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Coenzyme Q (CoQ) is a redox-active lipid molecule that acts as an electron carrier in the mitochondrial electron transport chain. In Saccharomyces cerevisiae, CoQ is synthesized in the mitochondrial matrix by a multisubunit protein-lipid complex termed the CoQ synthome, the spatial positioning of which is coordinated by the endoplasmic reticulum-mitochondria encounter structure (ERMES). The MDM12 gene encoding the cytosolic subunit of ERMES is coexpressed with COQ10, which encodes the putative CoQ chaperone Coq10, via a shared bidirectional promoter. Deletion of COQ10 results in respiratory deficiency, impaired CoQ biosynthesis, and reduced spatial coordination between ERMES and the CoQ synthome. While Coq10 protein content is maintained upon deletion of MDM12, we show that deletion of COQ10 by replacement with a HIS3 marker results in diminished Mdm12 protein content. Since deletion of individual ERMES subunits prevents ERMES formation, we asked whether some or all of the phenotypes associated with COQ10 deletion result from ERMES dysfunction. To identify the phenotypes resulting solely due to the loss of Coq10, we constructed strains expressing a functionally impaired (coq10-L96S) or truncated (coq10-R147∗) Coq10 isoform using CRISPR-Cas9. We show that both coq10 mutants preserve Mdm12 protein content and exhibit impaired respiratory capacity like the coq10Δ mutant, indicating that Coq10s function is vital for respiration regardless of ERMES integrity. Moreover, the maintenance of CoQ synthome stability and efficient CoQ biosynthesis observed for the coq10-R147∗ mutant suggests these deleterious phenotypes in the coq10Δ mutant result from ERMES disruption. Overall, this study clarifies the role of Coq10 in modulating CoQ biosynthesis.

Introduction: Diabetes is a metabolic disorder of glucose homeostasis that is a significant risk factor for neurodegenerative diseases, such as Alzheimer's disease, as well as mood disorders, which often precede neurodegenerative conditions. We examined the medial habenulainterpeduncular nucleus (MHb-IPN), as this circuit plays crucial roles in mood regulation, has been linked to the development of diabetes after smoking, and is rich in cholinergic neurons, which are affected in other brain areas in Alzheimer's disease. Methods: This study aimed to investigate the impact of streptozotocin (STZ)-induced hyperglycemia, a type 1 diabetes model, on mitochondrial and lipid homeostasis in 4% paraformaldehyde-fixed sections from the MHb and IPN of C57BL/6 J male mice, using a recently developed automated pipeline for mitochondrial analysis in confocal images. We examined different time points after STZ-induced diabetes onset to determine how the brain responded to chronic hyperglycemia, with the limitation that mitochondria and lipids were not examined with respect to cell type or intracellular location. Results: Mitochondrial distribution and morphology differentially responded to hyperglycemia depending on time and brain area. Six weeks after STZ treatment, mitochondria in the ventral MHb and dorsal IPN increased in number and exhibited altered morphology, but no changes were observed in the lateral habenula (LHb) or ventral IPN. Strikingly, mitochondrial numbers returned to normal dynamics at 12 weeks. Both blood glucose level and glycated hemoglobin (HbA1C) correlated with mitochondrial dynamics in ventral MHb, whereas only HbA1C correlated in the IPN. We also examined lipid homeostasis using BODIPY staining for neutral lipids in this model given that diabetes is associated with disrupted lipid homeostasis. BODIPY staining intensity was unchanged in the vMHb of STZ-treated mice but increased in the IPN and VTA and decreased in the LHb at 12 weeks. Interestingly, areas that demonstrated changes in mitochondria had little change in lipid staining and vice versa. Discussion: This study is the first to describe the specific impacts of diabetes on mitochondria in the MHb-IPN circuit and suggests that the cholinergic MHb is uniquely sensitive to diabetesinduced hyperglycemia. Further studies are needed to understand the functional and behavioral implications of these findings. [ABSTRACT FROM AUTHOR]

