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1.
Cell ; 186(23): 4996-5014.e24, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37949056

RESUMO

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.


Assuntos
Células-Tronco Embrionárias , Engenharia Genética , Haplorrinos , Animais , Feminino , Gravidez , Haplorrinos/genética , Nascido Vivo , Mamíferos , Células-Tronco Pluripotentes , Primatas , Engenharia Genética/métodos
2.
Nat Immunol ; 16(3): 246-57, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25642822

RESUMO

Immune responses need to be tightly controlled to avoid excessive inflammation and prevent unwanted host damage. Here we report that germinal center kinase MST4 responded dynamically to bacterial infection and acted as a negative regulator of inflammation. We found that MST4 directly interacted with and phosphorylated the adaptor TRAF6 to prevent its oligomerization and autoubiquitination. Accordingly, MST4 did not inhibit lipopolysaccharide-induced cytokine production in Traf6(-/-) embryonic fibroblasts transfected to express a mutant form of TRAF6 that cannot be phosphorylated at positions 463 and 486 (with substitution of alanine for threonine at those positions). Upon developing septic shock, mice in which MST4 was knocked down showed exacerbated inflammation and reduced survival, whereas heterozygous deletion of Traf6 (Traf6(+/-)) alleviated such deleterious effects. Our findings reveal a mechanism by which TRAF6 is regulated and highlight a role for MST4 in limiting inflammatory responses.


Assuntos
Inflamação/metabolismo , Fosforilação/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Sepse/sangue , Choque Séptico/induzido quimicamente , Choque Séptico/metabolismo
3.
Plant Cell ; 35(7): 2449-2463, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-36943796

RESUMO

Cryptophyte plastids originated from a red algal ancestor through secondary endosymbiosis. Cryptophyte photosystem I (PSI) associates with transmembrane alloxanthin-chlorophyll a/c proteins (ACPIs) as light-harvesting complexes (LHCs). Here, we report the structure of the photosynthetic PSI-ACPI supercomplex from the cryptophyte Chroomonas placoidea at 2.7-Å resolution obtained by crygenic electron microscopy. Cryptophyte PSI-ACPI represents a unique PSI-LHCI intermediate in the evolution from red algal to diatom PSI-LHCI. The PSI-ACPI supercomplex is composed of a monomeric PSI core containing 14 subunits, 12 of which originated in red algae, 1 diatom PsaR homolog, and an additional peptide. The PSI core is surrounded by 14 ACPI subunits that form 2 antenna layers: an inner layer with 11 ACPIs surrounding the PSI core and an outer layer containing 3 ACPIs. A pigment-binding subunit that is not present in any other previously characterized PSI-LHCI complexes, ACPI-S, mediates the association and energy transfer between the outer and inner ACPIs. The extensive pigment network of PSI-ACPI ensures efficient light harvesting, energy transfer, and dissipation. Overall, the PSI-LHCI structure identified in this study provides a framework for delineating the mechanisms of energy transfer in cryptophyte PSI-LHCI and for understanding the evolution of photosynthesis in the red lineage, which occurred via secondary endosymbiosis.


Assuntos
Diatomáceas , Complexos de Proteínas Captadores de Luz , Complexos de Proteínas Captadores de Luz/metabolismo , Clorofila A/metabolismo , Complexo de Proteína do Fotossistema I/metabolismo , Fotossíntese , Transferência de Energia , Diatomáceas/metabolismo
4.
Nano Lett ; 24(18): 5481-5489, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38639407

RESUMO

Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation. Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.


