RESUMEN
Antibody drug conjugates (ADCs) are novel drugs that exert specific cytotoxicity against tumor cells. China approved T-Dxd in May 2023, and their introduction has changed the nation's clinical practice. Although more than 700 ADCs are being investigated worldwide, the challenges that remain in antibody engineering, drug discovery, safety management, resistance, drug selection, and sequencing hinder the further promotion and application of ADCs. Experts in China have discussed the several critical concerns related to clinical practice since 2022. Here, the authors conducted a review of ADCs and then discussed several ADCs explored in China. This study proposes several solutions and strategies to maximize the potential benefit that ADCs can provide to patients with breast cancer.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Inmunoconjugados , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , China/epidemiologíaRESUMEN
Owing to the outstanding comprehensive properties of high energy density, excellent cycling ability, and reasonable cost, Ni-rich layered oxides (NCM) are the most promising cathode for lithium-ion batteries (LIBs). To further enhance the specific capacity of Ni-rich layered oxides, it is necessary to increase the cut-off voltage to a higher level. However, a higher cut-off voltage can lead to substantial structural changes and trigger interface side reactions, presenting significant challenges for practical applications (cycle life and safety). Herein, to solve above issues, tris(hexafluoroisopropyl)borate (TFPB) is introduced as a high voltage electrolyte additive for LiNi0.90Co0.06Mn0.04O2 cathode. Based on detail in situ/ex situ characterization, this study proves that TFPB forms a protective solid-state interphase (SEI) layer on the Li-anode. Additionally, derivatives of TFPB are easily oxidatively decomposed to create a dense cathode electrolyte interphase (CEI) film on the cathode. This CEI film effectively prevents the continuous oxidation of the electrolyte and mitigates the adverse effects of HF on the battery. Benefit from the protective SEI and CEI layer, the LiNi0.90Co0.06Mn0.04O2||Li battery with a TFPB-containing electrolyte maintains an unprecedented level of performance, with a capacity retention of 89.1% after 100 cycles under the ultrahigh cut-off voltage of 4.6 V (vs Li/Li+).
RESUMEN
BACKGROUND: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. METHODS: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg-1·d-1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg-1·d-1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. CONCLUSIONS: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR2300072686.
Asunto(s)
Aspirina , Enfermedad de la Arteria Coronaria , Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Niño , Estudios Prospectivos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulinas Intravenosas/administración & dosificación , Enfermedad de la Arteria Coronaria/prevención & control , Enfermedad de la Arteria Coronaria/etiología , Quimioterapia Combinada , Adolescente , Preescolar , Masculino , Femenino , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Vasos Coronarios/diagnóstico por imagen , China/epidemiología , Estudios de Equivalencia como AsuntoRESUMEN
BACKGROUND: We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about 2 years after cardiac surgery. METHODS: We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. RESULTS: EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). CONCLUSIONS: Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. IMPACT: Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.
RESUMEN
OBJECTIVE: To investigate characteristics associated with different COVID-19 outcomes of people with systemic lupus erythematosus (SLE) and COVID-19 during the second pandemic wave of COVID-19 in China. METHODS: In this retrospective study, people with SLE and COVID-19 who visited the First Affiliated Hospital of Nanchang University from December 2022 and February 2023 were subjected to this study. The three possible outcomes were listed in order of ordinal severity: (1) not hospitalized, (2) hospitalized but not receiving oxygenation, and (3) hospitalized with any ventilation or oxygenation. A multivariable ordinal logistic regression model was built to examine the association between COVID-19 severity and demographic traits, medications, comorbidities, and disease activity. Furthermore, among the 301 SLE patients included in our study, only two patients experienced mortality. In order to maintain statistical rigor, we have included these two deceased patients in the outcome measure of hospitalized with any ventilation or oxygenation. RESULTS: A total of 301 patients with SLE were enrolled in this study. The multivariate ordinal logistic regression analyses indicated that high SLE disease activity (vs remission; OR 39.04, 95% CI 3.08 to 494.44, p = .005) was associated with more severe outcomes. Three doses of COVID-19 vaccination (OR 0.19, 95% CI 0.07 to 0.51, p = .001), glucocorticoids dose (1-5 mg/day 0.14, 0.03 to 0.73, p = .020, and 6-9 mg/day 0.12, 0.02 to 0.61, p = .010), and more intensive immunosuppression drugs (0.34, 0.12 to 0.97, p = .044) were associated with better outcomes. In age-adjusted and sex-adjusted models, telitacicept (6.66, 1.35 to 32.86, p = .020) and rituximab (7.81, 1.87 to 32.66, p = .005) were associated with more severe outcomes. Hydroxychloroquine (0.47, 0.25 to 0.88, p = .018) was associated with favorable outcomes. CONCLUSION: Different COVID-19 outcomes in people with SLE are mostly driven by COVID-19 vaccination, medications, and activity SLE. More importantly, three doses of COVID-19 vaccination may be associated with better outcomes.