Highlights: Coelastrella sp. demonstrated strong lipid production potential, especially at pH 7.0 and 0.5% fertilizer concentration. Stress conditions enhanced lipid accumulation, indicating resilience and adaptability for cultivation. The fatty acid profile supports the use of Coelastrella sp. for sustainable biodiesel production.The study examined the lipid production potential of the freshwater microalga Coelastrella sp., isolated from a pond in Gundur, Tiruchirappalli, Tamil Nadu, India. The alga was cultured in BG-11 medium under different conditions of pH, salinity, and nutrient availability to optimize lipid yield. The cultures were incubated at 25 °C with constant illumination (3000 lx) and aeration for a period of three weeks. The effects of pH levels (6.0, 7.0, 8.0, 9.0), sodium chloride concentrations (0.2 mM to 0.8 mM), sodium nitrate levels (2 mM to 8 mM), and inorganic fertilizer concentrations (0.05% to 2.0%) on biomass and lipid productivity were assessed. The highest biomass productivity (0.199 g/L/day) and lipid productivity (0.108 g/L/day) were observed at pH 7.0, with nitrate concentrations of 0.4 mM yielding the most significant total lipid content (0.102 g/L/day). Optimal salinity was found at 0.8 mM, and fertilizer concentration of 0.5% significantly enhanced biomass and lipid yields, achieving a biomass productivity of 0.200 g/L/day and lipid productivity of 0.115 mg/L. Key findings included increased lipid accumulation under stress conditions, as indicated by Nile Red staining. FTIR analysis revealed the presence of functional groups linked to triacylglycerides (TAGs) and other lipids. Gas chromatography identified noteworthy fatty acids, such as linolelaidic acid (24%), cis-11,14-eicosadienoic acid (17%), and arachidonic acid (11%). Despite the presence of polyunsaturated fatty acids (PUFAs), particularly C18:2, C18:3, and C20:4, which are valuable for nutraceutical and pharmaceutical applications, the study identified fatty acid profile with monounsaturated (MUFA) and saturated fatty acids (SFA) that make Coelastrella sp. a promising candidate for biodiesel production. [ABSTRACT FROM AUTHOR]

Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity. Testosterone is known to cause muscle hypertrophy, reduced fat mass, and increased body strength. The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia. We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young, treated non-diabetic young, untreated diabetic young, and treated diabetic young rats, and 32 aged Wistar rats to groups of untreated non-diabetic elderly, treated non-diabetic elderly, untreated diabetic elderly, and treated diabetic elderly rats, with eight animals each group. The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston™. All the trained groups performed aquatic training with an overload of 5% of the body mass. Following the experiment, we anesthetized and euthanized the animals after exercise (exhaustion). Hemoglobin, erythrocytes, and hematocrit values were higher in the treated groups. The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups (p < 0.05). As for the lipid profile, untreated rats had the highest values. Glucose concentration was higher at rest and after exercise in the untreated diabetic groups (p < 0.05). Lactate was more elevated in the untreated diabetic groups, and the testosterone-treated groups performed the longest swimming time after the maximal test (p < 0.05). The use of testosterone in conjunction with physical exercise improved physical performance in water, blood glucose, and lipid profiles. [ABSTRACT FROM AUTHOR]

