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1.
Proc Natl Acad Sci U S A ; 121(1): e2220898120, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38150495

RESUMO

Like biological species, words in language must compete to survive. Previously, it has been shown that language changes in response to cognitive constraints and over time becomes more learnable. Here, we use two complementary research paradigms to demonstrate how the survival of existing word forms can be predicted by psycholinguistic properties that impact language production. In the first study, we analyzed the survival of words in the context of interpersonal communication. We analyzed data from a large-scale serial-reproduction experiment in which stories were passed down along a transmission chain over multiple participants. The results show that words that are acquired earlier in life, more concrete, more arousing, and more emotional are more likely to survive retellings. We reason that the same trend might scale up to language evolution over multiple generations of natural language users. If that is the case, the same set of psycholinguistic properties should also account for the change of word frequency in natural language corpora over historical time. That is what we found in two large historical-language corpora (Study 2): Early acquisition, concreteness, and high arousal all predict increasing word frequency over the past 200 y. However, the two studies diverge with respect to the impact of word valence and word length, which we take up in the discussion. By bridging micro-level behavioral preferences and macro-level language patterns, our investigation sheds light on the cognitive mechanisms underlying word competition.


Assuntos
Idioma , Psicolinguística , Humanos , Emoções/fisiologia , Nível de Alerta/fisiologia , Cognição
2.
Proc Natl Acad Sci U S A ; 121(14): e2317574121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38530899

RESUMO

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.


Assuntos
Poluentes Atmosféricos , Doenças Mitocondriais , Humanos , Poluentes Atmosféricos/análise , Fosforilcolina , Material Particulado/análise , Pulmão , Carbono/análise , Monitoramento Ambiental
3.
FASEB J ; 38(14): e23804, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39037422

RESUMO

Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.


Assuntos
NAD , Niacinamida , Ovário , Humanos , NAD/metabolismo , NAD/biossíntese , Ovário/metabolismo , Feminino , Animais , Niacinamida/metabolismo , Niacinamida/biossíntese , Vias Biossintéticas , Mononucleotídeo de Nicotinamida/metabolismo
4.
J Cell Mol Med ; 28(17): e18535, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39267250

RESUMO

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8+ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8+ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8+ T lymphocytes in H22 tumour-bearing mice. The CD8+ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8+ T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Luteolina , Linfócitos do Interstício Tumoral , Luteolina/farmacologia , Luteolina/uso terapêutico , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Camundongos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Linhagem Celular Tumoral , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Citocinas/metabolismo , Masculino , Granzimas/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Camundongos Endogâmicos C57BL
5.
PLoS Med ; 21(7): e1004419, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38980837

RESUMO

BACKGROUND: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. METHODS AND FINDINGS: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. CONCLUSIONS: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.


Assuntos
Intolerância à Glucose , Humanos , Masculino , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/complicações , Feminino , Pessoa de Meia-Idade , Teste de Tolerância a Glucose , China/epidemiologia , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Adulto
6.
Small ; 20(24): e2306447, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38152988

RESUMO

Due to their anisotropy, 1D semiconductor nanorod-based materials have attracted much attention in the process of hydrogen production by solar energy. Nevertheless, the rational design of 1D heterojunction materials and the modulation of photo-generated electron-hole transfer paths remain a challenge. Herein, a ZnxCd1-xS@ZnS/MoS2 core-shell nanorod heterojunction is precisely constructed via in situ growth of discontinuous ZnS shell and MoS2 NCs on the Zn─Cd─S nanorods. Among them, the Zn vacancy in the ZnS shell builds the defect level, and the nanoroelded MoS2 builds the electron transport site. The optimized photocatalyst shows significant photocatalytic activity without Platinum as an auxiliary catalyst, mainly due to the new interfacial charge transfer channel constructed by the shell vacancy level, the vertical separation and the de-accumulation process of photo-generated electrons and photo-generated holes. At the same time, spectral analysis, and density functional theory (DFT) calculations fully prove that shortening difference of speed between the photogenerated electron and hole movement process is another key factor to enhance the photocatalytic performance. This study provides a new path for the kinetic design of enhanced carrier density by shortening the carrier retention time of 1D heterojunction photocatalysts with improved photocatalytic performance.

7.
Small ; 20(32): e2311456, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38497893

RESUMO

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.


Assuntos
Colágeno , Mecanotransdução Celular , Células-Tronco Neurais , Proteínas Proto-Oncogênicas c-akt , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Animais , Porosidade , Células-Tronco Neurais/metabolismo , Colágeno/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Nicho de Células-Tronco , Biomimética , Diferenciação Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alicerces Teciduais/química , Materiais Biomiméticos/química , Proteínas de Sinalização YAP
8.
Cardiovasc Diabetol ; 23(1): 37, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245731

RESUMO

BACKGROUND: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. METHODS: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. RESULTS: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20-6.22). CONCLUSIONS: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Adulto , Humanos , Doenças Cardiovasculares/epidemiologia , Esfingomielinas , Seguimentos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , China/epidemiologia , Fatores de Risco
9.
Diabetes Obes Metab ; 26(4): 1188-1196, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38168886

RESUMO

AIM: We aimed to investigate the long-term influence of a diet and/or exercise intervention on long-term mortality and cardiovascular disease (CVD) events. METHODS: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet-only, exercise-only and diet-plus-exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow-up the participants for up to 24 years after the end of 6-year intervention. In total, 540 participants completed the follow-up, while 36 subjects lost in follow-up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. RESULTS: Compared with controls, the diet-only intervention in people with IGT was significantly associated with a reduced risk of all-cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61-0.97)], CVD death [HR 0.67, 95% CI (0.46-0.97)] and CVD events [HR 0.72, 95% CI (0.54-0.96)]. The diet-plus-exercise intervention was significantly associated with a decreased risk of all-cause death [HR 0.64, 95% CI (0.48-0.84)], CVD death [HR 0.54, 95% CI (0.30-0.97)] and CVD events [HR 0.68, 95% CI (0.52-0.90)]. Unexpectedly, the exercise-only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. CONCLUSIONS: A diet-only intervention and a diet-plus-exercise intervention in people with IGT were significantly associated with a reduced risk of all-cause death, CVD death and CVD events, while an exercise-only intervention was not. It suggests that diet-related interventions may have a potentially more reliable influence on long-term vascular complications and mortality.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Humanos , Intolerância à Glucose/complicações , Intolerância à Glucose/terapia , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Incidência , Dieta , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/complicações , Terapia por Exercício , Avaliação de Resultados em Cuidados de Saúde
10.
J Org Chem ; 89(15): 10831-10843, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38991973

RESUMO

Direct construction of gem-difluorinated heterocycles represents a long-standing challenge in organic chemistry. Herein, we developed a transition-metal-free photocatalytic radical addition/cyclization of BrCF2COR with 2-cyanoaryl acrylamides to give gem-difluorinated naphthyridinone scaffolds in moderate to good yields. Furthermore, some natural products were found to be suitable in the reaction system. The easily available substrates, mild reaction conditions, simple operation, and wide functionality tolerance show practical and environmental advantages in this method.

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