Metabolic Enzyme Activities Research Articles

Carvacrol enhances antioxidant activity and slows down cell wall metabolism by maintaining the energy level of 'Guifei' mango.

Postharvest mango fruit are highly susceptible to rapid ripening, softening and senescence, greatly limiting their distribution. In this study, we evaluated the potential effects of carvacrol (0.06 g L-1) on mango (25 ± 1 °C) and the mechanisms by which it regulates antioxidant activity, energy and cell wall metabolism. The results showed that carvacrol treatment delayed the 'Guifei' mango color transformation (from green to yellow) and the decrease in firmness, titratable acidity, weight loss and soluble solids content, and suppressed the increase in relative conductivity, malondialdehyde content and reactive oxygen species (H2O2 and O2 ·-) as well as enhancing antioxidant activity. In addition, carvacrol treatment increased ascorbic acid and reduced glutathione levels, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase activities in mango. Meanwhile, energy level (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate and energy charge) content and energy metabolizing enzyme activities (H+-ATPase, Ca2+-ATPase, succinate dehydrogenasepears and cytochrome C oxidase) were increased on carvacrol treatment, which resulted in the maintenance of higher energy levels. Finally, the application of carvacrol was effective in maintaining firmness and cell wall components by inhibiting the activities of polygalacturonase, cellulase, pectin methyl esterase and β-galactosidase. The current study demonstrates that carvacrol effectively delays the ripening and softening of mangoes by modulating energy metabolism and cell wall dynamics through the attenuation of oxidative stress. © 2024 Society of Chemical Industry.

Melatonin mitigates root growth inhibition and carbon-nitrogen metabolism imbalance in apple rootstock M9T337 under high nitrogen stress.

Nitrogen (N) is an essential element for plant growth, development, and metabolism. In apple production, the excessive use of N fertilizer may cause high N stress. Whether high N stress can be alleviated by regulating melatonin supply is unclear. The effects of melatonin on root morphology, antioxidant enzyme activity and 13C and 15N accumulation in apple rootstock M9T337 treated with high N were studied by soil culture. The results showed that correctly raising the melatonin supply level is helpful to root development of M9T337 rootstock under severe N stress. Compared with HN treatment, HN+MT treatment increased root and leaf growth by 11.38%, and 28.01%, respectively. Under high N conditions, appropriately increasing melatonin level can activate antioxidant enzyme activity, reduce lipid peroxidation in roots, protect root structural integrity, promote the transport of sorbitol and sucrose to roots, and promote further degradation and utilization of sorbitol and sucrose in roots, which is conducive to the accumulation of photosynthetic products, thereby reducing the inhibitory effect of high N treatment on root growth. Based on the above research results, we found that under high N stress, melatonin significantly promotes nitrate absorption, enhances N metabolism enzyme activity, and upregulates related gene expression, and regulate N uptake and utilization in the M9T337 rootstock. These results presented a fresh notion for improving N application and preserving carbon-nitrogen balance.

Enhancing biocontrol efficacy of Cryptococcus laurentii induced by carboxymethyl cellulose: Metabolic pathways and enzyme activities insights

The synergistic biocontrol effects of Cryptococcus laurentii cultured with carboxymethyl cellulose (CMC) were studied to control Penicillium italicum in postharvest grapefruit. The results showed that C. laurentii was cultured in 0.5 % (w/v) CMC (CMC-C. laurentii) significantly inhibited elongation of germ tubes, decreased germination of conidia in P. italicum, and reduced disease in grapefruit. Besides, CMC significantly increased ATP synthase and population proliferation of C. laurentii. Moreover, metabolomics analysis revealed 24 significantly differentially metabolites in CMC-C. laurentii including the citrate cycle, metabolism of glyoxylic acid, dicarboxylic acid, phenylalanine, tyrosine, and tryptophan and amino acid biosynthesis. These results demonstrate that CMC could significantly enhance the ATP synthase by promoting the citrate cycle, providing energy for strain growth, and thereby increasing the biocontrol effectiveness of C. laurentii. Furthermore, adding CMC enhanced the activities of strain extracellular hydrolases and antioxidases, which increased the resistance to stress, thus improving the antagonistic effect of C. laurentii.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Protective mechanisms of Hovenia dulcis Thunb extracts on acute alcoholism and liver injury

