Wastewater-born eviruses and bacteria, surveillance and biosensors at the interface of academia and field deployment.

Wastewater is a complex, but an ideal, matrix for disease monitoring and surveillance as it represents the entire load of enteric pathogens from a local catchment area. It captures both clinical and community disease burdens. Global interest in wastewater surveillance has been growing rapidly for infectious diseases monitoring and for providing an early warning of potential outbreaks. Although molecular detection methods show high sensitivity and specificity in pathogen monitoring from wastewater, they are strongly limited by challenges, including expensive laboratory settings and prolonged sample processing and analysis. Alternatively, biosensors exhibit a wide range of practical utility in real-time monitoring of biological and chemical markers. However, field deployment of biosensors is primarily challenged by prolonged sample processing and pathogen concentration steps due to complex wastewater matrices. This review summarizes the role of wastewater surveillance and provides an overview of infectious viral and bacterial pathogens with cutting-edge technologies for their detection. It emphasizes the practical utility of biosensors in pathogen monitoring and the major bottlenecks for wastewater surveillance of pathogens, and overcoming approaches to field deployment of biosensors for real-time pathogen detection. Furthermore, the promising potential of novel machine learning algorithms to resolve uncertainties in wastewater data is discussed.

Multifunctional Molybdenum-Based Nanoclusters Engineered Gelatin Methacryloyl as In Situ Photo-Cross-Linkable Hybrid Hydrogel Dressings for Enhanced Wound Healing.

Skin injuries and wounds present significant clinical challenges, necessitating the development of advanced wound dressings for efficient wound healing and tissue regeneration. In this context, the advancement of hydrogels capable of counteracting the adverse effects arising from undesirable reactive oxygen species (ROS) is of significant importance. This study introduces a hybrid hydrogel with rapid photocuring and excellent conformability, tailored to ameliorate the hostile microenvironment of damaged skin tissues. The hybrid hydrogel, composed of photoresponsive Gelatin Methacryloyl (GelMA) and Molybdenum-based nanoclusters (MNC), exhibits physicochemical characteristics conductive to skin regeneration. In vitro studies demonstrated the cytocompatibility and ROS-responsive behavior of the MNC/GelMA hybrid hydrogels, confirming their ability to promote human dermal fibroblasts (HDF) functions. The incorporation of MNC into GelMA not only enhances HDF adhesion, proliferation, and migration but also shields against oxidative damage induced by hydrogen peroxide (H2O2). Notably, in vivo evaluation in murine full-thickness skin defects revealed that the application of hybrid hydrogel dressings led to reduced inflammation, accelerated wound closure, and enhanced collagen deposition in comparison to control groups. Significantly, this study introduced a convenient approach to develop in situ ROS-scavenging hydrogel dressings to accelerate the wound healing process without the need for exogenous cytokines or medications. We consider that the nanoengineering approach proposed herein offers potential possibilities for the development of therapeutic hydrogel dressings addressing various skin-related conditions.

Bridging dolutegravir clinical viral response across doses and formulations using model-based exposure-response analysis in pediatrics.

OBJECTIVE: Dolutegravir (DTG) is a once-daily HIV-1 integrase inhibitor approved for the treatment of HIV-1 infection in adults and children from 4 weeks of age. The posology of DTG in children has been driven by exposure-matching relative to the adult dose for efficacy and safety. However, higher variability in pediatric exposures raises concern that efficacy may not be reliably extrapolated from adult trials. Therefore, we evaluated the relationship between DTG exposure and virologic response in children. DESIGN/METHODS: A population exposure-response analysis using logistic regression for virologic response was undertaken based on DTG exposure and covariate data from 146 pediatric participants with HIV-1 from age at least 4 weeks to less than 18 years treated for up to 48 weeks with DTG in IMPAACT P1093 study. RESULTS: None of the DTG exposure metrics were predictive of virologic response over the range of exposures in this analysis. Of the covariates tested, viral load at least 100 000 copies/ml at enrolment was a significant predictor of virologic response showing a lower probability of achieving a virologic response of HIV-1 RNA less than 50 copies/ml compared with participants with viral load less than 100 000 copies/ml at enrolment. Baseline viral load was also a significant predictor at week 48 whereby the probability of achieving a virologic response at week 48 decreased with increasing baseline viral load. CONCLUSION: This exposure-response analysis suggests that DTG exposures in children are all above the plateau of the exposure-response relationship. These results suggest that matching pediatric pharmacokinetic exposure parameters to those in adults is a reasonable approach for dose determination of DTG-containing formulations in pediatrics.

