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1.
Heliyon ; 10(18): e37908, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39328512

RESUMO

Background: The study aims to investigate the pharmacological basis and molecular mechanisms of resveratrol in the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD) through the approach of treating different diseases with the same method, guided by traditional Chinese medicine theory. Utilizing network pharmacology and bioinformatics methods, this research aims to provide modern medical evidence for the theory of treating different diseases with the same method in traditional Chinese medicine. Methods: Omnibus from Swiss Target Prediction, TCMSP, SuperPred, SEA, HIT, CTD, TCMIP and Gene Expression Disease datasets for resveratrol related genes, Alzheimer's disease, and Parkinson's disease were obtained from the GEO database. Core targets were identified by weighted gene coexpression network analysis (WGCNA) and minimum absolute contraction and selection operator (LASSO). The expression of core targets was verified in AD and PD cell models. The immune characteristics of AD and PD were analyzed by CIBERSORT algorithm. Finally, the potential mechanism of resveratrol intervention on the core target was studied by molecular docking technique. Results: The results of network pharmacological analysis showed that resveratrol acted on 85 common targets such as STAT3 and CASP3, affected AGE-RAGE signaling pathway and PI3K-Akt signaling pathway, and showed the effect of "same disease and different treatment" for AD and PD. Three core targets associated with AD and PD (PLK4, FCGRT, and PRKAR2A) were finally identified through comprehensive transcriptome analysis, and experimentally verified in cell models of AD and PD. At the same time, the analysis of immune cell infiltration suggested that AD and PD had dysregulation of inflammation, and the core target was significantly related to M2 macrophages. Conclusion: Resveratrol may play a potential mechanism of "treating the same disease with different diseases" and target three core targets (PLK4, FCGRT and PRKAR2A) to improve the disease process of AD and PD by participating in the regulation of immune and inflammatory pathways. These findings have potential implications for clinical practice and future research.

2.
Poult Sci ; 103(10): 104091, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39146920

RESUMO

The large-scale and intensive development of the meat pigeon breeding industry have resulted in the replacement of a large number of low-performance local breeds by a few breeds with excellent production performance. However, due to the characteristics of pigeon species that are monogamous, for which the W chromosome cannot be recovered and for which semen cannot be cryopreserved, the preservation of pigeon species is still mainly based on in-situ preservation. In this study, pigeons were classified into 6 classes of endangerment based on the criteria of the 100-year inbreeding coefficient of poultry populations in the "Assessment of Endangered Poultry Genetic Resources" (NY/T 2996-2016). The results show that when the generation interval was 1.5 yr, the number of ideal populations with the same gene frequency variance or the same heterozygosity decay rate of pigeons in class 1 to 5 was ≤149, 150 to 204, 205 to 316, 317 to 649 and ≥650. In random-reserved breeding, when the generation interval was 1.5 yr, the number of male (female) pigeons corresponding to class 1 to 5 was ≤74, 75 to 102, 103 to 157, 158 to 324 and ≥325. In family-equal-reserved breeding, when the generation interval was 1.5 yr, the number of male (female) pigeons corresponding to class 1 to 5 was ≤36, 37 to 50, 51 to 78, 79 to 162 and ≥163. When the generation interval was 1.5 yr, the inbreeding increments corresponding to class 1 to 5 were ≥0.00335, 0.00244 to 0.00334, 0.00159 to 0.00243, 0.00078 to 0.00158 and ≤0.00077; with the same population size, the inbreeding coefficient and inbreeding increment decreased with the increase of generation interval; the population effective content, inbreeding coefficient and inbreeding increment of family-equal-reserved pigeons were lower than those of random-reserved pigeons. The results of this study have certain reference value for analyzing the status quo of local and endangered species, constructing live gene banks and breeding farms of poultry genetic resources, and rescuing endangered species.


