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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 580-587, 2024 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-38948300

RESUMO

Objective: The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization (IVF) processes using gonadotrophin-releasing hormone (GnRH) antagonist protocol, GnRH agonist long protocol, and early follicular phase protocol. We aim to provide reliable reference for future clinical treatments. Methods: We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023. 1) In the overall patient population, we comprehensively compared the basic characteristics, the embryo development, and the clinical outcomes of patients treated with three different ovarian stimulation protocols, including the GnRH antagonist protocol group (n=4173), the agonist long protocol group (n=2410), and the early follicular phase long protocol group (n=341). 2) We divided the overall population into three age groups, one group for patients under 30 years old (n=2576), one for patients aged 30-35 (n=3249), and one for patients older than 35 years old (n=1099). Then, we compared the three stimulation protocols based on the group division. We separately compared the embryo development and clinical outcomes of patients using the three stimulation protocols in the under 30 years old, the 30-35 years old, and the over 35 years old age groups. With this analysis, we aimed to explore the response of different age groups to different stimulation protocols and their impact on the success rate of IVF. Results: 1) In the overall population, we found that the average number of oocytes retrieved in the GnRH agonist long protocol group was significantly higher than that in the GnRH antagonist protocol group ([13.85±7.162] vs. [13.36±7.862], P=0.0224), as well as the early follicular phase long protocol group ([13.85±7.162] vs. [11.86±6.802], P<0.0001). Patients in the GnRH antagonist protocol group not only had a significantly lower starting dose of gonadotrophin (Gn) compared to the other two groups (P<0.05) but also had a significantly lower number of days of Gn use (P<0.05). The blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.91% vs. 62.35%, P<0.0001) and the early follicular phase long protocol group (64.91% vs. 61.18%, P=0.0001). However, there were no significant differences in the clinical pregnancy rates or the live birth rates among the three groups treated with different ovarian stimulation protocols (P>0.05). 2) In the <30 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (66.12% vs. 63.33%, P<0.0001) and the early follicular phase long protocol group (66.12% vs. 62.13%, P=0.0094). In the 30-35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.88% vs. 62.93%, P=0.000 9) and the early follicular phase long protocol group (64.88% vs. 60.39%, P=0.0011). In the >35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was significantly higher than that in the GnRH agonist long protocol group (59.83% vs. 56.51%, P=0.0093), while there was no significant difference compared to that of the early follicular phase long protocol group (P>0.05). In the three age groups, we found that there were no significant differences in clinical pregnancy rate, live birth rate, and neonatal outcome indicators (fetal weight and Apgar score) among the three stimulation protocols (antagonist protocol, GnRH agonist long protocol, and early follicular phase long protocol) (P>0.05). The findings showed no significant differences between clinical and neonatal outcomes in patients of all ages, regardless of the ovarian stimulation protocol, suggesting that the three ovarian stimulation protocols have similar therapeutic effects in patients of different ages. The results of this study have important implications for the selection of an appropriate ovarian stimulation protocol and the prediction of treatment outcomes. Conclusion: In the younger than 30 and 30-35 age groups, the GnRH antagonist protocol showed a more significant advantage over the GnRH agonist long protocol and the early follicular phase long protocol. This suggests that for younger and middle-aged patients, the antagonist protocol may lead to better outcomes during ovarian stimulation. In the older than 35 age group, while the antagonist protocol still outperformed the GnRH agonist long protocol, there was no significant difference compared to the early follicular phase long protocol. This may imply that with increasing age, the early follicular phase long protocol may have effects similar to the antagonist protocol to some extent. The advantages of the antagonist protocol lie in its ability to reduce stimulation duration and the dosage of GnRH, while enhancing patient compliance with treatment. This means that patients may find it easier to accept and adhere to this treatment protocol, thereby improving treatment success rates. Particularly for older patients, the use of the antagonist protocol may significantly increase the blastocyst formation rate, which is crucial for improving the success rates. Although there were no significant differences in the clinical outcomes of patients treated with the three protocols in each age group, further research is still needed to validate these findings. Future multicenter studies and increased sample sizes may help comprehensively assess the efficacy of different stimulation protocols. Additionally, prospective studies are needed to further validate these findings and determine the optimal treatment strategies.


Assuntos
Desenvolvimento Embrionário , Fertilização in vitro , Hormônio Liberador de Gonadotropina , Indução da Ovulação , Taxa de Gravidez , Humanos , Indução da Ovulação/métodos , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/agonistas , Adulto , Fertilização in vitro/métodos , Gravidez , Desenvolvimento Embrionário/efeitos dos fármacos , Fatores Etários , Fase Folicular/fisiologia
2.
Environ Res ; 257: 119329, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38851372

RESUMO

Conventional methods, such as freshwater dilution and ammonia stripping, have been widely employed for microalgae-based piggery wastewater (PW) treatment, but they cause high freshwater consumption and intensive ammonia loss, respectively. This present work developed a novel fast microbial nitrogen-assimilation technology by integrating nitrogen starvation, zeolite-based adsorption, pH control, and co-culture of microalgae-yeast for the PW treatment. Among them, the nitrogen starvation accelerated the nitrogen removal and shortened the treatment period, but it could not improve the tolerance level of microalgal cells to ammonia toxicity based on oxidative stress. Therefore, zeolite was added to reduce the initial total ammonia-nitrogen concentration to around 300 mg/L by ammonia adsorption. Slowly releasing ammonia at the later phase maintained the total ammonia-nitrogen concentration in the PW. However, the pH increase could cause lots of ammonia loss air and pollution and inhibit the desorption of ammonia from zeolite and the growth and metabolism of microalgae during the microalgae cultivation. Thus, the highest biomass yield (3.25 g/L) and nitrogen recovery ratio (40.31%) were achieved when the pH of PW was controlled at 6.0. After combining the co-cultivation of microalgae-yeast, the carbon-nitrogen co-assimilation and the alleviation of pH fluctuation further enhanced the nutrient removal and nitrogen migration to high-protein biomass. Consequently, the fast microbial nitrogen-assimilation technology can help update the industrial system for high-ammonia wastewater treatment by improving the treatment and nitrogen recovery rates.


Assuntos
Amônia , Microalgas , Nitrogênio , Águas Residuárias , Nitrogênio/metabolismo , Águas Residuárias/química , Águas Residuárias/microbiologia , Amônia/metabolismo , Microalgas/metabolismo , Microalgas/crescimento & desenvolvimento , Animais , Zeolitas/química , Eliminação de Resíduos Líquidos/métodos , Suínos , Poluentes Químicos da Água , Criação de Animais Domésticos/métodos , Proteínas Alimentares
3.
J Am Chem Soc ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847839

RESUMO

Enhancing the catalytic oxidation activity of traditional transition-metal oxides to rival that of noble metals has been a prominent focus in the field of catalysis. However, existing synthesis strategies that focus on controlling the electronic states of metal centers have not yet fully succeeded in achieving this goal. Our current research reveals that manipulating the electronic states of oxygen centers can yield unexpected results. By creating electron-rich, aperiodic lattice oxygens through atomic topping of MnOx, we have produced a catalyst with performance that closely resembles supported Pt. Spherical aberration-corrected transmission electron microscopy and X-ray absorption spectra have confirmed that the atomic topping of the MnOx layer on Al2O3 can form an aperiodic arrangement oxide structure. Near-ambient pressure X-ray photoelectron spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy, reaction kinetics test, and theoretical calculations demonstrated that this structure significantly increases the electron density around the oxygen in MnOx, shifting the activation center for CO adsorption from Mn to O, thereby exhibiting catalytic activity and stability close to that of the precious metal Pt. This study presents a fresh perspective on designing efficient oxide catalysts by targeting electron-rich anionic centers, thereby deepening the understanding of how these centers can be altered to enhance catalytic efficiency in oxidation reactions.

