RESUMO
Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.
Assuntos
Redutases-Desidrogenases de Cadeia Curta , Stachybotrys , Oxirredutases , Catálise , Álcoois/químicaRESUMO
BACKGROUND: Saliva has a crucial role in determining the compatibility between piercing-sucking insects and their hosts. The brown planthopper (BPH) Nilaparvata lugens, a notorious pest of rice in East and Southeast Asia, secretes gelling and watery saliva when feeding on rice sap. Nlsalivap-5 (NlSP5) and Nlsalivap-7 (NlSP7) were identified as potential planthopper-specific gelling saliva components, but their biological functions remain unknown. RESULTS: Here, we showed by transcriptomic analyses that NlSP5 and NlSP7 were biasedly expressed in the salivary glands of BPHs. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome-editing system, we constructed NlSP5 and NlSP7 homozygous mutants (NlSP5-/- and NlSP7-/-). Electrical penetration graph assay showed that NlSP5-/- and NlSP7-/- mutants exhibited abnormal probing and feeding behaviors. Bioassays revealed that the loss-of-function of NlSP5 and NlSP7 significantly reduced the fitness of BPHs, with extended developmental duration, shortened lifespan, reduced weight, and impaired fecundity and hatching rates. CONCLUSION: These findings deepen our understanding of the BPH-host interaction and may provide potential targets for the management of rice planthoppers. © 2024 Society of Chemical Industry.
Assuntos
Hemípteros , Proteínas de Insetos , Proteínas e Peptídeos Salivares , Animais , Feminino , Comportamento Alimentar , Aptidão Genética , Hemípteros/genética , Hemípteros/fisiologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Oryza , Proteínas e Peptídeos Salivares/genética , Proteínas e Peptídeos Salivares/metabolismoRESUMO
BACKGROUND: Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA. METHODS: This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified. RESULTS: Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl. CONCLUSIONS: Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl.
Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Estudos Retrospectivos , Hemoglobinas Glicadas , Controle Glicêmico , Artroplastia do Joelho/efeitos adversos , Fatores de Risco , Artroplastia de Quadril/efeitos adversos , Artrite Infecciosa/etiologia , DexametasonaRESUMO
The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also non-motor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CNâzona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
RESUMO
Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs.