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Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases 1 – 3 . Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium . These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis. The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive—but not Gram-negative—multidrug-resistant pathogens.

Due to symptomatic gait imbalance and a high incidence of falls, patients with cervical disease—including degenerative cervical myelopathy—have a significantly increased risk of fragility fractures. To prevent such fractures in patients with cervical disease, treating osteoporosis is an important strategy. This study aimed to validate the diagnostic yield of a deep learning algorithm for detecting osteopenia/osteoporosis using cervical radiography and compare its diagnostic accuracy with that of spine surgeons. Samples were divided into training ( n  = 200) and test ( n  = 30) datasets. The deep learning algorithm, designed to detect T-scores of the femoral neck or lumbar spine <-1.0 using cervical radiography, was constructed using a convolutional neural network model. The number of correct diagnoses was compared between the algorithm and nine spine surgeons using the independent test dataset. The results indicated that the algorithm’s diagnostic accuracy, sensitivity, and specificity in the independent test dataset were 0.800, 0.818, and 0.750, respectively. The rate of corrected answers by the deep learning algorithm was significantly higher than that of nine spine surgeons in the test dataset (80.0% vs. 60.6%; p  = 0.032). In conclusion, the diagnostic yield of the algorithm was higher than that of spine surgeons.

Aging is a major risk factor for cancer, but the precise mechanism by which aging promotes carcinogenesis remains largely unknown. Here, using genetically modified mouse models, we show that p16 high senescent (p16 h -sn) fibroblasts accumulate with age, constitute inflammatory cancer-associated fibroblasts (CAFs) and promote tumor growth in bladder cancer models. Single-cell RNA sequencing of fibroblasts from aged mice revealed higher expression of the C–X–C motif chemokine 12 gene ( Cxcl12 ) in p16 h -sn fibroblasts than in p16 low fibroblasts. Elimination of p16 h -sn cells or inhibition of CXCL12 signaling notebly suppressed bladder tumor growth in vivo. We identified high expression levels of SMOC2 , GUCY1A1 ( GUCY1A3 ), CXCL12 , CRISPLD2 , GAS1 and LUM as a signature of p16 h -sn CAFs in humans and mice, which was associated with age and poor prognosis in patients with advanced and nonadvanced bladder cancer. Here we show that p16 h -sn fibroblasts in the aged bladder create a cancer-permissive niche and promote tumor growth by secreting CXCL12. Meguro et al. show an accumulation of p16 high senescent fibroblasts in the aging bladder that serves as a cancer-permissive niche and promotes tumor growth by secreting CXCL12. Inhibition of senescence or CXCL12 signaling suppresses bladder tumor growth.

Study Design Retrospective cohort study. Objective Condoliase is a chemonucleolysis for lumbar disc herniation (LDH) that enzymatically degrades herniated disc material with high specificity for chondroitin sulfate and hyaluronic acid. Few studies have compared condoliase treatment with surgical treatments. We compared the clinical outcomes of condoliase treatment and minimally invasive discectomy. Methods Patients who received condoliase treatment or minimally invasive discectomy at single institution were included. Propensity score matching was performed to adjust for age and sex. We included 146 patients with LDH (73 per group). The Japan Orthopaedic Association (JOA) score, visual analog scale (VAS) for leg pain, and disc height and degeneration were assessed at baseline and 2 weeks, 3 months, and 1 year after treatment. Results The JOA score and leg pain VAS improved significantly over time (P < .001, Friedman’s test). Two weeks after treatment, a marked improvement in JOA score and leg pain VAS was observed in the surgery group compared with the condoliase group (P < .001, mixed-effects model). However, 3 months and 1 year after treatment, the differences were not significant. In contrast, disc height reduction was significantly greater in the condoliase group than in the surgery group at 3 months and 1 year after treatment (P < .001, mixed-effects model). Condoliase treatment was identified as an independent risk factor for progression of disc degeneration (odds ratio, 23.60; P = .001, logistic regression analysis). Conclusion Condoliase treatment demonstrated mid-term efficacy comparable to surgical treatment; however, it required more time for pain relief and was potentially associated with progression of disc degeneration.

