternatives for oncologic patients with massive bone defects and limited residual bone and increased the opportunities for joint-preserving tumor resection. Several scientific methodologies utilized in this study may promote the clinical design proposals of 3D-printed implants.
Assuntos
Membros Artificiais , Neoplasias Ósseas , Neoplasias Femorais , Humanos , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/cirurgia , Estudos Retrospectivos , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Fêmur/patologia , Impressão Tridimensional , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Desenho de Prótese , Resultado do TratamentoRESUMO
In this study, R-phycoerythrin (R-PE) was isolated and characterized from Porphyra yezoensis by three-phase partitioning (TPP) method. The effects of temperature, time, pH, salt saturation, and volume ratio on the purity and recovery rate of R-PE were studied. The optimum extraction conditions were determined as follows: salt saturation of 70%, temperature of 25 °C, time of 45 min, pH of 7.0, and volume ratio of 1:1. Under the optimal extraction conditions, the purity of R-PE was 3.90. The results of SDS-PAGE showed that R-PE has three bands at 23 kDa, 22 kDa, and 18 kDa, corresponding to its α, ß, γ subunits. The structure and optical activity of R-PE did not change before and after purification based on ultraviolet, infrared, and fluorescence spectra. In addition, the purity and recovery rate of R-PE extracted by tert-butanol were evaluated. The results showed that the extraction performance of tert-butanol for R-PE remained unchanged in three recoveries. These show that TPP is an efficient, green, and recyclable extraction technology.
Assuntos
Porphyra , Rodófitas , Ficoeritrina/química , terc-Butil Álcool , Rodófitas/química , Eletroforese em Gel de PoliacrilamidaRESUMO
BACKGROUND: Cashew (Anacardium occidentale L.) is a commercially important plant. Cashew nuts are a popular food source that belong to the tree nut family. Tree nuts are one of the eight major food allergens identified by the Food and Drug Administration in the USA. Allergies to cashew nuts cause severe and systemic immune reactions. Tree nut allergies are frequently fatal and are becoming more common. AIM: We aimed to identify the key allergenic epitopes of cashew nut proteins by correlating the phage display epitope prediction results with bioinformatics analysis. DESIGN: We predicted and experimentally confirmed cashew nut allergen antigenic peptides, which we named Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily). The Ana o 2 and Ana o 3 epitopes were predicted using DNAstar and PyMoL (incorporated in the Swiss-model package). The predicted weak and strong epitopes were synthesized as peptides. The related phage library was built. The peptides were also tested using phage display technology. The expressed antigens were tested and confirmed using microtiter plates coated with pooled human sera from patients with cashew nut allergies or healthy controls. RESULTS: The Ana o 2 epitopes were represented by four linear peptides, with the epitopes corresponding to amino acids 108-111, 113-119, 181-186, and 218-224. Furthermore, the identified Ana o 3 epitopes corresponding to amino acids 10-24, 13-27, 39-49, 66-70, 101-106, 107-114, and 115-122 were also screened out and chosen as the key allergenic epitopes. DISCUSSION: The Ana o 3 epitopes accounted for more than 40% of the total amino acid sequence of the protein; thus, Ana o 3 is potentially more allergenic than Ana o 2. CONCLUSIONS: The bioinformatic epitope prediction produced subpar results in this study. Furthermore, the phage display method was extremely effective in identifying the allergenic epitopes of cashew nut proteins. The key allergenic epitopes were chosen, providing important information for the study of cashew nut allergens.