Assuntos
Columbidae , Animais , Columbidae/genética , Columbidae/fisiologia , Masculino , Feminino , Espécies em Perigo de Extinção , Endogamia , Cruzamento
3.
Nat Prod Res ; : 1-7, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913076

RESUMO

Two new limonoid glycosides, named limonosides A (1) and B (2), along with four known limonoids (3-6) were obtained from the seeds of Citrus limon. Their structures were deduced based on extensive spectroscopic analysis. Limonoside A (1) and nomilin (4) were found to possess moderate phosphodiesterase type 4D (PDE4D) inhibitory effect with values of 89.8 ± 2.4% and 98.9 ± 3.0% at 10 µM, respectively.

4.
Nat Commun ; 15(1): 4784, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839772

RESUMO

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin-orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

5.
Sci Rep ; 14(1): 11842, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783031

RESUMO

Limited research has explored the relationship between overactive bladder (OAB) and cardiovascular health (CVH). We aim to examine the correlation between OAB and CVH in American adults, utilizing the Life's Essential 8 (LE8). We included 70,190 individuals from the National Health and Nutrition Examination Survey spanning from 2005 to 2018. In our study, the independent variable is LE8 score, where higher scores denote better CVH. The dependent variable is the presence of OAB. We employed multivariable logistic regression along with restricted cubic splines to evaluate the association between LE8 and OAB. Additionally, we performed interaction analyzes on subgroups to validate the findings. There is a significant negative correlation between LE8 scores and OAB. Upon adjusting for all covariates, a 10-point increase in LE8 total score correlated with a 17% decrease in the odds of OAB [0.83 (95% CI 0.78, 0.89)]. Compared to participants with lower LE8 scores, those with higher LE8 scores had a 46% lower probability of developing OAB. Consistent results were also observed in the association between scores of four health behaviors and four health factors and OAB. Furthermore, a notable interaction was observed between LE8 scores and smoking status. This study showed a significant negative correlation between LE8 scores and OAB prevalence.


Assuntos
Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Inquéritos Nutricionais , Idoso , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Comportamentos Relacionados com a Saúde , Estados Unidos/epidemiologia
6.
Free Radic Biol Med ; 219: 153-162, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657753

RESUMO

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.


Assuntos
Benzofuranos , Hepcidinas , Homeostase , Interleucina-6 , Ferro , Animais , Camundongos , Anemia/metabolismo , Anemia/genética , Anemia/tratamento farmacológico , Anemia/patologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Ferritinas/metabolismo , Ferritinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/efeitos dos fármacos , Hepcidinas/genética , Hepcidinas/metabolismo , Homeostase/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Interleucina-6/metabolismo , Interleucina-6/genética , Ferro/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Benzofuranos/farmacologia
7.
Bioorg Chem ; 147: 107351, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593530

RESUMO

Eleven triterpenoid saponins, including five new compounds, which were named densiflorasides A - E (1 - 5), were isolated from aerial parts of Mussaenda densiflora (Rubiaceae). Their structures were elucidated based on spectroscopic and single-crystal X-ray diffraction analyses and chemical methods. All the isolated compounds and the aglycone heinsiagenin A were evaluated for their immunosuppressive and antiosteoclastogenic activities in vitro. Compounds 6 - 8 and heinsiagenin A inhibited osteoclastogenesis, with IC50 values ranging from 8.24 to 17.7 µM. Furthermore, compounds 3, 6 - 8, and heinsiagenin A significantly inhibited T-cell proliferation, with IC50 values ranging from 2.56 to 8.60 µM, and compounds 3 - 5 and 11 inhibited the proliferation of B lymphocytes, with IC50 values ranging from 1.29 to 8.49 µM. Further in vivo experiments indicated that heinsiagenin A could significantly attenuate IMQ-induced psoriasis and DSS-induced colitis in mice.


Assuntos
Proliferação de Células , Relação Dose-Resposta a Droga , Imunossupressores , Saponinas , Triterpenos , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Estrutura Molecular , Linfócitos T/efeitos dos fármacos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Osteoclastos/efeitos dos fármacos
8.
Materials (Basel) ; 17(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612057

RESUMO

High-entropy oxides (HEOs), as a new type of single-phase solid solution with a multi-component design, have shown great potential when they are used as anodes in lithium-ion batteries due to four kinds of effects (thermodynamic high-entropy effect, the structural lattice distortion effect, the kinetic slow diffusion effect, and the electrochemical "cocktail effect"), leading to excellent cycling stability. Although the number of articles on the study of HEO materials has increased significantly, the latest research progress in porous HEO materials in the lithium-ion battery field has not been systematically summarized. This review outlines the progress made in recent years in the design, synthesis, and characterization of porous HEOs and focuses on phase transitions during the cycling process, the role of individual elements, and the lithium storage mechanisms disclosed through some advanced characterization techniques. Finally, the future outlook of HEOs in the energy storage field is presented, providing some guidance for researchers to further improve the design of porous HEOs.

