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Imbalances in NAD + homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD + metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD + synthesis. 18 F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD + salvage pathways and improve age-related symptoms. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here, the authors show that low-dose nicotine promotes SIRT1 deacetylation of NAMPT and enhanced NAMPT activity which boosts NAD generation and improves age related symptoms.

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial lung disease of unknown etiology that leads rapidly to death. It is characterized by the replacement of healthy tissue through an altered extracellular matrix and damage to the alveolar structure. New pharmacological treatments and biomarkers are needed for pulmonary fibrosis to ensure better outcomes and earlier diagnosis of patients. Exosomes are nanoscale vesicles released by nearly all cell types that play a central role as mediators of cell-to-cell communication. Moreover, exosomes are emerging as a crucial factor in antigen presentation, immune response, immunomodulation, inflammation, and cellular phenotypic transformation and have also shown promising therapeutic potential in pulmonary fibrosis. This review summarizes current knowledge of exosomes that may promote pulmonary fibrosis and be utilized for diagnostics and prognostics. In addition, the utilization of exosomes and their cargo miRNAs as novel therapeutics and their potential mechanisms are also discussed. This review aims to elucidate the role of exosomes in the pathogenesis of pulmonary fibrosis and paves the way for developing novel therapeutics for pulmonary fibrosis. Further in-depth research and clinical trials on this topic are encouraged in the future.

Solid Earth tide represents the response of solid Earth to the lunar (solar) gravitational force. The yielding solid Earth due to the force has been thought to be a prolate ellipsoid since the time of Lord Kelvin, yet the ellipsoid’s geometry such as major semi-axis’s length, minor semi-axis’s length, and flattening remains unresolved. Additionally, the tidal displacement of reference point is conventionally resolved through a combination of expanded potential equations and given Earth model. Here we present a geometric model in which both the ellipsoid’s geometry and the tidal displacement of reference point can be resolved through a rotating ellipse with respect to the Moon (Sun). We test the geometric model using 23-year gravity data from 22 superconducting gravimeter (SG) stations and compare it with the current model recommended by the IERS (International Earth Rotation System) conventions (2010), the average Root Mean Square ( RMS ) deviation of the gravity change yielded by the geometric model against observation is 6.47 µGal (equivalent to 2.07 cm), while that yielded by the current model is 30.77 µGal (equivalent to 9.85 cm). The geometric model will greatly contribute to many application fields such as geodesy, geophysics, astronomy, and oceanography.

In order to obtain high yield pomelo peel pectin with better physicochemical properties, four pectin extraction methods, including hot acid extraction (HAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction, and enzymatic assisted extraction (EAE) were compared. MAE led to the highest pectin yield (20.43%), and the lowest pectin recovery was found for EAE (11.94%). The physicochemical properties of pomelo peel pectin obtained by different methods were also significantly different. Pectin samples obtained by MAE had the highest methoxyl content (8.35%), galacturonic acid content (71.36%), and showed a higher apparent viscosity, thermal and emulsion stability. The pectin extracted by EAE showed the highest total phenolic content (12.86%) and lowest particle size (843.69 nm), showing higher DPPH and ABTS scavenging activities than other extract methods. The pectin extracted by HAE had the highest particle size (966.12 nm) and degree of esterification (55.67%). However, Fourier-transform infrared spectroscopy showed that no significant difference occurred among the different methods in the chemical structure of the extracted pectin. This study provides a theoretical basis for the industrial production of pomelo peel pectin.

Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role and mechanism of eccDNAs have yet to be elucidated in non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, NSCLC cell lines (H1299, A549, and H460), and a normal lung cell line (MRC-5) were used as study objects. High-throughput eccDNA sequencing and bioinformatics analysis were performed to study the distribution pattern and level of eccDNA expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR and western blotting experiments were used to verify the expression level of PLCG2. Our results showed that the chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between the NSCLC and normal groups. Nevertheless, there were no significant differences in eccDNAs between NSCLC tissues and matched normal lung tissues. The eccDNA derived from PLCG2 was upregulated in NSCLC cells. TCGA analysis and immunohistochemistry showed that PLCG2 was highly expressed in lung cancer tissues and tended to be associated with poor outcome. We also demonstrated that PLCG2 can promote metastasis through the regulation of mitochondrial respiration. These results suggested that PLCG2 identified by eccDNA sequencing acts as an oncogene and might be a new biomarker for NSCLC diagnosis and prognosis evaluation.

Despite an increasing understanding of chronic obstructive pulmonary disease (COPD) pathogenesis, the mechanisms of diverse cell populations in the human lung remain unknown. Using single-cell RNA sequencing (scRNA-Seq), we can reveal changes within individual cell populations in COPD that are important for disease pathogenesis and characteristics. We performed scRNA-Seq on lung tissue obtained from donors with non-COPD and mild-to-moderate COPD to identify disease-related genes within different cell types. We testified the findings using qRT-PCR, immunohistochemistry, immunofluorescence and Western blotting from 25 additional subjects and RAW 264.7 macrophages. Targeting ferroptosis with the ferroptosis inhibitor ferrostatin-1, iron chelator deferoxamine or HO-1 inhibitor zinc protoporphyrin was administered in the experimental cigarette smoke COPD mouse model. We identified two populations of alveolar macrophages (AMs) in the human lung that were dysregulated in COPD patients. We discovered that M2-like AMs modulate susceptibility to ferroptosis by disrupting lipid and iron homeostasis both in vivo and in vitro. The discrepancy in sensitivity to ferroptosis can be determined and regulated by HO-1. In contrast, M1-like AMs showed the ability to attenuate oxidative stress and exert resistance to ferroptosis. In addition, the expression of genes within M2-like AMs is also involved in defects in phagocytosis and lysosome distortion. This ferroptotic phenotype was ameliorated by antiferroptotic compounds, iron chelators and HO-1 inhibitors. During COPD, the accumulation of lipid peroxidation drives ferroptosis-sensitive M2-like AMs, while M1-like AMs show characteristics of ferroptosis resistance. Ferroptotic M2 AMs lose their anti-inflammatory and repair functions but provoke inflammatory responses, resulting in consistent inflammation and tissue damage in the presence of M1 AMs in COPD. Appropriate interventions in ferroptosis can reduce the occurrence of infections and acute onset, and delay the COPD process.