Assuntos
Anacardium , Hipersensibilidade a Noz , Proteínas de Nozes , Humanos , Alérgenos/química , Epitopos , Anacardium/química , Proteínas de Plantas/metabolismo , Proteínas de Nozes/análise , Imunoglobulina E , Nozes/químicaRESUMO
Efficient biodegradation may offer a solution for the treatment of nitro-aromatic compounds (NACs) with toxicity, mutagenicity and persistence in the environment. In this study, dopamine (DA) functionalized magnetic nanoparticles with biocompatibility and hydrophilicity were synthesized and utilized for the immobilization of nitro-aromatic compounds degrading psychrophile Psychrobacter sp. ANT206 harboring the cold-adapted nitroreductase. The prepared nanocarriers were characterized using multiple methods. The highest immobilization yield of cells immobilized by Fe3O4@SiO2@DA was 90.67% under the optimized conditions of 10 °C, pH 7.5, 2 h and cell/support 1.2 mg/mg, and the activity recovery was 89.41%. In addition, the obtained immobilized cells displayed excellent salinity stability and reusability. Moreover, immobilized P. sp. ANT206 strains showed remarkable biodegradation capability on nitrobenzene and p-nitrophenol. This study introduced those novel Fe3O4@SiO2@DA nanoparticles could be applied as ideal and low-cost nanocarriers for the immobilization of cells and large-scale bioremediation of hazardous NACs with perspective applications under low temperature.
Assuntos
Nanopartículas de Magnetita , Psychrobacter , Biodegradação Ambiental , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/química , Nitrocompostos , Dióxido de Silício/química , TemperaturaRESUMO
BACKGROUND: Testosterone is a driver of prostate cancer (PC) growth via ligand-mediated activation of the androgen receptor (AR). Tumors that have escaped systemic androgen deprivation, castration-resistant prostate cancers (CRPC), have measurable intratumoral levels of testosterone, suggesting that a resistance mechanism still depends on androgen-simulated growth. However, AR activation requires an optimal intracellular concentration of androgens, a situation challenged by low circulating testosterone concentrations. Notably, PC cells may optimize their androgen levels by regulating the expression of steroid metabolism enzymes that convert androgen precursors into androgens. Here we propose that testosterone entry into the cell could be another control point. METHODS: To determine whether testosterone enters cells via a transporter, we performed in vitro 3 H-testosterone uptake assays in androgen-dependent LNCaP and androgen and AR-independent PC3 cells. To determine if the uptake mechanism depended on a concentration gradient, we modified UGT2B17 levels in LNCaP cells and measured androgen levels by liquid-liquid extraction-mass spectrometry. We also analyzed CRPC metastases for expression of AKR1C3 to determine whether this enzyme that converts adrenal androgens to testosterone was present in the tumor stroma (microenvironment) in addition to its expression in the tumor epithelium. RESULTS: Testosterone uptake followed a concentration gradient but unlike in passive diffusion, was saturable and temperature-dependent, thus suggesting facilitated transport. Suppression of UGT2B17 to abrogate a testosterone gradient reduced testosterone transport while overexpression of the enzyme enhanced it. The facilitated transport suggests a paracrine route of testosterone uptake for maintaining optimal intracellular levels. We found that AKR1C3 was expressed in the tumor microenvironment of CRPC metastases in addition to epithelial cells and the pattern of relative abundance of the enzyme in epithelium vs stroma varied substantially between the metastatic sites. CONCLUSIONS: Our findings suggest that in addition to testosterone transport and metabolism by tumor epithelium, testosterone could also be produced by components of the tumor microenvironment. Facilitated testosterone uptake by tumor cells supports a cell nonautonomous mechanism for testosterone signaling in CRPC.
Assuntos
Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias da Próstata/metabolismo , Testosterona/metabolismo , Ligação Competitiva , Células CACO-2 , Linhagem Celular Tumoral , Difusão , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células HEK293 , Células Hep G2 , Humanos , Imuno-Histoquímica , Masculino , Células PC-3 , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Testosterona/farmacocinética , Análise Serial de Tecidos , TrítioRESUMO
Playability is an important aspect of the evaluation of bowed string instruments. The well-known "wolf note" of a cello is a particularly obvious playability issue, and it has been suggested that susceptibility to wolfiness might be deduced directly from a measurement of the Schelleng minimum bow force for the playing of a steady note. This prediction is explored by comparing physical measurements with the experience of players after making controlled mechanical changes to a cello. Experienced luthiers and musicians made subjective judgements of changes in the severity of the wolf note, under blinded conditions. The results strongly suggest a direct and intimate link between the measurable acoustical parameter and perceptual discrimination. This simple acoustical measurement can help instrument makers to identify problem notes, and to assess the effectiveness of different possible interventions.