9.
Bioorg Chem ; 145: 107246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428283

RESUMO

Phytochemical investigation of the stems of Celastrus monospermus Roxb enabled isolation and identification of fifteen new macrolide sesquiterpene pyridine alkaloids (1-15) along with five known analogues. Their structures were elucidated by comprehensive spectroscopic analysis (NMR, HRESIMS, IR, UV), chemical hydrolysis, and single crystal X-ray diffraction analysis. Bioassay of the abundant isolates revealed that seven compounds inhibited the proliferation of B lymphocytes with IC50 values ranging between 1.4 and 19.9 µM. Among them, celasmondine C (3) could significantly promote the apoptosis of activated B lymphocyte, especially late-stage apoptosis. Besides, compounds 3, 16, and 20 exhibited potent suppression of osteoclast formation at a concentration of 1.0 µM. This investigation enriched the chemical diversity of macrolide sesquiterpene pyridine alkaloids, and supported evidence for the development of new immunosuppressive and anti-osteoclastogenesis agents.


Assuntos
Alcaloides , Celastrus , Sesquiterpenos , Celastrus/química , Macrolídeos , Estrutura Molecular , Piridinas/farmacologia , Piridinas/química , Alcaloides/farmacologia , Alcaloides/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química
10.
J Leukoc Biol ; 116(3): 621-631, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38456763

RESUMO

Immune evasion by cancer cells poses a significant challenge for natural killer cell-based immunotherapy. Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of natural killer cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting natural killer cell activity against cancer. In this study, various assays were conducted, including natural killer cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, to assess natural killer cell-mediated cell killing, as well as gene and protein expressions. The results indicated that euphohelioscopin A, a potential pyroptosis activator, enhances natural killer cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by natural killer cell depletion. Furthermore, we found that euphohelioscopin A significantly enhanced IFNγ production in natural killer cells and synergistically upregulated GSDME with IFNγ in cancer cells. Euphohelioscopin A also increased the cleavage of GSDME, promoting granzyme B-induced pyroptosis, which could be reversed by GSDME knockdown and IFNγ blockade. Overall, the findings suggested that euphohelioscopin A enhanced natural killer cell-mediated killing of cancer cells by triggering pyroptosis, making euphohelioscopin A a promising pyroptosis activator with great potential for use in natural killer cell-based cancer immunotherapy.


Assuntos
Interferon gama , Células Matadoras Naturais , Piroptose , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Gasderminas , Granzimas/metabolismo , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/patologia , Piroptose/efeitos dos fármacos , Piroptose/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Phytomedicine ; 128: 155456, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537446

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous metabolic and endocrine disorder that causes anovulatory infertility and abnormal folliculogenesis in women of reproductive age. Several studies have revealed inflammation in PCOS follicles, and recent evidence suggests that Berberine (BBR) effectively reduces inflammatory responses in PCOS, however, the underlying mechanisms remain unclear. PURPOSE: To determine the underlying mechanisms by which BBR alleviates inflammation in PCOS. STUDY DESIGN: Primary human GCs from healthy women and women with PCOS, and KGN cells were used for in vitro studies. ICR mice were used for in vivo studies. METHODS: Gene expression was measured using RT-qPCR. HAS2, inflammatory cytokines, and serum hormones were assayed by ELISA. Protein expression profiles were assayed by Western blot. Chronic low-grade inflammatory mouse models were developed by intraperitoneal injection with LPS, and PCOS mouse models were established by subcutaneous intraperitoneal injection of DHEA. BBR and 4-MU were administered by gavage. Ovarian morphologic changes were evaluated using H&E staining. HAS2 expression in the ovary was assayed using Western blot and immunohistochemistry. RESULTS: Our results confirmed that HAS2 expression and hyaluronan (HA) accumulation are closely associated with inflammatory responses in PCOS. Data obtained from in vitro studies showed that HAS2 and inflammatory genes (e.g., MCP-1, IL-1ß, and IL-6) are significantly upregulated in PCOS samples and LPS-induced KGN cells compared to their control groups. In addition, these effects were reversed by blocking HAS2 expression or HA synthesis using BBR or 4-MU, respectively. Furthermore, HAS2 overexpression induces the expression of inflammatory genes in PCOS. These results were further confirmed in LPS- and DHEA-induced mouse models, where inflammatory genes were reduced by BBR or 4-MU, and ovarian morphology was restored. CONCLUSIONS: Our results define previously unknown links between HAS2 and chronic low-grade inflammation in the follicles of women with PCOS. BBR exerts its anti-inflammatory effects by down-regulating HAS2. This study provides a novel therapeutic target for alleviating ovarian inflammation in women with PCOS.


