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OBJECTIVE: To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T). METHODS: A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts. RESULTS: It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P < 0.05). The secretion of killer cytokines TNF-α and IFN-γ in the EpCAM expression positive cell group was higher than that in the negative group (P < 0.05). In the experimental group treated with EpCAM-CAR-T cells, the survival rate of nude mice was higher (P < 0.05), and the tumour was smaller than that in the blank and control groups (P < 0.05). The secretion of serum killer cytokines TNF-α and IFN-γ in tumour-bearing nude mice in the experimental group treated with EpCAM-CAR-T cells was higher than that in the blank and control groups (P < 0.05). CONCLUSION: This study successfully constructed EpCAM-CAR cells and found that they can target and recognise EpCAM-positive tumour cells, secrete killer cytokines TNF-α and IFN-γ and better inhibit the growth and metastasis of colorectal cancer in vitro and in vivo than unmodified T cells.
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Neoplasias Colorrectales , Molécula de Adhesión Celular Epitelial , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Molécula de Adhesión Celular Epitelial/inmunología , Molécula de Adhesión Celular Epitelial/metabolismo , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/terapia , Humanos , Animales , Receptores Quiméricos de Antígenos/inmunología , Inmunoterapia Adoptiva/métodos , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Interferón gamma/metabolismo , Línea Celular Tumoral , Femenino , Ratones Desnudos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunologíaRESUMEN
INTRODUCTION: Homologous recombination repair during meiosis is essential for the exchange of genetic information between sister chromosomes, underpinning spermatogenesis and, consequently, fertility. The disruption of this process can lead to infertility, highlighting the importance of identifying the molecular actors involved. OBJECTIVES: This study aims to elucidate the role of the E3 ubiquitin ligase Rnf126 in spermatogenesis and its impact on fertility, particularly through its involvement in meiotic homologous recombination repair. METHODS: We used heterozygous and homozygous Rnf126 deletion models in mouse testes to examine the consequences on testicular health, sperm count, and the process of spermatogenesis. Additionally, we explored the association between RNF126 gene missense variants and nonobstructive male infertility in patients, with a focus on their functional impact on the protein's ubiquitin ligase activity. RESULTS: Rnf126 deletion led to testicular atrophy, disrupted seminiferous tubule structure, reduced sperm count, and spermatogenesis arrest at meiotic prophase I. Furthermore, male mice exhibited impaired homologous recombination repair and increased apoptosis within the seminiferous tubules. We identified four missense variants of the RNF126 gene (V68M, R241H, E261A, D253N) associated with male infertility. Specifically, the E261A and D253N variants, located in the RING domain, directly compromised the E3 ubiquitin ligase activity of RNF126. CONCLUSION: Our findings demonstrate the pivotal role of RNF126 in maintaining spermatogenesis and fertility, offering insights into the molecular mechanisms underlying male infertility. The identified RNF126 variants present novel targets for diagnostic and therapeutic strategies in treating nonobstructive male infertility.
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Biochar application to soil has proven to be an excellent approach for decreasing the concentration of auto-toxic compounds and promoting plant growth in continuous-cropping fields. However, the mechanisms underlying the action pathway among biochars, auto-toxic compounds and tobacco remain unknown. In this study, we conducted an experiment tracking the incidence rate of black rot and auto-toxic compounds for a 3-year continuous-cropping tobacco pot trial in response to biochar treatment intensity compared with that of non-biochar treatment. Biochar inhibited the incidence of black rot. Using ultra-high-performance liquid chromatography-mass spectrometry (UPLCâMS/MS), we revealed that biochar can effectively decrease the concentration of p-hydroxybenzoic acid (PHA), which is associated with the incidence rate of black rot (R2 = 0.890, p < 0.05). The sorption kinetics and isotherm of PHA sorption on biochar indicate that the coexistence of heterogeneous and monolayer sorption plays an important role in the adsorption process. Using Molecular dynamics (MD), Density functional theory (DFT) and Independent gradient model (IGM) analyses, we provide evidence that van der Waals force (vdW), π-π bonds and H-bonds between biochar and PHAs are the dominant factors that affect adsorption capacity. Moreover, the molecular adsorption rate (Nbiochar: NPHAs = 1:4) was theoretically calculated. In contrast, biochar dramatically increased nutrient retention capacity and improved soil properties, further enhancing tobacco quality, including its agronomic and physiological traits. Therefore, we considered that biochar not only relieved continuous cropping but also improved soil properties suitable for tobacco growth. Together, we demonstrate that the action of biochar in continuously cropped soil improves soil traits and alleviates auto-toxic compound toxicity. These data contribute to the direction of modified biochar application to improve continuous-cropping soil.
