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METTL3-mediated N6-methyladenosine (m6A) modification is critical for gametogenesis and early embryonic development. However, the function of METTL3-mediated m6A modification in the early development of somatic nuclear transfer embryos (SCNT) remains unclear. Here, we found that METTL3 mRNA and protein levels exhibit dynamic changes during the early development of porcine SCNT embryos. The levels of METTL3 mRNA and protein in SCNT embryos at specific developmental stages differ from those in parthenogenetic activation (PA) counterparts. SiRNA injection effectively reduced the levels of METTL3 mRNA and protein in 4-cell embryos and blastocysts. METTL3 knockdown significantly reduced the cleavage and blastocyst rates of SCNT embryos. METTL3 knockdown significantly reduced the number of total cells and trophectoderm (TE) cells in the resulting blastocysts and perturbed cell lineage allocation. In addition, METTL3 knockdown reduced the levels of m6A modification in 4-cell embryos and blastocysts. Importantly, METTL3 knockdown decreased the expression levels of CDX2, GATA3, NANOG and YAP, and increased the expression levels of SOX2 and OCT4. Taken together, these results demonstrate that METTL3-mediated m6A modification regulates early development and lineage differentiation of porcine SCNT embryos.
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Clonación de Organismos , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Metiltransferasas , Animales , Porcinos/embriología , Porcinos/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Clonación de Organismos/veterinaria , Clonación de Organismos/métodos , Técnicas de Transferencia Nuclear/veterinaria , Adenosina/análogos & derivados , Adenosina/metabolismo , Metilación , Técnicas de Silenciamiento del Gen , Blastocisto/metabolismo , Embrión de Mamíferos/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
The transition to a low-carbon economy emphasizes the importance of green and low-carbon consumption; yet, there is often a discrepancy between consumers' intentions and their actual behavior regarding organic foods. This study aims to identify strategies to bridge this gap. The research model of organic food consumption intention and behavior is constructed, and a structural equation model is used to test the research hypotheses based on a valid sample of 480 residents of Guangdong Province through an online questionnaire survey. Further, the intentionâbehavior gap is defined and its determinants are investigated through multiclass logistic regression. Finally, we categorize and forecast the alignment between consumption intentions and behaviors using machine learning algorithms. The results reveal that attitudes, social interactions, and cognitive information play crucial roles in aligning intentions with behaviors. By enhancing social information exchange or improving cognitive understanding, consumers can reduce their intentionâbehavior discrepancy. This research offers valuable policy recommendations for fostering green consumption among residents from various perspectives.
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In this study, the flavor characteristics and physicochemical properties of salted egg yolk (SEY) under different cooking methods (steaming/baking/microwaving) were investigated. The microwave-treated SEY exhibited the highest levels of salt content, cooking loss, lightness, and b* value, as well as the highest content of flavor amino acids. A total of 31, 27, and 29 volatile compounds were detected after steaming, baking, and microwave treatments, respectively, covering 10 chemical families. The partial least squares discriminant analysis confirmed that 21 compounds, including octanol, pyrazine, 2-pentyl-furan, and 1-octen-3-ol, were the key volatile compounds affecting the classification of SEY aroma. The electronic nose revealed a sharp distinction in the overall flavor profile of SEY with varying heat treatments. However, no dramatic differences were observed in terms of fatty acid composition. Microwave treatment was identified as presenting a promising approach for enhancing the aroma profile of SEY. These findings contribute novel insights into flavor evaluation and the development of egg products as ingredients for thermal processing.
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Visual object tracking often faces challenges such as invalid targets and decreased performance in low-light conditions when relying solely on RGB image sequences. While incorporating additional modalities like depth and infrared data has proven effective, existing multimodal imaging platforms are complex and lack real-world applicability. In contrast, near-infrared (NIR) imaging, commonly used in surveillance cameras, can switch between RGB and NIR based on light intensity. However, tracking objects across these heterogeneous modalities poses significant challenges, particularly due to the absence of modality switch signals during tracking. To address these challenges, we propose an adaptive cross-modal object tracking algorithm called modality-aware fusion network (MAFNet). MAFNet efficiently integrates information from both RGB and NIR modalities using an adaptive weighting mechanism, effectively bridging the appearance gap and enabling a modality-aware target representation. It consists of two key components: an adaptive weighting module and a modality-specific representation module. The adaptive weighting module predicts fusion weights to dynamically adjust the contribution of each modality, while the modality-specific representation module captures discriminative features specific to RGB and NIR modalities. MAFNet offers great flexibility as it can effortlessly integrate into diverse tracking frameworks. With its simplicity, effectiveness, and efficiency, MAFNet outperforms state-of-the-art methods in cross-modal object tracking. To validate the effectiveness of our algorithm and overcome the scarcity of data in this field, we introduce CMOTB, a comprehensive and extensive benchmark dataset for cross-modal object tracking. CMOTB consists of 61 categories and 1000 video sequences, comprising a total of over 799K frames. We believe that our proposed method and dataset offer a strong foundation for advancing cross-modal object-tracking research. The dataset, toolkit, experimental data, and source code will be publicly available at: https://github.com/mmic-lcl/ Datasets-and-benchmark-code.
