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1.
Cell ; 148(4): 780-91, 2012 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-22341448

RESUMO

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.


Assuntos
Neoplasias Faciais/veterinária , Instabilidade Genômica , Marsupiais/genética , Mutação , Animais , Evolução Clonal , Espécies em Perigo de Extinção , Neoplasias Faciais/epidemiologia , Neoplasias Faciais/genética , Neoplasias Faciais/patologia , Feminino , Estudo de Associação Genômica Ampla , Masculino , Dados de Sequência Molecular , Tasmânia/epidemiologia
2.
Development ; 149(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35929539

RESUMO

tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders; however, its function in embryonic neurogenesis remains unclear. This study identified an aars1cq71/cq71 mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. aars1 transcripts were highly expressed in primary neural progenitor cells, and their aberration resulted in protein overloading and activated Perk. nfe2l2b, a paralog of mammalian Nfe2l2, which encodes Nrf2, is a pivotal executor of Perk signaling that regulates neuronal phenotypes in aars1cq71/cq71 mutants. Interference of nfe2l2b in nfe2l2bΔ1/Δ1 mutants did not affect global larval development. However, aars1cq71/cq71;nfe2l2bΔ1/Δ1 mutant embryos exhibited increased neuronal cell survival and neurogenesis compared with their aars1cq71/cq71 siblings. nfe2l2b was harnessed by Perk at two levels. Its transcript was regulated by Chop, an implementer of Perk. It was also phosphorylated by Perk. Both pathways synergistically assured the nuclear functions of nfe2l2b to control cell survival by targeting p53. Our study extends the understanding of tRNA synthetase in neurogenesis and implies that Nrf2 is a cue to mitigate neurodegenerative pathogenesis.


Assuntos
Alanina-tRNA Ligase , Fator 2 Relacionado a NF-E2 , Animais , Diferenciação Celular/genética , Sobrevivência Celular/genética , Mamíferos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Peixe-Zebra
3.
Cancer Sci ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38932450

RESUMO

Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression-free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFRL858Q/M patients showed enhanced first-line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFRL858R.

4.
Microb Pathog ; 187: 106513, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38147968

RESUMO

Since pseudorabies (PR) re-emerged and rapidly spread in China at the end of 2011, researchers have focused on effective vaccine strategies to prevent and control pseudorabies virus (PRV) infection in pig herds. Due to the extensive application of an attenuated vaccine based on the Bartha-K61 strain isolated in Hungary in 1961 and the variation of the PRV strain, it has been suggested that traditional vaccines based on the Bartha-K61 strain offer only partial protection against variant strains. It was therefore evaluated whether the Porcilis® Begonia vaccine, which is based on the NIA-3 strain with deletions in the gE and TK genes, is efficacious against experimental infection with the virulent, contemporary Chinese PRV strain ZJ01. In this study, piglets were vaccinated with Porcilis® Begonia through either the intradermal (ID) route or the intramuscular (IM) route and subsequently challenged intranasally with strain ZJ01 at 4 weeks post-vaccination. An unvaccinated challenge group and an unvaccinated/nonchallenged group were also included in the study. All animals were monitored for 14 days after challenge. Vaccinated and negative control pigs stayed healthy during the study, while the unvaccinated control animals developed lesions associated with PRV ZJ01 challenge, and 44% of these pigs died before the end of the experiment. This study demonstrated that ID or IM vaccination of pigs with a vaccine based on the NIA-3 strain Porcilis® Begonia clinically protects against fatal PRV challenge with the ZJ01 strain.