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Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.
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The manufacture of damping alloy parts with stable damping properties and high mechanical performances in the selective laser melting (SLM) process is influenced by temperature evolution and residual stress distribution. Choosing an appropriate scanning strategy, namely the specific trajectory along which the laser head scans powders within given area, is crucial, but clearly defined criteria for scanning strategy design are lacking. In this study, a three-dimensional finite element model (FEM) of the SLM process for manufacturing a WE43 alloy component was established and validated against the published experimental data. Eleven different scanning strategies were designed and simulated, considering variables such as scanning track length, direction, Out-In or In-Out strategy, start point, and interlayer variation. The results showed that scanning strategy, geometry, and layer number collectively affect temperature, melt pool, and stress outputs. For instance, starting scanning at a colder part of the powder layer could lead to a high peak temperature and low melt pool depth. A higher layer number generally results in lower cooling rate, a lower temperature gradient, a longer melt pool life, and larger melt pool dimensions. Changing the start point between scanning circulations helps mitigate detrimental residual stress. This work highlights the potential of analyzing various scanning strategy-related variables, which contributes to reducing trial-and-error tests and selecting optimal scanning strategies under different product quality requirements. This article can assist in the design of appropriate scanning strategies to prevent defects such as element loss due to evaporation, poor bonding, and deformation or cracking from high residual stress. Additionally, identifying stress concentration locations and understanding the effects of geometry and layer number on thermal and mechanical behaviors can assist in geometry design.
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In this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management.
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Xenocoumacin 1 (Xcn 1), antibiotic discovered from secondary metabolites of Xenorhabdus nematophila, had the potential to develop into a new pesticide due to its excellent activity against bacteria, oomycetes and fungi. However, the current low yield of Xcn1 limits its development and utilization. To improve the yield of Xcn1, response surface methodology was used to determine the optimal composition of fermentation medium and one factor at a time approach was utilized to optimize the fermentation process. The optimal medium composed of in g/L: proteose peptone 20.8; maltose 12.74; K2HPO4 3.77. The optimal fermentation conditions were that 25 °C, initial pH 7.0, inoculum size 10%, culture medium 75 mL in a 250 mL shake flask with an agitation rate of 150 rpm for 48 h. Xenorhabdus nematophila YL001 was produced the highest Xcn1 yield (173.99 mg/L) when arginine was added to the broth with 3 mmol/L at the 12th h. Compared with Tryptic Soy Broth medium, the optimized fermentation process resulted in a 243.38% increase in Xcn1 production. The obtained results confirmed that optimizing fermentation technology led to an increase in Xcn1 yield. This work would be helpful for efficient Xcn1 production and lay a foundation for its industrial production.
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Medios de Cultivo , Fermentación , Xenorhabdus , Xenorhabdus/metabolismo , Medios de Cultivo/química , Concentración de Iones de Hidrógeno , Antibacterianos/biosíntesis , BenzopiranosRESUMEN
Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we develop GametesOmics, a comprehensive database that integrates the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification(s) of each gene; Tools with Differentially expressed gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell clusters and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Ortholog for tracking and comparing gene expression, DNA methylation, and chromatin accessibility between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.
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Metilación de ADN , Bases de Datos Genéticas , Gametogénesis , Animales , Humanos , Ratones , Gametogénesis/genética , Metilación de ADN/genética , Epigénesis Genética/genética , Masculino , Células Germinativas/metabolismo , Femenino , Espermatogénesis/genética , Oogénesis/genética , Genómica/métodos , MultiómicaRESUMEN
RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.
