Search

Joint pain is the defining symptom of osteoarthritis (OA) but its origin and mechanisms remain unclear. Here, we investigated an unprecedented role of osteoclast-initiated subchondral bone remodeling in sensory innervation for OA pain. We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rank!) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP- positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. These results suggest that intervention of the axonal guidance molecules (e.g., netrin-1) derived from aberrant subchondral bone remodeling may have therapeutic potential for OA pain., Introduction Osteoarthritis (OA) is a common musculoskeletal disease in adults, and it is estimated that it will affect 78 million people by 2040 (1), leading to disability and reduced quality [...]

Through the evaluation of the rural tourism development conditions of typical villages in Qilian County, the rural tourism level of Qilian County is divided at the current stage, and it provides reference suggestions for the promotion of rural revitalization of rural tourism in Qilian County. Based on the two perspectives of tourism basic conditions and tourism participation, the index evaluation system is constructed, the hierarchical analysis method is used to calculate the weights of each indicator, and the fuzzy comprehensive evaluation method is used to calculate the rural tourism development condition level of 17 typical villages in Qilian County. The tourism development conditions of typical villages in Qilian County are generally good, and they are divided into 3 types, 2 excellent-level villages, 13 better-level villages, and 2 general-level villages. Among them, the score of infrastructure conditions is 1.665 to 2.212 points, the gap is small, and the difference in tourism participation status score is 1.103 to 1.935 points, and the gap is significant. The overall tourism development conditions of Qilian County are better and the future development potential is large; the tourism development conditions of its typical tourist villages show a decreasing distance trend with Zhuoershan-Amidongsuo as the core; the rural tourism service system in the county is gradually improved but the endogenous development capacity is weak, and it is appropriate to establish a development route according to the spatial layout and the classification of each village.

Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistent mechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate, a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury. Because the different VGLUT isoforms generally have a non-redundant pattern of expression, we used Vglut3 knockout mice to assess the role of VGLUT3(+) primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3(+) neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs). The analysis of Vglut3(-/-) mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.

Background For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before surgery. For patients with clinical complete response (cCR), a 'Watch and Wait' (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). Methods and findings We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period. Conclusions The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks., Author(s): Yaqi Wang 1,2,3, Lifeng Yang 1,2,3, Hua Bao 4, Xiaojun Fan 4, Fan Xia 1,2,3, Juefeng Wan 1,2,3, Lijun Shen 1,2,3, Yun Guan 2,5, Hairong Bao 6, Xue Wu [...]

A composite bucket foundation (CBF) is a new foundation type of offshore wind turbine. The investigation of the bearing characteristic of CBF is a crucial part of the structural design and safety assessment of offshore wind turbines. This study investigates the bearing characteristic of CBF in sand and clay foundations using centrifuge model test and numerical simulation. Analysis revealed that as load increases, the rotation center of the CBF moves toward the central line and shallow area. The buried depth of the CBF rotation center in a clay foundation is shallower than in a sand foundation when the CBF is under ultimate loading. Due to the rotation and translation of CBF, the soil pressure–depth curves on the skirt wall in different directions will resemble parabolic, line, and triangle shapes, respectively. Under ultimate loading, the relationship between the depth and horizontal coordinate of the rotation center and embedment ratio is linear. The CBF's bearing capacity trend presents quadratic function characteristics as the embedment ratio increases. However, the bearing capacity ratio of the CBF in the clay foundation is faster than that in the sand foundation. The findings provide guidelines for offshore wind turbines. [ABSTRACT FROM AUTHOR]

In this study, a combination of an ozone gas producer and an ultrafine-bubble compressor was used to degrade tetracycline, which is a well-known antibiotic and medicine commonly used in human and animal care, and effects of varying the reaction parameters were studied. Experiments indicate that each gram of introducing ozone can degrade 2.72 g of tetracycline at pH 3 and 1.48 g at pH 11. However, basic conditions contribute to increased mineralization of tetracycline because of the ·OH radical oxidation mechanism. Higher reaction temperatures and higher ozone dosages enhance the reactivity between the ozone molecules, ·OH radicals, and tetracycline, resulting in a decline in the toxicity of the tetracycline solution as measured by cell viability. The mineralization of organic compounds is the key to decreasing the toxicity of the solution. Ultrafine-bubble ozonation can provide homogeneity of gas bubbles in solution hence it not only reduces the requirement of ozone and thus the operational cost of the reaction, but also extends the efficacy of the method to the treatment of solutions with high tetracycline concentrations.

The purpose of this paper is to investigate how optimistic bias, consumption cognition, news attention, information credibility, and social trust affect the purchase intention of food consumption. Data used in this study came from a questionnaire survey conducted in college students in Taipei and Beijing. Respondents in the two cities returned 258 and 268 questionnaires, respectively. Samples were analyzed through structural equation modelling (SEM) to test the model. Results showed that Taiwanese college students did not have optimistic bias but Chinese students did. The models showed that both Taiwanese and Chinese students’ consumption cognition significantly influenced their purchase intention, and news attention significantly influenced only Chinese students’ purchase intention. Model comparison analysis suggested significant differences between the models for Taiwan and mainland China. The results revealed that optimistic bias can be reduced in different social contexts as that of the Taiwan model and the mainland Chinese model found in this study were indeed different. This study also confirmed that people had optimistic bias on food safety issues, based on which recommendations were made to increase public awareness of food safety as well as to improve government’s certification system.