RESUMO
The accumulation and storage of maternal mRNA is crucial for oocyte maturation and embryonic development. PATL2 is an oocyte-specific RNA-binding protein, and previous studies have confirmed that PATL2 mutation in humans and knockout mice cause oocyte maturation arrest or embryonic development arrest, respectively. However, the physiological function of PATL2 in the process of oocyte maturation and embryonic development is largely unknown. Here, we report that PATL2 is highly expressed in growing oocytes and couples with EIF4E and CPEB1 to regulate maternal mRNA expression in immature oocytes. The germinal vesicle oocytes from Patl2-/- mice exhibit decreasing maternal mRNA expression and reduced levels of protein synthesis. We further confirmed that PATL2 phosphorylation occurs in the oocyte maturation process and identified the S279 phosphorylation site using phosphoproteomics. We found that the S279D mutation decreased the protein level of PATL2 and led to subfertility in Palt2S279D knock-in mice. Our work reveals the previously unrecognized role of PATL2 in regulating the maternal transcriptome and shows that phosphorylation of PATL2 leads to the regulation of PATL2 protein levels via ubiquitin-mediated proteasomal degradation in oocytes.
Assuntos
Fator de Iniciação 4E em Eucariotos , Proteínas Nucleares , RNA Mensageiro Estocado , Proteínas de Ligação a RNA , Animais , Feminino , Humanos , Camundongos , Gravidez , Fator de Iniciação 4E em Eucariotos/metabolismo , Homeostase , Camundongos Knockout , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , Proteínas Nucleares/metabolismo , Oócitos/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro Estocado/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Recent work indicates that killing of bacteria by diverse antimicrobial classes can involve reactive oxygen species (ROS), as if a common, self-destructive response to antibiotics occurs. However, the ROS-bacterial death theory has been challenged. To better understand stress-mediated bacterial death, we enriched spontaneous antideath mutants of Escherichia coli that survive treatment by diverse bactericidal agents that include antibiotics, disinfectants, and environmental stressors, without a priori consideration of ROS. The mutants retained bacteriostatic susceptibility, thereby ruling out resistance. Surprisingly, pan-tolerance arose from carbohydrate metabolism deficiencies in ptsI (phosphotransferase) and cyaA (adenyl cyclase); these genes displayed the activity of upstream regulators of a widely shared, stress-mediated death pathway. The antideath effect was reversed by genetic complementation, exogenous cAMP, or a Crp variant that bypasses cAMP binding for activation. Downstream events comprised a metabolic shift from the TCA cycle to glycolysis and to the pentose phosphate pathway, suppression of stress-mediated ATP surges, and reduced accumulation of ROS. These observations reveal how upstream signals from diverse stress-mediated lesions stimulate shared, late-stage, ROS-mediated events. Cultures of these stable, pan-tolerant mutants grew normally and were therefore distinct from tolerance derived from growth defects described previously. Pan-tolerance raises the potential for unrestricted disinfectant use to contribute to antibiotic tolerance and resistance. It also weakens host defenses, because three agents (hypochlorite, hydrogen peroxide, and low pH) affected by pan-tolerance are used by the immune system to fight infections. Understanding and manipulating the PtsI-CyaA-Crpmediated death process can help better control pathogens and maintain beneficial microbiota during antimicrobial treatment.
Assuntos
Anti-Infecciosos , Colicinas , Proteína Receptora de AMP Cíclico , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Transporte de Monossacarídeos , Estresse Oxidativo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato , Anti-Infecciosos/farmacologia , Colicinas/metabolismo , AMP Cíclico/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Tolerância a Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/fisiologia , Proteínas de Escherichia coli/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Colorectal cancer (CRC) is a prevalent malignancy affecting the human digestive tract. Triptonide has been shown to have some anticancer activity, but its effect in CRC is vague. Herein, we examined the effect of triptonide on CRC. In this study, the results of bioinformatics analysis displayed that triptonide may regulate ferroptosis in CRC by modulating GPX4 and SLC7A11. In HCT116 and LoVo cells, the expression levels of GPX4 and SLC7A11 were significantly reduced after triptonide management versus the control group. Triptonide inhibited proliferation, but promoted ferroptosis in CRC cells. SLC7A11 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide inhibited activation of the PI3K/AKT/Nrf2 signaling in CRC cells. Activation of the PI3K/AKT signaling or Nrf2 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide suppressed CRC cell growth in vivo by modulating SLC7A11 and GPX4. In conclusion, Triptonide repressed proliferation and facilitated ferroptosis of CRC cells by repressing the SLC7A11/GPX4 axis through inactivation of the PI3K/AKT/Nrf2 signaling.
