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1.
Biomed Pharmacother ; 178: 117176, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39059350

RESUMO

The class-III histone deacetylase SIRT1 is the most extensively investigated sirtuin deacetylase. It is resistant to the broad deacetylase inhibitor trichostatin A and depends on oxidized nicotinamide adenine nucleotide (NAD+). SIRT1 plays a crucial role in the tumorigenesis of numerous types of cancers, including colorectal cancer (CRC). Accumulating evidence indicates that SIRT1 is a therapeutic target for CRC; however, the function and underlying mechanism of SIRT1 in CRC still need to be elucidated. Herein, we provide a detailed and updated review to illustrate that SIRT1 regulates many processes that go awry in CRC cells, such as apoptosis, autophagy, proliferation, migration, invasion, metastasis, oxidative stress, resistance to chemo-radio therapy, immune evasion, and metabolic reprogramming. Moreover, we closely link our review to the clinical practice of CRC treatment, summarizing the mechanisms and prospects of SIRT1 inhibitors in CRC therapy. SIRT1 inhibitors as monotherapy in CRC or in combination with chemotherapy, radiotherapy, and immune therapies are comprehensively discussed. From epigenetic regulation to its potential therapeutic effect, we hope to offer novel insights and a comprehensive understanding of SIRT1's role in CRC.

2.
Nature ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987606

RESUMO

The fermionic Hubbard model (FHM)1 describes a wide range of physical phenomena resulting from strong electron-electron correlations, including conjectured mechanisms for unconventional superconductivity. Resolving its low-temperature physics is, however, challenging theoretically or numerically. Ultracold fermions in optical lattices2,3 provide a clean and well-controlled platform offering a path to simulate the FHM. Doping the antiferromagnetic ground state of a FHM simulator at half-filling is expected to yield various exotic phases, including stripe order4, pseudogap5, and d-wave superfluid6, offering valuable insights into high-temperature superconductivity7-9. Although the observation of antiferromagnetic correlations over short10 and extended distances11 has been obtained, the antiferromagnetic phase has yet to be realized as it requires sufficiently low temperatures in a large and uniform quantum simulator. Here we report the observation of the antiferromagnetic phase transition in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites. When the interaction strength, temperature and doping concentration are finely tuned to approach their respective critical values, a sharp increase in the spin structure factor is observed. These observations can be well described by a power-law divergence, with a critical exponent of 1.396 from the Heisenberg universality class12. At half-filling and with optimal interaction strength, the measured spin structure factor reaches 123(8), signifying the establishment of an antiferromagnetic phase. Our results provide opportunities for exploring the low-temperature phase diagram of the FHM.

3.
World J Diabetes ; 15(6): 1340-1352, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38983805

RESUMO

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

4.
J Am Chem Soc ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049158

RESUMO

The formation and preservation of the active phase of the catalysts at the triple-phase interface during CO2 capture and reduction is essential for improving the conversion efficiency of CO2 electroreduction toward value-added chemicals and fuels under operational conditions. Designing such ideal catalysts that can mitigate parasitic hydrogen generation and prevent active phase degradation during the CO2 reduction reaction (CO2RR), however, remains a significant challenge. Herein, we developed an interfacial engineering strategy to build a new SnOx catalyst by invoking multiscale approaches. This catalyst features a hierarchically nanoporous structure coated with an organic F-monolayer that modifies the triple-phase interface in aqueous electrolytes, substantially reducing competing hydrogen generation (less than 5%) and enhancing CO2RR selectivity (∼90%). This rationally designed triple-phase interface overcomes the issue of limited CO2 solubility in aqueous electrolytes via proactive CO2 capture and reduction. Concurrently, we utilized pulsed square-wave potentials to dynamically recover the active phase for the CO2RR to regulate the production of C1 products such as formate and carbon monoxide (CO). This protocol ensures profoundly enhanced CO2RR selectivity (∼90%) compared with constant potential (∼70%) applied at -0.8 V (V vs RHE). We further achieved a mechanistic understanding of the CO2 capture and reduction processes under pulsed square-wave potentials via in situ Raman spectroscopy, thereby observing the potential-dependent intensity of Raman vibrational modes of the active phase and CO2RR intermediates. This work will inspire material design strategies by leveraging triple-phase interface engineering for emerging electrochemical processes, as technology moves toward electrification and decarbonization.

5.
Front Endocrinol (Lausanne) ; 15: 1331488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050570

RESUMO

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain. Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP. Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB). Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes. Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.


