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1.
Immunity ; 56(12): 2773-2789.e8, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992711

RESUMO

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Esclerose Múltipla , Masculino , Feminino , Camundongos , Animais , Esclerose Múltipla/metabolismo , Modelos Animais de Doenças , Transdução de Sinais , Progressão da Doença , Receptores Dopaminérgicos
2.
Proc Natl Acad Sci U S A ; 120(5): e2215575120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36696445

RESUMO

Chloroplast division involves the coordination of protein complexes from the stroma to the cytosol. The Min system of chloroplasts includes multiple stromal proteins that regulate the positioning of the division site. The outer envelope protein PLASTID DIVISION1 (PDV1) was previously reported to recruit the cytosolic chloroplast division protein ACCUMULATION AND REPLICATION OF CHLOROPLAST5 (ARC5). However, we show here that PDV1 is also important for the stability of the inner envelope chloroplast division protein PARALOG OF ARC6 (PARC6), a component of the Min system. We solved the structure of both the C-terminal domain of PARC6 and its complex with the C terminus of PDV1. The formation of an intramolecular disulfide bond within PARC6 under oxidized conditions prevents its interaction with PDV1. Interestingly, this disulfide bond can be reduced by light in planta, thus promoting PDV1-PARC6 interaction and chloroplast division. Interaction with PDV1 can induce the dimerization of PARC6, which is important for chloroplast division. Magnesium ions, whose concentration in chloroplasts increases upon light exposure, also promote the PARC6 dimerization. This study highlights the multilayer regulation of the PDV1-PARC6 interaction as well as chloroplast division.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Plastídeos/metabolismo , Cloroplastos/metabolismo , Dissulfetos/metabolismo , Dinaminas/metabolismo
3.
Plant Cell ; 34(1): 419-432, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34755875

RESUMO

In bacteria and chloroplasts, the GTPase filamentous temperature-sensitive Z (FtsZ) is essential for division and polymerizes to form rings that mark the division site. Plants contain two FtsZ subfamilies (FtsZ1 and FtsZ2) with different assembly dynamics. FtsZ1 lacks the C-terminal domain of a typical FtsZ protein. Here, we show that the conserved short motif FtsZ1Carboxyl-terminus (Z1C) (consisting of the amino acids RRLFF) with weak membrane-binding activity is present at the C-terminus of FtsZ1 in angiosperms. For a polymer-forming protein such as FtsZ, this activity is strong enough for membrane tethering. Arabidopsis thaliana plants with mutated Z1C motifs contained heterogeneously sized chloroplasts and parallel FtsZ rings or long FtsZ filaments, suggesting that the Z1C motif plays an important role in regulating FtsZ ring dynamics. Our findings uncover a type of amphiphilic beta-strand motif with weak membrane-binding activity and point to the importance of this motif for the dynamic regulation of protein complex formation.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Cloroplastos/fisiologia , Sequência de Aminoácidos , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo
4.
Cell Mol Life Sci ; 81(1): 421, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367995

RESUMO

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.


Assuntos
Movimento Celular , Proliferação de Células , Proteínas da Matriz Extracelular , Quinase 1 de Adesão Focal , Camundongos Nus , Neoplasias Ovarianas , Proteínas de Ligação a RNA , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Transdução de Sinais , Ubiquitinação , Proteínas de Ligação a RNA/metabolismo , Proteínas da Matriz Extracelular/metabolismo
5.
Nano Lett ; 24(5): 1667-1672, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38241735

RESUMO

Researching optoelectronic memristors capable of integrating sensory and processing functions is essential for advancing the development of efficient neuromorphic vision. Here, we experimentally demonstrated an all-optical controlled and self-rectifying optoelectronic memristor (OEM) crossbar array with the function of multilevel storage under light stimuli. The NiO/TiO2 device exhibits an ultrahigh (>104) rectifying ratio (RR) thus overcoming the presence of sneak current. The reversible conductance modulation without electric signal involvement provides a novel way to realize ultrafast information processing. The proposed OEM array realized synaptic functions observed in the human brain, including long-term potentiation (LTP), long-term depression (LTD), paired-pulse facilitation (PPF), the transition from short-term memory (STM) to long-term memory (LTM), and learning experience behaviors successfully. The authors present a novel OEM crossbar that possesses complete light-modulation capabilities, potentially advancing the future development of efficient neuromorphic vision.

