Explore the vast range of titles available.

Long-term exposure to dietary xenobiotics can induce oxidative stress in the gastrointestinal tract, possibly causing DNA damage and contributing to the initiation of carcinogenesis. Halophytes are exposed to constant abiotic stresses, which are believed to promote the accumulation of antioxidant metabolites like polyphenols. The aim of this study was to evaluate the antioxidant and antigenotoxic properties of the ethanol extract of the aerial part of the halophyte Polygonum maritimum L. (PME), which can represent a dietary source of bioactive compounds with potential to attenuate oxidative stress-related damage. The PME exhibited a high antioxidant potential, revealed by the in vitro capacity to scavenge the free radical DPPH (IC50 = 2.29 +/- 0.10 mu g/mL) and the improved viability of the yeast Saccharomyces cerevisiae under oxidative stress (p < 0.001, 10 min). An antigenotoxic effect of PME against H2O2-induced oxidative stress was found in S. cerevisiae (p < 0.05) with the dominant deletion assay. In vitro colorimetric assays and LC-DAD-ESI/MSn analysis showed that PME is a polyphenol-rich extract composed of catechin, (epi)catechin dimer and trimers, quercetin and myricetin glycosides. Hence, P. maritimum is a source of antioxidant and antigenotoxic metabolites for application in industries that develop products to provide health benefits.

Triple-negative breast cancer (TNBC) is notoriously aggressive with high metastatic potential, which has recently been linked to high rates of fatty acid oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation in TNBC through the prometastatic protein, CUB-domain containing protein 1 (CDCP1). We show that a “low-lipid” phenotype is characteristic of breast cancer cells compared with normal breast epithelial cells and negatively correlates with invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two-photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and increased lipid utilization in the mitochondria through FAO, fueling oxidative phosphorylation. These findings are supported by CDCP1’s interaction with and inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1 knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1 knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In vivo, inhibiting CDCP1 activity with an engineered blocking fragment (extracellular portion of cleaved CDCP1) lead to increased LD abundance in primary tumors, decreased metastasis, and increased ACSL activity in two animal models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their corresponding primary tumors, indicating that LD abundance in primary tumor might serve as a prognostic marker for metastatic potential. Our studies have important implications for the development of TNBC therapeutics to specifically block CDCP1-driven FAO and oxidative phosphorylation, which contribute to TNBC migration and metastasis.

Reference evapotranspiration (ETo) is a critical parameter for assessing crop water requirement and formulating irrigation scheduling and water management practices under climate change conditions and water shortage. Classical approaches e.g., the FAO‐Penman‐Monteith (FPM‐56) equation generally require several meteorological data inputs, which are often unavailable or limited. In the present study, CNN‐RNN and GPU‐accelerated CNN (CNN‐GPU) models were utilized for temperature‐dependent ETo estimating. ‘SHapley Additive exPlanations’ (SHAP) analysis revealed that solar radiation and wind speed exerted high degrees of influence, even after their exclusion from the input matrix, which clarified these implicit nonlinear relationships captured by the model. CNN‐GPU model outperformed CNN‐RNN in both accuracy (RMSE = 0.23 mm/day, NS = 0.98) and computational efficiency with a faster training time by 20.4%. Despite training with limited input variables (temperature records), the proposed DL‐based models successfully captured complex temporal and spatial meteorological patterns in the study region. A comprehensive analysis of a computational model based on convolutional networks (CNN) using graphics processing units (GPU) was developed in the present study for reference evapotranspiration (ETo). The CNN‐GPU architecture demonstrates the high accuracy of the model by schematically showing the data flow from input to output, including convolutional and max‐pooling layers. Performance plots confirm the optimization of parameters with NS Score (0.98), RMSE (0.23), and while SHAP analysis highlights the importance of features such as Rs and Tmax. The spatial distribution of error and Taylor diagrams also evaluate the model's performance at spatial and statistical scales and demonstrate its application in advanced meteorology.

We found that a subset of signal transducer and activator of transcription 3 (STAT3) translocated into mitochondria in phagocytes, including macrophages isolated from individuals with sepsis. However, the role of mitochondrial STAT3 in macrophages remains unclear. To investigate the function of mitochondrial STAT3 , we generated inducible mitochondrial STAT3 knock-in mice. A cytokine array analysis, a CBA analysis, flow cytometry, immunofluorescence staining and quantification and metabolic analyses were subsequently performed in an LPS-induced sepsis model. Single-cell RNA sequencing, a microarray analysis, metabolic assays, mass spectrometry and ChIP assays were utilized to gain insight into the mechanisms of mitochondrial STAT3 in metabolic reprogramming in LPS-induced sepsis. We found that mitochondrial STAT3 induced NF-κB nuclear localization and exacerbated LPS-induced sepsis in parallel with a metabolic switch from mainly using glucose to an increased reliance on fatty acid oxidation (FAO). Moreover, mitochondrial STAT3 abrogated carnitine palmitoyl transferase 1a (CPT1a) ubiquitination and degradation in LPS-treated macrophages. Meanwhile, an interaction between CPT1a and ubiquitin-specific peptidase 50 (USP50) was observed. In contrast, knocking down USP50 decreased CPT1a expression and FAO mediated by mitochondrial STAT3. The ChIP assays revealed that NF-κB bound the USP50 promoter. Curcumin alleviated LPS-mediated sepsis by suppressing the activities of mitochondrial STAT3 and NF-κB. Our findings reveal that mitochondrial STAT3 could trigger FAO by inducing CPT1a stabilization mediated by USP50 in macrophages, at least partially.

