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Empathy is predominantly assessed with self-report questionnaires. However, their structural validities were not well-supported. This study aimed to re-explore and refine the factor structure of the Chinese version of the Questionnaire of Cognitive and Affective Empathy (QCAE) and investigate the pathways linked between dimensions of empathy and schizotypy. Data from a valid sample of 1,360 community-dwelling adults (aged 18-35) were subjected to the exploratory graph analysis (EGA) and bootstrap EGA for factor retention. A goodness-of-fit evaluation was conducted using confirmatory factor analysis (CFA). Lastly, a Gaussian graphical model with sum scores of the resultant empathy dimensions, positive, negative, and disorganized schizotypy, and paranoia as nodes was estimated. Results supported a three-factor structure for the revised 20-item QCAE, demonstrating a good model fit. The new Online simulation subscale was associated with reduced disorganized schizotypy, whereas the new Perspective-taking subscale was associated with decreased disorganized schizotypy and increased positive schizotypy. The composite Affective empathy subscale was associated with decreased negative schizotypy and increased positive and disorganized schizotypy and paranoia. Overall, the revised QCAE demonstrated good structural validity, measuring three separable and internally cohesive factors of empathy. Each factor possessed unique and differential relationships with schizotypy dimensions that merit research and clinical attention.

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Achelura yunnanensis is a destructive pest of forests, causing substantial damage on tree growth and severe economic losses. Additionally, as a daytime-active moth, this species also holds important scientific value for investigating the genetic mechanisms governing day-night activity patterns of Lepidoptera. To facilitate effective pest control and deepen our understanding of the diurnal behavior's genetic basis of moths, genomic data for this species are crucial. In this study, we present a chromosome-level reference genome of A. yunnanensis (368.15 Mb in 32 chromosomes; scaffold N50 = 12.61 Mb; BUSCO completeness = 98.0%). Genome annotation shows that the new assembly comprises 37.10% (136.55 Mb) repetitive elements, 1,828 non-coding RNAs, and 15,523 protein-coding genes. Genes involved in lipid metabolism and xenobiotics biodegradation and metabolism, such as cytochrome P450 families, experienced significant expansion in the A. yunnanensis genome. The chromosome-level genome of A. yunnanensis provides a valuable genomic resource for devising novel pest control strategies, and will also help to study the genetic mechanism of the shift of diurnal behavior in Lepidoptera.

Asunto(s)

Genoma de los Insectos , Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Cromosomas de Insectos/genética , Bosques

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Background: Diabetic kidney disease (DKD) is the primary contributor to renal failure and poses a severe threat to human health. Accumulating studies demonstrated that competing endogenous RNA (ceRNA) network is involved in cuproptosis and DKD progression. However, the role of cuproptosis-associated ceRNA network and immune infiltration in DKD remains largely unclear. This study aimed to investigate the cuproptosis-related ceRNA regulation network and immune infiltration in DKD. Methods: The rat model of DKD was induced by combining the nephrectomy of the left kidney, high-fat diet, and streptozotocin. Differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and DKD rats were obtained. DEGs were intersected with cuproptosis-related genes (CRGs) to obtain DE-CRGs. LncRNAs and miRNAs were predicted based on the DE-CRGs, and they were intersected with DEMs and DELs, respectively. Subsequently, a cuproptosis-associated lncRNA-miRNA-mRNA network was established in DKD. In addition, the relative proportion of 22 infiltrating immune cell types in each sample was calculated, and the relationship between hub DE-CRGs and immune cells was explored. Results: In total, there were 429 DEGs, 22 DEMs, and 48 DELs between CON and MOD groups. Then, 73 DE-CRGs were obtained, which were significantly enriched in 22 pathways, such as MAPK signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a core cuproptosis-related ceRNA network that included one lncRNA (USR0000B2476D), one miRNA (miR-34a-3p), and eight mRNAs (Mmp9, Pik3c3, Prom1, Snta1, Slc51b, Ntrk3, Snca, Egf) was established. In addition, 18 hub DE-CRGs were obtained. CIBERSORT algorithms showed that resting dendritic cells and resting NK cells were more infiltrated whereas regulatory T cells were less infiltrated in DKD rats than in normal rats. Spearman's correlation analysis revealed that hub DE-CRGs showed significant positive or negative correlations with naive B cells, regulatory T cells, resting NK cells, M0 macrophages, resting dendritic cells, and resting mast cells. Conclusion: A ceRNA network was comprehensively constructed, and 18 hub DE-CRGs were obtained, which will provide novel insights into the pathologic mechanism elucidation and targeted therapy development of DKD.

