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Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.
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Sistema de Señalización de MAP Quinasas , Meiosis , Ratones Noqueados , Espermatozoides , Animales , Masculino , Ratones , Meiosis/fisiología , Espermatozoides/fisiología , Espermatogénesis/fisiología , Fosfatasa 6 de Especificidad Dual/genética , Fosfatasa 6 de Especificidad Dual/metabolismo , Testículo/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismoRESUMEN
Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.
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Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/inmunología , Masculino , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Anciano , Quimioembolización Terapéutica/métodos , Pronóstico , Resultado del Tratamiento , Adulto , Quimioradioterapia/métodosRESUMEN
BACKGROUND: Dysphagia, or swallowing disorder, is a common complication following stroke, significantly impacting patients' quality of life. Electromyographic biofeedback (EMGBF) therapy has emerged as a potential rehabilitation technique to improve swallowing function, but its efficacy in comparison with conventional treatments remains to be further explored. AIM: To investigate the effects of different treatment intensities of EMGBF on swallowing function and motor speed after stroke. METHODS: The participants were divided into three groups, all of which received routine neurological drug therapy and motor function rehabilitation training. On the basis of routine swallowing disorder training, the EMGBF group received additional EMGBF training, while the enhanced EMGBF group received two additional training sessions. Four weeks before and after treatment, the degree of swallowing disorder was evaluated using the degree of swallowing disorder score (VGF) and the Rosenbek penetration-aspiration scale (PAS). RESULTS: Initially, there was no significant difference in VGF and PAS scores among the groups (P > 0.05). After four weeks, all groups showed significant improvement in both VGF scores and PAS scores. Furthermore, the standardized swallowing assessment and videofluoroscopic dysphagia scale scores also improved significantly post-treatment, indicating enhanced swallowing function and motor function of the hyoid-bone laryngeal complex, particularly in the intensive EMGBF group. CONCLUSION: EMGBF training is more effective than traditional swallowing training in improving swallowing function and the movement rate of the hyoid laryngeal complex in patients with post-stroke dysphagia.
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Toxoplasma gondii is an important protozoan pathogen, which can cause severe diseases in the newborns and immunocompromised individuals. Developing an effective vaccine against Toxoplasma infection is a critically important global health priority. Immunofluorescence staining analysis revealed that TgSAG2 and TgSRS2 are membrane associated and displayed on the surface of the parasite. Immunizations with pBud-SAG2, pBud-SRS2 and pBud-SAG2-SRS2 DNA vaccines significantly increased the production of specific IgG antibodies. Immunization with pBud-SAG2-SRS2 elicited cellular immune response with higher concentrations of IFN-γ and IL-4 compared to the control group. Antigen-specific lymphocyte proliferations in the pBud-SRS2 and pBud-SAG2-SRS2 groups were significantly higher compared to that in the control group. Furthermore, 30 % of mice immunized with pBud-SAG2-SRS2 survived after the challenge infection with virulent T. gondii RH tachyzoites. This study revealed that immunization with pBud-SAG2-SRS2 induced potent immune responses, and has the potential as a promising vaccine candidate for the control of T. gondii infection.
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Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Inmunoglobulina G , Proteínas Protozoarias , Vacunas Antiprotozoos , Toxoplasma , Toxoplasmosis Animal , Vacunas de ADN , Animales , Vacunas de ADN/inmunología , Vacunas de ADN/genética , Vacunas de ADN/administración & dosificación , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Toxoplasma/inmunología , Toxoplasma/genética , Anticuerpos Antiprotozoarios/sangre , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Vacunas Antiprotozoos/genética , Ratones , Inmunoglobulina G/sangre , Femenino , Toxoplasmosis Animal/prevención & control , Toxoplasmosis Animal/inmunología , Ratones Endogámicos BALB C , Interferón gamma/inmunología , Modelos Animales de Enfermedad , Proliferación Celular , Interleucina-4/inmunología , Análisis de SupervivenciaRESUMEN
OBJECTIVES: To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support. METHODS: A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital, involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS. The infants were randomly divided into a supine group (37 infants) and a prone group (40 infants). Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position, continuing in this cycle until weaning from the ventilator. The effectiveness and safety of the two approaches were compared. RESULTS: At 6 hours after enrollment, the prone group showed lower arterial blood carbon dioxide levels, inspired oxygen concentration, oxygenation index, rates of tracheal intubation bacterial colonization, and Neonatal Pain, Agitation and Sedation Scale scores compared to the supine group (P<0.05). There were no significant differences between the groups in terms of pH, arterial oxygen pressure, positive end-expiratory pressure, duration of mechanical ventilation, accidental extubation, ventilator-associated pneumonia, air leak syndrome, skin pressure sores, feeding intolerance, and grades II-IV intraventricular hemorrhage (P>0.05). CONCLUSIONS: Compared to supine positioning, prone ventilation effectively improves oxygenation, increases comfort, and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS, without significantly increasing adverse reactions.
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Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Posición Prona , Recién Nacido , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Masculino , Femenino , Estudios Prospectivos , Respiración Artificial/métodosRESUMEN
Energy recovery from low-strength wastewater through anaerobic methanogenesis is constrained by limited substrate availability. The development of efficient methanogenic communities is critical but challenging. Here we develop a strategy to acclimate methanogenic communities using conductive carrier (CC), electrical stress (ES), and Acid Orange 7 (AO7) in a modified biofilter. The synergistic integration of CC, ES, and AO7 precipitated a remarkable 72-fold surge in methane production rate compared to the baseline. This increase was attributed to an altered methanogenic community function, independent of the continuous presence of AO7 and ES. AO7 acted as an external electron acceptor, accelerating acetogenesis from fermentation intermediates, restructuring the bacterial community, and enriching electroactive bacteria (EAB). Meanwhile, CC and ES orchestrated the assembly of the archaeal community and promoted electrotrophic methanogens, enhancing acetotrophic methanogenesis electron flow via a mechanism distinct from direct electrochemical interactions. The collective application of CC, ES, and AO7 effectively mitigated electron flow impediments in low-strength wastewater methanogenesis, achieving an additional 34% electron recovery from the substrate. This study proposes a new method of amending anaerobic digestion systems with conductive materials to advance wastewater treatment, sustainability, and energy self-sufficiency.
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Scorpio, a commonly used animal medicine in China, is derived from Buthus martensii as recorded in the Chinese Pharmacopoeia. China harbors rich species of Scorpionida and adulterants exist in the raw medicinal material and deep-processed products of Scorpio. The microscopic characteristics of the deep-processed products may be incomplete or lost during processing, which makes the identification difficult. In this study, the maximum likelihood(ML) tree was constructed based on the morphology and cytochrome C oxidase subunit I(COâ ) to identify the species of Scorpio products. The results showed that the main adulterant of Scorpio was Lychas mucronatus. According to the specific SNP sites in the COâ sequence of B. martensii, the stable primers were designed for the identification of the medicinal material and formula granules of Scorpio. The polymerase chain reaction(PCR) at the annealing temperature of 61 â and 30 cycles produced bright specific bands at about 150 bp for both B. martensii and its formula particles and no band for adulterants. The adaptability of the method was investigated, which showed that the bands at about 150 bp were produced for Scorpio medicinal material, lyophilized powder, and formula granules, and commercially available formula granules. The results showed that the established method could be used to identify the adulterants of Scorpio and its formula granules, which could help to improve the quality control system and ensure the safe clinical application of Scorpio formula granules.
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Animales Ponzoñosos , Medicamentos Herbarios Chinos , Escorpiones , Animales , Reacción en Cadena de la Polimerasa/métodosRESUMEN
BACKGROUND: Inflammatory factors are associated with depression. We seek to investigate the correlation between inflammatory cytokines and prognosis of depression or suicidal ideation and behavior at 3 months in depression patients. METHODS: Eighty-two depressed outpatients were recruited and treated as usual. Plasma cytokines were measured at baseline. Patients were followed up with Patient Health Questionnaire-9 and suicidal ideation and behavior according to the item 3 of Hamilton depression scale for 3 months. RESULTS: Compared to the depression patients with low level of interleukin-1ß, the high one had severe depressive symptoms at month 2 and 3 (B 0.92, P < 0.01; B 0.86, P = 0.02; respectively). The incidence of suicidal ideation or behavior was 18.3% at 3 months. Depression patients with high levels of tumor necrosis factor-α showed high risk of suicidal ideation and behavior than the low one (OR 2.16, 95% CI 1.00-4.65, P = 0.04). CONCLUSIONS: High levels of interleukin-1ß and tumor necrosis factor-α were predictive of middle-term severe depressive symptoms and suicidal ideation and behavior respectively.
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Citocinas , Trastorno Depresivo Mayor , Humanos , Depresión , Estudios de Cohortes , Factor de Necrosis Tumoral alfa , Trastorno Depresivo Mayor/diagnóstico , Interleucina-1beta , Ideación SuicidaRESUMEN
Toxoplasma gondii is an opportunistic protozoan parasite that is highly prevalent in the human population and can lead to adverse health consequences in immunocompromised patients and pregnant women. Noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), play important regulatory roles in the pathogenesis of many infections. However, the differentially expressed (DE) miRNAs and circRNAs implicated in the host cell response during the lytic cycle of T. gondii are unknown. In this study, we profiled the expression of miRNAs and circRNAs in human foreskin fibroblasts (HFFs) at different time points after T. gondii infection using RNA sequencing (RNA-seq). We identified a total of 7, 7, 27, 45, 70, 148, 203, and 217 DEmiRNAs and 276, 355, 782, 1863, 1738, 6336, 1229, and 1680 DEcircRNAs at 1.5, 3, 6, 9, 12, 24, 36, and 48 h post infection (hpi), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DE transcripts were enriched in immune response, apoptosis, signal transduction, and metabolism-related pathways. These findings provide new insight into the involvement of miRNAs and circRNAs in the host response to T. gondii infection.
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MicroARNs , Toxoplasma , Embarazo , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Endógeno Competitivo , Perfilación de la Expresión Génica , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.
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Toxoplasma , Toxoplasmosis , Humanos , Animales , Ratones , Tilosina/farmacología , Tilosina/uso terapéutico , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/parasitología , Sulfadiazina/farmacología , Sulfadiazina/uso terapéutico , BazoRESUMEN
Photodynamic therapy (PDT) is a potential treatment strategy for melanoma. As a second-generation photosensitizer, Zinc phthalocyanine (ZnPc) has many advantages for anti-tumor PDTs, such as strong absorption in the red and near infrared regions, high photo and chemical stability, etc. However, ZnPc has a poor water solubility and is apt to aggregate due to the π-π interaction between molecules, which limits its applications. In this study, various solvents and surfactants were screened for dissolving ZnPc and preparing ZnPc@SDC-TPGS micelle and thermosensitive in situ gel. After the cytotoxic effects of thermosensitive gels on PDT were tested, the antitumor effects on PDT of them in mice by intratumoral injection were evaluated, including body weight, and tumor weight, volume and morphology. The cell death pathway and the relationship of reactive oxygen species yield with apoptotic rate of tumor cells induced by ZnPc in situ gel were investigated. The results were that N-methyl-pyrrolidone (NMP) mixed with 2 % SDC and aqueous solution containing 2 % TPGS and 2 % SDC were used to synthesize ZnPc@SDC-TPGS micelle and the thermosensitive in situ gel. The cytotoxic effects of thermosensitive gels showed good tumor suppression of ZnPc@SDC-TPGS in situ gel and no toxicity of the blank gel. Intratumoral injection in situ gel containing 3 µg ZnPc under irradiation demonstrated good tumor inhibition in mice with melanoma. Apoptosis has been established as the primary pathway of cell death, and the production of reactive oxygen species (ROS) plays a crucial role in cellular apoptosis induced by ZnPc@SDC-TPGS in situ gel. In conclusion, the intratumoral injection of ZnPc@SDC-TPGS thermosensitive in situ gel provides a promising local treatment option for melanoma.
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Antineoplásicos , Isoindoles , Melanoma , Compuestos Organometálicos , Fotoquimioterapia , Compuestos de Zinc , Ratones , Animales , Melanoma/tratamiento farmacológico , Micelas , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Inyecciones Intralesiones , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , GelesRESUMEN
BACKGROUND: Silver-Russell syndrome (SRS) is a rare genetic disorder that is mainly associated with prenatal and postnatal growth retardation. Loss of methylation on chromosome 11p15 and maternal uniparental disomy on chromosome 7 (upd(7)mat) are two common causes, accounting for approximately 50% and 10% of all patients, respectively. Pathogenic variants of genes, such as HMGA2, IGF2, CDKN1C, and PLAG1, have also been detected in patients with SRS. So far, SRS caused by PLAG1 alterations have only been described in two sporadic cases and three families. PATIENT PRESENTATION: The genetic and clinical manifestations of SRS in a patient carrying a novel variant of PLAG1 were reported and these results were compared with those of five previously reported cases. Trio-based whole-exome sequencing revealed a heterozygous variation in PLAG1 (NM_002655.3: c.131del; p.(Asn44Thrfs*6)) in an infant girl with clinical suspicion of SRS. Familial studies confirmed that the mutation was inherited from her father. As seen in previously reported cases, the patient presented with prenatal and postnatal growth retardation, relative macrocephaly at birth, prominent forehead during infancy, and triangular face. However, no clinical characteristics such as feeding difficulties, hypothyroidism, or psychomotor and speech delay. CONCLUSIONS: This study identified the sixth documented case of PLAG1 variants leading to SRS and expanded our knowledge of the molecular spectrum of SRS phenotypes.