Asunto(s)
COVID-19 , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Estudios Retrospectivos , Pandemias , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/complicacionesRESUMEN
The effective degradation of recalcitrant lignocellulose has emerged as a bottleneck for the humification of compost, and strategies are required to improve the efficiency of bagasse composting. Bioaugmentation is a promising method for promoting compost maturation and improving the quality of final compost. In this study, the bioaugmentation effects of microbial inoculants on humic acid (HA) formation during lignocellulosic composting were explored. In the inoculated group, the maximum temperature was increased to 72.5 °C, and the phenol-protein condensation and Maillard humification pathways were enhanced, thus increasing the HA content by 43.85%. After inoculation, the intensity of the microbial community interactions increased, particularly for fungi (1.4-fold). Macrogenomic analysis revealed that inoculation enriched thermophilic bacteria and lignocellulose-degrading fungi and increased the activity of carbohydrate-active enzymes and related metabolic functions, which effectively disrupted the recalcitrant structure of lignocellulose to achieve a high humification degree. Spearman correlation analysis indicated that Stappia of the Proteobacteria phylum, Ilumatobacter of the Actinomycetes phylum, and eleven genera of Ascomycota were the main HA producers. This study provides new ideas for bagasse treatment and recycling and realizing the comprehensive use of resources.
Asunto(s)
Celulosa , Compostaje , Sustancias Húmicas , Estiércol , Sustancias Húmicas/análisis , Estiércol/microbiología , Celulosa/metabolismo , Compostaje/métodos , Animales , Bovinos , Bacterias/metabolismo , Lignina/metabolismo , Hongos/metabolismoRESUMEN
OBJECTIVE: Brexanolone (Zulresso®) that was approved for the USA in March 2019 is indicated for the treatment of postpartum depression (PPD), but information on adverse drug reactions (ADRs) associated with its use is limited. The main aim of this study was to explore the postmarketing safety profile of brexanolone. METHODS: In our case/non-case pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS), the reporting odds ratio and information component with 95% confidence intervals were estimated as measures of disproportionate reporting. Primary disproportionality analyses were performed by comparing brexanolone with all other drugs or selective serotonin reuptake inhibitors (SSRIs). Sensitivity analyses were performed on a subset of perinatal depression. RESULTS: We identified 267 cases using brexanolone. Brexanolone was reported as a primary or secondary suspect drug in most cases (n = 260, 97.38%). Of the total brexanolone cases, positive dechallenge and discontinuation accounted for 12.36% (n = 33) and 26.22% (n = 70), respectively. Serious outcomes were reported in 11.61% (n = 31) patients. Compared to all the other drugs or SSRIs within the same time window, the reporting risks of brexanolone were mainly from psychiatric and nervous systems. Sensitivity analyses indicated that these significant disproportionalities were mostly retained. CONCLUSION: Our pharmacovigilance analysis showed a high reporting frequency of psychiatric and nervous system ADRs associated with the use of brexanolone. In additional prospective research, these signals urgently need to be clarified.