As a traditional Chinese medicine for anti-alcoholism, Hovenia dulcis Thunb (HDT) is widely used in the treatment of alcoholism and alcohol-related liver diseases. However, the scientific evidence of its mechanism has not been clearly established. In this study, a mouse model of acute alcoholism was established to explore the protective mechanisms of three kinds of HDT extracts on acute alcoholism and liver injury from the perspectives of behavioral indicators, serum and liver biochemical indicators, alcohol metabolic enzyme activity, intestinal flora, and liver metabolomics. The results showed that the extracts of HDT shortened the time of sobering up, significantly increased the activity of alcohol metabolic enzymes and antioxidant capacity, promoted ethanol metabolism, and had a certain preventive effect on alcoholic liver injury while preventing adverse reactions caused by alcohol. Notably, HDT water extract (HDTs) demonstrated superior anti-alcohol and liver protective properties compared to polysaccharide and polyphenol extracts of HDTs. It may be through the regulation of intestinal flora imbalance, specifically Muribaculaceae and Dubosiella to modulate biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, ultimately mitigating oxidative stress caused by ethanol consumption. This suggests that HDTs may have potential in preventing acute alcoholism and liver injury.

Polyacrylamide Regulated Phytohormone Balance and Starch Degradation to Promote Seed-Potato Sprouting and Emergence

Potatoes are typically seeded as tubers, and their slow sprouting significantly impacts production. Therefore, the effects of polyacrylamide (20 g·L−1, 30 g·L−1, and 40 g·L−1) as a seed potato dressing on sprouting, seedling growth, and biomass were investigated. The phytohormone content, respiratory intensity, and starch metabolism enzyme activity were analyzed to elucidate the physiological mechanisms involved. The sprouting rate significantly increased after 20 g·L−1 and 30 g·L−1 treatments by 40.63% and 15.63%, respectively. The sprouting energy was the highest (52.0%) at 20 g·L−1, 7.67 times higher than the control. The 20 g·L−1 and 30 g·L−1 treatments also promoted emergence and growth, with the emergence rate increasing by 18.18% and 27.27% and growth increasing by over 8.1% and 11.9%, respectively. These effects were related to changes in phytohormone content and accelerated starch conversion. After treatment, the auxin and cytokinin contents in the apical buds increased significantly at the germination initiation stage, and during the germination and vigorous growth phases, the auxin, cytokinin, and gibberellin contents increased. Polyacrylamide treatment activated α-amylase and promoted starch degradation, increasing soluble sugar content to provide nutrients and energy for sprouting. This study provides a promising approach for promoting potato tuber sprouting and seedling growth.

Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models

Cisplatin (CP) is a highly effective antitumor agent, but its clinical use is limited due to critical adverse reactions including neurotoxicity. Quercetin (QC) is a naturally occurring phytochemical with promising bioactive effects. This study investigated the Neuroprotective mechanisms and ameliorative activities of quercetin in cisplatin-induced cerebellum neurotoxicity in rat models.The rats were randomly divided into five groups of six (n = 6) rats. Group A, served as control. Group B, received a single dose of 10 mg/kg body weight (bwt) of CP (i.p.) on the first day. Group C received 30 mg/kg bwt of QC. Group D received a single dose of 10 mg/kg bwt CP on the first day followed by 30 mg/kg bwt of QC. Group E received 30 mg/kg bwt of QC per day followed by a single dose of 10 mg/kg bwt of CP on the last day. The treatment lasted for 35 days after which the novel-object recognition memory test (NORT) was used to assess non-spatial memory function. Brain neurochemical status was assessed and brain tissues were processed for histology.Quercetin increased weight loss and cognitive performance in CP-treated rats by enhancing the exploration of unfamiliar objects. Quercetin protects the brain from CP-mediated alterations in oxidative status, as well as brain metabolic enzyme indicators. It also decreased IL-6, IL-1, and TNF-α, and NF-ĸB expression, restored brain metabolic enzyme activities, increased neurotransmitters, and prevented neuromorphological alterations.In conclusion, quercetin protects rats’ brains against CP-induced cerebellum neurotoxicity via oxidative stress inhibition and down-regulation of inflammation.

