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1.
Cell ; 187(5): 1127-1144.e21, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38428393

RESUMO

Chloroplasts are green plastids in the cytoplasm of eukaryotic algae and plants responsible for photosynthesis. The plastid-encoded RNA polymerase (PEP) plays an essential role during chloroplast biogenesis from proplastids and functions as the predominant RNA polymerase in mature chloroplasts. The PEP-centered transcription apparatus comprises a bacterial-origin PEP core and more than a dozen eukaryotic-origin PEP-associated proteins (PAPs) encoded in the nucleus. Here, we determined the cryo-EM structures of Nicotiana tabacum (tobacco) PEP-PAP apoenzyme and PEP-PAP transcription elongation complexes at near-atomic resolutions. Our data show the PEP core adopts a typical fold as bacterial RNAP. Fifteen PAPs bind at the periphery of the PEP core, facilitate assembling the PEP-PAP supercomplex, protect the complex from oxidation damage, and likely couple gene transcription with RNA processing. Our results report the high-resolution architecture of the chloroplast transcription apparatus and provide the structural basis for the mechanistic and functional study of transcription regulation in chloroplasts.


Assuntos
RNA Polimerases Dirigidas por DNA , Plastídeos , Cloroplastos/metabolismo , Microscopia Crioeletrônica , RNA Polimerases Dirigidas por DNA/genética , Nicotiana/genética , Fotossíntese , Plastídeos/enzimologia
2.
Nature ; 628(8009): 887-893, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538796

RESUMO

Efficient termination is required for robust gene transcription. Eukaryotic organisms use a conserved exoribonuclease-mediated mechanism to terminate the mRNA transcription by RNA polymerase II (Pol II)1-5. Here we report two cryogenic electron microscopy structures of Saccharomyces cerevisiae Pol II pre-termination transcription complexes bound to the 5'-to-3' exoribonuclease Rat1 and its partner Rai1. Our structures show that Rat1 displaces the elongation factor Spt5 to dock at the Pol II stalk domain. Rat1 shields the RNA exit channel of Pol II, guides the nascent RNA towards its active centre and stacks three nucleotides at the 5' terminus of the nascent RNA. The structures further show that Rat1 rotates towards Pol II as it shortens RNA. Our results provide the structural mechanism for the Rat1-mediated termination of mRNA transcription by Pol II in yeast and the exoribonuclease-mediated termination of mRNA transcription in other eukaryotes.


Assuntos
Microscopia Crioeletrônica , Exorribonucleases , RNA Polimerase II , RNA Mensageiro , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Terminação da Transcrição Genética , Exorribonucleases/química , Exorribonucleases/metabolismo , Exorribonucleases/ultraestrutura , Modelos Moleculares , Ligação Proteica , RNA Polimerase II/química , RNA Polimerase II/metabolismo , RNA Polimerase II/ultraestrutura , RNA Mensageiro/biossíntese , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/ultraestrutura , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/ultraestrutura , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/ultraestrutura , Fatores de Elongação da Transcrição/química , Fatores de Elongação da Transcrição/metabolismo , Fatores de Elongação da Transcrição/ultraestrutura , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/ultraestrutura , Domínios Proteicos , RNA Fúngico/biossíntese , RNA Fúngico/química , RNA Fúngico/genética , RNA Fúngico/ultraestrutura
3.
Nat Mater ; 23(1): 116-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37957269

