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LINE-1 retrotransposons are fast-evolving mobile genetic entities that play roles in gene regulation, pathological conditions, and evolution. Here, we show that the primate LINE-1 5'UTR contains a primate-specific open reading frame (ORF) in the antisense orientation that we named ORF0. The gene product of this ORF localizes to promyelocytic leukemia-adjacent nuclear bodies. ORF0 is present in more than 3,000 loci across human and chimpanzee genomes and has a promoter and a conserved strong Kozak sequence that supports translation. By virtue of containing two splice donor sites, ORF0 can also form fusion proteins with proximal exons. ORF0 transcripts are readily detected in induced pluripotent stem (iPS) cells from both primate species. Capped and polyadenylated ORF0 mRNAs are present in the cytoplasm, and endogenous ORF0 peptides are identified upon proteomic analysis. Finally, ORF0 enhances LINE-1 mobility. Taken together, these results suggest a role for ORF0 in retrotransposon-mediated diversity.
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Pan troglodytes/genética , Retroelementos , Regiones no Traducidas 5' , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Citoplasma/genética , Humanos , Elementos de Nucleótido Esparcido Largo , Datos de Secuencia Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Sistemas de Lectura Abierta , Procesamiento Postranscripcional del ARN , ARN sin Sentido/genética , ARN Mensajero/química , ARN Mensajero/genética , Ribosomas/metabolismo , Alineación de SecuenciaRESUMEN
Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown of Grm2 resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused by Grm2 knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided in vivo and in vitro evidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.
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Giro Dentado , Sistema de Señalización de MAP Quinasas , Masculino , Femenino , Ratones , Animales , Giro Dentado/fisiología , Neuronas/fisiología , Hipocampo/fisiología , Quinasas de Proteína Quinasa Activadas por Mitógenos , Neurogénesis/fisiologíaRESUMEN
Bile acid-activated receptors (BARs) such as a G-protein bile acid receptor 1 and the farnesol X receptor are activated by bile acids (BAs) and have been implicated in the regulation of microbiota-host immunity in the intestine. The mechanistic roles of these receptors in immune signaling suggest that they may also influence the development of metabolic disorders. In this perspective, we provide a summary of recent literature describing the main regulatory pathways and mechanisms of BARs and how they affect both innate and adaptive immune system, cell proliferation, and signaling in the context of inflammatory diseases. We also discuss new approaches for therapy and summarize clinical projects on BAs for the treatment of diseases. In parallel, some drugs that are classically used for other therapeutic purposes and BAR activity have recently been proposed as regulators of immune cells phenotype. Another strategy consists of using specific strains of gut bacteria to regulate BA production in the intestine.
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2D metal-organic frameworks-based (2D MOF-related) materials benefit from variable topological structures, plentiful open active sites, and high specific surface areas, demonstrating promising applications in gas storage, adsorption and separation, energy conversion, and other domains. In recent years, researchers have innovatively designed multiple strategies to avoid the adverse effects of conventional methods on the synthesis of high-quality 2D MOFs. This review focuses on the latest advances in creative synthesis techniques for 2D MOF-related materials from both the top-down and bottom-up perspectives. Subsequently, the strategies are categorized and summarized for synthesizing 2D MOF-related composites and their derivatives. Finally, the current challenges are highlighted faced by 2D MOF-related materials and some targeted recommendations are put forward to inspire researchers to investigate more effective synthesis methods.
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"Perovskite / Carbon" interface has remained a key bottleneck for the hole-conductor-free perovskite solar cells based on carbon-electrode (CPSCs), due to problems like loose physics contact, defects, energy mismatch, poor chemical coupling, etc. A previous study shows that octylammonium iodide (OAI) blending in carbon paste induced a kind of "in-situ healing" effect for "perovskite / carbon" interface, and improved power conversion efficiency from ≈13% to >19%. Here the beneath mechanism is further explored by careful examination of the interaction between OAI molecule and carbon black (CB) nanoparticles. It comes to show that, the famous "CB adsorption" plays a key role during the "healing" processes. Due to CB adsorption behavior, the mass ratio between OAI and CB influences much on the healing effect. By suitably adjusting the mass ratio between OAI and CB, and increasing the light harvest of perovskite, an efficiency of 19.41% is achieved for the hole-conductor-free CPSCs. Device efficiency and the charge-extraction and recombination process are tracked with the storage period, continuous improvement appears for devices assembled by relatively higher CB mass. A kind of "slow-release effect" is revealed during the OAI-induced "in-situ healing" process, which is caused by the famous "CB adsorption" behavior.
