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Status researchers have recognized virtue, competence, and dominance as distinct, viable routes to attaining status. While acknowledging that these routes could be compatible and may not operate independently, prior research relying on a variable-centered perspective has largely neglected their potentially complex interactions. This article integrates a person-centered perspective with the variable-centered perspective to explore how different routes conjointly shape workplace status. Study 1A (N = 537) employs latent profile analysis, an inductive person-centered method, to re-analyze existing survey data, identifying seven distinct profiles of virtue, competence, and dominance that people use to attain status. Study 1B (N = 988) confirms the existence of these profiles in an independent sample of full-time U.S. workers, albeit with nuanced differences in levels. Across our initial studies, these profiles differ in status attainment, with a profile characterized by high virtue and competence but low dominance associated with the highest status-a key discovery challenging to uncover using the variable-centered approach alone. Study 2 (N = 792), a preregistered experiment manipulating the three routes in hypothetical scenarios, gathers causal evidence confirming these profiles' varying effectiveness. Study 3 (N = 785), another preregistered experiment using refined manipulations, corroborates the findings of Study 2 and provides evidence for the relevance of these causal insights to real-life workplace contexts. This research has several crucial implications: reaching the top requires a combination of multiple routes; conflating virtue and competence under the umbrella of "prestige" obscures their unique contributions; and dominance's positive effect on status is not universally applicable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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The abuse and excessive discharge of organic pollutants such as nitroaromatic compounds (NACs) have become a hot topic of concern for all humanity and society, and the development of fast, effective, and targeted technical means for detecting NACs also faces many challenges. Here, we reported a strontium-based metal-organic framework (MOF) {[Sr2(tcbpe)(H2O)4]}n (Sr-tcbpe), in which tcbpe represents deprotonated 4',4â´,4â³â´,4â´â´-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'biphenyl]-4-carboxylic acid)). In Sr-tcbpe, Sr-O polyhedron and deprotonated tcbpe4- ligand have a staggered connection to form a self-assembled three-dimensional network structure. In addition, it is found that Sr-tcbpe undergoes no luminescent color change when grinding under solvent protection, while mechanochromic fluorescence behavior is observed when grinding directly, leading to luminescent color changes from cyan to green (Sr-tcbpe-G). Additionally, Sr-tcbpe and Sr-tcbpe-G could selectively detect PNP, DNP, and TNP, and Sr-tcbpe achieves visual fluorescence sensing detection toward TNP at a limit of detection as low as 2.25 µM. Moreover, during the detection process, unexpectedly, TNP exhibits a selective etching effect on Sr-tcbpe, which could drill nano holes with different sizes on the surface area of MOF materials to a certain extent, achieving the conversion of chemical energy to mechanical energy. In addition, the successful preparation of a portable sensor Sr-tcbpe@gypsum block provides a platform for the perfect combination of mechanochromic fluorescence behavior and visualization detection toward TNP. It lays the foundation for the practical application of MOF materials in daily life.
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Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.
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Bactérias , Fermentação , RNA Ribossômico 16S , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , China , Microbiota , Filogenia , DNA Bacteriano/genética , Biodiversidade , Bebidas Alcoólicas/microbiologia , Bebidas Alcoólicas/análise , Microbiologia de Alimentos , Metagenoma , Alimentos Fermentados/microbiologiaRESUMO
The metal-free porphyrins protonation has gained interest over five decades because its structure modification and hardly monoacid intermediate isolation. Here, upon the hydrogen atom abstraction processes, one step diproptonated H3STTP(BF4)2 (STTP = 5,10,15,20-tetraphenyl-21-thiaporphyrin) (3) and stepwise protonated HS2TTPSbCl6 (5) and diprotonated H2S2TTP(BF4)2 (6) (S2TTP = 5,10,15,20-tetraphenyl-21,23-thiaporphyrin) compounds were obtained using HSTTP and S2TTP with oxidants. The closed-shell protonated compounds were fully characterized using XRD, UV-vis, IR and NMR spectra. In addition, the reduced 19π compounds [K(2,2,2)]HSTTP (2) and [K(2,2,2)]S2TTP (7) were synthesized by the ligands with reductant KC8 in THF solution. These two open-shell compounds were characterized with UV-vis, IR and EPR spectroscopies. The semiempirical ZINDO/S method was employed to analyze the HOMO/LUMO gap lever and identify the electronic transitions of the UV-vis spectra of the closed- and open-shell porphyrin compounds.
