In this study, the effects of naringin on hepatic yolk precursors formation and antioxidant capacity of Three-Yellow breeder hens during late laying period were evaluated. A total of 480 (54-wk-old) ...Three-Yellow breeder hens were randomly assigned to 4 groups (6 replicates of 20 hens): nonsupplemented control diet (C), and control diet supplemented with 0.1%, 0.2%, and 0.4% of naringin (N1, N2, and N3), respectively. Results showed that dietary supplemented with 0.1%, 0.2%, and 0.4% of naringin for 8 wk promoted the cell proliferation and attenuated the excessive fat accumulation in the liver. Compared with C group, increased concentrations of triglyceride (TG), total cholesterol (T-CHO), high-density lipoprotein cholesterol (HDL-C), and very low-density lipoprotein (VLDL), and decreased contents of low-density lipoprotein cholesterol (LDL-C) were detected in liver, serum and ovarian tissues (P < 0.05). After 8 wk of feeding with naringin (0.1%, 0.2%, and 0.4%), serum estrogen (E2) level, expression levels of proteins and genes of estrogen receptors (ERs) increased significantly (P < 0.05). Meanwhile, naringin treatment regulated expression of genes related to yolk precursors formation (P < 0.05). Furthermore, dietary naringin addition increased the antioxidants, decreased the oxidation products, and up-regulated transcription levels of antioxidant genes in liver tissues (P < 0.05). These results indicated that dietary supplemented with naringin could improve hepatic yolk precursors formation and hepatic antioxidant capacity of Three-Yellow breeder hens during the late laying period. Doses of 0.2% and 0.4% are more effective than dose of 0.1%.
Influenza virus infection poses a great threat to human health globally each year. Non-coding RNAs (ncRNAs) in the human genome have been reported to participate in the replication process of the ...influenza virus, among which there are still many unknowns about Long Intergenic Non-Coding RNAs (LincRNAs) in the cell cycle of viral infections. Here, we observed an increased expression of Linc01615 in A549 cells upon influenza virus PR8 infection, accompanied by the successful activation of the intracellular immune system. The knockdown of Linc01615 using the shRNAs promoted the proliferation of the influenza A virus, and the intracellular immune system was inhibited, in which the expressions of IFN-β, IL-28A, IL-29, ISG-15, MX1, and MX2 were decreased. Predictions from the catRAPID website suggested a potential interaction between Linc01615 and DHX9. Also, knocking down Linc01615 promoted influenza virus proliferation. The subsequent transcriptome sequencing results indicated a decrease in Linc01615 expression after influenza virus infection when DHX9 was knocked down. Further analysis through cross-linking immunoprecipitation and high-throughput sequencing (CLIP-seq) in HEK293 cells stably expressing DHX9 confirmed the interaction between DHX9 and Linc01615. We speculate that DHX9 may interact with Linc01615 to partake in influenza virus replication and that Linc01615 helps to activate the intracellular immune system. These findings suggest a deeper connection between DHX9 and Linc01615, which highlights the significant role of Linc01615 in the influenza virus replication process. This research provides valuable insights into understanding influenza virus replication and offers new targets for preventing influenza virus infections.
In this study, the effects of 3 graded dietary levels (0.1%, 0.2%, and 0.4%) of naringin were studied in Three-Yellow breeder hens during the late laying period (55–62 wk). A total of 480 ...Three-Yellow breeder hens (54-wk-old) were randomly divided into 4 groups (6 replicates of 20 hens): basal diet group (C), and basal diets supplemented with 0.1%, 0.2%, and 0.4% of naringin (N1, N2, and N3), respectively. Results showed that dietary supplementation with 0.1%, 0.2%, and 0.4% of naringin for 8 wk increased the laying rate and egg mass, enhanced egg yolk color, and decreased the feed egg ratio (P < 0.05). Meanwhile, compared with hens in C group, there were more preovulatory follicles and higher ovarian index as well as an enhanced ovarian somatic cell proliferation in hens of N2 and N3 groups (P < 0.05). With 0.2% and 0.4% naringin, glutathione concentration, the activity of catalase and total superoxide dismutase, and the total antioxidant capacity of ovarian tissues and serum increased (P < 0.05), while the contents of malondialdehyde and hydrogen peroxide decreased (P < 0.05). Moreover, compared to C group, the transcription levels of antioxidant genes in ovarian tissues increased in hens from N2 and N3 groups (P < 0.05). In conclusion, supplementation with 0.2% and 0.4% naringin both could improve the laying rate, ovarian and serum antioxidant capacity of Three-Yellow breeder hens during the late laying period.