4.
Chempluschem ; : e202400236, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895820

RESUMO

As both a critical chemical feedstock and an environmental pollutant, the production and utilization of ammonia (NH3) are accompanied by the progress of social civilization. In recent years, research on metal/covalent organic framework materials as NH3 adsorbents has attracted increasing attention due to their high porosity, versatile architecture and tunable functionality. This review was organized to highlight the recent advancement of MOF/COF materials for NH3 sorption, which successively presented the key properties of solid adsorbents and summarized the strategies along with their mechanisms for enhancing NH3 adsorption. In addition, perspectives and outlook regarding the future development of MOF/COF-based NH3 adsorbents were outlined to meet the requirements of practical applications in different environment.

5.
ACS Appl Mater Interfaces ; 16(24): 31464-31472, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38840337

RESUMO

One-step He purification from natural gas represents a crucial solution for addressing the global He shortages. The prevailing method to produce high-grade He involves cryogenic distillation and ultralow temperature adsorption processes, which is highly cost- and energy-intensive. Separating and purifying He at ambient temperature is a great challenge because the fundamental limitation lies in the boiling point, polarizability, and kinetic diameters of CH4/N2/He gases. In this study, we seek to implement a relay adsorption strategy using Ni(ina)2 and MIL-100(Cr) metal-organic frameworks (MOFs) to produce high-purity He from ternary mixtures (CH4, N2, and He) at ambient temperature. The CH4/He selectivity in Ni(ina)2 and N2/He selectivity in MIL-100(Cr) both reach record 15.39 and 128.49, respectively, making the relay adsorption for helium purification highly efficient. The breakthrough experiments show that the two MOFs can sequentially adsorb CH4 and N2 in ternary mixtures, producing He with a purity of up to 99.99% in one step. The remarkable separation performance and stability of these MOFs underscore the industrial potential in purifying He at ambient temperature.

6.
Sci Total Environ ; 937: 173556, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38806126

RESUMO

The patterns of organic carbon sequestration in lakes, along with their temporal dynamics, have profound implications for assessing the strength of terrestrial carbon sinks and the global carbon budget. The complexity of fluctuations in organic carbon burial in freshwater lake basins, along with the intricate interactions among various controlling factors over time, remains challenging to comprehend. By utilizing data on the organic carbon burial of sedimentary cores from twelve plateau lakes in a gradient of urbanization, this study employed a rigorous methodology to quantify the factors and origins that contribute to lacustrine carbon sequestration. The findings indicate that the rate of Total Organic Carbon (TOC) accumulation in lakes in highly urbanized areas has significantly surpassed that in areas with minimal urbanization since 1985. This trend of divergence has persisted for more than four decades. During the period from 1958 to 2008, soil nutrient characteristics (29.576 %) and human impact (16.684 %) were the major factors regulating the organic carbon burial in plateau lakes. Human pressures indirectly impact carbon sequestration through earth-surface processes in the lake basin, causing carbon burial to lag behind environmental indicators (e.g., δ13C and C/N) by approximately 5 years. Meanwhile, the carbon sequestration efficiency of plateau lakes shows a positive feedback to climatic warming with intensified urbanization, primarily regulated through the impacts on lake basin environments. The results will further enhance our understanding of the response of the lake ecosystem carbon cycle to anthropogenic influences.

7.
Chemosphere ; 362: 142458, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38810811

RESUMO

Membrane fouling is the major factor that restricts the furtherly widespread use of membrane bioreactor (MBR). As a new generation of MBR, biofilm membrane bioreactor (BF-MBR) demonstrates high treatment efficiency and low sludge growth rate, however the filtration performance improvement and membrane fouling control are still the challenges for its further development. This work investigated the filtration performance using resistance in series model and membrane fouling control via threshold flux for BF-MBR. At first, the flux behavior and filtration resistance under various operating conditions, including agitation speed, membrane and TMP, were explored by resistance in series model. Because of the desirable anti-fouling capacity, UP100 and UP030 had the high threshold flux (100 and 90 L m-2 h-1) and low irreversible fouling resistance (1 and 1.3 × 10-10 m-1). Higher shear stress produced by higher agitation speed could reduce membrane fouling, while greatly promote the threshold flux (138 L m-2 h-1) and membrane cleaning efficiency (96%). Moreover, increasing shear stress or selecting membrane with large pore size could decrease the fouling rate and raise the threshold flux. As for TMP, high TMP reduced the removal rate for organic and nutrient, and enhanced the irreversible fouling. Besides, the aerobic-BF-MBR (101 L m-2 h-1 and 1.3 × 10-10 m-1) with lower foulant concentration had a better filtration performance than anoxic-BF-MBR (90 L m-2 h-1 and 1.5 × 10-10 m-1). Additionally, the long-term tests with 10 cycles were conducted to evaluate the industrial application value of BF-MBR (45-58 L m-2 h-1). This work provides the technical support for sustainable filtration performance of BF-MBR.

