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Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.
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Febre Hemorrágica com Síndrome Renal , Ratos , Animais , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/etiologia , Clima , Zoonoses , China/epidemiologia , Murinae , IncidênciaRESUMO
Horizontal gene transfer has occurred across all domains of life and contributed substantially to the evolution of both prokaryotes and eukaryotes. Previous studies suggest that many horizontally transferred eukaryotic genes conferred selective advantages to bacterial recipients, but how these eukaryotic genes evolved into functional bacterial genes remained unclear, particularly how bacteria overcome the expressional barrier posed by eukaryotic introns. Here, we first confirmed that the presence of intron would inactivate the horizontally transferred gene in Escherichia coli even if this gene could be efficiently transcribed. Subsequent large-scale genetic screens for activation of gene function revealed that activation events could rapidly occur within several days of selective cultivation. Molecular analysis of activation events uncovered two distinct mechanisms how bacteria overcome the intron barrier: (i) intron was partially deleted and the resulting stop codon-removed mutation led to one intact foreign protein or (ii) intron was intactly retained but it mediated the translation initiation and the interaction of two split small proteins (derived from coding sequences up- and downstream of intron, respectively) to restore gene function. Our findings underscore the likelihood that horizontally transferred eukaryotic intron-containing genes could rapidly acquire functionality if they confer a selective advantage to the prokaryotic recipient.
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Escherichia coli , Transferência Genética Horizontal , Íntrons , Íntrons/genética , Escherichia coli/genética , Genes Bacterianos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismoRESUMO
Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics.
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Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H5N8 , Influenza Aviária , Animais , Aves , Genótipo , Vírus da Influenza A/fisiologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A Subtipo H5N8/genética , Vírus da Influenza A Subtipo H5N8/fisiologia , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Filogenia , Aves DomésticasRESUMO
Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.
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Alelos , Genoma de Planta , Populus , Populus/genética , Genoma de Planta/genética , Regulação da Expressão Gênica de Plantas , Haplótipos/genética , Hibridização Genética , Aprendizado de MáquinaRESUMO
A high-quality genome variation database derived from a large-scale population is one of the most important infrastructures for genomics, clinical and translational medicine research. Here, we developed the Chinese Millionome Database (CMDB), a database that contains 9.04 million single nucleotide variants (SNV) with allele frequency information derived from low-coverage (0.06×-0.1×) whole-genome sequencing (WGS) data of 141 431 unrelated healthy Chinese individuals. These individuals were recruited from 31 out of the 34 administrative divisions in China, covering Han and 36 other ethnic minorities. CMDB, housing the WGS data of a multi-ethnic Chinese population featuring wide geographical distribution, has become the most representative and comprehensive Chinese population genome database to date. Researchers can quickly search for variant, gene or genomic regions to obtain the variant information, including mutation basic information, allele frequency, genic annotation and overview of frequencies in global populations. Furthermore, the CMDB also provides information on the association of the variants with a range of phenotypes, including height, BMI, maternal age and twin pregnancy. Based on these data, researchers can conduct meta-analysis of related phenotypes. CMDB is freely available at https://db.cngb.org/cmdb/.
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Bases de Dados Genéticas , População do Leste Asiático , Humanos , Frequência do Gene , Mutação , China/etnologia , População do Leste Asiático/genética , Variação Genética , Genética PopulacionalRESUMO
BACKGROUND: The marbling trait of cattle muscles, being a key indicator, played an important role in evaluating beef quality. Two breeds of cattle, namely a high-marbling (Angus) and a low-marbling (Nanyang) one, with their cattle muscles selected as our samples for transcriptome sequencing, were aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and their targets associated with the marbling trait. RESULTS: Transcriptome sequencing identified 487 and 283 differentially expressed mRNAs and lncRNAs respectively between the high-marbling (Angus) and low-marbling (Nanyang) cattle muscles. Twenty-seven pairs of differentially expressed lncRNAs-mRNAs, including eighteen lncRNAs and eleven target genes, were found to be involved in fat deposition and lipid metabolism. We established a positive correlation between fourteen up-regulated (NONBTAT000849.2, MSTRG.9591.1, NONBTAT031089.1, MSTRG.3720.1, NONBTAT029718.1, NONBTAT004228.2, NONBTAT007494.2, NONBTAT011094.2, NONBTAT015080.2, NONBTAT030943.1, NONBTAT021005.2, NONBTAT021004.2, NONBTAT025985.2, and NONBTAT023845.2) and four down-regulated (NONBTAT000850.2, MSTRG.22188.3, MSTRG.22188.4, and MSTRG.22188.5) lncRNAs and eleven genes related to adiponectin family protein (ADIPOQ), cytochrome P450 family (CYP4V2), 3-hydroxyacyl-CoA dehydratase family (HACD4), kinesin family (KIF5C), lipin family (LPIN2), perilipin family (PLIN1), prostaglandin family (PTGIS), solute carrier family (SLC16A7, SLC2213, and SLCO4C1), and containing a transmembrane domain protein family (VSTM1). CONCLUSIONS: These candidate genes and lncRNAs can be regarded as being responsible for regulating the marbling trait of cattle. lncRNAs along with the variations in intramuscular fat marbling established a foundation for elucidating the genetic basis of high marbling in cattle.