Assuntos
Hidrogéis , Células Matadoras Naturais , Células Matadoras Naturais/imunologia , Animais , Camundongos , Hidrogéis/química , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia/métodos , Durapatita/química , Linhagem Celular Tumoral , Quitosana/química , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Interleucinas/imunologia , Interleucina-2/imunologia
5.
J Biol Chem ; 299(8): 104958, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380083

RESUMO

Nitrogen (N) is an essential element for microbial growth and metabolism. The growth and reproduction of microorganisms in more than 75% of areas of the ocean are limited by N. Prochlorococcus is numerically the most abundant photosynthetic organism on the planet. Urea is an important and efficient N source for Prochlorococcus. However, how Prochlorococcus recognizes and absorbs urea still remains unclear. Prochlorococcus marinus MIT 9313, a typical Cyanobacteria, contains an ABC-type transporter, UrtABCDE, which may account for the transport of urea. Here, we heterologously expressed and purified UrtA, the substrate-binding protein of UrtABCDE, detected its binding affinity toward urea, and further determined the crystal structure of the UrtA/urea complex. Molecular dynamics simulations indicated that UrtA can alternate between "open" and "closed" states for urea binding. Based on structural and biochemical analyses, the molecular mechanism for urea recognition and binding was proposed. When a urea molecule is bound, UrtA undergoes a state change from open to closed surrounding the urea molecule, and the urea molecule is further stabilized by the hydrogen bonds supported by the conserved residues around it. Moreover, bioinformatics analysis showed that ABC-type urea transporters are widespread in bacteria and probably share similar urea recognition and binding mechanisms as UrtA from P. marinus MIT 9313. Our study provides a better understanding of urea absorption and utilization in marine bacteria.


Assuntos
Prochlorococcus , Água do Mar , Transportadores de Cassetes de Ligação de ATP/metabolismo , Prochlorococcus/metabolismo , Ureia/metabolismo , Água do Mar/microbiologia
6.
J Hepatol ; 80(5): 792-804, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38331327

RESUMO

BACKGROUND & AIMS: Natural killer (NK) cell-based anti-hepatocellular carcinoma (HCC) therapy is an increasingly attractive approach that warrants further study. Siglec-9 interacts with its ligand (Siglec-9L) and restrains NK cell functions, suggesting it is a potential therapeutic target. However, in situ Siglec-9/Siglec-9L interactions in HCC have not been reported, and a relevant interventional strategy is lacking. Herein, we aim to illustrate Siglec-9/Siglec-9L-mediated cell sociology and identify small-molecule inhibitors targeting Siglec-9 that could improve the efficacy of NK cell-based immunotherapy for HCC. METHODS: Multiplexed immunofluorescence staining was performed to analyze the expression pattern of Siglec-7, -9 and their ligands in HCC tissues. Then we conducted docking-based virtual screening combined with bio-layer interferometry assays to identify a potent small-molecule Siglec-9 inhibitor. The therapeutic potential was further evaluated in vitro and in hepatoma-bearing NCG mice. RESULTS: Siglec-9 expression, rather than Siglec-7, was markedly upregulated on tumor-infiltrating NK cells, which correlated significantly with reduced survival of patients with HCC. Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival, further suggesting that Siglec-9/Siglec-9L interactions are a potential therapeutic target in HCC. In addition, we identified a small-molecule Siglec-9 inhibitor MTX-3937 which inhibited phosphorylation of Siglec-9 and downstream SHP1 and SHP2. Accordingly, MTX-3937 led to considerable improvement in NK cell function. Notably, MTX-3937 enhanced cytotoxicity of both human peripheral and tumor-infiltrating NK cells. Furthermore, transfer of MTX-3937-treated NK92 cells greatly suppressed the growth of hepatoma xenografts in NCG mice. CONCLUSIONS: Our study provides the rationale for HCC treatment by targeting Siglec-9 on NK cells and identifies a promising small-molecule inhibitor against Siglec-9 that enhances NK cell-mediated HCC surveillance. IMPACT AND IMPLICATIONS: Herein, we found that Siglec-9 expression is markedly upregulated on tumor-infiltrating natural killer (TINK) cells and correlates with reduced survival in patients with hepatocellular carcinoma (HCC). Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival. More importantly, we identified a small-molecule inhibitor targeting Siglec-9 that augments NK cell functions, revealing a novel immunotherapy strategy for liver cancer that warrants further clinical investigation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/metabolismo , Células Matadoras Naturais/patologia , Imunoterapia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Ligantes , Prognóstico
7.
Small ; 20(23): e2307309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38150611

RESUMO

Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.


