Changes in the combination of the triglyceride-glucose index and obesity indicators estimate the risk of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and CVD, as most studies have focused on baseline TyG-related indices. METHODS: The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into four classes (Class 1 to Class 4). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of CVD. RESULTS: In total, 3243 participants were included in this study, of whom 1761 (54.4%) were female, with a mean age of 57.62 years at baseline. Over a 5-year follow-up, 637 (19.6%) participants developed CVD. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of CVD. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident CVD. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.41 (95% confidence interval (CI) 1.08-1.84), the OR for participants in Class 3 was 1.54 (95% CI 1.15-2.07), and the OR for participants in Class 4 was 1.94 (95% CI 1.34-2.80). Moreover, cumulative TyG-WC exhibited the strongest association with incident CVD among cumulative TyG-related indices. Compared to the participants in Quartile 1 of cumulative TyG-WC, the OR for participants in Quartile 2 was 1.33 (95% CI 1.00-1.76), the OR for participants in Quartile 3 was 1.46 (95% CI 1.09-1.96), and the OR for participants in Quartile 4 was 1.79 (95% CI 1.30-2.47). CONCLUSIONS: Changes in TyG-related indices are independently associated with the risk of CVD. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of CVD.

Characteristics of the phyllosphere microbial community and its relationship with major aroma precursors during the tobacco maturation process.

Numerous bacteria, fungi and other microorganisms in the tobacco phyllosphere interstellar area participate in the physiological metabolism of plants by interacting with the host. However, there is currently little research on the characteristics of tobacco phyllosphere microbial communities, and the correlation between tobacco phyllosphere microbial communities and phyllosphere factor indicators is still unknown. Therefore, high-throughput sequencing technology based on the 16S rRNA/ITS1 gene was used to explore the diversity and composition characteristics of tobacco phyllosphere bacterial and fungal communities from different maturation processes, and to identify marker genera that distinguish phyllosphere microbial communities. In this study, the correlations between tobacco phyllosphere bacterial and fungal communities and the precursors of major aroma compounds were explored. The results showed that as the tobacco plants matured, the density of glandular trichomes on the tobacco leaves gradually decreased. The surface physicochemical properties of tobacco leaves also undergo significant changes. In addition, the overall bacterial alpha diversity in the tobacco phyllosphere area increased with maturation, while the overall fungal alpha diversity decreased. The beta diversity of bacteria and fungi in the tobacco phyllosphere area also showed significant differences. Specifically, with later top pruning time, the relative abundances of Acidisoma, Ralstonia, Bradyrhizobium, Alternaria and Talaromyces gradually increased, while the relative abundances of Pseudomonas, Filobassidium, and Tausonia gradually decreased. In the bacterial community, Acidisoma, Ralstonia, Bradyrhizobium, and Alternaria were significantly positively correlated with tobacco aroma precursors, with significant negative correlations with tobacco phyllosphere trichome morphology, while Pseudomonas showed the opposite pattern; In the fungal community, Filobasidium and Tausonia were significantly negatively correlated with tobacco aroma precursors, and significantly positively correlated with tobacco phyllosphere trichome morphology, while Alternaria showed the opposite pattern. In conclusion, the microbiota (bacteria and fungi) and aroma precursors of the tobacco phyllosphere change significantly as tobacco matures. The presence of Acidisoma, Ralstonia, Bradyrhizobium and Alternaria in the phyllosphere microbiota of tobacco may be related to the aroma precursors of tobacco.

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles.

Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies. Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: "neurodegenerative disease" OR "Alzheimer's disease" OR "Parkinson's disease" OR "Amyotrophic lateral sclerosis" AND "extracellular vesicles" OR "exosomes" OR "outer membrane vesicles" AND "drug delivery systems" AND "blood-brain barrier". MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.

B-cell lymphoma with cytokine storm in serosal effusion: A case report and literature review.

