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1.
Drug Des Devel Ther ; 18: 4017-4027, 2024.
Article in English | MEDLINE | ID: mdl-39258273

ABSTRACT

Objective: Ciprofol is a novel anesthetic agent, its efficacy and safety had been verified and its clinical implementation has been expanded. However, the knowledge about ciprofol in children is meager. The aim of study is to evaluate the safety and effectiveness of ciprofol in general anesthesia in children undergoing adenoidectomy and adenotonsillectomy, compared with propofol. Materials: We retrospectively analyzed data of children who underwent adenoidectomy or adenotonsillectomy with general anesthesia from June to August 2023 to evaluate the safety and effectiveness of ciprofol. The primary outcomes included hemodynamic changes during induction and postoperative complications in post-anesthesia care unit. The secondary outcomes were extubation time, pediatric anesthesia emergence delirium (PAED) score. Meanwhile, subgroup analysis was performed based on age. Results: 301 children met the inclusion criteria, 157 received ciprofol induction and 144 received propofol. Patient demographics and operation-related information were similar in the two groups. However, the dosage of dexmedetomidine in the propofol group was significantly higher than that of the ciprofol group (p=0.001). The trends of hemodynamic shift during induction and intubation were the same in the two groups. The PAED scores on post-extubation 10min and 20min were significantly reduced in the ciprofol group (p<0.001 and p=0.046). Moreover, in the ≤72 months and the >72 months subgroups, the scores were also significantly lower in the ciprofol group on post-extubation 10min. With the score of >10, the incidence of emergence delirium of the ciprofol group was significantly lower on post-extubation 10min and 20min in the population and the ≤72 months subgroups (p=0.03 and p=0.02). There were no obvious postoperative complications in both groups. Conclusion: Ciprofol exhibited advantageous characteristics in the induction of children, such as stable hemodynamics, a relatively lower incidence of postoperative delirium without apparent post-anesthesia complications. Ciprofol may emerge as a novel option for general anesthesia in pediatric patients.


Subject(s)
Adenoidectomy , Anesthesia, General , Tonsillectomy , Humans , Retrospective Studies , Male , Female , Child, Preschool , Child , Adenoidectomy/adverse effects , Anesthesia, General/adverse effects , Tonsillectomy/adverse effects , Propofol/administration & dosage , Propofol/adverse effects , Postoperative Complications , Infant , Cohort Studies
2.
Poult Sci ; 103(11): 104198, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39173216

ABSTRACT

Hybridization is used extensively in commercial layer production. However, heterosis for carcass performance and meat quality of spent laying hens remains unclear, especially under the trend of extended laying cycles. In this study, indigenous Beijing-You chickens (Y) and elite White Leghorn layers (W) were selected to generate purebreds (WW and YY) and reciprocal crosses (WY and YW). Data on traits including carcass compositions, meat quality, and main nutrients for breast muscle were collected when chickens were fed to 100 wk of age. Results showed that body weight (BW) and dressed weight for WY and YW with positive heterosis were significantly higher than WW (P < 0.05). YW had the heaviest breast and thigh of 232.28 g and 278.48 g, respectively. The abdominal fat weight for WY and YW were greatly higher than that for WW (P > 0.05). The yields of carcass compositions, including the dressed yield, half eviscerated yield, eviscerated yield, breast yield and thigh yield, did not differ among the four genetic groups (P > 0.05), except for the yield of abdominal fat. The largest heterosis differences appeared in breast weight (12.26% in YW vs. -0.46% in WY) and abdominal fat yield (15.26% in YW vs. 24.55% in WY). Although BW for crossbreds were similar, the specific parts of the carcass between them were different. For meat quality, WY had negative heterosis (P < 0.05) with the lowest lightness and yellowness, whereas YW had the completely opposite trend. Neither pH1h nor pH24h values had differences among purebreds and reciprocal crossbreds (P > 0.05). The drip loss and cooking loss were 4.01%-4.77% and 15.59%-21.31% respectively among the four genetic groups. The main nutrients of breast, including moisture, crude protein, intramuscular fat and unsaturated fatty acid, did not differ for purebreds and crossbreds (P > 0.05), except for saturated fatty acid. In general, the crossbreds even at the later laying period still showed divergent heterosis on carcass performance and meat characteristics. In view of the heterosis, Beijing-You chickens can be used as the sire line in the crossbreeding to improve carcass compositions of spent hens.

