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Phytoplankton blooms have become a global concern due to their negative impacts on public health, aquaculture, tourism, and the economic stability of coastal regions. Therefore, elucidating the shifts in phytoplankton community structure and abundance, as well as their environmental drivers, is crucial. However, existing studies often fail to capture the detailed dynamics of phytoplankton blooms and their environmental triggers due to low temporal observation resolution. In this study, high temporal resolution (daily) samples were collected over 43 days to investigate the influence of environmental factors on phytoplankton in Qinhuangdao in the summer. During the observation period, a total of 45 phytoplankton species were identified, comprising 26 Bacillariophyta species, 16 Dinophyta species, 2 Euglenophyta species, and 1 Chromophyta species. Interestingly, a lag bloom pattern of phytoplankton behind freshwater input was observed across day-to-day samples. Phytoplankton blooms typically lagged 1-3 days behind periods of decreased salinity and nutrient input, suggesting that freshwater influx provides the foundational materials and benefits for these blooms. Moreover, the phytoplankton blooms were triggered by six dominant species, i.e., Chaetoceros spp., Pseudo-nitzschia delicatissima, Skeletonema costatum, Protoperdinium spp., Leptocylindrus minimus, Pseudo-nitzschia pungens, and Thalassiosira spp. Consequently, the succession of phytoplankton showed a predominant genera shift in the following sequence: Nitzschia, Protoperdinium, and Prorocentrum - Skeletonema - Pseudo-nitzschia - Gymnodinium - Leptocylindrus. Besides that, a deterministic process dominated phytoplankton community assembly across time series, and DIP is a key factor in shifting the phytoplankton community structures in this area. In summary, our study offers high-resolution observations on the succession of phytoplankton communities and sheds light on the complex and differentiated responses of phytoplankton to environmental factors. These findings enhance our understanding of the dynamics of phytoplankton blooms and their environmental drivers, which is essential for the effective management and mitigation of their adverse impacts.
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Background: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis. Methods: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson's staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing. Results: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice. Conclusion: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.
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In order to investigate the effects of vegetation changes on runoff and to obtain recommendations for improving runoff in the Weihe River Basin (. In this study, a spatiotemporal geographic autocorrelation weighted regression analysis (SGAWRA) approach was newly developed based on previous studies. This approach investigates spatial non-stationarity of the dynamic response from vegetation variations to climatic change and human activity. Implications of spatial non-stationarity related to runoff variability were also discussed, which in turn yield the effect that vegetation changes have on runoff. The method systematically analysed the spatial non-stationarity of vegetation variations and its associated effects on runoff. Therefore, more closely related results with less error were produced at each step, and results with more accuracy were obtained. These results indicated that the average trend rates of NDVI in the annual average, each season, and the growing season (Growing season refers to April to September) exceeded 0. Areas where NDVI show a growing trend cover more than 50%, which is greater than the area with a decreasing trend. The GWR regression parameters of precipitation, average temperature, and NDVI are all greater than 0. The GWR regression parameters of human activities and NDVI also have more than 50% of the area greater than 0. Based on the visual analysis of the calculation results, it can be seen that there are obvious spatial trends in the data, and the spatial data are significantly different between different regions. Therefore, WRB can be regarded as spatio-temporally non-stationary. In the WRB, the underlying surface change with vegetation change as the prominent feature is the leading cause (about 60%) of the runoff attenuation. The results showed that WRB has spatial and temporal non-stationarity. The spatial non-stationarity of vegetation has a greater effect on runoff changes. The results of this study support recommendations for improving runoff in the WRB.
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Monitoramento Ambiental , Rios , Monitoramento Ambiental/métodos , Análise de Regressão , Estações do Ano , Análise Espaço-Temporal , Humanos , Regressão EspacialRESUMO
BACKGROUND: Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. METHODS: A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/ß-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). RESULTS: PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1ß, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/ß-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of ß-catenin, cyclin D1 and c-Myc in colonic tissues. CONCLUSIONS: PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/ß-catenin signaling pathway.