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Hexafluoropropylene oxide trimer acid (HFPO-TA) has been found to cause hepatotoxicity, lipotoxicity, and cytotoxicity. However, the effects of HFPO-TA exposure on nervous system toxicity are still unclear. Here, six-week-old male C57BL/6J mice were treated with 2, 20, and 200 µg/L HFPO-TA for six weeks. The untargeted transcriptome analysis was employed to identify differentially expressed mRNAs in the tissue of mouse hippocampi. Then, the levels of neurotransmitters were detected by ELISA analysis in hippocampal and colonic tissues. Real-time quantitative PCR and western blotting analysis were performed to detect the expression of genes associated with modulation of serotonin (5-HT) metabolism and blood-brain barrier. HFPO-TA exposure reduced the mRNA and protein expression of several tight junction protein-coded genes, including Occludin, Claudin-1, and ZO-1, in mice hippocampi, indicating that the blood-brain barrier was disrupted. Moreover, HFPO-TA exposure elevated the expression of neuroinflammatory factors, including TNF-α, IL-6, IL-1ß, TGF-α, and TGF-ß. Analysis of hippocampal transcriptomics suggested that HFPO-TA exposure would impair 5-HT generation and metabolic pathways. In keeping with this prediction, our findings confirmed that the levels of several neurotransmitters, including tryptophan (TRP), 5-HT, 5-HTP, and 5-HIAA, were all impaired by HFPO-TA exposure in the serum, colon, and hippocampus, as was the colonic and hippocampal expression of TRP and 5-HT metabolism-related genes such as SERT, MAO-A, and IDO. These results suggest that HFPO-TA nervous system toxicity in mice may be partly modulated by the brain-gut axis and that HFPO-TA exposure may negatively impact human mental health.
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Eje Cerebro-Intestino , Hipocampo , Ratones Endogámicos C57BL , Serotonina , Animales , Ratones , Masculino , Serotonina/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Fluorocarburos/toxicidadRESUMEN
Wounds represent a grave affliction that profoundly impacts human well-being. Establishing barriers, preventing infections, and providing a conducive microenvironment constitute the crux of wound therapy. Hydrogel, a polymer with an intricate three-dimensional lattice, serves as a potent tool in erecting physical barriers and nurturing an environment conducive to wound healing. This enables effective control over exudation, hemostasis, accelerated wound closure, and diminished scar formation. As a result, hydrogels have gained extensive traction in the realm of wound treatment. Metallic nanoparticle carriers, characterized by their multifaceted responses encompassing acoustics, optics, and electronics, have demonstrated efficacy in wound management. Nevertheless, these carriers encounter challenges associated with swift clearance and nonuniform effectiveness. The hybridization of metallic nanoparticle carriers with hydrogels overcomes the shortcomings inherent in metallic nanoparticle-based wound therapy. This amalgamation not only addresses the limitations but also augments the mechanical robustness of hydrogels. It confers upon them attributes such as environmental responsiveness and multifunctionality, thereby synergizing strengths and compensating for weaknesses. This integration culminates in the precise and intelligent management of wounds. This review encapsulates the structural classifications, design strategies, therapeutic applications, and underlying mechanisms of metal nanoparticle hybrid hydrogels in the context of acute and chronic wound treatment. The discourse delves into the generation of novel or enhanced attributes arising from hybridization and how the current paradigm of wound therapy leverages these attributes. Amidst this continually evolving frontier, the potential of metal nanoparticle hybrid hydrogels to revolutionize wound treatment is underscored.
