ABSTRACT
Trace elements in plants primarily derive from soils, subsequently influencing human health through the food chain. Therefore, it is essential to understand the relationship of trace elements between plants and soils. Since trace elements from soils absorbed by plants is a nonlinear process, traditional multiple linear regression (MLR) models failed to provide accurate predictions. Zinc (Zn) was chosen as the objective element in this case. Using soil geochemical data, artificial neural networks (ANN) were utilized to develop predictive models that accurately estimated Zn content within wheat grains. A total of 4036 topsoil samples and 73 paired rhizosphere soil-wheat samples were collected for the simulation study. Through Pearson correlation analysis, the total content of elements (TCEs) of Fe, Mn, Zn, and P, as well as the available content of elements (ACEs) of B, Mo, N, and Fe, were significantly correlated with the Zn bioaccumulation factor (BAF). Upon comparison, ANN models outperformed MLR models in terms of prediction accuracy. Notably, the predictive performance using ACEs as input factors was better than that using TCEs. To improve the accuracy, a two-step model was established through multiple testing. Firstly, ACEs in the soil were predicted using TCEs and properties of the rhizosphere soil as input factors. Secondly, the Zn BAF in grains was predicted using ACE as input factors. Consequently, the content of Zn in wheat grains corresponding to 4036 topsoil samples was predicted. Results showed that 85.69 % of the land was suitable for cultivating Zn-rich wheat. This finding offers a more accurate method to predict the uptake of trace elements from soils to grains, which helps to warn about abnormal levels in grains and prevent potential health risks.
Subject(s)
Neural Networks, Computer , Soil Pollutants , Soil , Triticum , Zinc , Triticum/chemistry , Zinc/analysis , Soil/chemistry , Soil Pollutants/analysis , Rhizosphere , Environmental Monitoring/methods , Trace Elements/analysis , Edible Grain/chemistryABSTRACT
Background: A bioprosthetic valve is recommended for women of childbearing age who require cardiac valve replacement in order to minimize the risk of blood clot formation. However, it should be noted that compared to mechanical valves, bioprosthetic valves have a shorter lifespan and a higher likelihood of requiring reoperation during follow-up. To assess the long-term postoperative results, including the incidence of structural valve deterioration (SVD) and other clinical outcomes, in female patients aged 50 years and younger who underwent BalMedic bovine pericardial bioprosthetic valve replacement, a multicenter retrospective study was implemented in China. Methods: Between 2004 and 2015, a cohort of 86 female patients across three medical centers underwent the implantation of 97 bioprosthetic valves. The primary outcome measure was overall survival (OS), while the secondary outcome measures were preliminary evidence of reoperation, SVD incidence, and bioprosthetic valve-related complications. Results: In this cohort study, 21 patients (24.4%, 21/86) died, while 37 patients (43.0%, 37/86) underwent a second valve replacement. The OS rates at 5 and 10 years were 97.56% and 71.93%, respectively. Additionally, the reoperation-free rates at 5 and 10 years were 92.83% and 80.68%, respectively. Similarly, the rates of freedom from SVD at 5 and 10 years were 95.65% and 51.82%, respectively, and the average duration of bioprosthetic valve replacement in our study was 9.34±3.31 years. Conclusions: Despite the recruitment of younger female patients of child-bearing age in our cohort, the OS, reoperation-free survival, and SVD-free rates of the BalMedic bovine pericardial bioprosthetic valve were not inferior to those of the other age groups in the study or those reported in the literature.