Assuntos
Sistema y+ de Transporte de Aminoácidos , Proliferação de Células , Neoplasias Colorretais , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Transdução de Sinais , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Linhagem Celular Tumoral , Células HCT116 , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.
RESUMO
BACKGROUND: Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). METHODS: TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2-5 days of COVID-19 diagnosis were performed. RESULTS: Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47-0.88]), arrhythmia outcomes (HR = 0.81 [0.68-0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35-0.74]) naming heart failure (HR = 0.41 [0.26-0.63]) and deep vein thrombosis (HR = 0.46 [0.24-0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44-0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66-0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11-0.40]), admission (HR = 0.68 [0.60-0.76]), and ICU admission rates (HR = 0.52 [0.33-0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. CONCLUSIONS: Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.
Assuntos
Doenças Autoimunes , COVID-19 , Doenças Cardiovasculares , Lactamas , Leucina , Nitrilas , Prolina , Doenças Reumáticas , Ritonavir , Humanos , Masculino , Recém-Nascido , COVID-19/complicações , COVID-19/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Estudos Retrospectivos , Teste para COVID-19 , Fatores de Risco , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Combinação de MedicamentosRESUMO
The ligament, which connects bones at the joints, has both high water content and excellent mechanical properties in living organisms. However, it is still challenging to fabricate fibrous materials that possess high water content and ligament-like mechanical characteristics simultaneously. Herein, the design and preparation of a ligament-mimicking multicomponent fiber is reported through stepwise assembly of polysaccharide, calcium, and dopamine. In simulated body fluid, the resulting fiber has a water content of 40 wt%, while demonstrating strength of ≈120 MPa, a Young's modulus of ≈3 GPa, and a toughness of ≈25 MJ m-3. Additionally, the multicomponent fiber exhibits excellent creep and fatigue resistance, as well as biocompatibility to support cell growth in vitro. These findings suggest that the fiber has potential for engineering high-performance artificial ligament.
RESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.
Assuntos
Nitrogênio da Ureia Sanguínea , Febre Grave com Síndrome de Trombocitopenia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/virologia , Idoso , Prognóstico , Biomarcadores/sangue , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement. METHODS: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission. RESULTS: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions. CONCLUSIONS: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis.
Assuntos
Doenças Cardiovasculares , Bases de Dados Factuais , Diabetes Mellitus Tipo 2 , Diálise Renal , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Fatores de Tempo , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Medição de Risco , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/terapia , Registros Eletrônicos de SaúdeRESUMO
Functional group interconversion is of great significance in organic synthesis. However, aerobic cleavage of C=N bonds to access carbonyl compounds still suffered from some limitations such as harsh reaction conditions, stoichiometric oxidants, poor substrate scope and use of toxic reagents. Herein, we report a catalyst-free and photo-induced aerobic cleavage of C=N bonds to afford diverse carbonyl compounds using oxygen from air as green oxidant. This mild methodology permits N-tosylhydrazones converted into the corresponding carbonyl compounds including ketones, amides, aldehydes and carboxylic acids, showing broad functional group tolerance and compatibility. Moreover, the gram-scale reaction and post-modification of complicated molecules proved the applicability and efficiency of this strategy. Finally, a plausible mechanism was proposed based on spectroscopic investigations and detailed mechanistic studies.