Abnormal placental development is a significant factor contributing to perinatal morbidity and mortality, affecting approximately 5-7% of pregnant women. Trophoblast syncytialization plays a pivotal ...role in the establishment and maturation of the placenta, and its dysregulation is closely associated with several pregnancy-related disorders, including preeclampsia and intrauterine growth restriction. However, the underlying mechanisms and genetic determinants of syncytialization are largely unknown.
We conducted a systematic drug screen using an epigenetic compound library to systematically investigate the epigenetic mechanism essential for syncytialization, and identified mixed lineage leukemia 1 (MLL1), a histone 3 lysine 4 methyltransferase, as a crucial regulator of trophoblast syncytialization. BeWo cells were utilized to investigate the role of MLL1 during trophoblast syncytialization. RNA sequencing and CUT&Tag were further performed to search for potential target genes and the molecular pathways involved. Human placenta tissue was used to investigate the role of MLL1 in TEA domain transcription factor 4 (TEAD4) expression and the upstream signaling during syncytialization. A mouse model was used to examine whether inhibition of MLL1-mediated H3K4me3 regulated placental TEAD4 expression and fetoplacental growth.
Genetic knockdown of MLL1 or pharmacological inhibition of the MLL1 methyltransferase complex (by MI-3454) markedly enhanced syncytialization, while overexpression of MLL1 inhibited forskolin (FSK)-induced syncytiotrophoblast formation. In human placental villous tissue, MLL1 was predominantly localized in the nuclei of cytotrophoblasts. Moreover, a notable upregulation in MLL1 expression was observed in the villus tissue of patients with preeclampsia compared with that in the control group. Based on RNA sequencing and CUT&Tag analyses, depletion of MLL1 inhibited the Hippo signaling pathway by suppressing TEAD4 expression by modulating H3K4me3 levels on the TEAD4 promoter region. TEAD4 overexpression significantly reversed the FSK-induced or MLL1 silencing-mediated trophoblast syncytialization. Additionally, decreased hypoxia-inducible factor 1A (HIF1A) enrichment at the MLL1 promoter was observed during syncytialization. Under hypoxic conditions, HIF1A could bind to and upregulate MLL1, leading to the activation of the MLL1/TEAD4 axis. In vivo studies demonstrated that the administration of MI-3454 significantly enhanced fetal vessel development and increased the thickness of the syncytial layer, thereby supporting fetoplacental growth.
These results revealed a novel epigenetic mechanism underlying the progression of syncytialization with MLL1, and suggest potential avenues for identifying new therapeutic targets for pregnancy-related disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ciprofol is a novel intravenous sedative and anesthetic. Studies have shown that it features a rapid onset of action, a fast recovery time, slight inhibition of respiratory and cardiovascular ...functions, and a low incidence of adverse reactions. This study aims to explore the median effective dose (ED
) and the 95% effective dose (ED
) of ciprofol in inhibiting responses to gastroscope insertion when combined with a low dose of alfentanil, and to evaluate its safety, to provide a reference for the rational use of ciprofol in clinical practices.
We included 25 patients aged 18-64 years of either sex who underwent gastroscopy under intravenous general anesthesia, with a Body Mass Index (BMI) 18-28 kg/m
, and an American Society of Anesthesiologists (ASA) grade I or II. In this study, the dose-finding strategy of ciprofol followed a modified Dixon's up-and-down method with an initial dose of 0.30 mg/kg and an increment of 0.02 mg/kg. Ciprofol was administered after intravenous injection of 7 µg/kg of alfentanil, and 2 min later a gastroscope was inserted. When the insertion response of one participant was positive (including body movement, coughing, and eye opening), an escalation of 0.02 mg/kg would be given to the next participant; otherwise, a de-escalation of 0.02 mg/kg would be administered. The study was terminated when negative response and positive response alternated 8 times. A Probit model was used to calculate the ED
and ED
of ciprofol in inhibiting responses to gastroscope insertion when combined with alfentanil. Patients' recovery time, discharge time, vital signs and occurrence of adverse reactions were recorded.