To explore the difference of peripheral immune indexes especially T subsets cell mitochondrial indexes in patients with chronic HBV infection (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC) and healthy controls (HCs). From May 2023 to December 2023, HBV infected patients aged 40–59 years (HBV infection group, 236 cases) and healthy people of the same age group (control group, 112 cases) were selected as the study objects. More than 80 parameters related to lymphocyte including cell percentage, absolute count, mitochondrial mass and mitochondrial low membrane potential were obtained by flow cytometry. The mitochondrial mass of memory T cells was found to be sequentially raised in the disease progression of hepatitis B patients from CHB to LC and eventually to HCC, and mitochondrial low membrane potential ratio was sequentially decreased. Then we screened out 4 main indicators related to the stage of disease progression in HBV-infected patients and distinguished the differences among the control group, CHB, LC, and HCC groups through the calculation of MPOLS (mitochondrial parameters of lymphocyte subsets) value, which can be used as a novel biomarker for hepatitis B disease progression. Mitochondrial parameters of peripheral lymphocytes in HBV-infected patients are significant indicators of different stages of disease progression. The MPOLS provides rich clinical data support for clinical early warning of high-risk hepatitis B patients, and we believe that the MPOLS can be combined with a variety of clinical characteristics to achieve more accurate diagnosis and treatment.

Ferroptosis is caused by the accumulation of cellular reactive oxygen species that exceed the antioxidant load that glutathione (GSH) and phospholipid hydroperoxidases with GSH-based substrates can carry When the antioxidant capacity of cells is reduced, lipid reactive oxygen species accumulate, which can cause oxidative death. Ferroptosis, an iron-dependent regulatory necrosis pathway, has emerged as a new modality of cell death that is strongly associated with cancer. Surgery, chemotherapy and radiotherapy are the main methods of cancer treatment. However, resistance to these mainstream anticancer drugs and strong toxic side effects have forced the development of alternative treatments with high efficiency and low toxicity. In recent years, an increasing number of studies have shown that traditional Chinese medicines (TCMs), especially herbs or herbal extracts, can inhibit tumor cell growth and metastasis by inducing ferroptosis, suggesting that they could be promising agents for cancer treatment. This article reviews the current research progress on the antitumor effects of TCMs through the induction of ferroptosis. The aim of these studies was to elucidate the potential mechanisms of targeting ferroptosis in cancer, and the findings could lead to new directions and reference values for developing better cancer treatment strategies.

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems can precisely manipulate DNA sequences to change the characteristics of cells and organs, which has potential in the mechanistic research on genes and the treatment of diseases. However, clinical applications are restricted by the lack of safe, targeted and effective delivery vectors. Extracellular vesicles (EVs) are an attractive delivery platform for CRISPR/Cas9. Compared with viral and other vectors, EVs present several advantages, including safety, protection, capacity, penetrating ability, targeting ability and potential for modification. Consequently, EVs are profitably used to deliver the CRISPR/Cas9 in vivo. In this review, the advantages and disadvantages of the delivery form and vectors of the CRISPR/Cas9 are concluded. The favorable traits of EVs as vectors, such as the innate characteristics, physiological and pathological functions, safety and targeting ability of EVs, are summarized. Furthermore, in terms of the delivery of the CRISPR/Cas9 by EVs, EV sources and isolation strategies, the delivery form and loading methods of the CRISPR/Cas9 and applications have been concluded and discussed. Finally, this review provides future directions of EVs as vectors of the CRISPR/Cas9 system in clinical applications, such as the safety, capacity, consistent quality, yield and targeting ability of EVs.

This study proposes a dynamic balancing method without trial weights for power turbine rotors and investigates how the axial location chosen for unbalance identification affects the balancing performance. A finite element model of the power turbine rotor system was established to compute transient vibration responses and principal modes. Both continuous and isolated unbalances are employed to identify unbalanced excitation forces, enabling the determination of unbalance parameters. Furthermore, variations in identification accuracy across four designated axial positions on the rotor were analyzed. Simulations and experiments conducted on boss 2 and boss 3 confirmed the method’s efficacy: the maximum vibration amplitudes were reduced by 70.48% and 45.81% for boss 2, and by 64.48% and 61.00% for boss 3, respectively. These results verify the effectiveness of the proposed method. The unbalance parameters identified from simulations exhibited errors within ±6°, ±0.12 g, and ±0.15 × 10−4 m, while experimental errors remained within ±5°, ±0.11 g, and ±0.10 × 10−4 m, demonstrating high accuracy and reliability. Notably, this method improves balancing efficiency by requiring only a single startup and facilitates vibration data acquisition in confined spaces.