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Although oncogenicity of the stem cell regulator SOX9 has been implicated in many solid tumors, its role in lymphomagenesis remains largely unknown. In this study, SOX9 was overexpressed preferentially in a subset of diffuse large B-cell lymphomas (DLBCLs) that harbor IGH-BCL2 translocations. SOX9 positivity in DLBCL correlated with an advanced stage of disease. Silencing of SOX9 decreased cell proliferation, induced G1/S arrest, and increased apoptosis of DLBCL cells, both in vitro and in vivo. Whole-transcriptome analysis and chromatin immunoprecipitation-sequencing assays identified DHCR24, a terminal enzyme in cholesterol biosynthesis, as a direct target of SOX9, which promotes cholesterol synthesis by increasing DHCR24 expression. Enforced expression of DHCR24 was capable of rescuing the phenotypes associated with SOX9 knockdown in DLBCL cells. In models of DLBCL cell line xenografts, SOX9 knockdown resulted in a lower DHCR24 level, reduced cholesterol content, and decreased tumor load. Pharmacological inhibition of cholesterol synthesis also inhibited DLBCL xenograft tumorigenesis, the reduction of which is more pronounced in DLBCL cell lines with higher SOX9 expression, suggesting that it may be addicted to cholesterol. In summary, our study demonstrated that SOX9 can drive lymphomagenesis through DHCR24 and the cholesterol biosynthesis pathway. This SOX9-DHCR24-cholesterol biosynthesis axis may serve as a novel treatment target for DLBCLs.
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Colesterol/genética , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas del Tejido Nervioso/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Factor de Transcripción SOX9/genética , Vías Biosintéticas , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Proteínas de Fusión Oncogénica/genética , Oncogenes , TranscriptomaRESUMEN
The aim of this study was to investigate the utility of serum soluble B7-H3 (sB7-H3) as a diagnostic marker for early-stage nonsmall cell lung cancer (NSCLC) and its potential for evaluating the prognosis of patients with advanced-stage NSCLC. In this study, an ELISA was employed to detect the expression levels of sB7-H3 in a cohort of patients diagnosed with NSCLC ( n = 122) and a control group ( n = 42) during the same observation period. Comparative analyses were conducted to ascertain the variations in sB7-H3 concentrations between the NSCLC cohort and the healthy control group, as well as across pathological types and the presence and absence of lymph node metastasis. (1) The concentration of sB7-H3 in patients diagnosed with NSCLC exhibited a statistically significant increase compared to that observed in the healthy control group ( P < 0.05). Elevated expression levels of sB7-H3 demonstrated a significant correlation with pathological type, lymph node metastasis, tumor, node and metastasis stage and programmed cell death ligand (PD-L1) expression ( P < 0.05). (2) The diagnostic utility of sB7-H3 for the diagnosis of NSCLC and the heightened expression of PD-L1 demonstrated high levels of sensitivity and specificity. (3) Elevated levels of sB7-H3 emerged as an independent risk factor impacting the overall survival of patients diagnosed with advanced NSCLC. The findings of this study suggest that sB7-H3 holds promise as a diagnostic tool for early-stage NSCLC. The elevated expression of sB7-H3 appears to serve as a reliable indicator for assessing the prognosis of patients diagnosed with advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Pronóstico , Antígeno B7-H1 , Neoplasias Pulmonares/diagnóstico , Metástasis Linfática , Antígenos B7/metabolismo , Factores de TranscripciónRESUMEN
Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.
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Artritis Reumatoide , Autofagia , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Animales , Humanos , Glucólisis , Masculino , Membrana Sinovial/metabolismo , Ácido Láctico/metabolismo , Células Endoteliales/metabolismoRESUMEN
We describe herein an N-heterocyclic-carbene-catalyzed atroposelective synthesis of axially chiral diaryl ethers. Through a sequentially enantioselective desymmetric process and a kinetic resolution process, the products could be constructed in good yields with excellent enantiopurities. Both alcohols and phenols were compatible with this catalytic system. The axially chiral carboxylic acids derived from the esters were proven to be potential chiral ligands for asymmetric synthesis, for example, Rh(III)-catalyzed enantioselective C-H functionalization.
