Persistent and Bioaccumulative Halogenated Natural Products in Various Tropical Reef Fish Species from the Seychelles, Western Indian Ocean.

Gas chromatography with electron capture negative ion mass spectrometry (GC/ECNI-MS) was used to quantify and compare halogenated natural products (HNPs) and selected anthropogenic persistent organic pollutants (POPs) in individual samples of 17 fish species from the Seychelles (Western Indian Ocean). The sum-HNP amounts (9.5-1100 ng/g lipid mass (lm)) were between 1 and 2 orders of magnitude higher than those of the sum of seven abundant polychlorinated biphenyl (PCB) congeners (0.2-15 ng/g lm) and dichlorodiphenyltrichloroethane-related compounds (DDTs) (<1.1-43 ng/g lm). Within the group of HNPs, the two tetrabrominated phenoxyanisoles (aka methoxylated diphenyl ethers, MeO-BDEs), 2'-MeO-BDE 68 ≫ 6-MeO-BDE 47, were predominant in most cases. Pearson correlation analysis showed that MeO-BDE levels were positively correlated with less abundant HNPs (2,2'-diMeO-BB 80, 2',6-diMeO-BDE 68, and Br6-DBP) (p < 0.01). Accordingly, HNPs, rather than PCBs and DDTs, were the predominant polyhalogenated contaminants in the current species.

Assessment of heavy metal contamination in leafy vegetables: implications for public health and regulatory measures.

Heavy metal contamination in leafy vegetables poses significant health risks, highlighting the urgent need for stringent monitoring and intervention measures to ensure food safety and mitigate potential adverse effects on public health. This study investigates the levels of heavy metals, including cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), and copper (Cu), in locally grown and commercially available leafy vegetables, comparing them to the safety limits established by WHO/FAO. The results revealed that levels of Cd, Cr, Ni, and Pb in the vegetables exceeded WHO/FAO limits, while Zn and Cu remained within permissible bounds. Marketed vegetables exhibited higher metal concentrations than those from nearby farms. For Cu (0.114-0.289 mg/kg) and Zn (0.005-0.574 mg/kg), the daily intake of metals (DIM) was below the dietary intake (DI) and upper limit (UL). Cd's DIM (0.031-0.062 mg/kg) remained below the UL but exceeded the DI. Marketed kale and mint surpassed both DI and UL limits for Ni, while local produce only exceeded the DI. All vegetables had DIM below the DI, except for mint and kale. For Pb, every vegetable exceeded DI limits, with market samples contributing significantly. Cr's DIM ranged from 0.028 to 1.335 mg/kg, for which no set maximum daily intake exists. The health risk index (HRI) values for Zn, Cd, Cu, Ni, and Pb suggested potential health risks associated with leafy greens, while Cr's HRI was below 1. The study underscores the need for stringent monitoring and intervention measures to mitigate the health risks posed by heavy metal contamination in leafy vegetables. These findings suggest that consuming these leafy greens may put consumers at considerable risk for health problems related to Cd, Cu, Ni, Pb, and Zn exposure.

Rv0547c, a functional oxidoreductase, supports Mycobacterium tuberculosis persistence by reprogramming host mitochondrial fatty acid metabolism.

