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Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.
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Pruebas Genéticas , Diagnóstico Preimplantación , Humanos , Diagnóstico Preimplantación/métodos , Femenino , Pruebas Genéticas/métodos , Blastocisto/metabolismo , Embarazo , Transcriptoma/genética , Mutación/genéticaRESUMEN
Chemotherapy is widely recognized as an important approach for the treatment of cholangiocarcinoma. Gemcitabine (GEM) has been considered a first-line drug for treating cholangiocarcinoma due to its ability to effectively inhibit the proliferation, migration, and invasion of liver cancer cells. However, the systemic toxicity, premature degradation, and lack of tumor-targeting properties of GEM limit its application in cholangiocarcinoma chemotherapy. Additionally, precise targeted delivery of GEM is necessary to align with the current concept of precision medicine. In this study, considering the overexpression of hyaluronic acid (HA) receptors (CD44) on cholangiocarcinoma cells, we designed GEM@ZIF-67-HA NPs by loading GEM onto ZIF-67 and modifying its surface with HA. The structure, size, morphology, and elemental composition of GEM@ZIF-67-HA were analyzed using transmission electron microscopy, Fourier transform infrared spectroscopy, ζ-potential, and isothermal adsorption. Cell toxicity experiments demonstrated that GEM@ZIF-67-HA NPs not only reduced cytotoxicity to normal cells but also effectively inhibited the viability of two types of cholangiocarcinoma tumor cells. In a subcutaneous tumor model, GEM@ZIF-67-HA significantly suppressed tumor growth. The tumor-targeting and controllable properties of GEM@ZIF-67-HA NPs hold promise for further development in the strategy of precise targeted therapy for cholangiocarcinoma.
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OBJECTIVES: This study aimed to explore the value of the Charlson comorbidity index (CCI) in predicting ICU admission in patients with aortic aneurysm (AA). METHODS: The clinical data of patients were obtained from the Medical Information Mart for Intensive Care-IV database. The association between CCI and ICU admission was explored by restricted cubic spline (RCS), threshold effect analysis, generalized linear model, logistic regression, interaction, and mediation analyses. Its clinical value was evaluated by decision curve analysis (DCA), receiver operating characteristic curve (ROC), DeLong's test, and net reclassification index (NRI) analyses. RESULTS: The ICU admission was significantly associated with the thoracic AA (TAA), unruptured status, and surgery status. Therefore, 288 candidate patients with unruptured TAA who received surgery were enrolled in the further analysis. We found that CCI was independently associated with the ICU admission of candidates (P = 0.005). Further, their nonlinear relationship was observed (adjusted P = 0.008), and a significant turning point of 6 was identified. The CCI had a favorable performance in predicting ICU admission (area under curve = 0.728) and achieved a better clinical net benefit. New models based on CCI significantly improved the accuracy of prediction. Besides the importance of CCI in ICU admission, CCI also exerted important interaction effect (rather than mediating effects) on the association of other variables (such as age and blood variables) with ICU admission requirements (all P < 0.05). CONCLUSIONS: The CCI is an important predictor of ICU admission after surgery in patients with unruptured TAA.
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Aneurisma de la Aorta Torácica , Hospitalización , Humanos , Curva ROC , Comorbilidad , Aneurisma de la Aorta Torácica/epidemiología , Aneurisma de la Aorta Torácica/cirugía , Unidades de Cuidados Intensivos , Estudios RetrospectivosRESUMEN
Due to the increasing cost of health insurance, for decades, many countries have endeavored to constrain the cost of insurance by utilizing a DRG payment system. In most cases, under the DRG payment system, hospitals cannot exactly know which DRG code inpatients are until they are discharged. This paper focuses on the prediction of what DRG code appendectomy patients will be classified with when they are admitted to hospital. We utilize two models (or classifiers) constructed using the C4.5 algorithm and back-propagation neural network (BPN). We conducted experiments with the data collected from two hospitals. The results show that the accuracies of these two classification models can be up to 97.84% and 98.70%, respectively. According to the predicted DRG code, hospitals can effectively arrange medical resources with certainty, then, in turn, improve the quality of the medical care patients receive.