Assuntos
Química Click , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Humanos , Linhagem Celular Tumoral , Animais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
8.
Hepatology ; 78(2): 468-485, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35815363

RESUMO

BACKGROUND AND AIMS: Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate and functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism and signaling transduction. Here, we identified NAD + metabolism as a central hub to determine the homeostasis and function of NK cells. APPROACH AND RESULTS: NAD + level was elevated in activated NK cells. NAD + supplementation not only enhanced cytokine production and cytotoxicity but also improved the proliferation and viability of NK cells. Intriguingly, the salvage pathway was involved in maintaining NAD + homeostasis in activated NK cells. Genetic ablation or pharmacological blockade of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD + salvage pathway, markedly destroyed the viability and function of NK cells. Mechanistically, NAD + salvage dictated the mitochondrial homeostasis and oxidative phosphorylation activity to support the optimal function of NK cells. However, in human HCC tissues, NAMPT expression and NAD + level were significantly down-regulated in tumor-infiltrating NK cells, which negatively correlated with patient survival. And lactate accumulation in the tumor microenvironment was at least partially responsible for the transcriptional repression of NAMPT in NK cells. Further, deficiency of Nampt in NK cells accelerated the growth of HCC and melanoma. Supplementation of the NAD + precursor nicotinamide mononucleotide (NMN) significantly improved NK antitumor response in both mouse and human cell-derived xenografts. CONCLUSIONS: These findings reveal NAD + salvage as an essential factor for NK-cell homeostasis and function, suggesting a potential strategy for invigorating NK cell-based immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , NAD/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Citocinas/metabolismo , Células Matadoras Naturais/metabolismo , Microambiente Tumoral
9.
Plant Cell Environ ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742574

RESUMO

Soil phosphorus (P) availability affects plant growth and distribution. However, it is still unknown how sex-specific variation in functional traits affects plants' P acquisition and soil P transformation. On wet sites, female poplars had a greater specific root length (SRL), and a higher diversity of arbuscular mycorrhizal fungi (AMF) and phosphate-solubilizing bacteria (PSB). Male poplars living on wet sites increased the abundance of AMF and PSB communities and enhanced moderately labile and highly resistant organic P mineralisation via increased phosphatase activity. In contrast, on the dry site, the abundance and diversity of AMF and PSB communities increased in females, enhancing moderately labile and highly resistant organic P mineralisation via elevating phosphatase activities. Males maintained greater SRL and promoted Ca-P mobilisation via the release of root carboxylic acids and rhizosphere acidification on the dry site. The AMF community diversity followed a similar pattern as that of the PSB community when altering the P availability of different-sex plants. Our results indicated that organic P and Ca-P are the major sources of plant-available P in natural P. euphratica forests. Seasonal shifts and geographic locations affected the share of organic and inorganic P pools, and AMF and PSB diversities, ultimately altering sex-specific P acquisition strategies of plants.

10.
Glob Chang Biol ; 30(2): e17198, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38379533

RESUMO

Males and females of dioecious plants have sex-specific adaptations to diverse habitats. The effects of inter- and intrasexual interactions in poplar plantations on composition, structure, and function of soil microbiota have not been explored in degraded areas. We conducted a series of greenhouse and field experiments to investigate how belowground competition, soil microbial communities, and seasonal variation nitrogen content differ among female, male, and mixed-sex Populus cathayana plantations. In the greenhouse experiment, female neighbors suppressed the growth of males under optimal nitrogen conditions. However, male neighbors enhanced stable isotope ratio of nitrogen (δ15 N) of females under intersexual competition. In the field, the root length density, root area density, and biomass of fine roots were lower in female plantations than in male or mixed-sex plantations. Bacterial networks of female, male, and mixed-sex plantations were characterized by different composition of hub nodes, including connectors, modules, and network hubs. The sex composition of plantations altered bacterial and fungal community structures according to Bray-Curtis distances, with 44% and 65% of variance explained by the root biomass, respectively. The total soil nitrogen content of mixed-sex plantation was higher than that in female plantation in spring and summer. The mixed-sex plantation also had a higher ß-1,4-N-acetyl-glucosaminidase activity in summer and a higher nitrification rate in autumn than the other two plantations. The seasonal soil N content, nitrification rate, and root distribution traits demonstrated spatiotemporal niche separation in the mixed-sex plantation. We argue that a strong female-female competition and limited nitrogen content could strongly impede plant growth and reduce the resistance of monosex plantations to climate change and the mixed-sex plantations constitutes a promising way to restore degraded land.