RESUMO
The purpose of this study was to investigate the antioxidant and hypolipidemic potential of bitter gourd (BG) leaf ethanol extract (LE) in mice fed a high-fat diet (HFD). Fifty mice were randomly separated into five groups with 10 animals of each group. The animals received normal diet (NC), HFD diet (HF), 200mg/kg/day LE with HFD (LLE), 400 mg/kg/day LE with HFD (MLE), 800mg/kg/day LE with HFD (HLE), respectively. After six weeks, HF group showed meaningfully (P<0.05) increased body weight, fat index, serum lipid and oxidant stress compared to NC group. However, serum TC, TG and LDL-c concentrations were lower in all LE treated groups compared with HF group (P<0.05). In addition to LLE group, HLD-c levels in LE treated groups were higher that that in HF group (P<0.05). Moreover, LE attenuated significantly (P<0.05) the MDA content and elevated the SOD activities of the liver tissues in a dose effect relationship. The histopathological examination confirmed the hepatoprotective effect of LE against liver damage induced by HFD. These findings illustrate that bitter gourd leaves may be valuable for preventing hyperlipidemia and oxidative stress induced by HFD.
Assuntos
Antioxidantes/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Momordica charantia , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network in primary prostate cancer specimens and in metastatic tumors. Betulinic acid (BA), is a triterpenoid that has been reported to be an effective inducer of apoptosis through modification of several signaling pathways. Our objective was to investigate the pathways involved in BA-induced apoptosis in human prostate cancer cells. We employed the androgen-responsive LNCaP cells harboring wild-type p53, and androgen-refractory DU145 cells possessing mutated p53 with high constitutive NF-κB activity. Inhibition of cell survival by BA at 10 and 20 µM concentrations occurred as a result of alteration in Bax/Bcl-2 ratio in both cell lines that led to an increased cytochrome C release, caspase activation and poly(ADP)ribose polymerase (PARP) cleavage, leading to apoptosis. BA treatment resulted in stabilization of p53 through increase in phosphorylation at Ser15 in LNCaP cells, but not in DU145 cells, and induction of cyclin kinase inhibitor p21/Waf1 in both cell types. Furthermore, treatment of both prostate cancer cells with BA decreased the phosphorylation of IκB kinase (IKK)α and I-kappa-B-alpha (IκBα) inhibiting the nuclear location of NF-κB/p65 causing cytosolic accumulation and resulting in its decreased nuclear binding. We demonstrate that BA may induce apoptosis by stabilizing p53 and downregulating NF-κB pathway in human prostate cancer cells, irrespective of the androgen association, and therefore can potentially be developed as a molecule of interest in cancer chemoprevention.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Triterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Masculino , NF-kappa B/metabolismo , Triterpenos Pentacíclicos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ácido BetulínicoRESUMO
This paper presents an experimental investigation of the motion of the bridge of a cello, in the frequency range up to 2 kHz. Vibration measurements were carried out on three different cellos, and the results used to determine the position of the Instantaneous Centre of rotation of the bridge, treated as a rigid body. The assumption of rigid body rotation is shown to give a good approximation up to at least 1 kHz. The instantaneous centre moves from the sound-post side of the bridge at the lowest frequencies towards the bass-bar side at higher frequencies, remaining close to the surface of the top plate of the instrument. The trajectory as a function of frequency sheds light on the response of the cello in response to excitation by bowing the different strings. The correlation between the motion at the four string notches and directly measured transfer functions at these four notches is examined and verified for some important low-frequency body resonances.
RESUMO
The input admittance at the bridge, measured by hammer testing, is often regarded as the most useful and convenient measurement of the vibrational behavior of a bowed string instrument. However, this method has been questioned, due especially to differences between human bowing and hammer impact. The goal of the research presented here is to investigate the reliability and accuracy of this classic hammer method. Experimental studies were carried out on cellos, with three different driving conditions and three different boundary conditions. Results suggest that there is nothing fundamentally different about the hammer method, compared to other kinds of excitation. The third series of experiments offers an opportunity to explore the difference between the input admittance measuring from one bridge corner to another and that of single strings. The classic measurement is found to give a reasonable approximation to that of all four strings. Some possible differences between the hammer method and normal bowing and implications of the acoustical results are also discussed.
