Objective: Radical hysterectomy has long been considered as the standard surgical treatment for early-stage cervical cancer (IA2 to IB1 stages), according to the 2009 International Federation of Obstetrics and Gynecology. This study aims to conduct an in-depth evaluation of the effectiveness and safety of non-radical surgery as an alternative treatment for patients with early-stage cervical cancer. Methods: A systematic search of online databases including PubMed, Embase, and the Cochrane Library was conducted to identify relevant literature on surgical treatment options for early-stage cervical cancer. Keywords such as "cervical cancer," "conservative surgery," "early-stage," "less radical surgery," and "simple hysterectomy" were used. Meta-analysis was performed using Stata 15.0 software, which included randomized controlled trials (RCTs) and cohort studies. Results: This meta-analysis included 8 eligible articles covering 9 studies, with 3,950 patients in the simple hysterectomy (SH) surgery group and 6,271 patients in the radical hysterectomy (RH) surgery group. The results indicate that there was no significant difference between the two groups in terms of the Overall Survival (OS) (HR = 1.04, 95% CI: 0.86-1.27, p = 0.671; Heterogeneity: I2 = 33.8%, p = 0.170), Disease Free Survival (DFS) (HR = 1.39, 95% CI: 0.59-3.29, p = 0.456; Heterogeneity: I2 = 0.0%, p = 0.374), Cervical Cancer Specific Survival (CCSS) (HR = 1.11, 95% CI: 0.80-1.54, p = 0.519; Heterogeneity: I2 = 11.9%, p = 0.287) and recurrence rate (RR = 1.16, 95% CI: 0.69-1.97, p = 0.583; Heterogeneity: I = 0.0%, p = 0.488). However, the mortality rate (RR = 1.35, 95% CI: 1.10-1.67, p = 0.006; Heterogeneity: I2 = 35.4%, p = 0.158) and the rate of postoperative adjuvant therapy (RR = 1.59, 95% CI: 1.16-2.19, p = 0.004; Heterogeneity: I2 = 92.7%, p < 0.10) were higher in the SH group compared to those in the RH group. On the other hand, the incidence of surgical complications was lower in the SH group (RR = 0.36, 95% CI: 0.21-0.59, p = 0.004; Heterogeneity: I2 = 0.0%, p = 0.857) than that in the RH group. Subgroup analysis revealed that patients in the IB1 stage SH group had a significantly higher mortality rate compared to those in the RH group (RR = 1.59, 95% CI: 1.23-2.07, p < 0.001; Heterogeneity: I2 = 0.0%, p = 0.332). However, there was no significant difference in mortality rates between the two groups for patients at stage IA2 (RR = 0.84, 95% CI: 0.54-1.30, p = 0.428; Heterogeneity: I2 = 26.8%, p = 0.243). In the subgroups positive for Lymphovascular Space Invasion (LVSI), patients in the SH group had a significantly higher mortality rate than those in the RH group (RR = 1.34, 95% CI: 1.09-1.65, p = 0.005; Heterogeneity: I2 = 41.6%, p = 0.128). However, in the LVSI-negative subgroups, there was no significant difference in mortality rates between the two groups (RR = 0.33, 95% CI: 0.01-8.04, p = 0.499). Conclusion: For patients with early-stage cervical cancer patients at IA2 without LVSI involvement, comparisons between the two groups in terms of OS, DFS, CCSS, recurrence rate, and mortality rates revealed no statistically significant differences, indicating that the choice of surgical approach does not affect long-term survival outcomes for this specific patient group. For patients at IB1 and IA2 stages with LVSI involvement, while there were no significant differences between the two groups in OS, DFS, CSS, and recurrence rate, a significant increase in mortality rates was observed in the SH group. This indicates a potential elevated risk of mortality associated with SH in this subset of patients. Notably, the incidence of surgical complications was significantly lower in the SH group compared to the RH group, highlighting the safety profile of SH in this context. Significantly, among patients in the SH group, an increase in the rate of postoperative adjuvant treatment is associated with a higher occurrence of treatment-related complications. To facilitate more precise patient selection for conservative surgical management, future prospective studies of superior quality are imperative to gain deeper insights into this matter. Systematic review registration: PROSPERO (CRD42023451609: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451609).
PURPOSE: This study aimed to assess the efficacy and safety outcome of covered stents (CSs), as compared with bare-metal stents (BMSs), for the treatment of patients with aortoiliac occlusive disease (AIOD). MATERIALS AND METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library up to August 2023 to identify all studies comparing efficacy and safety outcomes of CSs versus BMSs for treating AIOD. Our outcome was primary patency, secondary patency, technical success, ankle-brachial index (ABI) variation, target lesion revascularization (TLR), limb salvage, complications, and long-term survival. Dichotomous outcomes were pooled as relative risks (RR) or hazard ratio with the 95% confidence interval (CI). Continuous outcomes were pooled as weighted mean differences and 95% CI. Model selection was based on the heterogeneity of the included studies. RESULTS: There were 10 studies (2 randomized controlled trials, 8 retrospective cohort studies), comprising 1676 sample size. Compared with BMSs, CSs use was associated with better primary patency of patients with a Trans-Atlantic Inter-Society Consensus II (TASC) D lesion (RR, 1.15, 95% CI, 1.04 to 1.27, p=0.007), TLR (RR, 0.39, 95% CI, 0.27 to 0.56, p<0.001), technical success (RR, 1.01, 95% CI, 1.00 to 1.02, p=0.010), and long-term survival (RR, 1.06, 95% CI, 1.01 to 1.11, p=0.020). There is no difference between CSs and BMSs regarding primary patency of all patients, secondary patency, variation in ABI, limb salvage, and complications. CONCLUSIONS: Compared with BMSs, CSs used in AIOD was associated with more favorable primary patency in patients with TASC D lesions, TLR, technical success rates, and patient long-term survival. These results provide evidence of the advantages of using CSs for AIOD treatment. Future studies focusing on long-term variations in ABI, primary patency of different degrees of calcification, vascular segments, and TASC classification are warranted. CLINICAL IMPACT: Although several studies evaluated the clinical efficacy of CS in the context of AIOD treatment, the significance and consistency of these findings were not determined to date. We found that CS was used in AIOD associated with better technical success rate, long-term patient survival, lower target lesion revascularization, and higher primary patency of patients with a Trans-Atlantic Inter-Society Consensus II D lesion when compared with BMSs. Our study provides evidence supporting the superiority of CSs over BMSs in the treatment of AIOD, and furnishing clinicians with guidance for treatment decisions.
The feather growth rate in chickens included early and late feathering. We attempted to characterize the genes and pathways associated with the feather growth rate in chickens that are not in agreement with Mendelian inheritance. Gene expression profiles in the hair follicle tissues of late-feathering cocks (LC), early-feathering cocks (EC), late-feathering hens (LH), and early-feathering hens (EH) were acquired using RNA sequencing (RNA-seq), mass spectrometry (MS), and quantitative reverse transcription PCR (qRTPCR). A total of 188 differentially expressed genes (DEGs) were ascertained in EC vs. LC and 538 DEGs were identified in EH vs. LH. We observed that 14 up-regulated genes and 9 down-regulated genes were screened both in EC vs. LC and EH vs. LH. MS revealed that 41 and 138 differentially expressed proteins (DEPs) were screened out in EC vs. LC and EH vs. LH, respectively. Moreover, these DEGs and DEPs were enriched in multiple feather-related pathways, including JAK-STAT, MAPK, WNT, TGF-ß, and calcium signaling pathways. qRT-PCR assay showed that the expression of WNT8A was decreased in LC compared with EC, while ALK and GRM4 expression were significantly up-regulated in EH relative to LH. This study helps to elucidate the potential mechanism of the feather growth rate in chickens that do not conform to genetic law.
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are emerging tools that can be used in the diagnosis of deep venous thrombosis (DVT). This study aims to evaluate the diagnostic value of NLR and PLR for patients with DVT. Our meta-analysis included 11 eligible studies and extracted relevant diagnostic indicators. Of these studies, 4 focused on the NLR, 1 on the PLR, while 6 evaluated both. For the 10 studies on NLR, the pooled sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio were 74%, 66%, 2.16, and 0.4, respectively. The estimated diagnostic odds ratio (DOR) was 5.3, and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves was 0.74. For the 7 studies on the PLR, the pooled sensitivity, specificity, positive-likelihood ratio, and negative-likelihood ratio were 0.65, 0.77, 2.89, and 0.45, respectively. The estimated DOR was 6.64, and the SROC-AUC was 0.79. Our findings showed that the NLR and PLR exhibit moderate diagnostic accuracy and may be helpful biomarkers for the diagnosis of DVT. Future prospective, well-designed studies with large sample sizes will be required to provide additional evidence to establish cutoff values and clinical value of these indicators.
Neutrophils , Venous Thrombosis , Humans , Lymphocytes , Blood Platelets , Biomarkers , ROC Curve , Venous Thrombosis/diagnosis , Retrospective Studies
Layered transition metal dichalcogenides (TMDs) are two-dimensional materials exhibiting a variety of unique features with great potential for electronic and optoelectronic applications. The performance of devices fabricated with mono or few-layer TMD materials, nevertheless, is significantly affected by surface defects in the TMD materials. Recent efforts have been focused on delicate control of growth conditions to reduce the defect density, whereas the preparation of a defect-free surface remains challenging. Here, we show a counterintuitive approach to decrease surface defects on layered TMDs: a two-step process including Ar ion bombardment and subsequent annealing. With this approach, the defects, mainly Te vacancies, on the as-cleaved PtTe2 and PdTe2 surfaces were decreased by more than 99%, giving a defect density <1.0 × 1010 cm-2, which cannot be achieved solely with annealing. We also attempt to propose a mechanism behind the processes.
Granulosa cell (GC) apoptosis is the main trigger of follicular atresia. MicroRNAs (miRNAs) are 18-22 nt RNAs whose function is primarily determined by their extended seed region and are considered to be involved in the biological functions of follicular development, including follicular atresia, folliculogenesis, and oogenesis. MiR-138-5p is known to act on chicken GCs. In this study, we found that miR-138-5p was enriched in reproductive organs, such as the uterus and ovaries. To examine whether miR-138-5p could regulate the biological process of GCs, miR-138-5p was examined by transfection of cells with a mimic or inhibitor of miR-138-5p. Expression levels of caspase-3 and caspase-9 mRNA and protein were markedly increased or decreased after transfection of the mimic or inhibitor, respectively. Furthermore, following miR-138-5p inhibition, SIRT1, one of the target genes of miR-138-5p, was found to increase the mRNA, which is correlated with the increased levels of BCL2 expression, an anti-apoptotic gene in the chicken GCs. These results suggest that miR-138-5p promotes apoptosis in chicken GCs by targeting SIRT1.
Granulosa Cells , MicroRNAs , Female , Animals , Granulosa Cells/metabolism , Chickens/genetics , Chickens/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Follicular Atresia/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Apoptosis/genetics , RNA, Messenger/metabolism , Cell Proliferation/genetics
Broodiness, a maternal behavior, is accompanied by the atresia of follicles and the serious degradation of poultry reproductive performance. The comparison of follicles between brooding and laying hens is usually an ideal model for exploring the regulation mechanism of follicle atresia. In this study, we selected three brooding hens and three laying hens to collect their follicles for whole transcriptome sequencing. The results demonstrated different expression patterns between the follicles of brooding hens and laying hens. In the top 10 differentially expressed genes with the highest expression, MMP10 was relatively low expressed in the follicles of brooding hens, but other nine genes were relatively highly expressed, including LRR1, RACK1, SPECC1L, ABHD2, COL6A3, RPS17, ATRN, BIRC6, PGAM1 and SPECC1L. While miR-21-3p, miR-146a-5p, miR-142-5p and miR-1b-3p were highly expressed in the follicles of brooding hen, miR-106-5p, miR-451, miR-183, miR-7, miR-2188-5p and miR-182-5p were lowly expressed in brooding hen. In addition, we identified 124 lncRNAs specifically expressed in the follicles of brooding hens and 147 lncRNAs specifically expressed in the follicles of laying hens. Our results may provide a theoretical basis for further exploration of the molecular mechanism of broodiness in broilers.
MicroRNAs , RNA, Long Noncoding , Female , Animals , Chickens/genetics , RNA, Long Noncoding/genetics , Follicular Atresia , Gene Expression Profiling/veterinary , MicroRNAs/genetics , Transcriptome/genetics
Indoor environmental control is usually applied in poultry farming to ensure optimum growth conditions for birds. However, these control methods represent a considerable share of total energy consumption, and the trend of applying new equipment in the future for precision livestock farming would further increase energy demand, resulting in an increase in greenhouse gas emissions and management costs. Therefore, to ensure optimum efficiency of both energy use and livestock productivity, a customized hourly model was developed in the present study to interpret and analyze the electronically collected data. The modules for estimating indoor gas concentrations were incorporated into the present model, as this has not been properly considered in previous studies. A validation test was performed in a manure-belt layer house using sensors and meters to measure the indoor environmental parameters and energy consumption. The predicted results, including indoor temperature, relative humidity, carbon dioxide and ammonia concentrations, showed good agreement with the measured data, indicating a similar overall trend with acceptable discrepancies. Moreover, the corresponding differences between the measured and simulated energy consumption for heating, tunnel ventilation and base ventilation were 13.7, 7.5, and 0.1%, respectively. The total energy demand estimated by the model showed a limited discrepancy of approximately 10.6% compared with that measured in reality. Although human factors, including inspection, cleaning, vaccination, etc., were not included in the model, the validation results still suggested that the customized model was able to accurately predict the indoor environment and overall energy consumption during poultry farming. The validated model provides a tool for poultry producers to optimize production planning and management strategies, increase the production rate of unit energy consumption and achieve precision livestock farming from an energy consumption standpoint.
Studies have shown that prebiotics can affect meat quality; however, the underlying mechanisms remain poorly understood. This study aimed to investigate whether prebiotics affect the flavor of chicken meat via the gut microbiome and metabolome. The gut content was collected from chickens fed with or without prebiotics (galacto-oligosaccharides or xylo-oligosaccharides) and subjected to microbiome and metabolome analyses, whereas transcriptome sequencing was performed using chicken breast. Prebiotic supplementation yielded a slight improvement that was not statistically significant in the growth and production performance of chickens. Moreover, treatment with prebiotics promoted fat synthesis and starch hydrolysis, thus increasing meat flavor by enhancing lipase and α-amylase activity in the blood of broiler chickens. The prebiotics altered the proportions of microbiota in the gut at different levels, especially microbiota in the phyla Bacteroidetes and Firmicutes, such as members of the Alistipes, Bacteroides, and Faecalibacterium genera. Furthermore, the prebiotics altered the content of cecal metabolites related to flavor substances, including 8 types of lysophosphatidylcholine (lysoPC) and 4 types of amino acid. Differentially expressed genes (DEGs) induced by prebiotics were significantly involved in fatty acid accumulation processes, such as lipolysis in adipocytes and the adipocytokine signaling pathway. Changes in gut microbiota were correlated with metabolites, for example, Bacteroidetes and Firmicutes were positively and negatively correlated with lysoPC, respectively. Finally, DEGs interacted with cecal metabolites, especially meat-flavor-related amino acids and their derivatives. The findings of this study integrated and incorporated associations among the gut microbiota, metabolites, and transcriptome, which suggests that prebiotics affect the flavor of chicken meat.
Chickens , Microbiota , Animals , Chickens/metabolism , Transcriptome , Oligosaccharides/metabolism , Metabolome , Meat/analysis , Prebiotics/analysis
With the scaling of lateral dimensions in advanced transistors, an increased gate capacitance is desirable both to retain the control of the gate electrode over the channel and to reduce the operating voltage1. This led to a fundamental change in the gate stack in 2008, the incorporation of high-dielectric-constant HfO2 (ref. 2), which remains the material of choice to date. Here we report HfO2-ZrO2 superlattice heterostructures as a gate stack, stabilized with mixed ferroelectric-antiferroelectric order, directly integrated onto Si transistors, and scaled down to approximately 20 ångströms, the same gate oxide thickness required for high-performance transistors. The overall equivalent oxide thickness in metal-oxide-semiconductor capacitors is equivalent to an effective SiO2 thickness of approximately 6.5 ångströms. Such a low effective oxide thickness and the resulting large capacitance cannot be achieved in conventional HfO2-based high-dielectric-constant gate stacks without scavenging the interfacial SiO2, which has adverse effects on the electron transport and gate leakage current3. Accordingly, our gate stacks, which do not require such scavenging, provide substantially lower leakage current and no mobility degradation. This work demonstrates that ultrathin ferroic HfO2-ZrO2 multilayers, stabilized with competing ferroelectric-antiferroelectric order in the two-nanometre-thickness regime, provide a path towards advanced gate oxide stacks in electronic devices beyond conventional HfO2-based high-dielectric-constant materials.
In this work, the ferroelectric characteristic of a 5 nm Hf0.5Zr0.5O2 (HZO) metal-ferroelectric-insulator-semiconductor (MFIS) device is enhanced through strained complementary metal oxide semiconductor (CMOS)-compatible TiN electrode engineering. Strained TiN top-layer electrodes with different nitrogen (N) concentrations are deposited by adjusting the sputtering process conditions. The TiN electrode with 18% N exhibits a compressive characteristic, which induces tensile stress in a 5 nm HZO film. A device with 18% N in TiN shows a higher remanent polarization (2Pr) and larger capacitance value than the compared sample, indicating that the strained TiN is promising for enhancing the ferroelectricity of sub-5 nm HZO devices.
Previous studies have shown that the feather growth rate of chicks is determined by two alleles located on the sex chromosome Z; however, in chicken production, feathering is usually not consistently controlled by the sex chromosome. To identify whether the feathering rate is related to autosomal inheritance, whole-genome resequencing was performed in eight chickens with slow- and fast-feathering rate. A total of 54,984 autosomal single nucleotide polymorphisms (SNPs) were identified, including 393 and 376 exonic SNPs in slow-feathering and fast-feathering chickens, respectively. Mutated genes were mainly involved in response to stimuli and growth and reproduction processes. Mutated genes related to slow-feathering rate were mainly involved in wingless-type MMTV integration site signaling pathway and mitogen-activated protein kinase signaling pathway, whereas mutated genes associated with fast-feathering rate were primarily enriched in autophagy, calcium signaling pathway, extracellular matrix-receptor interaction, and Focal adhesion processes. Importantly, two SNPs, involved in feather development, were found in the exonic regions of Wnt signaling genes. These results shed new light on the relationship between genetic mutation and feather growth rate from the perspective of autosomal inheritance and may have economic significance in chicken breeding.
Chickens , Polymorphism, Single Nucleotide , Alleles , Animals , Chickens/genetics , Feathers , Mitogen-Activated Protein Kinases/genetics , Polymorphism, Single Nucleotide/genetics
The main advantage of having livestock, for example, the laying hens, in a controlled environment is that the optimum growth conditions can be achieved with accuracy. The indoor air temperature, humidity, gases concentration, etc., would significantly affect the animal performance, thus should be maintained within an acceptable range. In order to achieve the goals of precision poultry farming, various models have been developed by researchers all over the world to estimate the hourly indoor environmental parameters so as to provide decision suggestions. However, a key parameter of hourly manure area in the poultry house was missing in the literature to predict the ammonia emission using the recently developed mechanistic model. Therefore, in order to fill the gap of the understanding of hourly manure coverage proportion and area on the manure belt, experimental measurements were performed in the present study using laying hens from 10 weeks age to 30 weeks age. For each test, six polypropylene (pp) plates were applied to collect the manure dropped by the birds every hour, and photographs of the plates were taken at the same time using a pre-fixed camera. Binary images were then produced based on the color pictures to determine the object coverage proportion. It was demonstrated that for laying hens of stocking density around 14 birds/m2, the manure coverage proportion at the 24th hour after the most recent manure removal was about 60%, while the value was approximately 82% at the 48th hour. Meanwhile, for laying hens at different ages, the hourly increment of manure coverage proportion showed a similar pattern with four distinct stages within 48 h. The statistical analyses demonstrated no significant correlation between the hourly increment of manure weight and the hourly increment of manure coverage proportion. Finally, prediction models for estimating the hourly manure coverage proportion on the manure belt in typical laying hen houses were provided.
