Deletion of vitamin D receptor exacerbated temporomandibular joint pathological changes under abnormal mechanical stimulation.

AIMS: Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration. MAIN METHODS: Mice ablated for Vdr (Vdr-/-res) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr-/- chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined. KEY FINDINGS: Vdr-/-res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr-/-res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr-/-res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr-/- chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr-/- chondrocytes. SIGNIFICANCE: VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.

Titanium-doped phosphate glasses containing zinc and strontium applied in bone regeneration.

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.

Self-reported oral health habits, knowledge and conditions of schoolchildren and adolescents in mainland China.

To determine the oral health habits, knowledge and conditions of students in China and investigate the impact of associated factors. A self-reported online questionnaire was distributed through social networks in mainland China to assess the oral health habits, knowledge, and conditions of students aged 6-20 years attending primary, middle, and high schools. Factors potentially associated with oral health, such as oral health habits of their parents, family education level, and economic regions, were analyzed using McNemar's and Chi-square tests. Within one month, 5561 valid questionnaires were retrieved from all 31 provinces or equivalent regions in mainland China. The results showed that 46.9% of students suffered from bleeding when brushing their teeth, while only 11.8% reported professional teeth cleaning at a dental clinic. Soda beverages were widely consumed among them (75.4%). A significant minority of students brushed their teeth less than twice daily (22.8%) and for about 2 minutes each time (19.3%). Only 21.9% of the students had preventive oral health care. Students' toothbrushing habits and knowledge about interdental cleaning tools were associated with parental habits (p < 0.001). Overall, students from families with higher educational backgrounds and eastern China had better oral health habits, knowledge, and conditions. There is a need to pay more attention to gingival health and caries prevention among schoolchildren and adolescents in mainland China. Improving parental oral hygiene habits could have a positive impact on the oral health of students. Further research on oral health among students is needed in the middle and western regions of China.

Intelligent Cubic-Designed Piezoelectric Node (iCUPE) with Simultaneous Sensing and Energy Harvesting Ability toward Self-Sustained Artificial Intelligence of Things (AIoT).

The evolution of artificial intelligence of things (AIoT) drastically facilitates the development of a smart city via comprehensive perception and seamless communication. As a foundation, various AIoT nodes are experiencing low integration and poor sustainability issues. Herein, a cubic-designed intelligent piezoelectric AIoT node iCUPE is presented, which integrates a high-performance energy harvesting and self-powered sensing module via a micromachined lead zirconate titanate (PZT) thick-film-based high-frequency (HF)-piezoelectric generator (PEG) and poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) nanofiber thin-film-based low-frequency (LF)-PEGs, respectively. The LF-PEG and HF-PEG with specific frequency up-conversion (FUC) mechanism ensures continuous power supply over a wide range of 10-46 Hz, with a record high power density of 17 mW/cm3 at 1 g acceleration. The cubic design allows for orthogonal placement of the three FUC-PEGs to ensure a wide range of response to vibrational energy sources from different directions. The self-powered triaxial piezoelectric sensor (TPS) combined with machine learning (ML) assisted three orthogonal piezoelectric sensing units by using three LF-PEGs to achieve high-precision multifunctional vibration recognition with resolutions of 0.01 g, 0.01 Hz, and 2° for acceleration, frequency, and tilting angle, respectively, providing a high recognition accuracy of 98%-100%. This work proves the feasibility of developing a ML-based intelligent sensor for accelerometer and gyroscope functions at resonant frequencies. The proposed sustainable iCUPE is highly scalable to explore multifunctional sensing and energy harvesting capabilities under diverse environments, which is essential for AIoT implementation.

Preoperative homocysteine modifies the association between postoperative C-reactive protein and postoperative delirium.