Mycobacterium tuberculosis (Mtb) successfully thrives in the host by adjusting its metabolism and manipulating the host environment. In this study, we investigated the role of Rv0547c, a protein that carries mitochondria-targeting sequence (MTS), in mycobacterial persistence. We show that Rv0547c is a functional oxidoreductase that targets host-cell mitochondria. Interestingly, the localization of Rv0547c to mitochondria was independent of the predicted MTS but depended on specific arginine residues at the N- and C-terminals. As compared to the mitochondria-localization defective mutant, Rv0547c-2SDM, wild-type Rv0547c increased mitochondrial membrane fluidity and spare respiratory capacity. To comprehend the possible reason, comparative lipidomics was performed that revealed a reduced variability of long-chain and very long-chain fatty acids as well as altered levels of phosphatidylcholine and phosphatidylinositol class of lipids upon expression of Rv0547c, explaining the increased membrane fluidity. Additionally, the over representation of propionate metabolism and ß-oxidation intermediates in Rv0547c-targeted mitochondrial fractions indicated altered fatty acid metabolism, which corroborated with changes in oxygen consumption rate (OCR) upon etomoxir treatment in HEK293T cells transiently expressing Rv0547c, resulting in enhanced mitochondrial fatty acid oxidation capacity. Furthermore, Mycobacterium smegmatis over expressing Rv0547c showed increased persistence during infection of THP-1 macrophages, which correlated with its increased expression in Mtb during oxidative and nutrient starvation stresses. This study identified for the first time an Mtb protein that alters mitochondrial metabolism and aids in survival in host macrophages by altering fatty acid metabolism to its benefit and, at the same time increases mitochondrial spare respiratory capacity to mitigate infection stresses and maintain cell viability.

2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside promotes liver regeneration after partial hepatectomy in mice: The potential involvement of PPARα-mediated fatty acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

Analysis of factors affecting evapotranspiration zoning.

Reference evapotranspiration (ETo) has a significant role in water resource planning and management as well as analysis of crop production and other agricultural tasks. Methods for estimating ETo may require diurnal/monthly assessments to perceive the consequences of climatic changes on local regions. The spatial and temporal patterns of ETo were analyzed in the current work using data from 340 weather stations in Iran. The entropy theory was used to assess the uncertainty of the utilized variables and the modified Kendall test was applied for temporal trend analysis. The interpolation (e.g., kriging) and ordinary least squares (OLS) methods were used for spatio-temporal ETo classification/modeling. The spatial analysis demonstrated that the OLS method with a good fit measure (R2 = 0.985) successfully simulated the spatial relationships of ETo with climatic parameters. After examining error indices, the cokriging method with an exponential variogram was introduced as the best method of seasonal and annual ETo classification in Iran. Spatially and temporally calculated ETo patterns using modified Hargreaves (MHGR) and MODIS methods closely resembled the standard FAO Penman-Monteith (FPM-56) method, all indicating a gradual increase in ETo. MHGR and MODIS methods serve as suitable alternatives for estimating ETo in various climatic regions of Iran, provided data availability.

Mitochondria fission accentuates oxidative stress in hyperglycemia-induced H9c2 cardiomyoblasts in vitro by regulating fatty acid oxidation.

Oxidative stress plays a pivotal role in the development of diabetic cardiomyopathy (DCM). Previous studies have revealed that inhibition of mitochondrial fission suppressed oxidative stress and alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. However, no research has confirmed whether mitochondria fission accentuates hyperglycemia-induced cardiomyoblast oxidative stress through regulating fatty acid oxidation (FAO). We used H9c2 cardiomyoblasts exposed to high glucose (HG) 33 mM to simulate DCM in vitro. Excessive mitochondrial fission, poor cell viability, and lipid accumulation were observed in hyperglycemia-induced H9c2 cardiomyoblasts. Also, the cells were led to oxidative stress injury, lower adenosine triphosphate (ATP) levels, and apoptosis. Dynamin-related protein 1 (Drp1) short interfering RNA (siRNA) decreased targeted marker expression, inhibited mitochondrial fragmentation and lipid accumulation, suppressed oxidative stress, reduced cardiomyoblast apoptosis, and improved cell viability and ATP levels in HG-exposed H9c2 cardiomyoblasts, but not in carnitine palmitoyltransferase 1 (CPT1) inhibitor etomoxir treatment cells. We also found subcellular localization of CPT1 on the mitochondrial membrane, FAO, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) were suppressed after exposure to HG treatment, whereas Drp1 siRNA normalized mitochondrial CPT1, FAO, and NADPH. However, the blockade of FAO with etomoxir abolished the above effects of Drp1 siRNA in hyperglycemia-induced H9c2 cardiomyoblasts. The preservation of mitochondrial function through the Drp1/CPT1/FAO pathway is the potential mechanism of inhibited mitochondria fission in attenuating oxidative stress injury of hyperglycemia-induced H9c2 cardiomyoblasts.

