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In this work, we prepared a novel graphene-based composite by combination of mercapto-end capped polyhedral oligomeric silsesquioxane (POSS-SH) with graphene oxide (GO) through covalent bonding process. The composite was further conjugated with 4-vinyl pyridine (4-VP) through thiol-ene click reaction to fabricate pseudo-mercaptoethyl pyridine functionalized POSS-graphene composite (G-POSS-S-VP). The physicochemical properties were confirmed via FT-IR, TGA, XPS, and TEM characterizations and a high ligand density of ca. 87.3 μmol m -2 was obtained. G-POSS-S-VP composite displayed high selectivity toward antibody, i.e., immunoglobulin G (IgG) in this case based on the hydrophobic charge induced chromatography (HCIC) mechanism. A high adsorption efficiency of ca. 90% and large adsorption capacity of 500 mg g -1 were achieved for IgG at pH 7.4. At the same time, the non-specific adsorptions of co-existing proteins on graphene substrate were obviously hindered. The practical applicability of G-POSS-S-VP composite as adsorbent was verified by selective separation of IgG from human serum. SDS-PAGE assay and MALDI-TOF-MS analysis clearly demonstrated the successful isolation of IgG with high purity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Machine learning (ML) is a type of artificial intelligence (AI) and has been utilized in clinical research and practice to construct high-performing prediction models. Hidden blood loss (HBL) is prevalent during the perioperative period of spinal treatment and might result in a poor prognosis. The aim of this study was to develop a ML-based model for identifying perioperative HBL-related risk factors in patients with thoracolumbar burst fracture (TBF)., Methods: In this study, single-central TBF patients were chosen. The medical information on patients, including clinical characteristics, laboratory indicators, and surgery-related parameters, was extracted. After comparing various ML model algorithms, we selected the best model with high performance. The model was validated using the internal validation set before performing recursive feature elimination (RFE) to determine the importance of HBL-related risk factors. The area under the receiver operating characteristic (AUC) curve, accuracy (ACC), sensitivity, and specificity were reported as critical model measures for evaluating predictive performance., Results: In this study, 62 (38.5%) of the 161 TBF patients were positive for HBL. There was a significant statistical difference in age, body mass index (BMI), diabetes, hypertension, Beta (percentage of vertebral restoration), duration of operation, and other pre-operative laboratory indicators between the HBL-positive and HBL-negative groups. Nine ML-based models were built and validated, with the Random Forest model having the greatest AUC in both the training set (0.905) and internal validation set (0.864). Furthermore, following RFE, age, duration of operation, Beta, pre-operative fibrinogen (Fib), and activated partial thromboplastin time (APTT) were identified as the five main important risk factors in patients with TBF during the perioperative period., Conclusion: In this study, we built and validated ML algorithms for an individualized prediction of HBL-related risk factors in the perioperative period of TBF. The importance of HBL-related risk factors could be determined, which contributes to clinicians' decision-making and improves perioperative management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Gao, Wang, Wei, Xia, Liu and Zheng.)