8.
Transl Psychiatry ; 14(1): 213, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802377

RESUMO

Large cohort studies examining trends in cancer-related suicide are lacking. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 4,870,410 patients diagnosed with cancer from 1975 to 2017 in the United States. Joinpoint regression was used to estimate the annual percent change (APC) and average annual percentage change (AAPC) of age-adjusted rates of suicide. In the past 40 years, we revealed a gradual increase in cancer-related suicide rates from 1975 to 1989, followed by a gradual decrease from 1989 to 2013, and a marked decrease from 2013 to 2017. These trends suggested the potential impact of advancements in psychosocial care for patients with cancer in contributing to the observed decrease in suicide rates.


Assuntos
Neoplasias , Programa de SEER , Suicídio , Humanos , Estados Unidos/epidemiologia , Neoplasias/epidemiologia , Suicídio/estatística & dados numéricos , Suicídio/tendências , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais
9.
Environ Sci Ecotechnol ; 21: 100424, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38774191

RESUMO

Fruits, vegetables, and dairy products are typically the primary sources of household food waste. Currently, anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of biogas. However, to achieve a circular carbon economy, the organics in food waste should be converted to new chemicals with higher value than energy. Here we demonstrate the feasibility of medium-chain carboxylic acid (MCCA) production from expired dairy and beverage waste via a chain elongation platform mediated by lactate. In a two-stage fermentation process, the first stage with optimized operational conditions, including varying temperatures and organic loading rates, transformed expired dairy and beverage waste into lactate at a concentration higher than 900 mM C at 43 °C. This lactate was then used to produce >500 mM C caproate and >300 mM C butyrate via microbial chain elongation. Predominantly, lactate-producing microbes such as Lactobacillus and Lacticaseibacillus were regulated by temperature and could be highly enriched under mesophilic conditions in the first-stage reactor. In the second-stage chain elongation reactor, the dominating microbes were primarily from the genera Megasphaera and Caproiciproducens, shaped by varying feed and inoculum sources. Co-occurrence network analysis revealed positive correlations among species from the genera Caproiciproducens, Ruminococcus, and CAG-352, as well as Megasphaera, Bacteroides, and Solobacterium, indicating strong microbial interactions that enhance caproate production. These findings suggest that producing MCCAs from expired dairy and beverage waste via lactate-mediated chain elongation is a viable method for sustainable waste management and could serve as a chemical production platform in the context of building a circular bioeconomy.

12.
Chem Sci ; 15(7): 2545-2557, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38362424

RESUMO

Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.

