Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis.

Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: ß (95% confidence interval [CI]) - 0.150 (-0.270 to -0.031), P = .013; weighted median: ß (95%CI) - 0.195 (-0.336 to -0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: ß (95%CI) - 0.933 (-1.860 to -0.007), P = .048) and driving lumbar spine bone mineral density (IVW: ß (95%CI) - 0.649 (-1.175 to -0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Mechanism of Modified Erchentang on COPD Inflammation Based on TNF-α/TNFR1/RIPKs Pathway / 中国实验方剂学杂志

ObjectiveBased on tumor necrosis factor alpha （TNF-α）/tumor necrosis factor receptor 1 （TNFR1）/receptor-interacting protein kinases （RIPKs） signaling pathway， this paper aims to study the effect of modified Erchentang on inflammation in rats with chronic obstructive pulmonary disease （COPD） and explore its mechanism of action. MethodA total of 60 SD rats were randomly divided into normal group， model group， high， medium， and low-dose groups （20， 10， 5 g·kg-1·d-1） of modified Erchentang， and Xiaokechuan group （3.5 mL·kg-1·d-1）， with 10 rats in each group. The COPD rat model was established by cigarette smoke combined with lipopolysaccharide （LPS）. The normal group and model group were given the same amount of normal saline for 21 days by gavage administration. The contents of TNF-α and TNFR1 in bronchoalveolar lavage fluid （BALF） of rats were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expressions of RIPK1， RIPK3， and mixed lineage kinase domain-like （MLKL） in the lung tissue. The protein expressions of RIPK1， RIPK3， and MLKL in the lung tissue were detected by Western blot. The pathological changes in lung tissue were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， the contents of TNF-α and TNFR1 in BALF of the model group were significantly increased （P<0.01）， and the mRNA and protein expression levels of RIPK1， RIPK3， and MLKL in the lung tissue were significantly increased （P<0.01）. Compared with the model group， the contents of TNF-α and TNFR1 in BALF of high， medium， and low-dose groups of modified Erchentang and Xiaokechuan group were decreased （P<0.01）. The mRNA and protein expression levels of RIPK1， RIPK3， and MLKL in the lung tissue were decreased to different degrees （P<0.05， P<0.01）. ConclusionModified Erchentang can effectively improve the inflammatory response of lung tissue in COPD rats， and the mechanism may be by inhibiting the activation of the TNF-α/TNFR1/RIPKs signaling pathway.

A three-component reaction of cyclobutanone oxime esters, sulfur dioxide and N-alkyl-N-methacryloyl benzamides.

A three-component reaction of cyclobutanone oxime esters, DABCO·(SO2)2 and N-alkyl-N-methacryloyl benzamides is described. This reaction proceeds without the addition of any oxidant or transition metal, affording sulfonyl-containing isoquinoline-1,3-(2H,4H)-diones in moderate to good yields. Various functional groups are tolerated well in this transformation. Mechanistic studies suggest that a radical pathway is involved, including ß-scission, sulfur dioxide insertion, and intramolecular cyclization processes.

Reference values of gait parameters in healthy Chinese university students: A cross-sectional observational study.

BACKGROUND: Gait is influenced by race, age, and diseases type. Reference values for gait are closely related to numerous health outcomes. To gain a comprehensive understanding of gait patterns, particularly in relation to race-related pathologies and disorders, it is crucial to establish reference values for gait in daily life considering sex and age. Therefore, our objective was to present sex and age-based reference values for gait in daily life, providing a valuable foundation for further research and clinical applications. AIM: To establish reference values for lower extremity joint kinematics and kinetics during gait in asymptomatic adult women and men. METHODS: Spatiotemporal, kinematics and kinetics parameters were measured in 171 healthy adults (70 males and 101 females) using the computer-aided soft tissue foot model. Full curve statistical parametric mapping was performed using independent and paired-samples t-tests. RESULTS: Compared with females, males required more time (cycle time, double-limb support time, stance time, swing time, and stride time), and the differences were statistically significant. In addition, the step and stride lengths of males were longer. Compared to males, female cadence was faster, and statures-per-second and stride-per-minute were higher. There were no statistical differences in speed and stride width between the two groups. After adjusting for height, it was observed that women walked significantly faster than men, and they also had a higher cadence. However, in terms of step length, stride length, and stride width, both genders exhibited similarities. CONCLUSION: We established reference values for gait speed and spatiotemporal gait parameters in Chinese university students. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

Causal relationship between breakfast skipping and bone mineral density: a two-sample Mendelian randomized study.