Performance evaluation of different empirical models for reference evapotranspiration estimation over Udhagamandalm, The Nilgiris, India.

Evapotranspiration (ETo) is an important component of the hydrological cycle and reliable estimates of ETo 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 ETo 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 ETo 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 ETo 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 ETo 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 ETo and thus find potential application in agricultural water practices, hydrological processes, and irrigation management.

The effects of trade liberalization on inequality in nutrition intake: empirical evidence from Indian districts.

BACKGROUND: Despite the positive impact of trade liberalization on food availability in India, severe inequality in nutrition consumption at the district level persists. Empirical evidence on the relationship between trade liberalization and nutrition consumption inequality often offers a country-level perspective and generates disputed outcomes. The study aimed to explore the effects of trade liberalization on inequality in nutrition consumption at the district level in India and to examine the heterogeneity of the impact on different nutrition consumption. METHODS: Our study employed the Gini Index to measure nutrition consumption inequality of 2 macronutrients and 5 micronutrients at the district level in India during 2009-2011, utilizing the comprehensive FAO/WHO individual food consumption data. The import tariff was adopted as a proxy for trade liberalization, as its externally imposed nature facilitates a causal interpretation. We further identified the direct causal relationship between food trade liberalization and inequality in nutrition consumption using a fixed effects model. RESULTS: The results show that more than 50% of the individuals in the survey districts did not meet the dietary standards for both macronutrients and micronutrients. Food trade liberalization hindered the improvement of inequality in nutrition consumption. As import tariffs were reduced by 1%, the inequality in intake of calories, zinc, vitamin B1, and vitamin B2 increased significantly by 0.45, 0.56, 0.48, and 0.66, respectively, which might be related to food market performance. The results also highlight the positive role of the gender gap, female-headed households, and caste culture on inequality in nutrition consumption in India. CONCLUSIONS: To ease the shock of liberalization and minimize its inequality effects, complementary measures should be adopted, such as improving food logistic conditions in poor areas, and nutrition relief schemes.

TLR2 Supports γδ T cell IL-17A Response to ocular surface commensals by Metabolic Reprogramming.

The ocular surface is a mucosal barrier tissue colonized by commensal microbes, which tune local immunity by eliciting IL-17 from conjunctival γδ T cells to prevent pathogenic infection. The commensal Corynebacterium mastitidis (C. mast) elicits protective IL-17 responses from conjunctival Vγ4 T cells through a combination of γδ TCR ligation and IL-1 signaling. Here, we identify Vγ6 T cells as a major C. mast-responsive subset in the conjunctiva and uncover its unique activation requirements. We demonstrate that Vγ6 cells require not only extrinsic (via dendritic cells) but also intrinsic TLR2 stimulation for optimal IL-17A response. Mechanistically, intrinsic TLR2 signaling was associated with epigenetic changes and enhanced expression of genes responsible for metabolic shift to fatty acid oxidation to support Il17a transcription. We identify one key transcription factor, IκBζ, which is upregulated by TLR2 stimulation and is essential for this program. Our study highlights the importance of intrinsic TLR2 signaling in driving metabolic reprogramming and production of IL-17A in microbiome-specific mucosal γδ T cells.

Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy.

Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds up within the peripheral arteries, leading to reduced blood flow and oxygen supply to the outer extremities. Individuals who experience PAD suffer from ischemia, which is typically accompanied by significant damage to skeletal muscles. Additionally, this tissue damage affects mitochondria, causing them to become dysregulated and dysfunctional, resulting in decreased metabolic rates. As there is no known cure for PAD, researchers are exploring potential therapeutic targets by examining coexisting cardiovascular conditions and metabolic risk factors, such as the aging process. Among these comorbidities, type-two diabetes mellitus and obesity are particularly common in PAD cases. These conditions, along with aging itself, are associated with an elevated accumulation of ectopic lipids within skeletal muscles, similar to what is observed in PAD. Researchers have attempted to reduce excess lipid accumulation by increasing the rate of fatty acid beta oxidation. Manipulating acetyl coenzyme A carboxylase 2, a key regulatory protein of fatty acid beta oxidation, has been the primary focus of such research. When acetyl coenzyme A carboxylase 2 is inhibited, it interrupts the conversion of acetyl-CoA into malonyl-CoA, resulting in an increase in the rate of fatty acid beta oxidation. By utilizing samples from PAD patients and applying the pharmacological strategies developed for acetyl coenzyme A carboxylase 2 in diabetes and obesity to PAD, a potential new therapeutic avenue may emerge, offering hope for improved quality of life for individuals suffering from PAD.

Loss of OVOL2 in Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics.

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung-metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2-deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2-deficient TNBC.

Staphylococcus aureus oleate hydratase produces ligands that activate host PPARα.

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages. Cell-based transcriptional reporter assays show h18:0 selectively activates PPARα. Radiolabeling experiments with bone marrow-derived macrophages show [1-14C]h18:0 is not incorporated into cellular lipids, but is degraded by ß-oxidation, and mass spectrometry detected shortened fragments of h18:0 released into the media. The catabolism of h18:0 was >10-fold lower in bone marrow-derived macrophages isolated from Ppara -/- knockout mice, and we recover 74-fold fewer S. aureus cells from the skin infection site of Ppara -/- knockout mice compared to wildtype mice. These data identify PPARα as a target for oleate hydratase-derived hydroxy fatty acids and support the existence of an oleate hydratase-PPARα signaling axis that functions to suppress the innate immune response to S. aureus.

The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.

The accumulation of lipid droplets (LDs) and ceramides (Cer) is linked to non-alcoholic fatty liver disease (NAFLD), regularly co-existing with type 2 diabetes and decreased immune function. Chronic inflammation and increased disease severity in viral infections are the hallmarks of the obesity-related immunopathology. The upregulation of neutral sphingomyelinase-2 (NSM2) has shown to be associated with the pathology of obesity in tissues. Nevertheless, the role of sphingolipids and specifically of NSM2 in the regulation of immune cell response to a fatty acid (FA) rich environment is poorly studied. Here, we identified the presence of the LD marker protein perilipin 3 (PLIN3) in the intracellular nano-environment of NSM2 using the ascorbate peroxidase APEX2-catalyzed proximity-dependent biotin labeling method. In line with this, super-resolution structured illumination microscopy (SIM) shows NSM2 and PLIN3 co-localization in LD organelles in the presence of increased extracellular concentrations of oleic acid (OA). Furthermore, the association of enzymatically active NSM2 with isolated LDs correlates with increased Cer levels in these lipid storage organelles. NSM2 enzymatic activity is not required for NSM2 association with LDs, but negatively affects the LD numbers and cellular accumulation of long-chain unsaturated triacylglycerol (TAG) species. Concurrently, NSM2 expression promotes mitochondrial respiration and fatty acid oxidation (FAO) in response to increased OA levels, thereby shifting cells to a high energetic state. Importantly, endogenous NSM2 activity is crucial for primary human CD4+ T cell survival and proliferation in a FA rich environment. To conclude, our study shows a novel NSM2 intracellular localization to LDs and the role of enzymatically active NSM2 in metabolic response to enhanced FA concentrations in T cells.

The Global Framework for the Progressive Control of Transboundary Animal Diseases - Strengthening Infectious Disease Management and Veterinary Systems Across the Continents: Origins and Testimony.