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BACKGROUND: Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca2+ signaling participates in tissue fibrosis. However, whether an alteration of Ca2+ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca2+ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-ß1 induced in vitro TED model. METHODS: Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca2+ response on TGF-ß1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-ß1 induced in vitro TED model. The roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways. RESULTS: LTCC inhibitor nimodipine blocked the TGF-ß1 induced intracellular Ca2+ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway. CONCLUSIONS: TGF-ß1 induces an LTCC-mediated Ca2+ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.

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Unsustainable wildlife consumption and illegal wildlife trade (IWT) threaten biodiversity worldwide. Although publicly accessible data sets are increasingly used to generate insights into IWT, little is known about their potential bias. We compared three typical and temporally corresponding data sets (4204 court verdicts, 926 seizure news reports, and 219 bird market surveys) on traded birds native to China and evaluated their possible species biases. Specifically, we evaluated bias and completeness of sampling for species richness, phylogeny, conservation status, spatial distribution, and life-history characteristics among the three data sets when determining patterns of illegal trade. Court verdicts contained the largest species richness. In bird market surveys and seizure news reports, phylogenetic clustering was greater than that in court verdicts, where songbird species (i.e., Passeriformes) were detected in higher proportions in market surveys. The seizure news data set contained the highest proportion of species of high conservation priority but the lowest species coverage. Across the country, all data sets consistently reported relatively high species richness in south and southwest regions, but markets revealed a northern geographic bias. The species composition in court verdicts and markets also exhibited distinct geographical patterns. There was significant ecological trait bias when we modeled whether a bird species is traded in the market. Our regression model suggested that species with small body masses, large geographical ranges, and a preference for anthropogenic habitats and those that are not nationally protected were more likely to be traded illegally. The species biases we found emphasize the need to know the constraints of each data set so that they can optimally inform strategies to combat IWT.

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Cuantificación del sesgo por especies entre fuentes de datos múltiples para el mercado ilegal de fauna y lo que implica para la conservación Resumen El consumo insostenible y el comercio ilegal de fauna y flora silvestres amenazan la biodiversidad en todo el mundo. Aunque los conjuntos de datos de acceso público se utilizan cada vez más para obtener información sobre el mercado ilegal de especies silvestres, se sabe poco sobre su posible sesgo. Comparamos tres conjuntos de datos típicos con correspondencia temporal (4,204 sentencias judiciales, 926 informes de noticias sobre incautaciones y 219 encuestas sobre mercados de aves) de aves autóctonas de China objeto de comercio y evaluamos sus posibles sesgos por especie. En concreto, evaluamos el sesgo y la exhaustividad del muestreo de la riqueza de especies, la filogenia, el estado de conservación, la distribución espacial y las características del ciclo vital entre los tres conjuntos de datos a la hora de determinar los patrones del mercado ilegal. Las sentencias judiciales contenían la mayor riqueza de especies. En los estudios de mercado de aves y en los informes de noticias sobre incautaciones, la agrupación filogenética fue mayor que en las sentencias judiciales, donde las especies de aves canoras (Passeriformes) se detectaron en mayor proporción en los estudios de mercado. El conjunto de datos de noticias sobre decomisos contenía la mayor proporción de especies de alta prioridad para la conservación, pero la menor cobertura de especies. En todo el país, todos los conjuntos de datos informaron sistemáticamente de una riqueza de especies relativamente alta en las regiones sur y suroeste, pero los mercados revelaron un sesgo geográfico septentrional. La composición por especies en los veredictos judiciales y en los mercados también mostró patrones geográficos distintos. Hubo un sesgo significativo de rasgos ecológicos cuando modelamos si una especie de ave se comercializa en el mercado. Nuestro modelo de regresión sugería que las especies con masas corporales pequeñas, grandes áreas de distribución geográfica y preferencia por los hábitats antropogénicos y las especies que no están protegidas a nivel nacional tenían más probabilidades de ser objeto de comercio ilegal. Los sesgos de las especies que hallamos resaltan la necesidad de conocer las limitaciones de cada conjunto de datos para poder informar de manera óptima las estrategias de lucha contra el comercio ilegal de especies silvestres.

