Massive proteinuria, oedema, hypoalbuminemia, and hyperlipidemia are the hallmarks of nephrotic syndrome (NS). Recently, epigenetic pathways in renal diseases have been identified. The present work hypothesizes using the combination of two epigenetic drugs all-trans retinoic acid (ATRA) and valproic acid (VPA) as a prospective treatment method to lessen NS-related glomerulosclerosis, fibrosis, and increased renal function parameters along with attenuating inflammation and improving overall mitochondrial health. To induce NS, doxorubicin (8.5 mg/kg, n = 6) was injected intravenously into female Sprague Dawley rats. After 28 days, ATRA and VPA were orally administered to the rats, alone and in combination at a dose of 5 mg/kg (n = 6) and 200 mg/kg (n = 6) in sesame oil and saline, respectively. Prednisolone (3 mg/kg in saline; n = 6) was used as standard. Following 21-day treatment period, the rats were sacrificed prior to which 24 hrs urine samples were obtained. Blood samples were collected and kidneys were extracted for further analyses. Renal function parameters (proteinuria, BUN, albumin, creatinine), levels of tissue reengineering and fibrosis markers (TGF-β, MMP2 activity), cholesterol and triglyceride levels were significantly improved in the ATRA and VPA combination group as compared to positive control group. Histopathological analyses revealed a reduction in inflammation, glomerulosclerosis and fibrosis. The inflammatory markers, namely TNF-α, IL-1β, IL-6, NF-κB, determined by ELISA were downregulated. Mitochondrial biogenesis markers viz. PGC-1α, TFAM, NRF1, Nrf2, PPAR-γ, KEAP-1, analysed by RT-qPCR were upregulated thereby showing a significant improvement in the combination group as compared to positive control and standard group. The study overall contributes to a novel approach to treating NS and our findings will surely drive additional exploratory preclinical and clinical studies.
Carbon-based electrode as an economically benign choice is widely used in electrochemical or bio-electrochemical systems. However, its poor electrical conductivity that leading high overpotential and energy loss, especially in large scale facilities, remains a bottleneck for its application. Herein, a unique cross-stacking multi-layered reduced graphene oxide (rGO) and polyaniline (PANI) modified carbon brush is fabricated via one-step electro-depositing. In particular, the top-most layer of the modified electrode is orientated controlled to be rGO or PANI layer by adjusting the initial CV scanning in the positive or negative direction. As was indicated by cyclic voltammetry, the improved electrochemical activity is achieved by coupling the advantages of the highly conductive network offered by graphene with desirable stability provided by the well-dispersed deposition of nanoscale PANI particles. In comparison, the modified electrode with rGO on the top-most layer (LrGO) showed higher degree of sp2-hybridized -C-C- ordered structure in Raman profile, lower O/C ratio in XPS analysis, higher Zeta potential (−2.05 mV) and more hydrophilic than unmodified one. Moreover, benefiting from the unique cross-stacking multi-layered matrix of rGO and PANI, the best electrochemical performance was achieved on the electrode LrGO with high exerted electrochemical active surface area (ECSA) of 0.85 mF cm−2, and the charge transfer resistance as low as 0.32 Ω. The findings of this study provide a guidance for the modification and application of carbon-based electrode using rGO and PANI, which potentially enables the scaling-up of carbon-based electrode in various (bio-) electrochemical systems with high electrochemical performance.
Recently, researchers have shown concern about the ChatGPT-derived answers. Here, we conducted a series of tests using ChatGPT by individual researcher at multi-country level to understand the pattern of its answer accuracy, reproducibility, answer length, plagiarism, and in-depth using two questionnaires (the first set with 15 MCQs and the second 15 KBQ). Among 15 MCQ-generated answers, 13 70 were correct (Median : 82.5; Coefficient variance : 4.85), 3 0.77 were incorrect (Median: 3, Coefficient variance: 25.81), and 1 to 10 were reproducible, and 11 to 15 were not. Among 15 KBQ, the length of each question (in words) is about 294.5 97.60 (mean range varies from 138.7 to 438.09), and the mean similarity index (in words) is about 29.53 11.40 (Coefficient variance: 38.62) for each question. The statistical models were also developed using analyzed parameters of answers. The study shows a pattern of ChatGPT-derive answers with correctness and incorrectness and urges for an error-free, next-generation LLM to avoid users’ misguidance.