Assuntos
Cádmio , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Osteoporose , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/induzido quimicamente , Osteoporose/metabolismo , Osteoporose/patologia , Cádmio/toxicidade , Animais , Ratos , Apoptose/efeitos dos fármacos , Feminino , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Cápsulas
6.
medRxiv ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38826336

RESUMO

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7 °C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3 °C and 23.6-27.9 °C (95 % CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.

7.
PLoS Negl Trop Dis ; 18(6): e0011836, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857289

RESUMO

The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.


Assuntos
Schistosoma haematobium , Schistosoma mansoni , Temperatura , Animais , Humanos , Schistosoma haematobium/fisiologia , Schistosoma mansoni/fisiologia , África Subsaariana/epidemiologia , Biomphalaria/parasitologia , Esquistossomose/transmissão , Esquistossomose/epidemiologia , Esquistossomose mansoni/transmissão , Esquistossomose mansoni/epidemiologia , Bulinus/parasitologia , Esquistossomose Urinária/transmissão , Esquistossomose Urinária/epidemiologia , Prevalência
8.
Curr Med Chem ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38831674

RESUMO

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

9.
Arch Virol ; 169(5): 114, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700535

RESUMO

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virologia , Neoplasias Gástricas/patologia , Masculino , Feminino , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Pessoa de Meia-Idade , Herpesvirus Humano 4/genética , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , RNA Viral/genética , Gastrectomia
10.
Adv Healthc Mater ; : e2400752, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38794825

RESUMO

Atherosclerosis is a primary contributor to cardiovascular disease. Current studies have highlighted the association between the immune system, particularly immune cells, and atherosclerosis, although treatment options and clinical trials remain scarce. Immunotherapy for cardiovascular disease is still in its infancy. Bruton's tyrosine kinase (BTK), widely expressed in various immune cells, represents a promising therapeutic target for atherosclerosis by modulating the anti-inflammatory function of immune cells. This study introduces a polydopamine-based nanocarrier system to deliver the BTK inhibitor, ibrutinib, to atherosclerotic plaques with an active targeting property via an anti-CD47 antibody. Leveraging polydopamine's pH-sensitive reversible disassembly, the system offers responsive, controlled release within the pathologic microenvironment. This allows precise and efficient ibrutinib delivery, concurrently inhibiting the activation of the NF-κB pathway in B cells and the NLRP3 inflammasome in macrophages within the plaques. This treatment also modulates both the immune cell microenvironment and inflammatory conditions in atherosclerotic lesions, thereby conveying promising therapeutic effects for atherosclerosis in vivo. This strategy also provides a novel option for atherosclerosis treatment.

11.
Adv Sci (Weinh) ; 11(23): e2310239, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582519

RESUMO

Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor-Acceptor (D-A) bipolar polymer with n-type pyrene-4,5,9,10-tetraone unit storing Li cations and p-type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium-ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D-A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g-1 at 200 mA g-1, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g-1 at 10 A g-1 and a noteworthy energy density up to 554 Wh kg-1. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.

12.
Foods ; 13(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611353

RESUMO

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

13.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564326

RESUMO

Optical thin films with high-reflectivity (HR) are essential for applications in quantum precision measurements. In this work, we propose a coating technique based on reactive magnetron sputtering with RF-induced substrate bias to fabricate HR-optical thin films. First, atomically flat SiO2 and Ta2O5 layers have been demonstrated due to the assistance of radio-frequency plasma during the coating process. Second, a distributed Bragg reflector (DBR) mirror with an HR of ∼99.999 328% centered at 1397 nm has been realized. The DBR structure is air-H{LH}19-substrate, in which the L and H denote a single layer of SiO2 with a thickness of 237.8 nm and a single layer of Ta2O5 with a thickness of 171.6 nm, respectively. This novel coating method would facilitate the development of HR reflectors and promote their wide applications in precision measurements.

14.
Talanta ; 274: 126028, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38599126

RESUMO

Mechanical forces play a crucial role in cellular processes, including ferroptosis, a form of regulated cell death associated with various diseases. However, the mechanical aspects of organelle lipid droplets (LDs) during ferroptosis are poorly understood. In this study, we designed and synthesized a fluorescent probe, TPE-V1, to enable real-time monitoring of LDs' viscosity using a dual-channel fluorescence-on model (red channel at 617 nm and NIR channel at 710 nm). The fluorescent imaging of using TPE-V1 was achieved due to the integrated mechanisms of the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE). Through dual-emission channel fluorescence imaging, we observed the enhanced mechanical energy of LDs triggering cellular mechanosensing, including ferroptosis and cell deformation. Theoretical calculations confirmed the probe's behavior, showing that high-viscosity media prevented the rotation processes and restored fluorescence quenching in low viscosity. These findings suggest that our TICT-TPE design strategy provides a practical approach to study LDs' mechanical properties during ferroptosis. This development enhances our understanding of the interplay between mechanical forces and LDs, contributing to the knowledge of ferroptotic cell death and potential therapeutic interventions targeting dysregulated cell death processes.


