RESUMO
Sulfur (S) is an essential bioelement with vital roles in serving regulatory and catalytic functions and tightly coupled with N and P in plants. However, globally stoichiometric patterns of leaf S and its relationships to leaf N and P are less well studied. We compiled 31 939 records of leaf-based data for 2600 plant species across 6652 sites worldwide. All plant species were divided into different phylogenetic taxa and growth forms. Standard major axis analysis was employed to fit the bivariate element relationships. A phylogenetic linear mixed-effect model and a multiple-regression model were used to partition the variations of bioelements into phylogeny and environments, and then to estimate the importance of environmental variables. Global geometric mean leaf S, N and P concentrations were 1.44, 15.70 and 1.27 mg g-1, respectively, with significant differences among plant groups. Leaf S-N-P positively correlated with each other, ignoring plant groups. The scaling exponents of LN-LS, LP-LS and LN-LP were 0.64, 0.76 and 0.79, respectively, for all species, but differed among plant groups. Both phylogeny and environments regulated the bioelements. The variability, rather than mean temperature, controlled the bioelements. Phylogeny explained more for the concentrations of all the three bioelements than environments, of which S was the one most affected by phylogenetic taxa.
Assuntos
Nitrogênio , Fósforo , Filogenia , Folhas de Planta , Enxofre , Fósforo/metabolismo , Enxofre/metabolismo , Nitrogênio/metabolismo , Plantas , Meio AmbienteRESUMO
Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).
Assuntos
Imunoglobulinas Intravenosas , Púrpura Trombocitopênica Idiopática , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/efeitos adversos , Criança , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Relação Dose-Resposta a Droga , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêuticoRESUMO
INTRODUCTION: Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). However, the cost of IVIg is high. Higher doses of IVIg are associated with a more insupportable financial burden to paediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg can quickly stop bleeding and induce a durable response in treating children with newly diagnosed ITP is not yet established. METHODS AND ANALYSIS: We will extensively search five English databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature) and three Chinese databases (CNKI, Wanfang and VIP). International Clinical Trials Registry Platform and ClinicalTrials.gov will also be searched as supplementary. Randomised controlled trials and prospective observational studies compared the efficacy of low-dose IVIg and high-dose or moderate-dose IVIg will be included. The primary outcome is the proportion of patients achieving durable response. Estimates of effect will be pooled with either a random-effect model or a fixed-effect model according to the heterogeneity of studies. If significant heterogeneity exists, we will conduct subgroup analysis and sensitivity analysis to explore the source of heterogeneity and evaluate the robustness of the results. Publication bias will also be assessed, if possible. The risk of bias will be assessed using the Risk of Bias 2 and Risk Of Bias In Non-randomised Studies of Interventions tools. The certainty of evidence will be evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. ETHICS AND DISSEMINATION: No ethical approval is required since this systematic review is based on previously published studies. The findings of this study will be presented at international conferences or published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022384604.
Assuntos
Imunoglobulinas Intravenosas , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Bases de Dados Factuais , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Metanálise como Assunto , Estudos Observacionais como Assunto , Púrpura Trombocitopênica Idiopática/terapia , Revisões Sistemáticas como AssuntoRESUMO
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the leading cause of death among people with cirrhosis. HCC is typically diagnosed in advanced stages when tumors are resistant to both radio- and chemotherapy. Human ornithine aminotransferase (hOAT) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme involved in glutamine and proline metabolism. Because hOAT is overexpressed in HCC cells and a contributing factor for the uncontrolled cellular division that propagates malignant tumors (Ueno et al. J. Hepatol. 2014, 61, 1080-1087), it is a potential drug target for the treatment of HCC. (1S,3S)-3-Amino-4-(hexafluoropropan-2-ylidenyl)-cyclopentane-1-carboxylic acid (BCF3) has been shown in animal models to slow the progression of HCC by acting as a selective and potent mechanism-based inactivator of OAT (Zigmond et al. ACS Med. Chem. Lett. 2015, 6, 840-844). Previous studies have shown that the BCF3-hOAT reaction has a bifurcation in which only 8% of the inhibitor inactivates the enzyme while the remaining 92% ultimately acts as a substrate and undergoes hydrolysis to regenerate the active PLP form of the enzyme. In this manuscript, the rate-limiting step of the inactivation mechanism was determined by stopped-flow spectrophotometry and time-dependent 19F NMR experiments to be the decay of a long-lived external aldimine species. A crystal structure of this transient complex revealed both the structural basis for fractional irreversible inhibition and the principal mode of inhibition of hOAT by BCF3, which is to trap the enzyme in this transient but quasi-stable external aldimine form.