Application of hybrid multi-criteria decision-making approach to analyze wastewater microalgae culture systems for bioenergy production.

Bioenergy generation from microalgae can significantly contribute to climate mitigation and renewable energy production. In this regard, several multi-criteria decision-making method were employed to prioritize appropriate microalgae culture system for bioenergy production. Entropy weight, Criteria Importance Through Intercriteria Correlation (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) were the employed MCDA method. Fourteen microalgae culture systems were selected as a case study, which contain teen monoculture and four dual-culture. Initially, through ans in-depth review of the literature and expert views, four categories total eight indicators were selected as the evaluation indices of the study, namely 1) Proliferation: Half growth cycle and Max growth rate,2) Biomass output: Bio-crude yield and Lipid yield, 3) Nutrient utilization: residual concentration of total Nitrogen and total Phosphorus, and, 4) Stability: coefficient of variation of Bio-crude yield and Lipid yield. The result indicated that "Pediastrum sp. & Micractinium sp." was identified as the most bioenergy potential microalgae culture system, and the evaluation results of entropy weight method and CRITIC method are similar. It is pertinent to note that 1)the entropy weight method exhibits lower sample size requirements, 2) the critic method excels when dealing with larger sample sizes, and 3) the TOPSIS method necessitates the incorporation of appropriate weighting methods to ensure credible results. In the application stage, the key indicators related to cost can be further included in the evaluation indices.

H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation.

High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400-TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of SRCAP, P400, and VPS72 (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is particularly found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.

Reaction mechanisms of chlorinated disinfection byproducts formed from nitrophenol compounds with different structures during chlor(am)ination and UV/post-chlor(am)ination.

Nitrophenol compounds (NCs) have high formation potentials of disinfection byproducts (DBPs) in water disinfection processes, however, the reaction mechanisms of DBPs formed from different NCs are not elucidated clearly. Herein, nitrobenzene, phenol, and six representative NCs were used to explore the formation mechanisms of chlorinated DBPs (Cl-DBPs) during chlor(am)ination and UV/post-chlor(am)ination. Consequently, the coexistence of nitro and hydroxy groups in NCs facilitated the electrophilic substitution to produce intermediates of Cl-DBPs, and the different positions of nitro and hydroxy groups also induced different yields and formation mechanisms of Cl-DBPs during the chlorination and UV/post-chlorination processes. Besides, the amino, chlorine, and methyl groups significantly influenced the formation mechanisms of Cl-DBPs during the chlorination and UV/post-chlorination processes. Furthermore, the total Cl-DBPs yields from the six NCs followed a decreasing order of 2-chloro-3-nitrophenol, 3-nitrophenol, 2-methyl-3-nitrophenol, 2-amino-4-nitrophenol, 2-nitrophenol, and 4-nitrophenol during chlorination and UV/post-chlorination. However, the total Cl-DBPs yields from the six NCs during chloramination and UV/post-chloramination followed a quite different order, which might be caused by additional reaction mechanisms, e.g., nucleophilic substitution or addition might occur to NCs in the presence of monochloramine (NH2Cl). This work can offer deep insights into the reaction mechanisms of Cl-DBPs from NCs during the chlor(am)ination and UV/post-chlor(am)ination processes.

Formation and toxicity alteration of halonitromethanes from Chlorella vulgaris during UV/chloramination process involving bromide ion.

Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.

Population pharmacokinetic modeling of dolutegravir/lamivudine to support a once-daily fixed-dose combination regimen in virologically suppressed adults living with HIV-1.