Background: Homocysteine and C-reactive protein (CRP) may serve as biomarkers of postoperative delirium. We set out to compare the role of blood concentration of homocysteine versus CRP in predicting postoperative delirium in patients. Materials and methods: In this prospective observational cohort study, the plasma concentration of preoperative homocysteine and postoperative CRP was measured. Delirium incidence and severity within 3 days postoperatively were determined using the Confusion Assessment Method and Confusion Assessment Method-Severity algorithm. Results: Of 143 participants [69% female, median (interquartile range, 25th-75th) age of 71 (67-76) years] who had knee or hip surgery under general anesthesia, 44 (31%) participants developed postoperative delirium. Postoperative plasma concentration of CRP was associated with postoperative delirium incidence [adjusted odds ratio (OR) per one standard deviation change in CRP: 1.51; 95% Confidence Interval (CI): 1.05, 2.16; P = 0.026], and severity [in which each one standard deviation increase in postoperative CRP was associated with a 0.47 point (95% CI: 0.18-0.76) increase in the severity of delirium, P = 0.002] after adjusting age, sex, preoperative Mini-Mental State Examination score and the days when postoperative CRP was measured. A statistically significant interaction (adjusted P = 0.044) was also observed, in which the association between postoperative plasma concentration of CRP and postoperative delirium incidence was stronger in the participants with lower preoperative plasma concentrations of homocysteine compared to those with higher preoperative levels. Conclusion: Pending validation studies, these data suggest that preoperative plasma concentration of homocysteine modifies the established association between postoperative plasma concentration of CRP and postoperative delirium incidence.

Torsional Strain-Independent Catalytic Enantioselective Synthesis of Biaryl Atropisomers.

Catalytic asymmetric dynamic kinetic resolution of configurationally labile bridged biaryls is emerging as a powerful strategy for atropisomer synthesis. However, the reported examples suffer from an inherent challenge as the reactivity is highly dependent on the torsional strain of the biaryl substrates, which significantly narrows down the scope and hampers the application. Herein, we report our discovery and development of a torsional strain-independent reaction between biaryl thionolactones and activated isocyanides. By employing auto-tandem silver catalysis, a universal synthesis of both tri- and tetra-ortho-substituted thiazole-containing biaryls was realized in high yields with high enantioselectivities. In addition, these products could be facilely converted to a novel type of bridged biaryls bearing an eight-membered lactone. Mechanistic studies were carried out to elucidate the cause of this unusual torsional strain-independent reactivity.

Automatic Localization and Identification of Thoracic Diseases from Chest X-rays with Deep Learning.

BACKGROUND: There are numerous difficulties in using deep learning to automatically locate and identify diseases in chest X-rays (CXR). The most prevailing two are the lack of labeled data of disease locations and poor model transferability between different datasets. This study aims to tackle these problems. METHODS: We built a new form of bounding box dataset and developed a two-stage model for disease localization and identification of CXRs based on deep learning. The dataset marks anomalous regions in CXRs but not the corresponding diseases, different from all previous datasets. The advantages of this design are reduced labor of annotation and fewer possible errors associated with image labeling. The two-stage model combines the robustness of the region proposal network, feature pyramid network, and multi-instance learning techniques. We trained and validated our model with the new bounding box dataset and the CheXpert dataset. Then, we tested its classification and localization performance on an external dataset, which is the official split test set of ChestX-ray14. RESULTS: For classification result, the mean area under the receiver operating characteristic curve (AUC) metrics of our model on the CheXpert validation dataset was 0.912, which was 0.021, superior to the baseline model. The mean AUC of our model on an external testing set was 0.784, whereas the state-of-the-art model got 0.773. The localization results showed comparable performance to the stateof- the-art models. CONCLUSION: Our model exhibits a good transferability between datasets. The new bounding box dataset is proven to be useful and shows an alternative technique for compiling disease localization datasets.

Treatment of postoperative delirium with continuous theta burst stimulation: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative delirium is one of the most common postoperative complications among elderly patients (65 years old or older). However, there are no effective treatments for this condition. Recent research suggests that continuous theta burst stimulation (cTBS), a non-invasive brain stimulation, can reduce pain level, improve cognitive function and affective symptoms in multiple diseases or dysfunctions, including anxiety disorders, major depressive disorder, sleep disorders and pain. But the potential benefits of cTBS in reducing postoperative delirium have not been investigated. Therefore, we propose determining whether cTBS can prevent and/or treat postoperative delirium in senior patients. METHODS AND ANALYSIS: The study will be a double-blind, randomised controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, general anaesthesia) will be randomised to receive either cTBS or sham stimulation with a focal figure-of-eight coil over the right dorsolateral prefrontal cortex at 80% of the resting motor threshold. Every patient will receive 2-3 sets of stimulations during postoperative days (40 s per session, 3 sessions per set, 1 set per day). Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity and duration of postoperative delirium, cognitive function, pain, sleep quality, activities of daily living, length of hospital stay, discharge-to-facility or home, and rate of complication and mortality during the hospital stay. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committee of Shanghai 10th People's Hospital. The principal investigator will submit a research progress report to the ethics committee regularly. All participants will provide written informed consent. Study results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04661904.

