RESUMEN
Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.
Asunto(s)
Diabetes Mellitus Tipo 1 , Retrovirus Endógenos , Productos del Gen gag , Secuenciación de Nucleótidos de Alto Rendimiento , Ratones Endogámicos NOD , Sistemas de Lectura Abierta , Animales , Ratones , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/virología , Diabetes Mellitus Tipo 1/inmunología , Sistemas de Lectura Abierta/genética , Retrovirus Endógenos/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Productos del Gen gag/genética , Femenino , Islotes PancreáticosRESUMEN
BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Adulto , China/epidemiología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/terapia , Quimioradioterapia/métodos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anciano , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Adulto Joven , Adolescente , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. METHODS: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. RESULTS: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05). CONCLUSIONS: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. PLAIN LANGUAGE SUMMARY: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.
RESUMEN
Neuropathic pain is a chronic and severe syndrome for which effective therapy is insufficient and the release of ATP from microglia induced by sphingosine-1-phosphate (S1P) plays a vital role in neuropathic pain. Therefore, there is an urgent demand to develop highly sensitive and selective ATP biosensors for quantitative monitoring of low-concentration ATP in the complex nervous system, which helps in understanding the mechanism involved in neuropathic pain. Herein, we developed an electrochemical microsensor based on an entropy-driven bipedal DNA walker. First, the microsensor specifically recognized ATP via ATP aptamers, initiating the entropy-driven bipedal DNA walker. Subsequently, the bipedal DNA walker autonomously traversed the microelectrode interface, introducing methylene blue to the electrode surface and achieving cascade signal amplification. This microsensor showed excellent selectivity, stability, and a low limit of detection at 1.13 nM. The S1P-induced ATP release from BV2 cells was successfully monitored, and it was observed that dicumarol could inhibit this release, suggesting dicumarol as a potential treatment for neuropathic pain. The microsensor's small size exhibited significant potential for monitoring ATP level changes in neuropathic pain in vivo, which provides a new strategy for in situ and quantitative monitoring of nonelectroactive biomolecules associated with neurological diseases.
Asunto(s)
Técnicas Biosensibles , Lisofosfolípidos , Neuralgia , Esfingosina/análogos & derivados , Humanos , Entropía , Dicumarol , ADN/química , Microelectrodos , Adenosina Trifosfato , Técnicas Electroquímicas , Límite de DetecciónRESUMEN
Alternative splicing (AS) is an important regulatory mode at the post-transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a-4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above-mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering-related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Sulfuro de Hidrógeno , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Empalme de ARN/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sulfuro de Hidrógeno/metabolismo , Empalme Alternativo/genética , Precursores del ARN/genética , Regulación de la Expresión Génica de las Plantas , Flores/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.
Asunto(s)
Vendajes , Pie Diabético , Hidrogeles , Cicatrización de Heridas , Pie Diabético/terapia , Humanos , Hidrogeles/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Femenino , Masculino , Vendas Hidrocoloidales , Persona de Mediana EdadRESUMEN
Ixeris denticulata is a perennial herbal plant with important medical and economic value. In this study, a novel rhabdovirus from I. denticulata with leaf curling and mottle symptoms was identified through next-generation sequencing and molecular cloning approaches. Based on the host species and properties of this virus, it was tentatively named "Ixeris denticulata-associated rhabdovirus" (IdaRV). IdaRV has a negative-sense RNA genome that is 12,705 nucleotides in length and has five open reading frames (ORFs) in the order 3'-nucleoprotein -phosphoprotein -movement protein -matrix protein -large RNA-dependent RNA polymerase-5'. Pairwise sequence comparisons showed that IdaRV had 42.2-53.0% sequence identity to members of the genera Cytorhabdovirus, Varicosavirus, Betanucleorhabdovirus, Gammanucleorhabdovirus, Dichorhavirus, and Alphanucleorhabdovirus in the subfamily Betarhabdovirinae. BLASTp searches indicated that putative products of ORF1, ORF2, ORF3, ORF4, and ORF5 of IdaRV are most closely related to those of rudbeckia virus 1 (RudV1, GenBank accession number ON185810), with 32.1%, 21.3%, 52.4%, 37.6%, and 57.1% amino acid sequence identity, respectively, at the protein level. Phylogenetic analysis showed that IdaRV forms a smaller branch with RudV1, which belongs to the genus Cytorhabdovirus. These results establish IdaRV as a novel rhabdovirus in the genus Cytorhabdovirus of the family Rhabdoviridae.