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BACKGROUND: Tocilizumab is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vasculitis. However, tocilizumab in combination with glucocorticoids for successfully treating granulomatosis with polyangiitis (GPA) has rarely been reported. CASE SUMMARY: Here, we report a 40-year-old male patient who suffered GPA for 4 years. He was treated with multiple rounds of drugs, including cyclophosphamide, Tripterygium wilfordii, mycophenolate mofetil, and belimumab, with no improvement. In addition, he exhibited persistently high IL-6 levels. After tocilizumab treatment, his symptoms improved, and his inflammatory marker levels returned to normal. CONCLUSION: Tocilizumab may be effective for treating GPA.
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The present study has explored the role of calcitonin gene-related peptide (CGRP) and its receptor in inflammatory pain modulation in arcuate nucleus of hypothalamus (ARC). Our study demonstrated that intra-ARC injection of CGRP induced antinociceptive effects to naïve rats and rats with inflammatory pain, the effect could be inhibited by the selective CGRP receptor antagonist CGRP8-37. Interestingly, the CGRP-induced antinociception effect was decreased in rats with inflammatory pain compared to naïve rats. Similarly, we found that calcitonin receptor like receptor (CLR), a main component of CGRP receptor, had a low decreased expression levels in the ARC regions of rats with inflammatory pain. The CGRP-induced antinociceptive effect was significantly impaired after reducing CLR expression by intra-ARC administration of CLR targeted siRNA. These findings demonstrated that CGRP might play a crucial role in nociceptive modulation in the ARC during inflammatory pain, which was mediated by CGRP receptor in the ARC. This study shed light upon CGRP and its receptor interaction might be valuable strategies for the alleviation of inflammatory pain.
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Péptido Relacionado con Gen de Calcitonina , Receptores de Péptido Relacionado con el Gen de Calcitonina , Animales , Ratas , Analgésicos/efectos adversos , Núcleo Arqueado del Hipotálamo/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/farmacología , Nocicepción , Dolor/metabolismo , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismoRESUMEN
OBJECTIVE: Third-generation cephalosporins (3rd GCs) have recently become controversial as the first-line strategy for empirical spontaneous bacterial peritonitis (SBP) treatment. This study aimed to identify SBP treatment efficacy predictors of 3rd GCs. METHODS: In this retrospective cohort study, 279 cirrhosis patients with SBP who received 3rd GC monotherapy for initial empirical treatment from 2013 to 2019 were included. Nonresponse was defined as a decreased ascites polymorphonuclear (PMN) count < 25% from baseline after 48 hours of antibacterial treatment. Multivariate regression analysis was used to identify efficacy predictors of 3rd GCs in treating SBP. Kaplan-Meier analysis was used to evaluate survival data. RESULTS: The nonresponder group included 120 patients with no response, and the responder group included 159 patients with responses. The response rate to 3rd GCs was 57.0% among all patients. The common pathogens were Escherichia coli (40.6%), Staphylococcus (15.6%), Klebsiella pneumonia (12.5%), and Streptococcus (12.5%) in 32 ascites culture isolates. Nosocomial SBP (NSBP) (odds ratio [OR]: 2.371, 95% confidence interval [CI]: 1.323-4.249, P = .004), pneumonia (OR: 11.561, 95% CI: 1.876-71.257, P = .008), recurrent SBP (OR: 3.386, 95% CI: 1.804-6.357, P < .001), platelet count (≥113.5 × 109/L) (OR: 3.515, 95% CI: 1.973-6.263, P < .001), and ascites PMN count (≤0.760 × 109/L) (OR: 4.967, 95% CI: 2.553-9.663, P < .001) were independent predictors of nonresponse to 3rd GCs against SBP. Survival plot analysis at 30 days showed worse survival for the nonresponders (P = .003). CONCLUSION: NSBP, pneumonia, recurrent SBP, increased platelet count, and lower ascites PMN count were independent predictors of nonresponse to 3rd GC in treating SBP. Nonresponse to initial antibiotic treatment was associated with worse survival.