A fixed-dose combination (FDC) of 50 mg dolutegravir and 300 mg lamivudine is indicated for the treatment of HIV-1 infection. This analysis aimed to characterize the population pharmacokinetics (PK) of dolutegravir and lamivudine based on data from a phase 3 study (TANGO) in virologically suppressed adults living with HIV-1 switching to dolutegravir/lamivudine FDC. These analyses included 362 participants who contributed 2,629 dolutegravir and 2,611 lamivudine samples collected over 48 weeks. A one-compartment model with first-order absorption and elimination parameterized by apparent oral clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (Ka) described dolutegravir PK. Covariate search yielded body weight, bilirubin, and ethnicity as predictors of CL/F, and weight was predictive for V/F. The estimates of CL/F, V/F, and Ka were 0.858 L/h, 16.7 L, and 2.15 h-1, respectively. A two-compartment model with first-order absorption and elimination parameterized by CL/F, apparent intercompartmental clearance (Q/F), apparent central volume of distribution (V2/F), apparent peripheral volume of distribution (V3/F), and Ka described lamivudine PK. Covariate search yielded eGFR and race as predictors of CL/F, and weight was predictive for V2/F. The estimated parameter values were CL/F = 19.6 L/h, Q/F = 2.97 L/h, V2/F = V3/F = 105 L, and Ka = 2.30 h-1. The steady-state prediction suggested that the effect of covariates dolutegravir and lamivudine exposures was small (<20%) and not clinically relevant. Therefore, no dose adjustments are recommended based on these analyses. The results support the use of dolutegravir/lamivudine FDC in the treatment of HIV-1 infection in adults.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03446573.

Comparative analysis of chlorinated disinfection byproducts formation from 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination.

Nitrophenol compounds (NCs) are widely distributed in water environments and regarded as important precursors of disinfection byproducts (DBPs). Herein, 4-nitrophenol and 2-amino-4-nitrophenol were selected as representative NCs to explore chlorinated DBPs (Cl-DBPs) formation during UV/post-chlorination. Dichloronitromethane (DCNM), trichloronitromethane (TCNM), dichloroacetonitrile (DCAN), and trichloromethane (TCM) were formed from 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination, and the yields of individual Cl-DBPs from 2-amino-4-nitrophenol were higher than those from 4-nitrophenol. Meantime, increasing chlorine contact time, UV fluence, and free chlorine dose could enhance Cl-DBPs formation, while much higher values of the three factors might decrease the yields of Cl-DBPs. Besides, alkaline pH could decrease the yields of halonitromethane (HNMs) and DCAN but increase the yields of TCM. Also, higher concentrations of 4-nitrophenol and 2-amino-4-nitrophenol would induce more Cl-DBPs formation. Subsequently, the possible formation pathways of DCNM, TCNM, DCAN, and TCM form 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination were proposed according to transformation products (TPs) and density functional theory (DFT) calculation. Notably, Cl-DBPs formed from 2-amino-4-nitrophenol presented higher toxicity than those from 4-nitrophenol. Among these generated Cl-DBPs, DCAN and TCNM posed higher cytotoxicity and genotoxicity, respectively. Furthermore, 4-nitrophenol, 2-amino-4-nitrophenol, and their TPs exhibited ecotoxicity. Finally, 4-nitrophenol and 2-amino-4-nitrophenol presented a high potential to produce DCNM, TCNM, DCAN, and TCM in actual waters during UV/post-chlorination, but the Cl-DBPs yields were markedly different from those in simulated waters. This work can help better understand Cl-DBPs formation from different NCs during UV/post-chlorination and is conducive to controlling Cl-DBPs formation.

Effects of cupric ions on the formation of chlorinated disinfection byproducts from nitrophenol compounds during UV/post-chlorination.