Nanozymes, as substitutes for natural enzymes, have been used to construct some fast cheap sensing platforms by virtue of the high catalytic activity. Herein, we firstly study the peroxidase-like activity of CeO 2 /Co 3 O 4 @N-doped hollow carbon microspheres as nanozymes. In the presence of H 2 O 2 , CeO 2 /Co 3 O 4 @NCH exhibits high peroxidase-like activity evaluated by the catalytic oxidation of the chromogenic substrate, 3,3',5,5'-tetramethylbenzidine (TMB) into a blue oxTMB visually in 1 min. The larger surface area, pore-like structure, and oxygen vacancies contribute to the enhanced peroxidase-like activity of CeO 2 /Co 3 O 4 @NCH. The active species •O 2- is detected during the catalytic process. Thus, based on the excellent peroxidase-like activity of CeO 2 /Co 3 O 4 @NCH, a facile and effective biosensor is fabricated for sensitive and selective determination of H 2 O 2 and quercetin, respectively. CeO 2 /Co 3 O 4 @NCH shows high affinity towards H 2 O 2 (K m  = 4.001 mM) and TMB (K m  = 0.086 mM). The detection limit of H 2 O 2 and quercetin is as low as 0.086 mM and 1.19 μM (3σ/slope), respectively. This work remarkably extends the utilization of CeO 2 /Co 3 O 4 @NCH in designing a colorimetric sensing platform related to biosensing, food, and environmental monitoring. A fast colorimetric sensing platform for quercetin based on the excellent peroxidase-like activity of CeO 2 /Co 3 O 4 @NCH., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Acupuncture is recommended for the relief of chronic tinnitus in traditional Chinese medicine, but the underlying neural mechanism remains unclear. The human brain is a dynamic system, and it's unclear about acupuncture's effects on the dynamic functional connectivity (DFC) of chronic tinnitus. Therefore, this study based on resting-state functional magnetic resonance imaging (fMRI) investigates abnormal DFC in chronic tinnitus patients and the neural activity change evoked by acupuncture treatment for tinnitus. In this study, 17 chronic tinnitus patients and 22 age- and sex-matched normal subjects were recruited, and their tinnitus-related scales and hearing levels were collected. The fMRI data were measured before and after acupuncture, and then sliding-window and k-means clustering methods were used to calculate DFC and perform clustering analysis, respectively. We found that, compared with the normal subjects, chronic tinnitus patients had higher temporal variability of DFC between the supplementary motor area and medial part of the superior frontal gyrus, and it positively correlated with hearing loss. Clustering analysis showed higher transition probability (TP) between connection states in chronic tinnitus patients, and it was positively correlated with tinnitus severity. Furthermore, the findings showed that acupuncture treatment might improve tinnitus. DFC between the posterior cingulate gyrus and angular gyrus in chronic tinnitus patients after acupuncture showed significantly decreased, and it positively correlated with the improvement of tinnitus. Clustering analysis showed that acupuncture treatment might promote chronic tinnitus patients under lower DFC state, and it also positively correlated with the improvement of tinnitus. This study suggests that acupuncture as an alternative therapy method might decrease the tinnitus severity by decreasing the time variability of DFC in chronic tinnitus patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Zhang, Li, Liu, Zha, Hu, Wang, Wang, Yu, Yang and Qiu.)

It is necessary to develop nanoperoxidases with high activity to construct a fast and cheap sensing platform for real-time detection of some pollutants. In this study, the as-prepared N and S co-doped core-shell cobaltosic oxide nanospheres (N,S-Co 3 O 4 ) exhibit excellent peroxidase-like activity. The oxidation reaction of the colorless chromogenic substrate TMB by H 2 O 2 is used to evaluate the peroxidase-like behaviors of N,S-Co 3 O 4 . As expected, the N,S-Co 3 O 4 nanospheres accelerated the oxidation of TMB accompanied by a blue shift only in 1 min. Thus, the N,S-Co 3 O 4 nanoperoxidase exhibits high affinity towards TMB ( K m = 0.072 mM) and H 2 O 2 ( K m = 3.78 mM). Moreover, as the catalytic process of N,S-Co 3 O 4 can be inhibited in the presence of catechol, a fast inexpensive colorimetric sensor of catechol with high sensitivity and good selectivity was constructed. The enhanced catalytic activity of N,S-Co 3 O 4 is attributed to some active species, including h + and ˙O 2 - , owing to the more active sites on N,S-Co 3 O 4 . The colorimetric method has been validated by detecting catechol in real water samples for practical application.

Objective: This study evaluated the beneficial effect of fuscoside in the repair of bone defects (BDs) and the possible molecular mechanism thereof., Materials and Methods: In this experimental study, a BD was induced by drilling the rat tibia. The rats were then administered oral fuscoside, at 200 or 300 mg/kg, for 2 weeks. The effect of treatment was assessed based on the bone formation score and on the levels of cytokines and biochemical markers in serum. Tibial expression of the proteins involved in the Rankl/Nlrp3/Opg pathway was determined by quantitative reverse-transcription polymerase chain reaction and western blot assay, and histopathological changes by haematoxylin and eosin and TRAP staining., Results: In the fuscoside-treated BD rats, the bone formation score improved and inflammatory cytokine levels were reduced. The levels of biochemical markers improved as well, as did the expression of apoptosis proteins. Fuscoside also attenuated the expression of Rankl, Opg, Nlrp3, Runx2, Osterix, and Osteocalcin (Oc) proteins in the tibial tissue of the BD rats and reversed the abnormal histopathological changes., Conclusion: These results suggest that fuscoside improves BD repair by reducing the differentiation of osteoclasts and by regulating the Rankl/Nlrp3/Opg pathway., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Background: Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells., Methods: Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p., Results: Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells., Conclusions: Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.

