Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.

The importance of autophagy in atherosclerosis has garnered significant attention regarding the potential applications of autophagy inducers. However, the impact of TAT-Beclin1, a peptide inducer of autophagy, on the development of atherosclerotic plaques remains unclear. Single-cell omics analysis indicates a notable reduction in GAPR1 levels within fibroblasts, stromal cells, and macrophages during atherosclerosis. Tat-beclin1 (T-B), an autophagy-inducing peptide derived from Beclin1, could selectively bind to GAPR1, relieving its inhibition on Beclin1 and thereby augmenting autophagosome formation. To investigate its impact on atherosclerosic plaque progression, we established the ApoE-/- mouse model of carotid atherosclerotic plaques. Surprisingly, intravenous administration of Tat-beclin1 dramatically accelerated the development of carotid artery plaques. Immunofluorescence analysis suggested that macrophage aggregation and autophagosome formation within atherosclerotic plaques were significantly increased upon T-B treatment. However, immunofluorescence and transmission electron microscopy (TEM) analysis revealed a reduction in autophagy flux through lysosomes. In vitro, the interaction between T-B and GAPR1 was confirmed in RAW264.7 cells, resulting in the increased accumulation of p62/SQSTM1 and LC3-II in the presence of ox-LDL. Additionally, T-B treatment elevated the protein levels of p62/SQSTM1, LC3-II, and cleaved caspase 1, along with the secretion of IL-1β in response to ox-LDL exposure. In summary, our study underscores that T-B treatment amplifies abnormal autophagy and inflammation, consequently exacerbating atherosclerotic plaque development in ApoE-/- mice.

UNASSIGNED: Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production of extracellular matrix and inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, and aortic aneurysm. TGF-β (transforming growth factor-β) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-β activity and VSMC phenotypic regulation under in vivo conditions are poorly understood. The extracellular matrix protein TN-X (tenascin-X) has recently been shown to bind TGF-β and to prevent it from activating its receptor.
UNASSIGNED: We studied the role of TN-X in VSMCs in various murine disease models using tamoxifen-inducible SMC-specific knockout and adeno-associated virus-mediated knockdown.
UNASSIGNED: In hypertensive and high-fat diet-fed mice, after carotid artery ligation as well as in human aneurysmal aortae, expression of Tnxb, the gene encoding TN-X, was increased in VSMCs. Mice with smooth muscle cell-specific loss of TN-X (SMC-Tnxb-KO) showed increased TGF-β signaling in VSMCs, as well as upregulated expression of VSMC differentiation marker genes during vascular remodeling compared with controls. SMC-specific TN-X deficiency decreased neointima formation after carotid artery ligation and reduced vessel wall thickening during Ang II (angiotensin II)-induced hypertension. SMC-Tnxb-KO mice lacking ApoE showed reduced atherosclerosis and Ang II-induced aneurysm formation under high-fat diet. Adeno-associated virus-mediated SMC-specific expression of short hairpin RNA against Tnxb showed similar beneficial effects. Treatment with an anti-TGF-β antibody or additional SMC-specific loss of the TGF-β receptor reverted the effects of SMC-specific TN-X deficiency.
UNASSIGNED: In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-β signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.

UNASSIGNED: The association of cognitive function, its changes, and all-cause mortality has not reached a consensus, and the independence of the association between changes in cognitive function and mortality remains unclear. The purpose of this study was to evaluate the longitudinal association between baseline cognitive function and cognitive changes over 1 year with subsequent all-cause mortality among the older adults aged 60 and above.
UNASSIGNED: A prospective cohort study utilizing the Community Older Adults Health Survey data. Initiated in 2018, the study annually assessed all individuals aged 60+ in Dalang Town, Dongguan City. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). A total of 6,042 older adults individuals were included, and multivariate Cox proportional hazard models were used to examine cognitive function\'s impact on mortality.
UNASSIGNED: Participants\' median age was 70 years, with 39% men. Over a median 3.08-year follow-up, 525 died. Mortality risk increased by 6% per MMSE score decrease (adjusted HR = 1.06, 95%CI: 1.05-1.08). Compared to those with normal cognitive function at baseline, participants with mild cognitive impairment and moderate to severe cognitive impairment had significantly higher mortality risks (adjusted HR = 1.40, 95%CI: 1.07-1.82; HR = 2.49, 95%CI: 1.91-3.24, respectively). The risk of death was 5% higher for each one-point per year decrease in cognitive function change rate (HR = 1.05, 95%CI: 1.02-1.08). Compared with participants with stable cognitive function, those with rapid cognitive decline had a 79% increased risk of death (adjusted HR = 1.79, 95% CI: 1.11-2.87), with baseline cognitive function influencing this relationship significantly (P for interaction = 0.002).
UNASSIGNED: Baseline cognitive impairment and rapid cognitive decline are associated with higher all-cause mortality risks in Chinese older adults. Baseline function influences the mortality impact of cognitive changes.