Transboundary animal diseases are defined by the Food and Agriculture Organization (FAO) of the United Nation's Emergency Prevention System as those diseases that are of significant economic, trade and/or food security importance, which can easily spread to other countries and reach epidemic proportions, and where control/management including exclusion requires cooperation among several countries. The Global Framework for the Progressive Control of Transboundary Animal Diseases represents a platform of the FAO and World Organisation for Animal Health to engage regional sub-regional organizations and national veterinary authorities in developing and monitoring progress in animal disease management efforts.

Identification of fatty acid oxidation-related subtypes by integrated analysis of bulk- and single-cell transcriptome profiling in colorectal cancer.

Background: As one of the major metabolic reprogramming pathways, fatty acid oxidation (FAO) contributes to rapid progression in tumor cells. Nevertheless, the genomic patterns of patients' FAO levels in colorectal cancer (CRC) remain unknown. Hence, it is crucial to identify the interplay mechanisms of molecular biochemical features of FAO in CRC. Methods: Data of patients with CRC were accessed from The Cancer Genome Atlas (TCGA). Unsupervised consensus clustering related to FAO sores was conducted. The differentially expressed genes (DEGs) were screened by clustering according to FAO status polarized in TCGA, followed by the construction of the scores of genes related to FAO (GFAO_Score). Enrichment of FAO and carcinogenesis at the cell level were calculated based on the single-cell RNA (scRNA) sequencing analysis. The clinical values and drug analysis of GFAO_Score were evaluated by external validation cohorts from Gene Expression Omnibus (GEO) datasets. Results: We classified patients into two distinct FAO clusters which indicated those with lower FAO levels had poor prognosis and high enrichment of carcinogenic-gene pathways. Further, the high FAO-enriched subtypes in epithelial cells revealed carcinogenesis. Three FAO-related genes (ZFHX4, AQP8, and AKR1B10) were screened to construct the GFAO_Score. The high GFAO_Score group leaned toward advanced CRC and unfavorable survival outcomes in the validation cohort. The low GFAO_Score group possessed a better response to immunotherapy and exhibited lower IC50 (50% inhibition concentration) values for certain chemotherapy drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, paclitaxel, and camptothecin. Conclusions: FAO patterns vary in patients with CRC. The GFAO_Score might contribute to the precise screening of patients according to metabolism reprogramming and optimization of strategies in clinical practice.

River water pollution in Lebanon: the country's most underestimated public health challenge.

Background: Due to the several interconnected crises that Lebanon has been facing for the past 4 years, many important social and environmental issues have been overlooked until more "pressing" ones are dealt with. Consequently, water pollution in Lebanon continues to worsen. Aim: This study aimed to describe the microbiological and chemical properties of the 10 main rivers in Lebanon and to assess their suitability for irrigation, while exploring some of the solutions to the problem. Methods: This cross-sectional study evaluated the pollution level of water from 10 rivers in Lebanon in June 2023 and their suitability for irrigation. Samples were collected at 3°C and their quality parameters were measured. Statistical analysis was conducted using R statistical software version 4.0.2. Results: Compared to the Food and Agriculture Organization (FAO) guidelines for safe irrigation water use, 4 out of the 10 samples had pH levels exceeding the permissible threshold, resulting in severe limitations on their usability. Three rivers had nitrate concentrations that exceeded the approved range, thus constraining their severe usage. Among the rivers, 60% had Escherichia coli levels higher than the permissible spectrum and 40% had faecal coliform counts exceeding FAO's upper limit recommendation. All water sources, however, had total dissolved solid levels that were within the recommended range. Conclusions: Polluted water can have a negative impact on human, wildlife and ecosystem health. Most of the assessed rivers in our study contained bacterial colonies, above the maximum recommended internationally. There is therefore an urgent need to address pollution issues in Lebanese waters to make them suitable for irrigation and other uses.

Minimum Dietary Diversity for Adolescents: Multicountry Analysis to Define Food Group Thresholds Predicting Micronutrient Adequacy among Girls and Boys Aged 10-19 Years.