RESUMO
Latamoxef is a semi-synthetic, broad-spectrum oxacephem antibiotic used primarily to treat infectious diseases, but the adverse drug reactions, such as the risk of fatal bleeding, once caused physicians to use it less frequently. However, with the rise of antibiotic-resistant bacterial strains, latamoxef is being used again to treat infectious diseases, especially in pediatrics. The pharmacokinetic parameters of latamoxef are highly variable, given the changes in body composition, organ maturation, and development that occurs in pediatrics. Therefore, an appropriate dosing regimen is essential. Latamoxef dosing optimization in pediatrics should adequately account for current body weight, postnatal age, postmenstrual age, and different minimum inhibitory concentration (MIC) values. In addition, attention should also be paid to some of the adverse reactions associated with latamoxef, such as coagulation disorders and bleeding risks, disulfiram-like reactions, as well as hypersensitivity and anaphylactic shock. This review summarizes the dosing regimens and some key points of pharmaceutical care for latamoxef in pediatrics in order to provide a better reference for its application in clinical practice.
RESUMO
Background: Olfactory testing is emerging as a potentially effective screening method for identifying mild cognitive impairment in the elderly population. Objective: Olfactory impairment is comorbid with mild cognitive impairment (MCI) in older adults but is not well-documented in subdomains of either olfactory or subtypes of cognitive impairments in older adults. This meta-analysis was aimed at synthesizing the differentiated relationships with updated studies. Methods: A systematic search was conducted in seven databases from their availability to April 2023. A total of 38 publications were included, including 3,828 MCI patients and 8,160 healthy older adults. Two investigators independently performed the literature review, quality assessment, and data extraction. The meta-analyses were conducted with Stata to estimate the average effects and causes of the heterogeneity. Results: Compared to normal adults, MCI patients had severe impairments in olfactory function and severe deficits in specific domains of odor identification and discrimination. Olfactory impairment was more severe in patients with amnestic mild cognitive impairment than in patients with non-amnestic MCI. Diverse test instruments of olfactory function caused large heterogeneity in effect sizes. Conclusion: Valid olfactory tests can be complementary tools for accurate screening of MCI in older adults.
RESUMO
Carbonic anhydrase (CA) is currently under investigation because of its potential to capture CO2. A novel N-domain of ice nucleoproteins (INPN)-mediated surface display technique was developed to produce CA with low-temperature capture CO2 based on the mining and characterization of Colwellia sp. CA (CsCA) with cold-adapted enzyme structural features and catalytic properties. CsCA and INPN were effectively integrated into the outer membrane of the cell as fusion proteins. Throughout the display process, the integrity of the membrane of engineered bacteria BL21/INPN-CsCA was maintained. Notably, the study affirmed positive applicability, wherein 94 % activity persisted after 5 d at 15 °C, and 73 % of the activity was regained after 5 cycles of CO2 capture. BL21/INPN-CsCA displayed a high CO2 capture capacity of 52 mg of CaCO3/mg of whole-cell biocatalysts during CO2 mineralization at 25 °C. Therefore, the CsCA functional cell surface display technology could contribute significantly to environmentally friendly CO2 capture.
