Frontiers in bioscience (Elite edition)最新文献

Prostate cancer ranks as the second most frequently diagnosed cancer globally among men and stands as the fifth leading cause of cancer-related death in males. Hence, an early and precise diagnosis and staging are critical. Traditional staging is based on clinical nomograms but presents a lower performance than prostate multiparametric magnetic resonance imaging (mpMRI). Since tumor staging serves as the basis for risk stratification, prognosis, and treatment decision-making, the primary objective of mpMRI is to distinguish between organ-confined and locally advanced diseases. Therefore, this imaging modality has emerged as the optimal selection for the local staging of prostate cancer, offering incremental value in evaluating pelvic nodal disease and bone involvement, and supplying supplementary insights regarding the precise location and disease extension. As per the Prostate Imaging Reporting & Data System v2.1 guideline, a comprehensive and accurate mpMRI requires several key sequences, which include T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) for morphological assessment, with T2WI serving as the cornerstone for local staging. Additionally, diffusion-weighted imaging (DWI) and dynamic sequences acquired with intravenous administration of paramagnetic contrast medium (DCE) are crucial components. It is worth noting that while MRI exhibits high specificity, its sensitivity in diagnosing extracapsular extension, seminal vesicle invasion, and lymph node metastases is limited. Moreover, mpMRI has its own constraints and is not as effective in detecting distant metastases or evaluating lymph nodes, for which extended pelvic lymph node dissection remains the gold standard. This review aims to highlight the significance of mpMRI in prostate cancer staging and provide a practical approach to assessing extracapsular extension, seminal vesicle invasions, and the involvement of adjacent organs and lymph nodes.

Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS).

Materials and methods: Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed.

Results: We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2-3 versus 0-1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39-0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance.

Conclusions: Our analyses demonstrate the prognostic role of a multiparametric score based on easily exploitable blood parameters, such as Hb concentration, MCV, and RDW. The red blood cell-based score may underlie the upregulation of the HIF-1α pathway and VEGF axis, thereby identifying a selected population who is likely to benefit from TKI therapy.

Infection diagnosis and antibiotic sensitivity testing are important aspects of clinical microbiology that are in dire need of improvement owing to the inadequate current standards in the early detection of bacterial response to antibiotics. The increasing antimicrobial resistance is a serious global threat to human health. Current resistance-detecting methods, using the phenotypic antibiotic sensitivity test, which measures bacterial growth as affected by antibiotics, have long analysis times. Therefore, new and rapid methods are needed to detect antibiotic resistance. Here, we review the methods used to detect antibiotic resistance in bacteria, including that caused by biofilm development, and we look at the development of rapid methods for evaluating antimicrobial resistance (AMR).

Background: In the search of tools to deal with climate change-related effects along with the aim of avoiding the loss of aromatic typicity in wine, two native yeasts strains of Saccharomyces cerevisiae (CLI 271 and CLI 889) were evaluated to determine their influence on white Malvasia aromatica wines aroma composition and sensory characteristics.

Methods: The strains were tested versus a commercial yeast strain (LSA). The fermentations were performed on grape must of the Malvasia aromatica variety previously macerated. Wine quality was studied by analysis of oenological parameters together with volatile aroma components using gas chromatography coupled to flame ionization detector (GC-FID) to quantify major volatiles compounds and headspace-solid phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS) to determine terpenoids and C13-norisoprenoids. Sensorial analysis was also realized by an experienced taster panel.

Results: Wines from locally-selected yeasts strains used had lower volatile acidity levels and higher concentration of aromatic compounds compared to the commercial strain ones. The yeast strain S. cerevisiae CLI 271 provided wines with a higher concentration of esters related to fruity attributes, especially isoamyl acetate. The tasting panel highlighted the strong floral character of wines from S. cerevisiae CLI 889 fermentation.

Conclusions: The use of microorganisms well adapted to climatic conditions can be used to produce quality wines of the Malvasia aromatica variety.

