ABSTRACT
Background
This study aimed to investigate the effect of systemic inflammation, assessed by high sensitivity C‐reactive protein (hs‐CRP) levels, on prediabetes progression and regression in ...middle‐aged and older adults based on the China Health and Retirement Longitudinal Study (CHARLS).
Methods
Participants with prediabetes from CHARLS were followed up 4 years later with blood samples collected for measuring fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The level of hs‐CRP was assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow‐up was defined primarily according to the American Diabetes Association (ADA) criteria. Logistic regression models were used to estimate the odds ratios (ORs) and confidence intervals (CIs). We also performed stratified analyses according to age, gender, BMI, the presence of hypertension, and the disease history of heart disease and dyslipidemia and sensitivity analyses excluding a subset of participants with incomplete data.
Results
Of the 2,874 prediabetes included at baseline, 834 participants remained as having prediabetes, 146 progressed to diabetes, and 1,894 regressed to normoglycemia based on ADA criteria with a 4 year follow‐up. After multivariate logistics regression analysis, prediabetes with middle (0.67–1.62 mg/L) and high (>1.62 mg/L) hs‐CRP levels had an increased incidence of progressing to diabetes compared with prediabetes with low hs‐CRP levels (<0.67 mg/L; OR = 1.846, 95%CI: 1.129–3.018; and OR = 1.632, 95%CI: 0.985–2.703, respectively), and the incidence of regressing to normoglycemia decreased (OR = 0.793, 95%CI: 0.645–0.975; and OR = 0.769, 95%CI: 0.623–0.978, respectively). Stratified analyses and sensitivity analyses showed consistent results.
Conclusions
Low levels of hs‐CRP are associated with a high incidence of regression from prediabetes to normoglycemia and reduced odds of progression to diabetes.
This study found that low levels of hs‐CRP are associated with a high incidence of regression from prediabetes to normoglycemia and reduced odds of progression to diabetes. Subgroup analyses showed a stronger association between hs‐CRP and type 2 diabetes in women than in men. Thus, prediabetes may need to be closely monitored in middle‐aged and older women with elevated hs‐CRP. In addition, whether a lower cutoff value for hs‐CRP elevation in women should be proposed is a question worthy of future research.
The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal ...tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes.
Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway.
In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to HPDLSC proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking mechanical strain. The luciferase reporter assay demonstrated that miR-181b-5p may target phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. Real-time PCR and western blotting assay verified that miR-181b-5p enhanced the protein kinase B (PKB, also known as AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and promoted HPDLSC induced by inflammation.
This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation via the miR-181b-5p/PTEN/AKT signaling pathway and promote HPDLSC osteogenic differentiation by BMP2/Runx2, suggesting a potential mechanism for maintaining periodontal homeostasis.
Summary
We selected 42 early‐stage primary biliary cirrhosis (PBC) patients and 30 healthy controls (HC). Metagenomic sequencing of the 16S rRNA gene was used to characterize the fecal microbiome. ...UPLC‐MS/MS assaying of small molecules was used to characterize the metabolomes of the serum, urine and feces. Liquid chip assaying of serum cytokines was used to characterize the immune profiles. The gut of PBC patients were depleted of some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii and Ruminococcus bromii, but were enriched in some bacterial taxa containing opportunistic pathogens, such as γ‐Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara. Several altered gut bacterial taxa exhibited potential interactions with PBC through their associations with altered metabolism, immunity and liver function indicators, such as those of Klebsiella with IL‐2A and Neisseriaceae with urinary indoleacrylate. Many gut bacteria, such as some members of Bacteroides, were altered in their associations with the immunity and metabolism of PBC patients, although their relative abundances were unchanged. Consequently, the gut microbiome is altered and may be critical for the onset or development of PBC by interacting with metabolism and immunity.
This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among ...middle-aged and older adults.
Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression.
The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP.
Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.
Objectives
To gauge the relative accuracy of the use of passive and active dynamic navigation systems when placing dental implants, and to determine how registration areas affect the performance of ...these systems.
Materials and Methods
Eighty implants were assigned to be placed into 40 total resin mandible models missing either the left or right first molars using either passive or active dynamic navigation system approaches. U‐shaped tube registration devices were fixed in the edentulous site for 20 models each on the left or right side. Planned and actual implant positions were superimposed to assess procedural accuracy, and parameters including 3D entry deviation, angular deviation, and 3D apex deviation were evaluated with Mann–Whitney U tests and Wilcoxon signed‐rank tests.
Results
Respective angular, entry, and apex deviation values of 1.563 ± 0.977°, 0.725 ± 0.268 mm, and 0.808 ± 0.284 mm were calculated for all included implants, with corresponding values of 1.388 ± 1.090°, 0.789 ± 0.285 mm, and 0.846 ± 0.301 mm in the active group and 1.739 ± 0.826°, 0.661 ± 0.236 mm, and 0.769 ± 0.264 mm in the passive group. Only angular deviation differed significantly among groups, and the registration area was not associated with any significant differences among groups.
