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1.
Behav Brain Res ; 476: 115218, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39182624

RESUMO

Depression is associated with functional brain impairments, although comprehensive studies remain limited. This study reviews neural mechanisms underlying cognitive impairment in depression and identifies associated activation abnormalities in brain regions. The study also explores the underlying neural processes of cognitive benefits of exercise intervention for depression. Executive function impairments, including working memory, inhibitory control and cognitive flexibility are associated with frontal cortex and anterior cingulate areas, especially dorsolateral prefrontal cortex. Depression is associated with certain neural impairments of reward processing, especially orbitofrontal cortex, prefrontal cortex, nucleus accumbens and other striatal regions. Depressed patients exhibit decreased activity in the hippocampus during memory function. Physical exercise has been found to enhance memory function, executive function, and reward processing in depression patients by increasing functional brain regions and the brain-derived neurotrophic factor (BDNF) as a nutritional factor also plays a key role in exercise intervention. The study documents neurophysiological mechanisms behind exercise intervention's improved functions. In summary, the study provides insights into neural mechanisms underlying cognitive impairments in depression and the effectiveness of exercise as a treatment.


Assuntos
Disfunção Cognitiva , Depressão , Terapia por Exercício , Humanos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/etiologia , Terapia por Exercício/métodos , Depressão/terapia , Depressão/fisiopatologia , Exercício Físico/fisiologia , Função Executiva/fisiologia , Encéfalo/fisiopatologia , Encéfalo/metabolismo , Recompensa
2.
Angew Chem Int Ed Engl ; : e202415208, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363672

RESUMO

Creating new functional materials that efficiently support noble metal catalysts is important and in high demand. Herein, we develop a self-polycondensation flux synthesis strategy that can produce olefin-linked covalent organic framework (COF) platforms with high crystallinity and porosity as the supports of Pd nanoparticles for electrocatalytic nitrogen reduction reaction (ENRR). A series of "two in one" monomers integrating aldehyde and methyl reactive groups are rationally designed to afford COFs with square-shaped pores and ultrahigh chemical stability (e.g., strong acid or alkali environments for >1 month). Functionalizing Fluorine significantly boosts the hydrophobicity of fluoro-functionalized COFs, which can inhibit the competing hydrogen evolution reaction (HER) and enhance ENRR performances. The COFs loading Pd nanoparticles show high NH3 production yields up to 90.0 ± 2.6 µg·h-1·mgcat.-1 and the faradaic efficiency of 44% at -0.2 V versus reversible hydrogen electrode, the best comprehensive performance among all reported COFs. Meanwhile, the catalysts are easy to recover and recycle, as demonstrated by their use for 15 cycles and 17 hours, with good performance retention. This work not only provides a new synthesis strategy for olefin-linked COFs, but also paves a new avenue for the design of highly efficient ENRR catalysts.

3.
J Chem Phys ; 161(13)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39351946

RESUMO

Two-dimensional transition metal dichalcogenides possess a significant specific surface area, adjustable bandgaps, and excellent optical absorption properties, rendering them highly conducive to photocatalytic applications. Herein, a MoS2-like 2D superatomic Cd6S2 monolayer is predicted, wherein the octahedral Cd6 superatom unit connects with S atoms via six vertices. Chemical bonding analysis reveals that the remarkable dynamic, thermal, and mechanical stability of the Cd6S2 monolayer results from the covalent Cd-S bonds and the 6-center 8-electron (6c-8e) delocalized bond within the Cd6 core, which ensures the chemical octet rule for both the S atom and the Cd6 superatom. Demonstrating notable optical absorption coefficients and a strain-tuned energy band structure, the Cd6S2 monolayer emerges as a viable candidate for catalyzing the solar-powered splitting of water. This work offers an alternative avenue to modify or improve the properties of 2D materials for photocatalytic applications through superatomic assembly.