Globally, the growing production of food commodities generates significant quantities of agroindustrial residues, most of which are untreated and disposed of as waste through either burning, dumping into the land, or unplanned landfilling, thereby causing environmental pollution, public health problems, and decreased soil organic matter and soil productivity. A literature review has been conducted on the current crop residue biomass valorization, analyzing raw material properties and the potential risks associated with its incorrect or absent management, as well as the major microbial fermentation strategies that are used for converting residual crops into valuable products. Approximately 2445.2 million tons of crop residues are produced worldwide. Microbial fermentation is an efficient way of managing residues that are rich in nutrients (e.g., nitrogen, phosphorus, and potassium) and converting them into single-cell proteins, antibiotics, enzymes, bioalcohols, polysaccharides, fine chemicals, and others, thereby supporting a circular bioeconomy. Although separate saccharification and fermentation (SHF) represent the predominant fermentation strategy, it requires considerable equipment costs and a long process time, which can lead to the formation of contaminations and inhibitors. Alternative conversion strategies, including simultaneous saccharification and fermentation (SSF), simultaneous saccharification and co-fermentation (SSCF), and consolidated bioprocessing (CBP), can reduce time and production costs, contaminations, and inhibitor formation, and enhance process yields. Nevertheless, combining hydrolysis and fermentation into a single phase results in non-optimal temperature and pH. This review discusses crop residue valorization through fermentation strategies, and provides a 360-degree view of the topic. After investigating the major types of crop residues and the potential environmental risks associated with their incorrect or absent management, it analyzes the key steps in the crop residue bioconversion process, and the most common microorganisms and microbial cultures. In addition, this review reports on various examples of crop residues being converted into industrial products and analyzes the main fermentation strategies (SHF, SSF, SSCF, and CBP), highlighting their strengths and weaknesses. As a matter of fact, fermentation strategies need to be compared for their benefits and disadvantages before being implemented on a large scale. In addition, the properties and availability of the raw materials, investment, and operating costs, the skilled workforce availability, sustainability, and the return on investment all need to be evaluated. Finally, the discussion focus on future outlooks and challenges.

Background: Extrapulmonary tuberculosis (EPTB) accounts for a fifth of all Mycobacterium tuberculosis (M. tb) infections worldwide. The rise of multidrug resistance in M. tb alongside the hepatotoxicity associated with antibiotics presents challenges in managing and treating tuberculosis (TB), thereby prompting a need for new therapeutic approaches. Administration of liposomal glutathione (L-GSH) has previously been shown to lower oxidative stress, enhance a granulomatous response, and reduce the burden of M. tb in the lungs of M. tb-infected mice. However, the effects of L-GSH supplementation during active EPTB in the liver and spleen have yet to be explored.

Methods: In this study, we evaluated hepatic glutathione (GSH) and malondialdehyde (MDA) levels, and the cytokine profiles of untreated and L-GSH-treated M. tb-infected wild type (WT) mice. Additionally, the hepatic and splenic M. tb burdens and tissue pathologies were also assessed.

Results: L-GSH supplementation increased total hepatic levels and reduced GSH. A decrease in the levels of MDA, oxidized GSH, and interleukin (IL)-6 was also detected following L-GSH treatment. Furthermore, L-GSH supplementation was observed to increase interferon-gamma (IFN-γ) and tumor necrosis factor (TNF)-α production and decrease IL-10 levels. M. tb survival was significantly reduced in the liver and spleen following L-GSH supplementation. L-GSH treatment also provided a host-protective effect in the liver and spleen of M. tb-infected mice.

Conclusions: Overall, L-GSH supplementation elevated the levels of total and reduced forms of GSH in the liver and reduced the burden of M. tb by decreasing oxidative stress, enhancing the production of immunosupportive cytokines, and reducing the levels of immunosuppressive cytokines. These observed benefits highlight the potential of L-GSH supplementation during active EPTB and provide insight into novel therapeutic interventions against M. tb infections.

Biodegradation and biotransformation of contaminants in groundwater commonly occurs naturally. However, natural biodegradation rates can be slow leading to elongated contaminant plumes and prolonged risks that demand greater remedial intervention. Enhancement of the biodegradation of contaminants in groundwater can be induced by the addition of amendments to change the geochemical conditions to those that are more favorable for indigenous or added biota. Enhancing biodegradation requires collocation of the contaminant of concern with the 'right' microbial communities under the 'right' geochemical conditions, so that the microbiota thrive and bio-transform, degrade or lock up the contaminant of interest. This is most easily achievable at laboratory or bench scale where mixing is easily performed, and mass transfer limitations are minimized. However, inducing such changes at field scale in aquifers is non-trivial - amendments do not easily mix into groundwater because it is a laminar (non-turbulent) and low-energy flow environment. Bioaugmentation of cultured or genetically modified organisms have also been considered to add to groundwater to enhance contaminant degradation rates. Here we provide an overview of research studies over approximately 40 years that highlight the progression of understanding from natural biodegradation of plumes in groundwater to active bioremediation efforts that have been variably successful at field scale. Investigated contaminants providing insights include petroleum hydrocarbons, chlorinated and brominated hydrocarbons, ammonium, metals, munition compounds, atrazine and per- and polyfluorinated alkyl substances. The redox and electron acceptor/donor conditions that are inducive to biodegradation for a range of contaminants are highlighted. Biodegradation is challenged by the availability of electron donors/acceptors in the core of plumes and on plume fringes. Cases for bioaugmentation are identified. A long history of investigations provides examples of the importance of amendment delivery mechanisms, scale-up from laboratory to field, and field-scale demonstration of the effectiveness of groundwater bioremediation technologies. Advantages and disadvantages of remedial approaches are tabulated. The value and contributions of integrative modelling advances are identified. The literature review and example cases provide a deep understanding of what scale of bioremediation might be achievable for groundwater plumes. Limitations to bioremediation strategies outlined here will help direct future efforts. Addressing the sources of groundwater plumes as well as bioremediation of the plume itself will achieve more effective outcomes. Twelve 'lessons learnt' are synthesized from the review.