Ethiopian coffee (Coffea arabica) improves glucose uptake and modulates metabolic enzyme activities linked to hyperglycemia-induced infertility in isolated rats’ testes

The present study evaluated the inhibitory effect of Ethiopian coffee (Coffea arabica) on carbohydrate digestive enzymes and its protective effect against glucose-induced testicular dysfunction using in vitro and in silico study models. Testicular oxidative stress was initiated by co-incubating testocular tissue collected from male Sprague-Dawley rats in glucose solution with different concentrations of Ethiopian coffee aqueous extracts (hot and cold) for 2 h at 37ºC. Glucose-mediated oxidative stress significantly (p < 0.05) depleted reduced glutathione and total glycogen levels while it lowered catalase and superoxide dismutase (SOD) activities in the testicular tissue. Concomitantly, this led to elevated malondialdehyde and nitric oxide levels while it also increased glycogen phosphorylase, fructose-1,6-bisphosphatase, ATPase, and acetylcholinesterase activities. Treatment with different concentrations of coffee aqueous extracts restored the enzymes’ and markers’ levels and activities. Although both the cold and hot coffee extracts strongly inhibited α-glucosidase and α-amylase enzymes, the former showed better activities. The subjection of the coffee extracts to LC-MS analysis indicated the presence of several compounds, including chlorogenic acid, caffeic acid, cafestol, kahweol, caffeine, quinic acid, ferulic acid, and catechol which were further docked with the carbohydrate digestive enzymes. The in silico results displayed that among the various metabolites, chlorogenic acid strongly interacted and had the best binding affinity with α-glucosidase and α-amylase. Our findings implied that Ethiopian coffee may have a preventive effect against glucose-induced testicular damage. These are evidenced by the capacity of the plant product to decrease oxidative stress and protect against testicular dysfunction.Graphical

A-134 Comparative Analysis of ALT and AST Measurements: Impact of P5P Activators on Platform Discrepancies

Abstract Background Vitamin B6 (VB6), notably its active form pyridoxal 5'-phosphate (P5P or PLP), is essential for ALT and AST enzyme activity in amino acid metabolism. Insufficient P5P can yield inaccurately low ALT and AST measurements in individuals with VB6 deficiency. This study assesses VB6 deficiency prevalence and its impact on ALT and AST measurements on Beckman Coulter compared to Roche and Siemens platforms. Methods VB6 levels were analyzed in 996 patients, with &amp;lt; 20 nmol/L considered deficient. ALT and AST levels were compared between Beckman Coulter AU5800 versus Roche cobas c, and Beckman Coulter AU5800 versus Siemens Dimension Vista. Roche and Siemens assays included P5P supplements, while Beckman Coulter did not. 29 ALT specimens (23 VB6 deficient and 6 normal) and 34 AST specimens (28 VB6 deficient and 6 normal) were compared between Beckman Coulter and Roche. Additionally, 16 specimens (4 VB6 deficient and 12 normal) were tested for ALT and AST for the comparison between Beckman Coulter and Siemens. The study then assessed the impact of P5P-containing reagents on test results by comparing the percentage differences in average concentration and their clinical decision implications across different platforms, within the low, normal, and high ranges. Results Out of 996 patients, 356 exhibited VB6 results below 20 nmol/L, indicating a striking 36% prevalence of VB6 deficiency within our patient population. Beckman Coulter and Roche comparison: In VB6 deficient patients, ALT displayed an average concentration difference of 11.5%: Beckman ALT mean 23 (+/-24.6) U/L versus Roche ALT mean 26 (+/-30) U/L. AST demonstrated a 41% difference in average concentration: Beckman AST mean 28.2 (+/-28.9) U/L versus Roche AST 48.9 (+/-49) U/L. In normal patients, ALT displayed an average concentration difference of 2.4%: Beckman ALT mean 21.3 (+/-21.3) U/L versus Roche ALT mean 20.8 (+/-25.7) U/L. AST demonstrated a 23.5% difference in average concentration: Beckman AST mean 25.5. (+/-25.4) U/L versus Roche AST 33.3 (+/-37.5) U/L. Additionally, 13% of ALT and 18% of AST displayed noteworthy effects on clinical decisions, resulting in shifts from low abnormal to normal range or normal range to high abnormal. Beckman Coulter and Siemens comparison: In VB6 deficient patients, ALT displayed an average concentration difference of 36.8%: Beckman ALT mean 18 (+/-15.7) U/L versus Siemens ALT mean 28.5 (+/-20.5) U/L. AST demonstrated a 43.4% difference in average concentration: Beckman AST mean 18.3 (+/-8.1) U/L versus Siemens AST 32.3 (+/-17.2) U/L. In normal patients, ALT displayed an average concentration difference of 32.8%: Beckman ALT mean 22.2 (+/-16.1) U/L versus Siemens ALT mean 33.1 (+/-20.1) U/L. AST demonstrated a 31.3% difference in average concentration: Beckman AST mean 25.4 (+/-12.3) U/L versus Siemens AST 36.1 (+/-19.7) U/L. While 6% of ALT specimens would have altered clinical decisions, the impact was more pronounced for AST, with 50% of results changing to an upper reference point. Conclusions In clinical settings where accurate assessment of enzyme activity is vital for effective patient care, our study emphasizes the crucial necessity for standardizing AST and ALT methodologies to incorporate P5P supplementation.