Assuntos
Berberina , Modelos Animais de Doenças , Hialuronan Sintases , Inflamação , Camundongos Endogâmicos ICR , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/tratamento farmacológico , Berberina/farmacologia , Feminino , Animais , Humanos , Hialuronan Sintases/metabolismo , Inflamação/tratamento farmacológico , Camundongos , Ácido Hialurônico , Adulto , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Desidroepiandrosterona/farmacologia , Ovário/efeitos dos fármacos , Lipopolissacarídeos , Citocinas/metabolismo
12.
Phytomedicine ; 125: 155343, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290230

RESUMO

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.


Assuntos
Glioblastoma , Hidroxibenzoatos , Infecção por Zika virus , Zika virus , Animais , Recém-Nascido , Humanos , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/metabolismo , Zika virus/fisiologia , Proteínas do Envelope Viral , Glioblastoma/tratamento farmacológico , Simulação de Acoplamento Molecular , Replicação Viral , Linhagem Celular
13.
J Anim Physiol Anim Nutr (Berl) ; 108(2): 439-450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37975278

RESUMO

Chlorogenic acid (CGA), also known as 3-caffeioylquinic acid or coffee tannin, is a water-soluble polyphenol phenylacrylate compound produced through the shikimate pathway by plants during aerobic respiration. CGA widely exists in higher dicotyledons, ferns and many Chinese medicinal materials, and enjoys the reputation of 'plant gold'. Here, we summarized the source, chemical structure, biological activity functions of CGA and its research progress in pigs, aiming to provide a more comprehensive understanding and theoretical basis for the prospect of CGA replacing antibiotics as a pig feed additive.


Assuntos
Ácido Clorogênico , Café , Animais , Suínos , Ácido Clorogênico/química , Café/química , Antioxidantes
14.
Bioorg Chem ; 141: 106886, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37778191

RESUMO

Extensive phytochemical investigation of the seeds of Tripterygium wilfordii led to the identification of 54 polyesterified dihydro-ß-agarofuran-type sesquiterpenoids, including 27 previously undescribed ones, named Tripwilin I-XXVII (1-27). Comprehensive spectroscopic and single-crystal X-ray diffraction analyses, along with electronic circular dichroism (ECD) calculations were used for the structural elucidation of the new compounds. Biological assay revealed that 37 compounds among the isolates exhibited significant inhibition against osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL) at 10 µM. Further investigation indicated that Triptogelin C-3 (54), with the most potent osteoclastogenesis inhibitory activity, regulated the osteoclast marker genes (MMP-9, c-Fos, CTSK, and TRAP) and proteins in a dose-dependent manner in vitro. Besides, celaforin D-1 (28), 1α,6ß,15-triacetoxy-8α,9α-dibenzoyloxy-2α-hydroxydihydro-ß-agarofuran (34), triptogelin A-2 (37), and chiapen D (49) showed moderate suppressive effects on the proliferation of T and B lymphocytes with IC50 values ranging between 8.1 ± 0.8 and 19.0 ± 0.9 µM.