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As an emerging additive manufacturing technology, inkjet printing has been increasingly applied in microelectronics field. However, due to the impacting and rebounding behaviors of conductive ink droplets impinging onto flat substrates, it is challenging to fabricate conductive lines with desired quality, such as suitable line width and line thickness, and matching resistance when it is used for interconnecting multifarious electronic components if there is not a proper configuration of operating parameters. To address this research gap, this article aims to investigate the effect of process parameters on the quality of conductive lines, including the platform temperature, printing speed, number of layers, and delay time (droplet interarrival time), are selected to conduct a full factorial experiment. First, the approximate parameter ranges for ensuring the continuity of conductive lines are determined. Second, this study analyzes the interactive effect among process parameters on line quality. Third, an artificial neural network (ANN) is constructed to predict the quality of printed lines. Results show that the line width does not increase with an increased number of layers, while the line thickness shows an increasing trend. The low resistance and high aspect ratio of printed line are achieved by printing 5 layers with the platform temperature of 70°C, the delay time of 12.2 ms, and the printing speed of 1139.39 mm/min. Moreover, the ANN model can be used to predict line width and line thickness with excellent performance, except for the resistance due to the irregular line edge. This study provides a useful guide for the selection of appropriate printing parameters to realize a diverse range of quality properties for 3D printed conductive lines in integrated circuits.
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This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 µm to 5 µm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.
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Additive manufacturing of conductive layers on a dielectric substrate has garnered significant interest due to its promise to produce printed electronics efficiently and its capability to print on curved substrates. A considerable challenge encountered is the conductive layer's potential peeling due to inadequate adhesion with the dielectric substrate, which compromises the durability and functionality of the electronics. This study strives to facilitate the binding force through dielectric substrate surface modification using concentrated sulfuric acid and ultraviolet (UV) laser treatment. First, polyetheretherketone (PEEK) and nanoparticle silver ink were employed as the studied material. Second, the surface treatment of PEEK substrates was conducted across six levels of sulfuric acid exposure time and eight levels of UV laser scanning velocity. Then, responses such as surface morphology, roughness, elemental composition, chemical bonding characteristics, water contact angle, and surface free energy (SFE) were assessed to understand the effects of these treatments. Finally, the nanoparticle silver ink layer was deposited on the PEEK surface, and the adhesion force measured using a pull-off adhesion tester. Results unveiled a binding force of 0.37 MPa on unmodified surface, which escalated to 1.99 MPa with sulfuric acid treatment and 2.21 MPa with UV laser treatment. Additionally, cross-approach treatment investigations revealed that application sequence significantly impacts results, increasing binding force to 2.77 MPa. The analysis further delves into the influence mechanism of the surface modification on the binding force, elucidating that UV laser and sulfuric acid surface treatment methods hold substantial promise for enhancing the binding force between heterogeneous materials in the additive manufacturing of electronics.
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Background: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared with in vitro fertilization (IVF). Methods: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer (ET) treatment cycle from January 2019 to February 2021. In total, 2171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8702 and 2668 women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy, and live birth after the first ET cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. Results: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in the TAI-positive and IVF group vs. 0.7 [0.5-0.8] in the TAI-positive and ICSI group vs. 0.6 [0.5-0.8] the TAI-negative and IVF group vs. 0.7 [0.5-0.8] in the TAI-negative and ICSI group, p < 0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio [aOR]: 0.80 [confidence interval, CI: 0.67-0.97]; clinical pregnancy: 43.0% vs. 38.8%, aOR: 0.81 [CI: 0.67-0.97]; live birth: 36.2% vs. 32.4%, aOR: 0.81 [CI: 0.66-0.98]). Conclusion: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared with IVF. Further prospective clinical trials are needed to confirm our findings.
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Autoinmunidad , Fertilización In Vitro , Infertilidad Femenina , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Adulto , Fertilización In Vitro/métodos , Embarazo , Infertilidad Femenina/terapia , Infertilidad Femenina/inmunología , Estudios Retrospectivos , Nacimiento Vivo , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/terapia , Enfermedades de la Tiroides/complicaciones , Glándula Tiroides/inmunologíaRESUMEN
BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.
