Stabilizing High-Valence Copper(I) Sites with Cu-Ni Interfaces Enhances Electroreduction of CO2 to C2+ Products.

In this study, the copper-nickel (Cu-Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu-Ni, PIL-Cu and PIL-Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen-PIL@Ni(NO3)2 and Cu@Salen-PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu-Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen-PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC 2+) of 262.9 mA cm-2 at -0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen-PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm-2 at -0.78 V. Mechanistic studies indicates that the presence of Cu-Ni interfaces in Cu@Salen-PIL@Ni(NO3)2 accounts for the preserve of high-valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2-to-CO conversion and C-C coupling while inhibition of the competitive HER.

Identification of the cytochrome P450 gene AccCYP6A13 in Apis cerana cerana and its response to environmental stress.

Cytochrome P450 plays a crucial role in regulating insect growth, development, and resisting a variety of stresses. Insect metamorphosis and response to external stress are altered by deleting CYP450 genes. In this study, we identified and analyzed a novel gene of CYP450 family, AccCYP6A13, from Apis cerana cerana, and explored its role in the response of Apis cerana cerana to adverse external stressors. It was found that the expression of AccCYP6A13 was spatiotemporal specificity. The expression level increased with age and reached its highest value in the adult stage. The primarily expressiong location were legs, brain, and epidermis of honeybees. Stress conditions can affect the expression of AccCYP6A13 depending on treatment times. RNA interference experiments have shown that knocking down AccCYP6A13 reduces antioxidant activity and deactivates detoxification enzymes, resulting in oxidative damage accumulation and a decline in detoxification capability in bees, as well as inhibiting numerous antioxidant genes. Additionally, knockdown of the AccCYP6A13 gene in Apis cerana cerana resulted in increased sensitivity to pesticides and increased mortality when treated with neonicotinoid pesticides such as thiamethoxam. AccCYP6A13 overexpression in a prokaryotic system further confirmed its role in resistance to oxidative stress. To summarize, AccCYP6A13 may play an essential role in the normal development and response to environmental stress in Apis cerana cerana. Furthermore, this study contributed to the theoretical understanding of bee resistance biology.

Three methods to optimize polymyxin B dosing using estimated AUC after first dose: Validation with the data generated by Monte-Carlo simulation.

Objectives: To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Method: Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula. Sensitivity analysis was performed to examine the influence of each sampling time drifting on the estimated AUCSS,24h.Results: In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted. Three user-friendly and easy-to-use excel calculators were built based on these methods.Conclusions: Two-point PK approach may be sufficient to guide polymyxin B dosing in patients with normal renal function. For patients with renal insufficiency, three-point PK approach or four-point PK may be a better choice. The Excel calculators designed based on the three methods can be potentially used to optimize the dosing regimen of polymyxin B in the clinic.

Exploring the Link Between Exogenous Thyroid Hormones and Dementia Symptoms: A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System.

BACKGROUND: A growing body of evidence indicates a strong association between exogenous thyroid hormone (ETH) and brain health. Establishing the potential relationship between ETH therapy and dementia symptoms is crucial for patients with thyroid disorders. OBJECTIVE: In this study, we investigate the potential association between ETH therapy and dementia symptoms by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Disproportionality analysis (DPA) was conducted using postmarketing data from the FAERS repository (Q1 2004 to Q4 2023). Cases of dementia symptoms associated with ETH therapy were identified and analyzed through DPA using reporting odds ratios and information component methods. Dose and time-to-onset analyses were performed to assess the association between ETH therapy and dementia symptoms. RESULTS: A total of 9889 cases of ETH-associated symptoms were identified in the FAERS database. Dementia accounted for a consistent proportion of adverse drug reactions each year (3.4%-6.3%). The DPA indicated an association between ETH therapy and dementia symptoms, which remained significant even across sex, age, and indications. The median time-to-onset of dementia symptoms was 7.5 days, and the median treatment time was 40.5 days. No significant dose-response relationship was observed. CONCLUSION AND RELEVANCE: This study provides evidence for a link between ETH therapy and dementia. Clinicians are therefore advised to exercise vigilance, conduct comprehensive monitoring, and consider individualized dosing to mitigate potential reactions to ETH drug administration.