Assuntos
Begoniaceae , Herpesvirus Suídeo 1 , Doenças dos Suínos , Vacinas Virais , Suínos , Animais , Herpesvirus Suídeo 1/genética , Vacinas contra Pseudorraiva , Anticorpos Antivirais , Vacinação/veterinária , Vacinas Virais/genética
5.
Opt Lett ; 49(6): 1575-1578, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489454

RESUMO

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

6.
Langmuir ; 40(4): 2039-2049, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38239095

RESUMO

Digital holography, recognized for its noncontact nature and high precision in three-dimensional imaging, is effectively employed to measure the morphology of bubbles and droplets. However, in terms of near-wall bubbles and droplets, such as confined bubbles in microfluidic chips, the measurement of the interface morphology of bubbles near the glass surface has not yet been resolved due to the coherent noise resulting from glass surface reflections in microfluidic chips. Accordingly, an off-axis digital holography system was devised by using Linnik interferometry. Measuring the confined bubble interface near the wall within a microfluidic chip and droplet evaporation on solid surfaces was studied. Partially coherent LED sources and reference light modulation techniques were employed in the optical setup to mitigate the coherent noise. Dual exposure and weighted least-squares unwrapping algorithms were introduced to correct phase distortions, enhancing image quality. Imaging two confined CO2 bubbles was done near the wall in silicon oil within a porous microfluidic chip, and contact angles of 4.7 and 4.5° were measured. Additionally, the measurement of the three-dimensional morphology of vertically evaporating deionized water droplets on a glass surface was done, due to which calculation of contact angles at various orientations was possible. This work offers a feasible new method for measuring the 3D interface morphology of bubbles and droplets, particularly in microfluidic visualization, addressing current measurement gaps.

7.
J Org Chem ; 89(4): 2351-2363, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38301039

RESUMO

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

8.
Br J Anaesth ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38937217

RESUMO

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

9.
BMC Pediatr ; 24(1): 44, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218765

RESUMO

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS. METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1ß, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman's rank correlation coefficient was calculated to detect significant correlations between cytokine levels. RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1ß (p < 0.05). Serum levels of IL-1ß were significantly correlated with levels of IL-6 and TNF-α (p < 0.05). CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1ß. Given that activated Caspase-1 directly regulates the expression of mature IL-1ß and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1ß secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.


Assuntos
Proteína HMGB1 , Convulsões Febris , Criança , Humanos , Estudos de Casos e Controles , Caspases , Citocinas , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6 , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa
10.
J Clin Lab Anal ; 38(9): e25038, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590133

RESUMO

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.


Assuntos
Klebsiella pneumoniae , Reação em Cadeia da Polimerase Multiplex , beta-Lactamases , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/genética , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/diagnóstico , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Proteínas de Bactérias/genética , Recombinases/genética , Recombinases/metabolismo
11.
Environ Monit Assess ; 196(5): 430, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578570

RESUMO

Arsenic contamination in soils poses a critical global challenge, yet the influence of surfactants on arsenic adsorption behavior is often underestimated. This study aims to investigate the effects of three representative surfactants, namely cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and polyethylene glycol anhydrous sugar alcohol monooleate (Tween 80), on arsenic adsorption behavior in soils. The adsorption isotherm shifts from a single Temkin model without surfactants to both the Langmuir and Temkin models in the presence of surfactants, indicating the simultaneous occurrence of monolayer and multilayer adsorption for arsenic in soils. Moreover, the surfactants can inhibit the adsorption and hasten the attainment of adsorption equilibrium. SDS displayed the most inhibitory effect on arsenic adsorption, followed by Tween 80 and CTAB, due to the competitive adsorption, electrostatic interaction, and hydrophobic interaction. Variations in zeta potential with different surfactants further elucidate this inhibitory phenomenon. Through orthogonal experiment analyses, pH emerges as a primary factor influencing arsenic adsorption in soils, with surfactant concentration and type identified as secondary factors. Temperature notably affects CTAB, with the adsorption inhibition rate plummeting to a mere 0.88% at 50 °C. Sequential extraction analysis revealed that surfactants enhanced the bioavailability of arsenic. The FTIR, XRD, SEM, and CA analyses further support the mechanism underlying the effect of surfactants on arsenic adsorption in soil. These analyses indicate that surfactants modify the composition and abundance of functional groups, hinder the formation of arsenic-containing substances, and improve soil compactness, smoothness, and hydrophilicity. This study provides valuable insights into the effect of surfactants in arsenic-contaminated soils, which is often ignored in previous work.


Assuntos
Arsênio , Tensoativos , Tensoativos/química , Solo/química , Polissorbatos , Cetrimônio , Adsorção , Arsênio/química , Monitoramento Ambiental
12.
Int Wound J ; 21(4): e14867, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597295

RESUMO

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.