Asunto(s)
Asteraceae , Rhabdoviridae , Genoma Viral , Filogenia , Genómica , Sistemas de Lectura Abierta , ARN Viral/genética , ARN Viral/metabolismoRESUMEN
BACKGROUND: Associations between Helicobacter pylori infection and lifestyle factors vary greatly by geographic location. This study aims to evaluate the prevalence of Helicobacter pylori infection in the Hunan cohort of central China and analyze the associations between Helicobacter pylori infection and lifestyle factors in different occupations. METHODS: This was a cross-sectional study. Participants who received an annual physical examination were invited. Helicobacter pylori infection was detected by the 13 C-urea breath test. Self-reported physical examination questionnaires were used to analyze participants' demographic information, diet, exercise status, and sleep situations. RESULTS: 23254 participants finished this study. The Helicobacter pylori infection rate in the Hunan area was 25.8%, with the lowest prevalence in students (8.5%) and the highest prevalence in business managers (29.9%). The risk factors for Helicobacter pylori infection were marital status (divorced or married) (OR:1.16, 95%CI:1.090-1.234), overeating (OR:1.105, 95%CI: 1.001-1.220), and consumption of eggs (OR:1.047, 95%CI:1.004-1.092), animal viscera (OR: 1.077, 95%CI:1.014-1.144) and coffee (OR:1.074, 95%CI:1.019-1.132). Participants' education level (OR:0.911, 95%CI:0.881-0942), consumption of midnight snack (OR:0.926, 95%CI:0.877-0.977), and vegetable (OR:0.927, 95%CI: 0.884-0.972) were protective factors against Helicobacter pylori infection. Whether participants exercised regularly or had sleep problems had no significant effect on Helicobacter pylori infection. Different professionals showed significant differences in the rates of overeating, eating three meals on time, midnight snack, and consuming coffee, eggs, animal viscera, and vegetables > 3 times/week (P values < 0.05). CONCLUSIONS: Helicobacter pylori infection showed a significant relationship with dietary factors, but not significantly with sleep and exercise factors. Different occupations showed different dietary tendencies related to Helicobacter pylori infection. The design of an occupation-based Helicobacter pylori screening and prevention program is supported.
Asunto(s)
Dieta , Ejercicio Físico , Infecciones por Helicobacter , Helicobacter pylori , Sueño , Humanos , Infecciones por Helicobacter/epidemiología , Estudios Transversales , Femenino , Masculino , Adulto , Persona de Mediana Edad , China/epidemiología , Dieta/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Adulto Joven , Ocupaciones/estadística & datos numéricos , Estilo de Vida , Encuestas y Cuestionarios , Pruebas RespiratoriasRESUMEN
PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Histeroscopía , Leiomioma , Miomectomía Uterina , Humanos , Femenino , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Adulto , Miomectomía Uterina/métodos , Histeroscopía/métodos , Persona de Mediana Edad , Leiomioma/cirugía , Leiomioma/terapia , Estudios de Factibilidad , Resultado del Tratamiento , Neoplasias Uterinas/cirugíaRESUMEN
BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD. CONCLUSION: MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.
Asunto(s)
Índice Tobillo Braquial , Progresión de la Enfermedad , Enfermedad del Hígado Graso no Alcohólico , Rigidez Vascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Medición de Riesgo , Factores de Tiempo , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Análisis de la Onda del Pulso , Pronóstico , Delgadez/fisiopatología , Delgadez/epidemiología , Delgadez/diagnóstico , Obesidad/fisiopatología , Obesidad/epidemiología , Obesidad/diagnóstico , AncianoRESUMEN
BACKGROUND: Little has been done to establish biobanks for studying the environment and lifestyle risk factors for diseases among the school-age children. The Minhang Pediatric Biobank (MPB) cohort study aims to identify factors associated with health and diseases of school-aged children living in the urban or suburban area of Shanghai. METHODS: This population-based cohort study was started in all sub-districts/towns of Minhang district of Shanghai in 2014. First-grade students in elementary school were enrolled during the time of their routine physical examinations, with self-administered questionnaires completed by their primary caregivers. Additional information was extracted from multiple health information systems. Urine and saliva samples were collected during the baseline survey and follow-up visits. RESULTS: At the end of 2014 academic year, a total number of 8412 children and their parents were recruited, including 4339 boys and 4073 girls. All the participants completed the baseline survey and physical examination, and 7128 urine and 2767 saliva samples were collected. The five most prevalent childhood diseases in this population were dental caries, bronchitis, pneumonia, asthma and overweight/obese. CONCLUSIONS: The MPB cohort has been successfully established, serving as a useful platform for future research relating to the genetic, environmental and lifestyle risk factors for childhood diseases.