Asunto(s)

Biodiversidad , Aves , Comercio , Conservación de los Recursos Naturales , Conservación de los Recursos Naturales/legislación & jurisprudencia , Animales , China , Comercio/legislación & jurisprudencia , Crimen/estadística & datos numéricos , Animales Salvajes , Filogenia , Comercio de Vida Silvestre

RESUMEN

AIM: Angiogenesis is a key event in the successful healing of pulp injuries, and hypoxia is the main stimulator of pulpal angiogenesis. In this study, we investigated the effect of hypoxia on the proangiogenic potential of human dental pulp stem cells (hDPSCs) and the role of miR-143-5p in the process. METHODOLOGY: Human dental pulp stem cells were isolated, cultured and characterized in vitro. Cobalt chloride (CoCl2) was used to induce hypoxia in hDPSCs. CCK-8 and Transwell assays were used to determine the effect of hypoxia on hDPSCs proliferation and migration. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB) and ELISA were performed to assess the mRNA and protein levels of HIF-1α and angiogenic cytokines in hDPSCs. The effect of hypoxia on hDPSCs proangiogenic potential was measured in vitro using Matrigel tube formation and chick chorioallantoic membrane (CAM) assays. Recombinant lentiviral vectors were constructed to stably overexpress or inhibit miR-143-5p in hDPSCs, and the proangiogenic effects were assessed using qRT-PCR, WB, and tube formation assays. miR-143-5p target genes were identified and verified using bioinformatics prediction tools, dual-luciferase reporter assays and RNA pull-down experiments. Finally, a subcutaneous transplantation model in nude mice was used to determine the effects of hypoxia treatment and miR-143-5p overexpression/inhibition in hDPSCs in dental pulp regeneration. RESULTS: Hypoxia promotes hDPSCs proliferation, migration and proangiogenic potential. The in vivo experiments showed that hypoxia treatment (50 and 100 µM CoCl2) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl2 concentration. miR-143-5p inhibition significantly promoted proangiogenic potential of hDPSCs, whereas miR-143-5p overexpression inhibited angiogenesis in vitro. Dual-luciferase reporter assay identified retinoic acid receptor-related orphan receptor alpha (RORA) as an miR-143-5p target gene in hDPSCs. RNA pull-down experiments demonstrated that HIF-1α and RORA were pulled down by biotin-labelled miR-143-5p, and the levels of HIF-1α and RORA bound to miR-143-5p in the hypoxia group were lower than those in the normoxia group. Inhibition of miR-143-5p expression in hDPSCs promoted ectopic dental pulp tissue regeneration. CONCLUSIONS: CoCl2-induced hypoxia promotes hDPSCs-driven paracrine angiogenesis and pulp regeneration. The inhibition of miR-143-5p upregulates the proangiogenic potential of hDPSCs under hypoxic conditions by directly targeting HIF-1α and RORA.

RESUMEN

Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MßCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.

Asunto(s)

Anticuerpos Neutralizantes , Liposomas , Neoplasias Ováricas , Reoviridae , Femenino , Humanos , Neoplasias Ováricas/inmunología , Anticuerpos Neutralizantes/inmunología , Reoviridae/inmunología , Reoviridae/fisiología , Línea Celular Tumoral , Viroterapia Oncolítica/métodos , Apoptosis , Animales , Cationes , Virus Oncolíticos/inmunología , Ratones

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The function of some genetic variants associated with brain-relevant traits has been explained through colocalization with expression quantitative trait loci (eQTL) conducted in bulk postmortem adult brain tissue. However, many brain-trait associated loci have unknown cellular or molecular function. These genetic variants may exert context-specific function on different molecular phenotypes including post-transcriptional changes. Here, we identified genetic regulation of RNA editing and alternative polyadenylation (APA) within a cell-type-specific population of human neural progenitors and neurons. More RNA editing and isoforms utilizing longer polyadenylation sequences were observed in neurons, likely due to higher expression of genes encoding the proteins mediating these post-transcriptional events. We also detected hundreds of cell-type-specific editing quantitative trait loci (edQTLs) and alternative polyadenylation QTLs (apaQTLs). We found colocalizations of a neuron edQTL in CCDC88A with educational attainment and a progenitor apaQTL in EP300 with schizophrenia, suggesting that genetically mediated post-transcriptional regulation during brain development leads to differences in brain function.

Asunto(s)

Neurogénesis , Neuronas , Sitios de Carácter Cuantitativo , Humanos , Neurogénesis/genética , Neuronas/metabolismo , Edición de ARN/genética , Poliadenilación/genética , Esquizofrenia/genética , Regulación de la Expresión Génica , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Encéfalo/metabolismo , Procesamiento Postranscripcional del ARN/genética

RESUMEN

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.

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The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.