Asunto(s)
Farmacovigilancia , Inhibidores Selectivos de la Recaptación de Serotonina , beta-Ciclodextrinas , Femenino , Embarazo , Humanos , Estados Unidos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Estudios Prospectivos , Pregnanolona/efectos adversos , United States Food and Drug Administration , Combinación de MedicamentosRESUMEN
Heavy metals in soil significantly threaten human health, and their remediation is essential. Among the various techniques used, phytoremediation is one of the safest, most innovative, and effective. In recent years, the use of biodegradable chelators to assist plants in improving their remediation efficiency has gained popularity. These biodegradable chelators aid in the transformation of metal ions or metalloids, thereby facilitating their mobilization and uptake by plants. Developed countries are increasingly adopting biodegradable chelators for phytoremediation, with a growing emphasis on green manufacturing and technological innovation in the chelating agent market. Therefore, it is crucial to gain a comprehensive understanding of the mechanisms and market prospects of biodegradable chelators for phytoremediation. This review focuses on elucidating the uptake, translocation, and detoxification mechanisms of chelators in plants. In this study, we focused on the effects of biodegradable chelators on the growth and environmental development of plants treated with phytoremediation agents. Finally, the potential risks associated with biodegradable chelator-assisted phytoremediation are presented in terms of their availability and application prospects in the market. This study provides a valuable reference for future research in this field.
Asunto(s)
Metales Pesados , Contaminantes del Suelo , Humanos , Biodegradación Ambiental , Quelantes/farmacología , Estudios de Factibilidad , Contaminantes del Suelo/análisis , Plantas/metabolismo , Metales Pesados/análisis , SueloRESUMEN
Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.
Asunto(s)
Endófitos , Enfermedades de las Plantas , Ralstonia solanacearum , Ralstonia solanacearum/fisiología , Ralstonia solanacearum/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Endófitos/genética , Endófitos/fisiología , Endófitos/aislamiento & purificación , Pseudomonas/genética , Pseudomonas/fisiología , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Agentes de Control BiológicoRESUMEN
Extracellular matrix metalloproteinase inducer (EMMPRIN) plays critical roles in the regulation of inflammation and bone metabolism. The roles of EMMPRIN signaling in osteoclasts are worthy of deep study. The present study aimed to investigate bone resorption in periodontitis through the intervention of EMMPRIN signaling. The distribution of EMMPRIN in human periodontitis was observed. RANKL-induced osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) were treated with EMMPRIN inhibitor in vitro. Rats with ligation-induced periodontitis were treated with EMMPRIN inhibitor and harvested for microcomputed tomography scanning, histologic observation, immunohistochemistry, and double immunofluorescence analysis. Positive expressions of EMMPRIN could be found in the CD68+-infiltrating cells. Downregulated EMMPRIN restrained osteoclast differentiation of BMMs in vitro, which also inhibited MMP-9 expression (*P < 0.05). In vivo, EMMPRIN inhibitor restrained ligation-induced bone resorption by decreasing tartrate-resistant acid phosphatase-positive osteoclasts. Both EMMPRIN-positive and MMP-9-positive osteoclasts were less common in the EMMPRIN inhibitor groups than in the control groups. Intervention of EMMPRIN signaling in osteoclasts could probably provide a potential therapeutic target for attenuating ligation-induced bone resorption.
Asunto(s)
Resorción Ósea , Periodontitis , Ratones , Ratas , Humanos , Animales , Osteoclastos , Basigina/análisis , Basigina/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Microtomografía por Rayos X , Resorción Ósea/patología , Periodontitis/patología , Ligando RANK , Diferenciación CelularRESUMEN
BACKGROUND: This study examined the association between prenatal role overload and maternal responsiveness, with postnatal depressive symptoms as a mediator. METHODS: Participants were 127 first-time mothers in Hong Kong (M = 32.8, SD = 4.0). Participants completed data collection for self-report on prenatal role overload (Time 1) in the third trimester of pregnancy, postnatal depressive symptoms (Time 2) at 4-month postpartum and maternal responsiveness (Time 3) at 9-month postpartum. The hypothesised mediation model was tested with the Hayes PROCESS macro (model 4). RESULTS: Time 1 prenatal role overload was not directly predictive of later responsiveness (B = -0.06, p = .270). However, the indirect effect of Time 2 postnatal depressive symptoms in the association between Time 1 prenatal role overload and Time 3 responsiveness was significant (unstandardised effect = -0.03, 95% Bootstrapping CI = [-0.081, -0.001]; standardised effect = -0.06, 95% Bootstrapping CI = [-0.152, -0.002]). CONCLUSION: Findings highlighted that more attention is required to the support provided to first-time expectant mothers to prevent role overload, and that intervention for postnatal depressive symptoms may focus on role overload. The findings also highlighted that postnatal depressive symptoms could be a promising way to increase maternal responsiveness.