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Infecciones Bacterianas , Infección Hospitalaria , Peritonitis , Antibacterianos/uso terapéutico , Ascitis/patología , Líquido Ascítico/patología , Infecciones Bacterianas/complicaciones , Cefalosporinas/uso terapéutico , Infección Hospitalaria/microbiología , Humanos , Cirrosis Hepática , Peritonitis/microbiología , Estudios RetrospectivosRESUMEN
Brucella melitensis (B. melitensis) is an important facultative intracellular bacterium that causes global zoonotic diseases. Continuous intracellular survival and replication are the main obstruction responsible for the accessibility of prevention and treatment of brucellosis. Bacteria respond to complex environment by regulating gene expression. Many regulatory factors function at loci where RNA polymerase initiates messenger RNA synthesis. However, limited gene annotation is a current obstacle for the research on expression regulation in bacteria. To improve annotation and explore potential functional sites, we proposed a novel genome-wide method called Capping-seq for transcription start site (TSS) mapping in B. melitensis. This technique combines capture of capped primary transcripts with Single Molecule Real-Time (SMRT) sequencing technology. We identified 2,369 TSSs at single nucleotide resolution by Capping-seq. TSSs analysis of Brucella transcripts showed a preference of purine on the TSS positions. Our results revealed that -35 and -10 elements of promoter contained consensus sequences of TTGNNN and TATNNN, respectively. The 5' ends analysis showed that 57% genes are associated with more than one TSS and 47% genes contain long leader regions, suggested potential complex regulation at the 5' ends of genes in B. melitensis. Moreover, we identified 52 leaderless genes that are mainly involved in the metabolic processes. Overall, Capping-seq technology provides a unique solution for TSS determination in prokaryotes. Our findings develop a systematic insight into the primary transcriptome characterization of B. melitensis. This study represents a critical basis for investigating gene regulation and pathogenesis of Brucella.
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Brucella melitensis , Brucelosis , Bacterias/genética , Brucella melitensis/genética , Brucelosis/genética , Brucelosis/microbiología , Mapeo Cromosómico , Humanos , Sitio de Iniciación de la Transcripción , TranscriptomaRESUMEN
BACKGROUND: Previous studies have suggested a close association between transcription factor 7-like 2 (TCF7L2) polymorphisms and diabetic retinopathy (DR) susceptibility. However, the published results were inconsistent. This meta-analysis was conducted to review and examine the relationship between TCF7L2 rs7903146 C/T polymorphism and DR risk. MATERIALS AND METHODS: Online databases were searched and the related studies were identified in this meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power. Moreover, heterogeneity test, sensitivity accumulative analysis and publication bias were conducted to measure the statistical effect. RESULT: 6 studies involving 12,982 subjects were included in this meta-analysis to assess the association between rs7903146 C/T polymorphism and DR susceptibility. The synthetic results indicated that the mutation of rs7903146 C/T polymorphism maybe accompany with an increased risk for DR (T vs. C: OR=1.26, 95%CI=1.00-1.60, P=0.05, I2=83.5%; TT vs. CC: OR=1.79 95%CI=1.12-2.86, P=0.02, I2=80.2%; TT vs. CC+CT: OR=1.62, 95%CI=1.38-1.92, P<0.01, I2=32.3%). Moreover, the subgroup analysis also demonstrated an increasing risk for DR with T mutations in Caucasian descendants. CONCLUSION: The current evidences meta-analysis suggested that the TCF7L2 rs7903146 C/T polymorphism might be play an important role in DR susceptibility.
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DNA nanomachines, a delicate type of molecular machines, have been a research hotspot in biotechnology and materials. Here a two-dimensional (2D) DNA walking nanomachine with high working efficiency and low cost was easily assembled by using graphene oxide (GO) as the working platform for precisely fluorescent bioassay through the binding of target hepatitis B virus DNA (HBV-DNA) and the driving force of Exonuclease III (Exo III). The presence of HBV-DNA made continuous Exo III digestion of the FAM-modified DNA (FAM-DNA) in double-strand DNA (dsDNA) part in a burnt-bridge mechanism to output a "one-to-more" amplified signal. Accordingly, a 2D DNA walking nanomachine with simple operation and high cost-performance ratio was constructed. The walking speed of nanomachine was found to be regulated by loading DNA density on single sheet of GO. Furthermore, this nanomachine had low background since the dual energy transfer including fluorescence resonance energy transfer (FRET) from FAM to BHQ1 and the long-range resonance energy transfer (LrRET) from FAM to GO, making the biosensing applications highly promising.