6.
Nano Lett ; 24(6): 2018-2024, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315050

RESUMO

In recent years, memristors have successfully demonstrated their significant potential in artificial neural networks (ANNs) and neuromorphic computing. Nonetheless, ANNs constructed by crossbar arrays suffer from cross-talk issues and low integration densities. Here, we propose an eight-layer three-dimensional (3D) vertical crossbar memristor with an ultrahigh rectify ratio (RR > 107) and an ultrahigh nonlinearity (>105) to overcome these limitations, which enables it to reach a >1 Tb array size without reading failure. Furthermore, the proposed 3D RRAM shows advanced endurance (>1010 cycles), retention (>104 s), and uniformity. In addition, several synaptic functions observed in the human brain were mimicked. On the basis of the advanced performance, we constructed a novel 3D ANN, whose learning efficiency and recognition accuracy were enhanced significantly compared with those of conventional single-layer ANNs. These findings hold promise for the development of highly efficient, precise, integrated, and stable VLSI neuromorphic computing systems.

7.
Nano Lett ; 24(36): 11170-11178, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39148056

RESUMO

Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf0.1Zr0.9O2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.

8.
Small ; 20(24): e2310234, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38155520

RESUMO

The development of chiral nanostructures-based supramolecular catalysts with satisfied enantioselectivity remains a significantly more challenging task. Herein, the synthesis and self-assembly of various amino acid amphiphiles as chiral supramolecular catalysts after metal ion coordination is reported and systematically investigate their enantioselectivity in asymmetric Diels-Alder reactions. In particular, the self-assembly of l/d-phenylglycine-based amphiphiles (l/d-PhgC16) and Cu(II) into chiral supramolecular catalysts in the methanol/water solution mixture is described, which features the interesting M/P nanohelices (diameter ≈8 nm) and mostly well-aligned M/P nanoribbons (NRs). The M/P supramolecular catalysts show both high but inverse enantioselectivity (>90% ee) in Diels-Alder reactions, while their monomeric counterparts display nearly racemic products. Analysis of the catalytic results suggests the outstanding enantioselectivities are closely related to the specific stereochemical microenvironment provided by the arrangement of the amphiphiles in the supramolecular assembly. Based on the experimental evidence of chirality transfer from supramolecular nanohelices to coordinated Cu(II) and substrate aza-chalcone and the molecular dynamics simulations, the enantioselective catalytic mechanisms are proposed. Moreover, the relationships between molecular structures of amino acid amphiphiles (the hydrophilic head group and hydrophobic alkyl chain length) in supramolecular catalysts and enantioselectivity in Diels-Alder reactions are elaborated.

9.
BMC Microbiol ; 24(1): 309, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174950

RESUMO

BACKGROUND: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. RESULTS: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. CONCLUSIONS: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.


Assuntos
Antibacterianos , Bacteriemia , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Estudos Retrospectivos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/tratamento farmacológico , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Filogenia , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Fatores de Virulência/genética , Idoso de 80 Anos ou mais , Adulto
10.
Acc Chem Res ; 56(4): 500-513, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36734050

