RESUMEN
Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
Asunto(s)
Secuenciación del Exoma , Femenino , Humanos , Embarazo , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Pueblo Asiatico/genética , Variaciones en el Número de Copia de ADN , Pueblos del Este de Asia , Feto/anomalías , Hernia Diafragmática , Meningomielocele/genética , Meningomielocele/diagnóstico por imagen , Mutación , Glicosiltransferasas/genéticaRESUMEN
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.
Asunto(s)
Esclerosis Amiotrófica Lateral , Ferroptosis , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/patología , Humanos , Animales , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Hierro/metabolismo , Antioxidantes/uso terapéuticoRESUMEN
Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to the immunosuppressive tumor microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which, in turn, induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting guide RNA-liposomes could promote CD8+ T cell infiltration in tumor tissues; enhance the expression of proinflammatory cytokines, such as interleukin-12, tumor necrosis factor-α, and interferon-γ, and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting guide RNA-liposomes with immune checkpoint inhibitors and antiprogrammed death-1 antibodies produced highly effective antitumor effects. In addition, combination therapy induced immune memory in the cervical cancer model.
Asunto(s)
Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Liposomas , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/terapia , Sistemas CRISPR-Cas , Proteínas Represoras/genética , ARN , Proteínas E7 de Papillomavirus/genética , Microambiente TumoralRESUMEN
OBJECTIVE: To explore the clinical features, treatment and prognosis of ductal adenocarcinoma of the prostate (DAP) and get a deeper insight into the malignancy. METHODS: We retrospectively studied the clinical data on 45 cases of confirmed DAP, 26 in the high-risk group and 19 in the medium-risk group, treated from January 2013 to September 2020. We compared the time and rate of biochemical recurrence and the rate of imaging progression between the two groups of patients, and evaluated the effect of palliative transurethral bipolar plasma resection of the prostate (pTU-PKRP) on the lower urinary tract symptoms (LUTS). RESULTS: Of the 45 cases of DAP, 4 (8.9%) were of the simple type, and 41 (91.1%) complicated by prostatic acinar carcinoma (PAA). And of the latter 41 cases, 9 (21.9%) were complicated by neuroendocrine differentiation and another 4 (9.8%) by intraductal carcinoma. The time to biochemical recurrence was longer in the medium-risk than in the high-risk group (P < 0.05). No statistically significant differences were observed in the rates of biochemical recurrence and imaging progression between the two groups (P > 0.05). The maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), IPSS and QOL of the patients were significantly improved at 6 months after pTU-PKRP compared with the baseline (P < 0.05). CONCLUSION: Radical prostatectomy can improve the prognosis of early DAP, while for advanced DAP with serious LUTS, pTU-PKRP can improve the quality of life of the patients.
Asunto(s)
Adenocarcinoma , Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Neoplasias de la Próstata , Resección Transuretral de la Próstata , Masculino , Humanos , Próstata/patología , Calidad de Vida , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Estudios Retrospectivos , Neoplasias de la Próstata/patología , Resultado del Tratamiento , Síntomas del Sistema Urinario Inferior/patología , Adenocarcinoma/cirugíaRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.
Asunto(s)
Variación Genética , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/genética , Tamizaje Neonatal , Alelos , China/epidemiología , Mapeo Cromosómico , Análisis Mutacional de ADN/métodos , Femenino , Genes Ligados a X , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/historia , Historia del Siglo XXI , Humanos , Incidencia , Recién Nacido , Masculino , Mutación , Tamizaje Neonatal/métodos , Tamizaje Neonatal/normas , Vigilancia de la PoblaciónRESUMEN
LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages.
Asunto(s)
Aborto Espontáneo/genética , Aborto Espontáneo/metabolismo , Elementos de Nucleótido Esparcido Largo/fisiología , Retroelementos/fisiología , Aborto Espontáneo/etiología , Animales , Femenino , Humanos , EmbarazoRESUMEN
OBJECTIVE: To explore the genetic etiology for fetuses featuring intrauterine growth anomalies using array-based comparative genomic hybridization (aCGH). METHODS: Forty-nine fetuses were enrolled in this study. Genomic DNA of the abortive tissues was analyzed with aCGH. RESULTS: Fourteen (28.6%) samples were found with chromosomal aberrations, which included 8 chromosomal aneuploidies and 6 micro-aberrations (4 with known clinical pathogenecity and 2 with unknown clinical significance). CONCLUSION: Numerical and structural chromosomal aberrations underlie a significant proportion of fetal growth anomalies. aCGH has provided an effective method for delineating their genetic cause.