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RNA Longo não Codificante , RNA Mensageiro , Animais , Bovinos/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Músculo Esquelético/metabolismoRESUMO
Pore size sieving, Donnan exclusion, and their combined effects seriously affect ion separation of membrane processes. However, traditional polymer-based membranes face some challenges in precisely controlling both charge distribution and pore size on the membrane surface, which hinders the ion separation performance, such as heavy metal ion removal. Herein, the heterocharged covalent organic framework (COF) membrane is reported by assembling two kinds of ionic COF nanosheets with opposite charges and different pore sizes. By manipulating the stacking quantity and sequence of two kinds of nanosheets, the impact of membrane surface charge and pore size on the separation performance of monovalent and multivalent ions is investigated. For the separation of anions, the effect of pore size sieving is dominant, while for the separation of cations, the effect of Donnan exclusion is dominant. The heterocharged TpEBr/TpPa-SO3H membrane with a positively charged upper layer and a negatively charged bottom layer exhibits excellent rejection of multivalent anions and cations (Ni2+, Cd2+, Cr2+, CrO4 2-, SeO3 2-, etc). The strategy provides not only high-performance COF membranes for ion separation but also an inspiration for the engineering of heterocharged membranes.
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BACKGROUND: This study updated 3-year analyses to further characterize the impact of docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy followed by surgery. METHODS: This study was a single-center phase 2 clinical trial. Patients with a diagnosis of borderline resectable esophageal squamous cell carcinoma (BR-ESCC) because of the primary tumor or bulky lymph node that potentially invaded adjacent organs were eligible. The treatment started with TPF chemotherapy followed by surgery if the cancer was resectable, or by concurrent chemoradiation if it was unresectable. This updated report presents the 3-year overall survival (OS) and progression-free survival (PFS) rates. RESULTS: Surgery was performed for 27 patients (57.4%), and R0 resection was confirmed in 25 patients (53.2%). Pathologic complete response was confirmed in four patients (8.5%). The median follow-up time for the surviving patients was 44.8 months (range, 3.4-74.6 months). The median OS for all the patients was 41.9 months (95% confidence interval [CI], 18.6-65.3 months), with a median PFS of 38.7 months (95% CI, 23.5-53.9 months). The 3-year survival rate for all the patients was 54.4%. The 3-year survival rate for the R0 patients was 65.4%. CONCLUSION: Long-term follow-up evaluation confirmed that TPF followed by surgery is feasible and promising in terms of survival for BR-ESCC patients. Trial Registration ClinicalTrials.gov identifer: NCT02976909.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Cisplatino , Neoplasias Esofágicas/tratamento farmacológico , Quimioterapia de Indução , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel , FluoruracilaRESUMO
Efficiently regulating the rebound behavior of droplets post-impact is crucial for various fields, mainly including the development of self-cleaning applications, the design of surface functional materials, and the advancement of industrial techniques. By performing molecular dynamics simulations, we investigated the impact and jumping behavior of droplets on heterogeneous substrates with different wetting regions. We found that, during the impacting evolution process, the retracted droplets would move toward regions with stronger wettability due to the unbalanced force caused by the wettability difference, revealing the directional migration ability. The values of the wettability difference strongly affect the degree of oblique rebound and contact time when droplets can jump off the substrate. We then designed the surfaces with a wettability gradient and found that the oblique rebound angle could be well controlled and the contact time further reduced. Our findings may provide valuable insight into the relationship between the wettability gradient and the behavior of liquid droplets on surfaces, with broad implications for various fields such as surface engineering, materials science, microfluidics, etc.