RESUMO

Carbon monoxide (CO) separation relies on chemical adsorption but suffers from the difficulty of desorption and instability of open metal sites against O2, H2O and so on. Here we demonstrate quasi-open metal sites with hidden or shielded coordination sites as a promising solution. Possessing the trigonal coordination geometry (sp2), Cu(I) ions in porous frameworks show weak physical adsorption for non-target guests. Rational regulation of framework flexibility enables geometry transformation to tetrahedral geometry (sp3), generating a fourth coordination site for the chemical adsorption of CO. Quantitative breakthrough experiments at ambient conditions show CO uptakes up to 4.1 mmol g-1 and CO selectivity up to 347 against CO2, CH4, O2, N2 and H2. The adsorbents can be completely regenerated at 333-373 K to recover CO with a purity of >99.99%, and the separation performances are stable in high-concentration O2 and H2O. Although CO leakage concentration generally follows the structural transition pressure, large amounts (>3 mmol g-1) of ultrahigh-purity (99.9999999%, 9N; CO concentration < 1 part per billion) gases can be produced in a single adsorption process, demonstrating the usefulness of this approach for separation applications.

4.
J Am Chem Soc ; 146(20): 13886-13893, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739909

RESUMO

Guest-induced (crystal-to-crystal) transformation, i.e., periodic flexibility, is a typical feature of molecule-based crystalline porous materials, but its role for adsorptive separation is controversial. On the other hand, aperiodic flexibility is rarely studied. This work reports a pair of isomeric Cu(I) triazolate frameworks, namely, α-[Cu(fetz)] (MAF-2Fa) and ß-[Cu(fetz)] (MAF-2Fb), which show typical periodic and aperiodic flexibility for CO chemical adsorption, respectively. Quantitative mixture breakthrough experiments show that, while MAF-2Fa exhibits high adsorption capacity at high pressures but negligible adsorption below the threshold pressure and with leakage concentrations of 3-8%, MAF-2Fb exhibits relatively low adsorption capacity at high pressures but no leakage (residual CO concentration <1 ppb). Tandem connection of MAF-2Fa and MAF-2Fb can combine their advantages of high CO adsorption capacities at high and low pressures, respectively. MAF-2Fa and MAF-2Fb can both keep the separation performances unchanged at high relative humidities, but only MAF-2Fb shows a unique coadsorption behavior at a relative humidity of 82%, which can be used to improve purification performances.

5.
Int Microbiol ; 27(2): 535-544, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37505307

RESUMO

Cajaninstilbene acid (CSA), longistylin A (LLA), and longistylin C (LLC) are three characteristic stilbenes isolated from pigeon pea. The objective of this study was to evaluate the antibacterial activity of these stilbenes against Staphylococcus aureus and even methicillin-resistant Staphylococcus aureus (MRSA) and test the possibility of inhibiting biofilm formation. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these stilbenes were evaluated. And the results showed that LLA was most effective against tested strains with MIC and MBC values of 1.56 µg/mL followed by LLC with MIC and MBC values of 3.12 µg/mL and 6.25 µg/mL as well as CSA with MIC and MBC values of 6.25 µg/mL and 6.25-12.5 µg/mL. Through growth curve and cytotoxicity analysis, the concentrations of these stilbenes were determined to be set at their respective 1/4 MIC in the follow-up research. In an anti-biofilm formation assay, these stilbenes were found to be effectively inhibited bacterial proliferation, biofilm formation, and key gene expressions related to the adhesion and virulence of MRSA. It is the first time that the anti-S. aureus and MRSA activities of the three stilbenes have been systematically reported. Conclusively, these findings provide insight into the anti-MRSA mechanism of stilbenes from pigeon pea, indicating these compounds may be used as antimicrobial agents or additives for food with health functions, and contribute to the development as well as application of pigeon pea in food science.


Assuntos
Cajanus , Staphylococcus aureus Resistente à Meticilina , Estilbenos , Antibacterianos/farmacologia , Estilbenos/farmacologia , Testes de Sensibilidade Microbiana , Anticorpos/farmacologia , Biofilmes
6.
Oral Dis ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764349