Assuntos
Microbiota , Populus , Solo/química , Biomassa , Nitrogênio/metabolismo , Bactérias , Microbiologia do Solo
11.
Inorg Chem ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898577

RESUMO

Metal-anchored covalent organic frameworks (COFs), as a class of significant derivatives of COFs, are widely used as heterogeneous catalysts in diverse chemical reactions. However, they are typically synthesized via post-treatment strategies, which often lead to the decline of COF crystallinity, decrease of porous properties, instability in catalytic performances, generation of additional chemical waste, and consumption of excess time and energy. In this work, we demonstrate an approach to construct a metal-functionalized COF via a one-pot method induced by γ-ray radiation. Specifically, copper-coordinated COF was in situ synthesized by irradiating a mixture of monomers and copper salt under ambient conditions. Interestingly, the initial Cu2+ ions were reduced to Cu+ ions by the radiation-generated reducing species, affording a unique mixed-valent copper(I/II)-coordinated COF. Additionally, the copper-coordinated COF displayed enhanced crystallinity and porous properties compared to those of the parent COF, displaying an opposite trend to the postsynthetic method. Notably, the introduced copper on the COF skeleton endowed the parent COF with catalytic ability. The resulting copper-coordinated COF exhibited remarkable catalytic performances in the reduction of 4-nitrophenol to 4-aminophenol and maintained almost unchanged catalytic performance after five catalytic cycles.

12.
Angew Chem Int Ed Engl ; : e202406845, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687326

RESUMO

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3+2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol %), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclopentane rings involving an elusive but important all-carbon quaternary.

13.
Angew Chem Int Ed Engl ; 63(27): e202405213, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38637914

RESUMO

Metal-organic framework (MOF) based heterostructures, which exhibit enhanced or unexpected functionality and properties due to synergistic effects, are typically synthesized using post-synthetic strategies. However, several reported post-synthetic strategies remain unsatisfactory, considering issues such as damage to the crystallinity of MOFs, presence of impure phases, and high time and energy consumption. In this work, we demonstrate for the first time a novel route for constructing MOF based heterostructures using radiation-induced post-synthesis, highlighting the merits of convenience, ambient conditions, large-scale production, and notable time and energy saving. Specifically, a new HKUST-1@Cu2O heterostructure was successfully synthesized by simply irradiating a methanol solution dispersed of HKUST-1 with gamma ray under ambient conditions. The copper source of Cu2O was directly derived from in situ radiation etching and reduction of the parent HKUST-1, without the use of any additional copper reagents. Significantly, the resulting HKUST-1@Cu2O heterostructure exhibits remarkable catalytic performance, with a catalytic rate constant nearly two orders of magnitude higher than that of the parent HKUST-1.