Myeloid-derived suppressor cells (MDSCs) play crucial roles in tumorigenesis and their inhibition is critical for successful cancer immunotherapy. MDSCs undergo metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) and oxidative phosphorylation led by lipid accumulation in tumor. Increased exogenous fatty acid uptake by tumor MDSCs enhance their immunosuppressive activity on T-cells thus promoting tumor progression. Tumor-infiltrating MDSCs in mice may prefer FAO over glycolysis as a primary source of energy while treatment with FAO inhibitors improved anti-tumor immunity. This review highlights the immunosuppressive functions of lipid metabolism and its signaling pathways on MDSCs in the tumor microenvironment. The manipulation of these pathways in MDSCs is relevant to understand the tumor microenvironment therefore, could provide novel therapeutic approaches to enhance cancer immunotherapy.

Small-scale fisheries (SSF) have long been overshadowed by the concerns and perceived importance of the industrial sector in fisheries science and policy. Yet in recent decades, attention to SSF is on the rise, marked by a proliferation of scientific publications, the emergence of new global policy tools devoted to the small-scale sector, and concerted efforts to tally the size and impacts of SSF on a global scale. Given the rising tide of interest buoying SSF, it’s pertinent to consider how the underlying definition shapes efforts to enumerate and scale up knowledge on the sector—indicating what dimensions of SSF count and consequently what gets counted. Existing studies assess how national fisheries policies define SSF, but to date, no studies systematically and empirically examine how the definition of SSF has been articulated in science, including whether and how definitions have changed over time. We systematically analyzed how SSF were defined in the peer-reviewed scientific literature drawing on a database of 1,724 articles published between 1960 and 2015. We coded a 25% random sample of articles (n=434) from our database and found that nearly one-quarter did not define SSF. Among those that did proffer a definition, harvest technologies such as fishing boats and gear were the most common characteristics used. Comparing definitions over time, we identified two notable trends over the 65-year time period studied: a decreasing proportion of articles that defined SSF and an increasing reliance on technological dimensions like boats relative to sociocultural characteristics. Our results resonate with findings from similar research on the definition of SSF in national fisheries policies that also heavily rely on boat length. We call attention to several salient issues that are obscured by an overreliance on harvest technologies in definitions of SSF, including dynamics along the wider fisheries value chain and social relations such as gender. We discuss our findings considering new policies and emerging tools that could steer scientists and practitioners toward more encompassing, consistent, and relational means of defining SSF that circumvent some of the limitations of longstanding patterns in science and policy that impinge upon sustainable and just fisheries governance.

In the coming years, climate change is predicted to impact irrigation water demand considerably, particularly in semi-arid regions. The aim of this research is to investigate the expected adverse impacts of climate change on water irrigation management in Saudi Arabia. We focus on the influence of climate change on irrigation water requirements in the Al Quassim (97,408 ha) region. Different climate models were used for the intermediate emission SSP2-4.5 and the high emission SSP5-8.5 Coupled Model Intercomparison Project Phase 6 (CMIP6) scenarios. The FAO-CROPWAT 8.0 model was used to calculate reference evapotranspiration (ETo) using weather data from 13 stations from 1991 to 2020 and for both the SSP2-4.5 and SSP5-8.5 scenarios for the 2040s, 2060s, 2080s, and 2100s. The findings indicated that, for the 2100s, the SSP2-4.5 and SSP5-8.5 scenarios forecast annual average ETo increases of 0.35 mm/d (6%) and 0.7 mm/d (12.0%), respectively. Net irrigation water requirement (NIWR) and growth of irrigation water requirement (GIWR) for the main crops in the Al Quassim region were assessed for the current, SSP2-4.5, and SSP5-8.5 scenarios. For SSP5-8.5, the GIWR for the 2040s, 2060s, 2080s, and 2100s are expected to increase by 2.7, 6.5, 8.5, and 12.4%, respectively, compared to the current scenario (1584.7 million m3). As a result, there will be higher deficits in 2100 under SSP5-8.5 for major crops, with deficits of 15.1%, 10.7%, 8.3%, 13.9%, and 10.7% in the crop areas of wheat, clover, maize, other vegetables, and dates, respectively. Optimal irrigation planning, crop pattern selection, and modern irrigation technologies, combined with the proposed NIWR values, can support water resources management. The findings can assist managers and policymakers in better identifying adaptation strategies for areas with similar climates.