RESUMO

OBJECTIVES: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) exhibit varying degrees of halitosis. The author speculated that small intestinal bacterial overgrowth (SIBO) might lead to MASLD and subsequent extra-oral halitosis and aimed to test this hypothesis. METHODS: This retrospective cross-sectional study reviewed 885 extra-oral halitosis patients. Halitosis and exhaled dimethyl sulfide (DMS) were measured by organoleptic score (OLS) (0-5) and OralChroma, respectively. SIBO and MASLD were diagnosed by hydrogen breath test and Fibroscan combined with cardiometabolic criteria. RESULTS: In this study, 133/885 (15.05%) of the halitosis patients otherwise healthy had MASLD, while 87/133 (65.41%) of the MASLD patients were SIBO-positive. No significant differences were observed in physical parameters such as age, serum biochemical parameters such as lipids, or Fibroscan parameters between the SIBO-positive and SIBO-negative patients. However, the OLS was 4 (interquartile range: 3-4) and exhaled DMS level was 56 (43-75) parts per billion (ppb) in the SIBO-positive patients, significantly greater than 2 (2-3) and 43 (25-51) ppb in the SIBO-negative patients (both p < 0.001). Exhaled hydrogen levels positively correlated with the OLS and exhaled DMS levels (r = 0.774, r = 0.740, both p < 0.001). CONCLUSION: MASLD can cause halitosis by SIBO.

7.
Ann Intern Med ; 176(12): 1617-1624, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37956431

RESUMO

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.


Assuntos
Terapia por Acupuntura , Urticária Crônica , Urticária , Humanos , Terapia por Acupuntura/efeitos adversos , Urticária Crônica/terapia , Urticária Crônica/etiologia , China , Resultado do Tratamento , Urticária/terapia , Urticária/etiologia
8.
Fetal Diagn Ther ; : 1, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838656

RESUMO

INTRODUCTION: The aim of this study was to assess the short- and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies. METHODS: Retrospective analysis was conducted of a consecutive cohort of all monochorionic twin pregnancies treated with fetoscopy-guided bipolar cord coagulation between December 2015 and December 2022 in a single center in China. RESULTS: A total of 43 monochronic twin pregnancies undergoing fetoscopy-guided bipolar cord coagulation were analyzed. There were 5 intrauterine deaths with an 88.4% (38/43) survival rate overall. The preterm premature rupture of the membranes rate was 13.2%, and the preterm birth before 37 and 32 weeks was 42.1% and 13.1%, respectively. An uptrend in the survival rate (78.9 vs. 95.8%, p = 0.086) and a downtrend of procedure time (30 vs. 16.5 min, p = 0.036) were observed over time (period 1 from December 2015 to December 2019 verses period 2 from January 2020 to December 2022). Long-term outcome was assessed in 94.6% (35/37) of survivors, and 91.4% (32/35) had normal neurodevelopmental outcome. CONCLUSION: Fetoscopy-guided bipolar cord coagulation for fetal reduction in complicated monochorionic twin pregnancies could achieve a favorable short- and long-term outcome, especially in experienced hands.

9.
J Environ Manage ; 356: 120612, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537465

RESUMO

In this study, we synthesized a high removal efficiency catalyst using biochar-supported nanoscale zero-valent iron and g-C3N4, denoted as g-C3N4/nZVI@SBC, to activate persulfate (PS) for the degradation of total petroleum hydrocarbon (TPH) in groundwater. We characterized the morphology and physiochemical properties of g-C3N4/nZVI@SBC with scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). To assess the performance of the g-C3N4/nZVI@SBC catalyst, we investigated various reaction parameters, such as the mass ratio of g-C3N4 to nZVI@SBC, PS concentration, initial pH, initial TPH concentration, and the presence of coexisting ions in the system. The results from batch experiments and repeated use trials indicate that g-C3N4/nZVI@SBC exhibited both excellent catalytic activation capability and impressive durability, making it a promising choice for TPH degradation. Specifically, when the PS concentration reached 1 mM, the catalyst dosage was 0.3 g/L, and the g-C3N4 to nZVI@SBC mass ratio was 2, we achieved a remarkable TPH removal efficiency of 93.8%. Through electron paramagnetic resonance (EPR) testing and quenching experiments, we identified sulfate radicals, hydroxyl radicals, and superoxide radicals as the primary active substance involved in the TPH degradation process. Moreover, the g-C3N4/nZVI@SBC composite proved highly effective for in-situ TPH removal from groundwater and displayed an 86% removal rate, making it a valuable candidate for applications in permeable reactive barriers (PRB) aimed at enhancing environmental remediation. In summary, by skillfully utilizing g-C3N4/nZVI@SBC, this study has made notable advancements in synthesis and characterization, presenting a feasible and innovative approach to addressing TPH pollution in groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Poluentes Químicos da Água/química , Ferro/química , Microscopia Eletrônica de Varredura , Hidrocarbonetos , Água Subterrânea/química
10.
Immunology ; 168(1): 184-197, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36057099