Asunto(s)
Aberraciones Cromosómicas , Hibridación Genómica Comparativa/métodos , Anomalías Congénitas/genética , Diagnóstico Prenatal/métodos , Adulto , Variaciones en el Número de Copia de ADN , Femenino , Humanos , EmbarazoRESUMEN
The constituents of the whole plant of Orobanche coerulescens were isolated and purified by using various column chromatographic techniques including D101, silica gel and ODS. The structures were identified by spectroscopic analyses including NMR and MS. A new phenylethanol glycoside was isolated from the whole plant of O. coerulescens, and was identified as 2-(3-methoxy-4-hydroxyphenyl)-ethanol-1-O- [(1â3)-O-α-L-rhamnopyranosyl-4, 6-O-di-feruloyl]-ß-D-glucopyranoside, named as orobancheoside B. Through the antibacterial activity test, orobancheoside B was proved to have certain antibacterial activity, and be one of the main active components of O. coerulescens. The research result will laid a foundation for the medicinal materials and quality control research. Activity screening, broomrape orobancheoside B has certain antibacterial activity, as one of the main active components of O. coerulescens, and to constantly improve the quality of the medicinal materials laid a foundation.
Asunto(s)
Glicósidos/aislamiento & purificación , Orobanche/química , Alcohol Feniletílico/aislamiento & purificación , Estructura MolecularRESUMEN
Identifying protein-protein interactions is important in molecular biology. Experimental methods to this issue have their limitations, and computational approaches have attracted more and more attentions from the biological community. The semantic similarity derived from the Gene Ontology (GO) annotation has been regarded as one of the most powerful indicators for protein interaction. However, conventional methods based on GO similarity fail to take advantage of the specificity of GO terms in the ontology graph. We proposed a GO-based method to predict protein-protein interaction by integrating different kinds of similarity measures derived from the intrinsic structure of GO graph. We extended five existing methods to derive the semantic similarity measures from the descending part of two GO terms in the GO graph, then adopted a feature integration strategy to combines both the ascending and the descending similarity scores derived from the three sub-ontologies to construct various kinds of features to characterize each protein pair. Support vector machines (SVM) were employed as discriminate classifiers, and five-fold cross validation experiments were conducted on both human and yeast protein-protein interaction datasets to evaluate the performance of different kinds of integrated features, the experimental results suggest the best performance of the feature that combines information from both the ascending and the descending parts of the three ontologies. Our method is appealing for effective prediction of protein-protein interaction.
Asunto(s)
Ontología de Genes , Dominios y Motivos de Interacción de Proteínas , Humanos , Aprendizaje Automático , Anotación de Secuencia Molecular , Mapeo de Interacción de Proteínas , Máquina de Vectores de Soporte , LevadurasRESUMEN
Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.
Asunto(s)
Alcaloides/química , Hojas de la Planta/química , Rubiaceae/química , Alcaloides/aislamiento & purificación , Carbolinas/química , Carbolinas/aislamiento & purificación , Dicroismo Circular , Glucósidos/química , Glucósidos/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Extractos Vegetales/químicaRESUMEN
Medications administered during the neonatal period may mask the diagnosis of congenital hypothyroidism. Herein, we report a case of undiagnosed congenital hypothyroidism while the infant was on treatment with dopamine. Given the inhibitory effect of dopamine on thyroid-stimulating hormone, a high index of suspicion for potential congenital hypothyroidism is needed in such neonates.