Cupric ions (Cu2+) are ubiquitous in surface waters and can influence disinfection byproducts (DBPs) formation in water disinfection processes. This work explored the effects of Cu2+ on chlorinated DBPs (Cl-DBPs) formation from six representative nitrophenol compounds (NCs) during UV irradiation followed by a subsequent chlorination (i.e., UV/post-chlorination), and the results showed Cu2+ enhanced chlorinated halonitromethane (Cl-HNMs) formation from five NCs (besides 2-methyl-3-nitrophenol) and dichloroacetonitrile (DCAN) and trichloromethane (TCM) formation from six NCs. Nevertheless, excessive Cu2+ might reduce Cl-DBPs formation. Increasing UV fluences displayed different influences on total Cl-DBPs formation from different NCs, and increasing chlorine dosages and NCs concentrations enhanced that. Moreover, a relatively low pH (5.8) or high pH (7.8) might control the yields of total Cl-DBPs produced from different NCs. Notably, Cu2+ enhanced Cl-DBPs formation from NCs during UV/post-chlorination mainly through the catalytic effect on nitro-benzoquinone production and the conversion of Cl-DBPs from nitro-benzoquinone. Additionally, Cu2+ could increase the toxicity of total Cl-DBPs produced from five NCs besides 2-methyl-3-nitrophenol. Finally, the impacts of Cu2+ on Cl-DBPs formation and toxicity in real waters were quite different from those in simulated waters. This study is conducive to further understanding how Cu2+ affected Cl-DBPs formation and toxicity in chlorine disinfection processes and controlling Cl-DBPs formation in copper containing water.

Mechanophysical and Anti-Adhesive Properties of a Nanoclay-Containing PMMA Denture Resin.

Poly(methyl methacrylate) (PMMA) is commonly used for dental dentures, but it has the drawback of promoting oral health risks due to oral bacterial adhesion. Recently, various nanoparticles have been incorporated into PMMA to tackle these issues. This study aims to investigate the mechanophysical and antimicrobial adhesive properties of a denture resin by incorporating of nanoclay into PMMA. Specimens were prepared by adding 0, 1, 2, and 4 wt % surface-modified nanoclay (Sigma) to self-polymerizing PMMA denture resin. These specimens were then evaluated using FTIR, TGA/DTG, and FE-SEM with EDS. Various mechanical and surface physical properties, including nanoindentation, were measured and compared with those of pure PMMA. Antiadhesion experiments were conducted by applying a Candida albicans (ATCC 11006) suspension to the surface of the specimens. The antiadhesion activity of C. albicans was confirmed through a yeast-wall component (mannan) and mRNA-seq analysis. The bulk mechanical properties of nanoclay-PMMA composites were decreased compared to those of pure PMMA, while the flexural strength and modulus met the ISO 20795-1 requirement. However, there were no significant differences in the nanoindentation hardness and elastic modulus. The surface energy revealed a significant decrease at 4 wt % nanoclay-PMMA. The antiadhesion effect of Candida albicans was evident along with nanoclay content in the nanocomposites and confirmed by the reduced attachment of mannan on nanoclay-PMMA composites. mRNA-seq analysis supported overall transcriptome changes in altering attachment and metabolism behaviors on the surface. The nanoclay-PMMA materials showed a lower surface energy as the content increased, leading to an antiadhesion effect against Candida albicans. These findings indicate that incorporating nanoclay into PMMA surfaces could be a valuable strategy for preventing the fungal biofilm formation of denture base materials.

Pilot-scale membrane-covered composting of food waste: Initial moisture, mature compost addition, aeration time and rate.

The impact of different operational parameters on the composting efficiency and compost quality during pilot-scale membrane-covered composting (MCC) of food waste (FW) was evaluated. Four factors were assessed in an orthogonal experiment at three different levels: initial mixture moisture (IMM, 55 %, 60 %, and 65 %), aeration time (AT, 6, 9, and 12 h/d), aeration rate (AR, 0.2, 0.4, and 0.6 m3/h) and mature compost addition ratio (MC, 2 %, 4 %, and 6 %). Results indicated that 55 % IMM, 6 h/d AT, 0.4 m3/h AR, and 4 % MC addition ratio simultaneously provided the compost with the maximum cumulative temperature and the minimum moisture. It was shown that the IMM was the driving factor of this optimum composting process. On contrary, the optimal parameters for reducing carbon and nitrogen loss were 65 % IMM, 6 h/d AT, 0.4 m3/h AR, and 2 % MC addition ratio. The AR had the most influence on reducing carbon and nitrogen losses compared to all other factors. The optimal conditions for compost maturity were 55 % IMM, 9 h/d AT, 0.2 m3/h AR, and 6 % MC addition ratio. The primary element influencing the pH and electrical conductivity values was the AR, while the germination index was influenced by IMM. Protein was the main organic matter limiting the composting efficiency. The results of this study will provide guidance for the promotion and application of food waste MCC technology, and contribute to a better understanding of the mechanisms involved in MCC for organic solid waste treatment.