Objective: To explore the causal association between breakfast skipping and bone mineral density (BMD) through two-sample Mendelian randomisation (MR) analysis. Methods: A two-sample MR approach was adopted to explore the causal relationship of breakfast skipping with BMDs (across three skeletal sites and five age groups). Publicly available genome-wide association study summary data were used for MR analysis. We used five methods to estimate the causal associations between breakfast skipping and BMDs: inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. IVW was used for the main analysis and the remaining four methods were used as supplementary analyses. The heterogeneity of the MR results was determined using IVW and MR-Egger methods. The pleiotropy of the MR results was determined using MR-Egger intercept. Furthermore, a leave-one-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism. Results: With the IVW method, we did not find any causal relationship between breakfast skipping and forearm, femoral neck, and lumbar spine BMD. Subsequently, when we included BMD data stratified by five different age groups in the analysis, the results showed that there was no apparent causal effect between breakfast skipping and age-stratified BMD. This finding was supported by all four supplementary methods (P > 0.05 for all methods). No heterogeneity or horizontal pleiotropy was detected in any of the analyses (P > 0.05). The leave-one-out tests conducted in the analyses did not identify any single nucleotide polymorphism that could have influenced the MR results, indicating the reliability of our findings. Conclusion: No causal effect was found between breakfast skipping and BMD (across three skeletal sites and five age groups).

Arthroscopically assisted internal fixation for treatment of acute ankle fracture: A systematic review and meta-analysis of comparative studies.

BACKGROUND: Arthroscopically assisted reduction and internal fixation (ARIF) allows for the assessment of joint congruity following anatomic reduction, identification of occult intra-articular lesions, and treatment of traumatic intra-articular pathologies. The aim of this systematic review and meta-analysis was to provide evidence on whether ARIF is an alternative treatment protocol for ankle fractures. METHODS: The PubMed, Embase, and Cochrane Library databases were searched independently by two investigators from the inception dates to October 9, 2022, for comparative studies. The risk-of-bias tool of the Cochrane Collaboration for Randomized Controlled Trials and the methodological index for non-randomized studies (MINORS) were used for assessing the methodological quality. Outcomes were evaluated in terms of the Olerud-Molander Ankle Score (OMAS), American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, post-operative complications, arthroscopic findings, Visual Analogue Scale (VAS) score, and operation time. Cochrane Review Manager Software 5.4 was used to perform the statistical analysis. RESULTS: A total of 10 trials involving 755 patients were included in this meta-analysis. The results revealed that ARIF for ankle fractures was superior regarding functional outcomes and VAS scores when compared with open reduction and internal fixation (ORIF). No significant difference was noted in the post-operative complication rate and the operation time between the ARIF and ORIF groups. A high incidence of chondral or osteochondral lesions (OCLs), ligamentous injuries, and loose bodies with ankle fractures was found by ankle arthroscopy. CONCLUSIONS: ARIF for ankle fractures might be beneficial to offer superior functional outcomes and VAS score than ORIF. Orthopedic surgeons should take a high incidence of OCLs and ligamentous injuries into consideration for the treatment of acute ankle fractures. We believe that with the increase in surgical experience, the occurrence of post-operative complications and the extension of operation time will no longer be a potential concern for surgeons.

A Facile Crystallization Strategy to Turn Calcium Bisphosphonates into Novel Osteogenesis-Inducing Biomaterials.