Asunto(s)
Cardiotónicos/efectos adversos , Hipotiroidismo Congénito/inducido químicamente , Dobutamina/administración & dosificación , Dopamina/efectos adversos , Síndrome de Aspiración de Meconio/tratamiento farmacológico , Cardiotónicos/administración & dosificación , Preescolar , Hipotiroidismo Congénito/diagnóstico , Dobutamina/efectos adversos , Dopamina/administración & dosificación , Humanos , Recién Nacido , Infusiones Intravenosas , Masculino , Síndrome de Aspiración de Meconio/diagnóstico , Tamizaje Neonatal , Tirotropina/efectos de los fármacos , Resultado del TratamientoRESUMEN
Previous reports have demonstrated that embryonic stem cells were capable of differentiating into primordial germ cells through the formation of embryoid bodies that subsequently generated oocyte-like cells (OLCs). Such a process could facilitate studies of primordial follicle oocyte development in vitro and regenerative medicine. To investigate the pluripotency of human amniotic fluid stem cells (hAFSCs) and their ability to differentiate into germ cells, we isolated a CD117(+)/CD44(+) hAFSC line that showed fibroblastoid morphology and intrinsically expressed both stem cell markers (OCT4, NANOG, SOX2) and germ cell markers (DAZL, STELLA). To encourage differentiation into OLCs, the hAFSCs were first cultured in a medium supplemented with 5% porcine follicular fluid for 10 days. During the induction period, cell aggregates formed and syntheses of steroid hormones were detected; some OLCs and granulosa cell-like cells could be loosened from the surface of the culture dish. Cell aggregates were collected and replated in oocyte culture medium for an additional 7-10 days. OLCs ranging from 50 to 120 µm presenting zona pellucida were observed in cumulus-oocyte complexes; some OLCs developed spontaneously into multicell structures similar to preimplantation embryos. Approximately 2% of the hAFSCs differentiated to meiotic germ cells that expressed folliculogenesis- and oogenesis-associated markers. Although the in vitro maturation and fertilization potentials are as yet unproven, short-term (<25 days) and high-efficiency (>2%) derivation of OLCs from hAFSCs might provide a new approach to the study of human germ cell development in vitro.
Asunto(s)
Líquido Amniótico/citología , Oocitos/citología , Folículo Ovárico/citología , Células Madre/citología , Animales , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/fisiología , Línea Celular , Linaje de la Célula/fisiología , Medios de Cultivo/farmacología , Cuerpos Embrioides/citología , Femenino , Humanos , Oogénesis/fisiología , Partenogénesis/fisiología , Embarazo , Sus scrofaRESUMEN
OBJECTIVE: To investigate the feature of phenylalanine hydroxylase (PAH) gene mutations and provide guidance for genetic and prenatal diagnosis of patients with phenylketonuria from Shaanxi. METHODS: For 55 patients whose blood Phe concentration was over 2.0 mg/dL, potential mutations in 13 exons and flanking sequences of the PAH gene were detected by PCR and DNA sequencing. RESULTS: A total of 98 mutations were detected in 110 PAH alleles, with the detection rate being 89.10%. Nine mutations have been identified in exon 7, which accounted for 33.67% of all. Exon 12 (14.29%) and exon 3 (12.24%) have followed. Thirty eight mutations, locating in exon2-exon12 and the flanking sequence, were detected in the 55 PKU patients. p.R243Q (24.49%) was the commonest mutation, whilstp.A47E, p.I65S and p.A259T were first discovered in China. After querying international databases including PAHdb and HGMD, the p.C334X was verified as the novel PAH gene mutation. CONCLUSION: The mutation spectrum of the PAH gene in Shaanxi has been identified. And a novel mutation has been identified. This may facilitate the diagnosis of PKU in the future.
Asunto(s)
Mutación , Fenilalanina Hidroxilasa/genética , Fenilcetonurias/enzimología , Fenilcetonurias/genética , Alelos , Secuencia de Bases , Niño , Preescolar , China , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Fenilalanina Hidroxilasa/sangreRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a complex pathogenesis, which involves the formation of amyloid plaques and neurofibrillary tangles. Many recent studies have revealed a close association between ferroptosis and the pathogenesis of AD. Factors such as ferroptosis-associated iron overload, lipid peroxidation, disturbances in redox homeostasis, and accumulation of reactive oxygen species have been found to contribute to the pathological progression of AD. In this review, we explore the mechanisms underlying ferroptosis, describe the link between ferroptosis and AD, and examine the reported efficacy of ferroptosis inhibitors in treating AD. Finally, we discuss the potential challenges to ferroptosis inhibitors use in the clinic, enabling their faster use in clinical treatment.