Effects of cadmium on the intestinal health of the snail Bradybaena ravida Benson.

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg-1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution.

Differences in body condition and hepatic cellular metabolism among distinct populations of cestode-infected pumpkinseed sunfish (Lepomis gibbosus)

Host populations can vary in the prevalence and intensity of their parasites, which may influence the impacts of infection on host physiology and health. Parasite-induced effects on hosts may be due to underlying changes in cellular energy metabolism, predominantly driven by the mitochondria. However, limited research has been conducted on understanding variation in host–parasite interactions across populations. We sampled three wild populations of pumpkinseed sunfish ( Lepomis gibbosus (Linnaeus, 1758)), two of which are infected by cestodes, to study correlations among infection intensity, host body condition, and key metabolic enzyme activities in liver tissue. In both infected populations, cestode infection was associated with reduced hepatic lipid metabolism and increased hepatic lactic fermentation. Interestingly, Lake Cromwell fish showed a decrease in body condition, electron transport system activity, and antioxidant activity with cestode intensity, whereas the contrary was observed for Lake Long fish. This suggests that Lake Long fish could be boosting their immune system and food intake to better tolerate infection, unlike Cromwell fish. This study not only highlights how different populations can vary in their response to parasite infections but also the importance of accounting for infection when studying animal physiology.

CYP and non-CYP drug metabolizing enzyme families exhibit differential sensitivities towards pro-inflammatory cytokine modulation.

Compromised hepatic drug metabolism in response to pro-inflammatory cytokine release is primarily attributed to downregulation of cytochrome P450 (CYP) enzymes. However, whether inflammation also affects other phase I and phase II drug metabolizing enzymes (DMEs) like the flavin monooxygenases (FMOs), carboxylesterases (CESs) and UDP glucuronosyltransferases (UGTs) remains unclear. This study aimed to decipher the impact of physiologically relevant concentrations of pro-inflammatory cytokines on expression and activity of phase I and phase II enzymes, in order to establish a hierarchy of their sensitivity as compared to the CYPs. Hereto, HepaRG cells were exposed to interleukin-6 and interleukin-1β to measure alterations in DME gene expression (24h) and activity (72h). Sensitivity of DMEs towards pro-inflammatory cytokines was evaluated by determining IC50 (potency) and Imax (maximal inhibition) values from the concentration-response curves. Pro-inflammatory cytokine treatment led to nearly complete downregulation of CYP3A4 (~98%), but was generally less efficacious at reducing gene expression of the non-CYP DME families. Importantly, FMO, CES and UGT family members were less sensitive towards interleuking-6 induced inhibition in terms of potency, with IC50 values that were 4.3-7.4 fold higher than CYP3A4. Similarly, 18- to 31-fold more interleukin-1β was required to achieve 50% of the maximal downregulation of FMO3, FMO4, CES1, UGT2B4 and UGT2B7 expression. The differential sensitivity persisted at enzyme activity level, highlighting that alterations in DME gene expression during inflammation are predictive for subsequent alterations in enzyme activity. In conclusion, we have shown that FMOs, CES and UGTs enzymes are less impacted by inflammation as compared to CYP enzymes. Significance Statement While the impact of pro-inflammatory cytokines on CYP expression is well established, their effects on non-CYP phase I and phase II drug metabolism remains underexplored, particularly regarding alterations in drug metabolizing enzyme activity. This study provides a quantitative understanding of the sensitivity differences to inflammation between DME family members, suggesting that non-CYP DMEs may become more important for the metabolism of drugs during inflammatory conditions due to their lower sensitivity as compared to the CYPs.