Enhancement in the induction heating efficacy of sol-gel derived SiO2-CaO-Na2O-P2O5 bioglass-ceramics by incorporating magnetite nanoparticles.

Magnetite (Fe3O4) nanoparticle (MNP)-substituted glass-ceramic (MSGC) powders with compositions of (45 - x)SiO2-24.5CaO-24.5Na2O-6P2O5-xFe3O4 (x = 5, 8, and 10 wt%) have been prepared by a sol-gel route by introducing Fe3O4 nanoparticles during the synthesis. The X-ray diffraction patterns of the as-prepared MSGC nanopowders revealed the presence of combeite (Na2Ca2Si3O9), magnetite, and sodium nitrate (NaNO3) crystalline phases. Heat-treatment up to 700 °C for 1 h resulted in the complete dissolution of NaNO3 along with partial conversion of magnetite into hematite (α-Fe2O3). Optimal heat-treatment of the MSGC powders at 550 °C for 1 h yielded the highest relative percentage of magnetite (without hematite) with some residual NaNO3. The saturation magnetization and heat generation capacity of the MSGC fluids increased with an increase in the MNP content. The in vitro bioactivity of the MSGC pellets was evaluated by monitoring the pH and the formation of a hydroxyapatite surface layer upon immersion in modified simulated body fluid. Proliferation of MG-63 osteoblast cells indicated that all of the MSGC compositions were non-toxic and MSGC with 10 wt% MNPs exhibited extraordinarily high cell viability. The MSGC with 10 wt% MNPs demonstrated optimal characteristics in terms of cell viability, magnetic properties, and induction heating capacity, which surpass those of the commercial magnetic fluid FluidMag-CT employed in hyperthermia treatment.

Comparative evaluation of two different xenogenic acellular matrices on full-thickness skin wound healing.

OBJECTIVE: The purpose of the study was to compare the healing potential of bubaline small intestinal matrix (bSIM) and fish swim bladder matrix (FSBM) on full-thickness skin wounds in rabbits. METHOD: Four full-thickness skin wounds (each 20×20mm) were created on the dorsum of 18 rabbits that were divided into three groups based on treatment: untreated sham control (I), implanted with double layers of bSIM (II) and implanted with double layers of FSBM (III). Macroscopic, immunologic and histologic observations were made to evaluate wound healing. RESULTS: Gross healing progression in the bSIM and FSBM groups showed significantly (p<0.05) less wound contraction compared with the sham group. The IgG concentration in rabbit sera was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by enzyme-linked immunosorbent assay. The stimulation index of peripheral blood lymphocytes was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Implantation of FSBM resulted in improved re-epithelialisation, neovascularisation and fibroplasia. CONCLUSION: The FSBM is a more effective dermal substitute when compared with the bSIM for full-thickness skin wound repair in rabbit.

Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

Antioxidant constituents from Ribes glaciale Wall.: bioassay targeted in-vitro and in-silico evaluation.

Bioassay targeted phyto-investigation of dried green walnut husk of Ribes glaciale Wall. yielded one new compound as ß-D-glucopyrano (4'→3)-ß-D-glucopyranose (1) and four known compounds namely scoparone (2), apigenin (3), ß-sitosterol (4) and ß-sitosterol-D-glucoside (5). The structure of new compound was elucidated with the help of 1D, 2D and HRESIMS analysis. The antioxidant activity of extract, fractions and pure were evaluated using 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric ion reducing antioxidant power (FRAP) assays that found in the following order: butanol fr. (BF) > chloroform fr. (CF) > ethylacetate fr. (EF) > Petroleum ether fr. (PF). To search for potent antioxidant agents in extract, the isolated compounds 1, 2, 3, 4 and 5 were docked on the enzyme human NADPH oxidase, lipoxygenase, cytochrome P450 and myeloperoxidase. The compound 1 was found a potent inhibitor of target enzyme revealing its high free radical scavenging potential.

Challenges and barriers of using large language models (LLM) such as ChatGPT for diagnostic medicine with a focus on digital pathology - a recent scoping review.

BACKGROUND: The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation. METHODS: A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature. RESULTS: The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals' autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation. CONCLUSION: The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine.