3.
J Mech Behav Biomed Mater ; 159: 106647, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39178822

ABSTRACT

For designing trabecular (Tb) bone substitutes suffering from osteoporosis, finite element model (FEM) simulations were conducted on honeycombs (HCs) of 8 × 8 × 1 (2D) and 8 × 8 × 8 (3D) assemblies of cube cellular units consisting of 0.9 mm long Nylon® 66 (PA, Young's modulus E: 2.83 GPa) and polyethylene (PE, E: 1.1 GPa) right square prisms. Osteoporotic damage to the Tb bone was simulated by removing the inner vertical struts (pillars; the number of removed pillars: Δn ≤ 300) and by thinning the strut (thickness, d: 0.4-0.1 mm), while the six facade lattices were kept flawless. Uniform and uniaxial compressive loads on the HCs induced elastic deformation of the struts. The pillars held almost all the load, while the horizontal struts (beams) shared little. E for PA 3D HCs of all d smoothly decreased with Δn. PA 3D HCs of 0.2 mm struts deserved to be the substitutes for Tb bone, while PE 3D HCs of 0.05 mm struts were only for the Tb bone of the poorest bone quality. For the PA 3D HCs, the maximum von Mises stress (σM) first rapidly increased with Δn and showed a break at Δñ50, then gradually approached the yield stress of PA (50 MPa). Moreover, small portions of the stress were transferred from the façade pillars to the adjacent inner beams, especially those near the lost-pillar sites, denoted as X defects. The floor beams of thinner struts associated with the X-defects were lifted, and similar lifting effects in smaller amounts were propagated to the other floors. The 3DHCs of the thicker struts showed no such flexural deformations. The concept of force percolation through the remaining struts was proposed to interpret those mechanical behaviors of the HCs.


Subject(s)
Bone Substitutes , Finite Element Analysis , Materials Testing , Stress, Mechanical , Cancellous Bone
4.
Chem Commun (Camb) ; 60(58): 7503-7506, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38946591

ABSTRACT

Three iridium(III) complexes were designed with the purpose of elucidating the photo-physicochemical properties of iridium(III) complexes with narrow band gap at the electronic level. This study indicates that increasing the ligand rigidity and electron delocalization of the compounds can suppress the ring-stretching vibrations of the iridium(III) complex, thus improving their photo-chemical activity and photocytotoxicity.

5.
Animals (Basel) ; 14(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38997981

ABSTRACT

Trichomonas gallinae (T. gallinae) is a flagellated protozoan and the causative agent of trichomoniasis, or canker, in birds. In the current study, the prevalence of T. gallinae was firstly investigated in five breeds. According to the results of the prevalence study, White King pigeons were selected as the experimental animals. A total of 135 White King squabs at one day of age were randomly divided into two groups and raised in separate isolators. The challenged group (N = 100) was challenged intranasally with 5 × 106 parasites/mL of the T. gallinae strain, and the control group (N = 35) was intranasally administered medium of equivalent volume. At 1, 2, 3 and 5 days post infection (DPIs), the crops and esophagi were collected for RNA extraction and formaldehyde fixation. The results showed that prevalence of T. gallinae in the five breeds ranged from 27.13% (White Carneau) to 43.14% (White King). After the challenge, mild microscopic lesions were observed in both tissues. Apoptosis rates were higher in the challenged group than in the control group at 2 and 5 DPIs in the crop and at 1, 2 and 7 DPIs in the esophagus. For both tissues, relative expression of IL-1ß increased dramatically at the beginning and decreased at 5 DPIs, and TGF-ß increased stably in the challenged group.