Assuntos
Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Humanos , Animais , Camundongos , Cicatrização/fisiologia , Diabetes Mellitus Experimental/terapia , Células Endoteliais da Veia Umbilical Humana , Tecido Adiposo Branco
13.
Anal Chem ; 95(27): 10322-10329, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37339384

RESUMO

The level of 25-hydroxyvitamin D3 [25(OH)VD3] in human blood is considered as the best indicator of vitamin D status, and its deficiency or excess can lead to various health problems. Current methods for monitoring 25(OH)VD3 metabolism in living cells have limitations in terms of sensitivity and specificity and are often expensive and time-consuming. To address these issues, an innovative trident scaffold-assisted aptasensor (TSA) system has been developed for the online quantitative monitoring of 25(OH)VD3 in complex biological environments. Through the computer-aided design, the TSA system includes an aptamer molecule recognition layer that is uniformly oriented, maximizing binding site availability, and enhancing sensitivity. The TSA system achieved the direct, highly sensitive, and selective detection of 25(OH)VD3 over a wide concentration range (17.4-12,800 nM), with a limit of detection of 17.4 nM. Moreover, we evaluated the efficacy of the system in monitoring the biotransformation of 25(OH)VD3 in human liver cancer cells (HepG2) and normal liver cells (L-02), demonstrating its potential as a platform for drug-drug interaction studies and candidate drug screening.


Assuntos
Calcifediol , Colecalciferol , Humanos , Vitamina D/química , Colecalciferol/química
14.
Chembiochem ; 24(10): e202300034, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37040174

RESUMO

CRISPR-LbuCas13a has emerged as a revolutionary tool for in vitro diagnosis. Similar to other Cas effectors, LbuCas13a requires Mg2+ to maintain its nuclease activity. However, the effect of other divalent metal ions on its trans-cleavage activity remains less explored. Herein, we addressed this issue by combining experimental and molecular dynamics simulation analysis. In vitro studies showed that both Mn2+ and Ca2+ could replace Mg2+ as cofactors of LbuCas13a. In contrast, Ni2+ , Zn2+ , Cu2+ , or Fe2+ inhibits the cis- and trans-cleavage activity, while Pb2+ does not affect it. Importantly, molecular dynamics simulations confirmed that calcium, magnesium, and manganese hydrated ions have a strong affinity to nucleotide bases, thus stabilizing the conformation of crRNA repeat region and enhancing the trans-cleavage activity. Finally, we showed that combination of Mg2+ and Mn2+ can further enhance the trans-cleavage activity to allow amplified RNA detection, revealing its potential advantage for in vitro diagnosis.


Assuntos
Manganês , RNA , Cálcio/metabolismo , Conformação Molecular , Magnésio , Sistemas CRISPR-Cas
15.
Chemistry ; 29(10): e202202693, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36400714

RESUMO

CRISPR-based biosensing technology has been emerging as a revolutionary diagnostic tool for many disease-related biomarkers. In particular, RspCas13d, a newly identified RNA-guided Cas13d ribonuclease derived from Ruminococcus sp., has shown great promise for accurate and sensitive detection of RNA due to its RNA sequence-specific recognition and robust collateral trans-cleavage activity. However, its diagnostic utility is limited to detecting nucleic-acid-related biomarkers. To address this limitation, herein we present a proof-of-concept demonstration of a target-responsive CRISPR-Cas13d sensing system for protein biomarkers. This system was rationally designed by integrating a dual-aptamer-based transcription amplification strategy with CRISPR-Cas13d (DATAS-Cas13d), in which the protein binding initiates in-vitro RNA transcription followed by the activation of RspCas13d. Using a short fluorescent ssRNA as the signal reporter and cardiac troponin I (cTnI) as the model analyte, the DATAS-Cas13d system showed a wide linear range, low detection limit, and high specificity for the detection of cTnI in buffer and human serum. Thanks to the facile integration of various bioreceptors into the DATAS-Cas13d system, the method could be adapted to detecting a broad range of clinically relevant protein biomarkers, and thus broaden the medical applications of Cas13d-based diagnostics.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Humanos , RNA , Troponina I/genética , Técnicas Biossensoriais/métodos , Biomarcadores
16.
BMC Cancer ; 23(1): 784, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612621

RESUMO

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).