Asunto(s)
Depresión Posparto , Depresión , Femenino , Embarazo , Humanos , Madres , Periodo Posparto , Tercer Trimestre del EmbarazoRESUMEN
The homolysis of chemical bonds represents one of the most fundamental reactivities of excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike most contemporary radical-generating mechanisms, the direct excitation to homolyze chemical bonds and produce aliphatic carbon-centered radicals under visible light remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design of the dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation and homolytic C-C bond cleavage to release alkyl radicals without external photocatalysts. Spectroscopic and computational analysis reveal unique optical and structural features of DHPQs, rationalizing their faster kinetics in alkyl radical generation than a structurally similar but visible-light transparent radical precursor. Such a capability allows DHPQ to facilitate a wide range of Ni-metallaphotoredox cross couplings with aryl, alkynyl and acyl halides. Other catalytic and non-catalyzed alkylative transformations of DHPQs are also feasible with various radical acceptors. We believe this work would be of broad interest, aiding the synthetic planning with simplified operation and expanding the synthetic reach of photocatalyst-free approaches in cutting-edge research.
RESUMEN
In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.
Asunto(s)
Displasia Broncopulmonar , Recien Nacido Prematuro , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/cirugía , Displasia Broncopulmonar/etiología , Recién Nacido , Bronquios , Masculino , Neumonectomía , FemeninoRESUMEN
BACKGROUND: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. MATERIALS AND METHODS: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. CONCLUSIONS: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Inmunoconjugados , Femenino , Humanos , Ado-Trastuzumab Emtansina/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Inmunoconjugados/uso terapéutico , Receptor ErbB-2/metabolismo , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , /uso terapéuticoRESUMEN
Na3 V2 (PO4 )2 F3 (NVPF) is a suitable cathode for sodium-ion batteries owing to its stable structure. However, the large radius of Na+ restricts diffusion kinetics during charging and discharging. Thus, in this study, a phosphomolybdic acid (PMA)-assisted hydrothermal method is proposed. In the hydrothermal process, the NVPF morphologies vary from bulk to cuboid with varying PMA contents. The optimal channel for accelerated Na+ transmission is obtained by cuboid NVPF. With nitrogen-doping of carbon, the conductivity of NVPF is further enhanced. Combined with crystal growth engineering and surface modification, the optimal nitrogen-doped carbon-covered NVPF cuboid (c-NVPF@NC) exhibits a high initial discharge capacity of 121 mAh g-1 at 0.2 C. Coupled with a commercial hard carbon (CHC) anode, the c-NVPF@NC||CHC full battery delivers 118 mAh g-1 at 0.2 C, thereby achieving a high energy density of 450 Wh kg-1 . Therefore, this work provides a novel strategy for boosting electrochemical performance by crystal growth engineering and surface modification.
RESUMEN
BACKGROUND: We analysed the characteristics of abnormal electroencephalogram (EEG) patterns before, during, and 48 h after cardiac surgery in patients with heterogeneous congenital heart disease to assess their relationship to demographic and perioperative variables and to early patient outcomes. METHODS: In 437 patients enrolled in a single centre, EEG was evaluated for background (including sleep-wake cycle) and discharge (seizures, spikes/sharp waves, pathological delta brushes) abnormalities. Clinical data (arterial blood pressure, doses of inotropic drugs, and serum lactate concentrations) were recorded every 3 h. Postoperative brain MRI was performed before discharge. RESULTS: Preoperative, intraoperative, and postoperative EEG was monitored in 139, 215, and 437 patients, respectively. Patients with a degree of preoperative background abnormalities (n=40) had more severe intraoperative and postoperative EEG abnormalities (P<0.0001). Intraoperatively, 106/215 (49.3%) patients progressed into an isoelectric EEG. Longer durations of isoelectric EEG were associated with more severe postoperative EEG abnormalities and brain injury on MRI (Ps≤0.003). Postoperative background abnormalities occurred in 218/437 (49.9%) patients, and 119 (54.6%) of them had not recovered after surgery. Seizures occurred in 36/437 (8.2%) patients, spikes/sharp waves in 359/437 (82.2%), and pathological delta brushes in 9/437 (2.0%). Postoperative EEG abnormalities correlated with degree of brain injury on MRI (Ps≤0.02). Demographic and perioperative variables were significantly correlated with postoperative EEG abnormalities, which in turn correlated with adverse clinical outcomes. CONCLUSIONS: Perioperative EEG abnormalities occurred frequently and correlated with numerous demographic and perioperative variables and adversely correlated with postoperative EEG abnormalities and early outcomes. The relation of EEG background and discharge abnormalities with long-term neurodevelopmental outcomes remains to be explored.