Aspirin increases estrogen levels in the placenta to prevent preeclampsia by regulating placental metabolism and transport function

Preeclampsia is a unique multisystem progressive disease during pregnancy, which seriously endangers the health of pregnant women and fetuses. In clinical practice, aspirin is recommended for the prevention of preeclampsia, but the mechanism by which aspirin prevents preeclampsia has not yet been revealed. This report comprehensively evaluates the effects of aspirin on the expression and activity of placental metabolic enzymes and transporters. We found that after aspirin administration, only the expression of organic anion transporter 4 (OAT4) in the placenta showed a significant increase at both mRNA and protein levels, consistent with the results in JAR cells. Meanwhile, studies on the metabolic enzyme activity in the placenta showed a high upregulation of CYP19A1 activity. Subsequently, significant increases in endogenous substrates of OAT4 and CYP19A1 (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) as well as estrone were detected in placental tissue. In summary, aspirin enhances the transport of DHEAS through OAT4 and promotes the metabolism of androstenedione through CYP19A1, thereby increasing estrogen levels in the placenta. This may be the mechanism by which aspirin prevents preeclampsia and maintains pregnancy by regulating the metabolism and transport function of the placenta.

Adaptive Strategies and Underlying Response Mechanisms of Ciliates to Salinity Change with Note on Fluctuation Properties.

The adaptability of marine organisms to changes in salinity has been a significant research area under global climate change. However, the underlying mechanisms of this adaptability remain a debated subject. We hypothesize that neglecting salinity fluctuation properties is a key contributing factor to the controversy. The ciliate Euplotes vannus was used as the model organism, with two salinity fluctuation period sets: acute (24 h) and chronic (336 h). We examined its population growth dynamics and energy metabolism parameters following exposure to salinity levels from 15‱ to 50‱. The carrying capacity (K) decreased with increasing salinity under both acute and chronic stresses. The intrinsic growth rate (r) decreased with increasing salinity under acute stress. Under chronic stress, the r initially increased with stress intensity before decreasing when salinity exceeded 40‱. Overall, glycogen and lipid content decreased with stress increasing and were significantly higher in the acute stress set compared to the chronic one. Both hypotonic and hypertonic stresses enhanced the activities of metabolic enzymes. A trade-off between survival and reproduction was observed, prioritizing survival under acute stress. Under chronic stress, the weight on reproduction increased in significance. In conclusion, the tested ciliates adopted an r-strategy in response to salinity stress. The trade-off between reproduction and survival is a significant biological response mechanism varying with salinity fluctuation properties.

Composition and micromorphological determination of blue honeysuckle fruit (Lonicera caerulea L.) cuticular wax and its effects on fruit post-harvest quality

The chemical composition and structure of the cuticular wax in blue honeysuckle fruit were investigated using gas chromatography–mass spectrometry (GC–MS) and scanning electron microscopy (SEM). The results revealed that the cuticular wax was dense and uniform, taking on a tubular form. A total of 158 wax components were identified, including alkanes, terpenes, ketones, alcohols, fatty acids, and esters. The wax was found to be particularly rich in alkanes. After storage, the wax content decreased, whereas an increase in 1-undecanol. The destruction or reduction of cuticular wax resulted in a more rapid decline in storage quality, loss of nutrients, and a decrease in antioxidant phytochemicals. Meanwhile, wax metabolizing enzyme activity and gene expression increased. This study presents a deeper understanding of blue honeysuckle fruit cuticular wax composition and aids to developing effective measures to delay its postharvest fruit quality deterioration.

ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression.

Aberrant activation of IL-18 signaling regulates tumor immune evasion and progression. However, the underlying mechanism remains unclear. Here, we report that long-chain acyl-CoA synthase 6 (ACSL6) is highly expressed in liver cancer and correlated with poor prognosis. ACSL6 promotes tumor growth, metastasis, and immune evasion mediated by IL-18, independent of its metabolic enzyme activity. Mechanistically, upon IL-18 stimulation, ACSL6 is phosphorylated by ERK2 at S674 and recruits IL-18RAP to interact with IL-18R1, thereby reinforcing the IL-18R1-IL-18RAP heterodimer and triggering NF-κB-dependent gene expression to facilitate tumor development. Furthermore, the up-regulation of CXCL1 and CXCL5 by ACSL6 promotes tumor-associated neutrophil and tumor-associated macrophage recruitment, thereby inhibiting cytotoxic CD8+ T cell infiltration. Ablation or S674A mutation of ACSL6 potentiated anti-PD-1 therapeutic efficacy by increasing the effector activity of intertumoral CD8+ T cells. We revealed that ACSL6 is a potential adaptor that activates IL-18-NF-κB axis-mediated tumor immune evasion and provides valuable insights for developing effective immunotherapy strategies for cancer.

Identification of a highly efficient chloroplast-targeting peptide for plastid engineering.

Plastids are pivotal target organelles for comprehensively enhancing photosynthetic and metabolic traits in plants via plastid engineering. Plastidial proteins predominantly originate in the nucleus and must traverse membrane-bound multiprotein translocons to access these organelles. This import process is meticulously regulated by chloroplast-targeting peptides (cTPs). Whereas many cTPs have been employed to guide recombinantly expressed functional proteins to chloroplasts, there is a critical need for more efficient cTPs. Here, we performed a comprehensive exploration and comparative assessment of an advanced suite of cTPs exhibiting superior targeting capabilities. We employed a multifaceted approach encompassing computational prediction, in planta expression, fluorescence tracking, and in vitro chloroplast import studies to identify and analyze 88 cTPs associated with Arabidopsis thaliana mutants with phenotypes linked to chloroplast function. These polypeptides exhibited distinct abilities to transport green fluorescent protein (GFP) to various compartments within leaf cells, particularly chloroplasts. A highly efficient cTP derived from Arabidopsis plastid ribosomal protein L35 (At2g24090) displayed remarkable effectiveness in chloroplast localization. This cTP facilitated the activities of chloroplast-targeted RNA-processing proteins and metabolic enzymes within plastids. This cTP could serve as an ideal transit peptide for precisely targeting biomolecules to plastids, leading to advancements in plastid engineering.

The effects of all-trans retinoic acid on prednisolone-induced osteoporosis in zebrafish larvae

Glucocorticoids (GCs) are extensively used as anti-inflammatory and immunosuppressive medications in the long-term treatment of rheumatic disorders, respiratory diseases, renal diseases, and organ transplantation. Prolonged use of GCs can reduce bone mineral density, leading to osteoporosis (Glucocorticoid Induced Osteoporosis, GIOP) and fracture. All-trans retinoic acid (ATRA) is an active vitamin A metabolite that regulates embryonic development and adult organ function. ATRA has been found in studies to enhance osteogenesis. To examine the interventional effects of ATRA on GIOP and the mechanisms of ATRA activities, we first performed bioinformatic analysis to identify potential gene targets of ATRA. Zebrafish larvae were recruited as experimental animals, and the frequently used GC, prednisolone, was administered to larvae to construct a GIOP model. We evaluated the influence of exogenous ATRA on the activities of bone metabolic enzymes, the expression of genes linked to osteoblasts and osteoclasts, and the restoration of bone mineral density and bone mass in GIOP zebrafish larvae. Furthermore, we studied the influence of RBM14, a transcriptional coactivator and negative reciprocal factor of ATRA, on the regulation of osteoblastic gene expression during the anti-GIOP process of ATRA using the morpholino knockdown approach. The findings of bone metabolic enzyme activity (alkaline phosphatase, ALP and tartrate-resistant acid phosphatase, TRAP) and expression assays of osteoblastic marker genes (Runx2a, Runx2b, SP7, Csf1a, RANKL, and CTSK) indicated that ATRA had bidirectional effects on osteogenesis. However, in the GIOP model, ATRA reversed the GIOP-induced osteoporosis phenotype by inhibiting the GIOP-induced suppression of osteoblastic metabolic enzyme (ALP) activities and osteoblastic marker gene expression (Runx2a, Runx2b, and SP7), and this antagonism was concentration-dependent. We also observed that ATRA inhibited RBM14 expression in zebrafish larvae, while ATRA alone and RBM14 knockdown showed a consistent induction of osteoblast marker gene expression, implying that ATRA's inhibitory effect on RBM14 expression may underlie ATRA's osteogenic effects. Based on these data, we postulated that ATRA may ameliorate GIOP by decreasing RBM14 expression, thereby enhancing osteoblastic marker gene expression.