Insoluble metal bisphosphonates (BPs) are considered an ideal alternative to the soluble counterparts in regenerative medicine due to their increased BP release profile, but still present undesired properties (e.g., low stability, uncontrolled degradation, and poor biocompatibility). Through a simple crystallization on a solid calcium hydroxyapatite (HA)-based substrate from a BP precursor solution in 30 days, a series of insoluble calcium BP (CaBP) crystals are developed. These crystals, including calcium alendronate (CaAln), calcium pamidronate (CaPam), calcium incadronate (CaInc), calcium risedronate (CaRis), calcium zoledronate (CaZol), and calcium di-minodronate (Ca(Min)2 ), present high purity, regular morphologies and excellent biodegradability. It is demonstrated that these CaBPs can induce osteogenic differentiation of adipose-derived mesenchymal stem cells in vitro in the absence of other osteogenic inducers. It is further found that CaBP induces bone formation more effectively in a femur defect rabbit model in three months but with a lower in vivo hematotoxicity than the clinically used HA during osteogenesis. It is believed that these desired biological properties arise from the capability of the insoluble CaBPs in releasing BPs in a sustained manner for stimulating osteogenesis. This work provides a significant strategy for turning CaBPs into novel biomaterials for tissue regeneration and demonstrates their great potential in the clinic.

Effect of organic solvents on calcium minodronate crystal morphology in aqueous solution: an experimental and theoretical study.

The influence of nine organic solvents on the crystal morphology of calcium minodronate (Ca(Min)2) was investigated by experimental investigations and molecular simulations. Hirshfeld analysis was used to reveal the intermolecular interactions, and the modified attachment energy (AE) model was applied to constructing the Ca(Min)2-organic-water model in different organic-water solvents. The surface structure and the mass density profile were demonstrated and analyzed. The results showed that there were different adsorption conditions in different organic-water solvents. Furthermore, it was found that the (2 0 0)/(1 1 0) side ratio of Ca(Min)2 crystal had a linear relationship with the volume of organic solvent and had a certain correlation with some solvent properties. It is believed that the research developed in this work could have a promising application in prediction of Ca(Min)2 crystal morphology and could give guidance in the selection of organic solvents to control the desirable crystal morphology.

Modified Erchentang Alleviates Inflammation in Chronic Obstructive Pulmonary Disease via Midkine/Notch2/Hey1 Signaling Pathway in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the molecular mechanism of the anti-inflammatory effect of Erchentang in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） via the heparin-binding factor （Midkine）/transmembrane receptor protein （Notch2）/Hey1 signaling pathway. MethodSixty SD rats were randomized into normal group， model group， modified Erchentang （5， 10， 20 g·kg-1·d-1） groups， and Notch1 pathway inhibitor （γ-secretase inhibitor， DAPT， 0.02 g·kg-1） group， with 10 rats in each group. The rat model of COPD was established by cigarette smoke combined with lipopolysaccharide （LPS）. After the modeling， the rats were administrated with corresponding drugs by gavage， and those in the normal and model groups were administrated with normal saline by gavage for 21 days. The levels of Midkine， cytokine-induced neutrophil chemoattractant-1 （CINC-1）， macrophage-derived chemokine （MDC）， chemokine ligand 5 （CXCL5）， neutrophil elastase （NE）， and nuclear factor-kappa B （NF-κB） p65 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry were respectively employed to determine the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue. ResultCompared with the normal group， the modeling increased the levels of Midkine， CINC-1， MDC， CXCL5， NE， and NF-κB p65 in BALF （P<0.01） and up-regulated the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue （P<0.01）. Compared with the model group， medium- and high-dose modified Erchentang and DAPT lowered the levels of Midkine， CINC-1， MDC， CXCL5， and NF-κB p65 in BALF （P<0.01） and down-regulated the mRNA levels of Midkine， Notch2， and Hey1 （P<0.01）. ConclusionModified Erchentang may inhibit the inflammation in COPD rats by down-regulating the expression of Midkine， Notch2， and Hey1 and reducing the content of Midkine， CINC-1， MDC， and CXCL5.