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Endometriosis , Infertilidad , Embarazo , Masculino , Femenino , Humanos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Tasa de Natalidad , Estudios Retrospectivos , Autoinmunidad , Glándula Tiroides , Semen , Fertilización In Vitro/métodos , Nacimiento Vivo/epidemiología , Índice de EmbarazoRESUMEN
Early life stress (ELS) has been thought to increase vulnerability to developing psychiatric disorders later in life, while some researchers have found that adversity early in life may promote stress resilience. Studies investigating the resilient effect of maternal separation (MS) are still relatively few, and the underlying mechanisms remain unknown. In the current study, the effect of a single 24 h MS paradigm at postnatal day 9 (PND 9) in female C57BL/6J mice was investigated by assessing behavioral performance in middle adolescence. We demonstrated that, mice in MS group displayed decreased anxiety-like behavior and increased exploratory behavior than controls in the open field test and elevated plus maze test. Furthermore, MS mice exhibited improved hippocampal-dependent spatial learning in the Morris water maze test. This performance indicated behavioral resilience to early life stress. The protein expression levels of Homer1 isoforms, which are implicated in a variety of neuropsychiatric disorders, were evaluated using Western blot analysis. A significant increase in hippocampal Homer1a protein expression was observed immediately after MS, which subsequently decreased until adolescence (PND 27-42), when a significant increase was observed again. This distinctive change of hippocampal Homer1a protein expression pattern indicated that hippocampal Homer1a might play a role in behavioral resilience to MS in female C57BL/6J mice. In conclusion, this study demonstrated that exposure to a single 24 h MS at PND 9 promoted behavioral resilience of female C57BL/6J mice in middle adolescence. This behavioral resilience might be related to increased expression of hippocampal Homer1a.
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Sclerotinia sclerotiorum (Lib.) de Bary, a polyphagous necrotrophic fungal pathogen, has brought about significant losses in agriculture and floriculture. Until now, the most common method for controlling S. sclerotiorum has been the application of fungicides. Xenocoumacin 1 (Xcn1) is a potential biopesticide having versatile antimicrobial activities, generated by Xenorhabdus nematophila. This study was intended to isolate Xcn1 from X. nematophila YL001 and clarify its efficacies for S. sclerotiorum control. Xcn1 demonstrated a wider antifungal spectrum against 10 plant-pathogenic fungi. It also exhibited a strong inhibitory effect on the mycelial growth of S. sclerotiorum with an EC50 value of 3.00 µg/mL. Pot experiments indicated that Xcn1 effectively inhibited disease extension on oilseed rape and broad bean plants caused by S. sclerotiorum. Morphological and ultrastructural observations revealed that the hyphae of S. sclerotiorum became twisted, shriveled, and deformed at the growing points after treatment with Xcn1 at 3.00 µg/mL and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. Moreover, Xcn1 also increased cell membrane permeability and decreased the content of exopolysaccharide as well as suppressing the activities of polygalacturonase and cellulase of S. sclerotiorum, but exerted no effects on oxalic acid production. This study demonstrated that Xcn1 has great potential to be developed as a new biopesticide for the control of S. sclerotiorum.
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The aim of this study was to investigate the anti-Eimeria tenella mechanism of Qingchang Compound (QCC) and provide a basis for its clinical application. The active ingredients, active ingredient-disease intersection targets, and possible pathways of QCC for the treatment of chicken coccidiosis were analyzed, the binding ability of pharmacodynamic components and target proteins was determined by network pharmacology and the molecular docking, and a model of infection with coccidiosis was constructed to verify and analyze the mechanism of action of QCC against coccidiosis. Among the 57 components that met the screening conditions, the main bioactive components were quercetin, dichroine, and artemisinin, with IL-1ß, IL-6, IL-10, IFN-γ, and IL-8 as the core targets. Simultaneously, the KEGG signaling pathway of QCC anti-coccidiosis in chickens was enriched, including cytokine-cytokine receptor interactions. The results showed that the main pharmacodynamic components of QCC and the core targets could bind well; artemisinin and alpine possessed the largest negative binding energies and presented the most stable binding states. In addition, in vivo studies showed that QCC reduced blood stool in chickens with coccidiosis, restored cecal injury, and significantly reduced the mRNA and protein expression levels of IL-1ß, IL-10, and IFN-γ in ceca (p < 0.01). Our results suggest that the main active ingredients of QCC are artemisinin and alpine and its mechanism of action against coccidiosis may be related to the reduction of the inflammatory response by acting on specific cytokines.