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Regulating mixed ligands to change the functional properties of metal-organic frameworks (MOFs) has been an important topic; especially, the structural changes have significant implications for the transformation of sensing response in different solvent channels. Herein, two [Cd (DPNDI) (NH2-BDC)0.5(NO3)]·2.25DMF (1) and [Cd(DPNDI)(NH2-AIPA)]·0.5DMF (2) (DPNDI = N,N-di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxydiimide, NH2-BDC = 2-amino terephthalic acid, NH2-AIPA = 5-aminoisophthalic acid) were synthesized by the solvothermal method. Structural analysis shows that complex 1 has a two-dimensional planar network structure and complex 2 exhibits a three-dimensional network structure, endowing its potential as an efficient fluorescence sensor for phenolic compound detection under different solvent environments. Both complexes showed high fluorescence quenching sensitivity to phenolics in a water medium. Conversely, complex 1 showed a fluorescence enhancement response to phenolic pollutants in an ethanol system with significantly low detection limits and recyclability. The detection limits were 0.58 µM for TNP, 1.3 µM for DNP, and 2.43 µM for PCP. In addition, the uncoordinated amino groups in the complexes promote them to exhibit excellent iodine adsorption performance. Especially, complex 2 can serve as an adsorbent for iodine in cyclohexane solution with better adsorption efficiency than that of complex 1, and its adsorption capacity can reach 505 mg/g. The mixed ligands regulation strategy of NDI-based MOFs will open up an effective avenue for the conversion of fluorescence signals in dual-solvent channels and play simultaneously important roles in multiple applications.
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Retraction of 'Multifunctional luminescence sensing and white light adjustment of lanthanide metal-organic frameworks constructed from the flexible cyclotriphosphazene-derived hexacarboxylic acid ligand' by Meng Wang et al., Dalton Trans., 2021, 50, 14618-14628, https://doi.org/10.1039/D1DT02560K.
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Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4 weeks, 20 Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.
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Disfunção Cognitiva , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Masculino , Feminino , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Imageamento por Ressonância Magnética , Resultado do Tratamento , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Memória Episódica , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagemRESUMO
Effective utilization of glucose, xylose, and acetate, common carbon sources in lignocellulose hydrolysate, can boost biomanufacturing economics. However, carbon leaks into biomass biosynthesis pathways instead of the intended target product remain to be optimized. This study aimed to enhance α-carotene production by optimizing glucose, xylose, and acetate utilization in a high-efficiency Corynebacterium glutamicum cell factory. Heterologous xylose pathway expression in C. glutamicum resulted in strain m4, exhibiting a two-fold increase in α-carotene production from xylose compared to glucose. Xylose utilization was found to boost the biosynthesis of pyruvate and acetyl-CoA, essential precursors for carotenoid biosynthesis. Additionally, metabolic engineering including pck, pyc, ppc, and aceE deletion, completely disrupted the metabolic connection between glycolysis and the TCA cycle, further enhancing α-carotene production. This strategic intervention directed glucose and xylose primarily towards target chemical production, while acetate supplied essential metabolites for cell growth recovery. The engineered strain C. glutamicum m8 achieved 30 mg/g α-carotene, 67% higher than strain m4. In fed-batch fermentation, strain m8 produced 1802 mg/L of α-carotene, marking the highest titer reported to date in microbial fermentation. Moreover, it exhibited excellent performance in authentic lignocellulosic hydrolysate, producing 216 mg/L α-carotene, 1.45 times higher than the initial strain (m4). These labor-division strategies significantly contribute to the development of clean processes for producing various valuable chemicals from lignocellulosic resources.