RESUMO
A copper-catalyzed syn-hydrocarbonization of internal alkynes with N,N-dimethylformamide dimethylacetal and silanes has been disclosed that offers an efficient and expedient access to (E)-α,ß-unsaturated aldehydes. This highly selective process, which can be performed at gram-scale, enjoys operational simplicity, as well as syngas-free conditions.
RESUMO
OBJECTIVE: Asthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma. METHODS: We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case-control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS: The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference -0.05 [95% CI: -0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference -1.60 [95% CI: -6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]). CONCLUSIONS: SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches.
RESUMO
The scope of bioengineering is expanding from the design of single strain to the microbial communities, allowing for the division-of-labor in synthesizing the multi-protein systems. Predicting the composition of the final product during the biomanufacturing process, however, can be difficult. Consortia-based manufacturing has the potential to boost production efficiency, but this benefit primarily holds in the upstream. The current format of downstream process heavily relies on the centralized facility, and is not economical and flexible to address the demands in small-scale. Here, we present a concise and manageable platform to enable the multi-protein system assembly. We engineer a self-lysis microbial consortium, where each strain lyses autonomously at high densities and produces a single protein component. The product fraction can be precisely tuned by varying the inoculation ratio. Utilizing this platform, we assemble a classical 34-component PURE (protein synthesis using recombinant elements) system. We have further optimized the downstream process of the biomanufacturing by incorporating the porous structure of polymeric materials. The encapsulated autolysis consortium can produce and release the proteins while maintaining the cell factories enclosed in the materials by exporting the multi-protein system for collection. Our research provides a novel approach to the flexible and controllable production of multi-protein systems, opening up new possibilities for pathway assembly and portable biomanufacturing.
Assuntos
Bioengenharia , Consórcios Microbianos , Proteínas/químicaRESUMO
Oocyte maturation arrest (OMA) is a common phenotype observed in IVF/ICSI cycles, characterized by the production of immature oocytes which lead to infertility. Previous studies have demonstrated that genetic factors play an important role in OMA, but the genetic mechanisms underlying a group of patients remain to be elucidated. In the recent issue of Journal of Assisted Reproduction and Genetics, Hu et al. and Wan et al. identified novel PATL2 or ZFP36L2 variants in OMA patients, respectively. By conducting in vitro experiments, they demonstrated the destructive effect of the variants on protein function. These findings expand the mutational spectrum of PATL2 and ZFP36L2, and provide precise reference for genetic counseling of OMA patients.
Assuntos
Fertilização in vitro , Oócitos , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Injeções de Esperma Intracitoplásmicas/métodos , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Mutação/genética , Infertilidade Feminina/genética , Infertilidade Feminina/patologiaRESUMO
BACKGROUND: Acute suppurative terminal cholangitis (ASTC) is rarer than acute obstructive cholangitis and is not well studied. To explore this subtype of acute cholangitis, we described our clinical experience with ASTC. METHODS: We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020. We analyzed their clinical characteristics, including etiology, clinical manifestations, imaging features, treatment and prognosis. RESULTS: A total of 32 ASTC patients were included in the analysis. The majority of the patients had a history of biliary operations, and clinical manifestations were occult and atypical. The positive rate of bacterial culture was 46.9%. All the patients had typical imaging features on computed tomography and magnetic resonance imaging. Treatment with effective antibiotics was provided as soon as diagnosis was established. After treatment, most patients had a good outcome. Elevated levels of total bilirubin, aspartate aminotransferase, procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis. CONCLUSIONS: Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis, and that earlier diagnosis and more personalized treatments are needed.
