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BACKGROUND: Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. METHODS: The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. RESULTS: The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. CONCLUSIONS: This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.
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Movimiento Celular , Mitocondrias , Preeclampsia , Receptores Acoplados a Proteínas G , Trofoblastos , Regulación hacia Arriba , Preeclampsia/metabolismo , Preeclampsia/genética , Preeclampsia/patología , Humanos , Embarazo , Femenino , Mitocondrias/metabolismo , Regulación hacia Arriba/genética , Trofoblastos/metabolismo , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Movimiento Celular/genética , Lectinas/metabolismo , Placenta/metabolismo , Ratones , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos B/metabolismo , Antígenos de Diferenciación de Linfocitos B/genética , AdultoRESUMEN
OBJECTIVE: To explore the frequency and effect of extreme temperature on the non-accidental death rate in Hulunbuir, a Chinese ice city. METHODS: From 2014 to 2018, mortality data of residents residing in Hulunbuir City were collected. The lag and cumulative effects of extreme temperature conditions on non-accidental death and respiratory and circulatory diseases were analyzed by distributed lag non-linear models (DLNM). RESULTS: The risk of death was the highest during high-temperature conditions, the RR value was 1.111 (95% CI 1.031 ~ 1.198). The effect was severe and acute. The risk of death during extreme low-temperature conditions peaked on the fifth day, (RR 1.057; 95% CI 1.012 ~ 1.112), then decreased and was maintained for 12 days. The cumulative RR value was 1.289 (95% CI 1.045 ~ 1.589). Heat significantly influenced the incidence of non-accidental death in both men (RR 1.187; 95% CI 1.059-1.331) and women (RR 1.252; 95% CI 1.085-1.445). CONCLUSIONS: Regardless of the temperature effect, the risk of death in the elderly group (≥ 65 years) was significantly higher than that of the young group (0-64 years). High-temperature and low-temperature conditions can contribute to the increased number of deaths in Hulunbei. While high-temperature has an acute effect, low-temperature has a lagging effect. Elderly and women, as well as people with circulatory diseases, are more sensitive to extreme temperatures.
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Enfermedades Cardiovasculares , Dinámicas no Lineales , Masculino , Humanos , Femenino , Anciano , Temperatura , Estudios Longitudinales , Frío , Calor , China/epidemiologíaRESUMEN
UV filters, widely used in personal care products, are ubiquitous environmental pollutants detected and pose a significant public health concern. Benzophenone-3 (BP3) and titanium dioxide nanoparticles (nano-TiO2) are the predominant organic and inorganic UV filters in environmental media. However, few studies have explored the combined developmental neurotoxic (DNT) effects and the underlying mechanisms when co-exposed to BP3 and nano-TiO2. In the present study, zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations of BP3 (10 µg/L), nano-TiO2 (100 µg/L), and mixtures starting from 6 h post fertilization (hpf), respectively. Developmental indicators and motor behaviors were investigated at various developmental stages. Our results showed that BP3 alone or co-exposed with nano-TiO2 increased spontaneous movement at 24 hpf, co-exposure decreased touch response at 30 hpf and hatching rate at 60 hpf. Consistent with these motor deficits, co-exposure to BP3 and nano-TiO2 inhibited relative axon length of primary motor neuron during the early developmental stages, disturbed the expression of axonal growth-related genes at 30 and 48 hpf, increased cell apoptosis on the head region and mRNA levels of apoptosis-related genes, and also increased reactive oxygen species (ROS) levels in zebrafish, suggesting the functional relevance of structural changes. Taken together, our findings demonstrated that BP3 alone or in combination with nano-TiO2 at environmentally relevant concentrations induced evident neurotoxic effects on the developing embryos in zebrafish.
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Nanopartículas , Contaminantes Químicos del Agua , Animales , Pez Cebra/metabolismo , Nanopartículas/toxicidad , Titanio/química , Embrión no Mamífero/metabolismo , Larva , Contaminantes Químicos del Agua/metabolismoRESUMEN
Dupilumab inhibits T-helper 2 (Th2)-driven inflammation cascade by blocking interleukin-4 (IL-4) and IL-13 signaling, which has been recognized to play a crucial role in the pathogenesis of atopic dermatitis (AD) and shown encouraging efficacy on moderate to severe AD.1 We report an interesting Chinese AD case, which developed into pustular psoriasis after treatment with dupilumab.
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Dermatitis Atópica , Eccema , Psoriasis , Anticuerpos Monoclonales Humanizados/efectos adversos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Humanos , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
An instance of colorful k-center consists of points in a metric space that are colored red or blue, along with an integer k and a coverage requirement for each color. The goal is to find the smallest radius ρ such that there exist balls of radius ρ around k of the points that meet the coverage requirements. The motivation behind this problem is twofold. First, from fairness considerations: each color/group should receive a similar service guarantee, and second, from the algorithmic challenges it poses: this problem combines the difficulties of clustering along with the subset-sum problem. In particular, we show that this combination results in strong integrality gap lower bounds for several natural linear programming relaxations. Our main result is an efficient approximation algorithm that overcomes these difficulties to achieve an approximation guarantee of 3, nearly matching the tight approximation guarantee of 2 for the classical k-center problem which this problem generalizes. algorithms either opened more than k centers or only worked in the special case when the input points are in the plane.
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Conversion and storage of solar energy into fuels and chemicals by artificial photosynthesis has been considered as one of the promising methods to address the global energy crisis. However, it is still far from the practical applications on a large scale. Nanoarray structures that combine the advantages of nanosize and array alignment have demonstrated great potential to improve solar energy conversion efficiency, stability, and selectivity. This article provides a comprehensive review on the utilization of nanoarray structures in artificial photosynthesis of renewable fuels and high value-added chemicals. First, basic principles of solar energy conversion and superiorities of using nanoarray structures in this field are described. Recent research progress on nanoarray structures in both abiotic and abiotic-biotic hybrid systems is then outlined, highlighting contributions to light absorption, charge transport and transfer, and catalytic reactions (including kinetics and selectivity). Finally, conclusions and outlooks on future research directions of nanoarray structures for artificial photosynthesis are presented.
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Fotosíntesis , Energía Solar , Catálisis , Luz SolarRESUMEN
BACKGROUND: In recent years, methylene blue mediated-photodynamic therapy (MB-PDT) has proved to be an effective inhibitor to a variety of microorganisms, including Trichophyton rubrum, the most common dermatophyte worldwide. However, previous studies mainly focused on the spore form of T rubrum, but rarely on its hyphal form, although the latter is the main pathogenic form of T rubrum in vivo. OBJECTIVE: To investigate the inhibitory effect of MB-PDT on T rubrum in different growth phases in vitro. METHODS: The suspensions of spores and hyphae obtained from T rubrum (ATCC28188) were prepared, respectively, incubated with MB solution (0.15-40 µg/mL) and irradiated with 635 nm red light. Varied light energy and MB concentration were used. The specimen in the absence of light exposure or/and MB served as controls. MIC determination, colony counts and MTT assay were employed to evaluate the antifungal effect of MB-PDT. RESULTS: The MICs of MB-PDT for hyphae and spores of T. rubrum were 6.300 ± 1.072 µg/mL and 1.984 ± 1.072 µg/mL, respectively, at a fixed light dose of 60 J/cm2 . CFU counts gave the minimum critical combinations of MB concentration and light dose to achieve 100% inhibitory rate. For hyphae, they were 5 µg/mL + 100 J/cm2 or 10 µg/mL + 60 J/cm2 . For spores, they were 1.25 µg/mL + 40 J/cm2 or 5 µg/mL + 20 J/cm2 . The outcomes of MTT assay were consistent with those of CFU counts, but less accurate. CONCLUSION: MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose.
