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1.
Clin Exp Pharmacol Physiol ; 51(7): e13900, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843865

RESUMO

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.


Assuntos
Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia
2.
J Ethnopharmacol ; 333: 118411, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38824980

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown. AIM OF THE STUDY: The primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC. MATERIALS AND METHODS: The protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16S rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a "pseudo-sterile" mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC. RESULTS: XLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression. CONCLUSION: Our findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.

3.
Appl Opt ; 63(14): 3991-3997, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856363

RESUMO

Due to the substantial contrast in the output beam quality between the two directions of the semiconductor laser, efficiently coupling the beam directly into the fiber is difficult. In this study, an efficient shaping method based on step multiplexing of misaligned step prisms is proposed and investigated systematically. First, multiple laser stacks eliminate dark areas to improve the beam quality through the full utilization of the transmission and reflection surfaces of the misaligned stepped prisms, which also improves the efficiency of the stepped prisms. It also simultaneously realizes laser wavelength combining based on reflective surface multiplexing without affecting the quality of the beam on the premise of improving the output power. Finally, the whole beam shaping system is completed without using cut-transform-rearranging prisms. The method couples four groups of laser stacks into a single fiber with a fiber diameter of 400 µm and a numerical aperture of 0.22. It can be seen from the computer-simulated model outputs that the final fiber output power can reach 2255.4 W and that the system as a whole has a light-to-light translation rate of 88.1%.

4.
Nat Neurosci ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858608

RESUMO

The cortical patterning principle has been a long-standing question in neuroscience, yet how this translates to macroscale functional specialization in the human brain remains largely unknown. Here we examine age-dependent differences in resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks during early life, using a primarily cross-sectional but also longitudinal approach. We show that thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically influenced axonal projection. This pattern changes in childhood, when connectivity is established with the salience network, while decoupling externally and internally oriented functional systems. A developmental simulation using generative network models corroborated these findings, demonstrating that thalamic connectivity contributes to developing key features of the mature brain, such as functional segregation and the sensory-association axis, especially across 12-18 years of age. Our study suggests that the thalamus plays an important role in functional specialization during development, with potential implications for studying conditions with compromised internal and external processing.

5.
Gastroenterol Rep (Oxf) ; 12: goae057, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846986

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia. Methods: GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap. Results: We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P < 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported. Conclusions: Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.

6.
Heliyon ; 10(10): e30896, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38765026

RESUMO

Lower respiratory tract infections (LRTIs) represent some of the most globally prevalent and detrimental diseases. Metagenomic next-generation sequencing (mNGS) technology has effectively addressed the requirement for the diagnosis of clinical infectious diseases. This study aimed at identifying and classifying opportunistic pathogens from the respiratory tract-colonizing microflora in LRTI patients using data acquired from mNGS analyses. A retrospective study was performed employing the mNGS data pertaining to the respiratory samples derived from 394 LRTIs patients. Linear discriminant analysis effect size (LEfSe) analysis was conducted to discern the discriminant bacteria. Receiver operating characteristic curves (ROC) were established to demonstrate discriminant bacterial behavior to distinguish colonization from infection. A total of 443 discriminant bacteria were identified and segregated into three cohorts contingent upon their correlation profiles, detection frequency, and relative abundance in order to distinguish pathogens from colonizing microflora. Among them, 119 emerging opportunistic pathogens (cohort 2) occupied an average area under the curve (AUC) of 0.976 for exhibiting the most prominent predictability in distinguishing colonization from infection, 39 were colonizing bacteria (cohort 1, 0.961), and 285 were rare opportunistic pathogens (cohort 3, 0.887). The LTRIs patients appeared modular in the form of cohorts depicting complex microbial co-occurrence networks, reduced diversity, and a high degree of antagonistic interactions in the respiratory tract microbiome. The study findings indicate that therapeutic interventions should target interaction networks rather than individual microbes, providing an innovative perspective for comprehending and combating respiratory infections. Conclusively, this study reports a profile of LRTIs-associated bacterial colonization and opportunistic pathogens in a relatively large-scale cohort, which might serve as a reference panel for the interpretation of mNGS results in clinical practice.