Asunto(s)
Lesiones Encefálicas , Procedimientos Quirúrgicos Cardíacos , Humanos , Niño , Estudios Prospectivos , Alta del Paciente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Convulsiones , Lesiones Encefálicas/complicaciones , ElectroencefalografíaRESUMEN
Longitudinal traits, such as milk production traits in dairy cattle, are featured by having phenotypic values at multiple time points, which change dynamically over time. In this study, we first imputed SNP chip (50-100K) data to whole-genome sequence (WGS) data in a Chinese Holstein population consisting of 6,470 cows. The imputation accuracies were 0.88 to 0.97 on average after quality control. We then performed longitudinal GWAS in this population based on a random regression test-day model using the imputed WGS data. The longitudinal GWAS revealed 16, 39, and 75 quantitative trait locus regions associated with milk yield, fat percentage, and protein percentage, respectively. We estimated the 95% confidence intervals (CI) for these quantitative trait locus regions using the logP drop method and identified 581 genes involved in these CI. Further, we focused on the CI that covered or overlapped with only 1 gene or the CI that contained an extremely significant top SNP. Twenty-eight candidate genes were identified in these CI. Most of them have been reported in the literature to be associated with milk production traits, such as DGAT1, HSF1, MGST1, GHR, ABCG2, ADCK5, and CSN1S1. Among the unreported novel genes, some also showed good potential as candidate genes, such as CCSER1, CUX2, SNTB1, RGS7, OSR2, and STK3, and are worth being further investigated. Our study provided not only new insights into the candidate genes for milk production traits, but also a general framework for longitudinal GWAS based on random regression test-day model using WGS data.
Asunto(s)
Estudio de Asociación del Genoma Completo , Leche , Animales , Bovinos/genética , Femenino , Estudio de Asociación del Genoma Completo/veterinaria , Genotipo , Leche/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Estudios LongitudinalesRESUMEN
Functions of nerves on bone has been a subject of intense research. The aim of this study is to observe initial bone healing of rat tooth extraction socket after inferior alveolar nerve transection. The bilateral mandible second molars of eighteen Wistar rats were extracted in the study. The rats also suffered from right inferior alveolar nerve transection simultaneously (D + E group), only extraction as control (E group). One, two and four weeks after extraction, the mandibles were taken out for histological observation, TRAP staining, immunofluorescence, immunohistochemistry and micro-computed tomography (Micro-CT). Mouse bone marrow derived macrophages (BMMs) were cultured in vitro. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) were detected in vivo and vitro. The alveolar sockets had been filled to a large extent with new bone at 4 weeks, but BV/TV and BMD decreased in the D + E group. Accordingly, Expressions of osteocalcin (OCN) and osteopontin (OPN) were down-regulated in the D + E group. Denervation increased TRAP-positive osteoclasts and decreased expressions of Nrf2 at 2 weeks after extraction. Decreased Nrf2 promoted osteoclast differentiation of BMMs in vitro. Denervation delays initial bone healing of rat tooth extraction socket. Osteoclast activation induced by decreased Nrf2 might participated in the process.