Assuntos
Colangite , Humanos , Supuração/complicações , Prognóstico , Colangite/diagnóstico , Colangite/terapia , Hospitalização , Tomografia Computadorizada por Raios X , Doença Aguda , Estudos RetrospectivosRESUMO
In order to improve the accuracy and convergence speed of the steering law under the conditions of high dynamics, high bandwidth, and a small deflection angle, and in an effort to improve attitude measurement and control accuracy of the spacecraft, a spacecraft attitude measurement and control method based on variable speed magnetically suspended control sensitive gyroscopes (VSMSCSGs) and the fractional-order zeroing neural network (FO-ZNN) steering law is proposed. First, a VSMSCSG configuration is designed to realize attitude measurement and control integration in which the VSMSCSGs are employed as both actuators and attitude-rate sensors. Second, a novel adaptive steering law using FO-ZNN is designed. The matrix pseudoinverses are replaced by FO-ZNN outputs, which solves the problem of accuracy degradation in the traditional pseudoinverse steering laws due to the complexity of matrix pseudoinverse operations under high dynamics conditions. In addition, the convergence and robustness of the FO-ZNN are proven. The results show that the proposed FO-ZNN converges faster than the traditional zeroing neural network under external disturbances. Finally, a new weighting function containing rotor deflection angles is added to the steering law to ensure that the saturation of the rotor deflection angles can be avoided. Semi-physical simulation results demonstrate the correctness and superiority of the proposed method.
RESUMO
Aiming at the influence of the magnetic flux density uniformity error (MFDUE) of the Lorentz force magnetic bearing (LFMB) on the sensitivity accuracy of magnetically suspended control and sensing gyroscopes (MSCSGs) on the angular rate of a spacecraft, a high precision measurement method of the angular rate of a spacecraft based on the MFDUE compensation of LFMB is proposed. Firstly, the structure of MSCSG and the sensitivity principle of MSCSG to the spacecraft angular rate are introduced. The mechanism influencing the accuracy of MSCSG to spacecraft angular rate sensitivity is deduced based on the definition of magnetic flux density uniformity. Secondly, the 3D magnetic flux distribution of LFMB is analyzed using ANSYS. The relationship between the rotor tilt angle, tilt angular rate, and magnetic flux density is established. The induced current calculation model due to MFDUE is proposed, and the LFMB magnetic flux density error compensation is realized. Finally, the simulation results show that the estimation accuracy of the induced current by the proposed method can reach 96%, and the simulation and the experiment show that the error compensation method can improve the accuracy of MSCSG in measuring the spacecraft angular rate by 12.5%.
RESUMO
BACKGROUND: The formation of a tree's heartwood gives the wood properties such as natural decay resistance and aesthetic color, and often directly determines the value of wood products. Regulating the quantity and quality of heartwood is of great importance to the use of wood. However, the mechanism of heartwood formation has been poorly understood. RESULTS: Using Dalbergia odorifera as the study species, the number of starch grains, the morphology of the nuclei, the changes in the content of water and secondary metabolites were observed continuously in the radial direction of the xylem. The results show that from the outer toward inner sapwood, the starch grains are abundant, the length to diameter ratio of the nuclei is decreasing, and the morphology changes from elongated elliptical and then to round. In the outer transition zone, the starch grains begin to decrease abruptly and the nuclei shrink at a slower rate, with a radial width of approximately 2 mm. In the inner transition zone, the heartwood color begins to appear, the starch grains disappear and a few nuclei with reduced fluorescence are present, with a radial width of approximately 1 mm. Heartwood formation after complete disappearance of the nuclei. The moisture content of the heartwood is higher than that of the sapwood, and the inner transition zone is where the content rises. The secondary metabolites of the heartwood begin to accumulate in large quantities in the inner transition zone. CONCLUSION: Based on the physiological changes of parenchyma cells in the xylem, the radial width of the transition zone of Dalbergia odorifera is clearly defined as approximately 3 mm. Both the water and secondary metabolite abrupt changes occur at the final stage of programmed cell death, and neither is a direct cause of programmed cell death in parenchyma cells.