Formulation of arginine-loaded mesoporous silica nanoparticles (Arg@MSNs) modified orthodontic adhesive.

OBJECTIVES: The objective of this study was to synthesize arginine loaded mesoporous silica nanoparticles (Arg@MSNs), develop a novel orthodontic adhesive using Arg@MSNs as modifiers, and investigate the adhesive performance, antibacterial activity, and biocompatibility. METHODS: Arg@MSNs were synthesized by immobilizing arginine into MSNs and characterized using transmission electron microscope (TEM), dynamic light scattering (DLS), and Fourier Transform Infrared Spectrometer (FT-IR). Arg@MSNs were incorporated into Transbond XT adhesive with different mass fraction to form functional adhesives. The degree of conversion (DC), arginine release behavior, adhesive performance, antibacterial activity against Streptococcus mutans biofilm, and cytotoxicity were comprehensively evaluated. RESULTS: TEM, DLS, and FT-IR characterizations confirmed the successful preparation of Arg@MSNs. The incorporation of Arg@MSNs did not significantly affect DC and exhibited clinically acceptable bonding strength. Compared to the commercial control, the Arg@MSNs modified adhesives greatly suppressed the metabolic activity and polysaccharide production while increased the biofilm pH values. The cell counting kit (CCK)-8 test indicated no cytotoxicity. CONCLUSIONS: The novel orthodontic adhesive containing Arg@MSNs exhibited significantly enhanced antibacterial activities and inhibitory effects on acid production compared to the commercial adhesive without compromising their bonding strength or biocompatibility. CLINICAL SIGNIFICANCE: The novel orthodontic adhesive containing Arg@MSNs exhibits potential clinical benefits in preventing demineralization of enamel surfaces around or beneath orthodontic brackets due to its enhanced antibacterial activities and acid-producing inhibitory effects.

Effects of abamectin nanocapsules on bees through host physiology, immune function, and gut microbiome.

Pesticide usage is a common practice to increase crop yields. Nevertheless, the existence of pesticide residues in the surrounding environment presents a significant hazard to pollinators, specifically the potential undisclosed dangers related to emerging nanopesticides. This study examines the impact of abamectin nanocapsules (AbaNCs), created through electrostatic self-assembly, as an insecticide on honey bees. It was determined that AbaNCs upregulated detoxification genes, including CYP450, as well as antioxidant and immune genes in honey bees. Furthermore, AbaNCs affected the activity of crucial enzymes such as superoxide dismutase (SOD). Although no apparent damage was observed in bee gut tissue, AbaNCs significantly decreased digestive enzyme activity. Microbiome sequencing revealed that AbaNCs disrupted gut microbiome, resulting in a reduction of beneficial bacteria such as Bifidobacterium and Lactobacillus. Additionally, these changes in the gut microbiome were associated with decreased activity of digestive enzymes, including lipase. This study enhances our understanding of the impact of nanopesticides on pollinating insects. Through the revelation of the consequences arising from the utilization of abamectin nanocapsules, we have identified potential stress factors faced by these pollinators, enabling the implementation of improved protective measures.

Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling.