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Técnicas Biosensibles , Grafito , Bioensayo , Técnicas Biosensibles/métodos , ADN Viral/genética , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes/química , Grafito/químicaRESUMEN
Carbon dots have promising prospects for analytical and monitoring purposes, but are greatly hindered by the aggregation-induced luminescence quenching owing to the π-π interaction or the non-radiation-excited radical complex formation. Herein hydrothermally prepared orange-yellow fluorescent carbon dots (O-CDs) show an aggregation-induced fluorescence enhancement (AIFE) with Cu2+ owing to the complexation of Cu(II) and the O-CDs. Cu2+ was then sensitively and selectively detected in the linear range from 0.02 to 30 µM with the detection limit of 14 nM, making the detection of Cu2+ in fresh water and E. coli lysate successful, showing that the as-prepared O-CDs could be well applied to the environmental monitoring of heavy metals.
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Carbono , Puntos Cuánticos , Cobre , Escherichia coli , Colorantes Fluorescentes , Espectrometría de FluorescenciaRESUMEN
Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.
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Analgésicos/farmacología , Péptido Relacionado con Gen de Calcitonina/farmacología , Proteína Similar al Receptor de Calcitonina/agonistas , Dolor Nociceptivo/prevención & control , Umbral del Dolor/efectos de los fármacos , Núcleos Parabraquiales/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Receptores de Péptido Relacionado con el Gen de Calcitonina/agonistas , Ciática/prevención & control , Animales , Proteína Similar al Receptor de Calcitonina/genética , Proteína Similar al Receptor de Calcitonina/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Masculino , Dolor Nociceptivo/genética , Dolor Nociceptivo/metabolismo , Dolor Nociceptivo/fisiopatología , Núcleos Parabraquiales/metabolismo , Núcleos Parabraquiales/fisiopatología , Ratas Sprague-Dawley , Receptores de Péptido Relacionado con el Gen de Calcitonina/genética , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Ciática/genética , Ciática/metabolismo , Ciática/fisiopatologíaRESUMEN
STUDY QUESTION: Is it possible to evaluate the methylome of individual oocytes to investigate the DNA methylome alterations in metaphase II (MII) oocytes with reduced embryo developmental potential? SUMMARY ANSWER: The DNA methylome of each human first polar body (PB1) closely mirrored that of its sibling MII oocyte; hypermethylated long interspersed nuclear element (LINE) and long terminal repeats (LTRs) and methylation aberrations in PB1 promoter regions may indicate poor embryo development. WHAT IS KNOWN ALREADY: The developmental potential of an embryo is determined by the oocyte's developmental competence, and the PB1 is a good substitute to examine the chromosomal status of the corresponding oocyte. However, DNA methylation, a key epigenetic modification, also regulates gene expression and embryo development. STUDY DESIGN, SIZE, DURATION: Twelve pairs of PB1s and sibling MII oocytes were biopsied and sequenced to compare their methylomes. To further investigate the methylome of PB1s and the potential epigenetic factors that may affect oocyte quality, MII oocytes (n = 74) were fertilized through ICSI, while PB1s were biopsied and profiled to measure DNA methylation. The corresponding embryos were further cultured to track their development potential. The oocytes and sperm samples used in this study were donated by healthy volunteers with signed informed consent. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single-cell methylome sequencing was applied to obtain the DNA methylation profiles of PB1s and oocytes. The DNA methylome of PB1s was compared between the respective group of oocytes that progressed to blastocysts and the group of oocytes that failed to develop. DNA methylation levels of corresponding regions and differentially methylated regions were calculated using customized Perl and R scripts. RNA-seq data were downloaded from a previously published paper and reanalysed. MAIN RESULTS AND THE ROLE OF CHANCE: The results from PB1-MII oocyte pair validated that PB1 contains nearly the same methylome (average Pearson correlation is 0.92) with sibling MII oocyte. LINE and LTR expression increased markedly after fertilization. Moreover, the DNA methylation levels in LINE (including LINE1 and LINE2) and LTR were significantly higher in the PB1s of embryos that could not reach the blastocyst stage (Wilcoxon-Matt-Whitney test, P < 0.05). DNA methylation in PB1 promoters correlated negatively with gene expression of MII oocyte. Regarding the methylation status of the promoter regions, 66 genes were hypermethylated in the developmental arrested group, with their related functions (significantly enriched in several Gene Ontology terms) including transcription, positive regulation of adenylate cyclase activity, mitogen-activated protein kinase (MAPK) cascade and intracellular oestrogen receptor signalling pathway. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Data analysis performed in this study focused on the competence of human oocytes and compared them with maternal genetic and epigenetic profiles. Therefore, data regarding the potential regulatory roles of paternal genomes in embryo development are lacking. WIDER IMPLICATIONS OF THE FINDINGS: The results from PB1-oocyte pairs demonstrated that PB1s shared similar methylomes with their sibling oocytes. The selection of the good embryos for transfer should not only rely on morphology but also consider the DNA methylation of the corresponding PB1 and therefore MII oocyte. The application of early-stage analysis of PB1 offers an option for high-quality oocyte and embryo selection, which provides an additional tool for elective single embryo transfer in assisted reproduction. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2018YFC1004003, 2017YFA0103801), the National Natural Science Foundation of China (81730038, 3187144, 81521002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020703). The authors have no conflicts of interest to declare.
