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1.
Macromol Rapid Commun ; : e2400064, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594967

RESUMO

Polyethylene (PE), a highly prevalent non-biodegradable polymer in the field of plastics, presents a waste management issue. To alleviate this issue, bio-based PE (bio-PE), derived from renewable resources like corn and sugarcane, offers an environmentally friendly alternative. This review discusses various production methods of bio-PE, including fermentation, gasification, and catalytic conversion of biomass. Interestingly, the bio-PE production volumes and market are expanding due to the growing environmental concerns and regulatory pressures. Additionally, the production of PE and bio-PE biocomposites using agricultural waste as filler materials, highlights the growing demand for sustainable alternatives to conventional plastics. According to previous studies, addition of ≈50% defibrillated corn and abaca fibers into bio-PE matrix and a compatibilizer, results in the highest Young's modulus of 4.61 and 5.81 GPa, respectively. These biocomposites have potential applications in automotive, building construction, and furniture industries. Moreover, the advancement made in abiotic and biotic degradation of PE and PE biocomposites is elucidated to address their environmental impacts. Finally, the paper concludes with insights into the opportunities, challenges, and future perspectives in the sustainable production and utilization of PE and bio-PE biocomposites. In summary, production of PE and bio-PE biocomposites can contribute to a cleaner and sustainable future.

2.
Adv Sci (Weinh) ; : e2308522, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582526

RESUMO

Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host-pathogen binding, and immune recognition, through interactions with glycan-binding proteins. A key driving force for glycan-protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH-π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging. Here, computational modeling and molecular dynamics simulations are employed to design a chemical strategy that enhances the CH-π interaction between glycans and proteins by genetically incorporating electron-rich tryptophan derivatives into a lectin PhoSL, which specifically recognizes core fucosylated N-linked glycans. This significantly enhances the binding affinity of PhoSL with the core fucose ligand and enables sensitive detection and imaging of core fucosylated glycans in vitro and in xenograft tumors in mice. Further, the study showed that this strategy is applicable to improve the binding affinity of GafD lectin for N-acetylglucosamine-containing glycans. The approach thus provides a general and effective way to manipulate glycan-protein recognition for glycoscience applications.

3.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38605639

RESUMO

The accurate identification of disease-associated genes is crucial for understanding the molecular mechanisms underlying various diseases. Most current methods focus on constructing biological networks and utilizing machine learning, particularly deep learning, to identify disease genes. However, these methods overlook complex relations among entities in biological knowledge graphs. Such information has been successfully applied in other areas of life science research, demonstrating their effectiveness. Knowledge graph embedding methods can learn the semantic information of different relations within the knowledge graphs. Nonetheless, the performance of existing representation learning techniques, when applied to domain-specific biological data, remains suboptimal. To solve these problems, we construct a biological knowledge graph centered on diseases and genes, and develop an end-to-end knowledge graph completion framework for disease gene prediction using interactional tensor decomposition named KDGene. KDGene incorporates an interaction module that bridges entity and relation embeddings within tensor decomposition, aiming to improve the representation of semantically similar concepts in specific domains and enhance the ability to accurately predict disease genes. Experimental results show that KDGene significantly outperforms state-of-the-art algorithms, whether existing disease gene prediction methods or knowledge graph embedding methods for general domains. Moreover, the comprehensive biological analysis of the predicted results further validates KDGene's capability to accurately identify new candidate genes. This work proposes a scalable knowledge graph completion framework to identify disease candidate genes, from which the results are promising to provide valuable references for further wet experiments. Data and source codes are available at https://github.com/2020MEAI/KDGene.


Assuntos
Disciplinas das Ciências Biológicas , Reconhecimento Automatizado de Padrão , Algoritmos , Aprendizado de Máquina , Semântica
4.
J Endod ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642732

RESUMO

INTRODUCTION: This retrospective cohort study aimed to evaluate long-term healing outcomes (10-17.5 years) following contemporary endodontic microsurgery (EMS) and identify associated prognostic factors. METHODS: Clinical and radiographic data of an EMS cohort (2006-2013) from the electronic data base of Dental Hospital were reviewed retrospectively by two independent examiners to determine their survival and healing outcomes, and potential prognostic factors analyzed by Cox proportional hazards regression and logistic regression (α = 0.05). RESULTS: Through strict inclusion and exclusion criteria, and 721 EMS-treated teeth in the cohort, 309 (42.9%) were included (male, 35.0%; female, 65.0%; age, 45.83 ± 15.53 years) with mean final follow-up of 152.26 ± 26.37 months (range, 120-211; median, 148). Clinical and radiographic assessments found 80.5% of 10 years survival rate with 63.4% of success. Collectively, tooth type, tooth mobility, preoperative lesion size, clinical crown-root ratio, and crown restorations at follow-up were significantly associated with long-term success and survival over 10 years. CONCLUSIONS: The preoperative status and condition of the tooth including its alveolar bone support, and adequate full crown restorations may be relevant prognostic determinants of success and survival following EMS over time.

5.
Chem Asian J ; : e202400180, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650439

RESUMO

This review explores the potential of using different types of ash, namely fly ash, biomass ash, and coal ash etc., as mediums for CO2 capture and sequestration. The diverse origins of these ash types-municipal waste, organic biomass, and coal combustion-impart unique physicochemical properties that influence their suitability and efficiency in CO2 absorption. This review first discusses the environmental and economic implications of using ash wastes, emphasizing the reduction in landfill usage and the transformation of waste into value-added products. Then the chemical/physical treatments of ash wastes and their inherent capabilities in binding or reacting with CO2 are introduced, along with current methodologies utilize these ashes for CO2 sequestration, including mineral carbonation and direct air capture techniques. The application of using ash wastes for CO2 capture are highlighted, followed by the discussion regarding challenges associated with ash-based CO2 absorption approach. Finally, the article projects into the future, proposing innovative approaches and technological advancements needed to enhance the efficacy of ash in combating the increasing CO2 levels. By providing a comprehensive analysis of current strategies and envisioning future prospects, this review aims to contribute to the field of sustainable CO2 absorption and environmental management.

6.
ACS Omega ; 9(10): 11718-11729, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38496967

RESUMO

How shale reservoirs and gas contents are affected by the pore structure of shale is very important. Low-temperature nitrogen isothermal adsorption experiments were conducted by us to investigate the pore structure of the Dalong Formation shale. We measured the specific surface area and fractal dimension of the pores and also considered the mineral fraction and organic matter content of the rock. The results show that the Dalong Formation shale contains a lot of organic carbon, with a total organic carbon (TOC) value between 1.20 and 10.82% (mean: 5.02%). Quartz and clay minerals are the main components of the shale, with quartz making up 40.30 to 85.60% (mean: 67.21%) and clay minerals making up 9.20 to 34.10% (mean: 20.26%) of the shale. Most of the pore space in the shale of the Dalong Formation is formed by intragranular and intergranular pores, organic matter pores, and some microfissures. The pore structure is complex, with parallel-plate and ink-bottle pores being the most common types. Most of the pores are 0-2 or 2-5 nm in size. D1 and D2 are the fractal dimensions, with averages of 2.66 and 2.81, respectively. D1 can range from 2.55 to 2.78, while D2 can range from 2.66 to 2.94. The TOC content, mineral composition, and pore structure characteristics determine the fractal dimension. Higher levels of the TOC content, quartz mineral content, and specific pore surface area result in a higher fractal dimension, while higher levels of feldspar content result in a lower one. There is no apparent correlation to clay minerals or other mineral compositions.

7.
Mater Horiz ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506347

RESUMO

The synthesis of PVA hydrogels (PVA-Hy) requires a highly basic environment (e.g., an aqueous solution of sodium hydroxide, NaOH, 14% w/w, 4.2 M), but the rapid crosslinking of PVA due to high pH makes it challenging to perform layer-by-layer three-dimensional (3D) printing of PVA-Hy. This work demonstrated 3D printing of PVA-Hy in moderate alkaline conditions (e.g., NaOH, 1% w/w, 0.3 M) assisted by aqueous two-phase system (ATPS). Salting out of PVA to form ATPS allowed temporal shape retention of a 3D-printed PVA structure while it was physically crosslinked in moderate alkaline conditions. Crucially, the layer-to-layer adhesion of PVA was facilitated by delayed crosslinking of PVA that required additional reaction time and overlapping between the layers. To verify this principle, we studied the feasibility of direct ink write (DIW) 3D printing of PVA inks (5-25% w/w, µ = 0.1-20 Pa s, and MW = 22 000 and 74 800) in aqueous embedding media offering three distinct chemical environments: (1) salts for salting out (e.g., Na2SO4), (2) alkali hydroxides for physical crosslinking (e.g., NaOH), and (3) a mixture of salt and alkali hydroxide. Our study suggested the feasibility of 3D-printed PVA-Hy using the mixture of salt and alkali hydroxide, demonstrating a unique concept of embedded 3D printing enabled by ATPS for temporary stabilization of the printed structures to facilitate 3D fabrication.

8.
Adv Sci (Weinh) ; : e2400870, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553790

RESUMO

Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride-based alloys are still the best for near-room-temperature applications. In this work, a ≈38% enhancement of the average ZT (300-473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2-yTe3-based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6-based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high-density dislocations in the same region can effectively scatter the phonons, decoupling the electron-phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single-leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate-matrix interface microstructure in improving the performance of materials for relatively low-temperature applications.

9.
Cells ; 13(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38474413

RESUMO

Cardiomyocytes rely on proper mitochondrial homeostasis to maintain contractility and achieve optimal cardiac performance. Mitochondrial homeostasis is controlled by mitochondrial fission, fusion, and mitochondrial autophagy (mitophagy). Mitophagy plays a particularly important role in promoting the degradation of dysfunctional mitochondria in terminally differentiated cells. However, the precise mechanisms by which this is achieved in cardiomyocytes remain opaque. Our study identifies GRAF1 as an important mediator in PINK1-Parkin pathway-dependent mitophagy. Depletion of GRAF1 (Arhgap26) in cardiomyocytes results in actin remodeling defects, suboptimal mitochondria clustering, and clearance. Mechanistically, GRAF1 promotes Parkin-LC3 complex formation and directs autophagosomes to damaged mitochondria. Herein, we found that these functions are regulated, at least in part, by the direct binding of GRAF1 to phosphoinositides (PI(3)P, PI(4)P, and PI(5)P) on autophagosomes. In addition, PINK1-dependent phosphorylation of Parkin promotes Parkin-GRAF1-LC3 complex formation, and PINK1-dependent phosphorylation of GRAF1 (on S668 and S671) facilitates the clustering and clearance of mitochondria. Herein, we developed new phosphor-specific antibodies to these sites and showed that these post-translational modifications are differentially modified in human hypertrophic cardiomyopathy and dilated cardiomyopathy. Furthermore, our metabolic studies using serum collected from isoproterenol-treated WT and GRAF1CKO mice revealed defects in mitophagy-dependent cardiomyocyte fuel flexibility that have widespread impacts on systemic metabolism. In summary, our study reveals that GRAF1 co-regulates actin and membrane dynamics to promote cardiomyocyte mitophagy and that dysregulation of GRAF1 post-translational modifications may underlie cardiac disease pathogenesis.


Assuntos
Proteínas Ativadoras de GTPase , Mitofagia , Miócitos Cardíacos , Fosfatos de Fosfatidilinositol , Ubiquitina-Proteína Ligases , Animais , Humanos , Camundongos , Actinas , Proteínas Ativadoras de GTPase/metabolismo , Mitofagia/fisiologia , Miócitos Cardíacos/metabolismo , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
10.
Adv Sci (Weinh) ; : e2310115, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491872

RESUMO

In this work, 2D ferromagnetic M3 GeTe2 (MGT, M = Ni/Fe) nanosheets with rich atomic Te vacancies (2D-MGTv ) are demonstrated as efficient OER electrocatalyst via a general mechanical exfoliation strategy. X-ray absorption spectra (XAS) and scanning transmission electron microscope (STEM) results validate the dominant presence of metal-O moieties and rich Te vacancies, respectively. The formed Te vacancies are active for the adsorption of OH* and O* species while the metal-O moieties promote the O* and OOH* adsorption, contributing synergistically to the faster oxygen evolution kinetics. Consequently, 2D-Ni3 GeTe2v exhibits superior OER activity with only 370 mV overpotential to reach the current density of 100 mA cm-2 and turnover frequency (TOF) value of 101.6 s-1 at the overpotential of 200 mV in alkaline media. Furthermore, a 2D-Ni3 GeTe2v -based anion-exchange membrane (AEM) water electrolysis cell (1 cm2 ) delivers a current density of 1.02 and 1.32 A cm-2 at the voltage of 3 V feeding with 0.1 and 1 m KOH solution, respectively. The demonstrated metal-O coordination with abundant atomic vacancies for ferromagnetic M3 GeTe2 and the easily extended preparation strategy would enlighten the rational design and fabrication of other ferromagnetic materials for wider electrocatalytic applications.

11.
Phys Chem Chem Phys ; 26(14): 10568-10578, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38512104

RESUMO

Liquid-liquid phase separation (LLPS) plays a pivotal role in the organization and functionality of living cells. It is imperative to understand the underlying driving forces behind LLPS and to control its occurrence. In this study, we employed coarse-grained (CG) simulations as a research tool to investigate systems comprising oligolysine and adenosine triphosphate (ATP) under conditions of various ionic concentrations and oligolysine lengths. Consistent with experimental observations, our CG simulations captured the formation of LLPS upon the addition of ATP and tendency of dissociating under high ionic concentration. The electrostatic interaction between oligolysine and ATP is of great importance in forming LLPS. An in-depth analysis on the structural properties of LLPS was conducted, where the oligolysine structure remained unchanged with increased ionic concentration and the addition of ATP led to a more pronounced curvature, aligning with the observed enhancement of α-helical secondary structure in experiments. In terms of the dynamic properties, the introduction of ATP led to a significant reduction in translational and vibrational degrees of freedom but not rotational degrees of freedom. Through keeping the total number of charged residues constant and varying their entropic effects, we constructed two systems of similar biochemical significance and further validated the entropy effects on the LLPS formation. These findings provide a deeper understanding of LLPS formation and shed lights on the development of novel bioreactor and primitive artificial cells for synthesizing key chemicals for certain diseases.


Assuntos
Trifosfato de Adenosina , Células Artificiais , 60422 , Reatores Biológicos , Entropia
12.
ANZ J Surg ; 94(4): 655-659, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553889

RESUMO

OBJECTIVE: To investigate the safety and application value of combining Laennec extracapsular occlusion with ICG fluorescence imaging in laparoscopic anatomic hepatectomy. METHODS: Complete laparoscopic dissection was performed outside the Laennec sheath, blocking Glisson's pedicle of the corresponding liver segment or lobe. An appropriate amount of indocyanine green (ICG) dye was intravenously injected, and the boundary line between the pre-cut liver segment and liver lobe was identified using fluorescence laparoscopy. Complete resection of the liver segment or lobe was performed based on anatomical markers. Clinical data, including operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications, were collected. RESULTS: A total of 14 cases were included in the study, including seven cases of primary liver cancer, three cases of metastatic liver cancer, three cases of intrahepatic bile duct calculi, and one case of hepatic hemangioma. All 14 patients underwent anatomic hepatectomy under fluorescent laparoscopy, with four cases involving the right liver, seven cases involving the left liver, two cases involving the right anterior lobe, and one case involving the right posterior lobe. CONCLUSION: Combining laparoscopic follow-up of the Laennec membrane with Glisson outer sheath block and intraoperative ICG fluorescence imaging provides real-time guidance for locating the resection boundaries during anatomic hepatectomy. This approach helps in controlling intraoperative bleeding, reducing operation time, and ensuring high safety. It holds significant value in clinical application.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Humanos , Hepatectomia/métodos , Verde de Indocianina/farmacologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Laparoscopia/métodos , Imagem Óptica/métodos
13.
Sci China Life Sci ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38523237

RESUMO

Fucosyltransferase 8 (Fut8) and core fucosylation play critical roles in regulating various biological processes, including immune response, signal transduction, proteasomal degradation, and energy metabolism. However, the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown. We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells (aNSPCs) and postnatal brain development. Fut8 depletion reduces the proliferation of aNSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo, respectively. Additionally, Fut8 deficiency impairs learning and memory in mice. Mechanistically, Fut8 directly interacts with integrin α6 (Itga6), an upstream regulator of the PI3k-Akt signaling pathway, and catalyzes core fucosylation of Itga6. Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6. Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway. Moreover, the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency. In summary, our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

14.
J Am Chem Soc ; 146(12): 7956-7962, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38471146

RESUMO

Enantioenriched 2-azabicyclo[3.1.0]hexanes are accessed from readily available allyl substituted α-isocyanoesters by intramolecular (1 + 2) cycloaddition with the olefinic moiety and isocyano carbon as the respective C2 and C1 units. Cyclopropanation is initiated by 1,1-hydrocupration of isocyanide followed by formimidoylcopper to copper α-aminocarbenoid equilibration and subsequent (1 + 2) cycloaddition. The unprecedented copper/chiral phosphoric acid (CPA) catalytic system can be operated in the presence of water under air, delivering a variety of 2-azabicyclo[3.1.0]hexanes containing an angular all-carbon quaternary stereocenter in good to excellent yields and enantioselectivity.

15.
Pediatr Surg Int ; 40(1): 62, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430253

RESUMO

PURPOSE: Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. METHODS: We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. RESULTS: This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8 cm (range 0.5-10 cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. CONCLUSIONS: B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.


Assuntos
Cistos , Laparoscopia , Cisto Parovariano , Feminino , Criança , Humanos , Adolescente , Estudos Retrospectivos , Cisto Parovariano/patologia , Cisto Parovariano/cirurgia , Cistos/cirurgia , Ultrassonografia
16.
ACS Appl Mater Interfaces ; 16(8): 11043-11049, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349718

RESUMO

The nonlinear Hall effect (NLHE) holds immense significance in recognizing the band geometry and its potential applications in current rectification. Recent discoveries have expanded the study from second-order to third-order nonlinear Hall effect (THE), which is governed by an intrinsic band geometric quantity called the Berry Connection Polarizability tensor. Here we demonstrate a giant THE in a misfit layer compound, (SnS)1.17(NbS2)3. While the THE is prohibited in individual NbS2 and SnS due to the constraints imposed by the crystal symmetry and their band structures, a remarkable THE emerges when a superlattice is formed by introducing a monolayer of SnS. The angular-dependent THE and its scaling relationship indicate that the phenomenon could be correlated to the band geometry modulation, concurrently with the symmetry breaking. The resulting strength of THE is orders of magnitude higher compared to recent studies. Our work illuminates the modulation of structural and electronic geometries for novel quantum phenomena through interface engineering.

17.
Int J Biol Macromol ; 263(Pt 2): 130310, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382774

RESUMO

L-threo-p-nitrophenylserine (component 2) is an important intermediate during synthesis of chloramphenicol. However, its biosynthesis is limited by enzyme activity and stereoselectivity. In this study, we achieved a breakthrough in the high-efficiency production of 2 by employing engineered Chitiniphilus shinanonensis L-threonine transaldolase (ChLTTA) in conjunction with a by-product elimination system within a one-pot reaction. Notably, a novel visual stepwise high-throughput screening method was developed for the directed evolution of ChLTTA, leveraging its characteristic color. The engineered mutant F70D/F59A (Mu6 variant) emerged as a star performer, exhibiting a remarkable 2.6-fold increase in catalytic efficiency over the wild-type ChLTTA, coupled with an outstanding 91.5 % diastereoisomer excess (de). Molecular dynamics (MD) simulations unraveled the mechanism responsible for the enhanced catalytic performance observed in the Mu6 variant. Meanwhile, the Mu6 variant was coupled with Saccharomyces cerevisiae ethanol dehydrogenase (ScADH) and Candida boidinii formate dehydrogenase (CbFDH) to create a high-efficiency cascade system (E.coli/pRSF-Mu6-ScADH-CbFDH). Under optimized conditions, this cascade system demonstrated unparalleled performance, yielding 201.5 mM of 2 with an impressive conversion of 95.9 % and a de value of 94.5 %. This achievement represents the highest reported yield to date. This study offers a novel insight into the sustainable and efficient production of chloramphenicol intermediate.