RATIONALE: Cytokine storm is now considered to be a systemic inflammatory response, but local cytokine storm may exist in systemic diseases of the blood system. Monitoring of regional cytokine storm is an important clue for the diagnosis of systemic diseases. PATIENT CONCERNS: A 72-years-old male presented to our hospital with multiple serosal effusion without solid mass or enlarged lymph nodes. We found that the level of cytokines in ascites was tens to hundreds of times higher than that in plasma, mainly IL-6 and IL-8. DIAGNOSES: The patient was diagnosed with multiple serous effusion, hemophagocytic syndrome, B-cell lymphoma, Epstein-Barr virus infection, and hypoproteinemia. INTERVENTIONS: During hospitalization, the patient was treated with 5 courses of R-CVEP therapy and supportive treatment. OUTCOMES: After the first R-CVEP regimen, the patient's condition was evaluated as follows: hemophagocytic syndrome improved: no fever; Serum triglyceride 2.36 mmol/L; Ferritin 70.70 ng/L; no hemophagocyte was found in the bone marrow; the lymphoma was relieved, ascites disappeared, and bone marrow cytology showed: the bone marrow hyperplasia was reduced, and small platelet clusters were easily seen. Bone marrow flow cytometry showed that lymphocytes accounted for 13.7%, T cells increased for 85.7%, CD4/CD8 = 0.63, B cells decreased significantly for 0.27%, and NK cells accounted for 10.2%. Blood routine returned to normal: WBC 5.27 × 109/L, HB 128 g/L, PLT 129 × 109/L; Epstein-Barr virus DNA < 5.2E + 02 copies/mL; correction of hypoproteinemia: albumin 39.7 g/L. LESSONS: Cytokines in ascites are significantly higher than those in plasma by tens to hundreds of times, suggesting that "regional cytokine storms" may cause serosal effusion.

Retrospective Clinical Observation of Correlation between Galectin-3 and Early Herpes Zoster Neuralgia and Post-herpetic Neuralgia.

Background: Herpes Zoster Neuralgia (HZN) and Post-Herpetic Neuralgia (PHN) are neuropathic pain conditions following Varicella Zoster Virus infection. PHN primarily affects individuals aged 60 and above and the pervasive and severe neuropathic pain in PHN leads to significant emotional and psychological distress in approximately 80%-90% of patients, precipitating a decline in their overall quality of life and that of their families. Galectin-3, a pro-inflammatory factor, is implicated in inflammatory responses, potentially influencing neuronal damage and pain signal transmission. Objective: This study aims to evaluate the clinical relevance of serum Galectin-3 in HZN and PHN patients, alongside other contributing factors. Methods: We retrospectively analyzed data collected from 40 HZN patients, 40 non-HZN patients, and 20 healthy controls in our hospital between 2015 and 2017. Variables included demographic data, clinical characteristics, and inflammatory markers. Statistical analyses comprised t-tests, ANOVA, chi-square tests, and multivariate logistic regression. A Receiver Operating Characteristic (ROC) curve was constructed to evaluate Galectin-3's predictive value for PHN. Results: PHN patients showed significantly higher ages, NRS scores, and prevalence of shingles in the head and neck region compared to Non-PHN and Non-HZN groups (P < .05). Elevated levels of IL-6 (66.33±8.93 pg/mL) and Galectin-3 (2.44±0.29 ng/mL) were observed in HZN patients. Galectin-3 emerged as a significant risk factor for PHN development (P < .05), while other factors such as age, shingles location, IL-6, and T lymphocyte subsets did not show a significant impact. Conclusion: Galectin-3 may serve as a predictive biomarker for PHN development, offering insights into its pathophysiology and potential therapeutic targets. Patients with elevated Galectin-3 levels might benefit from specific targeted therapies or interventions aimed at reducing Galectin-3 levels and mitigating its effects.

Heterogeneity and tumoral origin of medulloblastoma in the single-cell era.

Medulloblastoma is one of the most common malignant pediatric brain tumors derived from posterior fossa. The current treatment includes maximal safe surgical resection, radiotherapy, whole cranio-spinal radiation and adjuvant with chemotherapy. However, it can only limitedly prolong the survival time with severe side effects and relapse. Defining the intratumoral heterogeneity, cellular origin and identifying the interaction network within tumor microenvironment are helpful for understanding the mechanisms of medulloblastoma tumorigenesis and relapse. Due to technological limitations, the mechanisms of cellular heterogeneity and tumor origin have not been fully understood. Recently, the emergence of single-cell technology has provided a powerful tool for achieving the goal of understanding the mechanisms of tumorigenesis. Several studies have demonstrated the intratumoral heterogeneity and tumor origin for each subtype of medulloblastoma utilizing the single-cell RNA-seq, which has not been uncovered before using conventional technologies. In this review, we present an overview of the current progress in understanding of cellular heterogeneity and tumor origin of medulloblastoma and discuss novel findings in the age of single-cell technologies.

Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. METHODS: A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. RESULTS: In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. CONCLUSION: This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.

Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.

Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment due to acquired drug resistance. Epigenetic regulation is known to contribute to cisplatin resistance; nevertheless, the underlying mechanisms remain poorly understood. Here, we showed that lysine-specific demethylase 5B (KDM5B) was overexpressed and correlates with tumor progression and cisplatin resistance in patients with NPC. We also showed that specific inhibition of KDM5B impaired the progression of NPC and reverses cisplatin resistance, both in vitro and in vivo. Moreover, we found that KDM5B inhibited the expression of ZBTB16 by directly reducing H3K4me3 at the ZBTB16 promoter, which subsequently increased the expression of Topoisomerase II- α (TOP2A) to confer cisplatin resistance in NPC. In addition, we showed that the deubiquitinase USP7 was critical for deubiquitinating and stabilizing KDM5B. More importantly, the deletion of USP7 increased sensitivity to cisplatin by disrupting the stability of KDM5B in NPC cells. Therefore, our findings demonstrated that USP7 stabilized KDM5B and promoted cisplatin resistance through the ZBTB16/TOP2A axis, suggesting that targeting KDM5B may be a promising cisplatin-sensitization strategy in the treatment of NPC.

Specific serum autoantibodies predict the development and progression of Alzheimer's disease with high accuracy.

Autoimmunity plays a key role in the pathogenesis of Alzheimer's disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Irradiated engineered tumor cell-derived microparticles remodel the tumor immune microenvironment and enhance antitumor immunity.

Radiotherapy (RT), administered to roughly half of all cancer patients, occupies a crucial role in the landscape of cancer treatment. However, expanding the clinical indications of RT remains challenging. Inspired by the radiation-induced bystander effect (RIBE), we used the mediators of RIBE to mimic RT. Specifically, we discovered that irradiated tumor cell-released microparticles (RT-MPs) mediated the RIBE and had immune activation effects. To further boost the immune activation effect of RT-MPs to achieve cancer remission, even in advanced stages, we engineered RT-MPs with different cytokine and chemokine combinations by modifying their production method. After comparing the therapeutic effect of the engineered RT-MPs in vitro and in vivo, we demonstrated that tIL-15/tCCL19-RT-MPs effectively activated antitumor immune responses, significantly prolonged the survival of mice with malignant pleural effusion (MPE), and even achieved complete cancer remission. When tIL-15/tCCL19-RT-MPs were combined with PD-1 monoclonal antibody (mAb), a cure rate of up to 60% was achieved. This combination therapy relied on the activation of CD8+ T cells and macrophages, resulting in the inhibition of tumor growth and the establishment of immunological memory against tumor cells. Hence, our research may provide an alternative and promising strategy for cancers that are not amenable to conventional RT.

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Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein purpura, has complex etiology and pathogenesis which have not been fully clarified. The latest research shows that SARS-CoV-2 and related vaccines, human papilloma vaccine, and certain biological agents can also induce IgAV. Most studies believe that the formation of galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complex plays a crucial role in the pathogenesis of IgAV. It is hypothesized that the pathogenesis of IgAV is associated with the binding of IgA1 to anti-endothelial cell antibodies. In addition, genetics also constitutes a major focus of IgAV research. This article reviews the new advances in the etiology of IgAV and summarizes the role of Gd-IgA1, Gd-IgA1-containing immune complex, anti-endothelial antibody, IgA1 conjugates, T lymphocyte immunity, and genetic factors in the pathogenesis of IgAV.

Wettability of HPMC/PEG/CS Thermosensitive Porous Hydrogels.

Thermosensitive hydrogels have been receiving attention in the development of fire extinguishing agents due to their stimuli responsivity. Conventional hydrogels are limited by their slow response rate, and their wettability has not been studied systematically. In the present study, a concentrate of a thermosensitive porous system has been successfully synthesized by adding Na2CO3/CH3COOH as a foaming agent into the mixture of hydroxypropyl methylcellulose (HPMC)/polyethylene glycol (PEG)/chitosan (CS). The systems with different concentrations were obtained by diluting the concentrate with water. Thermosensitivity, surface tension and contact angle were characterized. In addition, spreadability, wettability and adhesivity were investigated systematically. Results showed that the systems with a concentration greater than 15 wt% exhibited outstanding performance of thermosensitivity and coagulability. A total of 20 wt% of the system has the best spreadability and wettability on the wood surface, most likely due to favorable contributions brought by both adequate viscosity and hydrophilicity. The adhesive force and surface-free energy of the pre-gel droplet that reached deposition on the wood surface decreased by 46.78% and 20.71%, respectively. The gel has a great capacity of water retention over a long period of time, which makes this porous gel the best system when it comes to its wettability and adhesiveness towards the chosen wood surface. The equilibrium surface tension decreased by 45.50% compared with water. HPMC/PEG/CS thermosensitive porous hydrogel with excellent wettability presented wide-ranging possibilities for the further development of fire suppression agents of fast phase-transition thermosensitive hydrogel.

ABF1 Positively Regulates Rice Chilling Tolerance via Inducing Trehalose Biosynthesis.