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Epigenoma , Cuerpos Polares , China , Desarrollo Embrionario/genética , Humanos , Masculino , OocitosRESUMEN
BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk. METHODS: A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power. RESULTS: Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I2 = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I2 = 81.9%). CONCLUSIONS: In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.
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Aldehído Deshidrogenasa Mitocondrial/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de Cabeza y Cuello/genética , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Asia Oriental/epidemiología , Predisposición Genética a la Enfermedad/epidemiología , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/epidemiología , HumanosRESUMEN
Objectives: The 2019 novel coronavirus disease (COVID-19) pandemic is the biggest public health crises in the 21st century. While most patients infected with the COVID-19 virus have no to moderate symptoms, there is currently limited clinical information about these patients. Methods: In this study, we retrospectively investigated 41 patients infected with the COVID-19 virus in Nanchang, Jiangxi province, China, from February 4 to March 2, 2020. Nanchang is about 260 km southeast of Wuhan, the initial epicenter of the COVID-19 pandemic. We retrieved information on patient demographics, physical examination results, epidemiology, clinical manifestations, underlying conditions, laboratory analyses, radiological images, and treatment outcomes. Results: Most patients (70.7%) had a history of close contact with patients with confirmed COVID-19, and 16 patients (39.0%) showed a high degree of family clustering. All 41 patients had no to moderate symptoms. The median age was 39.9 years and common symptoms of illness were fever (69.2%), cough (65.4%), and fatigue (19.2%). The dominant patient group was middle-aged women, with hypertension (14.6%) and chronic liver disease (12.2%) as the most frequent underlying conditions. All patients recovered, with the mean time of viral nucleic acid clearance at 10.6 days. Chest CT scans presented ground-glass opacities in 53.7% of patients while 26.8% had normal CT images. Laboratory results showed that lymphocyte counts, lymphocyte percentages, ESR, CRP, IgG, Fib, and cytokines were correlated to patients' conditions. Approximately 60-90% of patients had abnormally high levels of cytokines IL-4, IL-6, IL-10, and/or TNF-α. Conclusions: Our results showed variable clinical and laboratory presentations among this group of patients infected with the COVID-19 virus. Though all 41 patients recovered, our results suggest that cytokine levels and other biochemical indicators should be monitored for patients infected with the COVID-19 virus showing no to moderate symptoms to ensure quick access for critical medical attention, if needed.
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It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.
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Sargassum horneri is a habitat-forming species in the Northwest Pacific and an important contributor to seaweed rafts. In this study, 131 benthic samples and 156 floating samples were collected in the Yellow Sea and East China Sea (ECS) to test the effects of seaweed rafts on population structure and connectivity. Our results revealed high levels of genetic diversity in both benthic and floating samples based on concatenated mitochondrial markers (rpl5-rps3, rnl-atp9, and cob-cox2). Phylogenetic analyses consistently supported the existence of two lineages (lineages I and II), with divergence dating to c. 0.692 Mya (95% HPD: 0.255-1.841 Mya), indicating that long-term isolation may have occurred during the mid-Pleistocene (0.126-0.781 Mya). Extended Bayesian skyline plots demonstrated a constant population size over time in lineage I and slight demographic expansion in lineage II. Both lineages were found in each marginal sea (including both benthic and floating samples), but PCoA, FST , and AMOVA analyses consistently revealed deep genetic variation between regions. Highly structured phylogeographic pattern supports limited genetic connectivity between regions. IMA analyses demonstrated that asymmetric gene flow between benthic populations in the North Yellow Sea (NYS) and ECS was extremely low (ECSâNYS, 2Nm = 0.6), implying that high dispersal capacity cannot be assumed to lead to widespread population connectivity, even without dispersal barriers. In addition, there were only a few shared haplotypes between benthic and floating samples, suggesting the existence of hidden donors for the floating masses in the Chinese marginal seas.