4.
Nanoscale ; 16(37): 17433-17441, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39219367

RESUMO

Bandgap engineering of graphene is of great significance for its potential applications in electronic devices. Herein, we used a sandwich compound Cr(C6H6)2 as the building block to construct Cr-intercalated bilayer graphene (BLG), namely a C12Cr monolayer. Chemical bonding analysis reveals that strong d-π interaction ensures π electrons of the graphene layers and d orbitals of the Cr atoms localized in C6CrC6 units to achieve the favored 18-electron rule, thus leading to a bandgap of 0.24 eV. Subsequently, a C48Cr monolayer with lower proportion of Cr is further designed using Cr(C54H18)2 as building units, where a newly developed two-dimensional (2D) superatomic-molecule theory is introduced to rationalize its electronic structure. The C48Cr monolayer not only satisfies the 18-electron rule, but also localizes extra π electrons to form two layers of 2D superatomic crystals composed of 2D superatoms (◊O and ◊N), resulting in a wider bandgap of 0.74 eV. This work opens an effective avenue to modulate the bandgap of BLG via combining the 18-electron rule and the 2D superatomic-molecule theory.

5.
Circulation ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229700

RESUMO

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

6.
3 Biotech ; 14(9): 204, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39161880

RESUMO

Heat shock protein 90 (HSP90) is important for many organisms, including plants. Based on the whole genome information, the gene number, gene structure, evolutionary relationship, protein structure, and active site of the HSP90 gene family in Rosa chinensis and Rubus idaeus were determined, and the expression of the HSP90 gene under salt, and drought stresses in two rose varieties Wangxifeng and Sweet Avalanche were analyzed. Six and eight HSP90 genes were identified from R. chinensis and Ru. idaeus, respectively. Phylogenetic analysis revealed that the analyzed genes were divided into two Groups and four subgroups (Classes 1a, 1b, 2a, and 2b). Although members within the same classes displayed highly similar gene structures, while the gene structures and conserved domains of Group 1 (Class 1a and 1b) and the Group 2 (Class 2a and 2b) are different. Tandem and segmental duplication genes were found in Ru. idaeus, but not in R. chinensis, perhaps explaining the difference in HSP90 gene quantity in the two analyzed species. Analysis of cis-acting elements revealed abundant abiotic stress, photolight-response, and hormone-response elements in R. chinensis HSP90s. qRT-PCR analysis suggested that RcHSP90-1-1, RcHSP90-5-1 and RcHSP90-6-1 in Sweet Avalanche and Wangxifeng varieties played important regulatory roles under salt and drought stress. The analysis of protein structure and active sites indicate that the potential different roles of RcHSP90-1-1, RcHSP90-5-1, and RcHSP90-6-1 in salt and drought stresses may come from the differences of corresponding protein structures and activation sites. These data will provide information for the breeding of rose varieties with high stress resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04052-0.

7.
J Diabetes ; 16(8): e13589, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39136595

RESUMO

BACKGROUND: The triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). METHODS: A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization. RESULTS: During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. CONCLUSION: Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.


Assuntos
Biomarcadores , Glicemia , Proteína C-Reativa , Triglicerídeos , Humanos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Glicemia/análise , Glicemia/metabolismo , Biomarcadores/sangue , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Prognóstico , Fatores de Risco , Seguimentos , Doença Crônica
8.
Nat Protoc ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112651