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Hidrogeles , Nanopartículas del Metal , Humanos , Hidrogeles/química , Cicatrización de Heridas , Nanopartículas del Metal/química , Polímeros/química , CicatrizRESUMEN
Recently, biomembrane nanostructures, such as liposomes, cell membrane-coated nanostructures, and exosomes, have demonstrated promising anticancer therapeutic effects. These nanostructures possess remarkable biocompatibility, multifunctionality, and low toxicity. However, their therapeutic efficacy is impeded by chemoresistance and radiotherapy resistance, which are closely associated with autophagy. Modulating autophagy could enhance the therapeutic sensitivity and effectiveness of these biomembrane nanostructures by influencing the immune system and the cancer microenvironment. For instance, autophagy can regulate the immunogenic cell death of cancer cells, antigen presentation of dendritic cells, and macrophage polarization, thereby activating the inflammatory response in the cancer microenvironment. Furthermore, combining autophagy-regulating drugs or genes with biomembrane nanostructures can exploit the targeting and long-term circulation properties of these nanostructures, leading to increased drug accumulation in cancer cells. This review explores the role of autophagy in carcinogenesis, cancer progression, metastasis, cancer immune responses, and resistance to treatment. Additionally, it highlights recent research advancements in the synergistic anticancer effects achieved through autophagy regulation by biomembrane nanostructures. The review also discusses the prospects and challenges associated with the future clinical translation of these innovative treatment strategies. In summary, these findings provide valuable insights into autophagy, autophagy-modulating biomembrane-based nanostructures, and the underlying molecular mechanisms, thereby facilitating the development of promising cancer therapeutics.
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Nanoestructuras , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Presentación de Antígeno , Autofagia , Membrana Celular , Microambiente TumoralRESUMEN
Circular RNAs (circRNAs) are special non-coding RNA (ncRNA) molecules that play a significant role in many diseases. However, the biogenesis and regulation of circRNAs in diabetic nephropathy (DN) are largely unknown. Here, we investigated the expression profile of circRNAs in kidney of DN mice through circular RNA sequencing (circRNA-seq). The renal biopsy samples of patients with DN had low circ -0,000,953 expression, which was significantly associated with renal function. Furthermore, loss-of-function and gain-of-function experiments were carried out to prove the role of circ -0,000,953 in DN. Podocyte conditional knockin (cKI) or systemic overexpression of circ -0,000,953 alleviated albuminuria and restored macroautophagy/autophagy in kidney of diabetic mice. However, circ -0,000,953 knockdown exacerbated albuminuria and podocyte injury. Mechanistically, we found circ -0,000,953 directly binds to Mir665-3p-Atg4b to perform its function. Silencing of Mir665-3p or overexpression of Atg4b recovered podocyte autophagy both in vitro and in vivo. To examine the cause of circ -0,000,953 downregulation in DN, bioinformatics prediction found that circ -0,000,953 sequence has a high possibility of containing an m6A methylation site. Additionally, METTL3 was proved to regulate the expression and methylation level of circ -0,000,953 through YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epithelial cells; MTOR: mechanistic target of rapamycin kinase; NC: normal control; ncRNA: non-coding RNA; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PAS: periodic acid-Schiff; RELA/p65: v-rel reticuloendotheliosis viral oncogene homolog A (avian); SDs: slit diaphragm proteins; Seq: sequencing; STZ: streptozotocin; SV40: SV40-MES13-cells, mouse mesangial cell line; T1D: type 1 diabetes mellitus; T2D: type 2 diabetes mellitus; TEM: transmission electron microscopy; TNF/TNF-α: tumor necrosis factor; VECs: vascular endothelial cells; WT1: WT1 transcription factor; YTHDF2: YTH N6-methyladenosine RNA binding protein 2.
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BACKGROUND: The alpine meadow is one of the most important ecosystems in the Qinghai-Tibet Plateau (QTP), and critically sensitive to climate change and human activities. Thus, it is crucial to precisely reveal the current state and predict future trends in the carbon budget of the alpine meadow ecosystem. The objective of this study was to explore the applicability of the Biome-BGC model (BBGC) in the Qinghai Lake Basin (QLB), identify the key parameters affecting the variation of net ecosystem exchange (NEE), and further predict the future trends in carbon budget in the QLB. RESULTS: The alpine meadow mainly acted as carbon sink during the growing season. For the eco-physiological factors, the YEL (Yearday to end litterfall), YSNG (Yearday to start new growth), CLEC (Canopy light extinction coefficient), FRC:LC (New fine root C: new leaf C), SLA (Canopy average specific leaf area), C:Nleaf (C:N of leaves), and FLNR (Fraction of leaf N in Rubisco) were confirmed to be the top seven parameters affecting carbon budget of the alpine meadow. For the meteorological factors, the sensitivity of NEE to precipitation was greater than that to vapor pressure deficit (VPD), and it was greater to radiation than to air temperature. Moreover, the combined effect of two different meteorological factors on NEE was higher than the individual effect of each one. In the future, warming and wetting would enhance the carbon sink capacity of the alpine meadow during the growing season, but extreme warming (over 3.84 â) would reduce NEE (about 2.9%) in the SSP5-8.5 scenario. CONCLUSION: Overall, the alpine meadow ecosystem in the QLB generally performs as a carbon sink at present and in the future. It is of great significance for the achievement of the goal of carbon neutrality and the management of alpine ecosystems.