7.
Sci Rep ; 14(1): 11981, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796634

RESUMO

Reservoir flood control scheduling is a challenging optimization task, particularly due to the complexity of various constraints. This paper proposes an innovative algorithm design approach to address this challenge. Combining the basic walrus optimization algorithm with the adaptive ε-constraint method and introducing the SPM chaotic mapping for population initialization, spiral search strategy, and local enhancement search strategy based on Cauchy mutation and reverse learning significantly enhances the algorithm's optimization performance. On this basis, innovate an adaptive approach ε A New Algorithm for Constraints and Multi Strategy Optimization Improvement (ε-IWOA). To validate the performance of the ε-IWOA algorithm, 24 constrained optimization test functions are used to test its optimization capabilities and effectiveness in solving constrained optimization problems. Experimental results demonstrate that the ε-IWOA algorithm exhibits excellent optimization ability and stable performance. Taking the Taolinkou Reservoir, Daheiting Reservoir, and Panjiakou Reservoir in the middle and lower reaches of the Luanhe River Basin as a case study, this paper applies the ε-IWOA algorithm to practical reservoir scheduling problems by constructing a three-reservoir flood control scheduling system with Luanxian as the control point. A comparative analysis is conducted with the ε-WOA, ε-DE and ε-PSO (particle swarm optimization) algorithms.The experimental results indicate that ε-IWOA algorithm performs the best in optimization, with the occupied flood control capacity of the three reservoirs reaching 89.32%, 90.02%, and 80.95%, respectively. The control points in Luan County can reduce the peak by 49%.This provides a practical and effective solution method for reservoir optimization scheduling models. This study offers new ideas and solutions for flood control optimization scheduling of reservoir groups, contributing to the optimization and development of reservoir scheduling work.

8.
Res Sq ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38699356

RESUMO

The brain's white matter connections are thought to provide the structural basis for its functional connections between distant brain regions but how our brain selects the best structural routes for effective functional communications remains poorly understood. In this study, we propose a Unified Structural and Functional Connectivity (USFC) model and use an "economical assumption" to create the brain's first "traffic map" reflecting how frequently each structural connection segment of the brain is used to achieve the global functional communication system. The resulting USFC map highlights regions in the subcortical, default-mode, and salience networks as the most heavily traversed nodes and a midline frontal-caudate-thalamus-posterior cingulate-visual cortex corridor as the backbone of the whole brain connectivity system. Our results further revealed a striking negative association between structural and functional connectivity strengths in routes supporting negative functional connections as well as much higher efficiency metrics in the USFC connectome when compared to structural and functional ones alone. Overall, the proposed USFC model opens up a new window for effective brain connectome modeling and provides a considerable leap forward in brain mapping efforts for a better understanding of the brain's fundamental communication mechanisms.

9.
J Sci Food Agric ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716684

RESUMO

BACKGROUND: Yangjiang douchi (YD) is a traditional fermented soybean product, which is popular in Chinese cuisine for its unique flavor. However, due to its high salt content and unstable flavor, its competitiveness in the international market is gradually weakening. Microorganisms have a key role in the production process of YD because it is a fermented food but the effect of microorganisms on the volatile compounds of YD is also not currently clear. RESULTS: In this paper, aroma compounds and microbial diversity in different fermentation stages of YD were analyzed using gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and IlluminaMiseq system sequencing. A total of 78 aroma-active compounds were detected throughout the fermentation process and they influenced the formation of flavor in YD. Fungi flora were relatively single in YD, and bacteria were rich and varied. A total of 418 species of bacteria were present during fermentation, with unclassified_Staphylococcus, Staphylococcus_kloosii, and Bacillus_velezensis_Bacillus predominating. There were 25 species of fungi at the species level, and Aspergillus minisclerotigenes (OTU 4) played a dominant role in the whole fermentation process. CONCLUSION: Staphylococcus and Bacillus in the bacterial genus were strongly correlated with most flavor compounds detected, and A. minisclerotigenes in the fungi were more relevant to flavor compounds. This research provides a theoretical basis for the enhancement of the flavor of traditional fermented douchi in China. © 2024 Society of Chemical Industry.