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This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.
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Melatonina , Criança , Humanos , Lactente , Melatonina/uso terapêutico , Estudos Prospectivos , Hormônio Adrenocorticotrópico/uso terapêutico , Método Duplo-Cego , Espasmo/tratamento farmacológico , Suplementos NutricionaisRESUMO
BACKGROUND: There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. METHODS: Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. FINDINGS: Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. CONCLUSIONS: Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.
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COVID-19 , Saúde Global , Aprendizado de Máquina , SARS-CoV-2 , Humanos , COVID-19/mortalidade , Fatores de Risco , Pandemias , Vacinas contra COVID-19 , VacinaçãoRESUMO
PURPOSE: This retrospective, single-center, case-control study evaluated the safety and efficacy of Computed tomography (CT)-guided microwave ablation (MWA) for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications. METHODS: Between May 2020 and April 2022, 71 patients with 71 RML pulmonary nodules underwent 71 MWA sessions. To comparison, 142 patients with 142 pulmonary nodules in non-RML were selected using propensity score matching. The technical success, technique efficacy, complications, and associated factors were analyzed. The duration of the procedure and post-ablation hospital stay were also recorded. RESULTS: Technical success was achieved in 100% of all patients. There were no significant differences in technique efficacy rates between the RML and non-RML groups (97.2% vs. 95.1%, p = 0.721). However, both major (47.9% vs. 19.7%, p < 0.001) and minor (26.8% vs. 11.3%, p = 0.004) pneumothorax were more common in the RML group than non-RML group. MWA for RML pulmonary nodules was identified as an independent risk factor for pneumothorax (p < 0.001). The duration of procedures (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group than non-RML group. CONCLUSIONS: CT-guided MWA for RML pulmonary nodules showed comparable efficacy compared with other lobes, but posed a higher risk of pneumothorax complications, necessitating longer MWA procedure times and extended hospital stays.
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Ablação por Cateter , Pneumotórax , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Pneumotórax/etiologia , Micro-Ondas/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Tomografia , Ablação por Cateter/métodosRESUMO
Horizontal gene transfer occurs frequently in bacteria, but the mechanism driving activation and optimization of the expression of horizontally transferred genes (HTGs) in new recipient strains is not clear. Our previous study found that spontaneous tandem DNA duplication resulted in rapid activation of HTGs. Here, we took advantage of this finding to develop a novel technique for tandem gene duplication, named tandem gene duplication selected by activation of horizontally transferred gene in bacteria (TDAH), in which tandem duplication was selected by the activation of horizontally transferred selectable marker gene. TDAH construction does not contain any reported functional elements based on homologous or site-specific recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection and 9-bp-microhomology border sequences for precise illegitimate recombination. One transformation and 3 days were enough to produce a high-copy strain, so its procedure is simple and fast. Without subsequent knockout of the endogenous recombination system, TDAH could also generate the relatively stable high-copy tandem duplication for plasmid-carried and genome-integrated DNA. TDAH also showed an excellent capacity for increase gene expression and worked well in different industrial bacteria. We also applied TDAH to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5 times and remained stable even after 12 subcultures. TDAH is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways. KEY POINTS: ⢠We develop a novel and efficient technique (TDAH) for tandem gene duplication in bacterium. TDAH is based on the mechanism of HTG rapid activation. TDAH does not contain any reported functional elements based on homologous recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection, so its construction and procedure are very simple and fast. ⢠TDAH is the first reported selected and stable tandem-gene-duplication technique in which the selected high-copy plasmid-carried and genome-integrated DNA could remain stable without the subsequent knockout of recombination system. ⢠TDAH showed an excellent capacity for regulating gene expression and worked well in different industrial bacteria, indicating it is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways. ⢠TDAH was applied to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5-fold and remained stable even after 12 subcultures.