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Antifúngicos/farmacología , Hifa/efectos de los fármacos , Azul de Metileno/farmacología , Fotoquimioterapia/métodos , Esporas Fúngicas/efectos de los fármacos , Trichophyton/efectos de los fármacos , Arthrodermataceae/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/farmacología , Células MadreRESUMEN
BACKGROUND: Over the last decade, the rapid development of high-throughput sequencing platforms has accelerated species description and assisted morphological classification through DNA barcoding. However, the current high-throughput DNA barcoding methods cannot obtain full-length barcode sequences due to read length limitations (e.g. a maximum read length of 300 bp for the Illumina's MiSeq system), or are hindered by a relatively high cost or low sequencing output (e.g. a maximum number of eight million reads per cell for the PacBio's SEQUEL II system). RESULTS: Pooled cytochrome c oxidase subunit I (COI) barcodes from individual specimens were sequenced on the MGISEQ-2000 platform using the single-end 400 bp (SE400) module. We present a bioinformatic pipeline, HIFI-SE, that takes reads generated from the 5' and 3' ends of the COI barcode region and assembles them into full-length barcodes. HIFI-SE is written in Python and includes four function modules of filter, assign, assembly and taxonomy. We applied the HIFI-SE to a set of 845 samples (30 marine invertebrates, 815 insects) and delivered a total of 747 fully assembled COI barcodes as well as 70 Wolbachia and fungi symbionts. Compared to their corresponding Sanger sequences (72 sequences available), nearly all samples (71/72) were correctly and accurately assembled, including 46 samples that had a similarity score of 100% and 25 of ca. 99%. CONCLUSIONS: The HIFI-SE pipeline represents an efficient way to produce standard full-length barcodes, while the reasonable cost and high sensitivity of our method can contribute considerably more DNA barcodes under the same budget. Our method thereby advances DNA-based species identification from diverse ecosystems and increases the number of relevant applications.
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Código de Barras del ADN Taxonómico , Ecosistema , Animales , ADN , Secuenciación de Nucleótidos de Alto Rendimiento , InsectosRESUMEN
OBJECTIVE: The aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens. METHODS: 287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides. RESULTS: Tumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⺠group and 2 months in the ARMSâ» group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⺠group and 7 months in the ARMSâ» group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⺠and Seqâ» groups (P = 0.227, P = 0.510, respectively), and Seqâº/ARMS⺠and Seqâ»/ARMS⺠groups (P = 0.354, P = 0.334, respectively). CONCLUSIONS: The detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.
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Receptores ErbB/genética , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Mutación , Tasa de Mutación , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk factor for preterm birth. However, there are currently no studies on the relationship of the related research in twin-pregnant women. METHODS: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were measured in the first trimester(6-14 weeks), the second trimester(18-28 weeks) and the third trimester(after 28 weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/ApoA1 ratio and preterm birth. RESULTS: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm. Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese dichorionic twin-pregnant women. CONCLUSIONS: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women.
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Apolipoproteína A-I , Embarazo Gemelar , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Embarazo Gemelar/sangre , Nacimiento Prematuro/sangre , Nacimiento Prematuro/epidemiología , Adulto , Factores de Riesgo , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangreRESUMEN
The maternal-fetal interface is defined as the interface between maternal tissue and sections of the fetus in close contact. RNA methylation modifications are the most frequent kind of RNA alterations. It is effective throughout both normal and pathological implantation and placentation during pregnancy. By influencing early embryo development, embryo implantation, endometrium receptivity, immune microenvironment, as well as some implantation and placentation-related disorders like miscarriage and preeclampsia, it is essential for the establishment of the maternal-fetal interface. Our review focuses on the role of dynamic RNA methylation at the maternal-fetal interface, which has received little attention thus far. It has given the mechanistic underpinnings for both normal and abnormal implantation and placentation and could eventually provide an entirely novel approach to treating related complications.
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Implantación del Embrión , Placentación , Femenino , Embarazo , Humanos , Metilación , Placentación/genética , Implantación del Embrión/genética , Desarrollo Embrionario , ARNRESUMEN
Owing to the superior photoluminescence property, low toxicity and good biocompatibility, nitrogen-doped graphene quantum dots (NGQDs) have been regarded as promising nanomaterials for biological applications such as bioimaging. However, many of the preparation methods are complicated, high cost, eco-unfriendly, and with a low product yield. Here, we demonstrate a novel top-down approach for NGQDs preparation, in which the low cost graphite was used as a precursor, ammonium persulfate as an oxidative molecule and nitrogen source, and H2O2 as an oxidative agent, N-methyl-2-pyrrolidone as a solvent and potential functionalizer. Meanwhile, the solvent extraction was applied for the first time to purify NGQDs. The separated NGQDs display green and blue fluorescence, deriving from the difference sizes and nitrogen doped types. The total product yield of NGQDs is calculated to be about 52%, containing 88% of green-emissive NGQDs and 12% of blue-emissive NGQDs. Meanwhile, our NGQDs own low cytotoxicity, and display a good bioimaging performance in the in vitro and in vivo investigation. The synthesis idea in our work might be also applicable to obtain other kinds of quantum dots from the readily obtainable bulk materials.