A Magnetic-Coupled Nonlinear Electromagnetic Generator with Both Wideband and High-Power Performance.

This paper proposed a high-performance magnetic-coupled nonlinear electromagnetic generator (MNL-EMG). A high-permeability iron core is incorporated to the coil. The strong coupling between the iron core and the vibrating magnets lead to significantly improved output power and a broadened operating bandwidth. The magnetic force of the iron core to the permanent magnets and the magnetic flux density inside the iron core are simulated, and the dimension parameters of the MNL-EMG are optimized. Under acceleration of 1.5 g, the MNL-EMG can maintain high output performance in a wide frequency range of 17~30 Hz, which is 4.3 times wider than that of linear electromagnetic generator (EMG) without an iron core. The maximum output power of MNL-EMG reaches 174 mW under the optimal load of 35 Ω, which is higher than those of most vibration generators with frequency less than 30 Hz. The maximum 360 parallel-connected LEDs were successfully lit by the prototype. Moreover, the prototype has an excellent charging performance such that a 1.2 V, 900 mAh Ni-MH battery was charged from 0.95 V to 0.98 V in 240 s. Both the simulation and experiments verify that the proposed bistable EMG device based on magnetic coupling has advantages of wide operating bandwidth and high output power, which could be sufficient to power micro electronic devices.

A high-performance triboelectric-electromagnetic hybrid wind energy harvester based on rotational tapered rollers aiming at outdoor IoT applications.

This article proposed a high-performance triboelectric-electromagnetic hybrid wind energy harvester (WEH). By adopting the revolution and rotation movements of tapered rollers, which serve as both the rotor of the electromagnetic generator (EMG) part and freestanding layers of the triboelectric nanogenerator (TENG) part, the WEH can work as a sustainable power source and a self-powered wind speed sensor. When the wind speed is 12 m/s, super-high open-circuit voltage peaks of 47.4 and 683 V can be achieved by the EMG and TENG, respectively, corresponding to the high-power outputs of 62 and 1.8 mW. It was demonstrated that the WEH can easily light up over 600 red light-emitting diodes and even a 5-W globe light. A self-powered wireless temperature and humidity sensing network was also systematically demonstrated. In summary, the proposed WEH exhibits bright future toward IoT applications, such as in border detection, smart buildings, and so on.

In(Ga)N Nanostructures and Devices Grown by Molecular Beam Epitaxy and Metal-Assisted Photochemical Etching.

This review summarizes the recent research on nitride nanostructures and their applications. We cover recent advances in the synthesis and growth of porous structures and low-dimensional nitride nanostructures via metal-assisted photochemical etching and molecular beam epitaxy. The growth of nitride materials on various substrates, which improves their crystal quality, doping efficiency, and flexibility of tuning performance, is discussed in detail. Furthermore, the recent development of In(Ga)N nanostructure applications (light-emitting diodes, lasers, and gas sensors) is presented. Finally, the challenges and directions in this field are addressed.

SOX11 promotes osteoarthritis through induction of TNF-α.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease and the molecular mechanism of OA remains unclear. Transcription factor SOX11 has been proved to be involved in the development progress of OA. The present study aimed to evaluate the potential function of SOX11 during the development of OA. METHODS: SOX11 expression in patients with OA and health donator was determined with qRT-PCR. Subsequently, in vitro OA model was established by treating the chondrocyte cells CHON-001 with IL-1ß. Next, we validated the function of SOX11 in in vitro OA model by using siRNAs. Finally, the relationship between SOX11 and TNF-α was explored. RESULTS: SOX11 was upregulated in patients with OA and in IL-1ß treated cells. IL-1ß significantly increased both the mRNA and protein levels of MMP13 and cleaved caspase 3, while decreased collagen II and aggrecan in CHON-001 cells. In addition, knockdown of SOX11 could significantly decrease IL-1ß-induced apoptosis in CHON-001 cells. Meanwhile, IL-1ß induced OA like phenomenon was significantly reversed by siRNA interference. Moreover, inhibition of SOX11 decreased the level of TNF-α in patients with OA and in IL-1ß treated cell supernatant. CONCLUSION: Inhibition of SOX11 could improve IL-1ß-induced OA like phenomenon in CHON-001 cells, which suggesting SOX11 played an important role during the pathogenesis of OA. Thus, we hypothesized that SOX11 could be a potential target for the treatment of patients with OA.