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Escherichia coli , Duplicação Gênica , Transferência Genética Horizontal , Plasmídeos , Escherichia coli/genética , Escherichia coli/metabolismo , Plasmídeos/genética , Bactérias/genética , Bactérias/metabolismo , Dosagem de Genes , Recombinação GenéticaRESUMO
Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.
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Schizothorax oconnori (S. oconnori) is an economically important fish in Tibet. Oocyte maturation is a physiological process that is of great significance to reproduction and seed production in S. oconnori, yet little is currently known regarding the molecular mechanisms of oocyte development in this species. To identify candidate genes involved in reproduction of female fish, a combination of PacBio and Illumina HiSeq technologies was employed to provide deep coverage of the oocyte transcriptome. Transcriptome analysis revealed several candidate genes that are potentially involved in the regulation of oocyte maturation in S. oconnori, including GIRK1, CHRM3, NPY2R, GABRA3, GnRH3, mGluR1α, GPER1, GDF9, HSP90, and ESR2. Genes that are significantly expressed during oocyte maturation mainly contribute to the GPCR signaling pathway and the estrogen signaling pathway. Neurotransmitter (Ach, NPY, and GABA) and peptide hormone (GnRH3) binding to G protein-coupled receptors (GPCRs) frees G-protein ßγ subunits to interact with the G protein-gated inward rectifier K+ channel 1 (GIRK1). This process helps release K+ from granulosa cells to maturing oocytes, allowing yolk globule fusion. This mechanism may play an important role in oocyte maturation in S. oconnori. In conclusion, this study provides a valuable basis for deciphering the reproductive system in S. oconnori during the oocyte maturation process.
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Cyprinidae , Cipriniformes , Feminino , Animais , Cipriniformes/genética , Oócitos/metabolismo , Oogênese/genética , Cyprinidae/genética , Perfilação da Expressão Gênica/veterinária , TranscriptomaRESUMO
Parity-time (PT)-symmetry brings various opportunities for electromagnetic field manipulation and light-matter interaction, such as modification of spontaneous emission. However, previous works mainly focused on the behavior of spontaneous emission at exceptional points or in the PT-symmetry situation. Here, we theoretically demonstrate loss-induced Purcell enhancement in PT-broken whispering gallery microcavities. In the PT-broken phase, one of the supermodes decays slowly thereby playing a leading role in spontaneous emission. As the loss increases, the quality factor of this supermode is higher and the mode volume is smaller, so that the Purcell factors will be larger if the emitter is placed near the lossless cavity. Our findings indicate that loss can enhance the interaction between light and matter, which could be applied to single photon emission, non-Hermitian photonic devices, etc.
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BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. A large number of studies have shown that pulmonary vascular endothelial cells (PVECs) dysfunction plays an important role in the initiation and development stages of HPH, but the mechanism of PVECs dysfunction after hypoxia remains unclear. In this study, we explored the exact mechanism of PVECs dysfunction after hypoxia. METHODS: In vitro, we used primary cultured PVECs hypoxia model to mimic HPH injury. We detected the expressions of mitochondrial biogenesis markers, mitochondrial transcription factor A (TFAM) level inside mitochondria, mitochondrial quantity and function, and the components expressions of translocase of outer mitochondrial membrane (TOM) at 24 h after hypoxia. To explore the effects of Tom70 on mitochondrial biogenesis and functions of PVECs after hypoxia, Tom70 overexpression adenovirus was constructed, and the expressions of mitochondrial biogenesis markers, TFAM level inside mitochondria, mitochondrial quantity and function, and the functions of PVECs were detected. And in vivo, we used cre-dependent overexpression adenovirus of Tom70 in the Cdh5-CreERT2 mouse model of HPH to verify the role of upregulating PVECs Tom70 in improving HPH. RESULTS: Hypoxia obviously increased the expressions of mitochondrial biogenesis markers for PGC-1α, NRF-1 and TFAM, but reduced the content of TFAM in mitochondria and the quantity and functions of mitochondria. In addition, only Tom70 expression among the TOM components was significantly decreased after hypoxia, and up-regulation of Tom70 significantly increased the content of TFAM in mitochondria of PVECs by transporting TFAM into mitochondria after hypoxia, enhanced the quantity and functions of mitochondria, improved the functions of PVECs, and ultimately alleviated HPH. CONCLUSION: The findings of present study demonstrated that hypoxia induced the decreased expression of Tom70 in PVECs, reduced the mitochondrial biogenesis-associated TFAM protein transporting into mitochondria, inhibited mitochondrial biogenesis, caused PVECs injury, and prompted the formation of HPH. However, up-regulation of Tom70 abolished the hypoxia-induced injurious effects on PVECs and alleviated HPH.