Stormwater pipeline is an essential pathway to transfer stormwater runoff into nearby receiving water bodies. Understanding the composition, co-occurrence patterns, and function of the microbial communities in stormwater pipeline sediments can help to provide management and control strategies for stormwater runoff pollution to safeguard water safety and ecological health of the urban water environment. This study employs 16S rRNA gene amplicon sequencing to probe the microbial communities in stormwater pipeline sediments of a highly urbanized area in Guangzhou, China. Results show that the sediment bacterial community is rich in Listeria, Prevotella, Stenotrophomonas, and Pseudomonas, which all pertain to pathogens. Methanogens (Methanobacterium, Methanosaeta, Methanosarcina, and Methanobrevibacter) and ammonia-oxidizing archaea (Ca. Nitrosopelagicus, Ca. Nitrososphaera, and Ca. Nitrosotenuis) dominated the archaeal community in stormwater pipeline sediments. These microbial functions are further validated by the function prediction of the overall microbial community. The co-occurrence network and microbe-environment correlation analyses suggest that particulate C-N-P components play a more crucial role, in comparison to dissolved ones in regulating the sediment microbiome, although not all samples follow this mechanism. These findings are expected to contribute to the pollution control of stormwater runoff in stormwater pipeline systems and provide valuable guidance for improving the environmental well-being of urban water ecosystems.
Bottom-up Synthetic Biology (buSynBio) is an approach focused on the artificial making of minimal functional biosynthetic systems by recombining existent biochemical modules or manufacturing them from scratch. Over the last decade, this emerging orientation has gained new momentum with the development of new bioengineering tools, theories, and technologies. Despite the growing acceptance of buSynBio, few studies have dedicated attention to the analysis of its organizational aspects. This article offers the first systematic investigation of emerging research initiatives in buSynBio and their meaning to bioengineering research. Our analysis is based on a multi-method qualitative study, including expert literature review, bibliometric research and a documentary analysis of online materials such as reports and project descriptions available in official grant data repositories. Our study found that publications of specialized articles on “bottom-up synthetic biology” have increased, both in absolute numbers and normalized to total number of publications. We show how that might be enabled by novel mechanisms of organization that reposition material, intellectual and political resources in synthetic biology. Drawing on theoretical analyses within Science and Technology Studies (STS), we examine 14 research initiatives in 5 selected countries (Germany, United Kingdom, United States, Netherlands, and Switzerland). The bottom-up approach is supported by a variety of “tentative regimes” of scientific governance in different stages of consolidation, but holding in common the establishment of novel basic research in Chemistry, Biology, Engineering and Physics. The study aims to contribute to social science research in synthetic biology by shedding light on the implications of buSynBio as trend driving the current organizational change of bioengineering research.
Penicillium subrubescens is a promising candidate for industrial applications as its plant cell wall-degrading enzyme production levels and saccharification abilities are similar to that of the well-established industrial species Aspergillus niger. Interestingly, it has an expanded repertoire of hemicellulases, pectinases and inulinases in its genome compared to other Penicillia, that may enable a more targeted degradation of the corresponding polysaccharides. The transcriptional factor XlnR is essential for the expression of xylanolytic genes and is commonly found in genomes of filamentous ascomycete fungi. AraR (a homolog of XlnR) controls the arabinanolytic system as well as L-arabinose catabolism in Eurotiomycetes.