MiR-564 promotes hypertrophic scar formation through TGF-ß1 upregulation.

BACKGROUND: To evaluate the role of microRNA564 (miR-564) in the development of hypertrophic scar and investigate the possible mechanism of this process. METHODS: The hypertrophic scar (HS) tissues and adjacent normal skin (NS) tissues were selected from 10 patients. The fibrosis-related proteins were detected via hematoxylin eosin (HE) staining, Masson staining and immunohistochemical detection. The relative expression difference of miR-564 in NS tissues and HS tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). The protein expression difference of transforming growth factor-ß1 (TGF-ß1) in NS tissues and HS tissues was detected via Western blotting. Moreover, the hypertrophic scar fibroblast (HSF) cells were isolated from HS tissues and divided into four groups according to different treatment methods: blank control group, scramble-transfected negative control group, miR-564 inhibitor-transfected miR-564 inhibitor group, and miR-564 plasmid-transfected miR-564 mimic group. The expressions of TGF-ß1 in blank control group, scramble group, miR-21 mimic group and miR-21 inhibitor group were detected via RT-PCR and Western blotting. RESULTS: MiR-564 was highly expressed in HSF cells. Compared with that of blank control group, the expression of TGF-ß1 was down-regulated through inhibiting the miR-564 expression, thus inhibiting the activation and proliferation of HSF cells. However, the overexpression of miR-564 achieved the opposite results. CONCLUSIONS: Up-regulated mir-564 promoted the development of hypertrophic scar via enhancing the expression of TGF-ß1. MiR-564 may be a potential novel molecular target for the treatment of hypertrophic scarring.

Selective Recovery of n-Butanol from Aqueous Solutions with Functionalized Poly(epoxide ionic liquid)-Based Polyurethane Membranes by Pervaporation.

In this study, hydroxyl-terminated polybutadiene-poly(epoxide ionic liquid)-poly(urethane urea) (HTPB-PEIL-PU) membranes, HTPB-PEIL1-PU and HTPB-PEIL2-PU, were prepared by the reaction of functionalized PEIL, poly(1-methylimidazole-3-methyl-ethyloxy)hexafluorophosphate or poly(1-methylimidazole-3-methyl-ethyloxy)bistrifluoromethanesulfonimidate, respectively, with HTPB using 4,4'-diphenylmethane diisocyanate (MDI) as the chain extender. The HTPB-PEIL-PU and HTPB membranes were investigated for the selective recovery of n-butanol from aqueous solutions by pervaporation. PEIL was confirmed to be successfully embedded in the PU membranes by 1H NMR, Fourier transform infrared, and differential scanning calorimetry measurements. According to our mechanical measurements, the HTPB-PEIL-PU membranes retain the mechanical properties of the original PU membrane. PEIL was shown to enhance the diffusion rate of n-butanol significantly based on swelling behavior tests. The pervaporation flux through the HTPB-PEIL1-PU membrane increased with increasing feed temperature and feed concentration. In contrast, the separation factor of the HTPB-PEIL1-PU membrane increased with increasing feed temperature but decreased with increasing feed concentration. In addition, the HTPB-PEIL2-PU membrane exhibited an optimal separation factor of up to 29.2 at a feed concentration of 3% and a feed temperature of 70 °C, which is superior to that (22.7) through pure HTPB membranes. Furthermore, the HTPB-PEIL1-PU and HTPB-PEIL2-PU membranes show better long-term stability than other supported ionic liquid membranes.

Pullulanibacillus camelliae sp. nov., isolated from Pu'er tea.