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Hipertensão Pulmonar , Animais , Camundongos , Células Endoteliais/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipóxia/complicações , Pulmão/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Biogênese de OrganelasRESUMO
Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.
Assuntos
Produtos Biológicos , Osteoporose , Plantas Medicinais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoclastos/metabolismo , Morte CelularRESUMO
PURPOSE: This retrospective study assessed the incidence rate, risk factors, and clinical course of early enlarging cavitation after percutaneous microwave ablation (MWA) of primary lung cancer (PLC). METHODS: This study included 557 lesions of 514 patients with PLC who underwent CT-guided percutaneous MWA between 1 January 2018 and 31 December 2021. Of these patients, 29 developed early enlarging cavitation and were enrolled in the cavity group, and 173 were randomly enrolled in the control group. Early enlarging cavitation of the lung was defined as the development of a cavity ≥30 mm within 7 days after MWA. RESULTS: Overall, 31 (5.57%, 31/557 tumors) early enlarging cavitations occurred at an average of 5.83 ± 1.55 d after MWA. The risk factors were lesion contact with a large vessel (diameter ≥3 mm), lesion contact with the bronchus (diameter ≥2 mm), and a large ablated parenchymal volume. The cavity group had a higher incidence rate of delayed hydropneumothorax (12.9%) and bronchopleural fistula (9.68%) than the control group, resulting in a longer hospitalization (9.09 ± 5.26 days). Until Dec 31, 2022, 27 cavities disappeared after a mean of 217.88 ± 78.57 d (range, 111-510 d), two persisted, and two were lost to follow-up. CONCLUSIONS: Early enlarging cavitation occurred in 5.57% PLC cases that underwent MWA, causing serve complications and longer hospitalization. The risk factors were ablated lesion contact with large vessels and bronchi, as well as a larger ablated parenchymal volume.
Assuntos
Técnicas de Ablação , Ablação por Cateter , Neoplasias Pulmonares , Ablação por Radiofrequência , Humanos , Estudos Retrospectivos , Micro-Ondas/uso terapêutico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Técnicas de Ablação/efeitos adversos , Ablação por Cateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: This retrospective study aimed to assess the safety and efficacy of synchronous biopsy and microwave ablation (MWA) for highly suspected malignant lung ground-glass opacities (GGOs) adjacent to the mediastinum (distance ≤10 mm). MATERIALS AND METHODS: Ninety patients with 98 GGOs (diameter range, 6-30 mm), located within 10 mm of the mediastinum, underwent synchronous biopsy and MWA at a single institution from 1 May 2020, to 31 October 2021 and were enrolled in this study. Synchronous biopsy and MWA involving the completion of the biopsy and MWA in a single procedure was performed. Safety, technical success rate, and local progression-free survival (LPFS) were evaluated. The risk factors for local progression were calculated using the Mann-Whitney U test. RESULTS: The technical success rate was 97.96% (96/98 patients). The LPFS rates at 3, 6, and 12 months were 95.0%, 90.0%, and 82.0%, respectively. The diagnostic rate of biopsy-proven malignancy was 72.45% (n = 71/98). Invasion of lesions into the mediastinum was a risk factor for local progression (p = 0.0077). The 30-day mortality rate was 0. The major complications were pneumothorax (13.27%), ventricular arrhythmias (3.06%), pleural effusion (1.02%), hemoptysis (1.02%), and infection (1.02%). Minor complications included pneumothorax (30.61%), pleural effusion (24.49%), hemoptysis (18.37%), ventricular arrhythmias (11.22%), structural changes in adjacent organs (3.06%), and infection (3.06%). CONCLUSIONS: Synchronous biopsy and MWA was effective for treating GGOs adjacent to the mediastinum without severe complications (Society of Interventional Radiology classification E or F). Invasion of lesions into the mediastinum was identified as a risk factor for local progression.