10.
ACS Chem Biol ; 19(5): 1151-1160, 2024 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-38648729

RESUMO

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.


Assuntos
Ferritinas , Campos Magnéticos , Espécies Reativas de Oxigênio , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células HEK293 , Ferritinas/metabolismo , Ferritinas/química , Ferro/metabolismo , Cálcio/metabolismo
11.
ACS Biomater Sci Eng ; 10(5): 2995-3005, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38654432

RESUMO

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.


Assuntos
Cálcio , Sobrevivência Celular , Hipertermia Induzida , Campos Magnéticos , Espécies Reativas de Oxigênio , Canais de Cátion TRPV , Cálcio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPV/metabolismo , Humanos , Hipertermia Induzida/métodos , Temperatura , Ferritinas/metabolismo , Hipertermia/metabolismo
12.
BMC Oral Health ; 24(1): 469, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632580

RESUMO

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. CONCLUSION: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Humanos , Metanálise em Rede , Dióxido de Carbono/uso terapêutico , Conforto do Paciente , Leucoplasia Oral , Lasers de Estado Sólido/uso terapêutico
13.
Micromachines (Basel) ; 15(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38675282

RESUMO

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via laser beam power bed fusion (LB-PBF), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 °C for 1 h. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also influencing the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 h and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving LB-PBF and heat treatment.

14.
Asian J Psychiatr ; 96: 104008, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38598933

RESUMO

BACKGROUND: The role of rumination in depression remains controversial. We aimed to establish the ruminative tendency style theory (RTST), discuss the occurrence of depression in adolescents with rumination as the core, and explore the different associations between adolescent ruminative tendency, ruminative style, and depression. METHODS: This study employed an online questionnaire survey of 1110 Chinese adolescents aged 12-17 years, assessing ruminative tendency, ruminative style, stressful life events, depressive state, depressive trait, the Big Five personality traits, and social support. Conditional process analysis was used to test the chain mediation effect with Ruminative Style as a moderator. After screening for the predictor variables, a logistic regression risk prediction model was established and validated internally. RESULTS: The chain mediation effect of ruminative tendency and depressive trait between stressful life events and depressive state was significant, with the indirect effect accounting for 63.4%. Ruminative Style negatively moderated the relationship between Ruminative Tendency and Depressive Trait (ß=-0.053,P<0.001). The risk prediction model for depressive state showed good calibration and clinical utility. Area under the curve values for the validation and training sets were 0.926 and 0.927, respectively. CONCLUSION: Different associations may exist between adolescent ruminative tendency, ruminative style, and depression, and the proposal of ruminative style is of great significance for intervention in adolescent depression.


Assuntos
Depressão , Humanos , Adolescente , Feminino , Masculino , Criança , Depressão/epidemiologia , Ruminação Cognitiva/fisiologia , China/epidemiologia , Comportamento do Adolescente , Transtorno Depressivo/epidemiologia
15.
Structure ; 32(6): 780-794.e5, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38503293

RESUMO

Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease AtARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in AtARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of AtARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Modelos Moleculares , Humanos , Arabidopsis/metabolismo , Arabidopsis/enzimologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , DNA/metabolismo , DNA/química , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/química , Furanos/metabolismo , Furanos/química , Ligação Proteica
16.
Environ Toxicol ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470012

RESUMO

Recurrence of breast cancer may be due to the presence of breast cancer stem cells (BCSC). Abnormal tumor cell growth is closely associated with increased reactive oxygen species (ROS) and disruption of redox homeostasis, and BCSCs exhibit low levels of ROS. The detailed mechanism between the low levels of ROS in BCSCs and their maintenance of stemness characteristics has not been reported. A growing number of studies have shown that tumor development is often accompanied by metabolic reprogramming, which is an important hallmark of tumor cells. As the first rate-limiting enzyme of pentose phosphate pathway (PPP), the expression of G6PD is precisely regulated in tumor cells, and there is a certain correlation between PPP and BCSCs. MiR-375 has been shown to inhibit stem cell-like properties in breast cancer, but the exact mechanism is not clear. Here, KLF5, as a transcription factor, was identified to bind to the promoter of G6PD to promote its expression, whereas miR-375 inhibited the expression of KLF5 by binding to the 3'UTR region of KLF5 mRNA and thus reduced the expression of G6PD expression, inhibits PPP to reduce NADPH, and increases ROS levels in breast cancer cells, thereby weakening breast cancer cell stemness. Our study reveals the specific mechanism by which miR-375 targets the KLF5/G6PD signaling axis to diminish the stemness of breast cancer cells, providing a therapeutic strategy against BCSCs.