RESUMO

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.


Assuntos
COVID-19 , Doenças Reumáticas , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Vacinas contra COVID-19 , Imunização , Imunoglobulina G , SARS-CoV-2 , Células T Auxiliares Foliculares , Vacinação , Estudos de Casos e Controles
11.
New Phytol ; 238(1): 383-392, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36564965

RESUMO

There is an urgent need to understand the coupled relationship between belowground microbes and aboveground plants in response to temperature under climate change. The metabolic theory of ecology (MTE) provides a way to predict the metabolic rate and species diversity, but the spatial scale dependence and connections between plants and microorganisms are still unclear. Here, we used two independent datasets to address this question. One is from comprehensive sampling of paddy fields targeting bacteria and microbial functional genes, and the other is a global metadata of spatial turnover for microorganisms (bacteria, fungi and archaea, n = 139) and plants (n = 206). Results showed that spatial turnover of bacterial communities and microbial functional genes increased with temperature and fitted MTE. Through meta-analysis, the temperature-dependent spatial scale pattern was further extended to the global scale, with the spatial turnover of microorganisms and plants being consistent with MTE. Belowground microorganisms and aboveground plants were closely linked with each other even when controlling for temperature, suggesting that factors other than shared relationships with temperature also contribute to their linkages. These results implied a broad application of MTE in biology and have important implications for predicting the ecological consequences of future climate warming.


Assuntos
Archaea , Bactérias , Temperatura , Bactérias/genética , Plantas/microbiologia , Fungos/genética
12.
Pacing Clin Electrophysiol ; 46(7): 684-692, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37345321

RESUMO

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Humanos , Fibrilação Atrial/terapia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Doença do Sistema de Condução Cardíaco/terapia , Estimulação Cardíaca Artificial/métodos
13.
Environ Res ; 222: 115298, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36642122

RESUMO

Plants can recruit soil microorganisms into the rhizosphere when experiencing various environmental stresses, including biotic (e.g., insect pests) and abiotic (e.g., heavy metal pollution, droughts, floods, and salinity) stresses. However, species coexistence in plant resistance has not received sufficient attention. Current research on microbial coexistence is only at the community scale, and there is a limited understanding of the interaction patterns between species, especially microbe‒microbe interactions. The relevant interaction patterns are limited to a few model strains. The coexisting microbial communities form a stable system involving complex nutritional competition, metabolic exchange, and even interdependent interactions. This pattern of coexistence can ultimately enhance plant stress tolerance. Hence, a systematic understanding of the coexistence pattern of rhizosphere microorganisms under stress is essential for the precise development and utilization of synthetic microbial communities and the achievement of efficient ecological control. Here, we integrated current analytical methods and introduced several new experimental methods to elucidate rhizosphere microbial coexistence patterns. Some advancements (e.g., network analysis, coculture experiments, and synthetic communities) that can be applied to plant stress resistance are also updated. This review aims to summarize the key role and potential application prospects of microbial coexistence in the resistance of plants to environmental stresses. Our suggestions, enhancing plant resistance with coexisting microbes, would allow us to gain further knowledge on plant-microbial and microbial-microbial functions, and facilitate translation to more effective measures.