UNASSIGNED: To examine the potential association between polycystic ovary syndrome (PCOS) and hyperuricemia and to elucidate the underlying contributory factors.
UNASSIGNED: Retrospective study on 603 women with PCOS and 604 women without PCOS. Anthropometric features, reproductive hormone profiles, and metabolic parameters were measured and compared between two groups of patients. Examinations of correlations between SUA levels and other parameters were conducted to discern potential correlations.
UNASSIGNED: Both serum uric acid levels and the incidence of hyperuricemia exhibited statistically significant elevations in women with PCOS when compared to their counterparts without PCOS. Nonetheless, this statistical difference was not found between the obese subgroup after stratifying study subjects by body mass index (BMI). Pearson\'s correlation analysis underscored the prominence of BMI as a robust factor influencing SUA levels in women, regardless of their PCOS status. Furthermore, multivariable linear regression model demonstrated significant positive associations between SUA levels and several variables, namely dehydroepiandrosterone sulfate (DHEA-S), free androgen index (FAI), total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), area under the curve for insulin (AUC-I), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, it is noteworthy that the prevalence of hyperuricemia exhibited a positive association with fasting plasma glucose (FPG) levels, while conversely, it displayed a negative association with estradiol (E2) levels.
UNASSIGNED: PCOS is associated with a significant elevation of SUA level and hyperuricemia prevalence. HA, IR, and dyslipidemia may be the mediators in the pathogenesis of hyperuricemia in women with PCOS.

UNASSIGNED: Despite the fact that China amounts to one-fifth of the world\'s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.
UNASSIGNED: Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.
UNASSIGNED: A diet rich in \"carnivorous\", \"vegetarian\", \"dairy, fruit, and egg\" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in \"beverage and fried food\" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.
UNASSIGNED: Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

UNASSIGNED: Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown.
UNASSIGNED: The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold.
UNASSIGNED: Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development.

BACKGROUND: We conducted analyses of the association between smoking and osteoporosis and osteoporotic fractures using a secondary dataset analysis of the National Health and Nutrition Examination Survey (NHANES) database and the two-sample Mendelian randomization (MR) method.
METHODS: The associations between smoking and osteoporosis or osteoporotic fractures were analyzed using weighted logistic regression models for both univariate and multivariable analyses using pooled 1999-2018 NHANES data. The summary-level data of genome-wide association studies (GWAS) of smoking and osteoporosis were extracted from the IEU Open GWAS project. The inverse variance weighted method was used as the main method for the two-sample MR analysis.
RESULTS: We obtained the following main findings based on the NHANES data: smoking was associated with osteoporosis according to the analyses of 30856 participants (OR=1.21; 95% CI: 1.06-1.39, p=0.004); smoking was associated with hip osteoporotic fracture according to the analyses of 30928 participants (OR=1.47; 95% CI: 1.14-1.90, p=0.004); smoking was associated with wrist osteoporotic fracture according to the analyses of 30923 participants (OR=1.33; 95% CI: 1.18-1.49, p<0.001); and smoking was associated with spine osteoporotic fracture according to the analyses of 30910 participants (OR=1.43, 95% CI: 1.18-1.73, p<0.001). In addition, we confirmed the potential causal effect of smoking on the risk of osteoporotic fracture (OR=24.5; 95% CI: 1.11-539, p=0.043) by conducting two-sample MR analyses.
CONCLUSIONS: Smoking was associated with increased risks of both osteoporosis and osteoporotic fracture. Smoking showed a potential causal effect on the risk of osteoporotic fracture.

Atherosclerosis (AS) is a complex disease caused by multiple pathological factors threatening human health-the pathogenesis is yet to be fully elucidated. In recent years, studies have exhibited that the onset of AS is closely involved with oral and gut microbiota, which may initiate or worsen atherosclerotic processes through several mechanisms. As for how the two microbiomes affect AS, existing mechanisms include invading plaque, producing active metabolites, releasing lipopolysaccharide (LPS), and inducing elevated levels of inflammatory mediators. Considering the possible profound connection between oral and gut microbiota, the effect of the interaction between the two microbiomes on the initiation and progression of AS has been investigated. Findings are oral microbiota can lead to gut dysbiosis, and exacerbate intestinal inflammation. Nevertheless, relevant research is not commendably refined and a concrete review is needed. Hence, in this review, we summarize the most recent mechanisms of the oral microbiota and gut microbiota on AS, illustrate an overview of the current clinical and epidemiological evidence to support the bidirectional connection between the two microbiomes and AS.

UNASSIGNED: During the COVID-19 pandemic, older adults were facing more mental health issues that may cause complex impacts on pandemic prevention, and turning to the internet for health information is a double-edged sword for them. This study aimed to investigate the reciprocal relationship between negative emotions and prevention behaviors in older adults, as well as the direct and moderating effects of online health information seeking (OHIS) on negative emotions and prevention behaviors.
UNASSIGNED: Based on the common-sense model of self-regulation (CSM) and a sample of more than 20,000 participants from the Survey of Health, Aging and Retirement in Europe (SHARE), this study first used an autoregressive cross-lagged panel model (CLPM) to analyze the longitudinal effect of negative emotions on prevention behaviors. Second, the study used ordinary least squares (OLS) regression to explore the influence of OHIS usage frequency changes on negative emotions and prevention behaviors. Third, the study used multigroup analysis to examine the moderating effect of OHIS usage frequency changes on the CLPM.
UNASSIGNED: The findings indicate a significant longitudinal association where initial negative emotions predicted later prevention behaviors (β = 0.038, p < 0.001), and increased OHIS frequency was linked to positive changes in prevention behavior (β = 0.109, p < 0.001). Multigroup analysis revealed that the connection between negative emotions or increased negative emotions and prevention behaviors remained significant for those with no change or an increase in OHIS frequency but not for those with a decrease.
UNASSIGNED: This study suggested that negative emotions may drive older adults to engage more in prevention behaviors and that OHIS can augment this effect. These results underscore the importance of addressing mental health and providing reliable online health information to support older adults in managing infectious disease risks.