E-waste: a global threat with an impact on nutrition

Introduction: The generation and increase of electronic waste (e-waste) represents a focus of attention in the biomedical area due to the devastating impact on health. The importance and study ranges from toxicological understanding in adults to teratological effects in neonates. Studies have shown that e-waste affects the uptake of micronutrients, in addition to environmental contamination. Objective: To describe the main nutritional effects of e-waste in vulnerable populations. Methods: A retrospective descriptive model was performed following the PRISMA model, including manuscripts that were published since 2015. Results: Of the total number of articles identified, 21 articles were selected that met the established criteria. E-waste has a great impact on the environment by contaminating soil, food, vegetables, and air. Through these routes, children, pregnant women, and recyclers can acquire different toxic compounds. The main affectations described are alterations in iron metabolism and glycemic index, metabolic alterations, changes in the microbiota, affectation in the synthesis of antibodies and metabolic activity of reparative enzymes. Conclusions: Personnel in nutrition and related areas should understand the mechanism of action of e-waste, nutrient utilization, and the effect of metals and compounds derived from e-waste to avoid nutritional deficiencies

The effects of polypropylene microplastics on the removal of nitrogen and phosphorus from water by Acorus calamus, Iris tectorum and functional microorganisms

Polypropylene microplastics (PP-MPs), an emerging pollutant, adversely affect the ability of aquatic plants to restore water bodies, thereby compromising the functionality and integrity of wetland ecosystems. This study examines the effects of microplastic stress on the nitrogen and phosphorus removal capacities of Acorus calamus and Iris tectorum, as well as on functional microorganisms within the aquatic system. The findings indicate that under PP-MP stress, the nitrogen and phosphorus absorption capabilities of both plants were diminished. Additionally, there was a significant reduction in the metabolic enzyme activities related to nitrogen and phosphorus in the plants, alongside a notable decrease in leaf nitrogen content. PP-MPs hinder the nutrient uptake of plants, affecting their growth and indirectly reducing their ability to utilize nitrogen and phosphorus. Specifically, in the 10 mg L−1 treatment group, A. calamus and I. tectorum showed reductions in leaf nitrogen content by 23.1% and 31.0%, respectively, and by 14.8% and 27.7% in the 200 mg L−1 treatment group. Furthermore, I. tectorum had higher leaf nitrogen levels than A. calamus. Using fluorescent tagging, the distribution of PP-MPs was traced in the roots, stems, and leaves of the plants, revealing significant growth impairment in both species. This included a considerable decline in photosynthetic pigment synthesis, enhanced oxidative stress responses, and increased lipid peroxidation in cell membranes. PP-MP exposure also significantly reduced the abundance of functional microorganisms involved in denitrification and phosphorus removal at the genus level in aquatic systems. Ecological function predictions revealed a notable decrease in nitrogen cycling functions such as nitrogen respiration and nitrite denitrification among water microorganisms in both treatment groups, with a higher ecological risk potential in the A. calamus treatment group. This study provides new insights into the potential stress mechanisms of PP-MPs on aquatic plants involved in water body remediation and their impacts on wetland ecosystems.