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AIM: To investigate the perspectives of clinical nurse educators regarding the challenges and essential elements of teaching competence in blended learning environments during nursing internships to inform the development of a competency-based teaching model. BACKGROUND: Competency-based teaching and blended learning play important roles in enhancing the learning experience of nursing internship trainees. Internship trainees refer to nursing students undergoing supervised practical training in clinical settings. However, clinical nurse educators frequently encounter challenges in acquiring the necessary competence for successful implementation of blended learning strategies. DESIGN: A descriptive qualitative study. METHODS: This study used semi-structured interviews with 11 certified nurse educators (CNEs) from diverse clinical disciplines in a tertiary hospital in China. Purposive sampling ensured diversity across key characteristics. Ethical approval was obtained and interviews were digitally recorded, transcribed and analyzed thematically. Theoretical saturation guided data collection, with precise measures taken to ensure confidentiality and anonymity. Thematic analysis, employing a constant comparison technique, systematically identified various themes related to blended teaching competence. This approach provided valuable insights into CNEs' perspectives and practices. The analysis involved theoretical sampling, line-by-line coding and comparative evaluation with supporting text materials. RESULTS: The in-depth analysis of teaching competence among clinical nurse educators in blended learning settings during nurse internships revealed five key themes: professionalism, teaching literacy, subject expertise, information literacy and interpersonal communication. CONCLUSION: These themes recognized clinical nurse educators' perspectives towards establishing a competency-based nursing teaching model for a blended learning environment for nurse internships. Moreover, these perspectives are also crucial in enhancing teaching literacy through effective instructional methods, engagement strategies and the promotion of critical thinking skills. Identifying these themes contributes to efforts to improve teaching effectiveness and enhance learning outcomes for internship trainees in a blended learning context.
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The micro-arc oxidation (MAO) technique was used to grow in situ oxidation coating on the surface of R60705 zirconium alloy in Na2SiO3, Na2EDTA, and NaOH electrolytes. The thickness, surface morphology, cross-section morphology, wear resistance, composition, and structure of the micro-arc oxidation coating were analyzed by an eddy current thickness measuring instrument, XPS, XRD, scanning electron microscopy, energy spectrometer, and wear testing machine. The corrosion resistance of the coating was characterized by a polarization curve and electrochemical impedance spectroscopy (EIS). The results show that, with the increase in frequency, the single-pulse discharge energy decreases continuously, and the coating thickness shows a decreasing trend, from the highest value of 152 µm at 400 Hz to the lowest value of 87.5 µm at 1000 Hz. The discharge pore size on the surface of the coating gradually decreases, and the wear resistance and corrosion resistance of the coating first increase and then decrease. The corrosion resistance is the best when the frequency is 400 Hz. At this time, the corrosion potential is -0.215 V, and the corrosion current density is 2.546 × 10-8 A·cm-2. The micro-arc oxidation coating of zirconium alloy is mainly composed of monoclinic zirconia (m-ZrO2) and tetragonal zirconia (t-ZrO2), in which the content of monoclinic zirconia is significantly more than that of tetragonal zirconia.
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Herein, the precise fabrication of Sb2S3 and low Se content Sb2SeyS3-y indoor photovoltaics is reported, and a measurement protocol for photovoltaic performance is suggested and applied. Insertion of the SnO2 buried layer decreases the thickness and parasitic absorption of the CdS layer. The introduction of minor Se into Sb2S3 and the use of spiro-OMeTAD:TMT-TTF improve the charge transport of indoor photovoltaics. Using a white light-emitting diode (LED) under illuminance of 1000, 500, and 200 lx with color temperatures of 3347 and 6103 K, indoor photovoltaics with fluorine doped tin oxide (FTO)/SnO2 (17 nm)/CdS (20 nm)/Sb2S3/spiro-OMeTAD:TMT-TTF/Au exhibit power conversion efficiency (PCE) values of 17.59, 16.66, 16.44, 16.56, 15.50, and 14.07%, respectively. Indoor photovoltaics with FTO/SnO2 (17 nm)/CdS (20 nm)/Sb2SeyS3-y(Sb/S/Se = 1:1.42:0.06)/spiro-OMeTAD:TMT-TTF/Au achieve PCE values of 18.53, 17.62, 17.07, 17.30, 16.24, and 15.38%, respectively. The PCE values of 17.59, 16.66, and 16.44% are the highest values reported for Sb2S3 indoor photovoltaics, and the other PCEs are all reported for the first time. Considering the trillion-dollar-sized market from the Internet of Things (IoT), this work can further bring an unprecedented thrust to the development of self-powered IoT devices by harvesting energy from indoor photovoltaics, thereby realizing the recycling of photon energy and reducing the use of batteries and the emission of CO2.
ABSTRACT
Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S.aureus within host cells may cause long-term colonization and clinical failure. Current treatments have poor efficacy in clearing intracellular bacteria. Antibody-antibiotic conjugates (AACs) is a novel strategy for eliminating intracellular bacteria. Herein, we use KRM-1657 as payload of AAC for the first time, and we conjugate it with anti S. aureus antibody via a dipeptide linker (Valine-Alanine) to obtain a novel AAC (ASAK-22). The ASAK-22 exhibits good in vitro pharmacokinetic properties and inhibitory activity against intracellular MRSA, with 100 µg/mL of ASAK-22 capable of eliminating intracellular MRSA to the detection limit. Furthermore, the in vivo results demonstrate that a single administration of ASAK-22 significantly reduces the bacterial burden in the bacteremia model, which is superior to the vancomycin treatment.
Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Animals , Humans , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , Immunoconjugates/chemistry , Immunoconjugates/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice, Inbred BALB C , Molecular Structure , Staphylococcal Infections/drug therapy , Structure-Activity Relationship , Rifamycins/chemistry , Rifamycins/pharmacologyABSTRACT
Microemulsions are one of the most promising directions in enhanced oil recovery, but conventional screening methods are time-consuming and labor-intensive and lack the means to analyze them at the microscopic level. In this paper, we used the Clint model to predict the changes in the synergistic effect of the mixed system of anionic surfactant sodium dodecyl benzenesulfonate and nonionic surfactant polyethoxylated fatty alcohols (C12E6), generated microemulsions using surfactant systems with different mole fractions, and used particle size to analyze the performance and stability of microemulsions, analyze the properties and stability of microemulsions using particle size, and analyze the interfacial behaviors and changes of microemulsions when different systems constitute microemulsions from the point of view of mesoscopic microemulsion self-assembly behaviors by combining with dissipative particle dynamics. It has been shown that microemulsion systems generated from anionic and nonanionic surfactants with a synergistic effect, based on the Clint model, exhibit excellent performance and stability at the microscopic level. The method proposed in this paper can dramatically improve the screening efficiency of microemulsions of anionic and nonanionic surfactants and accurately analyze the properties of microemulsions, so as to provide a theoretical basis for the subsequent research on microemulsions.
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Background: Craniocerebral injuries carry high disability and mortality rates. In clinical practice, timely determination of the condition and immediate rescue interventions are crucial for patients with emergency craniocerebral injuries. Nurses play a pivotal role in providing proactive nursing services to save patients' lives. Objective: This study aims to examine the practical implications of implementing operating room nursing pathways in the care of patients undergoing emergency craniocerebral injury surgery. Design: A randomized controlled study was conducted. Setting: The study was conducted at the Department of Operating Room at Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine. Participants: A total of 80 patients undergoing emergency craniocerebral injury surgery in our hospital from August 2020 to August 2022 were included. They were randomly divided into control and observation groups through a lottery, with 40 cases in each. Interventions: The control group received conventional nursing, while the observation group received operating room nursing pathways. Primary Outcome Measures: (1) Surgical preparation time, surgical time, and hospitalization time; (2) Pupil scores; (3) Brain injury grading; and (4) Nursing satisfaction score. Results: The observation group exhibited a significant decrease in surgical preparation time and hospitalization time compared to the control group (P < .05). After the intervention, severe craniocerebral injury pupil scores in the observation group showed improvement compared to the control group (P < .05). The total satisfaction rate in the observation group (92.5%) was higher than that in the control group (80.0%) (P = .012). Conclusions: The application of operating room nursing pathways in patients undergoing emergency craniocerebral injury surgery can lead to a shortened length of stay, substantial improvement in patients' consciousness status, and high satisfaction rates from both patients and their family members. This intervention holds significant clinical value and merits further promotion.
ABSTRACT
RN-9893, a TRPV4 antagonist identified by Renovis Inc., showcased notable inhibition of TRPV4 channels. This research involved synthesizing and evaluating three series of RN-9893 analogues for their TRPV4 inhibitory efficacy. Notably, compounds 1b and 1f displayed a 2.9 to 4.5-fold increase in inhibitory potency against TRPV4 (IC50 = 0.71 ± 0.21 µM and 0.46 ± 0.08 µM, respectively) in vitro, in comparison to RN-9893 (IC50 = 2.07 ± 0.90 µM). Both compounds also significantly outperformed RN-9893 in TRPV4 current inhibition rates (87.6 % and 83.2 % at 10 µM, against RN-9893's 49.4 %). For the first time, these RN-9893 analogues were profiled in an in vivo mouse model, where intraperitoneal injections of 1b or 1f at 10 mg/kg notably mitigated symptoms of acute lung injury induced by lipopolysaccharide (LPS). These outcomes indicate that compounds 1b and 1f are promising candidates for acute lung injury treatment.