Asunto(s)
Bancos de Muestras Biológicas , Humanos , Masculino , Femenino , Niño , China/epidemiología , Estudios de Cohortes , Saliva/química , Factores de Riesgo , Asma/epidemiología , Estilo de Vida , Caries Dental/epidemiologíaRESUMEN
A liquid chromatography-tandem mass spectrometry method with vonoprazan fumarate-d4 as a stable isotope-labeled internal standard was developed and validated aiming at quantification of vonoprazan fumarate in human plasma for a bioequivalence study. Chromatographic separation was achieved by acetonitrile one-step protein precipitation using a gradient elution of 0.1% formic acid aqueous solution and acetonitrile with a run time of 3.65 min. Detection was carried out on a tandem mass spectrometer in multiple reaction monitoring mode via a positive electrospray ionization interface. The multiple reaction monitoring mode of precursor-product ion transitions for vonoprazan fumarate and vonoprazan fumarate-d4 were m/z 346.0 â 315.1 and 350.0 â 316.0, respectively. The linear range was 0.150-60.000 ng/ml. This method was fully validated with acceptable results in terms of selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, dilution effect, matrix effect, stability, recovery and incurred sample reanalysis. A successful application of this method was realized in the bioequivalence study of vonoprazan fumarate tablet (20 mg) among healthy Chinese volunteers.
Asunto(s)
Pirroles , Sulfonamidas , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Humanos , Espectrometría de Masas en Tándem/métodos , Sulfonamidas/sangre , Sulfonamidas/farmacocinética , Sulfonamidas/química , Pirroles/farmacocinética , Pirroles/sangre , Pirroles/química , Reproducibilidad de los Resultados , Modelos Lineales , Cromatografía Liquida/métodos , Límite de Detección , Masculino , Adulto , Cromatografía Líquida con Espectrometría de MasasRESUMEN
Hibiscus latent Singapore virus (HLSV) and Hibiscus latent Fort Pierce virus (HLFPV) both belong to the genus Tobamovirus in the family Virgaviridae. The genomes of both HLSV and HLFPV consist of a linear positive sense single-stranded RNA of about 6.3 kb. HLSV is the causal agent of hibiscus leaf crinkle disease. Infections of HLSV in hibiscus (Hibiscus rosa-sinensis) have so far only been reported in Singapore, Japan and Malaysia (Srinivasan et al., 2002; Yoshida et al., 2018; Yusop et al., 2021). In 2017, leaf curling and chlorosis symptoms of lantana (Lantana camara) plants were found in Chenshan Botanical Garden, Shanghai, China. To detect potential virus(es) in these lantana samples, leaves from one lantana plant were collected and total RNA was extracted with RNAiso Plus (TaKaRa). A cDNA library was prepared by TruSeq RNA Sample Prep Kit (Illumina) after removing ribosomal RNA by Ribo-ZeroTM rRNA Removal Kit (Epicentre). The paired-end sequencing was then performed on an Illumina NovaSeq 6000. A total of 61,085,018 high quality reads were obtained and de novo assembly by StringTie revealed 124,516 contigs (greater than 50 bp, N50=719 bp) with an average length of 537 bp. BLASTx analyses in the National Center for Biotechnology Information (NCBI) database showed that 1 long contig of 6,305 bp, assembled of 1794 clean reads, shared significant nucleotide similarities with the genomic sequence of HLSV, and 1 contig of 6,271 bp, assembled of 3174 clean reads, shared significant similarities with the genomic sequence of HLFPV, yielding an average coverage of the whole genome at 42.65 and 75.83 per million reads, respectively. To obtain the complete genome of the viral RNA in this lantana sample, eleven overlapping regions covering the entire HLSV viral genome, and nine overlapping regions covering the entire HLFPV viral genome were amplified by reverse transcription-PCR (RT-PCR) and sequenced. In addition, the exact 5' and 3' ends of the genomic RNA of each virus were determined by rapid amplification of the cDNA ends (RACE) (Wang et al. 2020). The complete genome of the identified HLSV, deposited in GenBank: MZ020960, is 6,486 nt in length and shows 98.4% nucleotide sequence identity with HLSV Singapore isolate (GenBank: AF395898). Similar to other HLSV isolates, this virus isolate possesses an internal poly(A) tract of 87 nucleotides, which is crucial to virus replication (Niu et al., 2015). The complete genome of the Lantana HLFPV isolate is 6,463 nt (GenBank MZ020961) including a 73 nt internal poly(A) tract, and has 98.4% nt identity to HLFPV-Japan (AB917427). In two other lantana plants from the same site, the presence of HLSV and HLFPV was confirmed by RT-PCR using the primer pairs (5'-GCATCTGCATAACACGGTTG-3'/5'-ACGTTGTAGTAGACGTTGTTGTAG-3' and 5'-GGACCTTGCTAATCCGCTAAAGTTG-3'/5'-GGTCCATGTCCATCCAGATGCAATC-3'). In addition to the HLSV and HLFPV genomes, BLASTx analysis of three contigs of 3,006 bp, 2,845 bp and 2,200 bp, assembled of 1328, 352 and 2280 clean reads respectively, showed high identity to RNAs 1 (MG182148), 2 (DQ412731) and 3 (KY794710) of cucumber mosaic virus. To the best of our knowledge, this is the first report of L. camara as a new natural host of HLSV and HLFPV, and first identification of a mixed infection of HLSV and HLFPV.