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Background: Many investigations have revealed that alterations in m6A modification levels may be linked to coronary heart disease (CHD). However, the specific link between m6A alteration and CHD warrants further investigation. Methods: Gene expression profiles from the Gene Expression Omnibus (GEO) databases. We began by constructing a Random Forest model followed by a Nomogram model, both aimed at enhancing our predictive capabilities on specific m6A markers. We then shifted our focus to identify distinct molecular subtypes based on the key m6A regulators and to discern differentially expressed genes between the unique m6A clusters. Following this molecular exploration, we embarked on an in-depth analysis of the biological characteristics associated with each m6A cluster, revealing profound differences between them. Finally, we delved into the identification and correlation analysis of immune cell infiltration across these clusters, emphasizing the potential interplay between m6A modification and the immune system. Results: In this research, 37 important m6Aregulators were identified by comparing non-CHD and CHD patients from the GSE20680, GSE20681, and GSE71226 datasets. To predict the risk of CHD, seven candidate m6A regulators (CBLL1, HNRNPC, YTHDC2, YTHDF1, YTHDF2, YTHDF3, ZC3H13) were screened using the logistic regression model. Based on the seven possible m6A regulators, a nomogram model was constructed. An examination of decision curves revealed that CHD patients could benefit from the nomogram model. On the basis of the selected relevant m6A regulators, patients with CHD were separated into two m6A clusters (cluster1 and cluster2) using the consensus clustering approach. The Single Sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT methods were used to estimate the immunological characteristics of two separate m6A Gene Clusters; the results indicated a close association between seven candidate genes and immune cell composition. The drug sensitivity of seven candidate regulators was predicted, and these seven regulators appeared in numerous diseases as pharmacological targets while displaying strong drug sensitivity. Conclusion: m6A regulators play crucial roles in the development of CHD. Our research of m6A clusters may facilitate the development of novel molecular therapies and inform future immunotherapeutic methods for CHD.
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Cancer is the second leading cause of death worldwide. Its incidence has been increasing in recent years, and it is becoming a major threat to human health. Conventional cancer treatment strategies, including surgery, chemotherapy, and radiotherapy, have faced problems such as drug resistance, toxic side effects and unsatisfactory therapeutic efficacy. Therefore, better development and utilization of biomaterials can improve the specificity and efficacy of tumor therapy. Algae, as a novel living material, possesses good biocompatibility. Although some reviews have elucidated several algae-based biomaterials for cancer treatment, the majority of the literature has focused on a limited number of algae. As a result, there is currently a lack of comprehensive reviews on the subject of anticancer algae. This review aims to address this gap by conducting a thorough examination of algal species that show potential for anticancer activity. Furthermore, our review will also elucidate the engineering strategies of algae and discuss the challenges and prospects associated with their implementation.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Materiales BiocompatiblesRESUMEN
Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy and extracellular matrix accumulation in vivo and in vitro. These effects delayed CKD progression. Immunoprecipitation assays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.
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Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.
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Chemotherapeutic drugs have been found to activate the immune response against tumors by inducing immunogenic cell death, in addition to their direct cytotoxic effects toward tumors, therefore broadening the application of chemotherapy in tumor immunotherapy. The combination of other therapeutic strategies, such as phototherapy or radiotherapy, could further strengthen the therapeutic effects of immunotherapy. Nanostructures can facilitate multimodal tumor therapy by integrating various active agents and combining multiple types of therapeutics in a single nanostructure. Biomembrane nanostructures (e.g., exosomes and cell membrane-derived nanostructures), characterized by superior biocompatibility, intrinsic targeting ability, intelligent responsiveness and immune-modulating properties, could realize superior chemoimmunotherapy and represent next-generation nanostructures for tumor immunotherapy. This review summarizes recent advances in biomembrane nanostructures in tumor chemoimmunotherapy and highlights different types of engineering approaches and therapeutic mechanisms. A series of engineering strategies for combining different biomembrane nanostructures, including liposomes, exosomes, cell membranes and bacterial membranes, are summarized. The combination strategy can greatly enhance the targeting, intelligence and functionality of biomembrane nanostructures for chemoimmunotherapy, thereby serving as a stronger tumor therapeutic method. The challenges associated with the clinical translation of biomembrane nanostructures for chemoimmunotherapy and their future perspectives are also discussed.