Assuntos
Dalbergia , Dalbergia/metabolismo , Xilema/metabolismo , Madeira/metabolismo , Água/metabolismo , Amido/metabolismoRESUMO
BACKGROUND: Dalbergia odorifera is a precious tree species with unique economic and medicinal values, which is difficult to distinguish from Dalbergia tonkinensis by traditional identification methods such as morphological characteristics and wood structure characteristics. It has been demonstrated that the identification of tree species can be effectively achieved using DNA barcoding, but there is a lack of study of the combined sequences used as DNA barcodes in the two tree species. In this study, 10 single sequences and 4 combined sequences were selected for analysis, and the identification effect of each sequence was evaluated by the distance-based method, BLAST-based search, character-based method, and tree-based method. RESULTS: Among the single sequences and the combined sequences, the interspecies distance of trnH-psbA and ITS2 + trnH-psbA was greater than the intraspecies distance, and there was no overlap in their frequency distribution plots. The results of the Wilcoxon signed-rank test for the interspecies distance of each sequence showed that the interspecies differences of the single sequences except trnL-trnF, trnH-psbA, and ycf3 were significantly smaller than those of the combined sequences. The results of BLAST analysis showed that trnH-psbA could accurately identify D. odorifera and D. tonkinensis at the species level. In the character-based method, single sequences of trnL-trnF, trnH-psbA with all the combined sequences can be used for the identification of D. odorifera and D. tonkinensis. In addition, the neighbor-joining (NJ) trees constructed based on trnH-psbA and ITS2 + trnH-psbA were able to cluster D. odorifera and D. tonkinensis on two clades. CONCLUSIONS: The results showed that the character-based method with the BLOG algorithm was the most effective among all the evaluation methods, and the combined sequences can improve the ability to identify tree species compared with single sequences. Finally, the trnH-psbA and ITS2 + trnH-psbA were proposed as DNA barcodes to identify D. odorifera and D. tonkinensis.
Assuntos
Código de Barras de DNA Taxonômico , Dalbergia , Código de Barras de DNA Taxonômico/métodos , Dalbergia/genética , DNA de Plantas/genética , Análise de Sequência de DNARESUMO
The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 µM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.
Assuntos
Tratamento Farmacológico da COVID-19 , Inibidores de Proteases/química , SARS-CoV-2/química , Bibliotecas de Moléculas Pequenas/química , Antivirais/química , Antivirais/uso terapêutico , Inteligência Artificial , COVID-19/genética , COVID-19/virologia , Descoberta de Drogas , Humanos , Ligantes , Inibidores de Proteases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Bibliotecas de Moléculas Pequenas/uso terapêuticoRESUMO
BACKGROUND: Endothelial-mesenchymal transition (EndMT) plays a crucial role in promoting myocardial fibrosis and exacerbating cardiac dysfunction. Dapagliflozin (DAPA) is a sodium-glucose-linked transporter 2 (SGLT-2) inhibitor that has been shown to improve cardiac function in non-diabetic patients with heart failure (HF). However, the precise mechanisms by which DAPA exerts its beneficial effects are yet to be fully elucidated. METHODS: Isoproterenol (ISO) was used to generate a HF model in mice. For in vitro experiments, we used TGF-ß1-stimulated human umbilical vein endothelial cells (HUVECs) and mouse aortic endothelial cells (MAECs). RESULTS: Both our in vivo and in vitro results showed that EndMT occurred with decreased SIRT1 (NAD+-dependent deacetylase) protein expression, which could be reversed by DAPA therapy. We found that the protective effect of DAPA was significantly impaired upon SIRT1 inhibition. Mechanistically, we observed that SIRT1 phosphorylation, a required modification for its ubiquitination and degradation, was reduced by DAPA treatment, which induces the nucleus translocation of SIRT1 and promotes its binding to the active intracellular domain of Notch1 (NICD). This interaction led to the deacetylation and degradation of NICD, and the subsequent inactivation of the Notch1 signaling pathway which contributes to ameliorating EndMT. CONCLUSIONS: Our study revealed that DAPA can attenuate EndMT induced by ISO in non-diabetic HF mice. This beneficial effect is achieved through SIRT1-mediated deacetylation and degradation of NICD. Our findings provide greater insight into the underlying mechanisms of the therapeutic effects of DAPA in non-diabetic HF.