Queen and worker bees are natural models for aging research, as their lifespans vary considerably independent of genetic variation. Investigating the reasons why queens live longer than workers is of great significance for research on the universal processes of aging in animals. The gut microbiome has received attention as a vital regulator of host health, while its precise role in honeybee aging needs further investigation. The effects and mechanisms behind the relationship between gut microbiota and worker lifespan were measured by transplanting queen bee gut bacteria (QG) and worker bee gut bacteria (WG) into microbiota-free (MF) workers. The transplantation of QG to MF bees significantly extended the workers' lifespans compared with MF and WG bees. Untargeted metabolomics identified 49 lifespan-related differential metabolites, and Kyoto Encyclopedia of Genes and Genomes analysis of these revealed three lifespan-related metabolic pathways: insulin/insulin-like growth factor signaling, immune, and ketone body metabolism pathways. Further verification showed that QG inhibited the expression of insulin-like peptides (ILPs), and the expression of ILPs was lower in natural queens than in natural workers. QG transplantation also stimulated the expression of antioxidant genes and lowered oxidative damage products in natural queen bees. However, gut microbiota transplantation failed to mimic the immune properties and ketone body metabolism profiles of natural queens and workers. Concisely, QG could increase the antioxidant capacity to extend lifespan by inhibiting insulin signaling. These findings may help determine the mechanisms behind queen longevity and provide further insights into the role of gut symbionts. IMPORTANCE: Queen and worker bees share the same genetic background but have vastly different lifespans. The gut microbiome regulates host health, suggesting that differences in lifespan between queen and worker bees could be related to gut bacteria. Herein, we used an innovative method to transplant gut microbiota from adult queen or worker bees to microbiota-free bees. The transplantation of queen gut microbiota to microbiota-free bees extended their lifespan. Insulin/insulin-like growth factor signaling, a highly conserved metabolic pathway related to lifespan, displayed identical expression profiles in natural queen bees and microbiota-free bees transplanted with queen microbiota. This finding significantly expands our understanding of the relationships between intestinal bacteria, host health, and the biology of aging.

Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database.

BACKGROUND: Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) is crucial for public safety. This study investigated the potential association between GLP-1RAs and SSIBs by exploring the FDA Adverse Event Reporting System (FAERS) database. METHODS: A disproportionality analysis was conducted using post-marketing data from the FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with GLP-1RAs were identified and analyzed through disproportionality analysis using the information component. The parametric distribution with a goodness-of-fit test was employed to analyze the time-to-onset, and the Ω shrinkage was used to evaluate the potential effect of co-medication on the occurrence of SSIBs. RESULTS: In total, 204 cases of SSIBs associated with GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, and albiglutide, were identified in the FAERS database. Time-of-onset analysis revealed no consistent mechanism for the latency of SSIBs in patients receiving GLP-1RAs. The disproportionality analysis did not indicate an association between GLP-1RAs and SSIBs. Co-medication analysis revealed 81 cases with antidepressants, antipsychotics, and benzodiazepines, which may be proxies of mental health comorbidities. CONCLUSIONS: We found no signal of disproportionate reporting of an association between GLP-1RA use and SSIBs. Clinicians need to maintain heightened vigilance on patients premedicated with neuropsychotropic drugs. This contributes to the greater acceptance of GLP-1RAs in patients with type 2 diabetes mellitus or obesity.

Isolation of the AccCDK8 gene of Apis cerana cerana and its functional analysis under pesticide and heavy metal stress.

Environmental pollution has gained negative attention in recent years. The pesticides and heavy metals are top list of environmental toxicants directly endangering the survival and development of Apis cerana cerana. Cyclin-dependent kinases (CDKs) are heteromeric serine/threonine kinases that participate in cell cycle regulation and have a vital role in pesticide and heavy metal stress in Apis cerana cerana. In this experiment, we filtered out CDK8 gene from Apis cerana cerana (AccCDK8) and investigated its functions of pesticide and heavy metals resistance. Sequence analysis indicated that AccCDK8 is highly homologous to multiple CDK8s and contains a highly conserved CDK active site sequence. Phylogenetic analysis showed that AmCDK8 and AccCDK8 were closely related evolutionarily in Apis mellifera. Transcriptome analysis revealed that AccCDK8 expression was differentially affected after exposure to pesticide and heavy metal stresses. This indicates that AccCDK8 has a significant role in the resistance of Apis cerana cerana to pesticide and heavy metal stresses. It has implications for studying the function of CDK in other insects in response to stress.

Limited Sampling Strategies for Estimating Busulfan Area Under the Concentration-Time Curve: Based on Peak and Trough Concentrations in Saliva.

Therapeutic drug monitoring for busulfan is currently performed by multiple plasma sampling. Saliva is considered a noninvasive therapeutic drug monitoring matrix. This study aimed to investigate intravenous busulfan pharmacokinetics (PK) in plasma and saliva, and establish a limited sampling strategy (LSS) for predicting the area under the concentration-time curve from time zero to infinity in plasma (AUC0-∞,p) by using saliva samples. Therefore, the PK of busulfan was studied in 37 Chinese patients. Pearson correlation analysis was used to evaluate the correlation between the AUC of busulfan in plasma and saliva. LSS models were established by the multiple linear regression analysis. The prediction error, the mean prediction error, and the root mean square error were used to evaluate the predictive accuracy. The agreement between the predicted and observed AUC0-∞ in saliva was investigated by the intraclass correlation coefficient and Bland-Altman analysis. The accuracy and robustness of the models were evaluated by using the bootstrap procedure. The result of PK analysis 62.2% of patients (23/37) was within the target range of AUC0-∞,p . A good correlation between saliva and plasma busulfan AUC0-∞ was observed (r = 0.63, p < .01). The bias and precision of the models 7 and 13 were less than 15%. The intraclass correlation coefficient exceeded 0.9, and the limits of agreement were within ±15%. The 2-point LSS model in saliva is a convenient and desirable approach to predict the AUC0-∞ of 4 times daily intravenous busulfan in plasma, which can be used to design personalized dosing for busulfan.

Preparation of arginine-loaded mesoporous silica nanoparticles (Arg@MSNs) to improve the mechanical and antibacterial properties of denture base resin.

STATEMENT OF PROBLEM: Whether the incorporation of arginine-loaded mesoporous silica nanoparticles (Arg@MSNs) into denture base resin can improve the mechanical and antibacterial properties is unclear. PURPOSE: The purpose of this in vitro study was to synthesis Arg@MSNs and explore how Arg@MSNs incorporation affects the mechanical and antibacterial properties of denture base resin. MATERIAL AND METHODS: Arg@MSNs were synthesized via a sol-gel process and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray diffraction (XRD). The prepared Arg@MSNs at different weight ratio concentrations were added into denture base resin as the experimental group, and unmodified denture base resin was the control. The fracture surface and arginine release behavior of each specimen were detected using scanning electron microscopy (SEM) and ultra-high-performance liquid chromatography-tandem mass spectrometer (UHPLC-HESI-MS/MS), respectively. Three-point bend tests were applied using a universal testing machine for evaluation of the mechanical properties of each group (n=5). Antibacterial efficiency (n=3) was evaluated by both quantitative and qualitative analysis using Streptococcus mutans. The cytotoxic effect of the Arg@MSN-modified denture base resin was investigated using a cell counting kit (CCK)-8 test. Data were subjected to 1-way analysis of variance followed by the post hoc Tukey honestly significant difference test (ɑ=.05). RESULTS: The prepared Arg@MSNs had good monodispersity and spherical morphology. Arg@MSN concentration at 0.5 wt%, 1 wt%, and 2.5 wt% resulted in enhanced mechanical properties, while those at 5 wt% were adversely impacted. Biofilm pH values increased with the incorporation of Arg@MSNs, and the antibacterial performance was improved. The CCK-8 test revealed that all formulations were not cytotoxic. CONCLUSIONS: The addition of Arg@MSNs into denture base resin can enhance its mechanical properties and improve its antibacterial performance without any apparent cytotoxic effect.

Toxic effects of the heavy metal Cd on Apis cerana cerana (Hymenoptera: Apidae): Oxidative stress, immune disorders and disturbance of gut microbiota.