Background: Excessive submental fat under the chin is a known aesthetic concern because of its negative impact on facial appearance and psychological well-being. AYP-101 is a newly developed injectable agent containing 93% soybean phosphatidylcholine (SPC) designed to reduce submental fat. We conducted a phase 1 study to evaluate the safety, pharmacokinetic (PK), and lipid profile effects of AYP-101. Methods: This study was a randomized, double-blind, placebo-controlled, single-dose, two-cohort trial. Participants were randomized into groups receiving 250 mg of AYP-101, 500 mg of AYP-101, or placebo at a 9:9:8 ratio across both cohorts. Safety was assessed through standard clinical evaluations. Blood samples were collected up to 144 h postdose in cohort 1 and up to 48 h postdose in cohort 2. The PK parameters were calculated via noncompartmental analysis. Results: All 26 randomized subjects completed the study. A total of 72 solicited adverse drug reactions (ADRs) were reported by 24 subjects, all of which were mild. The most common ADRs were injection site pain and bruising. There were 29 ADR cases in the 250 mg group; 26 cases in the 500 mg group; and 18 cases in the placebo group, indicating that there were no clinically significant differences in the safety profiles between the groups. All the dose groups presented similar PK profiles, with Cmax values of 12.86, 13.44, and 13.61 µg/L and AUC0−24 h values of 278.06, 274.79, and 267.63 µg*h/L, respectively. No clinically significant differences in PK or lipid profiles were observed between the postdose group and the baseline group for any of the dose groups. Conclusions: AYP-101 appears to be a safe candidate for treating submental fat, with localized reactions and no systemic exposure at single subcutaneous doses of up to 500 mg. Trial registration: ClinicalTrials.gov NCT05476094. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is an inherited disorder mainly marked by increased low-density lipoprotein cholesterol (LDL-C) concentrations and a heightened risk of early-onset arteriosclerotic cardiovascular disease (ASCVD). This study seeks to characterize the genetic spectrum and genotype‒phenotype correlations of FH in Chinese pediatric individuals. Methods: Data were gathered from individuals diagnosed with FH either clinically or genetically at multiple hospitals across mainland China from January 2016 to June 2024. Results: In total, 140 children and adolescents (mean age of 6.00 years) with clinically and genetically diagnosed FH were enrolled in the study, with 87 distinct variants identified in the LDLR, APOB and PCSK9 genes. Among the variants, 11 variants were newly identified worldwide, with 9 classified as "pathogenic" or "likely pathogenic", and 2 classified as "variants of uncertain significance". Additionally, the 5 most common variants in the study were c.1448G > A (p.W483*), c.1879G > A (p.A627T), c.1216C > A (p.R406R), and c.1747C > T (p.H583Y) in the LDLR gene, as well as c.10579C > T (p.R3527W) in the APOB gene, accounting for 49.29% (69/140) of all patients. These variants are primarily observed in the Asian or Chinese population and are distinct from those present in Caucasian groups. In this cohort, 105 patients were diagnosed with heterozygous FH (HeFH), while 35 were diagnosed with homozygous FH (HoFH). Finally, only 28.57% of the patients (40/140) were using lipid-lowering medications with 33.33% of HoFH patients initiating treatment after the age of 8. Additionally, only 3 compound heterozygous patients (2.14%) underwent liver transplantation because of significantly high lipid levels. Conclusion: This study reveals the variable genotypes and phenotypes of children with FH in China and illustrates that the genotypes in the Chinese population differ from those in Caucasians, providing a valuable dataset for the clinical genetic screening of FH in China. Furthermore, the older age at diagnosis and treatment highlights the underdiagnosis and undertreatment of Chinese FH pediatric patients, suggesting that early identification should be improved through lipid or genetic screening, and that more timely and regular pharmacological treatments should be implemented. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic drugs and may lead to cardiometabolic comorbidities. There is an urgent public health need to identify patients at high risk of AIWG and determine potential biomarkers for AIWG. Methods: In the Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) trail, first-episode schizophrenia patients were randomly assigned to olanzapine, risperidone, perphenazine, amisulpride or aripiprazole for 8 weeks. We applied absolute quantitative lipidomics at baseline and after 8 weeks of antipsychotic treatment in 80 patients. To evaluate the effects of AIWG on lipid profile, 25 patients with ≥ 7% weight changes (weight gain, WG) and 28 patients with <|3|% weight changes (weight stable, WS) were investigated, separately. Results: We found that baseline CerP(d40:3) and PC(20:1_22:6) were positively associated with weight changes at follow-up (r > 0.4, pFDR < 0.05). Additionally, baseline CerP(d40:3) and PC(20:1_22:6) independently predicted rapid weight gain, with receiver operating curve (ROC) of 0.76 (95% CI: 0.63–0.90), and 0.75 (95% CI: 0.62–0.88), respectively. Compared with baseline, levels of 45 differential lipid metabolites (fold change > 1.2, VIP > 1 and pFDR < 0.05) were significantly higher in the WG group. Interestingly, no differential lipid metabolites were identified in the WS group. The LASSO regression model identified 18 AIWG lipid signatures, including 2 cholesterol esters (ChEs), 1 diglyceride (DG), 12 phosphatidylcholines (PCs), 1 phosphatidylglycerol (PG), 1 phosphatidylinositol (PI), and 1 sphingomyelin (SM), with the ChE(16:1) contributing the most. Furthermore, the level changes of ChE(16:1) were positively associated with weight gain(r = 0.67, pFDR < 0.05). Conclusion: Our findings indicate that lipid profile may serve as predictors of rapid weight gain in schizophrenia and provide useful markers for AIWG intervention. [ABSTRACT FROM AUTHOR]

The development of fluorescence-based methods for bioassays and medical diagnostics requires the design and synthesis of specific markers to target biological microobjects. However, biomolecular recognition in real cellular systems is not always as selective as desired. A new concept for creating fluorescent biomolecular probes, utilizing a fluorogenic dye and biodegradable, biocompatible nanomaterials, is demonstrated. The synthesis of a new dicationic asymmetric monomethine cyanine dye with benzo[d]thiazolium-N-propionamide and chloroquinoline end groups is presented. The photophysical properties of the newly synthesized dye were examined through the combined application of spectroscopic and theoretical methods. The applicability of the dye as a fluorogenic nucleic acid probe was proven by UV-VIS spectroscopy and fluorescence titration. The dye–nucleic acid interaction mode was investigated by UV-Vis and CD spectroscopy. The newly synthesized dicationic dye, like other similar fluorogenic structures, limited permeability, which restricts its use as a probe for RNA and DNA. To enhance cellular delivery, we utilized a patented technology that employs solid, insoluble lipid nanoparticles. This method ensures the complete introduction of the dye into cells while minimizing activity outside the cells. In our study involving two human cell lines, we observed improved penetration through the cell membrane and distinctive selectivity in visualizing nucleic acids within the cytoplasm and nucleus. [ABSTRACT FROM AUTHOR]

Background: Remnant cholesterol (RC) is a novel lipid metabolism indicator; however, its relationship with sarcopenia has not been clearly established. This study was conducted to explore the association between RC and sarcopenia. Methods: An analysis was performed utilizing cross-sectional data from the NHANES 2011–2018. The variable RC was subjected to a logarithmic transformation to address its skewness. Logistic regression studies were conducted to examine the association between RC and sarcopenia. This study used restricted cubic spline (RCS) and threshold saturation techniques to investigate nonlinear connections. Subgroup, sensitivity, and additional analyses were performed to assess the robustness and validity of the findings. Results: The study included 4636 participants. Participants with sarcopenia had significantly higher RC levels. Logistic regression demonstrated a substantial positive association between the prevalence of sarcopenia and log RC (OR=1.69, 95% CI=1.32-2.17). RCS analysis revealed a nonlinear relationship, identifying a threshold at RC=25. When the RC is below this threshold, every one-unit increase in RC increases the chance of sarcopenia by 7% (OR=1.07, 95% CI=1.04-1.10); above this threshold, changes in RC were not significant. Subgroup analysis confirmed that RC was an independent risk factor for sarcopenia. The sensitivity and supplementary analyses supported the main findings. Conclusion: This study demonstrates a significant positive association between RC levels and the prevalence of sarcopenia in U.S. adults, offering novel evidence that RC may serve as a valuable indicator for sarcopenia assessment. [ABSTRACT FROM AUTHOR]