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Sleep deprivation (SD) negatively affects many cognitive functions, such as language performance. However, what remains unclear is whether and how SD affects the language-related brain network based on gender and age differences. The current study of 86 healthy adults used resting-state functional magnetic resonance imaging (rs-fMRI) to measure language-related functional connectivity after full sleep or partial SD. Gender and age differences in functional connectivity were assessed across four linguistic aspects: phonetics, morphology, semantics, and syntax. The results showed that SD can affect the connectivity status of language-related brain networks, especially syntax-related networks. Furthermore, the influence of SD on the functional connectivity in language-related networks differed between male and female groups, and between younger and older groups. Specifically, there were gender differences in the temporal association cortex and age differences in the parietal association cortex, during full sleep versus partial SD. These findings highlight changes in the brain's functional connectivity in response to SD as a potential source of gender and age differences in brain function.
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Mapeo Encefálico , Encéfalo , Lenguaje , Imagen por Resonancia Magnética , Caracteres Sexuales , Privación de Sueño , Humanos , Masculino , Femenino , Adulto , Privación de Sueño/fisiopatología , Privación de Sueño/diagnóstico por imagen , Adulto Joven , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Vías Nerviosas/fisiopatología , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Persona de Mediana Edad , Envejecimiento/fisiología , AdolescenteRESUMEN
RATIONALE: Most Chinese patients with locally advanced gastric cancer at diagnosis have an overall 5-year survival rate of <50%. Surgical resection alone is not suitable for patients with locally advanced gastric cancer. Currently, comprehensive treatment is the focus of locally advanced gastric cancer. PATIENTS CONCERNS: The patient, a 56-year-old female, was admitted to the hospital because of "4â +â months of double hydronephrosis found during a physical examination." Who was admitted for computer tomography and gastroscopy examinations, and take pathological tissue specimens during endoscopic examination. DIAGNOSES: Computed tomography assessment indicated ulcerative gastric cancer with an abdominal implant, bladder, and bone metastases. An endoscopic examination revealed that the ulcer of the gastric angle was huge, and through relevant auxiliary examinations, the diagnosis of this disease is gastric cancer complicated with multiple metastases to bladder, rectum, lumbar spine, and peritoneum. Clinically diagnosed as cT4bN3M1. INTERVENTIONS: The patient is currently undergoing first, second, and third line neoadjuvant therapy, combined with immunotherapy, targeted therapy, neoadjuvant intraperitoneal systemic chemotherapy, nutritional support, and other treatment plans. OUTCOMES: After 15 cycles of treatment, the progression-free survival had reached 15 months. The patient had an NRS2002 score of 1, an ECOG score of I, a quality of life score of 55, albumin of 35.27 g/L, and a decrease in abdominal and pelvic fluid accumulation and exudation compared to before. LESSONS: We demonstrated high survival of almost 3 years in a patient with gastric cancer that was complicated by bone, peritoneal, rectal, and bladder metastases. The combination of immunotherapy, targeted therapy, and neoadjuvant intraperitoneal systemic chemotherapy, along with the maintenance of nutritional status and CTCs could be a valuable modality for the subsequent treatment and observation of similar patients.
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Anticuerpos Monoclonales , Neoplasias Gástricas , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Calidad de Vida , Oligopéptidos , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
There is no converging evidence on how a word's semantic transparency affects morphemes' potential semantic activation. The inconsistent results may be due to the limitation of traditional univariate analyses, in which the semantic transparency was treated as discrete categories. In the current study, Chinese two-character words were used as stimuli and functional magnetic resonance imaging (fMRI) techniques were combined with a priming paradigm. Unlike most previous studies, the multivariate representation similarity analysis (RSA) was used to treat semantic transparency as a continuous variable. The RSA results showed that widespread regions in the frontal-parietal-temporal network represent the semantic perception of characters in all words and transparent words, but no brain areas were identified in opaque words. Unlike RSA results, univariate analyses showed no significant difference between the opaque and transparent words. These results suggest that RSA is more suitable to examine the neural mechanism related to continuous variables such as semantic transparency.