Assuntos
Doença Trofoblástica Gestacional , Metotrexato , Humanos , Gravidez , Feminino , Dactinomicina/efeitos adversos , Metotrexato/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Doença Trofoblástica Gestacional/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
17.
Inorg Chem ; 62(41): 16913-16918, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37797212

RESUMO

CdE (E = S, Se) quantum dots (QDs) with a broad and large Stokes shift PL emission have emerged as potential materials for white-light LEDs. However, this surface-related emission of nanocrystals is currently limited by low quantum efficiency. Herein, a convenient noninjected one-pot method at a relatively low temperature to prepare CdS QDs was readily achieved. The CdS-368 QD displays intense broad yellow emission in both solution and the solid state at room temperature. The coligation of organic and inorganic ligands passivates the electron trap states at the QD surface and suppresses nonradiative recombination, which is responsible for the high stability of colloids in organic solvents and the distinct fluorescence quantum yield.

18.
Dig Dis ; 41(3): 506-512, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36288720

RESUMO

BACKGROUND: With the increasing incidence of upper digestive tract tumors, more upper digestive tract surgeries are performed each year, and surgeons have difficulty in the postoperative management of gastrointestinal anastomotic fistula. The use of a new minimally invasive technique, endoluminal vacuum-assisted closure (E-VAC), has increased the success rate of the treatment of gastrointestinal fistula. METHODS: We present 6 cases of gastrointestinal fistula treated in our hospital in 2021: 3 cases of anastomotic fistula after esophageal cancer surgery, 2 cases of anastomotic fistula after gastric cancer surgery, and one case of esophageal rupture after trauma. With E-VAC and other adjuvant treatment measures, the gastrointestinal fistulas were eventually closed or significantly reduced. RESULTS: Both local and systemic infections in all 6 patients were controlled with the use of E-VAC device, resulting in significant reduction or closure of fistulas. CONCLUSION: E-VAC devices can effectively help in the removal of the exudate and necrotic tissue around the fistula, promote the proliferation of granulation tissue, and support closure of the fistula. However, further improvements to the device are needed to improve patient comfort and operational safety.


Assuntos
Fístula , Tratamento de Ferimentos com Pressão Negativa , Trato Gastrointestinal Superior , Humanos , Tratamento de Ferimentos com Pressão Negativa/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/métodos , Estômago , Anastomose Cirúrgica/efeitos adversos , Fístula/etiologia , Fístula/cirurgia , Fístula Anastomótica/etiologia , Fístula Anastomótica/terapia
19.
Mol Breed ; 43(1): 5, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37312866

RESUMO

For mechanized maize production, a low grain water content (GWC) at harvest is necessary. However, as a complex quantitative trait, understand the genetic mechanism of GWC remains a large gap, especially in hybrids. In this study, a hybrid population through two environments including 442 F1 was used for genome-wide association analysis of GWC and the grain dehydration rate (GDR), using the area under the dry down curve (AUDDC) as the index. Then, we identified 19 and 17 associated SNPs for GWC and AUDDC, including 10 co-localized SNPs, along with 64 and 77 pairs of epistatic SNPs for GWC and AUDDC, respectively. These loci could explain 11.39-68.2% of the total phenotypic variation for GWC and 41.07-67.02% for AUDDC at different stages, whose major effect was the additive and epistatic effect. By exploring the candidate genes around the significant sites, a total of 398 and 457 possible protein-coding genes were screened, including autophagy pathway and auxin regulation-related genes, and five inbred lines with the potential to reduce GWC in the combined F1 hybrid were identified. Our research not only provides a certain reference for the genetic mechanism analysis of GWC in hybrids but also provides an added reference for breeding low-GWC materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01349-x.

20.
Nature ; 549(7670): 43-47, 2017 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-28825707

RESUMO

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD-a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks.

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