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BACKGROUND: Cancer-derived exosomes contribute significantly in intracellular communication, particularly during tumorigenesis. Here, we aimed to identify two immune-related ovarian cancer-derived exosomes (IOCEs) subgroups in ovarian cancer (OC) and establish a prognostic model for OC patients based on immune-related IOCEs. METHODS: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq data, as well as clinical and prognostic information. Consensus clustering analysis was performed to identify two IOCEs-associated subgroups. Kaplan-Meier analysis was used to compare the overall survival (OS) between IOCEs-high and IOCEs-low subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to investigate the mechanisms and biological effects of differentially expressed genes (DEGs) between the two subtypes. Besides, an IOCE-related prognostic model of OC was constructed by Lasso regression analysis, and the signature was validated using GSE140082 as the validation set. RESULTS: In total, we obtained 21 differentially expressed IOCEs in OC, and identified two IOCE-associated subgroups by consensus clustering. IOCE-low subgroup showed a favorable prognosis while IOCE-high subgroup had a higher level of immune cell infiltration and immune response. GSEA showed that pathways in cancer and immune response were mainly enriched in IOCE-high subgroup. Thus, IOCE-high subgroup may benefit more in immunotherapy treatment. In addition, we constructed a risk model based on nine IOCE-associated genes (CLDN4, AKT2, CSPG5, ALDOC, LTA4H, PSMA2, PSMA5, TCIRG1, ANO6). CONCLUSION: We developed a novel stratification system for OV based on IOCE signature, which could be used to estimate the prognosis as well as immunotherapy for OC patient.
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Exosomas , Neoplasias Ováricas , ATPasas de Translocación de Protón Vacuolares , Femenino , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Pronóstico , Inmunoterapia , Análisis por ConglomeradosRESUMEN
BACKGROUND: To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. METHODS: A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. RESULTS: Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P < 0.05), and negatively correlated with PSS-FA total score (P < 0.05). Fear of recurrence, family support level, number of children, educational background, treatment modality, and fertility intention were influencing factors for reproductive concerns in patients of childbearing age with gynecologic malignancies (all P < 0.05). CONCLUSION: The reproductive concerns, fear of recurrence and family support are all at moderate levels in patients of childbearing age with gynecologic malignancies, and reproductive concerns are positively correlated with fear of recurrence and negatively correlated with family support.
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Apoyo Familiar , Miedo , Neoplasias de los Genitales Femeninos , Recurrencia Local de Neoplasia , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , China/epidemiología , Miedo/psicología , Neoplasias de los Genitales Femeninos/psicología , Recurrencia Local de Neoplasia/psicología , Encuestas y CuestionariosRESUMEN
Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.
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COVID-19 , Humanos , Masculino , COVID-19/prevención & control , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2 , Peptidil-Dipeptidasa A , Fertilidad , Hormonas Esteroides Gonadales , VacunaciónRESUMEN
Phosphorus pollution poses a significant challenge in addressing water contamination. The coagulant is one of the effective methods to remove phosphorus from wastewater. Abundant Al and Fe oxides in sludge residue make it have great potential to synthesize water treatment coagulants. However, the utilization of sludge residue for preparation of coagulant was seldom investigated. In this study, we fabricated a novel coagulant, polyaluminum ferric chloride (SM-PAC), using sludge residue as a raw material through acid leaching and polymerization processes. Characterization results confirm that the parameters of SM-PAC meet the specifications outlined in the national standard (GB/T 22627-2022). We investigated the effects of pH, dosage, initial phosphorus concentration, and contact time on the removal efficiency of SM-PAC. As anticipated, the prepared SM-PAC exhibited a significant efficacy in removing phosphorus, meeting the discharge standards set for municipal sewage. Furthermore, the adsorption kinetics analysis suggests that the predominant mode of phosphorus adsorption on SM-PAC is chemical adsorption. Furthermore, the SM-PAC was employed in the actual wastewater treatment plant and exhibited excellent efficiency in phosphorus removal. The utilization of SM-PAC can not only effectively address the issue of sludge disposal but also achieve the goal of "treating waste with waste." It is expected that the proposed method of reusing sludge residue as a resource can provide a sustainable way to synthesize a coagulant for phosphorus removal.
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Fósforo , Reciclaje , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua , Fósforo/análisis , Fósforo/química , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Reciclaje/métodos , Adsorción , Compuestos Férricos/química , Aguas Residuales/químicaRESUMEN
Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.