Assuntos
Sesquiterpenos , Tripterygium , Tripterygium/química , Osteogênese , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sementes , Estrutura Molecular
15.
Phys Rev Lett ; 131(8): 086501, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37683154

RESUMO

Strong electron correlation under two-dimensional limit is intensely studied in the transition metal dichalcogenides monolayers, mostly within their charge density wave (CDW) states that host a star of David period. Here, by using scanning tunneling microscopy and spectroscopy and density functional theory calculations with on-site Hubbard corrections, we study the VTe_{2} monolayer with a different 2sqrt[3]×2sqrt[3] CDW period. We find that the dimerization of neighboring Te-Te and V-V atoms occurs during the CDW transition, and that the strong correlation effect opens a Mott-like full gap at Fermi energy (E_{F}). We further demonstrate that such a Mott phenomenon is ascribed to the combination of the CDW transition and on-site Coulomb interactions. Our work provides a new platform for exploring Mott physics in 2D materials.

16.
Medicine (Baltimore) ; 102(39): e34952, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773857

RESUMO

BACKGROUND: Dyslipidemia is a global health concern with an increasing prevalence worldwide. Lycium barbarum (L. barbarum) is widely used as a medicinal and functional food, and evidence suggests that it may be beneficial for lipid management. In this study, we performed a systematic review and meta-analysis of randomized controlled trials investigating the effects of L. barbarum supplementation on lipid profiles in adults. METHODS: PubMed, China National Knowledge Infrastructure, The Cochrane Library, Web of Science, and Wanfang Database were searched from inception until October 2022. The random-effect model was applied, and the pooled effect sizes were expressed as mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: The meta-analysis of 5 randomized controlled trials involving 259 subjects indicated that L. barbarum supplementation significantly decreased the triglyceride (TG) concentration (MD: 0.14 mmol/L, 95% CI: 0.08-0.20) and increased the high-density lipoprotein cholesterol concentration (HDL-C) (MD: -0.07 mmol/L, 95% CI: -0.13 to -0.01). However, the reductions in total cholesterol (TC) concentration (MD: 0.11 mmol/L, 95% CI: -0.37 to 0.59) and low-density lipoprotein cholesterol (LDL-C) concentration (MD: 0.21 mmol/L, 95% CI: -0.46 to 0.89) were not statistically significant. CONCLUSION: The present study showed that L. barbarum supplementation might have some beneficial effects on TG and HDL-C concentrations in adults, and L. barbarum fruit has an even greater effect on TG and HDL-C concentrations. Considering the sensitivity analyses and limitations of the study included, further large-scale studies are needed to confirm these findings.


Assuntos
Lycium , Humanos , Adulto , Triglicerídeos , HDL-Colesterol , LDL-Colesterol , Suplementos Nutricionais
17.
J Cancer Res Clin Oncol ; 149(14): 13185-13200, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37479756

RESUMO

PURPOSE: The advent of immune checkpoint blockade (ICB) therapies this year has changed the way glioblastoma (GBM) is treated. Meanwhile, some patients with strong PD-L1 expression remain immune checkpoint resistant. To better understand the molecular processes that influence the immune environment, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to predict patient survival outcomes. PATIENTS AND METHODS: Our study analyzed RNA-sequencing data from 178 GBM samples. Their unique gene expression patterns in the tumor microenvironment were analyzed by an unsupervised clustering algorithm. Through these expression patterns, a panel of T-cell exhaustion signatures, immunosuppressive cells, and clinical features correlates with immunotherapy response. The presence or absence of immune status and prognostic signatures was then validated with the test dataset. RESULTS: 38.2% of GBM patients showed increased expression of anti-inflammatory cytokines, significant enrichment of T cell exhaustion signals, higher proportion of immunosuppressive cells (macrophages and CD4 regulatory T cells) and nine inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA). The immunodepleted class (IDC) was used to classify these immunocompromised individuals. Despite the high density of tumor-infiltrating lymphocytes shown by IDC, such patients have a poor prognosis. Although PD-L1 was highly expressed in IDC, it suggested that there might be ICB resistance. There are many IDC predictive signatures to discover. CONCLUSION: PD-1 is strongly expressed in a novel immunosuppressive class of GBM, but this cluster may be resistant to ICB therapy. A comprehensive description of this drug-resistant tumor microenvironment could provide new insights into drug resistance mechanisms and improved immunotherapy techniques.