Anti-inflammatory Mechanism of Modified Erchentang on Chronic Obstructive Pulmonary Disease Through Jagged1/Notch1/Hes1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease （COPD） and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose modified Erchentang groups （5， 10， 20 g·kg-1）， and γ-secretase inhibitor DAPT group （0.02 g·kg-1）， with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide （LPS）. Rats were treated with corresponding drugs by gavage， while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1， soluble intercellular adhesion molecule-1 （sICAM-1）， activated leukocyte cell adhesion molecule （ALCAM）， and soluble vascular adhesion molecule-1 （sVCAM-1） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of Jagged1， Notch1， and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of Jagged1， Notch1， Notch1 intracellular domain （NICD1）， and Hes1 in lung tissues of rats was detected by immunohistochemistry （IHC）. ResultCompared with the normal group， the model group showed increased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.01）， increased mRNA expression of Jagged1， Notch1， and Hes1 in lung tissues （P<0.01）， and increased protein expression of Jagged1， Notch1， NICD1， and Hes1 （P<0.01）. Compared with the model group， the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.05， P<0.05）， down-regulated mRNA expression of Jagged1， Notch1， and Hes1 （P<0.05， P<0.01）， and reduced protein expression of Jagged1， Notch1， NICD1， and Hes1（P<0.05， P<0.01）. ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats， and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1， Notch1， and Hes1 and inhibiting the release of Notch1， sICAM-1， ALCAM， and sVCAM-1.

Effect of Modified Erchentang on Bronchioles of Rats with Chronic Obstructive Pulmonary Disease by HMGB1/RAGE/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of modified Erchentang on the expression of key molecules in the high mobility group Box 1 protein （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway in bronchioles of rats with chronic obstructive pulmonary disease （COPD）， to explore the mechanism of modified Erchentang against bronchiolar inflammation of COPD rats via HMGB1/RAGE/NF-κB signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， modified Erchentang low-， medium- and high-dose groups （5， 10， 20 g·kg-1·d-1） and ethyl pyruvate （HMGB1 inhibitor） group， with 10 in each group. The COPD rat model was prepared by cigarette smoke combined with tracheal injection of lipopolysaccharide （LPS）. After modeling， the modified Erchentang groups were given corresponding drugs （ig） and Ringer's solution （4 mL， ip）， while the EP group was treated with equal volume of normal saline （ig） and EP （0.04 g·kg-1·d-1， ip）. The normal group and the model group received equal volume of normal saline （ig） and Ringer's solution （ip） for 21 consecutive days. The contents of HMGB1， chemokine （C-X-C motif） ligand 1 （CXCL1）， CXCL2 and monocyte chemotactic protein-1 （MCP-1） in bronchoalveolar lavage fluid （BALF） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of HMGB1， RAGE and NF-κB p65 were determined by Real-time polymerase chain reaction （Real-time PCR）， and the protein expressions of HMGB1， RAGE， p-NF-κB p65， and alpha-smooth muscle actin （α-SMA） in bronchioles tissue of rats were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the forced vital capacity （FVC）， forced expiratory volume in the first second （FEV1） and FEV1/FVC in the model group were decreased （P<0.01） while the contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF were increased （P<0.01）. And the model group presented higher mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01） than the normal group. Compared with the model group， the modified Erchentang medium- and high-dose groups had increased FEV1/FVC （P<0.05， P<0.01）， lowered contents of HMGB1， CXCL1， CXCL2 and MCP-1 in BALF （P<0.05， P<0.05）， and reduced mRNA expressions of HMGB1， RAGE and NF-κB p65 （P<0.05， P<0.01） and protein expressions of HMGB1， RAGE， p-NF-κB p65 and α-SMA （P<0.05， P<0.01）. ConclusionModified Erchentang can resist bronchiolar inflammation of COPD rats. The mechanism may be related to down-regulating the mRNA expressiona of HMGB1 and RAGE， inhibiting the activity of NF-κB， and reducing the release of HMGB1， CXCL1， CXCL2 and MCP-1， thus suppressing the inflammatory injury and abnormal repair of bronchioles.