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Arbuscular mycorrhizal fungi (AMF) are widely distributed microorganisms in the soil, playing an important role in vegetation succession, plant community diversity, and improving soil physicochemical properties. In this study, morphological identification and high-throughput sequencing technology were used to comprehensively analyze the AMF community composition and diversity at different succession stages of Songnen saline-alkali grassland. To determine the root colonization status of plants collected in the field, a colonization system was established using late-succession plants as host plants to verify the existence of mycorrhizal symbiosis and the matching phenomenon of AMF in Songnen saline-alkali grassland. The results indicated that both morphological methods and high-throughput sequencing technology showed that glomus was the dominant genus of AMF in Songnen saline grassland. Redundancy analysis (RDA) and linear regression analysis showed that electrical conductivity (EC) and pH were the main environmental factors affecting AMF species diversity and community structure in the succession sequence of Songnen saline grassland. In addition, the results of root colonization identification and the colonization system test in the field showed that AMF successfully colonized vegetation at different succession stages and had mycorrhizal symbiosis. The results of this study could help to understand the AMF community of Songnen saline-alkali grassland as well as provide a reference and basis for optimizing the AMF community structure of Songnen saline-alkali grassland through human intervention in the future and using mycorrhizal technology to restore and rebuild the degraded ecosystem of Songnen saline-alkali grassland.
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Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.
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Envejecimiento , Apoptosis , Células de la Granulosa , Peróxido de Hidrógeno , Factores de Transcripción de Tipo Kruppel , Lisofosfolípidos , Fosfotransferasas (Aceptor de Grupo Alcohol) , Esfingosina , Femenino , Humanos , Envejecimiento/metabolismo , Retroalimentación Fisiológica , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Peróxido de Hidrógeno/farmacología , Técnicas In Vitro , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Factores de Transcripción de Tipo Kruppel/biosíntesis , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Lisofosfolípidos/biosíntesis , Lisofosfolípidos/metabolismo , Técnicas de Cultivo de Órganos , Estrés Oxidativo/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Regiones Promotoras Genéticas , Esfingosina/biosíntesis , Esfingosina/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Objectives: Locally advanced rectal cancer (LARC) has a high risk of distant metastasis (DM). Currently, many treatment courses of LARC have arisen, but patients' DM status has not significantly improved. This study was designed to compare the effect between preoperative regional transarterial chemoembolization combined with neoadjuvant chemoradiotherapy and standard neoadjuvant therapy on preventing DM in patients with LARC. Methods: A total of 81 LARC patients between July 2013 and May 2018 were enrolled in this retrospective study. Among them, 44 patients received preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy (the interventional group), and 37 patients received only neoadjuvant chemoradiotherapy (the control group). The baseline data; preoperative toxicities; postoperative DM rate within 1, 2, and 3 years; and postoperative complications were compared between the two groups. Results: All patients successfully completed their treatments. There were no significant differences between the two groups in age, gender, tumor size, distance between the tumor and anal verge, CEA level, lymphovascular invasion, or tumor stage before treatment. The pathological T staging post-treatment in the interventional group was significantly reduced compared to that of the control group (p = 0.025). There were no significant differences between groups in DM rates within 1 and 2 years after surgery. In terms of DM rate within 3 years after surgery, the interventional group was significantly lower than that of the control group (9.1% vs. 29.7%, p = 0.036). Conclusion: Preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy may play an important role in reducing postoperative DM in LARC.