Subject(s)
Acute Lung Injury , Benzenesulfonamides , Sulfonamides , TRPV Cation Channels , Structure-Activity Relationship , TRPV Cation Channels/antagonists & inhibitors , TRPV Cation Channels/metabolism , Acute Lung Injury/drug therapy , Sulfonamides/chemistry , Sulfonamides/pharmacology , Sulfonamides/chemical synthesis , Animals , Mice , Humans , Molecular Structure , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice, Inbred C57BLABSTRACT
PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.
Subject(s)
Cholesterol , Dementia, Vascular , Hypercholesterolemia , Humans , Dementia, Vascular/etiology , Dementia, Vascular/epidemiology , Dementia, Vascular/metabolism , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Risk Factors , Cholesterol/metabolism , Cholesterol/bloodABSTRACT
The development of acute lung injury (ALI), a common respiratory condition with multiple causes, is significantly influenced by the pro-inflammatory environment of signal transducer and activator of transcription 3 (STAT3) in macrophages. Our study aimed to evaluate the anti-inflammatory effects of B9 (N-(4-hydroxyphenyl)-9, 10-dioxo-9, 10-dihydroanthracene-2-sulfonamide), a novel inhibitor targeting the STAT3 SH2 domain, in macrophages and to assess its therapeutic potential for ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI. We found that B9 (30 mg/kg) significantly reduced lung pathological damage and neutrophil infiltration caused by the intratracheal administration of LPS. Additionally, the high expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in alveolar lavage fluid was also inhibited by B9 treatment. The decreased expression of CD86 and increased CD206 in lung tissue demonstrated the anti-inflammatory effect of B9, which was due to its inhibition of the STAT3 signaling pathway in macrophages of ALI mice. Furthermore, B9 suppressed the activation of RAW264.7 cells induced by LPS, characterized by its ability to inhibit the activation of iNOS and STAT3 in a dose-dependent manner, as well as reduce the secretion of IL-6 and IL-1ß. The in vivo preliminary safety evaluation indicated that B9 had a favorable safety profile at the administered doses. These results suggest that B9 exerts a therapeutic effect on LPS-induced ALI, potentially by preventing the phosphorylation of STAT3 Y705 and S727 without affecting the STAT3 protein level. Taken together, these findings provide a foundation for developing B9 as a novel anti-inflammatory agent for ameliorating LPS-induced ALI.
Subject(s)
Acute Lung Injury , Anti-Inflammatory Agents , Cytokines , Lipopolysaccharides , Macrophages , STAT3 Transcription Factor , Animals , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/immunology , Acute Lung Injury/pathology , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/antagonists & inhibitors , Mice , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , RAW 264.7 Cells , Male , Macrophages/drug effects , Macrophages/immunology , Cytokines/metabolism , Lung/pathology , Lung/drug effects , Lung/immunology , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Mice, Inbred C57BL , Signal Transduction/drug effects , Disease Models, AnimalABSTRACT
Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting the E2/E6/E7 of both HPV16 and HPV18. mHTV-03E2 dramatically induced antigen-specific cellular immune responses, leading to significant CD8+ T cell infiltration and cytotoxicity in TC-1 tumors derived from primary lung epithelial cells of C57BL/6 mice expressing HPV E6/E7 antigens, mediated significant tumor regression, and prolonged animal survival, in a dose-dependent manner. We further demonstrated significant T cell immunity against HPV16/18 E6/E7 antigens for up to 4 months post-vaccination in immunological and distant tumor rechallenging experiments, suggesting robust memory T cell immunity against relapse. Finally, mHTV-03E2 synergized with immune checkpoint blockade to inhibit tumor growth and extend animal survival, indicating the potential in combination therapy. We conclude that mHTV-03E2 is an excellent candidate therapeutic mRNA vaccine for treating malignancies caused by HPV16 or HPV18 infections.