The ED
of single-dose intravenous ciprofol injection with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED
was 0.247 mg/kg. Patients' recovery time and discharge time were 11.04 ± 1.49 min and 9.64 ± 2.38 min, respectively. The overall incidence of adverse reactions was 12%.
The ED
of ciprofol combined with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED
was 0.247 mg/kg. Ciprofol showed a low incidence of anesthesia-related adverse events.
http://www.chictr.org.cn (ChiCTR2200061727).
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, ...is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol (10 μM) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-1α signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.
The H9N2 subtype of avian influenza virus (AIV) has been reported to infect not only birds, but also humans. The hemagglutinin (HA) protein is the main surface antigen of AIV and plays an important ...role in the viral infection. For treatment strategies and vaccine development, HA protein has been an important target for the development of broadly neutralizing antibodies against influenza A virus. To investigate the vital target determinant cluster in HA protein in this work, HA gene was cloned and expressed in the prokaryotic expression vector pET28a. The spleen lymphocytes from BALC/c mice immunized with the purified recombinant HA protein were fused with SP2/0 cells. After Hypoxanthine-Aminopterin-Thymidine (HAT) medium screening and indirect ELISA detection, six hybridoma cell lines producing anti-HA monoclonal antibodies were screened. The gradually truncated HA gene expression and western blotting were used to identify their major locations in epitopes specific to these monoclonal antibodies. It was found that the epitopes were located in three areas:
NVENLEEL
,
EELRSLFS
, and
PIQDAQ
. Epitope
NVENLEEL
has a partial amino acid crossover with
EELRSLFS
, which is located in the vestigial esterase domain "110-helix" of HA, and the monoclonal antibody recognizing these epitopes showed the neutralizing activity, suggesting that the region
NVENLEELRSLFS
might be a novel neutralizing epitope. The results of the homology analysis showed that these three epitopes were generally conserved in H9N2 subtype AIV, and will provide valuable insights into H9N2 vaccine design and improvement, as well as antibody-based therapies for treatment of H9N2 AIV infection.
Protection suits are vital for firefighters’ safety. Traditional protection suits physically protect firemen from burns, but cannot locate the position of bodily injuries caused by impact debris. ...Herein, we present a wearable impact debris positioning system for firefighter protection suits based on an accelerometer array. Wearable piezoelectric accelerometers are distributed regularly on the suit to detect the vibration on different body parts, which is conducive to determining the position of injured body parts. In addition, the injured parts can be displayed on a dummy body model on the upper computer with a higher localization accuracy of 4 cm. The positioning alarm system has a rapid response time of 0.11 ms, attributed to the smart signal processing method. This work provides a reliable and smart method for locating and assessing the position of bodily injuries caused by impact debris, which is significant because it enables fire commanders to rescue injured firefighters in time.
Avian Influenza (AI) caused by the H9N2 subtype of the avian influenza virus (AIV) poses a serious threat to both the poultry industry and to public health safety. NP is one of the major structural ...proteins in influenza viruses. B-cell determinants located on NP proteins have attracted increasing attention. In this study, based on the NP sequence of the H9N2 (A/chicken/Shandong/LY1/2017) strain, the truncated NP gene (71 AA–243 AA) was cloned and prokaryotically expressed in a pET-28a (+) vector. BALB/c mice were immunized with a purified recombinant of an NP protein to prepare a monoclonal antibody against NP proteins. The prokaryotic expression of four overlapping fragments, NP-N-96, NP-C-103, NP-C-54 and NP-C-49, were used to recognize an antigenic epitope of the NP protein. The results show that, after cell fusion, one hybridoma cell clone secreted the antibody specific to the NP protein, following screening with ELISA and indirect immunofluorescence, which is named the 4F5 monoclonal antibody (mAb). Western blotting on the overlapping fragments showed that the 230FQTAAQRA237 motif was identified as the minimal motif recognized by 4F5mAb, which was represented as the linear B-cell epitope of the NP protein. Homology analysis of this epitope shows that it was highly conserved in 18 AIVs analyzed in this study, and the epitope prediction results indicate that the epitope may be located on the surface of the NP protein. These results provide a strong experimental basis for studying the function of the NP protein of the H9N2 AIV and also strong technical support for the development of a universal assay based on an anti-NP monoclonal antibody.
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