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Temperature is one of the key environmental factors influencing crop fertility and yield. Understanding how plants sense and respond to temperature changes is, therefore, crucial for improving agricultural production. In this study, we characterized a temperature-sensitive male-sterile mutant in rice (Oryza sativa), glutamyl-tRNA synthetase 1-2 (ers1-2), that shows reduced fertility at high temperatures and restored fertility at low temperatures. Mutation of ERS1 resulted in severely delayed pollen development and meiotic progression at high temperatures, eventually leading to male sterility. Moreover, meiosis-specific events, including synapsis and crossover formation, were also delayed in ers1-2 compared with the wild type. However, these defects were all mitigated by growing ers1-2 at low temperatures. Transcriptome analysis and measurement of ascorbate, glutathione, and hydrogen peroxide (H2O2) contents revealed that the delayed meiotic progression and male sterility in ers1-2 were strongly associated with changes in reactive oxygen species (ROS) homeostasis. At high temperatures, ers1-2 exhibited decreased accumulation of ROS scavengers and overaccumulation of ROS. In contrast, at low temperatures, the antioxidant system of ROS was more active, and ROS contents were lower. These data suggest that ROS homeostasis in ers1-2 is disrupted at high temperatures but restored at low temperatures. We speculate that ERS1 dysfunction leads to changes in ROS homeostasis under different conditions, resulting in delayed or rescued meiotic progression and thermosensitive male fertility. ers1-2 may hold great potential as a thermosensitive material for crop heterosis breeding.
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Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
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Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.
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Antibacterianos , Infecções Bacterianas , Aprendizado de Máquina , Humanos , Recém-Nascido , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/diagnóstico , Tomada de Decisão Clínica , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/diagnósticoRESUMO
Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.
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Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Pareamento Cromossômico , Meiose , Oryza , Meiose/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Oryza/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Coesinas , Mitose , Complexo Sinaptonêmico/metabolismo , Complexo Sinaptonêmico/genética , Sistemas CRISPR-CasRESUMO
The challenges of drug development in pediatric, pregnant and geriatric populations are a worldwide concern shared by regulatory authorities, pharmaceutical companies, and healthcare professionals. Model-informed drug development (MIDD) can integrate and quantify real-world data of physiology, pharmacology, and disease processes by using modeling and simulation techniques to facilitate decision-making in drug development. In this article, we reviewed current MIDD policy updates, reflected on the integrity of physiological data used for MIDD and the effects of physiological changes on the drug PK, as well as summarized current MIDD strategies and applications, so as to present the state of the art of MIDD in pediatric, pregnant and geriatric populations. Some considerations are put forth for the future improvements of MIDD including refining regulatory considerations, improving the integrity of physiological data, applying the emerging technologies, and exploring the application of MIDD in new therapies like gene therapies for special populations.
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Desenvolvimento de Medicamentos , Humanos , Desenvolvimento de Medicamentos/métodos , Gravidez , Feminino , Criança , Idoso , Modelos BiológicosRESUMO
Infectious bronchitis virus (IBV) is caused by avian coronavirus and poses a global economic threat to the poultry industry. In 2023, a highly pathogenic IBV strain, IBV/CN/GD20230501, was isolated and identified from chickens vaccinated with IBV-M41 in Guangdong, China. This study comprehensively investigated the biological characteristics of the isolated IBV strain, including its genotype, whole genome sequence analysis of its S1 gene, pathogenicity, host immune response, and serum non-targeted metabolomics. Through the analysis of the S1 gene sequence, serum neutralization tests, and comparative genomics, it was proven that IBV/CN/GD20230501 belongs to the GI-I type of strain and is serotype II. One alanine residue in the S1 subunit of the isolated strain was mutated into serine, and some mutations were observed in the ORF1ab gene and the terminal region of the genome. Animal challenge experiments using the EID50 and TCID50 calculations showed that IBV/CN/GD20230501 possesses strong respiratory pathogenicity, with early and long-term shedding of viruses and rapid viral spread. Antibody detection indicated that chickens infected with IBV/CN/GD20230501 exhibited delayed expression of early innate immune genes, while those infected with M41 showed rapid gene induction and effective viral control. Metabolomics analysis demonstrated that this virus infection led to differential expression of 291 ions in chicken serum, mainly affecting the citric acid cycle (tricarboxylic acid cycle).IMPORTANCEThis study identified an infectious bronchitis virus (IBV) strain isolated from vaccinated chickens in an immunized population that had certain sequence differences compared to IBV-M41, resulting in significantly enhanced pathogenicity and host defense. This strain has the potential to replace M41 as a more suitable challenge model for drug research. The non-targeted metabolomics analysis highlighting the citric acid cycle provides a new avenue for studying this highly virulent strain.