Subject(s)
Oncogene Proteins, Viral , Papillomavirus Infections , Papillomavirus Vaccines , RNA, Messenger , Animals , Mice , Papillomavirus Vaccines/immunology , Humans , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Papillomavirus Infections/therapy , Papillomavirus Infections/prevention & control , Female , Oncogene Proteins, Viral/immunology , Oncogene Proteins, Viral/genetics , RNA, Messenger/genetics , RNA, Messenger/immunology , Nanoparticles/chemistry , Human papillomavirus 16/immunology , Human papillomavirus 16/genetics , Mice, Inbred C57BL , Human papillomavirus 18/immunology , Human papillomavirus 18/genetics , Papillomavirus E7 Proteins/immunology , Papillomavirus E7 Proteins/genetics , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Cell Line, Tumor , Disease Models, Animal , CD8-Positive T-Lymphocytes/immunology , Repressor Proteins/immunology , Repressor Proteins/genetics , DNA-Binding Proteins , LiposomesABSTRACT
Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored. Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators. Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro. Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.
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Anaerobic granular sludge (AGS) has been regarded as the core of lots of advanced anaerobic reactors. Formation of biogenic Fe products and their incorporation into AGS could influence interspecies electron transfer and methanogenesis performance. In this study, with anaerobic granular sludge (AGS) from different sources (brewery, chemical plant, paper mill, citric acid factory, and food factory) as the research targets, the formation of biogenic iron products in AGS through the biologically induced mineralization process was studied. Furthermore, the influences of physicochemical properties and microbial community on methanogenesis were investigated. Results showed that all the AGS of different sources possessed the capacity to form biogenic Fe products through dissimilatory iron-reduction process, and diverse Fe minerals including magnetite (Fe3O4), hematite (Fe2O3), goethite (FeOOH), siderite (FeCO3) and wustite (FeO) were incorporated into AGS. The AGS loaded with Fe minerals (Fe-AGS) showed increased conductivity, magnetism and zeta-potential comparing to the control. Those Fe-AGS of different sources demonstrated different methanogenesis performance during the long-term operation (50 days). Methane production was increased for the Fe-AGS of citric acid (6.99-32.50%), food (8.33-37.46%), chemical (2.81-7.22%) and brewery plants (2.27-2.81%), but decreased for the Fe-AGS of paper mill (54.81-72.2%). The changes of microbial community and microbial correlations in AGS as a response to Fe minerals incorporation were investigated. For the Fe-AGS samples with enhanced methane production capability, it was widely to find the enriched populations of fermentative and dissimilatory iron reducing bacteria Clostridium_sensu_stricto_6, Bacteroidetes_vadinHA17 and acetoclastic methanogens Methanosaeta, and positive correlations between them. This study provides comprehensive understanding on the effects of incorporation biogenic Fe products on AGS from different sources.
Subject(s)
Microbiota , Sewage , Sewage/chemistry , Anaerobiosis , Iron/chemistry , Ferrosoferric Oxide , Methane , Citric Acid , BioreactorsABSTRACT
The solution-phase ligand-exchange strategy offers a simple pathway to prepare PbS quantum dots (QDs) and their corresponding solar cells. However, the production of high-quality PbS QDs with reduced surface trap state density for efficient PbS QD solar cells (QDSCs) still faces challenges. As the hydroxyl group (-OH) has been demonstrated to be the primary source of the surface trap states on PbS QDs in the general oleic acid method, here, we present an effective and facile strategy for reducing the surface -OH content of PbS QDs by using acetonitrile (ACN) as precipitant to wash the surface of QDs, which significantly decreases the trap state density and enables the preparation of superior PbS QDs. The resulting solar cell with an ITO/SnO2/n-PbS/p-PbS/Au structure obtained an improved photoelectric conversion efficiency (PCE) from 8.53 to 10.49% with an enhanced air storage stability, realizing a high PCE for SnO2-based PbS QDSCs.