Hf1-xZrxO2 (HZO) is a complementary metal-oxide-semiconductor (CMOS)-compatible ferroelectric (FE) material with considerable potential for negative capacitance field-effect transistors, ferroelectric memory, and capacitors. At present, however, the deployment of HZO in CMOS integrated circuit (IC) technologies has stalled due to issues related to FE uniformity. Spatially mapping the FE distribution is one approach to facilitating the optimization of HZO thin films. This paper presents a novel technique based on synchrotron X-ray nanobeam absorption spectroscopy capable of mapping the three main phases of HZO (i.e., orthorhombic (O), tetragonal (T), and monoclinic (M)). The practical value of the proposed methodology when implemented in conjunction with kinetic-nucleation modeling is demonstrated by our development of a T â O annealing (TOA) process to optimize HZO films. This process produces an HZO film with the largest polarization values (Ps = 64.5 µC cm-2; Pr = 35.17 µC cm-2) so far, which can be attributed to M-phase suppression followed by low-temperature annealing for the induction of a T â O phase transition.
BACKGROUND: The adaptation to hypoxia in high altitude areas has great research value in the field of biological sciences. Tibetan chicken has unique adaptability to high-altitude, low pressure and anoxic conditions, and served as a biological model to search for genetic diversity of hypoxia adaption. METHODS: The whole genome re-sequencing technology was conducted to investigate the genetic diversity. RESULTS: In this study, we obtained quantity genetic resource, contained 5164926 single nucleotide polymorphisms (SNPs), 237504 Insertion/Deletion (InDel), 55606 structural variation types in all chromosomes of Tibetan chicken. Moreover, 17154 non-synonymous mutations, 45763 synonymous mutations, 258 InDel mutations and 9468 structural mutations were detected in coding sequencing (CDS) region. Furthermore, SNPs occur in 591 genes, including HIF1A, VEGF, MAPK 8/9/10/11, PPARA/D/G, NOTCH2, and ABCs, which were involved in 14 hypoxia-related pathways, such as VEGF signaling pathway, MAPK signaling pathway, PPAR signaling pathway and Notch signaling pathway. Among them, 19 genes with non-synonymous SNP variation in CDS were identified. Moreover, structure variation in CDS also occurred in the mentioned above genes with SNPs. CONCLUSIONS: This study provides useful targets for clarifying the hypoxia adaptability of the domestication of chickens in Tibetan and may help breeding efforts to develop improved breeds for the highlands.
Adaptation, Physiological , Altitude , Chickens/genetics , Polymorphism, Single Nucleotide , Animals , Avian Proteins/genetics , Chickens/physiology , INDEL Mutation , Metabolic Networks and Pathways
As a ubiquitous heavy metal, cadmium (Cd) is highly toxic to various organs. However, the effects and molecular mechanism of Cd toxicity in the chicken heart remain largely unknown. The goal of our study was to investigate the cardiac injury in chickens' exposure to Cd. We detected the levels of oxidative stress-related molecules in the Cd-induced chicken heart, and assessed the histopathological changes by hematoxylin and eosin staining. RNA sequencing was performed to identify differentially expressed mRNAs between the Cd-induced group and control group. The expression of candidate genes involved in oxidative stress was certified by quantitative reverse transcription PCR. Our results showed that the expression of glutathione, peroxidase, and superoxide dismutase was significantly decreased and malondialdehyde was increased in the heart of chickens by Cd induction. The disorderly arranged cardiomyocytes, swelled and enlarged cells, partial cardiomyocyte necrosis, blurred morphological structure, and notable inflammatory cell infiltration were observed in the Cd-induced chicken heart. RNA sequencing identified 23 upregulated and 11 downregulated mRNAs in the heart tissues of the chicken in the Cd-induced group, and functional pathways indicated that they were associated with oxidative stress. Moreover, CREM, DUSP8, and ITGA11 expressions were significantly reduced, whereas LAMA1 expression was induced in heart tissue of chickens by Cd treatment. Overall, our findings revealed that oxidative stress and pathological changes in the chicken heart could be triggered by Cd. The mRNA transcriptional profiles identified differentially expressed genes in the chicken heart by Cd induction, revealing oxidative stress-related key genes and enhancing our understanding of Cd toxicity in the chicken heart.