In this study, we generated P. subrubescens ΔxlnR, ΔaraR and ΔxlnRΔaraR mutants and analyzed the transcriptional response of these strains to the monosaccharides D-xylose and L-arabinose, and the polysaccharide wheat arabinoxylan to identify the genes and pathways regulated by these TFs in P. subrubescens. Transcriptomic data revealed that AraR plays a more dominant role in plant biomass conversion in P. subrubescens than XlnR.
Filamentous fungi are known for their significant potential in biotechnology, thanks to their versatile enzyme systems with various applications. However, dealing with their growth patterns and structural configurations presents significant challenges. To tackle these issues, fungal pellets are emerging as potential solutions, providing compact biomass aggregates that offer distinct advantages for bioprocesses. This study delves into characterization and optimizing pellet formation for Pleurotus ostreatus and Rhizopus stolonifer using the Taguchi methodology, aiming to enhance their biotechnological applications. By systematically varying parameters such as agitation level (AL), glucose concentration (GC), and inoculum size (IS), we identified key factors influencing pellet formation. Results indicate that P. ostreatus forms pellets in rich media from mycelium, while R. stolonifer requires a minimal medium with pH modifications for pelletization via a coagulative mechanism. The optimization process reveals that agitation level is a crucial factor for maximizing pellet production in both models, while the other factors do not seem to influence the process significantly but impact the morphology and quantity of pellets. The results suggest that by optimizing parameters using the Taguchi method, it is possible to achieve acceptable pellet formation performance in both fungi. Understanding these factors is essential for improving the efficiency of biotechnological processes involving fungal biomass, providing valuable insights into enhancing fungal pellet production for various applications.
Electrode biofilm and planktonic microorganisms are two important parts in bioelectrochemical system, but the mechanism of planktonic microorganisms affect biofilms is not clear. Waste sludge lysate produced from sludge pyrolysis contains melanoidins as complex carbon source that are refractory. Anaerobic digestion companied with weak electrostimulation is adopted to treat the wastewater and explore the mechanism in electron transfer, biofilm activity and microbial community structure. In the presence of planktonic microorganisms, electrode biofilm still plays a major role that about 70% of organics was removed by biofilm, the energy recovery efficiency increased by 10.81%, and the main electron transfer mechanism of biofilm is unchanged, but extra electron transfer pathway (Ef = 0.404 V vs Ag/AgCl) is generated. More cytochrome is produced in biofilm and charge transfer resistance decreases to facilitate electron transfer. The planktonic microorganisms cause more electrochemically active microorganisms and methanogens enrich in the electrode biofilm to enhance the direct interspecies electron transfer.
Traditional Chinese Medicine (TCM) introduces a potentially effective strategy in the realm of cancer therapy, whereas network pharmacology provides a reliable mechanism for clarifying the complex interplay between active constituents and their corresponding targets. Although Dan-Shen-Yin (DSY) has demonstrated remarkable efficacy in the treatment of various diseases, its potential anti-pancreatic cancer effects and underlying mechanisms remain unexplored. The present study aims to validate the anti-pancreatic cancer efficacy of DSY both in vivo and in vitro, while also elucidating its mechanism through a combination of network pharmacology, molecular docking, and related experiments. The in vivo effectiveness of DSY was validated using the patient-derived xenograft (PDX) model, which was chosen due to its remarkable capacity to maintain the essential histological and genetic attributes of the primary tumor. Network pharmacology predicted the anti-pancreatic cancer efficacy of DSY, which was confirmed by in vitro experiments showing inhibitory effects on proliferation, pro-apoptosis, migration, and colony formation of PC cells. Molecular docking studies further confirmed that the active components of DSY exhibited good nucleophilicity for the selected target proteins through their ability to interact via hydrogen bonding and Van der Waals forces. The PDX model showed that DSY effectively inhibited tumor growth and improved prognosis. Experiments conducted both in vivo and in vitro have demonstrated that DSY is an effective treatment for PC. Moreover, mechanistic investigations have provided evidence of the ability to impede the EGFR/SRC/STAT3 signaling pathway.