Conclusions
Passive and active dynamic navigation approaches can achieve comparable in vitro accuracy. Registration on one side of the missing single posterior tooth area in the mandible can complete single‐tooth implantation on both sides of the posterior teeth, highlighting the promise of further clinical research focused on this topic.
Photocatalytic syngas (CO and H2) production with CO2 as gas source not only ameliorates greenhouse effect, but also produces valuable chemical feedstocks. However, traditional photocatalytic systems ...require noble metal or suffers from low yield. Here, we demonstrate that S vacancies ZnIn2S4 (VS‐ZnIn2S4) nanosheets are an ideal photocatalyst to drive CO2 reduction into syngas. It is found that building S vacancies can endow ZnIn2S4 with stronger photoabsorption, efficient electron–hole separation, and larger CO2 adsorption, finally promoting both hydrogen evolution reaction (HER) and CO2 reduction reaction (CO2RR). The syngas yield of CO and H2 is therefore significantly increased. In contrast to pristine ZnIn2S4, the syngas yield over VS‐ZnIn2S4 can be improved by roughly ≈4.73 times and the CO/H2 ratio is modified from 1:4.18 to 1:1. Total amount of syngas after 12 h photocatalysis is as high as 63.20 mmol g−1 without use of any noble metals, which is even higher than those of traditional noble metal‐based catalysts in the reported literatures. This work demonstrates the critical role of S vacancies in mediating catalytic activity and selectivity, and highlights the attractive ability of defective ZnIn2S4 for light‐driven syngas production.
Efficient syngas production from CO2 photoreduction is achieved by S vacancies ZnIn2S4 (VS‐ZnIn2S4) nanosheets. The critical role of S vacancies in tuning catalysis activity and selectivity is emphasized.
Layered Ni‐rich lithium transition metal oxides are promising battery cathodes due to their high specific capacity, but their poor cycling stability due to intergranular cracks in secondary particles ...restricts their practical applications. Surface engineering is an effective strategy for improving a cathode's cycling stability, but most reported surface coatings cannot adapt to the dynamic volume changes of cathodes. Herein, a self‐adaptive polymer (polyrotaxane‐co‐poly(acrylic acid)) interfacial layer is built on LiNi0.6Co0.2Mn0.2O2. The polymer layer with a slide‐ring structure exhibits high toughness and can withstand the stress caused by particle volume changes, which can prevent the cracking of particles. In addition, the slide‐ring polymer acts as a physicochemical barrier that suppresses surface side reactions and alleviates the dissolution of transition metallic ions, which ensures stable cycling performance. Thus, the as‐prepared cathode shows significantly improved long‐term cycling stability in situations in which cracks may easily occur, especially under high‐rate, high‐voltage, and high‐temperature conditions.
A slide‐ring polymer featuring high elasticity and self‐adaptive ability is designed to improve the performance of lithium‐ion batteries via relieving the cracks of cathode particles and retarding parasitic interfacial side reactions during cycling.
An optimized nanostructure design for high‐power, high‐energy lithium‐ion batteries and supercapacitors is realized by fabricating a nanocomposite with highly dispersed nanoparticles of active ...materials in a nanoporous carbon matrix. A nano‐LiFePO4/nanoporous carbon matrix nanocomposite forms a bridge between a supercapacitor and a battery electrode and offers a reasonable compromise between rate and capacity.
To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor‐associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was ...determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 polarization of macrophages. Immunofluorescence, western blot and qRT‐PCR were performed to detect the expression of neuropilin‐1 (Nrp‐1) and carbonic anhydrase IX (CAIX). An intermittent hypobaric hypoxia (IH) animal model was established to evaluate the role of hypoxia in activating M2‐like TAMs in vivo. We also used immunohistochemistry to analyze the association between CAIX, CD163+ macrophages and Nrp‐1 in a series of 72 human cervical cancer specimens. We found that the hypoxic cervical TME educated the recruited macrophages to transform into the M2 phenotype. Nrp‐1 expression was significantly increased in hypoxia‐primed cervical cancer cells. Blocking Nrp‐1 expression prevented hypoxic cells from recruiting and polarizing macrophages towards the M2 phenotype. Hypoxia exposure significantly increased the expression of Nrp‐1 as well as the infiltration of macrophages in vivo. Consistently, immunochemical staining in serial tissue sections of cervical cancer revealed upregulated levels of Nrp‐1 in CAIX‐positive hypoxic regions along with a concurrent significant elevation of M2 macrophages. Nrp‐1 and M2‐like TAMs were related to the malignant properties of cervical cancer, such as the FIGO stage and lymph node metastasis. Nrp‐1 plays critical roles in hypoxic TME‐induced activation and pro‐tumoral effects of TAMs in cervical cancer. Interfering with Nrp‐1 may be a potential therapeutic strategy in treating cervical cancer.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
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