Asunto(s)

5-Metilcitosina , Citosina , Metilación de ADN , Proteínas de Unión al ADN , Dioxigenasas , Desarrollo Embrionario , Regulación del Desarrollo de la Expresión Génica , Factores de Transcripción Otx , Proteínas Proto-Oncogénicas , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Humanos , Animales , Factores de Transcripción Otx/metabolismo , Factores de Transcripción Otx/genética , Ratones , Dioxigenasas/metabolismo , Dioxigenasas/genética , Citosina/análogos & derivados , Citosina/metabolismo , Desarrollo Embrionario/genética , Femenino , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Masculino , Blastocisto/metabolismo , Linaje de la Célula/genética , Oocitos/metabolismo , Epigénesis Genética , Sitios de Unión

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Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.

Asunto(s)

Homeostasis , Minociclina , Mitocondrias , Especies Reactivas de Oxígeno , Retinitis Pigmentosa , Minociclina/farmacología , Minociclina/uso terapéutico , Animales , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Homeostasis/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/patología , Degeneración Retiniana/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Células Fotorreceptoras de Vertebrados/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , Retina/efectos de los fármacos , Retina/patología , Retina/metabolismo , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico

RESUMEN

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

RESUMEN

Stress is an emotional state caused by an unexpected external environmental change or stimulus, and several experiments have demonstrated its negative impact on ovarian function, ultimately affecting reproductive ability. Melatonin (MT) has been shown to facilitate oocyte maturation and enhance ovarian function by regulating mitochondrial function. However, the specific effect and underlying molecular mechanisms of MT on stress-induced ovarian dysfunction remain largely unknown. In this study, we established a mouse model of chronic unpredictable mild stress (CUMS) to investigate its impact on ovarian function. Our findings revealed that CUMS led to premature ovarian insufficiency (POI) in mice, characterized by a reduction in follicle numbers and decreased levels of anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP15). Furthermore, CUMS caused decreased expression of mitochondrial fission protein 1 (FIS1) and enhanced level of mitochondrial fusion protein optic atrophy 1(OPA1), mitofusin1(MFN1), as well as nucleus-encoded protein succinate dehydrogenase complex A (SDHA), reflecting mitochondrial dyshomeostasis. Additionally, CUMS resulted in excessive autophagy and apoptosis. However, MT reversed these effects and improved ovarian damage. Importantly, the protective effects of MT were mediated through the inhibition of the eIF2α-AFT4 pathway. Overall, this study provides valuable insights into the treatment of POI caused by CUMS.

RESUMEN

In this paper, we present a new type of isolator based on one-way surface magnetoplasmons (SMPs) at microwave frequencies, and it is the first time that an experimental prototype of isolator with wideband and ultra-high isolation is realized using SMP waveguide. The proposed model with gyromagnetic and dielectric layers is systematically analyzed to obtain the dispersion properties of all the possible modes, and a one-way SMP mode is found to have the unidirectional transmission property. In simulation and experiment with metallic waveguide loaded with yttrium-iron-garnet (YIG) ferrite, the scattering parameters and the field distributions agree well with the analysis and verify the one-way transmission property. The isolation is found to be as high as 80 dB and the typical value of insertion loss is 1 dB. Besides, the one-way transmission band can be controlled by changing the magnetic bias. From theoretical analysis and simulation, it is found that with a tiny value of 10 Oe of the magnetic bias, the relative bandwidth can be tuned to be greater than 50%. Compared with conventional isolators, this one-way SMP isolator has the advantages of ultra-high isolation, wide relative frequency band, and requires much smaller bias field, which has promising potential in non-reciprocal applications.

RESUMEN

Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.

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OBJECTIVE: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. METHODS: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. RESULTS: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. CONCLUSION: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3.

RESUMEN

Purpose: The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. Methods: We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Results: Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Conclusion: Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.

Asunto(s)

Diagnóstico Tardío , Neoplasias de Células Germinales y Embrionarias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Adulto , Adulto Joven , Adolescente , Pronóstico , Sistemas Neurosecretores/fisiopatología , Persona de Mediana Edad , Estudios de Seguimiento

RESUMEN

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.

Asunto(s)

Autoanticuerpos , Biomarcadores , Proteína C-Reactiva , Cirrosis Hepática , Índice de Severidad de la Enfermedad , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Femenino , Pronóstico , Masculino , Cirrosis Hepática/inmunología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Persona de Mediana Edad , Biomarcadores/sangre , Adulto , Progresión de la Enfermedad , Hepatitis B/inmunología , Hepatitis B/sangre

RESUMEN

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducted a case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (ß = 0.048, 95% CI = 0.002 ~ 0.094), T (ß = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (ß = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.