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Corynebacterium glutamicum , Engenharia Metabólica , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Glucose/metabolismo , Xilose/metabolismo , Carotenoides/metabolismo , Carbono/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/biossínteseRESUMO
INTRODUCTION: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior-temporal (AT) and posterior-medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI. METHODS: Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response. RESULTS: Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group. CONCLUSIONS: Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.
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Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana , Humanos , Masculino , Feminino , Estimulação Magnética Transcraniana/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Idoso , Disfunção Cognitiva/terapia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Lobo Temporal/fisiopatologia , Lobo Temporal/diagnóstico por imagemRESUMO
Lignocellulose presents a promising alternative to fossil fuels. Monitoring the mass and size changes of lignocellulosic particles without disrupting the process can assist in adjusting pretreatment and enzymatic hydrolysis, where conventional sieving methods fall short. A method utilizing focused beam reflectance measurement (FBRM) was developed to establish mathematical correlations between FBRM chord information (chord length and count) and particle characteristics (weight and size) quantified through sieving. Results indicate particle size exhibits a linear correlation with the square weighted median chord length (Lsqr) with R2 at 0.93. Further, real-time bulk particle mass can be predicted using Lsqr and chord count (R2 0.98). These correlations are applicable in range 53 µm to 358.5 µm. Real-time monitoring of enzymatic hydrolysis of corn stalks has demonstrated the practical applicability of FBRM. This study introduces a novel approach for online characterization of lignocellulosic particles, thereby enhancing lignocellulosic biorefineries.
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Lignina , Tamanho da Partícula , Lignina/química , Zea mays/química , Hidrólise , Biotecnologia/métodosRESUMO
The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.
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Antifúngicos , Mutagênese , Animais , Camundongos , Humanos , Virulência/genética , Antifúngicos/farmacologia , China , Temperatura Corporal , Modelos Animais de Doenças , Ascomicetos/genética , Ascomicetos/patogenicidade , Ascomicetos/efeitos dos fármacos , Caspofungina/farmacologia , Testes de Sensibilidade Microbiana , Fluconazol/farmacologia , Micoses/microbiologia , Farmacorresistência Fúngica Múltipla/genética , Farmacorresistência Fúngica/genéticaRESUMO
It can provide ideas for the use of uranium elements in the treatment of spent fuel from nuclear wastewater to explore the application potential of uranium element. Thus, it is necessary to research the structure and properties of a novel uranyl coordination polymer (CP) for uranium recovery and reuse. Herein, we designed and prepared a new uranyl CP U-CMNDI based on UO22+ and H2CMNDI (H2CMNDI = N, N'-bis(carboxymethyl)-1,4,5,8-naphthalenediimide). Structural analysis shows that two uranyl ions are connected by two parallel deprotonated CMNDI ligands to form a discrete uranyl dimer structure. U-CMNDI can act as a potential stimulus-responsive halide ion sensor by a fluorescence "turn on" response in water. The limit of detection for fluoride (F-), bromide (Br-), iodide (I-), and chloride (Cl-) is 5.00, 5.32, 5.49, and 5.73 µM, respectively. The fluorescence "turn on" behavior is based on the photoinduced electron transfer (PET) mechanism between halide ions and electron-deficient NDI cores. In addition, U-CMNDI demonstrates a color response to ultraviolet light, exhibiting reversible photochromic behavior with a notable color change. The color change mechanism can contribute to the PET process and the radical process.