14.
Semin Cancer Biol ; 86(Pt 2): 463-475, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35660001

RESUMO

Urologic cancers accounted for more than two million new cases and around 0.8 million deaths in 2020. Although surgery, chemotherapy, and radiotherapy, as well as castration for prostate cancer, remain the cornerstones for managing urologic neoplasms, they can result in severe adverse effects, poor patient compliance, and unsatisfactory survival rates, thus, it is essential to develop novel options that enable the early detection of these malignancies, together with providing accurate diagnoses, and more efficient treatment strategies. Nanomedicine represents an emerging approach that can deliver formulations or drugs across traditional biological barriers in the body and be directed to specific cell types within target organs via active targeting or passive targeting, thus, showing potential to improve the management of urologic cancers. In this review, we discussed the most recent updates on the application of nanomedicines in the diagnosis and treatment of urologic cancers, with focus on prostate, bladder and kidney tumors. We also presented the anti-tumor molecular mechanisms of newly designed nanomedicine for treating urologic cancers, mainly including image-guided surgery, chemotherapy, radiotherapy, gene therapy, immunotherapy, and their synergetic therapy. Current studies have demonstrated the potential advantages of nanomedicine over conventional approaches. However, most developments and new findings in this area have not been validated in clinical trials yet, and therefore, efforts shall be made to translate these research insights into clinical practices for urologic cancers.


Assuntos
Neoplasias da Próstata , Neoplasias Urológicas , Masculino , Humanos , Nanomedicina , Neoplasias Urológicas/terapia , Neoplasias Urológicas/tratamento farmacológico , Imunoterapia , Fatores Imunológicos
15.
J Am Chem Soc ; 145(43): 23651-23658, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37859406

RESUMO

Defects in metal-organic frameworks (MOFs) can significantly change their local microstructures, thus notably leading to an alteration-induced performance in sorption or catalysis. However, achieving de novo defect engineering in MOFs under ambient conditions without the scarification of their crystallinity remains a challenge. Herein, we successfully synthesize defective ZIF-7 through 60Co gamma ray radiation under ambient conditions. The obtained ZIF-7 is defect-rich but also has excellent crystallinity, enhanced BET surface area, and hierarchical pore structure. Moreover, the amount and structure of these defects within ZIF-7 were determined from the two-dimensional (2D) 13C-1H frequency-switched Lee-Goldburg heteronuclear correlation (FSLG-HETCOR) spectra, continuous rotation electron diffraction (cRED), and high-resolution transmission electron microscopy (HRTEM). Interestingly, the defects in ZIF-7 all strongly bind to CO2, leading to a remarkable enhancement of the CO2 sorption capability compared with that synthesized by the solvothermal method.

16.
Apoptosis ; 28(3-4): 313-325, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36652128

RESUMO

Apoptosis repressor with caspase recruitment domain (ARC) acts as a potent and multifunctional inhibitor of apoptosis, which is mainly expressed in postmitotic cells, including cardiomyocytes. ARC is special for its N-terminal caspase recruitment domain and caspase recruitment domain. Due to the powerful inhibition of apoptosis, ARC is mainly reported to act as a cardioprotective factor during ischaemia‒reperfusion (I/R) injury, preventing cardiomyocytes from being devastated by various catastrophes, including oxidative stress, calcium overload, and mitochondrial dysfunction in the circulatory system. However, recent studies have found that ARC also plays a potential regulatory role in tumorigenesis especially in colorectal cancer and renal cell carcinomas, through multiple apoptosis-associated pathways, which remains to be explored in further studies. Therefore, ARC regulates the body and maintains the balance of physiological activities with its interesting duplex. This review summarizes the current research progress of ARC in the field of tumorigenesis and ischaemia/reperfusion injury, to provide overall research status and new possibilities for researchers.


Assuntos
Apoptose , Traumatismo por Reperfusão , Humanos , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Domínio de Ativação e Recrutamento de Caspases , Traumatismo por Reperfusão/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Reperfusão
17.
Environ Microbiol ; 25(7): 1238-1249, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36808192

RESUMO

Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse marine microorganisms catabolize DMSP via DMSP lyases to generate the climate-cooling gas and info-chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H-12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin-containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.