RESUMO

ConspectusProteins exhibit high-binding affinity and selectivity, as well as remarkable catalytic performance. Their binding pockets are hydrophobic but also contain polar and charged groups to contribute to the binding of polar organic molecules in aqueous solution. In the past decades, the synthesis of biomimetic receptors featuring sizable aromatic cavities equipped with converging polar groups has received considerable attention. "Temple" cages, naphthotubes, and aryl-extended calix[4]pyrroles are privileged examples of synthetic scaffolds displaying functionalized hydrophobic cavities capable of binding polar substrates. In particular, calix[4]pyrroles are macrocycles containing four pyrrole rings connected through their pyrrolic 2- and 5-positions by tetra-substituted sp3 carbon atoms (meso-substituents). In 1996, Sessler introduced the meso-octamethyl calix[4]pyrrole as an outstanding receptor for anion binding. Independently, Sessler and Floriani also showed that the introduction of aryl substituents in the meso-positions produced aryl-extended calix[4]pyrroles as a mixture of configurational isomers. In addition, aryl-extended calix[4]pyrroles bearing two and four meso-aryl substituents (walls) were reported. The cone conformation of "two-wall" αα-aryl-extended calix[4]pyrroles features an aromatic cleft with a polar binding site defined by four converging pyrrole NHs. On the other hand, "four-wall" αααα-calix[4]pyrrole isomers possess a deep polar aromatic cavity closed at one end by the converging pyrrole NHs. Because of their functionalized interior, aryl-extended calix[4]pyrroles are capable of binding anions, ion-pairs, and electron-rich neutral molecules in organic solvents. However, in water, they are restricted to the inclusion of neutral polar guests.Since the early 2000s, our research group has been involved in the design and synthesis of "two-wall" and "four-wall" aryl-extended calix[4]pyrroles and their derivatives, such as aryl-extended calix[4]pyrrole cavitands and super aryl-extended calix[4]pyrroles. In this Account, we mainly summarize our own results on the binding of charged and neutral polar guests with these macrocyclic receptors in organic solvents and in water. We also describe the applications of calix[4]pyrrole derivatives in the sensing of creatinine, the facilitated transmembrane transport of anions and amino acids, and the monofunctionalization of bis-isonitriles. Moreover, we explain the use of calix[4]pyrrole receptors as model systems for the quantification of anion-π interactions and the hydrophobic effect. Finally, we discuss the self-assembly of dimeric capsules and unimolecular metallo-cages based on calix[4]pyrrole scaffolds. We comment on their binding properties, as well as on those of bis-calix[4]pyrroles having a fully covalent structure.In molecular recognition, aryl-extended calix[4]pyrroles and their derivatives are considered valuable receptors owing to their ability to interact with a wide variety of electron-rich, neutral, and charged guests. Calix[4]pyrrole scaffolds have also been applied in the development of molecular sensors, ionophores, transmembrane carriers, supramolecular protecting groups and molecular containers modulating chemical reactivity, among others. We believe that the design of new calix[4]pyrrole receptors and the investigation of their binding properties may lead to promising applications in many research areas, such as supramolecular catalysis, chemical biology and materials science. We hope that this Account will serve to spread the knowledge of the supramolecular chemistry of calix[4]pyrroles among supramolecular and nonsupramolecular chemists alike.

11.
Langmuir ; 40(28): 14555-14560, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38940619

RESUMO

Understanding the interaction between metal ions as catalytic centers and supramolecular scaffolds as chiral substrates plays an important role in developing chiral supramolecular catalysts with high enantioselectivity. Herein, we found that compared with l-norleucine chiral amphiphile (l-NorC16), l-methionine chiral amphiphile (l-MetC16) with the only heteroatom of S site difference in the hydrophilic group can form a similar supramolecular chiral nanoribbon (NR) with the bilayer structure through the self-assembly approach; yet, the interaction between the Cu(II) ion catalytic centers and supramolecular scaffolds is reinforced, favoring the chirality transfer and therefore enhancing their catalytic enantioselectivity of Diels-Alder reaction from 23% [l-NorC16-NR-Cu(II)] to 78% [l-MetC16-NR-Cu(II)]. Our work demonstrates a new strategy from the perspective of strengthening the metal ion-supramolecular scaffold interaction for the preparation of chiral supramolecular catalysts with good catalytic enantioselectivity.

12.
Inorg Chem ; 63(21): 9975-9982, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38747890

RESUMO

The ability to control the catalytic activity of enzymes in chemical transformations is essential for the design and development of artificial catalysts. Herein, we report the synthesis and characterization of functional ligands featuring two 1,4,7,10-tetraazacyclododecane units linked by an azobenzene group and their corresponding dinuclear Zn(II) complexes. We show that the configuration switching (E/Z) of the azobenzene spacer in the ligands and their dinuclear Zn(II) complexes is reversibly controlled by irradiation with UV and visible light. The Zn(II)-metal complexes are light-responsive catalysts for the hydrolytic cleavage of nerve agent simulants, i.e., p-nitrophenyl diphenyl phosphate and methyl paraoxon. The catalytic activity of the Z-isomers of the dinuclear Zn(II) complexes outperformed that of the E-counterparts. Moreover, combining the less active E-isomers with gold nanoparticles induced an enhancement in the hydrolysis rate of p-nitrophenyl diphenyl phosphate. Kinetic analysis has shown that the catalytic site appears to involve a single metal ion. We explain our results by considering the different desolvation effects occurring in the catalyst's configurations in the solution and the catalytic systems involving gold nanoparticles.