6.
Hepatol Int ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39003652

ABSTRACT

BACKGROUND: The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. METHODS: Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. RESULTS: Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3 months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16 mmol/L decrease in HDL-C and a 0.18 g/L decrease in ApoA1. CONCLUSION: Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

7.
Cancer Med ; 13(13): e7424, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38988047

ABSTRACT

BACKGROUND: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Minichromsome maintenance proteins family member 8 (MCM8) assists DNA repair and DNA replication. MCM8 exerts tumor promotor function in multiple digestive system tumors. MCM8 is also considered as a potential cancer therapeutic target. METHODS: Bioinformatics methods were used to analyze MCM8 expression and clinicopathological significance. MCM8 expression was detected by immunohistochemistry (IHC) staining and qRT-PCR. MCM8 functions in GC cell were explored by Celigo cell counting, colony formation, wound-healing, transwell, and annexin V-APC staining assays. The target of MCM8 was determined by human gene expression profile microarray. Human phospho-kinase array kit evaluated changes in key proteins after ribosomal protein S15A (RPS15A) knockdown. MCM8 functions were reassessed in xenograft mouse model. IHC detected related proteins expression in mouse tumor sections. RESULTS: MCM8 was significantly upregulated and predicted poor prognosis in GC. High expression of MCM8 was positively correlated with lymph node positive (p < 0.001), grade (p < 0.05), AJCC Stage (p < 0.001), pathologic T (p < 0.01), and pathologic N (p < 0.001). MCM8 knockdown inhibited proliferation, migration, and invasion while promoting apoptosis. RPS15A expression decreased significantly after MCM8 knockdown. It was also the only candidate target, which ranked among the top 10 downregulated differentially expressed genes (DEGs) in sh-MCM8 group. RPS15A was identified as the target of MCM8 in GC. MCM8/RPS15A promoted phosphorylation of P38α, LYN, and p70S6K. Moreover, MCM8 knockdown inhibited tumor growth, RPS15A expression, and phosphorylation of P38α, LYN, and p70S6K in vivo. CONCLUSIONS: MCM8 is an oncogene and predicts poor prognosis in GC. MCM8/RPS15A facilitates GC progression.


Subject(s)
Cell Proliferation , Gene Expression Regulation, Neoplastic , Ribosomal Proteins , Stomach Neoplasms , Humans , Ribosomal Proteins/metabolism , Ribosomal Proteins/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Animals , Mice , Prognosis , Female , Male , Cell Line, Tumor , Disease Progression , Middle Aged , Minichromosome Maintenance Proteins/metabolism , Minichromosome Maintenance Proteins/genetics , Apoptosis , Mice, Nude , Cell Movement , Xenograft Model Antitumor Assays , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics
8.
Poult Sci ; 103(9): 104053, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39033573

ABSTRACT

The freezability of chicken spermatozoa is low, therefore, effective cryoprotectants is desiderated. Antifreeze proteins (AFPs) are widely found in cold-tolerant species and help them to survive in freezing environments. This study was the first to evaluate the effects of different concentrations of plant-originated antifreeze glycoprotein (AFGP) (0, 0.1, 1, and 5 µg/mL) on post-thawed sperm motion characteristics, morphology, mitochondrial function, antioxidant activity, and fertilizing potential in chickens. Results showed that the total motility of 0.1 to 1 µg/mL AFGP groups were significantly higher than those of the 5 µg/mL AFGP group (P < 0.05). The post-thawed sperm viability of 0.1 µg/mL AFGP group was significantly higher than any of test groups (P < 0.05). Higher abnormal morphology rate of post-thawed sperm was observed in the control group (0 µg/mL AFGP) than in the 0.1, 1, and 5 µg/mL AFGP groups (P < 0.05). The concentrations of malondialdehyde (MDA) decreased gradually with the increase of AFGP concentration. ATP was significantly higher in the 0.1 and 1 µg/mL AFGP groups than those of control and any of test groups (P < 0.05). The 0.1 to 1 µg/mL AFGP groups had increased mitochondrial membrane potential (MMP) level (P > 0.05). The 0.1 µg/mL AFGP group had the highest average fertility (61.36%) compared with control group (57.02%) and any of test groups of chickens at 31 wk of age, and the 1 µg/mL AFGP group had the highest average fertility (37.72%) compared with control group (21.73%) and any of test groups of chickens at 65 wk of age. In conclusion, the results from this study suggest lower concentration of AFGP (0.1-1 µg/mL) showed positive effect for sperm function. This study inspires the continuous evaluation and seeking right way of adopting different kinds of AFPs in rooster semen cryopreservation.