RESUMEN
The diversity in the petal morphology of chrysanthemums makes this species an excellent model for investigating the regulation mechanisms of petal size. However, our understanding of the molecular regulation of petal growth in chrysanthemums remains limited. The GASA (gibberellic acid [GA]-stimulated Arabidopsis) protein plays a significant role in various aspects of plant growth and development. Previous studies have indicated that GEG (a gerbera homolog of the gibberellin-stimulated transcript 1 [GAST1] from tomato) is involved in regulating ray petal growth by inhibiting cell expansion in gerberas. In this study, we successfully cloned the GASA family gene from chrysanthemums, naming it CmGEG, which shares 81.4% homology with GEG. Our spatiotemporal expression analysis revealed that CmGEG is expressed in all tissues, with the highest expression levels observed in the ray florets, particularly during the later stages of development. Through transformation experiments, we demonstrated that CmGEG inhibits petal elongation in chrysanthemums. Further observations indicated that CmGEG restricts cell elongation in the top, middle, and basal regions of the petals. To investigate the relationship between CmGEG and GA in petal growth, we conducted a hormone treatment assay using detached chrysanthemum petals. Our results showed that GA promotes petal elongation while downregulating CmGEG expression. In conclusion, the constrained growth of chrysanthemum petals may be attributed to the inhibition of cell elongation by CmGEG, a process regulated by GA.
Asunto(s)
Proteínas de Arabidopsis , Asteraceae , Chrysanthemum , Chrysanthemum/genética , Chrysanthemum/metabolismo , Flores/metabolismo , Giberelinas/farmacología , Giberelinas/metabolismo , Asteraceae/metabolismo , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Pollen cells require large amounts of sugars from the anther to support their development, which is critical for plant sexual reproduction and crop yield. Sugars Will Eventually be Exported Transporters (SWEETs) have been shown to play an important role in the apoplasmic unloading of sugars from anther tissues into symplasmically isolated developing pollen cells and thereby affect the sugar supply for pollen development. However, among the 17 CsSWEET genes identified in the cucumber (Cucumis sativus L.) genome, the CsSWEET gene involved in this process has not been identified. Here, a member of the SWEET gene family, CsSWEET5a, was identified and characterized. The quantitative real-time PCR and ß-glucuronidase expression analysis revealed that CsSWEET5a is highly expressed in the anthers and pollen cells of male cucumber flowers from the microsporocyte stage (stage 9) to the mature pollen stage (stage 12). Its subcellular localization indicated that the CsSWEET5a protein is localized to the plasma membrane. The heterologous expression assays in yeast demonstrated that CsSWEET5a encodes a hexose transporter that can complement both glucose and fructose transport deficiencies. CsSWEET5a can significantly rescue the pollen viability and fertility of atsweet8 mutant Arabidopsis plants. The possible role of CsSWEET5a in supplying hexose to developing pollen cells via the apoplast is also discussed.