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Proteína HMGB1 , Ligusticum , Osteoartritis , Humanos , Ratas , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Condrocitos , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacología , Dinoprostona , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Transducción de Señal , Inflamación/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Apoptosis , ARN Mensajero/metabolismoRESUMEN
Fear of possible negative effects of coronavirus disease 2019 (COVID-19) vaccine on fertility is the main reason for vaccine hesitancy among the public especially women of childbearing age. Despite the high coverage of COVID-19 vaccination in China, more scientific evidence is still needed to address their concerns and guide fertility counseling and management in the future. Herein, we performed a retrospective cohort study at a single large center for reproductive medicine in China between August 2020 and May 2023. Patients aged 20-42 years with no history of laboratory-confirmed COVID-19 were included and categorized into different groups according to their vaccination status. The serum sex hormone levels, anti-Müllerian hormone concentrations, embryo quality, and pregnancy outcomes were evaluated and compared among them. We found there were no significant differences in the concentrations of follicle-stimulating hormone, luteinizing hormone and progesterone between the unvaccinated, first-dose, second-dose, and booster vaccinated groups. However, the estradiol showed a highly significant increase in the one-dose vaccinated group compared with its levels in other groups. Among unvaccinated and either vaccinated patients, anti-Müllerian hormone levels were comparable (p = 0.139). The number of oocytes retrieved, fertilization rate and good-quality embryo rate were all similar between each group of in vitro fertilization and intracytoplasmic sperm injection. No significant differences were observed regarding other laboratory parameters. Moreover, the vaccination status of infertile couples did not exert any adverse effect on the pregnancy outcomes in all assisted reproductive technologies cycles. In short, we comprehensively evaluated the reproductive safety of inactivated severe acute respiratory syndrome coronavirus 2 vaccine and found any dose of vaccination wouldn't negatively affect female fertility parameters such as sex hormone levels and ovarian reserve. Moreover, this is the first study to complete the live birth follow-up of the cohort after receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccine, further dispelling the misconception and providing reassurance for decision-making by clinicians.
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Vacunas contra la COVID-19 , COVID-19 , Fertilidad , Femenino , Humanos , Masculino , Embarazo , Hormona Antimülleriana , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Fertilización In Vitro , Hormonas Esteroides Gonadales , Índice de Embarazo , Estudios Retrospectivos , SARS-CoV-2 , SemenRESUMEN
Classical non-homologous end joining (cNHEJ) and homologous recombination compete for the repair of double-stranded DNA breaks during the cell cycle. Homologous recombination is inhibited during the G1 phase of the cell cycle, but both pathways are active in the S and G2 phases. However, it is unclear why cNHEJ does not always outcompete homologous recombination during the S and G2 phases. Here we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ. Suppression of CYREN allows cNHEJ to occur at telomeres and intrachromosomal breaks during the S and G2 phases, and cells lacking CYREN accumulate chromosomal aberrations upon damage induction, specifically outside the G1 phase. CYREN acts by binding to the Ku70/80 heterodimer and preferentially inhibits cNHEJ at breaks with overhangs by protecting them. We therefore propose that CYREN is a direct cell-cycle-dependent inhibitor of cNHEJ that promotes error-free repair by homologous recombination during cell cycle phases when sister chromatids are present.
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Reparación del ADN por Unión de Extremidades/fisiología , Fase G2 , Reparación del ADN por Recombinación/fisiología , Fase S , Línea Celular , Cromátides/genética , Cromátides/metabolismo , Aberraciones Cromosómicas , Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades/genética , Fase G1 , Humanos , Autoantígeno Ku/química , Autoantígeno Ku/metabolismo , Unión Proteica , Reparación del ADN por Recombinación/genética , Telómero/genética , Telómero/metabolismoRESUMEN
This study aimed to improve the removal of nitrogen treating rural domestic sewage by developing a novel strategy for achieving partial nitrification-anammox (PNA) in an integrated vertical subsurface flow constructed wetland (VSFCW). The influent ammonia was oxidized to nitrite in the partial nitrification VSFCW (VSFCWPN), and 5 mg/L of hydroxylamine was added under the appropriate dissolved oxygen concentration level (1.2 ± 0.2 mg/L) to stabilize the average nitrite accumulation rate at 88.24% and maintain the effluent NO2--N/NH4+-N ratio at 1.26 ± 0.15. The effluent from VSFCWPN was introduced to the following chamber (VSFCWAN), where ammonia and nitrite were removed by the autotrophic anammox process. This implementation achieved high removal efficiencies for chemical oxygen demand, total nitrogen, and PO43--P, reaching 86.26%, 90.22%, and 78.94%, respectively, with influent concentrations of 120.75 mg/L, 60.02 mg/L, and 5.05 mg/L. Substrate samples were collected from 10 cm height (PN1, AN1) and 25 cm height (PN2, AN2). Microbial community analysis showed that Nitrosomonas dominated the community composition in VSFCWPN, with an increase from 1.61% in the inoculated sludgePN to 16.31% (PN1) and 12.09% (PN2). Meanwhile, Ca. Brocadia accounted for 44.81% (AN1) and 36.50% (AN2) in VSFCWAN. These results confirm the feasibility of the proposed strategy for establishing PNA and efficiently treating rural domestic sewage in an integrated VSFCW.