Cadmium (Cd) is a toxic non-essential metal element that can enter the honey bee body through air, water and soil. Currently, there is a lack of sufficient research on the effects of Cd on A. cerana cerana, especially the potential risks of long-term exposure to sublethal concentrations. In order to ascertain the toxicological effects of the heavy metal Cd on bees, we performed laboratory-based toxicity experiments on worker bees and conducted analyses from three distinctive facets: antioxidative, immunological, and gut microbiota. The results showed that exposure of bees to high concentrations of Cd resulted in acute mortality, and the increase in mortality was concentration dependent. In long-term exposure to sublethal concentrations, Cd reduced the number of transcripts of antioxidant genes (AccSOD1, AccTPx3 and AccTPx4) and superoxide dismutase activity, causing an increase in malondialdehyde content. Simultaneously, the transcription of immune-related genes (AccAbaecin and AccApidaecin) and acetylcholinesterase activities was inhibited. Furthermore, Cd changes the structural characteristics of bacterial and fungal communities in the gut, disrupting the balance of microbial communities. In conclusion, the health and survival of honey bees are affected by Cd. This study provides a scientific basis for investigating the toxicological mechanisms and control strategies of the heavy metal Cd on honey bees, while facilitating a better understanding and protection of these valuable honey bees.

The gene AccCyclin H mitigates oxidative stress by influencing trehalose metabolism in Apis cerana cerana.

BACKGROUND: Environmental stress can induce oxidative stress in Apis cerana cerana, leading to cellular oxidative damage, reduced vitality, and even death. Currently, owing to an incomplete understanding of the molecular mechanisms by which A. cerana cerana resists oxidative damage, there is no available method to mitigate the risk of this type of damage. Cyclin plays an important role in cell stress resistance. The aim of this study was to explore the in vivo protection of cyclin H against oxidative damage induced by abiotic stress in A. cerana cerana and clarify the mechanism of action. We isolated and identified the AccCyclin H gene in A. cerana cerana and analysed its responses to different exogenous stresses. RESULTS: The results showed that different oxidative stressors can induce or inhibit the expression of AccCyclin H. After RNA-interference-mediated AccCyclin H silencing, the activity of antioxidant-related genes and related enzymes was inhibited, and trehalose metabolism was reduced. AccCyclin H gene silencing reduced A. cerana cerana high-temperature tolerance. Exogenous trehalose supplementation enhanced the total antioxidant capacity of A. cerana cerana, reduced the accumulation of oxidants, and improved the viability of A. cerana cerana under high-temperature stress. CONCLUSION: Our findings suggest that trehalose can alleviate adverse stress and that AccCyclin H may participate in oxidative stress reactions by regulating trehalose metabolism. © 2023 Society of Chemical Industry.

Deciphering the interplay between LPS/TLR4 pathways, neurotransmitter, and deltamethrin-induced depressive-like behavior: Perspectives from the gut-brain axis.

The improper use of deltamethrin (DM) can result in its accumulation in soil, water, food, and even the human body, which is associated with an elevated risk of neurotoxicity and behavioral abnormalities; however, the underlying mechanisms remain insufficiently investigated. Emerging evidence underscores the significance of the gut-brain axis in central nervous system (CNS) dysfunctions. Accordingly, this study investigates the role of the gut-brain axis in DM-induced behavioral anomalies in mice. The results showed that DM exposure induced depressive-like behavior, and the hippocampus, the region that is responsible for the modulation of emotional behavior, showed structural integrity disrupted (neuronal nuclear shrinkage and decreased tight junction protein expression). In addition, DM exposure led to compromised gut barrier integrity (disruptions on crypt surfaces and decreased tight junction protein expression), which might contribute to the gut bacterial-derived lipopolysaccharide (LPS) leakage into the bloodstream and reaching the brain, triggering LPS/toll-like receptor (TLR) 4 -mediated increases in brain pro-inflammatory cytokines. Subsequently, we observed a disturbance in neurotransmitter metabolic pathways following DM exposure, which inhibited the production of 5-hydroxytryptamine (5-HT). Additionally, DM exposure resulted in gut microbiota dysbiosis. Characteristic bacteria, such as Alistipes, Bifidobacterium, Gram-negative bacterium cTPY-13, and Odoribacter exhibited significant correlations with behavior, tight junction proteins, inflammatory response, and neurotransmitters. Further fecal microbiota transplantation (FMT) experiments suggested that DM-induced gut microbiota dysbiosis might contribute to depressive-like behavior. These results provide a new perspective on the toxicity mechanism of DM, indicating that its neurotoxicity may be partially regulated by the microbiota-gut-brain axis.