Background: Metformin, a commonly prescribed medication for managing diabetes, has garnered increasing interest as a potential therapeutic option for combating cancer and aging. Methods: The current study investigated the effects of metformin treatment on human meibomian gland epithelial cells (hMGECs) at morphological, molecular, and electron microscopy levels. HMGECs were stimulated in vitro with 1 mM, 5 mM, and 10 mM metformin for 24, 48, and 72 h. The assessed outcomes were cell proliferation assays, lipid production, ultrastructural changes, levels of IGF-1, Nrf2, HO-1, apoptosis-inducing factor 1 (AIF1) at the protein level, and the expression of oxidative stress factors (matrix metallopeptidase 9, activating transcription factor 3, CYBB, or NADPH oxidase 2, xanthine dehydrogenase). Results: Morphological studies showed increased lipid production, the differentiation of hMGECs after stimulation with metformin, and the differentiation effects of undifferentiated hMGECs. Proliferation tests showed a reduction in cell proliferation with increasing concentrations over time. AIF1 apoptosis levels were not significantly regulated, but morphologically, the dying cells at a higher concentration of 5-10 mM showed a rupture and permeabilization of the plasma membrane, a swelling of the cytoplasm, and vacuolization after more than 48 h. The IGF-1 ELISA showed an irregular expression, which mostly decreased over time. Only at 72 h and 10 mM did we have a significant increase. Mitochondrial metabolic markers such as Nrf2 significantly increased over time, while HO-1 decreased partially. The RT-PCR showed a significant increase in MMP9, CYBB, XDH, and ATF with increasing time and metformin concentrations, indicating cell stress. Conclusions: Our results using a cell line suggest that metformin affects the cellular physiology of meibomian gland epithelial cells and induces cell stress in a dose- and duration-dependent manner, causing changes in their morphology and ultrastructure. [ABSTRACT FROM AUTHOR]

Alcohol consumption is believed to affect Alzheimer's disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression. The purpose of this study is to explore whether chronic alcohol consumption worsens the age-related decline in TFEB-mediated lysosomal biogenesis in the brain and exacerbates cognitive decline associated with aging. To explore the effect of alcohol on brain TFEB and autophagy, we exposed young (3-month-old) and aged (23-month-old) mice to two alcohol-feeding paradigms and assessed biochemical, transcriptome, histology, and behavioral endpoints. In young mice, alcohol decreased hippocampal nuclear TFEB staining but increased SQSTM1/p62, LC3-II, ubiquitinated proteins, and phosphorylated Tau. Hippocampal TFEB activity was lower in aged mice than it was in young mice, and Gao-binge alcohol feeding did not worsen the age-related reduction in TFEB activity. Morris Water and Barnes Maze spatial memory tasks were used to characterize the effects of aging and chronic alcohol exposure (mice fed alcohol for 4 weeks). The aged mice showed worse spatial memory acquisition in both tests. Alcohol feeding slightly impaired spatial memory in the young mice, but had little effect or even slightly improved spatial memory acquisition in the aged mice. In conclusion, aging produces greater reductions in brain autophagy flux and impairment of spatial memory than alcohol consumption. [ABSTRACT FROM AUTHOR]

Globally, aquaculture is evolving in new directions achieving the critical goal of sustainable global aquaculture. A good larval-rearing diet is essential for the cultivation of aquaculture species, especially in larvae growth, survival and disease resistance. However, the success of larval rearing has been limited by the early use of artificial meals. Zooplankton are used as feed to fish/shrimp larvae in aquaculture due to their high nutrient content and easy digestibility. Enrichment methods are practised because they can manipulate the nutritional composition of zooplankton to meet the nutritional requirements of the fish/shrimp larvae. It is necessary for the improvement, growth and development during the first feeding phase of the larvae because fish require balanced and high-protein diets. Examining the most recent advancements in this field, this review focuses on the techniques for enriching zooplankton with vital nutrients and probiotics. It emphasizes how these improvements affect the nutritional value of zooplankton and the well-being of organisms cultivated. We also address the challenges and constraints of the enrichment method. This review attempts to offer insights into the future directions and potential advantages of zooplankton enrichment in boosting aquaculture productivity and sustainability through a thorough analysis of previous studies and breakthroughs. [ABSTRACT FROM AUTHOR]