A novel Gram-stain-positive, strictly aerobic, endospore-forming, rod-shaped bacterial strain 7578-24T was isolated from ripened Pu'er tea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 7578-24T clustered with species of the genus Pullulanibacillus in the family Sporolactobacillaceae with 97.8-95.2 % sequence similarities, and was most closely related to Pullulanibacillus pueri YN3T with 97.8 % 16S rRNA gene sequence similarity. The DNA-DNA relatedness value between strain 7578-24T and P. pueri YN3T was 35 %. Strain 7578-24T had a cell-wall type A1γ peptidoglycan with meso-diaminopimelic acid as the diagnostic diamino acid. The major menaquinone was menaquinone 7 (MK-7). C18 : 1ω7c (45.4 %), anteiso-C17 : 0 (30.6 %) and anteiso-C15 : 0 (10.1 %) were the predominant fatty acids, and diphosphatidylglycerol, phosphatidylglycerol, five unknown phospholipids and one unknown aminolipid were the major polar lipids. The DNA G+C content of strain 7578-24T was 45.2 mol%. Strain 7578-24T could be differentiated from other related species of the genus Pullulanibacillus based on phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA hybridization data. On the basis of polyphasic evidence from this study, a novel species of the genus Pullulanibacillus named Pullulanibacillus camelliae sp. nov. is proposed, with strain 7578-24T (=CGMCC 1.15371T=JCM 31236T) as the type strain.

Current Status of Biological Therapies for the Treatment of Metastatic Melanoma.

Compared to early-stage melanoma when surgical excision is possible, metastatic disease continues to offer a much grimmer prognosis as traditional chemotherapy treatment regimens offer relatively little survival benefit. This has led to changes in treatment approaches over the preceding two decades as contemporary methods for the treatment of advanced or metastatic melanoma now involve a number of biological modalities, which include immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. Clinically available immunotherapeutic agents include interleukin 2 (IL-2), as well as drugs targeting the important immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v-Raf murine sarcoma viral oncogene homolog B (BRAF), receptor tyrosine kinases, MEK inhibitors and potential future therapeutic targets, such as the CDK4/CDK6, PTEN and GNAQ/GNA11 genes. Additionally, an increasing understanding of the role of epigenetic alterations in the development and progression of melanoma now offers a new potential drug target. Several of these agents have shown promising results; however, in many investigations, combinations of different therapeutic approaches, each with different mechanisms of action, have yielded improved outcomes as treatment regimens continue to be further optimized by active research and patient disease sub-group analyses. This review summarizes the novel biological agents and new treatments, directly contributing to the significant improvement of biological therapies and markedly advancing knowledge of clinical application of newly approved and developed therapies in treatment of patients with metastatic melanoma.

AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue.

The role of AMP-activated protein kinase (AMPK) in promoting fatty acid (FA) oxidation in various tissues, such as liver and muscle, has been well understood. However, the role of AMPK in lipolysis and FA metabolism in adipose tissue has been controversial. To investigate the role of AMPK in the regulation of adipose lipolysis in vivo, we generated mice with adipose-tissue-specific knockout of both the α1 and α2 catalytic subunits of AMPK (AMPK-ASKO mice) by using aP2-Cre and adiponectin-Cre. Both models of AMPK-ASKO ablation show no changes in desnutrin/ATGL levels but have defective phosphorylation of desnutrin/ATGL at S406 to decrease its triacylglycerol (TAG) hydrolase activity, lowering basal lipolysis in adipose tissue. These mice also show defective phosphorylation of hormone-sensitive lipase (HSL) at S565, with higher phosphorylation at protein kinase A sites S563 and S660, increasing its hydrolase activity and isoproterenol-stimulated lipolysis. With higher overall adipose lipolysis, both models of AMPK-ASKO mice are lean, having smaller adipocytes with lower TAG and higher intracellular free-FA levels. Moreover, FAs from higher lipolysis activate peroxisome proliferator-activated receptor delta to induce FA oxidative genes and increase FA oxidation and energy expenditure. Overall, for the first time, we provide in vivo evidence of the role of AMPK in the phosphorylation and regulation of desnutrin/ATGL and HSL and thus adipose lipolysis.