Background: Adolescents' diets have been overlooked in nutrition information systems, interventions, and policies. The minimum dietary diversity for women (MDD-W) indicator has been validated to signal greater micronutrient adequacy among nonpregnant women from low- and middle-income countries, but there is limited evidence for valid food group thresholds among boys or nonpregnant nonlactating girls. Objective: To define a food group threshold that reflects minimum dietary diversity for adolescents. Methods: This multicountry study evaluated the test characteristics of a 10-point food group diversity score (FGDS)-underlying MDD-W-and food group thresholds to predict the micronutrient adequacy of diets from single 24-h recalls or food diaries (24-HRs) among 83,935 adolescents aged 10-19 y and repeated 24-HRs among 75,480 adolescents from upper-middle and high-income countries. Results: FGDS was lowest among adolescents in lower-middle countries (3.5 ± 1.1) and greatest in high-income countries (5.4 ± 1.3 points). Using single 24-HRs, 1-point increments in FGDS performed identically to predict a higher mean adequacy ratio among boys and girls (5.1 percentage points; 95% confidence interval: 5.0, 5.2; P < 0.001). MDD-W (i.e., ≥5 food groups) performed well in predicting a mean adequacy ratio of >0.60 among adolescents from upper-middle and high-income countries, whereas a ≥4 food group cutoff showed a superior balance between sensitivity, specificity, and percentage correctly classified in low (only girls) and lower-middle-income countries (boys and girls). In contrast, using repeated 24-HRs, the mean probability of adequacy levels among adolescents were too high and homogeneous (i.e., all mean probability of adequacies > 0.60) to define an optimal food group threshold. Conclusions: MDD-W can be extended to boys and girls aged 10-19 y from upper-middle and high-income countries. Furthermore, an adapted indicator using a ≥4 food group threshold signals higher micronutrient adequacy in low and lower-middle-income countries. Food group cutoffs to predict the micronutrient adequacy of usual intakes should be validated using repeated 24-HRs in populations where a lower proportion of adolescents meet mean dietary requirements.

ACSL1-Mediated Fatty Acid ß-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer.

BACKGROUND: Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies. METHODS: Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS). RESULTS: Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid ß-oxidation and 5'-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid ß-oxidation. CONCLUSIONS: This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid ß-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.

MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.

Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/ß-catenin signaling. ß-catenin knockout blocked 2-AG/CB2-induced fatty acid ß-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.

Innovative approach for predicting daily reference evapotranspiration using improved shallow and deep learning models in a coastal region: A comparative study.

Accurate and reliable estimation of Reference Evapotranspiration (ETo) is crucial for water resources management, hydrological processes, and agricultural production. The FAO-56 Penman-Monteith (FAO-56PM) approach is recommended as the standard model for ETo estimation; nevertheless, the absence of comprehensive meteorological variables at many global locations frequently restricts its implementation. This study compares shallow learning (SL) and deep learning (DL) models for estimating daily ETo against the FAO-56PM approach based on various statistic metrics and graphic tool over a coastal Red Sea region, Sudan. A novel approach of the SL model, the Catboost Regressor (CBR) and three DL models: 1D-Convolutional Neural Networks (1D-CNN), Long Short-Term Memory (LSTM), and Gated Recurrent Unit (GRU) were adopted and coupled with a semi-supervised pseudo-labeling (PL) technique. Six scenarios were developed regarding different input combinations of meteorological variables such as air temperature (Tmin, Tmax, and Tmean), wind speed (U2), relative humidity (RH), sunshine hours duration (SSH), net radiation (Rn), and saturation vapor pressure deficit (es-ea). The results showed that the PL technique reduced the systematic error of SL and DL models during training for all the scenarios. The input combination of Tmin, Tmax, Tmean, and RH reflected higher performance than other combinations for all employed models. The CBR-PL model demonstrated good generalization abilities to predict daily ETo and was the overall superior model in the testing phase according to prediction accuracy, stability analysis, and less computation cost compared to DL models. Thus, the relatively simple CBR-PL model is highly recommended as a promising tool for predicting daily ETo in coastal regions worldwide which have limited climate data.