Assuntos
Liases de Carbono-Enxofre , Compostos de Sulfônio , Sequência de Aminoácidos , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Oceanos e Mares , Compostos de Sulfônio/metabolismo , Sulfetos/metabolismo
18.
New Phytol ; 240(4): 1519-1533, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37615210

RESUMO

Little is known about how sex differences in root zone characteristics, such as contents of allelochemicals and soil microbial composition, mediate intra- and intersexual interactions in dioecious plants. We examined the processes and mechanisms of sex-specific belowground interactions mediated by allelochemicals and soil microorganisms in Populus cathayana females and males in replicated 30-yr-old experimental stands in situ and in a series of controlled experiments. Female roots released a greater amount and more diverse phenolic allelochemicals into the soil environment, resulting in growth inhibition of the same sex neighbors and deterioration of the community of soil microorganisms. When grown with males, the growth of females was consistently enhanced, especially the root growth. Compared with female monocultures, the presence of males reduced the total phenolic accumulation in the soil, resulting in a shift from allelopathic inhibition to chemical facilitation. This association was enhanced by a favorable soil bacterial community and increased bacterial diversity, and it induced changes in the orientation of female roots. Our study highlighted a novel mechanism that enhances female performance by males through alterations in the allelochemical content and soil microbial composition. The possibility to improve productivity by chemical mediation provides novel opportunities for managing plantations of dioecious plants.


Assuntos
Populus , Animais , Populus/fisiologia , Solo/química , Feromônios , Plantas , Raízes de Plantas
19.
Plant Physiol ; 190(3): 1883-1895, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35947692

RESUMO

Efficient solar energy conversion is ensured by the organization, physical association, and physiological coordination of various protein complexes in photosynthetic membranes. Here, we visualize the native architecture and interactions of photosynthetic complexes within the thylakoid membranes from a fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 (Syn2973) using high-resolution atomic force microscopy. In the Syn2973 thylakoid membranes, both photosystem I (PSI)-enriched domains and crystalline photosystem II (PSII) dimer arrays were observed, providing favorable membrane environments for photosynthetic electron transport. The high light (HL)-adapted thylakoid membranes accommodated a large amount of PSI complexes, without the incorporation of iron-stress-induced protein A (IsiA) assemblies and formation of IsiA-PSI supercomplexes. In the iron deficiency (Fe-)-treated thylakoid membranes, in contrast, IsiA proteins densely associated with PSI, forming the IsiA-PSI supercomplexes with varying assembly structures. Moreover, type-I NADH dehydrogenase-like complexes (NDH-1) were upregulated under the HL and Fe- conditions and established close association with PSI complexes to facilitate cyclic electron transport. Our study provides insight into the structural heterogeneity and plasticity of the photosynthetic apparatus in the context of their native membranes in Syn2973 under environmental stress. Advanced understanding of the photosynthetic membrane organization and adaptation will provide a framework for uncovering the molecular mechanisms of efficient light harvesting and energy conversion.


Assuntos
Complexos de Proteínas Captadores de Luz , Complexo de Proteína do Fotossistema I , Complexos de Proteínas Captadores de Luz/metabolismo , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Tilacoides/metabolismo , Aclimatação
20.
Chemistry ; 29(9): e202203212, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36563113

RESUMO

The design of molecular cages with low symmetry could allow for more specific tuning of their properties and better mimic the unsymmetrical and complex environment of protein pockets. However, the added value of lowering symmetry of molecular receptors has been rarely demonstrated. Herein, C3 - and C1 -symmetrical cages, presenting the same recognition sites, have been synthesized and investigated as hosts for carbohydrate recognition. Structurally related derivatives of glucose, galactose and mannose were found to have greater affinity to the receptor with the lowest symmetry than to their C3 -symmetrical analogue. According to the host cavity modelling, the C1 symmetry receptor exhibits a wider opening than its C3 -symmetrical counterpart, providing easier access and thus promoting guest proximity to binding sites. Moreover, our results show the high stereo- and substrate selectivity of the C1 symmetry cage with respect to its C3 counterpart in the recognition of sugars.


Assuntos
Carboidratos , Galactose , Modelos Moleculares , Sítios de Ligação , Galactose/química , Glucose/metabolismo , Proteínas de Transporte/química
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