Subject(s)
Antifreeze Proteins , Chickens , Cryopreservation , Semen Preservation , Animals , Male , Antifreeze Proteins/chemistry , Chickens/physiology , Cryopreservation/veterinary , Cryoprotective Agents/pharmacology , Dose-Response Relationship, Drug , Semen Preservation/veterinary , Sperm Motility/drug effects , Spermatozoa/physiology , Spermatozoa/drug effects , Triticum/chemistry
9.
Int J Biol Macromol ; 277(Pt 1): 134022, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39038569

ABSTRACT

MicroRNAs (miRNAs) are bio-active elements cargoed by seminal plasma extracellular vesicles extracellular vesicles (SPEVs) which are crucial for sperm function and fertility modulation. This study aimed to isolate, characterize, and identify the miRNA expression profiles in the SPEVs from high (HSM) and low sperm motility (LSM) groups that could serve as fertility biomarkers and explain the underlying mechanisms. The isolated SPEVs were round spherical structures of approximately 50-200 nm in diameter expressing molecular markers. A total of 1006 and 1084 miRNAs were detected in HSM and LSM, respectively, with 34 being differentially expressed. Their targeted genes involved in SNARE interactions in vesicular transport, Metabolic pathways, and Apelin signaling pathway, etc. The joint analysis with mRNAs of sperm and sperm storage tubules cells highlighted the cellular communication mediated by SPEVs miRNAs, where they may rule fertility by affecting sperm maturation and amino acid metabolism. SPEVs as additives could improve fertility of fresh and frozen sperm, while the knockdown of one of the differentially expressed miRNAs, miR-24-3p, diminished this effect, indicating its crucial roles. This study expands our understanding of SPEVs miRNAs mediated sperm maturation and fertility modulation, and may help to develop new therapeutic strategies for infertility and sperm storage.


Subject(s)
Chickens , Extracellular Vesicles , MicroRNAs , Semen , Sperm Motility , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Animals , Sperm Motility/genetics , Semen/metabolism , Gene Expression Regulation , Spermatozoa/metabolism , Gene Expression Profiling
10.
CNS Neurosci Ther ; 30(6): e14764, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828629

ABSTRACT

AIMS: Neuropathic pain is a common chronic pain disorder, which is largely attributed to spinal central sensitization. Calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) activation in the spinal dorsal horn (SDH) is a major contributor to spinal sensitization. However, the exact way that CaMKIIα-positive (CaMKIIα+) neurons in the SDH induce neuropathic pain is still unclear. This study aimed to explore the role of spinal CaMKIIα+ neurons in neuropathic pain caused by chronic constriction injury (CCI) and investigate the potential epigenetic mechanisms involved in CaMKIIα+ neuron activation. METHODS: CCI-induced neuropathic pain mice model, Sirt1loxP/loxP mice, and chemogenetic virus were used to investigate whether the activation of spinal CaMKIIα+ neurons is involved in neuropathic pain and its involved mechanism. Transcriptome sequence, western blotting, qRT-PCR, and immunofluorescence analysis were performed to assay the expression of related molecules and activation of neurons. Co-immunoprecipitation was used to observe the binding relationship of protein. Chromatin immunoprecipitation (ChIP)-PCR was applied to analyze the acetylation of histone H3 in the Scn3a promoter region. RESULTS: The expression of sodium channel Nav1.3 was increased and the expression of SIRT1 was decreased in the spinal CaMKIIα+ neurons of CCI mice. CaMKIIα neurons became overactive after CCI, and inhibiting their activation relieved CCI-induced pain. Overexpression of SIRT1 reversed the increase of Nav1.3 and alleviated pain, while knockdown of SIRT1 or overexpression of Nav1.3 promoted CaMKIIα+ neuron activation and induced pain. By knocking down spinal SIRT1, the acetylation of histone H3 in the Scn3a (encoding Nav1.3) promoter region was increased, leading to an increased expression of Nav1.3. CONCLUSION: The findings suggest that an aberrant reduction of spinal SIRT1 after nerve injury epigenetically increases Nav1.3, subsequently activating CaMKIIα+ neurons and causing neuropathic pain.