13.
J Chem Phys ; 160(4)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38270240

RESUMO

Due to the limitation of inherent ultra-high electron concentration, the electrical properties of In2O3 resemble those of conductors rather than semiconductors prior to special treatment. In this study, the effect of various annealing treatments on the microstructure, optical properties, and oxygen vacancies of the films and transistors is systematically investigated. Our finding reveals a progressive crystallization trend in the films with increasing annealing temperature. In addition, a higher annealing temperature is also associated with the reduction in the concentration of oxygen vacancies, as well as an elevation in both optical transmittance and optical bandgap. Furthermore, with the implementation of annealing process, the devices gradually transform from no pronounced gate control to exhibit with excellent gate control and electrical performances. The atomic layer deposited Hf-doped In2O3 thin film transistor annealed at 250 °C exhibits optimal electrical properties, with a field-effect mobility of 18.65 cm2 V-1 s-1, a subthreshold swing of 0.18 V/dec, and an Ion/Ioff ratio of 2.76 × 106. The results indicate that the impact of varying annealing temperatures can be attributed to the modulation of oxygen vacancies within the films. This work serves as a complementary study for the existing post-treatment of oxide films and provides a reliable reference for utilization of the annealing process in practical applications.

14.
Nano Lett ; 23(10): 4675-4682, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-36913490

RESUMO

Hafnium oxide (HfO2)-based ferroelectric tunnel junctions (FTJs) have been extensively evaluated for high-speed and low-power memory applications. Herein, we investigated the influence of Al content in HfAlO thin films on the ferroelectric characteristics of HfAlO-based FTJs. Among HfAlO devices with different Hf/Al ratios (20:1, 34:1, and 50:1), the HfAlO device with Hf/Al ratio of 34:1 exhibited the highest remanent polarization and excellent memory characteristics and, thereby, the best ferroelectricity among the investigated devices. Furthermore, first-principal analyses verified that HfAlO thin films with Hf/Al ratio of 34:1 promoted the formation of the orthorhombic phase against the paraelectric phase as well as alumina impurities and, thus, enhanced the ferroelectricity of the device, providing theoretical support for supporting experimental results. The findings of this study provide insights for developing HfAlO-based FTJs for next-generation in-memory computing applications.

15.
J Environ Manage ; 362: 121222, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833928

RESUMO

The carbon generalized system of preferences (CGSP) is an innovative incentive mechanism implemented by the Chinese government, which has also become an important part of carbon emission reduction at the living end, and it is of great significance to study whether the Pilot Policy can reduce the carbon emissions of residents. This study firstly accounts for the total carbon emissions and per capita carbon emissions of the residents of 284 cities in China, and on this basis, adopts the SCM method to quantitatively study and analyze the overall and local implementation effects of CGSP in China by taking the first batch of CGSP pilots in China as an example, and further applies the mediation effect model to test the pathways of the role of CGSP. The main findings of the study are as follows: (1) During the period of 2010-2020, the total carbon emissions from urban residents' living in China showed a yearly growth trend, from 36,623.98 ×10-2Mt in 2010-85,241.20 ×10-2Mt in 2020, an increase of 8.83%. Total carbon emissions present a structural difference of "electricity consumption > central heating > private transport > gas (oil, natural gas) consumption". (2) Overall, the implementation of the CGSP had a robust positive impact on the overall carbon emission reduction in the pilot cities, with an average annual emission reduction effect value of 36.53 ×10-2Mt. Locally, the annual net policy effect values of Dongguan, Zhongshan, Heyuan, and Guangzhou are 6169.79 ×10-2, 26,600.17 ×10-2, 17,081.34 ×10-2 and 9393.36 ×10-2Mt respectively. (3) CGSP has a good carbon emission reduction effect by suppressing the impact on residents' carbon emissions through enhancing the city's innovation capacity and promoting electricity saving and consumption reduction, while the mediating effect played by the promotion of green and low-carbon travel in the pilot policy is not significant. Finally, based on the research findings, relevant suggestions are targeted.