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Bioaccessible fractions of particle-bound hydrophobic organic compounds (HOCs) are critical to evaluating human inhalation exposure risk. However, the key factors for controlling the release of HOCs into the lung fluid are not adequately examined. To address this issue, eight particle size fractions (0.056-18 µm) from different particle emission sources (barbecue and smoking) were collected and incubated with an in vitro method for determining inhalation bioaccessibilities of polycyclic aromatic hydrocarbons (PAHs). The bioaccessible fractions of particle-bound PAHs were 35-65% for smoke-type charcoal, 24-62% for smokeless-type charcoal, and 44-96% for cigarette. The size distributions of bioaccessible fractions of 3-4 ring PAHs were symmetric with the patterns of their masses, characterized as a unimodal distribution with both the trough and peak at 0.56-1.0 µm. Analysis from machine learning showed that chemical hydrophobicity appeared to be the most significant factor affecting inhalation bioaccessibility of PAHs, followed by organic carbon and elemental carbon contents. Particle size seemed to have little effect on the bioaccessibility of PAHs. A compositional analysis of human inhalation exposure risk from total concentration, deposition concentration, and bioaccessible deposition concentration in alveolar region showed a shift in the key particle size from 0.56-1.0 µm to 1.0-1.8 µm and an increasing in the contributions of 2-3 ring PAHs to risk for cigarette due to the high bioaccessible fractions. These results suggested the significance of particle deposition efficiency and bioaccessible fractions of HOCs in risk assessment.
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Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Humanos , Tamaño de la Partícula , Contaminantes Atmosféricos/análisis , Carbón Orgánico/análisis , Carbono/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Compuestos Orgánicos/análisis , Monitoreo del Ambiente/métodos , Material Particulado/análisisRESUMEN
Objective: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future. Methods: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed. Results: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all). Conclusions: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.
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OBJECTIVE: To determine the impact of a solitary lifestyle on health-related quality of life (HRQoL) in adults with obstructive sleep apnea (OSA). METHODS: This was a prospective cohort study; patients diagnosed with OSA but not receiving continuous positive airway pressure (CPAP) therapy were enrolled in our study. These participants completed basic information and the Short Form-36 Health Survey (SF-36) at baseline and were divided into the living alone and living with others groups. Telephone follow-up was performed 1 year later to re-evaluate the SF-36. Differences in health status between and within groups were assessed. In addition, variables associated with changes in the health of the whole population were examined. RESULTS: A total of 402 patients with OSA were enrolled, including 120 in the living alone group and the rest in the living with others group. After a year, mental health scores of the living alone group decreased (55.7 ± 21.5 versus 54.1 ± 22.7, p = 0.001), while physical functioning scores of the living with others group increased significantly (82.1 ± 24.7 versus 82.6 ± 24.2, p = 0.006). In the whole population, the determinants of mental health change after 1 year from baseline were alcohol drinking (beta coefficient - 1.169, 95% CI - 2.03 to - 0.309, p = 0.008) and solitary living (beta coefficient - 1.135, 95% CI - 2.072 to - 0.199, p = 0.018). CONCLUSION: Regarding all initial variables, alcohol drinking and solitary living seem to be the predictors of mental health change of patients with OSA in China. We speculate that to improve the quality of life of such people, the medical staff could provide certain social support for them.
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Calidad de Vida , Apnea Obstructiva del Sueño , Humanos , Adulto , Calidad de Vida/psicología , Estudios de Cohortes , Estudios Prospectivos , Ambiente en el Hogar , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Toxoplasma gondii is an obligate intracellular protozoan parasite which seriously threatens the health of domestic animals and humans. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts greater than 200 nucleotides, which are widely involved in transcriptional and epigenetic regulations. However, little is known about the roles of host lncRNAs in the response to T. gondii infections. In this study, using Illumina sequencing technology, we analyzed the expression profiles of mRNAs and lncRNAs in BALB/c mouse brain following infection by T. gondii PRU strain (type II genotype) cysts. The identified differentially expressed (DE) RNAs were subjected to bioinformatics analysis. A total of 2,090 annotated lncRNAs along with 3,577 novel lncRNAs were identified. In the acutely infected mouse brain, a total of 330 mRNAs and 19 lncRNAs were dys-regulated, whereas 136 DE mRNAs and 9 DE lncRNAs were identified in chronically infected mouse brain. GO analysis revealed that these DE mRNAs identified at acute infection stage were involved in immune response, whereas DE mRNAs found at chronic infection stage were mostly enriched in response to protozoan. KEGG analysis showed that DE mRNAs were significantly enriched in disease related pathways. In addition, the putative mRNA-lncRNA co-expression network was constructed, and several hub regulatory RNAs were identified based on the transcriptome data. This study firstly characterized the co-expression profile of mRNAs and lncRNAs in mouse brain infected with T. gondii and provided a framework for further studies of the roles of lncRNAs in host neuropathology during toxoplasmosis progression.