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Sargassum , Teorema de Bayes , China , ADN Mitocondrial , Variación Genética , Genética de Población , Haplotipos , Océanos y Mares , Filogenia , Filogeografía , Sargassum/genéticaRESUMEN
Concentrating on the ion conductivity of anion exchange membranes (AEMs), we present a magnetic-field-oriented strategy to address the insufficient ion conductivity and the lifetime problem of AEMs used in alkali membrane fuel cells (AMFCs). Magnetic ferroferric oxide (Fe3O4) is functionalized with quaternary ammonium (QA) groups to endow the QA-Fe3O4 with ion-exchange ability. A series of aligned QA-Fe3O4/poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) hybrid membranes were fabricated by doping QA-Fe3O4 in a triple-ammonium-functionalized PPO (TA-PPO) solution in an applied magnetic field. The structure of aligned QA-Fe3O4 in the TA-PPO membrane is clearly observed by using a scanning electron microscope (SEM). More importantly, the aligned QA-Fe3O4 constructs successive and effective ion-transport channels in the QA-Fe3O4/TA-PPO membrane, which dramatically improves the ion conductivity of the membranes. Notably, the magnetic-field-induced ion channels (MICs) are different from microscopic phase-induced ion channels (PICs). These MICs display much shorter ion transport distances and broader water channels than traditional PICs in AEMs. The aligned QA-Fe3O4/TA-PPO hybrid membrane displays a further 55% increase in ion conductivity after magnetic-field orientation compared to the normal QA-Fe3O4/TA-PPO membrane. Surprisingly, the aligned QA-Fe3O4 also improves the alkali stability and fuel cell performance of the hybrid membrane. The aligned 6%-QA-Fe3O4/TA-PPO hybrid membrane realizes a maximal power density of 224 mW cm-2. In summary, this work provides a novel and effective method to prepare high-performance AEMs.
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Quantum key distribution with polarized qubits has not yet been realized over the aerial fiber, due to rapid polarization changes. Here, we report our recent work towards quantum communication through an aerial fiber channel. We designed a fast polarization feedback module featuring high efficiency, fast speed, and good stability. With this module, we implemented long-distance quantum key distribution over different types of aerial fiber links based on polarization encoding. Our work takes a significant step towards the application of quantum communications in complex environments.
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Herein, we present a three-decker layered double hydroxide (LDH)/poly(phenylene oxide) (PPO) for hydroxide exchange membrane (HEM) applications. Hexagonal LDH is functionalized with highly stable 3-hydroxy-6-azaspiro [5.5] undecane (OH-ASU) cations to promote it's ion-exchange capacity. The ASU-LDH is combined with triple-cations functionalized PPO (TC-PPO) to fabricate a three-decker ASU-LDH/TC-PPO hybrid membrane by an electrostatic-spraying method. Notably, the ASU-LDH layer with a porous structure shows many valuable properties for the ASU-LDH/TC-PPO hybrid membranes, such as improving hydroxide conductivity, dimensional stability, and alkaline stability. The maximum OH- conductivity of ASU-LDH/TC-PPO hybrid membranes achieves 0.113 S/cm at 80 °C. Only 11.5% drops in OH- conductivity was detected after an alkaline stability test in 1 M NaOH at 80 °C for 588 h, prolonging the lifetime of the TC-PPO membrane. Furthermore, the ASU-LDH/TC-PPO hybrid membrane realizes a maximum power density of 0.209 W/cm2 under a current density of 0.391 A/cm2. In summary, the ASU-LDH/TC-PPO hybrid membranes provide a reliable method for preparing high-performance HEMs.