Assuntos
Carbono , Cidades , China , Humanos , Poluição do Ar/prevenção & controle , Dióxido de Carbono/análise
16.
Theor Appl Genet ; 136(5): 111, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37052704

RESUMO

KEY MESSAGE: A mutation of CsARC6 not only causes white fruit color in cucumber, but also affects plant growth and fruit quality. Fruit color of cucumber is a very important agronomic trait, but most of the genes affecting cucumber white fruit color are still unknow, and no further studies were reported on the effect of cucumber fruit quality caused by white fruit color genes. Here, we obtained a white fruit mutant em41 in cucumber by EMS mutagenesis. The mutant gene was mapped to a 548 kb region of chromosome 2. Through mutation site analysis, it was found to be a null allele of CsARC6 (CsaV3_2G029290). The Csarc6 mutant has a typical phenotype of arc6 mutant that mesophyll cells contained only one or two giant chloroplasts. ARC6 protein was not detected in em41, and the level of FtsZ1 and FtsZ2 was also reduced. In addition, FtsZ2 could not form FtsZ ring-like structures in em41. Although these are typical arc6 mutant phenotypes, some special phenotypes occur in Csarc6 mutant, such as dwarfness with shortened internodes, enlarged fruit epidermal cells, decreased carotenoid contents, smaller fruits, and increased fruit nutrient contents. This study discovered a new gene, CsARC6, which not only controls the white fruit color, but also affects plant growth and fruit quality in cucumber.


Assuntos
Cucumis sativus , Cucumis sativus/genética , Cucumis sativus/metabolismo , Frutas/genética , Frutas/metabolismo , Mutação , Cloroplastos/metabolismo , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
17.
J Biochem Mol Toxicol ; 37(10): e23446, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37354072

RESUMO

Breast cancer (BC) with high HER2 expression has higher recurrence rate and worse prognosis, and its immunotherapy is promising. Based on the high expression of HER2, develop Chimeric Antigen Receptor T-cell (CAR-T) and PDL-1 immunotherapy, and study the molecular pathways of related immune cells and recurrence. HER2-CAR-T cells were constructed using retroviruses, and their specific recognition and immune effects on HER2+ BC cells were verified by in vivo and in vitro experiments. PDL-1 was used as adjuvant immunotherapy, knocking down PDL-1 in tumor cells or dendritic cells, or depleted macrophages to study immune pathways. The negative regulation of HER2 by cbl was determined by IP, ubiquitination experiments, and segmented plasmids, elucidating the molecular mechanism of HER2+ BC recurrence after immunotherapy. HER2-CAR-T specifically recognizes HER2-positive tumor cells and inhibits tumor growth in vivo and in vitro, and anti-PDL1 treatment enhances the therapeutic effect of HER2-CAR-T on tumors. HER2-CART therapy eradicated solid tumors after PDL1 knockdown in dendritic cells. Immunotherapy of relapsed tumors lost HER2 expression by upregulating cbl. HER2-CAR-T shows specific recognition of HER2+ cells and can mediate immune response therapy with the cooperation of PDL-1.

18.
J Chem Phys ; 159(17)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37916595

RESUMO

The relocation of peripheral transistors from the front-end-of-line (FEOL) to the back-end-of-line (BEOL) in fabrication processes is of significant interest, as it allows for the introduction of novel functionality in the BEOL while providing additional die area in the FEOL. Oxide semiconductor-based transistors serve as attractive candidates for BEOL. Within these categories, In2O3 material is particularly notable; nonetheless, the excessive intrinsic carrier concentration poses a limitation on its broader applicability. Herein, the deposition of Hf-doped In2O3 (IHO) films via atomic layer deposition for the first time demonstrates an effective method for tuning the intrinsic carrier concentration, where the doping concentration plays a critical role in determine the properties of IHO films and all-oxide structure transistors with Au-free process. The all-oxide transistors with In2O3: HfO2 ratio of 10:1 exhibited optimal electrical properties, including high on-current with 249 µA, field-effect mobility of 13.4 cm2 V-1 s-1, and on/off ratio exceeding 106, and also achieved excellent stability under long time positive bias stress and negative bias stress. These findings suggest that this study not only introduces a straightforward and efficient approach to improve the properties of In2O3 material and transistors, but as well paves the way for development of all-oxide transistors and their integration into BEOL technology.