RESUMO

Covalent organic frameworks (COFs) are crystalline porous polymers constructed from organic building blocks into ordered two- or three-dimensional networks through dynamic covalent bonds. Attributed to their high porosity, well-defined structure, tailored functionality and excellent chemical stability, COFs have been considered ideal sorbents for various separation applications. The synthesis of COFs mainly employs the solvothermal method, which usually requires organic solvents in sealed Pyrex tubes, resulting in unscalable powdery products and environmental pollution that seriously limits their practical applications. Herein, our protocol focuses on an emerging synthesis method for COFs based on organic flux synthesis without adding solvents. The generality of this synthesis protocol has been applied in preparing various types of COFs, including olefin-linked, imide-linked, Schiff-based COFs on both gram and kilogram scales. Furthermore, organic flux synthesis avoids the disadvantages of solvothermal synthesis and enhances the crystallization and porosity of COFs. Typically, COF synthesis takes 3-5 d to complete, and subsequent washing procedures leading to pure COFs need 1 d. The procedure for kilogram-scale production of COFs with commercially available monomers is also provided. The resulting COFs are suitable for separation applications, particularly as adsorbent materials for industrial gas separation and water treatment applications. The protocol is suited for users with prior expertise in the synthesis of inorganic materials and porous organic materials.

9.
Theranostics ; 14(10): 3945-3962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994035

RESUMO

Rationale: NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. Methods: We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR. Lastly, we accessed the effect of decreased NLRP3 levels on ovariectomized (OVX) rats. To specifically deliver NLRP3 siRNA to osteoblasts, we constructed NLRP3 siRNA wrapping osteoblast-specific aptamer (CH6)-functionalized lipid nanoparticles (termed as CH6-LNPs-siNLRP3). Results: We found that the levels of NLRP3 inflammasome were significantly increased in patients with PMOP, and were negatively correlated with estradiol levels. NLRP3 knock-down influenced signal pathways including immune system process, interferon signal pathway. Notably, of the top ten up-regulated genes in NLRP3-reduced osteoblasts, nine genes (except Mx2) were enriched in immune system process, and five genes were related to interferon signal pathway. The in vitro results showed that CH6-LNPs-siNLRP3 was relatively uniform with a dimeter of 96.64 ± 16.83 nm and zeta potential of 38.37 ± 1.86 mV. CH6-LNPs-siNLRP3 did not show obvious cytotoxicity and selectively delivered siRNA to bone tissue. Moreover, CH6-LNPs-siNLRP3 stimulated osteoblast differentiation by activating ALP and enhancing osteoblast matrix mineralization. When administrated to OVX rats, CH6-LNPs-siNLRP3 promoted bone formation and bone mass, improved bone microarchitecture and mechanical properties by decreasing the levels of NLRP3, IL-1ß and IL-18 and increasing the levels of OCN and Runx2. Conclusion: NLRP3 inflammasome may be a new biomarker for PMOP diagnosis and plays a key role in the pathology of PMOP. CH6-LNPs-siNLRP3 has potential application for the treatment of PMOP.


Assuntos
Inflamassomos , Lipossomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Nanopartículas , Osteoblastos , Osteoporose Pós-Menopausa , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Feminino , Humanos , Ratos , Inflamassomos/metabolismo , Nanopartículas/química , Osteoporose Pós-Menopausa/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ratos Sprague-Dawley , RNA Interferente Pequeno/administração & dosagem , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/administração & dosagem , Modelos Animais de Doenças , Pessoa de Meia-Idade , Ovariectomia
10.
Nat Commun ; 15(1): 6040, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39019927

RESUMO

The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.


Assuntos
Antibacterianos , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Camundongos , Simulação de Acoplamento Molecular , Farmacorresistência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino
11.
Anal Bioanal Chem ; 416(23): 5121-5131, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39046504