Assuntos
Treonina , Transaldolase , Cloranfenicol , Escherichia coli/genética
18.
Cell Death Dis ; 15(2): 146, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360839

RESUMO

Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficient macrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors. Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients. Schematic illustration of macrophage TSC1-mediated AKT/MST1/NRF2 signaling pathway in I/R-triggered liver inflammation. Macrophage TSC1 can be activated in I/R-stressed livers. TSC1 activation promotes phosphorylation of AKT and MST1, which in turn increases NRF2 expression and inhibits ROS production and TLR4/NF-κB activation, resulting in reduced hepatocellular apoptosis in I/R-triggered liver injury.


Assuntos
Traumatismo por Reperfusão , Esclerose Tuberosa , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Esclerose Tuberosa/metabolismo , Fígado/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Inflamação/metabolismo , Traumatismo por Reperfusão/metabolismo
19.
Adv Mater ; 36(16): e2311327, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221508

RESUMO

Severe capacity decay under subzero temperatures remains a significant challenge for lithium-ion batteries (LIBs) due to the sluggish interfacial kinetics. Current efforts to mitigate this deteriorating interfacial behavior rely on high-solubility lithium salts (e.g., Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), Lithium bis(fluorosulfonyl)imide (LiFSI))-based electrolytes to construct anion participated solvation structures. However, such electrolytes bring issues of corrosion on the current collector and increased costs. Herein, the most commonly used Lithium hexafluorophosphate (LiPF6) instead, to establish a peculiar solvation structure with a high ratio of ion pairs and aggregates by introducing a deshielding NO3 - additive for low-temperature LIBs is utilized. The deshielding anion significantly reduces the energy barrier for interfacial behavior at low temperatures. Benefiting from this, the graphite (Gr) anode retains a high capacity of ≈72.3% at -20 °C, which is far superior to the 32.3% and 19.4% capacity retention of counterpart electrolytes. Moreover, the LiCoO2/Gr full cell exhibits a stable cycling performance of 100 cycles at -20 °C due to the inhibited lithium plating. This work heralds a new paradigm in LiPF6-based electrolyte design for LIBs operating at subzero temperatures.

20.
Forensic Sci Int Genet ; 69: 103008, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38244524

RESUMO

Inferring the number of contributors (NoC) is a crucial step in interpreting DNA mixtures, as it directly affects the accuracy of the likelihood ratio calculation and the assessment of evidence strength. However, obtaining the correct NoC in complex DNA mixtures remains challenging due to the high degree of allele sharing and dropout. This study aimed to analyze the impact of allele sharing and dropout on NoC inference in complex DNA mixtures when using microhaplotypes (MH). The effectiveness and value of highly polymorphic MH for NoC inference in complex DNA mixtures were evaluated through comparing the performance of three NoC inference methods, including maximum allele count (MAC) method, maximum likelihood estimation (MLE) method, and random forest classification (RFC) algorithm. In this study, we selected the top 100 most polymorphic MH from the Southern Han Chinese (CHS) population, and simulated over 40 million complex DNA mixture profiles with the NoC ranging from 2 to 8. These profiles involve unrelated individuals (RM type) and related pairs of individuals, including parent-offspring pairs (PO type), full-sibling pairs (FS type), and second-degree kinship pairs (SE type). Our results indicated that how the number of detected alleles in DNA mixture profiles varied with the markers' polymorphism, kinship's involvement, NoC, and dropout settings. Across different types of DNA mixtures, the MAC and MLE methods performed best in the RM type, followed by SE, FS, and PO types, while RFC models showed the best performance in the PO type, followed by RM, SE, and FS types. The recall of all three methods for NoC inference were decreased as the NoC and dropout levels increased. Furthermore, the MLE method performed better at low NoC, whereas RFC models excelled at high NoC and/or high dropout levels, regardless of the availability of a priori information about related pairs of individuals in DNA mixtures. However, the RFC models which considered the aforementioned priori information and were trained specifically on each type of DNA mixture profiles, outperformed RFC_ALL model that did not consider such information. Finally, we provided recommendations for model building when applying machine learning algorithms to NoC inference.


Assuntos
Algoritmos , Impressões Digitais de DNA , Humanos , Genótipo , Impressões Digitais de DNA/métodos , DNA/genética , Aprendizado de Máquina
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