Assuntos
Ferroptose , Corantes Fluorescentes , Gotículas Lipídicas , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Corantes Fluorescentes/química , Humanos , Imagem Óptica , Viscosidade , Fluorescência
15.
J Org Chem ; 89(9): 6149-6158, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38635972

RESUMO

The detailed mechanism of transition metal-free-catalyzed monomethylation of 2-naphthyl acetonitrile (1a) with CO2 in the presence of triazabicyclodecene (TBD) and BH3NMe3 was investigated using density functional theory. The C-methylation process proved to generate formaldehyde followed by the formation of the product via an alcohol rather than a methoxyborane intermediate. During the reaction, CO2 is activated to form the TBD-CO2 adduct and BH3NMe3 is changed into TBD-BH2 (IM2) in the presence of TBD. IM2 plays a real reducing role within the system due to the unique coordination capability of the B atom. In addition to enhancing the nucleophilicity of 1a through deprotonation by tBuOK, our research also indicates that the generated tBuOH not only assists in proton transfer to generate an alcohol intermediate but also promotes the regeneration of TBD.

16.
Chem Commun (Camb) ; 60(40): 5232-5244, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38683172

RESUMO

The electrosynthesis of hydrogen peroxide (H2O2) via a selective two-electron oxygen reduction reaction (2e- ORR) presents a green and low-energy-consumption alternative to the traditional, energy-intensive anthraquinone process. This review encapsulates the principles of designing relational electrocatalysts for 2e- ORR and explores remaining setups for large-scale H2O2 production. Initially, the review delineates the fundamental reaction mechanisms of H2O2 production via 2e- ORR and assesses performance. Subsequently, it methodically explores the pivotal influence of microstructures, heteroatom doping, and metal hybridization along with setup configurations in achieving a high-performance catalyst and efficient reactor for H2O2 production. Thereafter, the review introduces a forward-looking methodology that leverages the synergistic integration of catalysts and reactors, aiming to harmonize the complementary characteristics of both components. Finally, it outlines the extant challenges and the promising avenues for the efficient electrochemical production of H2O2, setting the stage for future research endeavors.

17.
CNS Neurosci Ther ; 30(3): e14563, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38481068

RESUMO

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor in adults. TTFields is a therapy that use intermediate-frequency and low-intensity alternating electric fields to treat tumors. For patients with ndGBM, the addition of TTFields after the concurrent chemoradiotherapy phase of the Stupp regimen can improve prognosis. However, TTFields still has the potential to further prolong the survival of ndGBM patients. AIM: By summarizing the mechanism and application status of TTFields in the treatment of ndGBM, the application prospect of TTFields in ndbm treatment is prospected. METHODS: We review the recent literature and included 76 articles to summarize the mechanism of TTfields in the treatment of ndGBM. The current clinical application status and potential health benefits of TTFields in the treatment of ndGBM are also discussed. RESULTS: TTFields can interfere with tumor cell mitosis, lead to tumor cell apoptosis and increased autophagy, hinder DNA damage repair, induce ICD, activate tumor immune microenvironment, reduce cancer cell metastasis and invasion, and increase BBB permeability. TTFields combines with chemoradiotherapy has made progress, its optimal application time is being explored and the problems that need to be considered when retaining the electrode patches for radiotherapy are further discussed. TTFields shows potential in combination with immunotherapy, antimitotic agents, and PARP inhibitors, as well as in patients with subtentorial gliomas. CONCLUSION: This review summarizes mechanisms of TTFields in the treatment of ndGBM, and describes the current clinical application of TTFields in ndGBM. Through the understanding of its principle and application status, we believe that TTFields still has the potential to further prolong the survival of ndGBM patients. Thus,research is still needed to explore new ways to combine TTFields with other therapies and optimize the use of TTFields to realize its full potential in ndGBM patients.