RESUMO

Accurate measurement of serum glycocholic acid (GCA) is crucial for evaluating the activity of chronic hepatitis. Moreover, GCA is a novel identified biomarker for hepatocellular carcinoma. Although some laboratories have used the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure GCA in recent years, the problem of potential interference of GCA analogues has not been solved well yet. Neither reference measurement procedures nor reference materials for GCA have been listed in the Joint Committee for Traceability in Laboratory Medicine (JCTLM) database. For standardization of GCA, it is urgent to establish a candidate measurement procedure for GCA. In this study, a candidate reference measurement procedure for the quantification of GCA in human serum based on isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) by a two-step sample pretreatment of protein precipitation and MAX solid-phase extraction was developed and validated. GCA can be completely separated from its structural analogues with gradient elution in 9 min compared with short time gradients published in previous literature by Huang's group. Method validation indicated perfect quantitation precision with intra-day and inter-day values that were ≤1.30% and ≤1.80%, respectively. The method showed excellent linearity with high regression coefficients (R2 > 0.999) over a range of 0.92 ng/g-38.38 µg/g and perfect recoveries at three spiked levels (99.87-100.43%). No interference, matrix effect, and carryover were observed. Moreover, the cRMP was successfully applied to measure GCA in serum samples and compared with two immunoassays in a clinical laboratory. As a candidate reference method, this method can promote a GCA standardization program.


Assuntos
Ácido Glicocólico , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Ácido Glicocólico/sangue , Padrões de Referência , Limite de Detecção , Reprodutibilidade dos Testes , Técnicas de Diluição do Indicador , Extração em Fase Sólida/métodos
12.
Int J Mol Sci ; 25(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39000365

RESUMO

Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.


Assuntos
Afídeos , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Sorghum , Estresse Fisiológico , Triazóis , Sorghum/genética , Sorghum/metabolismo , Afídeos/genética , Afídeos/fisiologia , Animais , Triazóis/farmacologia , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Arabidopsis/genética , Regiões Promotoras Genéticas , Família Multigênica , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Filogenia , Doenças das Plantas/parasitologia , Doenças das Plantas/genética , Genoma de Planta
13.
Virology ; 597: 110156, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38981316

RESUMO

This study aims to elucidate the role of TIP30 (30 KDa HIV-1 TAT-Interacting Protein) in the progression of coxsackievirus B3 (CVB3)-induced viral myocarditis. TIP30 knockout and wildtype mice were intraperitoneally infected with CVB3 and evaluated at day 7 post-infection. HeLa cells were transfected with TIP30 lentiviral particles and subsequently infected with CVB3 to evaluate viral replication, cellular pathogenesis, and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Deletion of the TIP30 gene heightened heart virus titers and mortality rates in mice with CVB3-induced myocarditis, exacerbating cardiac damage and fibrosis, and elevating pro-inflammatory factors level. In vitro experiments demonstrated the modulation of mTORC1 signaling by TIP30 during CVB3 infection in HeLa cells. TIP30 overexpression mitigated CVB3-induced cellular pathogenesis and VP1 expression, with rapamycin, an mTOR1 inhibitor, reversing these effects. These findings suggest TIP30 plays a critical protective role against CVB3-induced myocarditis by regulating mTORC1 signaling.


Assuntos
Infecções por Coxsackievirus , Enterovirus Humano B , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos Knockout , Miocardite , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Infecções por Coxsackievirus/virologia , Infecções por Coxsackievirus/metabolismo , Modelos Animais de Doenças , Enterovirus Humano B/fisiologia , Células HeLa , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Miocardite/virologia , Miocardite/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Replicação Viral
14.
Adv Healthc Mater ; 13(23): e2400943, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38856967

RESUMO

Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells. However, the significant biological barrier presented by the tumor microenvironment imposes greater demands and challenges for drug design. This study constructs the multifunctional nanocomposite ZnFe2O4@TiO2@CHC@Orl-FA (ZTCOF), which has great potential to overcome the aforementioned drawbacks. ZnFe2O4@TiO2 could produce 1O2 with ultrasound, and stimulate the Fenton-like conversion of endogenous H2O2 to ·OH, achieving a combined therapeutic effect of sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Orl (Orlistat) and CHC (α-cyano-4-hydroxycinnamic acid) not only block tumor cell energy metabolism but also increase sensitivity to reactive oxygen species, enhancing the cytotoxic effect on tumor cells. Furthermore, combining the treatment strategies with FMD condition control can further inhibit cancer cell energy metabolism, achieving significant synergistic anti-tumor therapy. Both in vitro and in vivo experiments confirm that ZTCOF with SDT/CDT/starvation can achieve effective tumor suppression and destruction. This work provides theoretical and technical support for anti-tumor multimodal synergistic therapy.