Asunto(s)
Enfermedad de Alzheimer , Ferroptosis , Ferroptosis/fisiología , Ferroptosis/efectos de los fármacos , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Animales , Especies Reactivas de Oxígeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiologíaRESUMEN
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders predominantly characterized by impaired corticosteroid synthesis. Clinical phenotypes include hypoadrenocorticism, electrolyte disturbances, abnormal gonadal development, and short stature, of which severe hyponadrenocorticism and salt wasting can be life-threatening. Genetic analysis can help in the clinical diagnosis of CAH. However, the 21-OHD-causing gene CYP21A2 is arranged in tandem with the highly homologous CYP21A1P pseudogene, making it difficult to determine the exact genotypes using the traditional method of multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing or next-generation sequencing (NGS). We applied a long-read sequencing-based approach termed comprehensive analysis of CAH (CACAH) to 48 newborns with CAH that were diagnosed by clinical features and the traditional MLPA plus Sanger sequencing method for retrospective analysis, to evaluate its efficacy in the clinical diagnosis of neonatal CAH. Compared with the MLPA plus Sanger sequencing method, CACAH showed 100 % consistency in detecting SNV/indel variants located in exons and exon-intron boundary regions of CAH-related genes. It can directly determine the cis-trans relationship without the need to analyze parental genotypes, which reduces the time to diagnosis. Moreover, CACAH was able to distinguish different CYP21A1P/CYP21A2 and TNXA/TNXB chimeras, and detect additional variants (CYP21A2 variants c.-121C > T, c.*13G > A, c.*52C > T, c.*440C > T, c.*443 T > C, and TNXB variants c.12463 + 2 T > C, c.12204 + 5G > A). We also identified the TNXB variant c.11435_11524 + 30del alone instead of as a part of the TNXA/TNXB-CH-1 chimera in two newborns, which might be introduced by gene conversion. All of these characteristics enabled clinicians to better explain the phenotype of subjects and manage them more effectively. CACAH has a great advantage over the traditional MLPA and Sanger sequencing methods, showing substantial potential in the genetic diagnosis and screening of neonatal CAH.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Enanismo , Recién Nacido , Humanos , Hiperplasia , Estudios Retrospectivos , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Tenascina , Esteroide 21-Hidroxilasa/genéticaRESUMEN
Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.
RESUMEN
BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Tamizaje Neonatal , Humanos , Recién Nacido , Proyectos Piloto , Secuenciación del Exoma , Tamizaje Neonatal/métodos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
Purpose: The study aimed to quantify the global trends of the incidence rates of multidrug-resistant (MDR) tuberculosis (MDR-TB) and extensively drug-resistant (XDR) tuberculosis (XDR-TB). Methods: Cases, age-standardized rates (ASRs), and incidence rates of MDR-TB and XDR-TB during 2010-2019 were obtained from the Global Burden of Disease Study 2019. The incidence trends of MDR-TB and XDR-TB were evaluated using the estimated annual percentage changes (EAPCs) in ASRs. The relationships among the ASRs of MDR-TB and XDR-TB, the MDR rate, the XDR rate, and socio-demographic index (SDI) were assessed using locally weighted regression and Pearson's correlation coefficient. Results: The global ASR of MDR-TB on average decreased by 1.36% (EAPC = -1.36, 95% confidence interval [CI] = -2.19 to -0.52) per year whereas that of XDR-TB was stable (EAPC = 0.69, 95% CI = -0.15-1.54) during 2010-2019. The incidence trends of MDR-TB in most regions and countries were decreasing, but those of XDR-TB were increasing. People aged 35-44 and 55-64 years had the highest incidence rates for MDR-TB and XDR-TB. The MDR and XDR rates both peaked in those aged 35-44 years. Areas with higher SDI tended to have lower ASRs of MDR-TB (p < 0.001, ρ = -0.43). Conclusion: The current achievements for the incidence trends of MDR-TB and XDR-TB are insufficient. More strategies and tools need to be developed to further curb MDR-TB and XDR-TB, especially in high-risk areas and age groups, and in low SDI regions.
RESUMEN
The demand of microwave absorption materials (MAMs) with unique morphologies and electromagnetic (EM) balance has become necessary in recent years. Due to the ease of synthesis and tunable structure, metal-organic frameworks (MOFs) are widely used for this special MAMs. In this study, a new three-dimensional hybrid MOF is proposed that is co-doped with six equally branched star morphologies. The Co-C composite has the same six-branched morphology as that of the precursor. When the EM wave is incident, this special structure makes it easier for the EM wave to enter the material vertically due to the expansion of the incident surface, which is effective in adjusting the transmission path of the electron and the reflection and distribution of the EM wave. Because of the special morphology and magneto-dielectric synergy, the Co-C composite shows a minimum reflection loss (RLmin) of -48.5 dB at 11.0 GHz at an absorption thickness of 3.0 mm, with a microwave absorption bandwidth (EAB) of 6.1 GHz. This research provides a practical guidance for preparing the MAMs of special star structure.
RESUMEN
Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.