13.
J Environ Manage ; 353: 120191, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38325286

RESUMO

The daily discharge of rural sewage in China occupies 30 % of the national wastewater discharge, and developing an energy-efficient, easy to operate, and decentralized rural sewage treatment technology becomes an important task. In this work, a novel rural sewage treatment technology, Electrocoagulation enhanced Gravity-Driven Membrane Bioreactor (EC-GDMBR) was exploited for the rural sewage treatment under long-term operation (160 days). Two EC-GDMBRs with various module structures of ceramic membrane (horizontal module and side module) not only displayed the desirable effluent quality, but also sustained the stable flux (8-13 LMH). The electrocoagulation, electrooxidation, biodegradation, and separation in EC-GDMBRs were able to synergistically remove the particle matter, organic (CODCr effluent <11.6 ± 1.2 mg/L) and nutrients (NH3-N effluent <0.1 mg/L, TN effluent <8.5 mg/L, TP effluent <0.05 mg/L). Besides, the high permeability of ceramic membrane and large porosity of biofilm on its surface improved the sustainability of stable flux during the long-term operation. Moreover, by analyzing bacterial abundance, Extracellular Polymeric Substances, Adenosine Tri-Phosphate and Confocal Laser Scanning Microscopy, a large number of microorganisms grew and accumulated on the carrier, as well as formed the biofilm (23.46-659.9 µm), while Nitrobacteria (1.6-4.1 %) and Nitrate (0.01-0.06 %) exited in the carrier biofilms, promoting the nitrogen removal. Compared with EC-GDMBR with side module of ceramic membrane, EC-GDMBR with horizontal module of ceramic membrane has advantages in flux behavior, organic/nutrient removal, microbial abundance/activity, abundance of nitrogen removal functional bacteria and water permeability of biofilm, because the ceramic membrane of horizontal module can promote the uniform growth of biofilm and improve the uniformity of flow penetration distribution. In general, the findings of this work verify the reliability of EC-GDMBR for the sustainable operation of wastewater treatment and improve its application value of rural sewage treatment.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Esgotos/química , Reprodutibilidade dos Testes , Membranas Artificiais , Reatores Biológicos , Nitrogênio/metabolismo , Bactérias/metabolismo
14.
Cell Death Dis ; 15(1): 78, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245510

RESUMO

The circadian-controlled DNA repair exhibits a strong diurnal rhythm. Disruption in circadian clock and DNA repair is closely linked with hepatocellular carcinoma (HCC) progression, but the mechanism remains unknown. Here, we show that polymerase beta (POLB), a critical enzyme in the DNA base excision repair pathway, is rhythmically expressed at the translational level in mouse livers. Hepatic POLB dysfunction dampens clock homeostasis, whereas retards HCC progression, by mediating the methylation of the 4th CpG island on the 5'UTR of clock gene Per1. Clinically, POLB is overexpressed in human HCC samples and positively associated with poor prognosis. Furthermore, the hepatic rhythmicity of POLB protein expression is orchestrated by Calreticulin (CALR). Our findings provide important insights into the molecular mechanism underlying the synergy between clock and food signals on the POLB-driven BER system and reveal new clock-dependent carcinogenetic effects of POLB. Therefore, chronobiological modulation of POLB may help to promote precise interventions for HCC.


Assuntos
Carcinoma Hepatocelular , Relógios Circadianos , DNA Polimerase beta , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Relógios Circadianos/genética , Ritmo Circadiano/genética , Desmetilação , DNA Polimerase beta/genética , DNA Polimerase beta/metabolismo , Epigênese Genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Circadianas Period/genética
15.
Plant Cell ; 36(5): 1892-1912, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262703

RESUMO

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.


Assuntos
Endosperma , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Amido , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Endosperma/metabolismo , Endosperma/genética , Amido/metabolismo , Amido/biossíntese , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Amilopectina/metabolismo , Mutação , Plantas Geneticamente Modificadas
17.
Nature ; 624(7991): 433-441, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38030726

RESUMO

FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity1-5. However, the molecular mechanisms of FOXP3 remain unclear. Here we here show that FOXP3 uses the forkhead domain-a DNA-binding domain that is commonly thought to function as a monomer or dimer-to form a higher-order multimer after binding to TnG repeat microsatellites. The cryo-electron microscopy structure of FOXP3 in a complex with T3G repeats reveals a ladder-like architecture, whereby two double-stranded DNA molecules form the two 'side rails' bridged by five pairs of FOXP3 molecules, with each pair forming a 'rung'. Each FOXP3 subunit occupies TGTTTGT within the repeats in a manner that is indistinguishable from that of FOXP3 bound to the forkhead consensus motif (TGTTTAC). Mutations in the intra-rung interface impair TnG repeat recognition, DNA bridging and the cellular functions of FOXP3, all without affecting binding to the forkhead consensus motif. FOXP3 can tolerate variable inter-rung spacings, explaining its broad specificity for TnG-repeat-like sequences in vivo and in vitro. Both FOXP3 orthologues and paralogues show similar TnG repeat recognition and DNA bridging. These findings therefore reveal a mode of DNA recognition that involves transcription factor homomultimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.