Chilling stress seriously limits grain yield and quality worldwide. However, the genes and the underlying mechanisms that respond to chilling stress remain elusive. This study identified ABF1, a cold-induced transcription factor of the bZIP family. Disruption of ABF1 impaired chilling tolerance with increased ion leakage and reduced proline contents, while ABF1 over-expression lines exhibited the opposite tendency, suggesting that ABF1 positively regulated chilling tolerance in rice. Moreover, SnRK2 protein kinase SAPK10 could phosphorylate ABF1, and strengthen the DNA-binding ability of ABF1 to the G-box cis-element of the promoter of TPS2, a positive regulator of trehalose biosynthesis, consequently elevating the TPS2 transcription and the endogenous trehalose contents. Meanwhile, applying exogenous trehalose enhanced the chilling tolerance of abf1 mutant lines. In summary, this study provides a novel pathway 'SAPK10-ABF1-TPS2' involved in rice chilling tolerance through regulating trehalose homeostasis.

Exogenous abscisic acid represses rice flowering via SAPK8-ABF1-Ehd1/Ehd2 pathway.

INTRODUCTION: Rice flowering is a major agronomic trait, determining yield and ecological adaptability in particular regions. ABA plays an essential role in rice flowering, but the underlying molecular mechanism remains largely elusive. OBJECTIVES: In this study, we demonstrated a "SAPK8-ABF1-Ehd1/Ehd2" pathway, through which exogenous ABA represses rice flowering in a photoperiod-independent manner. METHODS: We generated abf1 and sapk8 mutants using the CRISPR-Cas9 method. Using yeast two-hybrid, Pull down, BiFC and kinase assays, SAPK8 interacted and phosphorylated ABF1. ABF1 directly bound to the promoters of Ehd1 and Ehd2 using ChIP-qPCR, EMSA, and LUC transient transcriptional activity assay, and suppressed the transcription of these genes. RESULTS: Under both long day and short day conditions, simultaneous knock-out of ABF1 and its homolog bZIP40 accelerated flowering, while SAPK8 and ABF1 over-expression lines exhibited delayed flowering and hypersensitivity to ABA-mediated flowering repression. After perceiving the ABA signal, SAPK8 physically binds to and phosphorylates ABF1 to enhance its binding to the promoters of master positive flowering regulators Ehd1 and Ehd2. Upon interacting with FIE2, ABF1 recruited PRC2 complex to deposit H3K27me3 suppressive histone modification on Ehd1 and Ehd2 to suppress these genes transcription, thereby leading to later flowering. CONCLUSION: Our work highlighted the biological functions of SAPK8 and ABF1 in ABA signaling, flowering control and the involvement of a PRC2-mediated epigenetic repression mechanism in the transcription regulation governed by ABF1 on ABA-mediated rice flowering repression.

[Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism].

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1ß, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION: Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Nomograms incorporating primary tumor response at mid-radiotherapy to predict survival in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: A nomogram that incorporates tumor response at mid-radiotherapy (mid-RT) to predict the prognosis of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) has not been established. METHODS: This study retrospectively reviewed 583 patients with LA-NPC who underwent magnetic resonance imaging scans at mid-RT (the fourth week of RT) between 2015 and 2019. RESULTS: Primary tumor (PT) response at mid-RT was found to predict disease-free survival (DFS) and overall survival (OS). Independent factors from multivariable analysis to predict DFS and OS were assembled into nomograms with (nomograms Amid-RT and Bmid-RT ) or without (nomograms Abaseline and Bbaseline ) PT response. Internal validation revealed good performance of these nomograms in discrimination: C-statistics = 0.761 for nomogram Amid-RT and 0.809 for nomogram Bmid-RT , which showed better discrimination performance than (C-statistics: 0.755) nomogram Abaseline and (C-statistics: 0.798) nomogram Bbaseline (Z-statistic = 2.476, p < 0.05; Z-statistic = 1.971, p < 0.05). CONCLUSION: The nomograms based on PT response at mid-RT showed favorable predictive accuracy for DFS and OS in patients with LA-NPC.

Mendelian randomization analyses of smoking and Alzheimer's disease in Chinese and Japanese populations.

Background: Previous epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer's disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis. Methods: We used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively. Results: Genetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149-1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790-1.734, p = 0.434). Conclusion: This MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.

Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease.

Inadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer's disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. Here, we show that brain-derived extracellular vesicles (EVs) from adult AD or wild-type mice can cross the blood-brain barrier to reach the distal bone tissue, while only AD brain-derived EVs (AD-B-EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone-fat imbalance. MiR-483-5p is highly enriched in AD-B-EVs, brain tissues from AD mice, and plasma-derived EVs from AD patients. This miRNA mediates the anti-osteogenic, pro-adipogenic, and pro-osteoporotic effects of AD-B-EVs by inhibiting Igf2. This study identifies the role of B-EVs as a promoter of osteoporosis in AD by transferring miR-483-5p.