Assuntos
Microbiota , Rizosfera , Microbiologia do Solo , Plantas , Solo , Raízes de Plantas
14.
Public Health Nutr ; 26(5): 1014-1021, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36093642

RESUMO

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Glicemia , Estudos Retrospectivos , População do Leste Asiático , China/epidemiologia , Ácido Fólico
15.
BMC Pediatr ; 23(1): 429, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641008

RESUMO

BACKGROUND: Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations. CASE PRESENTATION: A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory. CONCLUSIONS: KS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.


Assuntos
Anormalidades Múltiplas , Hipertensão Pulmonar , Humanos , Feminino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Fenótipo , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Testes Genéticos
16.
Mediators Inflamm ; 2023: 2252255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741074

RESUMO

Background: Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient's prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective: NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods: In this study, we used wild-type mice and hsf1 -/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results: The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1 -/- mouse model compared to hsf1 +/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion: These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.


Assuntos
Lesões Encefálicas , Fatores de Transcrição de Choque Térmico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse , Animais , Camundongos , Ratos , Fatores de Transcrição de Choque Térmico/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , RNA Interferente Pequeno , Sepse/metabolismo
17.
Ecotoxicol Environ Saf ; 254: 114728, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36889208

RESUMO

Tris(2-chloroethyl) phosphate (TCEP) has been detected all over the world as a typical refractory organic phosphate, especially in groundwater. This work applied a calcium-rich biochar derived from shrimp shell as a low-cost adsorbent for TCEP removal. Based on the kinetics and isotherm studies, the adsorption of TCEP on biochar was monolayer adsorbed on a uniform surface, with SS1000 (the biochar was prepared at the carbonization temperature of 1000 °C) achieving the maximum adsorption capacity of 264.11 mg·g-1. The prepared biochar demonstrated stable TCEP removal ability throughout a wide pH range, in the presence of co-existing anions, and in diverse water bodies. A rapid removal rate of TCEP was observed during the adsorption process. When the dosage of SS1000 was 0.2 g·L-1, 95% of TCEP could be removed within the first 30 min. The mechanism analysis indicated that the calcium species and basic functional groups on the SS1000 surface were highly involved in the TCEP adsorption process.


Assuntos
Cálcio , Poluentes Químicos da Água , Adsorção , Poluentes Químicos da Água/análise , Organofosfatos , Carvão Vegetal , Fosfatos , Cinética
18.
J Craniofac Surg ; 34(6): 1789-1794, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37010314

RESUMO

BACKGROUND: The purpose of this study was to investigate the clinical effect and bone resorption of iliac crest cortical-cancellous bone block grafts combined with concentrated growth factor (CGF) compared with iliac crest cortical-cancellous bone block grafts only in secondary alveolar bone grafting. MATERIALS AND METHODS: Eighty-six patients (43 in the CGF group and 43 in the non-CGF group) with unilateral alveolar clefts were examined. Patients (17 in the CGF group and 17 in the non-CGF group) were randomly chosen for radiologic evaluation. Quantitative evaluation of the bone resorption rate was made with cone-beam computed tomography and Mimics 19.0 software at 1 week and 12 months after surgery. RESULTS: The success rate of bone grafting was 95.3% and 79.1% in the CGF and non-CGF groups, respectively ( P =0.025). The mean bone resorption rate at 12 months postoperatively was 35.66±15.80% and 41.39±19.57% in the CGF and non-CGF groups, respectively ( P =0.355). The bone resorption patterns of the 2 groups were similar on the labial, alveolar process, and palatal sides, and there was no obvious bone resorption on the labial side in either group. Nasal side bone resorption in the CGF group was significantly less than that in the non-CGF group ( P =0.047). CONCLUSIONS: Cortical-cancellous bone block grafts reduce labial bone resorption, while CGF reduces nasal bone resorption and improves the success rate. The combination of bone block and CGF in secondary alveolar bone grafting is worthy of further clinical application.