Nanozyme-Engineered Hydrogels for Anti-Inflammation and Skin Regeneration.

Inflammatory skin disorders can cause chronic scarring and functional impairments, posing a significant burden on patients and the healthcare system. Conventional therapies, such as corticosteroids and nonsteroidal anti-inflammatory drugs, are limited in efficacy and associated with adverse effects. Recently, nanozyme (NZ)-based hydrogels have shown great promise in addressing these challenges. NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels. The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation. This review highlights the current state of the art in NZ-engineered hydrogels (NZ@hydrogels) for anti-inflammatory and skin regeneration applications. It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness. Additionally, the challenges and future directions in this ground, particularly their clinical translation, are addressed. The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels, offering new possibilities for targeted and personalized skin-care therapies.

Effect of different bulking agents on fed-batch composting and microbial community profile.

The current study focused on analyzing the effect of different types of bulking agents and other factors on fed-batch composting and the structure of microbial communities. The results indicated that the introduction of bulking agents to fed-batch composting significantly improved composting efficiency as well as compost product quality. In particular, using green waste as a bulking agent, the compost products would achieve good performance in the following indicators: moisture (3.16%), weight loss rate (85.26%), and C/N ratio (13.98). The significant difference in moisture of compost products (p < 0.05) was observed in different sizes of bulking agent (green waste), which was because the voids in green waste significantly affected the capacity of the water to permeate. Meanwhile, controlling the size of green waste at 3-6 mm, the following indicators would show great performance from the compost products: moisture (3.12%), organic matter content (63.93%), and electrical conductivity (EC) (5.37 mS/cm). According to 16S rRNA sequencing, the relative abundance (RA) of thermophilic microbes increased as reactor temperature rose in fed-batch composting, among which Firmicutes, Proteobacteria, Basidiomycota, and Rasamsonia were involved in cellulose and lignocellulose degradation.

Monitoring viruses and beta-lactam resistance genes through wastewater surveillance during a COVID-19 surge in Suwon, South Korea.

The present study reports data on a long-term campaign for monitoring SARS-CoV-2, norovirus, hepatitis A virus, and beta-lactam resistance genes in wastewater samples from a wastewater treatment plant during COVID-19 surge in Suwon, South Korea. Real-time digital PCR (RT-dPCR) assays indicated 100 % occurrence of all but hepatitis A virus and blaNDM gene in influent wastewater samples. CDC-N1 assay detected SARS-CoV-2 in all influent samples with an average log-transformed concentration of 5.1 ± 0.39 and the highest level at 6.02 gene copies/L. All samples were also positive for norovirus throughout the study with a mean concentration 5.67 ± 0.65 log10 gene copies/L. On the contrary, all treated wastewater (effluent) tested negative for both viruses' genetic materials. Furthermore, plasmid-mediated AmpC ß-lactamases (PABLs) genes blaDHA, blaACC, and blaFOX, extended-spectrum ß-lactamases (ESBLs) genes blaTEM and blaCTX, and Klebsiella pneumoniae carbapenemase (blaKPC) gene were measured at average concentrations of 7.05 ± 0.26, 5.60 ± 0.35, 7.82 ± 0.43, 8.38 ± 0.20, 7.64 ± 0.29, and 7.62 ± 0.41 log10 gene copies/L wastewater, respectively. Beta-lactam resistance genes showed strong correlations (r), the highest being 0.86 for blaKPC - blaFOX, followed by 0.82 for blaTEM - blaCTX and 0.79 for blaTEM - blaDHA. SARS-CoV-2 RNA occurrence in the wastewater was strongly associated (r = 0.796) with COVID-19 cases in the catchment during the initial study period of six months. A positive association of the SARS-CoV-2 RNA with the prevalence of COVID-19 cases showed a promising role of community-scale monitoring of pathogens to provide considerable early signals of infection dynamics. High concentrations of beta-lactam resistance genes in wastewater indicated a high concern for one of the biggest global health threats in South Korea and the need to find control measures. Moreover, antibiotic-resistance genes in treated wastewater flowing through water bodies and agricultural environments indicate further dissemination of antibiotic resistance traits and increasing microbial antibiotic resistance.