Treatment of vitiligo with 308-nm light emitting diode: Our experience from a two-year follow-up of Chinese patients.

BACKGROUND: A light emitting diode (LED), with a wavelength of 308 nm, has been utilized in the dermatologic treatment of vitiligo. OBJECTIVES: We investigated the efficacy and safety of 308-nm LED for use in the treatment of vitiligo. METHODS: We conducted a retrospective study of 70 stable-stage vitiligo patients (with a total of 99 lesions) who received 308-nm LED treatment at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to June 2020. Treatment efficacy was evaluated after 8 treatment sessions, 16 treatment sessions, and the final treatment session, to estimate the percentage of re-pigmentation in the treated area. The Kruskal-Wallis test was used for data analysis. RESULTS: Based on the final treatment session analysis of all 99 lesions, 0 lesions showed no response, 21 lesions showed poor response, 29 lesions showed moderate response, 23 lesions showed good response, and 26 lesions showed excellent response. The efficacy rate was 49.49%, and there was a significant correlation between the six distinct anatomical regions treated and re-pigmentation grade (χ2  = 13.419, p = .009). Among these regions, facial lesions showed the best response to treatment, while the hands and feet lesions showed the poorest response. CONCLUSIONS: The clinical efficacy of 308-nm LED treatment is limited based on the treatment area. It demonstrated significant practical application in the treatment of vitiligo.

TNF-α-stimulated nucleus pulposus cells induce cell apoptosis through the release of exosomal miR-16 targeting IGF-1 and IGF-1R in rats.

BACKGROUND: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism. METHODS: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs. RESULTS: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings. CONCLUSIONS: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs.

2D High-Entropy Hydrotalcites.

High-entropy materials (HEMs) with unique configuration and physicochemical properties have attracted intensive research interest. However, 2D HEMs have not been reported yet. To find out unique properties of combining 2D materials and HEMs, a series of 2D high-entropy hydrotalcites (HEHs) is created by coprecipitation method, including quinary, septenary, and even novenary metallic elements. It is found that the fast synthetic kinetics of coprecipitation process conquers the thermodynamically solubility limitation of different elements, which is the prerequisite condition to form HEHs. As the oxygen evolution reaction (OER) electrocatalysts, HEHs show significantly decreased apparent activation energy compared with low-entropy hydrotalcites (LEHs) due to the lattice distortion induced by the multimetallic character of HEHs. This work opens up a new avenue for the development of 2D HEMs, which broadens the family of HEMs and presents a most promising platform for exploring the unknown properties of HEMs.

Structural basis for the dimerization mechanism of human transcription factor E3.

The transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) is a member of the microphthalmia (MiT/TFE) transcription factor family. Dysregulation of TFE3 due to chromosomal abnormalities is associated with a subset of human renal cell carcinoma. Little structural information of this key transcription factor has been reported. In this study, we determined the crystal structure of the helix-loop-helix leucine zipper (HLH-Lz) domain of human TFE3 to a resolution of 2.6 Å. The HLH-Lz domain is critical for the dimerization and function of TFE3. Our structure showed that the conserved HLH region formed a four-helix bundle structure with a predominantly hydrophobic core, and the leucine zipper region contributed to the function of TFE3 by promoting dimer interaction and providing partner selectivity. Together, our results elucidated the dimerization mechanism of this important transcription factor, providing the structural basis for the development of inhibiting strategies for treating TFE3 dysregulated diseases.

Photoluminescence properties of Er3+ and Eu3+ ions based on oxide host for optical temperature sensing with high sensitivity.