18.
J Hazard Mater ; 458: 131988, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37418963

RESUMO

Lipopolysaccharide (LPS), also known as endotoxin, is a component of the outer membrane of gram-negative bacteria. LPS is released into the surrounding environment during bacterial death and lysis. Due to its chemical and thermal stability, LPS can be detected anywhere and easily exposed to humans and animals. Previous studies have shown that LPS causes hormonal imbalances, ovarian failure, and infertility in mammals. However, the potential mechanisms remain unclear. In this study, we investigated the effects and mechanisms of LPS on tryptophan degradation, both in vivo and in vitro. The effects of kynurenine, a tryptophan derivative, on granulosa cell function and reproductive performance were explored. Results showed that p38, NF-κB, and JNK signaling pathways were involved in LPS-induced Ido1 expressions and kynurenine accumulation. Furthermore, the kynurenine decreased estradiol production, but increased granulosa cell proliferation. In vivo, experiments showed that kynurenine decreased estradiol and FSH production and inhibited ovulation and corpus luteum formation. Additionally, pregnancy and offspring survival rates decreased considerably after kynurenine treatment. Our findings suggest that kynurenine accumulation disrupts hormone secretion, ovulation, corpus luteal formation, and reproductive performance in mammals.


Assuntos
Cinurenina , Ovário , Gravidez , Feminino , Humanos , Animais , Cinurenina/metabolismo , Ovário/metabolismo , Triptofano/metabolismo , Lipopolissacarídeos/farmacologia , Estradiol/metabolismo , Mamíferos/metabolismo
19.
Sensors (Basel) ; 23(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36904900

RESUMO

Deep learning has been successfully utilized in many applications, but it is vulnerable to adversarial samples. To address this vulnerability, a generative adversarial network (GAN) has been used to train a robust classifier. This paper presents a novel GAN model and its implementation to defend against L∞ and L2 constraint gradient-based adversarial attacks. The proposed model is inspired by some of the related work, but it includes multiple new designs such as a dual generator architecture, four new generator input formulations, and two unique implementations with L∞ and L2 norm constraint vector outputs. The new formulations and parameter settings of GAN are proposed and evaluated to address the limitations of adversarial training and defensive GAN training strategies, such as gradient masking and training complexity. Furthermore, the training epoch parameter has been evaluated to determine its effect on the overall training results. The experimental results indicate that the optimal formulation of GAN adversarial training must utilize more gradient information from the target classifier. The results also demonstrate that GANs can overcome gradient masking and produce effective perturbation to augment the data. The model can defend PGD L2 128/255 norm perturbation with over 60% accuracy and PGD L∞ 8/255 norm perturbation with around 45% accuracy. The results have also revealed that robustness can be transferred between the constraints of the proposed model. In addition, a robustness-accuracy tradeoff was discovered, along with overfitting and the generalization capabilities of the generator and classifier. These limitations and ideas for future work will be discussed.

20.
Nat Commun ; 14(1): 177, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635279

RESUMO

The formation of inactive lithium by side reactions with liquid electrolyte contributes to cell failure of lithium metal batteries. To inhibit the formation and growth of inactive lithium, further understanding of the formation mechanisms and composition of inactive lithium are needed. Here we study the impact of gas producing reactions on the formation of inactive lithium using ethylene carbonate as a case study. Ethylene carbonate is a common electrolyte component used with graphite-based anodes but is incompatible with Li metal anodes. Using mass spectrometry titrations combined with 13C and 2H isotopic labeling, we reveal that ethylene carbonate decomposition continuously releases ethylene gas, which further reacts with lithium metal to form the electrochemically inactive species LiH and Li2C2. In addition, phase-field simulations suggest the non-ionically conducting gaseous species could result in an uneven distribution of lithium ions, detrimentally enhancing the formation of dendrites and dead Li. By optimizing the electrolyte composition, we selectively suppress the formation of ethylene gas to limit the formation of LiH and Li2C2 for both Li metal and graphite-based anodes.

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