In this work, a thrombin photoelectrochemical aptasensor was reported based on a photoanode of perylene-3,4,9,10-tetracarboxylic acid (PTCA), Au nanoparticle co-functionalized ZnO nanorods (ZnO NRs) and the "signal-off" amplification effect of Ag@Ag2S. The photocurrent response of the ZnO NRs was improved greatly due to the excellent visible-light photoelectric performance of PTCA and the surface plasmon resonance (SPR) effect of Au nanoparticles. Due to the specific recognition between thrombin and aptamers, the non-conductive complex with a steric hindrance structure blocked the diffusion path of the electron donating ascorbic acid (AA) and then the "signal-off" Ag@Ag2S quencher was captured. The quencher blocked the irradiation light toward the ZnO NRs/PTCA/Au electrode and competitively consumed the electron donor AA that could have been involved in the oxidation reaction with photogenerated holes of PTCA, resulting in the further decrease of the photocurrent. Based on the evident photocurrent response of the photoanode and the superior quenching strategies, the detection limit of thrombin is as low as 33 fM with a wide linear detection range from 0.0001 nM to 50 nM. The prepared biosensor also exhibited good specificity, reproducibility and stability, suggesting potential application in thrombin specific detection.

Objectives: To determine the independent relationship between depressive symptoms and arterial stiffness in the general Chinese population, and to explore possible interactive factors in the relationship., Design: A cross-sectional study., Setting and Participants: Consecutive participants who received routine health physical examination in an affiliated hospital of a comprehensive university in Hunan Province, China, between September 2013 and March 2014 were examined. After exclusion of subjects not meeting the criteria, a total of 1334 subjects aged 22-77 years were recruited for final analysis., Measures: The Patient Health Questionnaire-9 was employed to assess the degree of depressive symptoms: 0-4 no depressive symptoms, 5-9 mild depressive symptoms and 10-27 moderate to severe depressive symptoms. Brachial-ankle pulse wave velocity (baPWV) was measured to determine arterial stiffness., Results: There was a slight increase in baPWV across elevated degrees of depressive symptoms (p=0.025). Multivariate linear regression analysis revealed that mild depressive symptoms and moderate to severe depressive symptoms were independently associated with baPWV compared with no depressive symptoms after adjusting for baseline confounders (beta-coefficient: 40.3, 95% CI 6.6 to 74.1; beta-coefficient: 87.7, 95% CI 24.0 to 151.5, respectively). Further stratified analyses indicated that the relationship between degree of depressive symptoms and baPWV was predominant in subjects who had normal or normal-high blood pressure, or combined with hypertension (p for interaction=0.016), or in subjects with diabetes mellitus (p for interaction=0.004), examined in multivariate linear regressions. In addition, after adjustment, a significant association between moderate to severe depressive symptoms and baPWV was also found in female subjects younger than 60 years, although the interactive effect was not significant (p for interaction=0.056)., Conclusions: Depressive symptoms are independently associated with arterial stiffness, especially in subjects whose blood pressures are beyond the optimal range and combined with diabetes mellitus., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dual antiplatelet therapy (DAPT) score and PRECISE-DAPT score were recommended for decision making of optimal DAPT in discriminating the risk of thrombosis and bleeding. But the relationships between 2 scoring tools with the extent of coronary stenosis have not been established.We retrospectively enrolled 359 patients of acute coronary syndrome (ACS) who received percutaneous coronary intervention. Both DAPT score and PRECISE-DAPT score were calculated, and patients were divided by their recommended cut-offs. Gensini score and triple-vessel disease (3-VD) were chosen to evaluate the severity of coronary stenosis.Overall, 54.9% and 10.0% of the patients had higher DAPT score (≥2) or PRECISE-DAPT score (≥25). Patients with higher DAPT score had increased stent counts, total length of stents, Gensini score, and proportion of 3-VD, but decreased minimum diameter of stent. But these differences were not found in PRECISE-DAPT subgroups. When divided into quartiles of both scoring systems, the highest Gensini score and proportions of 3-VD were found in the fourth quartile of both DAPT score and PRECISE-DAPT score. Moreover, both DAPT score and PRECISE-DAPT score were independent risk factors of Gensini score after adjustment (P < .001 and P = .047). Furthermore, an increase of 1 point of DAPT score and 5 points of PRECISE-DAPT score resulted by 51% (odds ratios [OR]: 1.51, 95% confidence interval [CI]:1.19-1.91, P = .001) and 34% (OR: 1.34, 95% CI: 1.11-1.62, P = .003) increase in risk of 3-VD after adjustment.Both DAPT score and PRECISE-DAPT score were independently associated with the degree of coronary stenosis in patients with ACS.