Recently, hexaazatriphenylene (HA)‐based covalent organic frameworks have garnered attention as polymer electrolyte membranes (PEMs) in polymer electrolyte fuel cells due to their robust framework and strong ion‐trapping capabilities. In this study, quinone‐functionalized HA‐based covalent organic frameworks (HAQ‐COFs) are synthesized by hydrothermal synthesis. This method is much simpler than the synthesis methods previously reported, and is also suitable for mass production. X‐ray diffraction (XRD) and Fourier‐transform infrared measurements reveal that HAQ‐COF exhibits a crystal structure where 2D molecular layers, formed by HA units and bridging paraquinone units, are stacked, creating pores that align to form channels for ion transport. Thermogravimetry and XRD measurements, as a function of temperature, demonstrate that HAQ‐COF exhibits high water retention capacity at room temperature and atmospheric pressure and has greater thermal stability than other PEMs. Electrochemical impedance spectroscopy measurements indicate that the proton conductivity of HAQ‐COF remains nearly unaffected by changes in external humidity, allowing it to sustain high proton conductivity even under sudden humidity drops. Moreover, the activation energy for proton hopping conduction in HAQ‐COF is significantly lower compared to that of similar proton conductors. A quinone‐functionalized hexaazatriphenylene‐based covalent organic framework (HAQ‐COF) is synthesized, making HAQ‐COF a promising polymer electrolyte membrane material for polymer electrolyte fuel cells. HAQ‐COF exhibits high water retention at room temperature and atmospheric pressure, along with high thermal stability. Additionally, the activation energy for proton hopping conduction in HAQ‐COF is very low compared to similar proton conductors.

As organs undergo the process of aging, they exhibit signs of progressive fibrosis, a hallmark of aging that is observed in various organs, including the liver, kidneys, and lungs. Liver fibrosis is a particularly deleterious outcome of the healing processes that occur during the repair of chronic liver injury. It is widely accepted that the majority of these injuries are initially triggered by hepatocytes. Indeed, elderly patients have been shown to be more prone to developing liver fibrosis following hepatic injury. However, the mechanisms by which aging promotes fibrotic processes remain to be elucidated. The preceding observation, indicating a robust correlation between the severity of fibrosis in human cirrhotic patients and the population of hepatocytes expressing elevated levels of p16Ink4a (p16h), proposes that p16h hepatocytes might serve as initiators of fibrogenic processes in response to liver injury. In this study, we employed a CCl4‐induced hepatitis model to promote a fibrogenic process and observed the accumulation of p16h hepatocytes in zone 3. These p16h cells manifest numerous senescent characteristics, and their accumulation has been strongly correlated with the severity of liver fibrosis. Selective elimination of p16h hepatocytes has been shown to ameliorate CCl4‐induced liver fibrosis, presumably through the suppression of hepatic stellate cell activation. Single‐cell transcriptomic analysis revealed that murine and human hepatocytes up‐regulated Ctf1 or Lif, the ligands of the LIFR signaling pathway. The administration of LIFR ligands has been demonstrated to enhance the phosphorylation of STAT3, and the LIFR inhibitor rescued the fibrogenic phenotype in hepatic stellate cells induced by secreted factors from senescent hepatocytes. This finding offers potential therapeutic insights for the management of liver fibrosis. This study found that, following the long‐term CCl4 treatment, p16high hepatocytes appeared in zone 3, spatially co‐localizing with fibrotic areas. A specific cluster of p16high hepatocytes upregulated CTF1/LIF expression which induced HSC activation and further liver fibrosis, as revealed by single cell transcriptomic analysis. The transcriptomic signatures of mouse p16high hepatocytes exhibited a significantly enrichment in a subset of human hepatocytes derived from liver cirrhotic patients, as opposed to those from healthy donors.

Study Design Retrospective cohort study. Objectives Spinal surgeons face a dilemma regarding the continuation or discontinuation of antiplatelet agents during the perioperative period. Guidelines recommend considering the balance between thrombotic and bleeding risks. However, no consensus exists for the use of these agents for patients who undergo minimally invasive lumbar decompression. This study aimed to assess the effect of continued antiplatelet medication on minimally invasive posterior lumbar decompression surgery outcomes, focusing on perioperative outcomes and 1-year postoperative clinical results. Methods This study included 106 patients who underwent minimally invasive posterior lumbar decompression between 2017 and 2022 and were taking antiplatelet medications before spinal surgery. Patient characteristics, antiplatelet medication type, and perioperative data were analyzed. Patients were divided into “continuation” and “discontinuation” groups based on preoperative antiplatelet medication status. Univariate and multivariate linear regression analyses were performed. Results No significant differences were observed between groups in terms of surgical time, intraoperative blood loss, postoperative drain volume, complication rates, and Japanese Orthopedic Association scores and EuroQoL-5 dimensions 5-level at 1 year postoperatively. Similar results were noted in groups focusing exclusively on patients treated with aspirin. Multivariate linear regression revealed that surgical time per level was significantly associated with total blood loss, whereas antiplatelet medications did not show a significant relationship (operative time per level, P < 0.01; antiplatelet drugs, P = 0.459). Conclusions This study suggests that minimally invasive posterior lumbar spine decompression can be performed safely and effectively under continuous antiplatelet medication. Further studies with more evidence are required to validate our findings.

