Uniaxially aligned cellulose nanofibers with well oriented cellulose nanocrystals (CNCs) embedded were fabricated via electrospinning using a rotating drum as the collector. Scanning electron microscope (SEM) images indicated that most cellulose nanofibers were uniaxially aligned. The incorporation of CNCs into the spinning dope resulted in more uniform morphology of the electrospun cellulose/CNCs nanocomposite nanofibers (ECCNN). Polarized light microscope (PLM) and transmission electron microscope (TEM) showed that CNCs dispersed well in ECCNN nonwovens and achieved considerable orientation along the long axis direction. This unique hierarchical microstructure of ECCNN nonwovens gave rise to remarkable enhancement of their physical properties. By incorporating 20% loading (in weight) of CNCs, the tensile strength and elastic modulus of ECCNN along the fiber alignment direction were increased by 101.7 and 171.6%, respectively. Their thermal stability was significantly improved as well. In addition, the ECCNN nonwovens were assessed as potential scaffold materials for tissue engineering. It was elucidated from MTT tests that the ECCNN were essentially nontoxic to human cells. Cell culture experiments demonstrated that cells could proliferate rapidly not only on the surface but also deep inside the ECCNN. More importantly, the aligned nanofibers of ECCNN exhibited a strong effect on directing cellular organization. This feature made the scaffold particularly useful for various artificial tissues or organs, such as blood vessel, tendon, nerve, and so on, in which cell orientation was crucial for their performance.

Objective: To investigate the dynamic amplitude of low-frequency fluctuations (dALFFs) in patients with Parkinson's disease (PD) and healthy controls (HCs) and further explore whether dALFF can be used to test the feasibility of differentiating PD from HCs.Methods: Twenty-eight patients with PD and 28 demographically matched HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and neuropsychological tests. A dynamic method was used to calculate the dALFFs of rs-fMRI data obtained from all subjects. The dALFF alterations were compared between the PD and HC groups, and the correlations between dALFF variability and disease duration/neuropsychological tests were further calculated. Then, the statistical differences in dALFF between both groups were selected as classification features to help distinguish patients with PD from HCs through a linear support vector machine (SVM) classifier. The classifier performance was assessed using a permutation test (repeated 5,000 times).Results: Significantly increased dALFF was detected in the left precuneus in patients with PD compared to HCs, and dALFF variability in this region was positively correlated with disease duration. Our results show that 80.36% (p < 0.001) subjects were correctly classified based on the SVM classifier by using the leave-one-out cross-validation method.Conclusion: Patients with PD exhibited abnormal dynamic brain activity in the left precuneus, and the dALFF variability could distinguish PD from HCs with high accuracy. Our results showed novel insights into the pathophysiological mechanisms of PD.

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Recapitulation of embryonic endochondral bone formation is a promising alternative approach to bone tissue engineering. However, the time-consuming process is one of the reasons the approach is unpractical. Here, we aimed at accelerating the in vitro endochondral ossification process of tissue engineering by using a pulsed electromagnetic field (PEMF). The rat bone marrow-derived stem cells were chondrogenic or hypertrophic differentiated in a three-dimensional pellet culture system, and treated with different intensities of PEMF (1, 2, and 5 mT with modulation frequency 750 Hz, carrier frequency 75 Hz and a duty ratio of 0.8, 3 h/day for 4 weeks). The effects of PEMF on hypertrophy and endochondral ossification were assessed by safranin O staining, immunohistochemistry, and quantitative real-time polymerase chain reaction. The results suggest that PEMF at 1, 2, and 5 mT may inhibit the maintenance of the cartilaginous phenotype and increase cartilage-specific extracellular matrix degradation in the late stage of chondrogenic differentiation. In addition, among the three different intensities, only PEMF at 1 mT directed the differentiation of chondrogenic-induced stem cell pellets to the hypertrophic stage and promoted osteogenic differentiation. Our findings provide the feasibility to optimize the process of in vitro endochondral ossification with PEMF stimulation.

Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain–containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB1 in the plasma membrane.

Background: The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain unknown, with no unified evaluation criteria or standard treatments. This study aimed to assess the etiology and features of GLM, as well as the effects of surgery (lesion excision + stage I breast reconstruction; LE + BR) for GLM.Methods: This study evaluated 178 female GLM patients retrospectively in 2006-2015. The surgery and non-surgery groups included 164 and 14 patients, respectively. All patients received conservative therapy (traditional Chinese medicine combined with regional wet compress and pus drainage). In addition, the surgery group (n=164) underwent LE + BR. Clinical data, including disease course, causes, lesion size, marital status, and treatment approaches, were assessed.Results: Follow-up was 13-117 months. Seventy-five of the 178 patients had no overt causes (42.1%); meanwhile, 63 (35.4%) and 16 (9.0%) had congenital nipple retraction and a history of psychotropic drugs for >1 year, respectively. The surgery group showed lesions significantly shrunk (≤1 quadrant) with acute inflammation fully controlled; 8 showed recurrence, indicating a cure rate of 95.1% (156/164). In the nonsurgery group, 4 cases showed relapse after 6-14 months (cure rate =71.4%; 10/14). Therefore, surgical treatment was significantly more efficient than non-surgical treatment (P=0.001). Kaplan-Meier survival curves for the two treatment types showed a significant difference in recurrence (log rank =11.84, P<0.001). Conclusions:In GLM patients, LE + BR is safe and effective with respect to cosmetic results, recovery time, and recurrence. Successful surgery should be performed for patients whose lesions ≤1 quadrant, aim to achieve optimal GLM treatment.

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Objective: To explore the optimal handling of the patella during total knee arthroplasty (TKA) without the intraoperative application of a tourniquet. Methods: A total of 104 patients undergoing primary unilateral TKA without the intraoperative use of tourniquets from December 2018 to March 2019 in our center were included in this prospective randomized double-blinded study, including 42 men and 62 women with a mean age of 66.3 ± 7.8 years and a minimum follow-up of 1 year. Patients were randomly divided into an eversion group (n = 52) and a retraction group (n = 52) based on the intraoperative handling of the patella (eversion or lateral retraction). Primary outcome measures, including the visual analog scale at rest (rVAS) and the visual analog scale in motion (mVAS) for both anterior knee pain and thigh pain, opioid consumption, active range of motion (aROM), passive range of motion (pROM), the time needed for return of the straight-leg raise (SLR), and 90 knee flexion, were recorded by an independent observer, who also noted secondary outcome measures, including operation time, length of stay (LOS), patella-related (patellar tilt and baja) and other complications, knee swelling, Hospital for Special Surgery (HSS) scores, and the 12-item Short Form Health Survey (SF-12) scores. Results: There were no significant differences between the two groups in terms of baseline parameters. At 24, 48, and 72 h postoperatively (PO), patients in the eversion group experienced more severe thigh pain than those in the retraction group (24 h: 2.