ABSTRACT
The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 µM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B virus , Animals , Mice , Antiviral Agents/pharmacology , ZidovudineABSTRACT
Supplementation of conductive materials has been proved to be a promising approach for enhancing microbial interspecies electron transfer (IET) in anaerobic digestion systems. In this study, magnetic bamboo-based biochar was prepared at temperatures of 400-800 °C via a ball milling/carbonization method, and it immobilized in mature anaerobic granular sludge (AGS) aimed to enhance methane production by improving the IET process between syntrophic microbial communities in the AGS. Results showed that the AGS with magnetic biochar immobilization demonstrated increased glucotrophic and acetotrophic methane production by 69.54-77.56 % and 39.96-54.92 %, respectively. Magnetic biochar prepared at 800 °C with a relatively higher Fe content (0.37 g/g magnetic biochar) displayed a stronger electron charge/discharge capacity (36.66 F/g), and its immobilization into AGS promoted methane production most. The conductivity of AGS increased by 52.13-87.32 % after incorporating magnetic biochar. Furthermore, the extracellular polymeric substance (EPS) of AGS showed an increased capacitance and decreased electron transfer resistance possibly due to the binding of magnetic biochar and more riboflavin secretion in EPS, which could contribute to the accelerated IET process in the inner AGS. In addition, the immobilization of magnetic biochar could promote the production of volatile fatty acids by 15.36-22.50 %. All these improvements may jointly lead to the enhanced methane production capacity of AGS. This study provided a fundamental understanding of the role of incorporated magnetic biochar in AGS in promoting anaerobic digestion performance.
Subject(s)
Electrons , Sewage , Anaerobiosis , Extracellular Polymeric Substance Matrix/metabolism , Bioreactors , Methane/metabolism , Charcoal/metabolismABSTRACT
Grape (Vitis L.), a highly valued fruit crop, poses significant challenges in genetic transformation and functional characterization of genes. Therefore, there is an urgent need for the development of a rapid and effective method for grape transformation and gene function identification. Here, we introduce a streamlined Agrobacterium-mediated transient transformation system for grape calli. Optimal conditions were established with a leaf-derived callus induction medium; chiefly B5 medium supplemented with 0.05 mg/L NAA, 0.5 mg/L 2,4-D, and 2.0 mg/L KT; and a callus proliferation medium (B5 medium supplemented with 0.5 mg/L NAA and 2.0 mg/L 6-BA), respectively. Notably, GUS enzyme activity peaked (352.96 ± 33.95 mol 4-MU/mg/min) by sonication with Agrobacterium tumefaciens EHA105 and 100 µM AS for 4 min, followed by vacuum infection for 5 min, and co-culture at 25 °C in the dark for 1 day using callus as explants at an optical density (OD600) of 0.8. VaCIPK18 gene was transiently transformed into calli, and transcripts of the gene (endogenous and exogenous) were detected at higher levels than in non-transformed calli (endogenous). Moreover, after 10 days of treatment at 4 °C or -4 °C, the callus net weight of transformed callus was significantly higher than that of the untransformed callus, indicating that the VaCIPK18-overexpressing grape callus could improve cold tolerance. Overall, we establish a simple but effective transient transformation approach for grape callus, which could serve as a useful tool for the rapid assessment of gene function in this important crop.
Subject(s)
Vitis , Vitis/genetics , Plants, Genetically Modified/genetics , Transformation, Genetic , Agrobacterium tumefaciens/geneticsABSTRACT
In globally cultivated grapevines, low-temperature stress poses a persistent challenge. Although COLD1 is recognized as a cold receptor in rice, its function in grapevine cold signaling is unclear. Here, we identified VaCOLD1, a transmembrane protein from the cold-tolerant Vitis amurensis Rupr, which is primarily located on plasma and endoplasmic reticulum membranes. Broadly expressed across multiple tissues, VaCOLD1 responds to various environmental stresses, particularly to cold. Its promoter contains distinct hormone- and stress-responsive elements, with GUS assays confirming widespread expression in Arabidopsis thaliana. Validation of interaction between VaCOLD1 and VaGPA1, together with their combined expression in yeast and grape calli, notably improved cold endurance. Overexpression of VaCOLD1 enhances cold tolerance in Arabidopsis by strengthening the CBF-COR signaling pathway. This is achieved through shielding against osmotic disturbances and modifying the expression of ABA-mediated genes. These findings emphasize the critical role of the VaCOLD1-VaGPA1 complex in mediating the response to cold stress via the CBF-COR pathway.