Assuntos
Neoplasias Encefálicas , Terapia por Estimulação Elétrica , Glioblastoma , Glioma , Adulto , Humanos , Glioblastoma/patologia , Terapia Combinada , Glioma/terapia , Terapia por Estimulação Elétrica/métodos , Prognóstico , Neoplasias Encefálicas/patologia , Microambiente Tumoral
18.
Nature ; 626(7998): 288-293, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326594

RESUMO

The microscopic origin of high-temperature superconductivity in cuprates remains unknown. It is widely believed that substantial progress could be achieved by better understanding of the pseudogap phase, a normal non-superconducting state of cuprates1,2. In particular, a central issue is whether the pseudogap could originate from strong pairing fluctuations3. Unitary Fermi gases4,5, in which the pseudogap-if it exists-necessarily arises from many-body pairing, offer ideal quantum simulators to address this question. Here we report the observation of a pair-fluctuation-driven pseudogap in homogeneous unitary Fermi gases of lithium-6 atoms, by precisely measuring the fermion spectral function through momentum-resolved microwave spectroscopy and without spurious effects from final-state interactions. The temperature dependence of the pairing gap, inverse pair lifetime and single-particle scattering rate are quantitatively determined by analysing the spectra. We find a large pseudogap above the superfluid transition temperature. The inverse pair lifetime exhibits a thermally activated exponential behaviour, uncovering the microscopic virtual pair breaking and recombination mechanism. The obtained large, temperature-independent single-particle scattering rate is comparable with that set by the Planckian limit6. Our findings quantitatively characterize the pseudogap in strongly interacting Fermi gases and they lend support for the role of preformed pairing as a precursor to superfluidity.

19.
World J Psychiatry ; 14(1): 76-87, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38327892

RESUMO

BACKGROUND: Occult breast cancer (OBC) has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer. Due to the small number of cases and limited clinical ex-perience, treatments vary greatly around the world and no standardized treat-ment has yet been established. AIM: To investigate the clinicopathological features, psychological status and prog-nostic features of patients with OBC. METHODS: The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed. The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale. Patients' emotions, stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule, the Chinese Perceived Stress Scale, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Patient survival was calculated using the Kaplan-Meier method, and survival curves were plotted for analysis with the log-rank test. Univariate and multivariate survival analyses were performed using the Cox regression model. RESULTS: The 33 OBC patients included 32 females and 1 male. Of the 33 patients, 30 (91%) had axillary tumors, 3 (9%) had a neck mass as the primary symptom; 18 (54.5%) had estrogen receptor-positive tumors, 17 (51.5%) had progesterone receptor-positive tumors, and 18 (54.5%) had Her-2-positive tumors; 24 (72.7%) received surgical treatment, including 18 patients who underwent modified radical mastectomy, 1 patient who underwent breast-conserving surgery plus axillary lymph node dissection (ALND), and 5 patients who underwent ALND alone; 12 patients received preoperative neoadjuvant therapy. All 30 patients developed anxiety and depression, with low positive affect scores and high negative affect scores, accompanied by a high stress level and poor psychological resilience. There were no differences in the psychological status of patients according to age, body mass index, or menopausal status. The overall survival and disease-free survival (DFS) of all the patients were 83.3% and 55.7%, respectively. Univariate analysis demonstrated that the initial tumor site (P = 0.021) and node stage (P = 0.020) were factors that may affect patient prognosis. The 5-year DFS rate of OBC patients who received radiotherapy was greater (P < 0.001), while the use of different surgical methods (P = 0.687) had no statistically significant effect on patient outcomes. Multivariate analysis revealed that radiotherapy (P = 0.031) was an independent prognostic factor. Receiving radiotherapy had a significant effect on the CD-RISC score (P = 0.02). CONCLUSION: OBC is a rare breast disease whose diagnosis and treatment are currently controversial. There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy. In addition, radiotherapy can significantly improve patient outcomes. We should pay attention to the psychological state of patients while they receive antitumor therapy.

20.
Behav Sci (Basel) ; 14(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38392451

RESUMO

The NEET phenomenon (not in education, employment or training) has significant implications, both for individuals and society at large. While China's higher education students are particularly susceptible to becoming NEET, relatively little attention has been given to understanding this issue. To address this research gap and contribute to the study of NEET in China, this paper collected a total of 12,616 samples from current higher education students and those who graduated within the past three years from universities in seven provinces of Southwest China, finding that 21.91% of the students surveyed fall into the NEET-prone student category. The underlying factors contributing to NEET-prone status are identified through logit regression analysis and categorized into three levels: individual, family, and society. At the individual level, factors such as personal ability, confidence in job-hunting, and attitude towards NEET significantly influence a student's likelihood of being NEET-prone. Family-level factors include being an only child, consumption level, economic dependence on family members, and the presence of NEET relatives. And social-level factors encompass school provision (or non-provision) of employment services, the number of employment services offered, and the possibility of obtaining loans from society. Finally, this paper concludes by offering recommendations, which are drawn from individual, family, and social perspectives, to help Chinese higher education students avoid NEET status.

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