Asunto(s)
Factor 2 Relacionado con NF-E2 , Cicatrización de Heridas , Ratones , Ratas , Animales , Ratas Wistar , Cicatrización de Heridas/fisiología , Microtomografía por Rayos X , Extracción Dental/métodos , DesnervaciónRESUMEN
Mulberry plants (Morus alba) have leaf shapes, ranging from unlobed to lobed, which are crucial for yield, growth, and adaptability, indicating their ability to adapt to their environment. Competing endogenous RNAs (ceRNAs) constitute a web of RNAs within the organism's transcriptional regulatory system, including protein-coding genes (mRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and others. In this study, samples for ceRNA sequencing were categorized into two groups: whole leaves and lobed leaves, each group with three replicates. In addition, we isolated, cloned, and characterized the precursor miRNA (miR156x) from the leaves of M. alba. miR156x precursor had a length of 107 base pairs and a minimum folding free energy of 50.27 kcal/mol. We constructed a pCAMBIA-35S-GUS-miR156x dual overexpression vector and established a transient transformation system for mulberry. At an optimal transformation solution (OD600 = 0.7), the GUS gene showed a higher expression in the leaves of transiently transformed mulberry with miR156x overexpression, four days after transformation, while the target genes of miR156x had decreased expression in the same leaves. Investigations into the transgenic mulberry plants uncovered various modifications to physio-chemical parameters including POD, SOD, PRO, MDA, soluble proteins and sugars, and chlorophyl content. miRNAs in the plants were found to act as negative regulators of gene expression in response to changes in leaf shape regulation, which was confirmed in vitro using dual-luciferase reporter assays. Subsequently, we cloned Maspl3 in vitro and conducted GST-Pull down assays, obtaining multiple proteins that interacted with the Maspl3 gene. This indicates that the miR156x/Maspl3/MSTRG.25812.1 regulatory module contributes to the differences in mulberry leaf shape.
Asunto(s)
MicroARNs , Morus , Morus/química , ARN Endógeno Competitivo , Hojas de la Planta/metabolismo , MicroARNs/metabolismo , Plantas Modificadas Genéticamente/genética , Genes ReguladoresRESUMEN
Mulberry (Morus alba) is a significant plant with numerous economic benefits; however, its growth and development are affected by nutrient levels. A high level of magnesium (Mg) or magnesium nutrient starvation are two of the significant Mg factors affecting plant growth and development. Nevertheless, M. alba's metabolic response to different Mg concentrations is unclear. In this study, different Mg concentrations, optimal (3 mmol/L), high (6 mmol/L and 9 mmol/L), or low (1 and 2 mmol/L) and deficient (0 mmol/L), were applied to M. alba for three weeks to evaluate their effects via physiological and metabolomics (untargeted; liquid chromatography-mass spectrometry (LC-MS)) studies. Several measured physiological traits revealed that Mg deficiency and excess Mg altered net photosynthesis, chlorophyll content, leaf Mg content and fresh weight, leading to remarkable reductions in the photosynthetic efficiency and biomass of mulberry plants. Our study reveals that an adequate supply of the nutrient Mg promoted the mulberry's physiological response parameters (net photosynthesis, chlorophyll content, leaf and root Mg content and biomass). The metabolomics data show that different Mg concentrations affect several differential metabolite expressions (DEMs), particularly fatty acyls, flavonoids, amino acids, organic acid, organooxygen compounds, prenol lipids, coumarins, steroids and steroid derivatives, cinnamic acids and derivatives. An excessive supply of Mg produced more DEMs, but negatively affected biomass production compared to low and optimum supplies of Mg. The significant DEMs correlated positively with mulberry's net photosynthesis, chlorophyll content, leaf Mg content and fresh weight. The mulberry plant's response to the application of Mg used metabolites, mainly amino acids, organic acids, fatty acyls, flavonoids and prenol lipids, in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. These classes of compounds were mainly involved in lipid metabolism, amino acid metabolism, energy metabolism, the biosynthesis of other secondary metabolites, the biosynthesis of other amino acids, the metabolism of cofactors and vitamin pathways, indicating that mulberry plants respond to Mg concentrations by producing a divergent metabolism. The supply of Mg nutrition was an important factor influencing the induction of DEMs, and these metabolites were critical in several metabolic pathways related to magnesium nutrition. This study provides a fundamental understanding of DEMs in M. alba's response to Mg nutrition and the metabolic mechanisms involved, which may be critical to the mulberry genetic breeding program.