Assuntos
Enxerto de Osso Alveolar , Reabsorção Óssea , Fissura Palatina , Humanos , Estudos Retrospectivos , Ílio/cirurgia , Osso Esponjoso , Transplante Ósseo/métodos , Fissura Palatina/cirurgia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
19.
J Biol Chem ; 297(3): 101022, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34332978

RESUMO

Transient receptor potential vanilloid 1 (TRPV1) ion channel serves as the detector for noxious temperature above 42 °C, pungent chemicals like capsaicin, and acidic extracellular pH. This channel has also been shown to function as an ionotropic cannabinoid receptor. Despite the solving of high-resolution three-dimensional structures of TRPV1, how endocannabinoids such as anandamide and N-arachidonoyl dopamine bind to and activate this channel remains largely unknown. Here we employed a combination of patch-clamp recording, site-directed mutagenesis, and molecular docking techniques to investigate how the endocannabinoids structurally bind to and open the TRPV1 ion channel. We found that these endocannabinoid ligands bind to the vanilloid-binding pocket of TRPV1 in the "tail-up, head-down" configuration, similar to capsaicin; however, there is a unique interaction with TRPV1 Y512 residue critical for endocannabinoid activation of TRPV1 channels. These data suggest that a differential structural mechanism is involved in TRPV1 activation by endocannabinoids compared with the classic agonist capsaicin.


Assuntos
Capsaicina/farmacologia , Endocanabinoides/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Células HEK293 , Humanos , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Técnicas de Patch-Clamp , Ligação Proteica , Canais de Cátion TRPV/agonistas
20.
Opt Express ; 30(11): 19360-19389, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36221716

RESUMO

Photonic spiking neural networks (PSNNs) potentially offer exceptionally high throughput and energy efficiency compared to their electronic neuromorphic counterparts while maintaining their benefits in terms of event-driven computing capability. While state-of-the-art PSNN designs require a continuous laser pump, this paper presents a monolithic optoelectronic PSNN hardware design consisting of an MZI mesh incoherent network and event-driven laser spiking neurons. We designed, prototyped, and experimentally demonstrated this event-driven neuron inspired by the Izhikevich model incorporating both excitatory and inhibitory optical spiking inputs and producing optical spiking outputs accordingly. The optoelectronic neurons consist of two photodetectors for excitatory and inhibitory optical spiking inputs, electrical transistors' circuits providing spiking nonlinearity, and a laser for optical spiking outputs. Additional inclusion of capacitors and resistors complete the Izhikevich-inspired optoelectronic neurons, which receive excitatory and inhibitory optical spikes as inputs from other optoelectronic neurons. We developed a detailed optoelectronic neuron model in Verilog-A and simulated the circuit-level operation of various cases with excitatory input and inhibitory input signals. The experimental results closely resemble the simulated results and demonstrate how the excitatory inputs trigger the optical spiking outputs while the inhibitory inputs suppress the outputs. The nanoscale neuron designed in our monolithic PSNN utilizes quantum impedance conversion. It shows that estimated 21.09 fJ/spike input can trigger the output from on-chip nanolasers running at a maximum of 10 Gspike/second in the neural network. Utilizing the simulated neuron model, we conducted simulations on MNIST handwritten digits recognition using fully connected (FC) and convolutional neural networks (CNN). The simulation results show 90% accuracy on unsupervised learning and 97% accuracy on a supervised modified FC neural network. The benchmark shows our PSNN can achieve 50 TOP/J energy efficiency, which corresponds to 100 × throughputs and 1000 × energy-efficiency improvements compared to state-of-art electrical neuromorphic hardware such as Loihi and NeuroGrid.


Assuntos
Redes Neurais de Computação , Neurônios , Simulação por Computador , Fótons
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