The experiment sought to determine the effects of substituting Flammulina velutipes residue (FVR) for corn on growth performance, serum biochemical parameters, slaughter performance and caecum microbiota of geese. One hundred and ninety-two 35old Hordobagy geese were used in this experiment, and they were divided into four groups and fed with various diets for 28 d. The geese in the control group were fed with a basal diet. The other groups substituted 12%, 24% and 32% FVR for corn in their diets, respectively. There was no significant difference in the feed/gain ratio between the addition of 12% and 24% FVR to the diet, however, these additions considerably raised final body weight, average daily feed intake, and average daily growth (p < 0.05). When 24% FVR was substituted for corn in the diet, the levels of albumin (ALB) and high-density lipoprotein cholesterol (HDL-C) dramatically rose (p < 0.05). The examination of caecal microbiota revealed that the substitution of FVR for corn greatly increased both the variety and quantity of the caecal microbiota as well as the amount of bacteria that produce short-chain fatty acids (SCFAs). In conclusion, FVR has the potential to be an effective corn replacement with a 24% acceptable substitution level. HIGHLIGHTS: Partial replacement of corn with Flammulina velutipes residue (FVR) can increase the average daily feed intake and final body weight of geese. Partial replacement of corn with 24% FVR can increase the levels of albumin (ALB) and high-density lipoprotein cholesterol (HDL-C) in goose serum. Partial replacement of corn with 24% FVR increases the abundance of short-chain fatty acid (SCFA) producing bacteria in the goose caecum. [ABSTRACT FROM AUTHOR]

Lipids are essential components of eukaryotic membranes, playing crucial roles in membrane structure, energy storage, and signaling. They are predominantly synthesized in the endoplasmic reticulum (ER) and subsequently transported to other organelles. Diacylglycerol kinases (DGKs) are a conserved enzyme family that phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), both of which are key intermediates in lipid metabolism and second messengers involved in numerous cellular processes. Dysregulation of DGK activity is associated with several diseases, including cancer and metabolic disorders. In this review, we provide a comprehensive overview of DGK types, functions, cellular localization, and their potential as therapeutic targets. We also discuss DGKs' roles in lipid metabolism and their physiological functions and related diseases. [ABSTRACT FROM AUTHOR]

Background: To analyse changes in lipid levels during the development of intrahepatic cholestasis of pregnancy (ICP) and identify new biomarkers for predicting ICP. Methods: A retrospective case-control study was conducted to analyse 473 pregnant women who underwent regular prenatal examinations and delivered at the Women and Children's Hospital, School of Medicine, Xiamen University, between June 2020 and June 2023, including 269 normal pregnancy controls and 204 pregnant women with cholestasis. Results: Patients with ICP with gestational diabetes mellitus (GDM) have lower high-density lipoprotein (HDL) levels than in those without GDM. Total bile acid (TBA) levels were significantly higher in pregnant women with GDM than those without. The apolipoprotein A (APOA) level was lower in patients with ICP and hypothyroidism than those without hypothyroidism. TBA levels were significantly higher in pregnant women with hypothyroidism than those without. Triglyceride (TG) levels were significantly higher in patients with preeclampsia (PE) than those without. HDL and APOA levels were lower in women with ICP complicated by preterm delivery than those with normal delivery. The AUC (area under the curve) of the differential diagnosis of cholestasis of pregnancy for the APOA/APOB (apolipoprotein B) ratio was 0.727, with a sensitivity of 85.9% and specificity of 47.5%. Conclusions: The results suggested that dyslipidaemia is associated with an increased risk of ICP and its complications. The timely detection of blood lipid and bile acid levels can assist in the diagnosis of ICP and effectively prevent ICP and other complications. PLAIN LANGUAGE SUMMARY: Intrahepatic cholestasis of pregnancy (ICP) is recognized as one of the most severe complications during pregnancy. Currently, elevated fasting serum total bile acid (TBA) levels are commonly used as diagnostic markers for ICP. However, it has been observed that women diagnosed with ICP often do not exhibit elevated TBA levels. Additionally, other medical conditions can also lead to increased TBA levels. Our study has revealed a potential correlation between abnormal lipid metabolism and the occurrence and progression of ICP and its associated complications. Specifically, we found that patients with ICP who have higher serum bile acid levels tend to have more disrupted lipid metabolism, as well as a higher risk of complications and adverse pregnancy outcomes. This manuscript is the first to investigate the link between dyslipidemia and ICP, as well as other pregnancy complications. As a result, our findings offer a foundation for the clinical diagnosis and treatment of ICP and its comorbidities during pregnancy, while also highlighting the need for further research in this area. [ABSTRACT FROM AUTHOR]