Obese individuals are at high risk for developing type 2 diabetes mellitus, cardiovascular diseases, and nonalcoholic fatty liver disease. The aim of this review was to analyze the scientific literature and databases to reveal the fundamental role of neuregulin 4 (NRG4) and its receptors in the development of obesity-associated metabolic disorders. This review demonstrates that NRG4 and its receptors are promising therapeutic targets for the treatment of socially significant obesity-associated pathologies. The review contains nine chapters. Information on the structure of ERBB4 and NRG4 splice isoforms and subsequent activation of downstream targets is presented. The tissue-specific features of the NRG4 and ERBB4 genes and protein production are also highlighted. The role of NRG4 and ERBB3/4 in the pathophysiological mechanisms of the development of metabolic disorders in obesity is discussed in detail. The final chapter of the review is devoted to the miRNA-dependent regulation of NRG4 and ERBB4. Recent studies have shown that several miRNAs regulate ERBB4 expression, but no information was found on the interaction of NRG4 with miRNAs. We now demonstrate the putative relationships between NRG4 and let-7a-5p, let-7c-5p, miR-423-5p, miR-93-5p, miR-23a-3p, and miR-15b-5p for the first time. In addition, we found SNP mutations affecting the interaction of NRG4 and ERBB4 with miRNA in these genes as well as in miRNAs. In summary, this review provides a detailed and comprehensive overview of the role of NRG4 in obesity-associated metabolic disorders. The review summarizes all current studies on this topic and opens perspectives for future research.

Microbes are traditionally regarded as planktonic organisms, individual cells that live independently from each other. Although this is true, microbes in nature mostly live within large multi-species communities forming complex ecosystems. In these communities, microbial cells are held together and organised spatially by an extracellular matrix (ECM). Unlike the ECM from the tissues of higher eukaryotes, microbial ECM, mostly that of yeasts, is still poorly studied. However, microbial biofilms are a serious cause for concern, for being responsible for the development of nosocomial infections by pharmacological drugs-resistant strains of pathogens, or for critically threatening plant health and food security under climate change. Understanding the organization and behaviour of cells in biofilms or other communities is therefore of extreme importance. Within colonies or biofilms, extremely large numbers of individual microbial cells adhere to inert surfaces or living tissues, differentiate, die or multiply and invade adjacent space, often following a 3D architectural programme genetically determined. For all this, cells depend on the production and secretion of ECM, which might, as in higher eukaryotes, actively participate in the regulation of the group behaviour. This work presents an overview of the state-of-the-art on the composition and structure of the ECM produced by yeasts, and the inherent physicochemical properties so often undermined, as well as the available information on its production and delivery pathways.

Background: The change in the corrected flow time of the common carotid artery (ccFTΔ) has been used as a surrogate of changing stroke volume (SVΔ) in the critically-ill. Thus, this relatively easy-to-obtain Doppler measure may help clinicians better define the intended effect of intravenous fluids. Yet the temporal evolution of SVΔ and ccFTΔ has not been reported in volunteers undergoing a passive leg raise (PLR).

Methods: We recruited clinically-euvolemic, non-fasted, adult, volunteers in a local physiology lab to perform 2 PLR maneuvers, each separated by a 5 minute 'wash-out'. During each PLR, SV was measured by a non-invasive pulse contour analysis device. SV was temporally-synchronized with a wireless, wearable Doppler ultrasound worn over the common carotid artery that continuously measured ccFT.

Results: 36 PLR maneuvers were obtained across 19 ambulatory volunteers. 8856 carotid Doppler cardiac cycles were analyzed. The ccFT increased nearly ubiquitously during the PLR and within 40-60 seconds of PLR onset; the rise in SV from the pulse contour device was more gradual. SVΔ by +5% and +10% were both detected by a +7% ccFTΔ with sensitivities, specificities and areas under the receiver operator curve of 59%, 95% and 0.77 (p < 0.001) and 66%, 76% and 0.73 (p < 0.001), respectively.

Conclusions: The ccFTΔ during the PLR in ambulatory volunteers was rapid and sustained. Within the limits of precision for detecting a clinically-significant rise in SV by a non-invasive pulse contour analysis device, simultaneously-acquired ccFT from a wireless, wearable ultrasound system was accurate at detecting 'preload responsiveness'.