Subject(s)
Neuralgia , Neurons , Sirtuin 1 , Animals , Male , Mice , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Mice, Inbred C57BL , Neuralgia/metabolism , Neurons/metabolism , Sirtuin 1/metabolism , Sirtuin 1/genetics , Spinal Cord/metabolism
11.
Int Immunopharmacol ; 136: 112386, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38850794

ABSTRACT

Epilepsy is a severe central nervous system disorder characterized by an imbalance between neuronal excitation and inhibition, resulting in heightened neuronal excitability, particularly within the hippocampus. About one-third of individuals with epilepsy experience difficult-to-manage seizures, known as refractory epilepsy. Epilepsy is closely linked to inflammatory immune response, with elevated levels of inflammatory mediators observed in individuals with this condition. This inflammation of the brain can lead to seizures of various types and is further exacerbated by the release of inflammatory factors, which heighten the excitability of peripheral neurons and worsen the progression of epilepsy. Pyroptosis is an inflammatory programmed cell death which has been shown to be involved in the pathological process of epilepsy. Inflammatory factors released during pyroptosis increase neuronal excitability and promote abnormal discharge in epilepsy, increasing susceptibility to epilepsy. This article provides an overview of the current knowledge on cell pyroptosis and its potential mechanisms, including both canonical and noncanonical pathways. Additionally, we discuss the potential mechanisms of pyroptosis occurrence in epilepsy and the potential therapeutic drugs targeting pyroptosis as a treatment strategy. In summary, this review highlights the promising potential of pyroptosis as a target for developing innovative therapies for epilepsy.


Subject(s)
Epilepsy , Pyroptosis , Humans , Epilepsy/metabolism , Epilepsy/immunology , Animals , Neurons/metabolism , Neurons/pathology
12.
RSC Adv ; 14(27): 19581-19585, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38895521

ABSTRACT

A facile and efficient strategy for modular access to furo[3,2-c]chromen-4-ones using 4-hydroxycoumarin and ß-nitroalkenes via Lewis acid-catalyzed formal [3 + 2] annulation protocol is described. This reaction proceeds via cascade Michael addition/nucleophilic addition/elimination in the presence of Yb(OTf)3, which involves the formation of two new σ (C-C and C-O) bonds for the construction of a novel furan ring in a single operation. This protocol affords a variety of functional groups, thereby providing a practical and efficient method for the fabrication of a furo[3,2-c]chromen-4-one framework.

13.
EJNMMI Res ; 14(1): 55, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38880858

ABSTRACT

BACKGROUND: Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging. METHODS: In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT. RESULTS: In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of 68Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of 68Ga-NOTA-RM26 than those with high GS (P = 0.001). CONCLUSIONS: This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.

14.
Nat Med ; 30(5): 1395-1405, 2024 May.
Article in English | MEDLINE | ID: mdl-38693247

ABSTRACT

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.