Background: Observational studies have found a link between lipid metabolism disorders and aplastic anemia (AA). However, due to confounding variables and reverse causation, it is difficult to conclude such a causal link. The precise mechanism and potential implications of lipid metabolism disorder in AA remain unclear, necessitating further studies in this area. Method: This study aimed to examine the causal relationship between 38 different subtypes of triacylglycerols and AA using two-sample Mendelian randomization (MR). Additionally, two-step MR analyses were conducted to investigate the mediating effects of vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio. Results: MR analysis showed that triacylglycerol (53:3) levels were positively associated with the risk of AA [inverse variance weighting (IVW): odds ratio (OR) = 1.131,95% confidence interval (CI):1.029-1.243, P = 0.011; Bayesian weighted MR (BWMR): OR = 1.137,95% CI:1.031-1.254, P = 0.010]. Triacylglycerol (53:3) level showed no inverse causality with AA (IVW:P = 0.834; BWMR:P = 0.349). Mediation analyses showed that increasing the vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio can decrease the risk of AA. Conclusion: This study revealed the association between vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio, triacylglycerol (53:3) levels and AA, and indicated that lowering triacylglycerol (53:3) levels can reduce the risk of AA. [ABSTRACT FROM AUTHOR]

Microalgae Chlorella vulgaris, Scenedesmus obliquus, and Monoraphidium sp were cultivated in effluent from the household appliance industry as an alternative medium for bioremediation due to the high variability of chemical and biological substances in wastewater. The experiments were carried out using biological effluent (BE), chemical effluent (CE), and a combination of the two (MIX). The results showed a maximum biomass yield of 1056 mg/L (± 0.216) in the BE cultivation of the microalga Scenedesmus obliquus, 969 mg/L (± 0.20) in the BE of the microalga Monoraphidium sp. and 468 mg/L (± 0.46) in the CE of Chlorella vulgaris. In addition, they showed N O 3 - removal (100%) in the CE and MIX for cultivation with Chlorella vulgaris and 100% BE and 75% MIX with Monoraphidium sp. For the P O 3 4 - (75.3%, 99% e 97.9%) in the cultures with C. vulgaris BE, CE, and MIX respectively, with Monoraphidium sp. 58% in BE and 42% in CE and MIX. With S. obliquus, 100% removal was observed in all 3 treatments. Metal removal was also observed. The C. vulgaris culture showed lipid contents of 16%, 12%, and 17% for BE, CE, and MIX, respectively. For Monoraphidium sp., 14.5% for BE, 16% for CE, and 14% for MIX. In the culture of S. obliquus, 17%, 15.5%, and 16.5% for BE, CE, and MIX, respectively. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Scientific knowledge about ruminal biohydrogenation (BH) has improved greatly since this metabolic process was empirically confirmed in 1951. For years, BH had mostly been perceived as a process to be avoided to increase the postruminal flow of UFA from the diet. Two milestones changed this perception and stimulated great interest in BH intermediates themselves: In 1987, the in vitro anticarcinogenic properties of CLA were described, and in 2000, the inhibition of milk fat synthesis by trans -10, cis -12 CLA was confirmed. Since then, numerous BH metabolites have been described in small and large ruminants, and the major deviation from the common BH pathway (i.e., the trans -10 shift) has been reasonably well established. However, there are some less well-characterized alterations, and the comprehensive description of new BH intermediates (e.g., using isotopic tracers) has not been coupled with research on their biological effects. In this regard, the low quality of some published fatty acid profiles may also be limiting the advance of knowledge in BH. Furthermore, although BH seems to no longer be considered a metabolic niche inhabited by a few bacterial species with a highly specific metabolic capability, researchers have failed to elucidate which specific microbial groups are involved in the process and the basis for alterations in BH pathways (i.e., changes in microbial populations or their activity). Unraveling both issues may be beneficial for the description of new microbial enzymes involved in ruminal lipid metabolism that have industrial interest. From the perspective of dairy science, other knowledge gaps that require additional research in the coming years are evaluation of the relationship between BH and feed efficiency and enteric methane emissions, as well as improving our understanding of how alterations in BH are involved in milk fat depression. Addressing these issues will have relevant practical implications in dairy science. [ABSTRACT FROM AUTHOR]

Lipids and volatile organic compounds (VOCs) are essential contributors to meat flavor. However, no studies to date have comprehensively explored the lipids and VOCs in raw pork from Ningxiang (NX) pigs and their hybrid breed Berkshire × Ningxiang (BN) pigs. This study aimed to identify the lipids and VOCs and reveal the crucial lipids for characteristic flavor formation. Samples were collected from the longissimus dorsi muscle of six NX and BN 8-month-old pigs each. The intramuscular fat (IMF) content of NX pork was 5.43%, almost twice that of BN pork (p <.01). Total 187 significantly different lipids were identified between NX and BN pork (variable importance in projection scores > 1, p <.05). Further analysis suggested 38 lipids were potential markers. Out of 66 identified VOCs, 16 key VOCs were screened both in NX and BN pork. Furtherly, hexanal-D, 2-methylbutanal, 3-methylbutanal, 1-penten-3-one, 1-octen-3-ol, and ethyl acetate-D were found to be key differential VOCs. Comparing with NX pork, BN pork significantly improved pungent odor. Correlation between the lipid markers and key VOCs demonstrated that phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylcholine (PC), and triglyceride (TG) were identified as key differentiating compounds for characteristic flavor. Our findings provided a novel understanding of pork identification and a basis for improving the flavor quality of NX and BN pork. [ABSTRACT FROM AUTHOR]