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Galinhas , Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas , Animais , Vírus da Bronquite Infecciosa/genética , Vírus da Bronquite Infecciosa/patogenicidade , Vírus da Bronquite Infecciosa/imunologia , Vírus da Bronquite Infecciosa/isolamento & purificação , Galinhas/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , China , Genoma Viral/genética , Filogenia , Virulência , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Sequenciamento Completo do Genoma , Genótipo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.
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Digital rural construction is a key strategic direction to promote China's rural revitalization and alleviate global climate problems. In order to put forward feasible suggestions for the subsequent development and ensure the smooth development of digital village construction, how to reflect the development level of the digital village through scientific and reasonable comprehensive evaluation has become an urgent problem to be solved. This paper establishes a comprehensive evaluation index system through the Delphi method and principal component analysis method, then assigns weights to the evaluation indicators based on the improved CRITIC-G1 method, and then grades the development level of digital villages according to the extension matter element method. Finally, taking Jiangxi Province in China as an example, the overall development level of digital villages in Jiangxi Province is evaluated from the provincial level according to the proposed method. And put forward the corresponding countermeasures and suggestions. Results: Firstly, the development level of digital villages in Jiangxi Province is good, and there is a trend of excellent development level. Secondly, from different aspects of digital rural development, the digitalization of infrastructure, services, economy, and green production in Jiangxi Province is at a good level, and the digitalization of life has reached an excellent level. Thirdly, from the perspective of development trends, the digitization of infrastructure has a progressive trend towards an excellent level of development, while the digitization of services, economy and green production has signs of development regression. According to the analysis results, the relevant countermeasures and suggestions are put forward from four aspects: talent, capital, governance system and development planning. Other regions can evaluate the development level of the digital village according to the evaluation model proposed in this paper so as to analyze the existing problems and put forward targeted solutions to promote the construction of the digital village.
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População Rural , China , Humanos , Análise de Componente Principal , Técnica DelphiRESUMO
Background and Aims: China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China. Methods: Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted. Results: In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021-2030 is predicted to have a downward trend. Conclusions: Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.
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BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.
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Doenças Cardiovasculares , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêuticoRESUMO
Background and Aims: China accounts for 14.9% of total cirrhosis deaths worldwide. A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in China is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis worldwide. The study aimed to report the cirrhosis mortality rates in our whole country or province over time. Methods: Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System (DSPs) of the Chinese Center for Disease Control and Prevention. The crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex, residential location, and region. The average annual percentage change (AAPC) in cirrhosis mortality rates from 2008 to 2020 was also calculated. Results: The crude mortality rate of cirrhosis was 4.57/100,000 people in 2020. Compared with females and individuals living in urban areas, males and people living in rural areas had greater age-standardized mortality. The crude mortality rate and age-standardized mortality rate in provinces in Southwest China (Guangxi, Yunnan, Guizhou, and Qinghai) were greater than those in other provinces. Moreover, with increasing age, the age-specific mortality rate increased significantly. From 2008 to 2020, the mortality rate of cirrhosis in China decreased except for in males aged 50-59 years, females aged 45-49 years and females aged 80-84 years. Conclusions: The mortality rate of patients with cirrhosis in China decreased from 2008 to 2020. In the future, interventions of cirrhosis mortality control need to pay more attention to all males, females aged 45-49 and 80-84 years, and people living in rural areas and in provinces in Southwest China.
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The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.
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Meiose , Mitose , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Meiose/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Citocininas/metabolismoRESUMO
During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends toward the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.