Cadmium , Chickens , Animals , Antioxidants , Cadmium/toxicity , Chickens/genetics , Oxidative Stress , Transcriptome
The tumor suppressor p53 serves important roles in cell cycle arrest and apoptosis, and its activation increases the sensitivity of cancer cells to radiotherapy or chemotherapy. In the present study, the small molecule 2-[1-(4-(benzyloxy)phenyl)-3-oxoisoindolin-2-yl)-2-(4-methoxyphenyl)] acetic acid (CDS-3078) significantly increased p53 mRNA expression levels in a dose-dependent manner. Treatment with CDS-3078 increased p53 expression levels and p53-mediated activation of its downstream target genes in HeLa cells. Additionally, p53+/+ HeLa cells treated with CDS-3078 presented with dysfunctional mitochondria, as indicated by the decrease in Bcl-2 levels, the increase in Bcl-2 homologous antagonist killer and the increase in cytochrome c release from the mitochondria to the cytoplasm. The present results suggested that CDS-3078 treatment significantly induced G2/M phase cell cycle arrest. Therefore, CDS-3078 administration induced apoptosis via p53-mediated cell cycle arrest, causing mitochondrial dysfunction and resulting in apoptotic cell death in cervical cancer cells. Collectively, the present results suggested that CDS-3078 may be a potential anticancer agent.
Although several cross-sectional studies have shown an association of metabolic syndrome (MetS) with nodular thyroid disease, related prospective studies are scarce. This study investigated the association of MetS with thyroid nodule (TN) incidence in Chinese adults, and explored whether the development of or recovery from MetS is associated with changes in the risk of developing TNs. A total of 4,749 Chinese aged 18-65 years were involved in this 6-year prospective study. The association of MetS with TN prevalence was examined. TN-free individuals at baseline (n = 3,133) were further examined. TN incidence rates in groups with different MetS statuses (MetS-free, MetS-developed, MetS-recovery and MetS-chronic) were analyzed. Of all participants, 18.21 and 31.65% had MetS and TNs, respectively. MetS patients had a higher TN prevalence than the non-MetS group (31.08 vs. 19.81% in males, p < 0.01; 59.52 vs. 39.59% in females, p < 0.01). Sex, age and MetS were independent risk factors for TNs. At a median follow up of 5.94 years, the MetS-chronic group (4.37/100 person-years) had a higher risk of TNs (adjusted incidence rate ratio [IRR] = 1.288 [95% CI 1.014-1.636]) compared with the MetS-free group (2.72/100 person-years) in the whole cohort. In males, the MetS-chronic group (3.76/100 person-years) had a higher risk of TNs (adjusted IRR = 1.367 [95% CI 1.017-1.835]) compared with the MetS-free group (2.31/100 person-years). In females, the risk of TNs was significantly higher in the MetS-chronic (6.44/100 person-years) and MetS-developed (6.31/100 person-years) groups compared with the MetS-free group (3.23/100 person-years).
Metabolic Syndrome/epidemiology , Thyroid Nodule/epidemiology , Adolescent , Adult , Aged , China/epidemiology , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Prevalence , Risk , Young Adult
Hypoxia affects the physiology of cells and organisms; however, the mechanisms associated with hypoxia adaptation remain unknown in Tibetan chickens. In this study, we aimed to identify long noncoding RNAs (lncRNAs) involved in hypoxia adaptation in Tibetan chickens and Daheng broilers, to provide insights into the mechanisms underlying hypoxia induction. RNA sequencing results revealed that a total of 5504 lncRNAs and 16,779 microRNAs were differentially expressed in four Tibetan chickens and four Daheng broilers; 70 lncRNAs were up-regulated and 113 lncRNAs were down-regulated in the Tibetan chickens compared to the expression levels in the Daheng broilers. The differentially expressed lncRNAs (DElncRNAs) were enriched in the following Gene ontology terms: protein complex localization, small-molecule metabolic process, and RNA splicing. Kyoto Encyclopedia of Genes and Genomes analyses revealed that the DElncRNAs were mainly enriched in pathways that regulate cell junctions and intercellular spaces and oxygen or energy metabolism, mainly involved in hypoxic adaption. Moreover, a predicted ceRNA network with five DElncRNAs interacted with three miRNAs that acted on 42 pathways through 19 target genes. Quantitative real-time polymerase chain reaction was used to verify that the expression levels of ENSGALG00000008047, ENSGALG00000050044, and ENSGALG00000053982 were significantly lower in Tibetan chickens than in the Daheng broilers, consistent with the RNA sequencing results. We obtained lncRNA expression profiles for the heart tissue of Tibetan chickens for the first time and have provided novel data that may aid research on biological adaptation to hypoxic stress.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