Background: An ideal glucose-lowering drug is expected to not only improve glycemic control, but also have positive effects on weight, blood pressure, dyslipidemia, and also cardiovascular and renal outcomes. Objective: To investigate and compare the impact of Sodium-glucose transport protein 2 (SGLT2) inhibitors on glycemic and extraglycemic laboratory parameters and the parameters which affect this impact. Methods: This retrospective study was conducted between January 2022 and December 2022. A total of 250 patients diagnosed with type 2 diabetes mellitus (T2DM) using SGLT2i were included in the study. Results: Patients had a mean age of 55.4 ± 9.6, and 53.6% (n = 134) were male. Among the patients, 19.6% (n = 49) used dapagliflozin and 80.4% (n = 201) used empagliflozin. Glucose, HbA1c, and triglyceride levels at 3 and 6 months showed significant reductions compared to baseline, while serum sodium and HDL-C levels showed significant increases (p < 0.001). Additionally, creatinine and serum potassium levels at 6 months were significantly higher than baseline, while LDL-C and urine albumin-to-creatinine ratio levels were significantly lower. Empagliflozin users exhibited significantly higher creatinine levels only at 3. months, higher serum sodium levels only at 6. months, and lower HbA1c levels only at 6. months compared to dapagliflozin users. Conclusion: While SGLT2i seem to provide positive effects on the lipid profile, as well as their well-recognized effects on glycemic parameters, there may be value in further evaluating renal safety and the long-term alterations in lipid profile. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a major health problem, causing thousands of deaths each year worldwide. Although current medications can often inhibit viral replication and reduce the risk of liver carcinoma, several obstacles still hinder their effectiveness. These include viral resistance, prolonged treatment duration, and low efficacy in clearing viral antigens. To address these challenges in current HBV treatment, numerous approaches have been developed with remarkable success. Among these strategies, small-interfering RNA (siRNA) stands out as one of the most promising therapies for hepatitis B. However, naked siRNAs are vulnerable to enzymatic digestion, easily eliminated by renal filtration, and unable to cross the cell membrane due to their large, anionic structure. Therefore, effective delivery systems are required to protect siRNAs and maintain their functionality. In this review, we have discussed the promises of siRNA therapy in treating HBV, milestones in their delivery systems, and products that have entered clinical trials. Finally, we have outlined the future perspectives of siRNA-based therapy for HBV treatment. [ABSTRACT FROM AUTHOR]

Cellular lipid membranes serve as the primary barrier preventing viral infection of the host cell and provide viruses with a critical initial point of contact. Occasionally, viruses can utilize lipids as viral receptors. Viruses depend significantly on lipid rafts for infection at virtually every stage of their life cycle. The pivotal role that proprotein convertase subtilisin/kexin Type 9 (PCSK9) plays in cholesterol homeostasis and atherosclerosis, primarily by post-transcriptionally regulating hepatic low-density lipoprotein receptor (LDLR) and promoting its lysosomal degradation, has garnered increasing interest. Conversely, using therapeutic, fully humanized antibodies to block PCSK9 leads to a significant reduction in high LDL cholesterol (LDL-C) levels. The Food and Drug Administration (FDA) has approved PCSK9 inhibitors, including inclisiran (Leqvio®), alirocumab (Praluent), and evolocumab (Repatha). At present, active immunization strategies targeting PCSK9 present a compelling substitute for passive immunization through the administration of antibodies. In addition to the current inquiry into the potential therapeutic application of PCSK9 inhibition in human immunodeficiency virus (HIV)-infected patients for hyperlipidemia associated with HIV and antiretroviral therapy (ART), preclinical research suggests that PCSK9 may also play a role in inhibiting hepatitis C virus (HCV) replication. Furthermore, PCSK9 inhibition has been suggested to protect against dengue virus (DENV) potentially and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses. Recent evidence regarding the impact of PCSK9 on a variety of viral infections, including HCV, HIV, DENV, and SARS-CoV-2, is examined in this article. As a result, PCSK9 inhibitors and vaccines may serve as viable host therapies for viral infections, as our research indicates that PCSK9 is significantly involved in the pathogenesis of viral infections. [ABSTRACT FROM AUTHOR]