Assuntos
Jejum , Nanocompostos , Nanocompostos/química , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Titânio/química , Titânio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Nutrientes , Dieta , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia , Antineoplásicos/farmacologia , Antineoplásicos/química , Terapia por Ultrassom/métodos
15.
Microbiol Spectr ; 12(8): e0377423, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38916358

RESUMO

Stripe rust of wheat is caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Breeding durably resistant wheat varieties by disrupting the susceptibility (S) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of Pst. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to Pst have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of "MX169" and high-resistance wheat "Zhong4" at 24, 48, and 120 h post-inoculation (hpi) with Pst. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169's response to Pst. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst. IMPORTANCE: Our study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.


Assuntos
Resistência à Doença , Doenças das Plantas , Puccinia , Transcriptoma , Triticum , Triticum/microbiologia , Triticum/genética , Triticum/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Doenças das Plantas/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Basidiomycota/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
J Am Chem Soc ; 146(27): 18387-18395, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38904843

RESUMO

Flexible metal-organic materials (FMOMs) with stepped isotherms can offer enhanced working capacity in storage applications such as adsorbed natural gas (ANG) storage. Unfortunately, whereas >1000 FMOMs are known, only a handful exhibit methane uptake of >150 cm3/cm3 at 65 atm and 298 K, conditions relevant to ANG. Here, we report a double-walled 2-fold interpenetrated diamondoid (dia) network, X-dia-6-Ni, [Ni2L4(µ-H2O)]n, comprising a new azo linker ligand, L- (L- = (E)-3-(pyridin-4-yldiazenyl)benzoate) and 8-connected dinuclear molecular building blocks. X-dia-6-Ni exhibited gas (CO2, N2, CH4) and liquid (C8 hydrocarbons)-induced reversible transformations between its activated narrow-pore ß phase and γ, a large-pore phase with ca. 33% increase in unit cell volume. Single-crystal X-ray diffraction (SCXRD) studies of the as-synthesized phase α, ß, and γ revealed that structural transformations were enabled by twisting of the azo moiety and/or deformation of the MBB. Further insight into these transformations was gained from variable temperature powder XRD and in situ variable pressure powder XRD. Low-temperature N2 and CO2 sorption revealed stepped Type F-II isotherms with saturation uptakes of 422 and 401 cm3/g, respectively. X-dia-6-Ni exhibited uptake of 200 cm3/cm3 (65 atm, 298 K) and a high CH4 working capacity of 166 cm3/cm3 (5-65 bar, 298 K, 33 cycles), the third highest value yet reported for an FMOM and the highest value for an FMOM with a Type F-II isotherm.

17.
Free Radic Biol Med ; 221: 215-224, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38796028

RESUMO

BACKGROUND: Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood. This study examined the role of mitoGSH in regulating NET-induced ferroptosis of smooth muscle cells (SMCs) during AAA formation. METHODS: Concentrations of NET markers were tested in plasma samples. Western blotting and immunofluorescent staining were performed to detect the expression and localization of NET and ferroptosis markers in tissue samples. The role of NETs and SMC ferroptosis during AAA formation was investigated using peptidyl arginine deiminase 4 gene (Padi4) knockout or treatment with a PAD4 inhibitor, ferroptosis inhibitor or activator in an angiotensin II-induced AAA mouse model. The regulatory effect of SLC25A11, a mitochondrial glutathione transporter, on mitoGSH and NET-induced ferroptosis of SMCs was investigated using in vitro and in vivo experiments. Transmission electron microscopy was used to detect mitochondrial damage. Blue native polyacrylamide gel electrophoresis was used to analyze the dimeric and monomeric forms of the protein. RESULTS: Significantly elevated levels of NETosis and ferroptosis markers in aortic tissue samples were observed during AAA formation. Specifically, NETs promoted AAA formation by inducing ferroptosis of SMCs. Subsequently, SLC25A11 was identified as a potential biomarker for evaluating the clinical prognosis of patients with AAA. Furthermore, NETs decreased the stability and dimerization of SLC25A11, leading to the depletion of mitoGSH. This depletion induced the ferroptosis of SMCs and promoted AAA formation. CONCLUSION: During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11, leading to the depletion of mitoGSH and subsequent activation of NET-induced ferroptosis of SMCs. Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA.