Bee wisdom: exploring bee control strategies for food microflora by comparing the physicochemical characteristics and microbial composition of beebread.

IMPORTANCE: Bees are a valuable model for investigating the relationship between environmental factors, gut microbiota, and organismal health. Beebread, produced from collected pollen, is a natural food source and a primary reservoir of gut microorganisms. Although pollen typically has diverse bacterial species, beebread has low species richness and bacterial abundance. Consequently, considerable attention has been paid to the adaptive strategies employed by honey bees to cope with the microorganisms within their food environment during co-evolution with plants. This study identified the distribution patterns of beebread's physicochemical characteristics, showing how bees use fermentation to enrich specific microbes. These findings help understand the relationship between environmental and food-associated microbes and bee intestinal microbiota. They also bridge gaps in the literature and provide a valuable reference for studying the complex interplay between these factors.

Functional analysis of AccCDK2-like and AccCINP-like genes in Apis cerana cerana under pesticide and heavy metal stress.

Heavy metals and pesticides represent prominent sources of pollution in the natural habitat of Apis cerana cerana, potentially endangering their health through the induction of oxidative stress reactions. This study aimed to address this issue by isolating AccCDK2-like and AccCINP-like proteins from Apis cerana cerana and investigating their functional roles in honey bee resistance against pesticide and heavy metal stresses. Bioinformatics analysis revealed significant homology of these proteins with those found in other species. Functional studies confirmed their participation in interaction with each other, alongside demonstrating distinct patterns of expression and localization. Specifically, AccCDK2-like exhibited higher expression levels in prepupae and muscle tissues, while AccCINP-like showed maximal expression in brown pupae and abdomen. Furthermore, the expression levels of these proteins were found to be modulated in response to pesticide and heavy metal stresses. Notably, overexpression of AccCDK2-like and AccCINP-like led to a noticeable alteration in E. coli's ability to withstand external stresses. Additionally, silencing of the AccCDK2-like and AccCINP-like genes resulted in a significant reduction in antioxidant enzyme activity and the expression levels of genes related to antioxidant function. Consequently, the mortality rate of Apis cerana cerana under pesticide and heavy metal stresses conspicuously increased. Hence, our findings suggest that AccCDK2-like and AccCINP-like proteins potentially play a crucial role in the response of Apis cerana cerana to pesticide and heavy metal stress, likely by modulating the antioxidant pathway.

Oleic Acid Promotes the Biosynthesis of 10-Hydroxy-2-decenoic Acid via Species-Selective Remodeling of TAGs in Apis mellifera ligustica.