The makapuno coconut endosperm is distinguished by its soft and irregular texture, in contrast to the solid endosperm of regular coconuts. To establish a scientific foundation for studying makapuno coconuts, callus was induced from makapuno endosperm using a combination of plant growth regulators. The induction was successful, and the resulting callus was subsequently subcultured for further study. Transcriptome sequencing of the makapuno callus identified 429 differentially expressed genes (DEGs), with 273 upregulated and 156 downregulated, compared to callus derived from regular coconut endosperm. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these DEGs were involved in key metabolic pathways, including fructose and mannose metabolism, carbon fixation in photosynthetic organisms, galactose metabolism, and amino sugar and nucleotide sugar metabolism. Furthermore, lipid content analysis of the makapuno callus revealed a significantly higher total lipid level compared to regular callus, with notable differences in the levels of specific fatty acids, such as myristic acid, palmitic acid, and linoleic acid. This study establishes a novel platform for molecular biological research on makapuno coconuts and provides valuable insights into the molecular mechanisms underlying the formation of makapuno callus tissue. The findings also lay the groundwork for future research aimed at elucidating the unique properties of makapuno endosperm and exploring its potential applications. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have investigated links between body mass index (BMI) trajectories and cardiovascular risk, yet discrepancies in BMI measurement duration and timing of the cardiovascular-related outcome evaluation have led to inconsistent findings. Methods: We included participants from the Swedish birth cohort (BAMSE) and applied latent class mixture modeling to identify BMI trajectories using data of multiple BMI measures (≥ 4 times) from birth until 24-year follow-up (n = 3204). Subsequently, we analyzed the associations of BMI trajectories with lipids (n = 1974), blood pressure (n = 2022), HbA1c (n = 941), and blood leukocytes (n = 1973) using linear regression. We also investigated the circulating levels of 92 inflammation-related proteins (n = 1866) across BMI trajectories. Results: Six distinct BMI groups were identified, denoted as increasing—persistent high (n = 74; 2.3%), high—accelerated increasing (n = 209; 6.5%), increasing—accelerated resolving (n = 142; 4.4%), normal—above normal (n = 721; 22.5%), stable normal (n = 1608; 50.2%), and decreasing—persistent low (n = 450; 14.1%) BMI groups. The increasing—persistent high and high—accelerated increasing BMI groups had higher levels of total cholesterol [mean difference (95% confidence intervals): 0.30 (0.04–0.56) and 0.16 (0.02–0.31) mmol/L], triglyceride, low-density lipoprotein, hemoglobin A1C [3.61 (2.17–5.54) and 1.18 (0.40–1.98) mmol/mol], and low-density lipoprotein/high-density lipoprotein ratios, but a lower level of high-density lipoprotein than the stable normal BMI group. These two groups also had higher leukocyte cell counts and higher circulating levels of 28 inflammation-related proteins. No increased cardiometabolic markers were observed in the increasing—accelerated resolving BMI group. Conclusions: Participants with persistently high or accelerated increasing BMI trajectories from birth to young adulthood have elevated levels of cardiometabolic risk markers at young adulthood than those with stable normal BMI. However, a raised BMI in childhood may not be inherently harmful to cardiometabolic health, provided it does not persist into adulthood. [ABSTRACT FROM AUTHOR]

The impact of dietary protein and lipid levels on the growth performance, feed utilization, and serum biochemical indices of Furong crucian carp was examined. Five hundred and forty carp (2.35 ± 0.08 g) were randomly assigned to nine groups and fed diets with three different protein levels (30.0, 35.0, and 40.0%) and three different lipid levels (4.0, 7.0, and 10.0%) for 60 days. The current findings revealed that the interaction effect between dietary lipid and protein levels exhibited significance for the final average weight (FAW), weight gain rate (WGR), specific growth rate (SGR), feed efficiency (FE), energy deposition rate (EDR), whole-fish energy, ash, and fat content (p < 0.05). Specifically, there was a significant reduction in FAW, WGR, and SGR with increasing dietary fat supplementation. Conversely, FE, EDR, and protein efficiency ratios were significantly decreased with increasing dietary protein levels (p < 0.05). Furthermore, serum albumin and globulin levels exhibited significant increases in response to dietary lipid inclusion (p < 0.05). The findings collectively indicate that Furong crucian carp fed a diet comprising 4% lipid and 30% protein exhibited the optimal growth and feed utilization. Conversely, excessive protein and lipid supplementation were detrimental to growth and resulted in the aggravation of metabolic disorders. [ABSTRACT FROM AUTHOR]

Artificial lipids have become increasingly important in generating novel nanoenzymes and nanoparticles. Imidazole has been well established as a versatile catalyst in synthetic chemistry and through its related amino acid histidine in enzymes. By exploiting the transphosphatidylation reaction of phospholipase D, the choline headgroup of phosphatidyl choline was exchanged for the imidazole moiety containing histidinol. Here, we introduce a novel phosphatidylhistidinol (PtdHisOH) lipid and characterise it with respect to its catalytic abilities and its ability to modulate vesicle size. Our data reveal a zinc-dependent esterase activity that was strongest in vesicles and micelles, with slower catalytic rates being observed in flat lipid presentation systems and two-phase systems, indicating the importance of surface presentation and curvature effects on the catalytic activity of PtdHisOH. Such lipids offer the opportunity to impart de novo catalytic functionality to self-assembled lipid systems such as synthetic cells, leading to the development of new technologies for biocatalysis applications. [ABSTRACT FROM AUTHOR]