Asunto(s)
Arabidopsis , Cucumis sativus , Arabidopsis/genética , Arabidopsis/metabolismo , Cucumis sativus/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hexosas/metabolismo , Polen/genética , Polen/metabolismo , Saccharomyces cerevisiae/metabolismo , Fertilidad/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Macrophyte overgrowth in eutrophic lakes can hasten the decline of shallow water bodies, yet the impact of macrophyte deposition on sediment phosphorus (P) accumulation in the ice-on season remains unclear. Comparative analyses of P variations among 13 semi-connected sub-lakes in Wuliangsu Lake in China, a typical MDE lake, considered external flow and macrophyte decomposition as driving forces. Sediment P fractions and water total phosphorus (TP) were analyzed at 35 sampling points across three ice-on season stages, along with macrophyte TP content to assess debris contributions. Our findings reveal that phosphorus accumulation occurs during the ice-on season in the MDE lake, with an average TP content increase of 16 mg/kg. However, we observed a surprisingly small sediment nutrient accumulation ratio (ΔTP/ΔTN=0.006) compared to macrophyte nutrient levels before decomposition. Further analysis of the dominant species, Potamogeton pectinatus, indicates that a significant portion (55%) of macrophyte phosphorus is released before the ice-on season. This highlights the critical importance of timing macrophyte harvesting to precede the phosphorus leaching process, which has implications for lake management and ecosystem restoration efforts. Additionally, our research demonstrates similar transformations among different sediment fractions as previously reported. Macrophyte debris decomposition likely serves as the primary source of Residual P (Res-P) or TP accumulation. In addition, Ca-bound P (Ca-P) generally showed a decrease, which mainly caused by its transformation to Fe/Al-bound P (Fe/Al-P), Exchange-P (Ex-P), and sometimes to Res-P. However, we emphasize the significant impacts of flow dynamics on Ca-P transport and transformations. Its hydrodynamic action increases water dissolved oxygen, which accelerates the transformation of Ca-P to more easily released Fe/Al-P and Ex-P. Furthermore, hydrodynamic transport also leads to upstream Ca-P transport to downstream. This underscores the necessity of considering flow dynamics when estimating phosphorus variations and formulating phosphorus restoration strategies.
Asunto(s)
Eutrofización , Lagos , Fósforo , Estaciones del Año , Fósforo/análisis , Fósforo/metabolismo , Ecosistema , China , Sedimentos Geológicos , Monitoreo del Ambiente , HieloRESUMEN
BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Estudios de Cohortes , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Colesterol , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Covalent organic frameworks (COFs) have recently shown great potential for photocatalytic hydrogen production. Currently almost all reports are focused on two-dimensional (2D) COFs, while the 3D counterparts are rarely explored due to their non-conjugated frameworks derived from the sp3 carbon based tetrahedral building blocks. Here, we rationally designed and synthesized a series of fully conjugated 3D COFs by using the saddle-shaped cyclooctatetrathiophene derivative as the building block. Through molecular engineering strategies, we thoroughly discussed the influences of key factors including the donor-acceptor structure, hydrophilicity, specific surface areas, as well as the conjugated/non-conjugated structures on their photocatalytic hydrogen evolution properties. The as-synthesized fully conjugated 3D COFs could generate the hydrogen up to 40.36â mmol h-1 g-1. This is the first report on intrinsic metal-free 3D COFs in photocatalytic hydrogen evolution application. Our work provides insight on the structure design of 3D COFs for highly-efficient photocatalysis, and also reveals that the semiconducting fully conjugated 3D COFs could be a useful platform in clear energy-related fields.
Asunto(s)
Resistencia a la Enfermedad , Oryza , Enfermedades de las Plantas , Virus de Plantas , Plantas Modificadas Genéticamente , Oryza/genética , Oryza/virología , Plantas Modificadas Genéticamente/genética , Virus de Plantas/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
CISD2 and ferroptosis participate in cancer development, but are rarely reported in ovarian cancer. This study aimed to clarify interaction between CISD2 and ferroptosis and evaluate related mechanisms. si-CISD2, wt-p53 and mut-p53 lentiviruses were transfected into SKOV-3 cells. CISD2 and p53 (wild/mutant p53) gene transcriptions were evaluated by RT-PCR. Cell viability, invasion ability, and migration capacity were determined. Expressions of ferroptosis-associated CISD2, p53, elastin, ß-catenin and levels of Gpx4 and TRF were examined. CISD2 downregulation (si-CISD2) has a significant inhibitory effect on cell activity and exerts a synergistic effect with p53. si-CISD2 and Wt-p53 markedly inhibited SKOV-3 invasion and migration capacity, compared to the downregulation control (si-NC) and overexpression control (ov-NC) group (p < 0.001). p53 expression was increased significantly in si-CISD2 treated SKOV-3, compared to si-NC treated cells (p < 0.05). si-CISD2 markedly decreased elastin and ß-catenin expression compared to the si-NC and ov-NC group (p < 0.001). si-CISD2 modulated ferroptosis-associated molecules (CDKN1A, GLS2, SAT1, SLC7A11), decreased Gpx4 and increased TRF levels in SKOV-3. si-CISD2 and Wt-p53 played an obvious synergistic role in regulating ferroptosis-associated molecules and Gpx4/TRF pathway molecules. In conclusion, CISD2 downregulation was involved in ferroptosis process of SKOV-3 cells. This effect of CISD2 was mediated by wild-type p53-associated GLS2/SAT1/SLC7A11 and Gpx4/TRF pathway.