Assuntos
DNA , Fatores de Transcrição Forkhead , Repetições de Microssatélites , Sequência de Bases , Sequência Consenso , Microscopia Crioeletrônica , DNA/química , DNA/genética , DNA/metabolismo , DNA/ultraestrutura , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/ultraestrutura , Repetições de Microssatélites/genética , Mutação , Motivos de Nucleotídeos , Domínios Proteicos , Multimerização Proteica , Linfócitos T Reguladores/metabolismo
18.
bioRxiv ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37986949

RESUMO

FoxP3 is a transcription factor (TF) essential for development of regulatory T cells (Tregs), a branch of T cells that suppress excessive inflammation and autoimmunity 1-5 . Molecular mechanisms of FoxP3, however, remain elusive. We here show that FoxP3 utilizes the Forkhead domain--a DNA binding domain (DBD) that is commonly thought to function as a monomer or dimer--to form a higher-order multimer upon binding to T n G repeat microsatellites. A cryo-electron microscopy structure of FoxP3 in complex with T 3 G repeats reveals a ladder-like architecture, where two double-stranded DNA molecules form the two "side rails" bridged by five pairs of FoxP3 molecules, with each pair forming a "rung". Each FoxP3 subunit occupies TGTTTGT within the repeats in the manner indistinguishable from that of FoxP3 bound to the Forkhead consensus motif (FKHM; TGTTTAC). Mutations in the "intra-rung" interface impair T n G repeat recognition, DNA bridging and cellular functions of FoxP3, all without affecting FKHM binding. FoxP3 can tolerate variable "inter-rung" spacings, explaining its broad specificity for T n G repeat-like sequences in vivo and in vitro . Both FoxP3 orthologs and paralogs show similar T n G repeat recognition and DNA bridging. These findings thus reveal a new mode of DNA recognition that involves TF homo-multimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.

19.
Angew Chem Int Ed Engl ; 62(42): e202310235, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37658513

RESUMO

Xe is an ideal anesthetic gas, but it has not been widely used in practice due to its high cost and low output. Closed-circuit Xe recovery and recycling is an economically viable method to ensure adequate supply in medical use. Herein, we design an innovative way to recover Xe by using a stable fluorinated metal-organic framework (MOF) NbOFFIVE-1-Ni to eliminate CO2 from moist exhaled anesthetic gases. Unlike other Xe recovery MOFs with low Xe/CO2 selectivity (less than 10), NbOFFIVE-1-Ni could achieve absolute molecular sieve separation of CO2 /Xe with excellent CO2 selectivity (825). Mixed-gas breakthrough experiments assert the potential of NbOFFIVE-1-Ni as a molecular sieve adsorbent for the effective and energy-efficient removal of carbon dioxide with 99.16 % Xe recovery. Absolute CO2 /Xe separation in NbOFFIVE-1-Ni makes closed-circuit Xe recovery and recycling can be easily realized, demonstrating the potential of NbOFFIVE-1-Ni for important anesthetic gas regeneration under ambient conditions.

20.
Chemistry ; 29(66): e202302462, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37642408

RESUMO

Efficient and inherently safe NH3 storage and separation are of significant importance for the chemical industry. Herein, we proposed zwitterionic COF as a porous host to disperse LiCl for highly efficient NH3 storage and separation with record adsorption capacity. The equivalently cationic and anionic groups in the channels of zwitterionic COF could act as two separated sites to facilitate the dispersion of LiCl, hence the optimal composite exhibits a high capture capacity of 44.98 mmol/g at 25 °C and 1 bar, far exceeding other existing porous materials. Notably, the adsorption capacity is completely reversible and the efficient separation of NH3 from NH3 /CO2 /N2 mixture is achieved through breakthrough experiments. DFT calculation combined with XPS and 7 Li NMR experimental results give insight into the interaction between zwitterionic COF and LiCl. This work extends possibilities for the development of efficient adsorbents for NH3 storage and separation.

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