Subject(s)
Cerebral Palsy , DNA Copy Number Variations , Exome Sequencing , Genetic Heterogeneity , Humans , Cerebral Palsy/genetics , Female , Male , Child , Child, Preschool , DNA Copy Number Variations/genetics , Exome/genetics , Infant , Genetic Testing , Cohort Studies , Genetic Predisposition to Disease , Infant, Newborn
15.
RSC Adv ; 14(24): 17178-17183, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38808243

ABSTRACT

Cyclic N-sulfonyl aldimines are well-known aza-[2C]-synthons for various [2 + n] annulation reactions. Herein we describe a novel base mediated [2 + 1] annulation and a regioselective aziridine ring-opening reaction cascade, which provides an efficient and distinct synthetic strategy from readily available cyclic N-sulfonyl aldimines and α-carbonyl sulfonium salts leading to ß-amino ketone derivatives through the corresponding fused tri-substituted aziridines. This one-pot, two-step process involves formation of C-C and C-N bonds and subsequent cleavage of a C-N bond. The features of the developed reaction include the use of mild reaction conditions, broad substrate scope, and excellent yields. The synthetic utility of this approach was demonstrated by gram-scale operation and further product derivatizations.

16.
Poult Sci ; 103(7): 103783, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38713987

ABSTRACT

Heterosis has been widely utilized in chickens. The nonadditive inheritance of genes contributes to this biological phenomenon. However, the role of circRNAs played in the heterosis is poorly determined. In this study, we observed divergent heterosis for residual feed intake (RFI) between 2 crossbreds derived from a reciprocal cross between White Leghorns and Beijing You chickens. Then, circRNA landscape for 120 samples covering the hypothalamus, liver, duodenum mucosa and ovary were profiled to elucidate the regulatory mechanisms of heterosis. We detected that a small proportion of circRNAs (7.83-20.35%) were additively and non-additively expressed, in which non-additivity was a major inheritance of circRNAs in the crossbreds. Tissue-specific expression of circRNAs was prevalent across 4 tissues. Weighted gene co-expression network analysis revealed circRNA-mRNA co-expression modules associated with feed intake and RFI in the hypothalamus and liver, and the co-expressed genes were enriched in oxidative phosphorylation pathway. We further identified 8 nonadditive circRNAs highly correlated with 16 nonadditive genes regulating negative heterosis for RFI in the 2 tissues. Circ-ITSN2 was validated in the liver tissue for its significantly positive correlation with PGPEP1L. Moreover, the bioinformatic analysis indicated that candidate circRNAs might be functioned by binding the microRNAs and interacting with the RNA binding proteins. The integration of multi-tissue transcriptome firstly linked the association between tissue-specific circRNAs and the heterosis for feed intake and efficiency in chicken, which provide novel insights into the molecular mechanism underlying heterosis for feed efficiency. The validated circRNAs can act as potential biomarkers for predicting RFI and its heterosis.


Subject(s)
Chickens , Gene Expression Profiling , Hybrid Vigor , RNA, Circular , Animals , Chickens/genetics , Chickens/metabolism , Hybrid Vigor/genetics , Gene Expression Profiling/veterinary , RNA, Circular/genetics , RNA, Circular/metabolism , Female , Eating/genetics , Transcriptome , Male
17.
Plant Cell Rep ; 43(6): 157, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819475

ABSTRACT

KEY MESSAGE: CmMYB308 was identified as a key regulator in chrysanthemum flower color variation from purple to pink by conducting transcriptome and metabolome analysis. CmMYB308 can inhibit anthocyanin biosynthesis by suppressing the expression of CmPAL, CmC4H, and Cm4CL. Flower color variation is a widespread natural occurrence that plays a significant role in floral breeding. We discovered a variation in the flower of the chrysanthemum cultivar 'Dante Purple' (abbreviated as 'DP'), where the flower color shifted from purple to pink. We successfully propagated these pink flowers through tissue culture and designated them as DPM. By conducting transcriptome and metabolome analysis, we identified a reduction in the expression of critical genes involved in anthocyanin biosynthesis-CmPAL, CmC4H, and Cm4CL-in the DPM. This downregulation led to an accumulation of phenylalanine and cinnamic acid within the general phenylpropanoid pathway (GPP), which prevented their conversion into cyanidin and cyanidin 3-glucoside. As a result, the flowers turned pink. Additional transformation and biochemical experiments confirmed that the upregulation of CmMYB308 gene expression in the DPM directly suppressed CmPAL-1 and CmC4H genes, which indirectly affected Cm4CL-3 expression and ultimately inhibited anthocyanin biosynthesis in the DPM. This study offers a preliminary insight into the molecular mechanism underlying chrysanthemum flower color mutation, paving the way for genetic improvements in chrysanthemum flower color breeding.


Subject(s)
Anthocyanins , Chrysanthemum , Flowers , Gene Expression Regulation, Plant , Pigmentation , Plant Proteins , Chrysanthemum/genetics , Chrysanthemum/metabolism , Flowers/genetics , Flowers/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Anthocyanins/metabolism , Pigmentation/genetics , Transcriptome/genetics , Metabolomics/methods , Metabolome/genetics , Gene Expression Profiling , Color , Transcription Factors/genetics , Transcription Factors/metabolism
18.
J Biol Chem ; 300(6): 107376, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38762176

ABSTRACT

Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl4- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl4-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl4-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of interleukin 6 (IL-6), and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the profibrotic response inspired by Fendrr in the CCl4-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory cross talk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.


Subject(s)
Hepatocytes , Interleukin-6 , Liver Cirrhosis , RNA, Long Noncoding , Animals , Humans , Male , Mice , Carbon Tetrachloride/toxicity , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Hepatocytes/metabolism , Hepatocytes/pathology , Interleukin-6/metabolism , Interleukin-6/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Mice, Inbred C57BL , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , STAT2 Transcription Factor/metabolism , STAT2 Transcription Factor/genetics
19.
Front Public Health ; 12: 1374522, 2024.
Article in English | MEDLINE | ID: mdl-38584914

ABSTRACT

Background: Mobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students. Methods: To explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students. Results: The results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness. Conclusion: This study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.


Subject(s)
Depression , Loneliness , Humans , Fear , Students , Technology Addiction
20.
Poult Sci ; 103(5): 103489, 2024 May.
Article in English | MEDLINE | ID: mdl-38518666

ABSTRACT

This study aimed to systematically determined the effect of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, uterine morphological characteristics, and gene expression of hens during the late laying period. At 74 wk, 260 Hy-Line Brown layers were randomly divided into 2 groups of 130 birds each and in duplicates. Both a regular (16L:8D) and an ahemeral light cycle (16L:12D) were provided to the hens. The oviposition pattern in an ahemeral cycle shifted into darkness, with oviposition mostly occurring 3 to 5 h after light out. Production performance was unaffected by light cycle (P > 0.05). Nonetheless, compared to the normal group, the ahemeral group exhibited increased egg weight, eggshell weight, eggshell percentage, yolk percentage, eggshell thickness, and eggshell strength (P < 0.05). There were rhythmic changes in the uterine morphological structure in both cycles, however, the ahemeral group maintained a longer duration and had more uterine folds than the normal group. In the ahemeral cycle, the phases of the CLOCK and PER2 genes were phase-advanced for 3.96 h and 4.54 h compared to the normal cycle. The PHLPP1 gene, which controls clock resetting, exhibited a substantial oscillated rhythm in the ahemeral group (P < 0.05), while the expression of genes presenting biological rhythm, such as CRY2 and FBXL3, was rhythmically oscillated in normal cycle (P < 0.05). The ITPR2 gene, which regulates intracellular Ca2+ transport, displayed a significant oscillated rhythm in ahemeral alone (P < 0.05), while the CA2 gene, which presents biomineralization, rhythmically oscillated in both cycles (P < 0.05). The ahemeral cycle caused 2.5 h phase delays in the CA2 gene compared to the normal cycle. In conclusion, the 28 h ahemeral light cycle preserved the high condition of the uterine folds and changed the uterine rhythms of CLOCK, PER2, ITPR2, and CA2 gene expression to improve ion transport and uterine biomineralization.


Subject(s)
Chickens , Oviposition , Photoperiod , Uterus , Animals , Chickens/physiology , Chickens/genetics , Chickens/blood , Female , Uterus/physiology , Uterus/anatomy & histology , Oviposition/physiology , Ovum/physiology , Random Allocation , Egg Shell/physiology , Gene Expression
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