As organs undergo the process of aging, they exhibit signs of progressive fibrosis, a hallmark of aging that is observed in various organs, including the liver, kidneys, and lungs. Liver fibrosis is a particularly deleterious outcome of the healing processes that occur during the repair of chronic liver injury. It is widely accepted that the majority of these injuries are initially triggered by hepatocytes. Indeed, elderly patients have been shown to be more prone to developing liver fibrosis following hepatic injury. However, the mechanisms by which aging promotes fibrotic processes remain to be elucidated. The preceding observation, indicating a robust correlation between the severity of fibrosis in human cirrhotic patients and the population of hepatocytes expressing elevated levels of p16 Ink4a (p16 h ), proposes that p16 h hepatocytes might serve as initiators of fibrogenic processes in response to liver injury. In this study, we employed a CCl 4 ‐induced hepatitis model to promote a fibrogenic process and observed the accumulation of p16 h hepatocytes in zone 3. These p16 h cells manifest numerous senescent characteristics, and their accumulation has been strongly correlated with the severity of liver fibrosis. Selective elimination of p16 h hepatocytes has been shown to ameliorate CCl 4 ‐induced liver fibrosis, presumably through the suppression of hepatic stellate cell activation. Single‐cell transcriptomic analysis revealed that murine and human hepatocytes up‐regulated Ctf1 or Lif, the ligands of the LIFR signaling pathway. The administration of LIFR ligands has been demonstrated to enhance the phosphorylation of STAT3, and the LIFR inhibitor rescued the fibrogenic phenotype in hepatic stellate cells induced by secreted factors from senescent hepatocytes. This finding offers potential therapeutic insights for the management of liver fibrosis.

The static and dynamic flying characteristics of a slider in a hard disk drive have become an important consideration owing to recent increases in recording density. In the present paper, the characteristics of a plane inclined slider (Case 1) and a step slider flying in either air or He (Case 2) over a running boundary wall with local temperature distributions are analyzed using the thermo-molecular gas-film lubrication (t-MGL) equation. For a plane inclined slider (Case 1), the fundamental static and dynamic characteristics are analyzed numerically and are examined through two limiting approximations: the approximation for infinite bearing number and the incompressible short bearing approximation. For a step slider (Case 2), the decreases in the minimum spacing for a slider flying in He are significant because the mean free path of He, λ He , is approximately three times that of air, λ air . The increases in the minimum spacing due to laser heating are negligible in both air and He because the heat spot size is very small. Moreover, the decrease in the minimum spacing produced by thermal deformation (projection height, d max ) by laser heating in the thermal fly-height control slider is reduced by the total additional pressure of (1) MGL pressures produced by the air-film wedge effect, (2) t-MGL pressures produced by the applied temperature distribution, and (3) van der Waals attractive pressure due to the ultra-small spacing. The spacing fluctuation in He caused by a running wavy disk is smaller than that in air, because the inlet-to-outlet spacing ratio ( h 1 / h 0 ) in He is larger than that in air.

Background: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-33 is believed to play an important role in the pathogenesis of RA. We recently reported that FcγRI is responsible for producing abundant tumor necrosis factor alpha (TNF-α) from cultured synovium-derived MCs (SyMCs) in response to aggregated immunoglobulin G (IgG). However, whether or not IL-33 affects immune complex (IC)-induced synovial MC activation remains unknown. This study sought to evaluate the effect of IL-33 on IC-induced synovial MC activation. Methods: Cultured SyMCs were generated by culturing synovial cells with stem cell factor. ST2 expression was analyzed using FACS and immunohistochemical techniques. Mediators released from the MCs were measured using EIAs or ELISAs. Results: SyMCs obtained from patients with RA or osteoarthritis (OA) expressed ST2 on their surfaces. We confirmed the expression of ST2 in MCs using immunofluorescence staining in joint tissue obtained from RA patients. IC-triggered histamine release was not enhanced by IL-33. However, IL-33 synergistically enhanced IC-induced IL-8 and TNF-α production in SyMCs. Conclusions: ICs and IL-33 may exacerbate inflammation associated with RA by abundantly producing TNF-α and IL-8 from SyMCs.