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Pareamento Cromossômico , Cromossomos de Plantas , Meiose , Oryza , Oryza/genética , Pareamento Cromossômico/genética , Cromossomos de Plantas/genética , Meiose/genética , Telômero/genética , Hibridização in Situ Fluorescente , Prófase Meiótica I/genéticaRESUMO
OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.
Assuntos
Apoptose , Proliferação de Células , Neoplasias Colorretais , Inibidor de Quinase Dependente de Ciclina p21 , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Proteína Supressora de Tumor p53/metabolismo , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Animais , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Células HCT116 , Regulação para Baixo/efeitos dos fármacosRESUMO
OBJECTIVE: To retrospectively evaluate the efficacy and safety of CT-guided microcoil localization of pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: A total of 1059 consecutive patients with 1331 pulmonary nodules treated between July 2018 and April 2021 were included in this study. Of the 1331 nodules, 1318 were localized using the tailed method and 13 were localized using the non-tailed method. The localization technical success rate and complications of the microcoil localization procedure were assessed. Univariate and multivariate logistic regression analyses were used to determine potential risk factors for technical failure, pneumothorax, and pulmonary hemorrhage. RESULTS: The technical success rate of the localization procedure was 98.4% (1310/1331 nodules). Nodule location in the lower lobes (p = 0.015) and need for a longer needle path (p < 0.001) were independent predictors of technical failure. All localization procedure-related complications were minor (grade 1 or 2) adverse events, with the exception of one grade 3 complication. The most common complications were pneumothorax (302/1331 nodules [22.7%]) and pulmonary hemorrhage (328/1331 nodules [24.6%]). Male sex (p = 0.001), nodule location in the middle (p = 0.003) and lower lobes (p = 0.025), need for a longer needle path (p < 0.001), use of transfissural puncture (p = 0.042), and simultaneous multiple localizations (p < 0.001) were independent risk factors for pneumothorax. Female sex (p = 0.015), younger age (p = 0.023), nodules location in the upper lobes (p = 0.011), and longer needle path (p < 0.001) were independent risk factors for pulmonary hemorrhage. CONCLUSIONS: CT-guided microcoil localization of pulmonary nodules before VATS using either the tailed or non-tailed method is effective and safe. CLINICAL RELEVANCE STATEMENT: CT-guided microcoil localization of pulmonary nodules before VATS resection is effective and safe when using either the tailed or non-tailed method. Nodules requiring transfissural puncture and multiple nodules requiring simultaneous localizations can also be successfully localized with this method. KEY POINTS: ⢠Pre-VATS CT-guided microcoil localization of pulmonary nodules by tailed or non-tailed method was effective and safe. ⢠When the feasible puncture path was beyond the scope of wedge resection, localization could be performed using the non-tailed method. ⢠Although transfissural puncture and simultaneous multiple localization were independent risk factors for pneumothorax, they remained clinically feasible.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumotórax , Nódulo Pulmonar Solitário , Humanos , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Cirurgia Torácica Vídeoassistida/métodos , Pneumotórax/etiologia , Estudos Retrospectivos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia Computadorizada por Raios X/métodos , Hemorragia/etiologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgiaRESUMO
Cuproptosis is a type of programmed cell death triggered by accumulation of intracellular copper which was considered closely related to tumor progression. The study of cuproptosis in multiple myeloma (MM) is however limited. To determine the prognostic significance of cuproptosis-related gene signature in MM, we interrogated gene expression and overall survival with other available clinical variables from public datasets. Four cuproptosis-related genes were included to establish a prognostic survival model by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, which showed a good performance on prognosis prediction in both training and validation cohorts. Patients with higher cuproptosis-related risk score (CRRS) exhibited worse prognosis compared with lower risk score. Survival prediction capacity and clinical benefit were elevated after integrating CRRS to existing prognostic stratification system (International Staging System, ISS or Revised International Staging System, RISS) both on 3-year and 5-year survival. Based on CRRS groups, functional enrichment analysis and immune infiltration in bone marrow microenvironment revealed correlation between CRRS and immunosuppression. In conclusion, our study found that cuproptosis-related gene signature is an independent poor prognostic factor and functions negatively on immune microenvironment, which provides another perspective on prognosis assessment and immunotherapy strategy in MM.