Assuntos
Dióxido de Carbono , Anidrases Carbônicas , Dióxido de Carbono/metabolismo , Anidrases Carbônicas/metabolismo , Técnicas de Visualização da Superfície Celular , Bactérias/metabolismo , CatáliseRESUMO
PURPOSE: Omadacycline is a new broad-spectrum aminomethylcycline antibiotic. However, there have been limited pharmacokinetic and pharmacodynamic (PK/PD) studies of omadacycline in patients with hepatic impairment. The aim of this study was to explore the PK/PD of omadacycline intravenous administration in healthy and hepatically impaired populations. METHODS: A physiologically based pharmacokinetic (PBPK) model of omadacycline was developed and validated based on published demographic data and the physiochemical properties of omadacycline. The PK processes in healthy adults were simulated and then extrapolated to a hepatically impaired population. Monte Carlo simulations were performed for PD evaluation by calculating the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the approved dosages. FINDINGS: In the hepatically impaired population, there was no significant difference in the maximum concentration (Cmax) compared with the healthy population, while the area under the plasma concentration-time curve from the first data point extrapolated to infinity (AUC_inf) showed a slight increase. Monte Carlo simulations indicated that the dosage of 200 mg once daily or 100 mg twice daily intravenously (loading dose) and 100 mg once daily intravenously (maintenance dose) could cover the common pathogens of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) : Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. IMPLICATIONS: Hepatic impairment exerts little impact on the PK properties of omadacycline, and no dosage adjustments are necessary for patients with mild and moderate hepatic impairment. Current dosing regimens are predicted to produce satisfactory therapeutic effects against non-drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae but may not produce the desired AUC/MIC ratios in patients with Escherichia coli or Klebsiella pneumoniae.
RESUMO
To eliminate efficiency restriction of polyethylene microplastics low-temperature biodegradation, a novel InaKN-mediated Escherichia coli surface display platform for cold-active degrading laccase PsLAC production was developed. Display efficiency of 88.0% for engineering bacteria BL21/pET-InaKN-PsLAC was verified via subcellular extraction and protease accessibility, exhibiting an activity load of 29.6 U/mg. Cell growth and membrane integrity revealed BL21/pET-InaKN-PsLAC maintained stable growth and intact membrane structure during the display process. The favorable applicability was confirmed, with 50.0% activity remaining in 4 days at 15 °C, and 39.0% activity recovery retention after 15 batches of activity substrate oxidation reactions. Moreover, BL21/pET-InaKN-PsLAC possessed high polyethylene low-temperature depolymerizing capacity. Bioremediation experiments proved that the degradation rate was 48.0% within 48 h at 15 °C, and reached 66.0% after 144 h. Collectively, cold-active PsLAC functional surface display technology and its significant contributions to polyethylene microplastics low-temperature degradation constitute an effective improvement strategy for biomanufacturing and microplastics cold remediation.
Assuntos
Lacase , Polietileno , Lacase/metabolismo , Microplásticos , Plásticos , Temperatura , Biodegradação AmbientalRESUMO
It is important to elucidate the changing distribution pattern of net primary productivity (NPP) to mechanistically understand the changes in aboveground and belowground ecosystem functions. In water-scarce desert environments, snow provides a crucial supply of water for plant development and the spread of herbaceous species. Yet uncertainty persists regarding how herbaceous plants' NPP allocation responds to variation in snow cover. The goal of this study was to investigate how variation in snow cover in a temperate desert influenced the NPP allocation dynamics of herbaceous species and their resistance to environmental change in terms aboveground and belowground productivity. In the Gurbantunggut Desert, wintertime snow cover depth was adjusted in plots by applying four treatments: snow removal (-S), ambient snow, double snow (+S), and triple snow (+2S). We examined their species richness, aboveground NPP (ANPP), belowground NPP (BNPP), and the resistance of ANPP and BNPP. We found that species diversity of the aboveground community increased significantly with increasing snow cover and decreased significantly Pielou evenness in plots. This resulted in greater ANPP with increasing snow cover; meanwhile, BNPP first increased and then decreased with increasing snow cover. However, this productivity in different soil layers responded differently to changed snow cover. In the 0-10 cm soil layer, productivity first rose and then declined, while it declined linearly in both the 10-20 cm and 20-30 cm soil layers, whereas in the 30-40 cm soil layer it showed an increasing trend. Belowground resistance would increase given that greater snow cover improved the BNPP in deeper soil and maintained the resource provisioning for plant growth, thus improving overall belowground stability. These results can serve as a promising research foundation for future work on how the functioning of desert ecosystems becomes altered due to changes in plant community expansion and, in particular, changes in snow cover driven by global climate change.