19.
BMC Womens Health ; 23(1): 345, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391747

RESUMO

PURPOSE: This paper was mainly conducted to investigate the effect of chronic endometritis (CE) on the clinical outcome of patients with unexplained infertility. MATERIALS AND METHODS: 145 patients with unexplained infertility from the Reproductive Center of our hospital from January 2018 to December 2021 were selected as the unexplained infertility group. 42 patients with definite infertility causes were selected as the control group during the same period. Both groups of patients underwent hysteroscopy and immunohistochemical tests for CD38 and CD138. According to the results of hysteroscopy and immunohistochemistry, the incidence of CE between the two groups was analyzed. Patients with CE as CE group accepted oral antibiotic therapy for 14 days. Another 58 patients with unexplained infertility who did not undergo hysteroscopy and immunohistochemical tests for CD38 and CD138 were selected as the unexamined group. Both groups of patients were expected natural pregnancy. Follow-up lasted for 1 year, and the pregnant patients were followed up until delivery.The clinical pregnancy rate, spontaneous abortion rate and baby-carrying home rate of the two groups were compared. RESULTS: There were 75 patients with CE in the unexplained infertility group, and the prevalence rate was 51.7% (75/145). Compared with the control group (28.6%), the incidence of CE was significantly higher (P < 0.05). After treated with antibiotic treatment, the patients' clinical pregnancy rate was 61.3% (46/75) and baby-carrying home rate was 60% (45/75) in the CE group, which were higher than those in the unexamined group(43.1% & 36.2%) (P < 0.05), while the spontaneous abortion rate was 2.2% (1/46),which was lower than that in the unexamined group (16.0%) (P < 0.05). CONCLUSIONS: For patients with unexplained infertility, hysteroscopy combined with endometrial immunohistochemical detection of CD38 and CD138 should be performed in time to exclude CE. The clinical pregnancy outcome of CE patients can be significantly improved by antibiotic treatment.


Assuntos
Aborto Espontâneo , Endometrite , Infertilidade , Feminino , Lactente , Humanos , Gravidez , Endometrite/complicações , Endometrite/tratamento farmacológico , Endometrite/epidemiologia , Administração Oral , Doença Crônica
20.
Skin Res Technol ; 29(9): e13445, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753682

RESUMO

OBJECTIVE: To observe the application effect of double-tube negative pressure drainage in the repair of refractory wounds. METHODS: From January 2020 to April 2023, 50 patients undergoing refractory wound repair in the Department of Burn and Plastic Surgery of Jingjiang People's Hospital, Jiangsu were selected. According to different treatment methods, they were divided into an observation group and a control group, with 25 patients in each group. The observation group was treated with double-tube negative pressure drainage inside and outside the wound, while the control group was treated with negative pressure drainage inside the wound. By two-week observation, the wound healing status and complication rate after treatment, as well as the wound bacterial clearance rate, wound pain score and patient satisfaction 3, 7 and 14 d after treatment were compared between the two groups. Statistical analysis was carried out to determine the efficacy. RESULTS: After treatment for two weeks, the observation group showed a higher grade A healing rate (92% vs. 60%, X2  = 7.018, P = 0.008), a higher wound bacterial clearance rate (100% vs. 76%, X2  = 6.818, P = 0.03), a lower pain score (1.44 ± 0.51 vs. 2.36 ± 0.49, t = -6.53, P < 0.01), a higher patient satisfaction score (8.48 ± 0.96 vs. 6.64 ± 0.95, t = 6.80, P < 0.01), and a lower complication rate (8% vs. 40%, X2 = 7.018, P = 0.008) compared with the control group. CONCLUSION: Double-tube negative pressure drainage has a significant application effect in the repair of refractory wounds. It can accelerate wound healing, shorten treatment time, effectively eliminate bacteria, relieve wound infection, reduce complications, alleviate pain and improve patient satisfaction. Therefore, the application, promotion and research of double-tube negative pressure drainage should be strengthened in clinical practice.


Assuntos
Drenagem , Procedimentos de Cirurgia Plástica , Humanos , Dor/etiologia , Satisfação do Paciente
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