This study aimed to assess the impact of oleic acid (OA) supplementation on the biosynthesis of 10-hydroxy-2-decenoic acid (10-HDA) in Apis mellifera ligustica. In experiment 1, varying concentrations of OA (2%, 4%, 6% and 8%) were added to an artificial diet for newly emerged bees reared in cages. Analysis of 10-HDA content and gene expression in the mandibular gland (MG) revealed that the 8% OA treatment had the greatest impact on promoting the synthesis of 10-HDA. Subsequent investigations utilized RNA-seq and lipidomics to characterize the molecular signature in the MG after feeding the 8% OA diet. Phosphatidylcholine (PC) and triacylglycerol (TAG) were found to be the predominant lipids in the MG of worker bees. A total of 154 TAGs were identified, with TAG (18:1-18:1-18:1) exhibiting the highest abundance, which increased by 1.5 times. The major TAG species contained palmitic acid (16:0) and oleic acid (18:1) in their structure, which was associated with fatty acid composition of diet. The increase in abundance of main TAGs may be attributed to the upregulation of glycerol-3-phosphate acyltransferase (Gpat) and glycerol kinase (GK) gene expression at the transcriptional level. The upregulation of differentially expressed genes (DEGs) related to carbohydrate metabolism may contribute to meeting the heightened metabolic demands of the MGs in worker bees. Royal jelly (RJ) samples from bee colonies fed with the 8% OA diet exhibited higher 10-HDA level than RJ collected from bee colonies fed with the artificial diet. These results indicate that 8% OA addition in the diet enhanced biosynthesis of 10-HDA in the mandibular gland, which was accompanied by significant and highly species-selective remodeling of TAGs.

Ame-miR-980-3p participates in autophagy-mediated midgut remodelling in Apis mellifera via targeting Atg2B.

Autophagy is a process that serves to degrade damaged proteins and organelles, thereby promoting cell homeostasis, differentiation, development and survival. Many miRNAs have been found to have regulatory roles in autophagy. In insects, it has been shown that autophagy is involved in hormone-regulated programmed cell death during metamorphic midgut remodelling. However, whether this is also true during the remodelling of the honey bee midgut is unclear. In the present study, we explored the relationship between autophagy and midgut remodelling and sought to identify miRNAs involved in this physiological process. We found that autophagy occurred during midgut remodelling and that the inhibition of autophagy resulted in midgut dysplasia in prepupae. Differentially expressed miRNAs enriched in the autophagy signalling pathway during midgut remodelling were identified by small RNA-seq. Ame-miR-980-3p, which targets the autophagy-related gene Atg2B, was screened out. Furthermore, abnormal expression of ame-miR-980-3p in the pupal stage led to the thinning of the midgut wall of newly emerged bees (NE). When ame-miR-980-3p expression was inhibited, the intestinal villi of NE bees became significantly shorter and sparse, and the lipid signal in the peritrophic matrix of Pb almost disappeared, indicating that the adult midgut was underdeveloped and the lipid absorption ability was weakened. Taken together, ame-miR-980-3p targeted Atg2B to participate in the regulation of midgut autophagy in the pupae, and the abnormal expression of ame-miR-980-3p would interfere with cell proliferation and death in the process of midgut remodelling, hinder the formation of adult midgut and eventually lead to adult midgut dysplasia and affect the lipid absorption function of the midgut in Apis mellifera.

Effects of Sucrose Feeding on the Quality of Royal Jelly Produced by Honeybee Apis mellifera L.

Royal jelly (RJ) is a highly nutritious secretion of the honeybees' hypopharyngeal glands (HPGs). During RJ production, colonies are occasionally subjected to manual interventions, such as sucrose feeding for energy supplementation. This study aimed to assess the impact of sucrose feeding on the composition of RJ. The results indicated that RJ obtained from sucrose-fed colonies exhibited significantly higher levels of fructose, alanine, glycine, tyrosine, valine, and isoleucine compared to the honey-fed group. However, no significant differences were observed in terms of moisture content, crude protein, 10-HDA, glucose, sucrose, minerals, or other amino acids within the RJ samples. Moreover, sucrose feeding did not have a significant effect on midgut sucrase activity, HPGs development, or the expression levels of MRJP1 and MRJP3 in nurse bees. Unsealed stored food samples from sucrose-fed bee colonies demonstrated significantly higher sucrose levels compared to sealed combs and natural honey. Additionally, natural honey exhibited higher moisture and Ca levels, as well as lower levels of Zn and Cu, in comparison to honey collected from bee colonies fed sucrose solutions. Based on these findings, we conclude that sucrose feeding has only a minor impact on the major components of RJ.