Evapotranspiration (ET o ) is an important component of the hydrological cycle and reliable estimates of ET o are essential for assessing crop water requirements and irrigation management. Direct measurement of evapotranspiration is both costly and involves complex and intricate procedures. Hence, empirical models are commonly utilized to estimate ET o using accessible meteorological data. Given that empirical methods operate on various assumptions, it is essential to assess their performance to pinpoint the most suitable methods for ET o calculation based on the availability of input data and the specific climatic conditions of a region. This study aims to evaluate different empirical methods of ET o in the tropical highland Udhagamandalam region of Tamil Nadu, India, utilizing sixty years of meteorological data from 1960–2020. In this study, 8 temperature-based and 10 radiation-based empirical models are evaluated against ET o estimates derived from pan evaporation observation and the FAO Penman–Monteith method (FAO-PM), respectively. Statistical error metrics indicate that both temperature and radiation-based models perform better for the Udhagamandalam region. However, radiation-based models performed better than the temperature based models. This is possibly due to the high humidity of the study region throughout the year. The results suggest that simple temperature and radiation-based models using minimum meteorological information are adequate to estimate ET o and thus find potential application in agricultural water practices, hydrological processes, and irrigation management.

Fatty acid oxidation (FAO) plays a vital role in drug resistance in cancer cells. Carnitine palmitoyltransferase 1A (CPT1A), a key enzyme of FAO, is widely recognized as an emerging therapeutic target. Here, we confirmed that CPT1A was heterogeneously expressed in colon cancer cells, with a high expression in oxaliplatin‐resistant cells but low expression in oxaliplatin‐sensitive cells, and expression could be increased by oxaliplatin stimulation. In addition, we verified that CPT1A was more highly expressed in colon cancer tissues than in noncancerous tissues. Silencing CPT1A by siRNA or etomoxir, a specific small‐molecule inhibitor of CPT1A, could reverse the sensitivity of drug‐resistant colon cancer cells to oxaliplatin. Subsequently, the combination of oxaliplatin with CPT1A inhibition promoted apoptosis and inhibited proliferation. In addition, exosomes were generated with the iRGD peptide on the surface, which showed highly efficient targeting compared with control exosomes in vivo. Furthermore, we loaded and therapeutically applied iRGD‐modified exosomes with siCPT1A to specifically deliver siCPT1A into tumours to suppress FAO. As a consequence, iRGD‐modified exosomes showed the significant inhibition of CPT1A in tumour tissues and exhibited the ability to reverse oxaliplatin resistance and inhibit tumour growth by inhibiting FAO with high safety in vivo. Fatty acid oxidation (FAO) plays a vital role in drug resistance in cancer cells. High expression of Carnitine palmitoyltransferase 1A (CPT1A), a key enzyme in FAO, was observed in colon cancer tissues. Here, we demonstrated that silencing of CPT1A by iRGD‐exosome‐siCPT1A efficiently suppressed FAO, inhibited tumorigenesis and reversed oxaliplatin resistance in colon cancer. Altogether, iRGD‐exosome‐siCPT1A mediated silencing of FAO may serve as an effective approach to treat oxaliplatin‐resistant patient with colon cancer and may propel the clinical application of iRGD‐engineered exosomes for siRNA delivery in cancer treatment.

Lipid metabolism involves multiple biological processes. As one of the most important lipid metabolic pathways, fatty acid oxidation (FAO) and its key rate-limiting enzyme, the carnitine palmitoyltransferase (CPT) system, regulate host immune responses and thus are of great clinical significance. The effect of the CPT system on different tissues or organs is complex: the deficiency or over-activation of CPT disrupts the immune homeostasis by causing energy metabolism disorder and inflammatory oxidative damage and therefore contributes to the development of various acute and chronic inflammatory disorders and cancer. Accordingly, agonists or antagonists targeting the CPT system may become novel approaches for the treatment of diseases. In this review, we first briefly describe the structure, distribution, and physiological action of the CPT system. We then summarize the pathophysiological role of the CPT system in chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, chronic granulomatous disease, nonalcoholic fatty liver disease, hepatic ischemia–reperfusion injury, kidney fibrosis, acute kidney injury, cardiovascular disorders, and cancer. We are also concerned with the current knowledge in either preclinical or clinical studies of various CPT activators/inhibitors for the management of diseases. These compounds range from traditional Chinese medicines to novel nanodevices. Although great efforts have been made in studying the different kinds of CPT agonists/antagonists, only a few pharmaceuticals have been applied for clinical uses. Nevertheless, research on CPT activation or inhibition highlights the pharmacological modulation of CPT-dependent FAO, especially on different CPT isoforms, as a promising anti-inflammatory/antitumor therapeutic strategy for numerous disorders.