Assuntos
Aneurisma da Aorta Abdominal , Armadilhas Extracelulares , Ferroptose , Glutationa , Mitocôndrias , Miócitos de Músculo Liso , Proteína-Arginina Desiminase do Tipo 4 , Ferroptose/genética , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/induzido quimicamente , Animais , Camundongos , Armadilhas Extracelulares/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/genética , Humanos , Glutationa/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Proteína-Arginina Desiminase do Tipo 4/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Masculino , Modelos Animais de Doenças , Estresse Oxidativo , Neutrófilos/metabolismo , Neutrófilos/patologia , Camundongos Knockout , Camundongos Endogâmicos C57BL , Angiotensina II/metabolismo
18.
Bioresour Technol ; 403: 130859, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777228

RESUMO

The effects of microbial agents on nitrogen (N) conversion during cotton straw composting remains unclear. In this study, inoculation increased the germination index and total nitrogen (TN) by 24-29 % and 7-10 g/kg, respectively. Inoculation enhanced the abundance of nifH, glnA, and amoA and reduced that of major denitrification genes (nirK, narG, and nirS). Inoculation not only produced high differences in the assembly process and strong community replacement but also weakened environmental constraints. Partial least squares path modelling demonstrated that enzyme activity and bacterial community were the main driving factors influencing TN. In addition, network analysis and the random forest model showed distinct changing patterns of bacterial communities after inoculation and identified keystone microorganisms in maintaining network complexity and synergy, as well as system function to promote nitrogen preservation. Findings provide a novel perspective on high-quality resource recovery of agricultural waste.


Assuntos
Bactérias , Compostagem , Gossypium , Nitrogênio , Gossypium/microbiologia , Gossypium/genética , Compostagem/métodos , Bactérias/genética , Genes Bacterianos , Desnitrificação , Microbiologia do Solo , Solo/química
19.
Angew Chem Int Ed Engl ; 63(28): e202405769, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38656752

RESUMO

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

20.
Clin Microbiol Rev ; 37(2): e0016123, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38634634

RESUMO

SUMMARYLincosamides constitute an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. However, due to the misuse of lincosamide and co-selection pressure, the resistance to lincosamide has become a serious concern. It is urgently needed to carefully understand the phenomenon and mechanism of lincosamide resistance to effectively prevent and control lincosamide resistance. To date, six mobile lincosamide resistance classes, including lnu, cfr, erm, vga, lsa, and sal, have been identified. These lincosamide resistance genes are frequently found on mobile genetic elements (MGEs), such as plasmids, transposons, integrative and conjugative elements, genomic islands, and prophages. Additionally, MGEs harbor the genes that confer resistance not only to antimicrobial agents of other classes but also to metals and biocides. The ultimate purpose of discovering and summarizing bacterial resistance is to prevent, control, and combat resistance effectively. This review highlights four promising strategies, including chemical modification of antibiotics, the development of antimicrobial peptides, the initiation of bacterial self-destruct program, and antimicrobial stewardship, to fight against resistance and safeguard global health.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Lincosamidas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Lincosamidas/farmacologia , Lincosamidas/uso terapêutico , Humanos , Farmacorresistência Bacteriana/genética , Bactérias/efeitos dos fármacos , Bactérias/genética
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