17.
Food Chem X ; 22: 101201, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38550883

RESUMO

Carrots as a representative type of delicious and healthy vegetables has become increasingly popular due to its unique flavors and nutritional value. Vast amount of research has been completed on chemical composition and aroma profile of fresh carrot. However, the knowledge of fresh carrot is only scattered. Therefore, a more comprehensive review to fresh carrot is requisite to be reported. This review first describes the botany of carrots; then, the chemical ingredients and their various functions are discussed. The volatile constituents and the effects of terpenoids on aroma profiles of fresh carrot are also discussed. Finally, sources of variation in the formation and development of carrot aroma through heat processing and dehydration are analyzed. This information will further help researchers to solve the problem of insufficient aroma of carrot products and standardize for each type of carrot through improving the production process.

18.
Sci Total Environ ; 919: 170757, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38340851

RESUMO

Water resources carrying capacity (WRCC) is indispensable for sustainable development, acting as a crucial determinant for harmonizing ecological preservation with socio-economic advancement. This research delineates an advanced evaluation index system for WRCC, focusing on Henan Province, China, a region straddling the Yangtze, Huaihe, Yellow, and Haihe river basins. Leveraging the analytic hierarchy process (AHP) with a system dynamics (SD) model, our analysis dissects the nonlinear interplays among demographic expansion, economic activities, land use patterns, water resources, and water environment. We introduce a novel integration of the "Four Determinations with Water" principle with sustainable development tenets, thereby sculpting six exploratory scenarios that chart Henan's potential paths from 2022 to 2035. Through these scenarios, we forecast and scrutinize the evolution of population dynamics, GDP, water supply, and sewage discharge volumes, employing rigorous quantitative analyses for a holistic evaluation. The results show that: WRCC in Henan Province becomes larger gradually, and, in Scenario 6, the WRCC indicator is the largest (0.643 in 2035) and the prediction effect is the best, while in Scenario 1, the WRCC indicator is the smallest (0.472 in 2035) and the prediction effect is the worst. Based on the prediction results, suggestions were made to adjust the industrial structure and strengthen the awareness of water conservation to improve the regional water resources carrying capacity.

19.
Heliyon ; 10(4): e25964, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38375291

RESUMO

The molybdenum and nitrogen content of super austenitic stainless steel in Cl- solution is shown to influence pitting resistance using immersion, electrochemical testing, and simulation. Variations in Mo and N content affect the defect density, resistance, and densification of the passive film, thereby reducing the number of pitting. A higher local pH associated with the pitting pits and an increase in NH3(NH4+) are the results of increased N content, which also slows the rate of pitting expansion. The combined effects of fewer actively reactive spots within the passive film retarded pitting, and decreased corrosion rates due to NH3(NH4+) mitigation of local acidity which serves to reduce the corrosion rate. The work function is improved to a greater extent when Mo and N are co-doped compared with individual Mo and N doping, and the adsorption energy is significantly increased when Mo and N are co-doped, indicating a synergistic role for Mo and N in the prevention of corrosion by Cl-.

20.
bioRxiv ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38352542

RESUMO

Background: Evidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. Methods: A sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1, and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. Results: We found six age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or the temporal pole, which has direct anatomical pathways to the prefrontal cortex. Sex differences in functional connectivity only emerge when associated with behavior, and not in functional connectivity alone. Furthermore, at neonate and 2 years of age, these age-specific connections displayed greater connectivity in males and lower connectivity in females in association with better behavioral scores. Conclusions: Taken together, we critically capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development.

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