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Formate as an ideal mediator between the physicochemical and biological realms can be obtained from electrochemical reduction of CO2 and used to produce bio-chemicals. Yet, limitations arise when employing natural formate-utilizing microorganisms due to restricted product range and low biomass yield. This study presents a breakthrough: engineered Corynebacterium glutamicum strains (L2-L4) through modular engineering. L2 incorporates the formate-tetrahydrofolate cycle and reverse glycine cleavage pathway, L3 enhances NAD(P)H regeneration, and L4 reinforces metabolic flux. Metabolic modeling elucidates C1 assimilation, guiding strain optimization for co-fermentation of formate and glucose. Strain L4 achieves an OD600 of 0.5 and produces 0.6 g/L succinic acid. 13C-labeled formate confirms C1 assimilation, and further laboratory evolution yields 1.3 g/L succinic acid. This study showcases a successful model for biologically assimilating formate in C. glutamicum that could be applied in C1-based biotechnological production, ultimately forming a formate-based bioeconomy.
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Biomassa , Corynebacterium glutamicum , Formiatos , Engenharia Metabólica , Ácido Succínico , Corynebacterium glutamicum/metabolismo , Formiatos/metabolismo , Engenharia Metabólica/métodos , Ácido Succínico/metabolismo , Fermentação , Modelos Biológicos , Glucose/metabolismoRESUMO
Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance.
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Fontes de Energia Bioelétrica , Biocombustíveis , Eletrólise , Anaerobiose , Fontes de Energia Bioelétrica/microbiologia , Reatores Biológicos , Metano/metabolismoRESUMO
Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 µM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.
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Desenho de Fármacos , Inibidores Enzimáticos , Herbicidas , Nicotiana , Proteínas de Plantas , Protoporfirinogênio Oxidase , Piridazinas , Protoporfirinogênio Oxidase/antagonistas & inibidores , Protoporfirinogênio Oxidase/metabolismo , Protoporfirinogênio Oxidase/química , Protoporfirinogênio Oxidase/genética , Piridazinas/química , Piridazinas/farmacologia , Herbicidas/farmacologia , Herbicidas/química , Herbicidas/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Nicotiana/metabolismo , Nicotiana/enzimologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Simulação de Acoplamento Molecular , Estrutura Molecular , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , CinéticaRESUMO
Reaction of tetraphenyl-21-thiaporphyrin (HSTPP) with cobalt salt yields a pentacoordinated high-spin 3/2 [CoIICl(STTP)] (1). Through ion exchange, a roughly square-planar-geometry low-spin 1/2 CoIISTTP(BArF24) (2) complex was isolated. These two paramagnetic precursors were examined by single X-ray diffraction, nuclear magnetic resonance, electron paramagnetic resonance, superconducting quantum interference device, and density functional theory calculations. These two allowed the development of one electron reduction and oxidation to give [CoI(STTP)] (3), [CoIII(STTP)Cl(CH3CN)](BF4) (4), and [CoIII(STTP)Cl2] (5). The products of the chemical redox reactions were isolated and fully characterized. In addition, the reactivity of [CoIICl(STTP)] (1) was examined by azide (N3), cyanate (OCN), and thiocyanate (SCN) and featured a preferential N-coordination to the cobalt metal.
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BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.
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Neoplasias Mamárias Animais , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Camundongos , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Dano ao DNA , Reparo do DNA , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologiaRESUMO
Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.
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Aldosterona , Hiperaldosteronismo , Hipertensão , Renina , Espironolactona , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Aldosterona/sangue , Espironolactona/uso terapêutico , Renina/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/terapia , Hiperaldosteronismo/tratamento farmacológico , Idoso , Adulto , Doenças Cardiovasculares/etiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pressão SanguíneaRESUMO
Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE176 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.
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Solanaceae , Solanum lycopersicum , Solanum lycopersicum/genética , Domesticação , Melhoramento Vegetal , EsteroidesRESUMO
A pair of isomeric Py-BT-COFs with the same composition, but slightly different atomic arrangements, were designed and synthesized. The minute structural variations of the Py-BT-COF isomers generated significantly different redox and photophysical properties and correspondingly led to different photocatalytic manifestations in H2 evolution and rhodamine B degradation.