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Nitrificación , Aguas del Alcantarillado , Desnitrificación , Oxidación Anaeróbica del Amoníaco , Nitrógeno , Humedales , Amoníaco/química , Nitritos , Oxidación-Reducción , Reactores BiológicosRESUMEN
OBJECTIVE: We aimed to perform a qualitative synthesis of evidence on the role of 68Ga-Pentixafor PET in atherosclerosis. METHODS: A systematic search of the PubMed and Embase databases for studies reporting the evaluation of atherosclerotic lesions by 68Ga-Pentixafor PET was performed with a search time frame from database creation to 2022-12-26. The diagnostic test evaluation tool QUADAS-2 was used to evaluate the quality of the included literature and to perform descriptive analyses of relevant outcome indicators. RESULTS: A total of 6 studies with 280 patients were included. One study reported only imaging outcome metrics, while the other five studies reported imaging outcome metrics and clinical correlation metrics. For imaging outcomes, three studies reported imaging results for 68Ga-Pentixafor PET only, and the other three studies reported imaging results for comparative analysis of 68Ga-Pentixafor PET with 18F-FDG PET. For clinical correlation, three studies reported the correlation between tracer uptake and cardiovascular risk factors, one study reported the correlation between tracer uptake and plaque calcification, and one study reported the correlation between all three: tracer uptake, cardiovascular risk factors, and plaque calcification. CONCLUSION: 68Ga-Pentixafor PET has a good imaging effect on atherosclerotic lesions, and it is a promising imaging modality that may replace 18F-FDG PET for atherosclerosis imaging in the future. In patients with atherosclerosis, there is a clear clinical correlation between cardiovascular risk factors, tracer uptake, and plaque calcification.
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Aterosclerosis , Calcinosis , Placa Aterosclerótica , Humanos , Radioisótopos de Galio , Fluorodesoxiglucosa F18 , Relevancia Clínica , Receptores CXCR4 , Aterosclerosis/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
Wheat straw, a typical agricultural solid waste, was employed to clarify the effects of torrefaction on the structural features and combustion reactivity of biomass. Two typical torrefaction temperatures (543 K and 573 K), four atmospheres (argon, 6 vol.% O2, dry flue gas and raw flue gas) were selected. The elemental distribution, compositional variation, surface physicochemical structure and combustion reactivity of each sample were identified using elemental analysis, XPS, N2 adsorption, TGA and FOW methods. Oxidative torrefaction tended to optimize the fuel quality of biomass effectively, and the enhancement of torrefaction severity improved the fuel quality of wheat straw. The O2, CO2 and H2O in flue gas could synergistically enhance the desorption of hydrophilic structures during oxidative torrefaction process, especially at high temperatures. Meanwhile, the variations in microstructure of wheat straw promoted the conversion of N-A into edge nitrogen structures (N-5 and N-6), especially N-5, which is a precursor of HCN. Additionally, mild surface oxidation tended to promote the generation of some new oxygen-containing functionalities with high reactivity on the surface of wheat straw particles after undergoing oxidative torrefaction pretreatment. Due to the removal of hemicellulose and cellulose from wheat straw particles and the generation of new functional groups on the particle surfaces, the ignition temperature of each torrefied sample expressed an increasing tendency, while the Ea clearly decreased. According to the results obtained from this research, it could be concluded that torrefaction conducted in a raw flue gas atmosphere at 573 K would improve the fuel quality and reactivity of wheat straw most significantly.
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Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.