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Antineoplásicos , Nanoestructuras , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Inmunoterapia , Nanoestructuras/química , Microambiente TumoralRESUMEN
Stem cell injection is an effective approach for treating diabetic wounds; however, shear stress during injections can negatively affect their stemness and cell growth. Cell-laden porous microspheres can provide shelter for bone mesenchymal stem cells (BMSC). Herein, curcumin-loaded flower-like porous microspheres (CFPM) are designed by combining phase inversion emulsification with thermally induced phase separation-guided four-arm poly (l-lactic acid) (B-PLLA). Notably, the CFPM shows a well-defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of -BMSC and curcumin. The BMSC-carrying CFPM (BMSC@CFPM) maintains the proliferation, retention, and stemness of -BMSCs, which, in combination with their sustainable curcumin release, facilitates the endogenous production of growth/proangiogenic factors and offers a local anti-inflammatory function. An in vivo bioluminescence assay demonstrates that BMSC@CFPM can significantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, could significantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction, and M2 macrophage polarization. RNA sequencing further unveils the mechanisms by which BMSC@CFPM promotes diabetic wound healing by increasing -growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing.
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Curcumina , Diabetes Mellitus , Humanos , Curcumina/farmacología , Microesferas , Polímeros/farmacología , Porosidad , Quinasas Janus/farmacología , Factores de Transcripción STAT/farmacología , Transducción de Señal , Cicatrización de Heridas , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Alpinia oxyphylla Fructus, called Yizhi in Chinese, is the dried fruit of Alpinia oxyphylla Miquel. It has been used in traditional Chinese medicine to treat dementia and memory defects of Alzheimer's disease for many years. However, the underlying mechanism is still unclear. In this study, we used a rat Alzheimer's disease model on intrahippocampal injection of aggregated Aß1-42 to study the effects of Alpinia oxyphylla Fructus. A brain and plasma dual-channel metabolomics approach combined with multivariate statistical analysis was further performed to determine the effects of Alpinia oxyphylla Fructus on Alzheimer's disease animals. As a result, in the Morris water maze test, Alpinia oxyphylla Fructus had a clear ability to ameliorate the impaired learning and memory of Alzheimer's disease rats. 11 differential biomarkers were detected in AD rats' brains. The compounds mainly included amino acids and phospholipids; after Alpinia oxyphylla Fructus administration, 9 regulated biomarkers were detected compared with the AD model group. In the plasma of AD rats, 29 differential biomarkers, primarily amino acids, phospholipids and fatty acids, were identified; After administration, 23 regulated biomarkers were detected. The metabolic pathways of regulated metabolites suggest that Alpinia oxyphylla Fructus ameliorates memory and learning deficits in AD rats principally by regulating amino acid metabolism, lipids metabolism, and energy metabolism. In conclusion, our results confirm and enhance our current understanding of the therapeutic effects of Alpinia oxyphylla Fructus on Alzheimer's disease. Meanwhile, our work provides new insight into the potential intervention mechanism of Alpinia oxyphylla Fructus for Alzheimer's disease treatment.
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Alpinia , Enfermedad de Alzheimer , Ratas , Animales , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Aprendizaje por Laberinto , Metabolómica , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Antibiotics present in the natural environment would induce the generation of antibiotic-resistant bacteria (ARB), causing great environmental risks. The effects of antibiotic resistance genes (ARGs) and antibiotics on bacterial transport/deposition in porous media yet are unclear. By using E. coli without ARGs as antibiotic-susceptible bacteria (ASB) and their corresponding isogenic mutants with ARGs in plasmids as ARB, the effects of ARGs and antibiotics on bacterial transport in porous media were examined under different conditions (1-4 m/d flow rates and 5-100 mM NaCl solutions). The transport behaviors of ARB were comparable with those of ASB under antibiotic-free conditions, indicating that ARGs present within cells had negligible influence on bacterial transport in antibiotic-free solutions. Interestingly, antibiotics (5-1000 µg/L gentamicin) present in solutions increased the transport of both ARB and ASB with more significant enhancement for ASB. This changed bacterial transport induced by antibiotics held true in solution with humic acid, in river water and groundwater samples. Antibiotics enhanced the transport of ARB and ASB in porous media via different mechanisms (ARB: competition of deposition sites; ASB: enhanced motility and chemotaxis effects). Clearly, since ASB are likely to escape sites containing antibiotics, these locations are more likely to accumulate ARB and their environmental risks would increase.
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Antibacterianos , Genes Bacterianos , Antibacterianos/farmacología , Porosidad , Escherichia coli/genética , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Bacterias/genética , Farmacorresistencia Microbiana/genéticaRESUMEN
Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.