Motivated from increasing demands of non-contact optical temperature sensing, the Yb3+-Er3+ and Eu3+ doped NaY9Si6O26 (NYS) oxide phosphors were designed by high-temperature solid-state reaction method. The phase purity of the as-prepared samples was checked from XRD patterns. For the upconversion luminescence in NYS:Yb3+,Er3+, the optimal Er3+ doping content was determined to be 1 mol%, and the characteristic emission peaks of Er3+ were observed in the region of 500-700 nm. In Eu3+ activated NYS phosphors, it has been found that the emissions originating in 5D1 and 5D0 levels demonstrate different change tendencies in intensity with Eu3+ doping concentration. By studying the temperature-dependent luminescent spectra, it was indicated that the emissions intensities from different excited states of Er3+ change differently with temperature. Two kinds of fluorescence intensity ratio (FIR) strategies were used in NYS:10%Yb3+,1%Er3+, containing thermally-coupled levels and non-thermally-coupled levels. In the NYS:3%Eu3+ phosphor, it was found that the FIR for 577 and 536 nm emissions follows a linear relation with temperature. The high sensitivities in the present phosphors indicate the potential application in optical temperature sensing.

Efficacy of intramedullary nail fixation for the tretament of tibial shaft fracture with difference approachs / 中国骨伤

OBJECTIVE@#To compare clinical effect of intramedullary nailing through suprapatellar, infrapatellar and paracpatellar approach in treating tibial shaft fracture.@*METHODS@#From June 2012 to June 2018, 36 patients with tibial shaft fracture were treated with intramedullary nails, and were divided into three groups according to surgical approach. Twleve patients were through suprapatellar approach, including 7 males and 5 females aged from 25 to 53 years old with an average of (37.8±11.4) years old;and 4 patients were type A, 4 patients were type B, and 4 patients were type C according to AO classification. Ten patients were through infrapatellar approach, including 6 males and 4 females aged from 19 to 56 years old with an average of (35.6±10.0) years old;and 3 patients were type A, 4 patients were type B, and 3 patients were type C according to AO classification. Forteen patients were through paracpatellar approach, including 8 males and 6 females aged from 21 to 58 years old with an average of (36.6±10.0) years old;and 4 patients were type A, 6 patients were type B, and 4 patients were type C according to AO classification. Operation time, intraoperative blood loss, fluoroscopy times, fracture healing time and complications among three groups were observed, and knee joint functions were evaluated by Lysholm score.@*RESULTS@#All patients were followed up from 12 to 18 months with an average of (15.0±3.0) months. There were no difference in intraoperative blood loss and fracture healing time among three groups (@*CONCLUSION@#intramedullary nailing through suprapatellar for the treatment of tibial shaft fracture is benefit for fracture healing and recovery of knee joint function, while infrapatellar and paracpatellar approach have advantages in exposure of insertion point. We should select approach reasonably according to our experience.

Oral cavity flow distribution and pressure drop in balaenid whales feeding: a theoretical analysis.

Balaenid whales, as continuous ram filter feeders, can efficiently separate prey from water by baleen. The feeding process of balaenid whales is extremely complex, in which the flow distribution and pressure drop in the oral cavity play a significant role. In this paper, a theoretical model coupled with oral cavity velocity and pressure in balaenid whales is established based on mass conservation, momentum conservation and pressure drop equations, considering both the inertial and the friction terms. A discrete method with section-by-section calculation is adopted to solve the theoretical model. The effects of four crucial parameters, i.e. the ratio of filtration area to inlet area (S), the Reynolds number of entrance (Re in ), the ratio of thickness to permeability of the porous media formed by the fringe layer (ϕ) and the width ratio of the anteroposterior canal within the mouth along the tongue (APT channel) to that along the lip (APL channel) (H) are discussed. The results show that, for a given case, the flow distribution and the pressure drop both show increasing trends with the flow direction. For different cases, when S is small, Re in is small and ϕ is large, a good flow pattern emerges with a smoother flow speed near the oropharynx, better drainage, better shunting and filtration, and higher energy efficiency. However, for smaller values of H, some energy efficiency is sacrificed to achieve additional average transverse flow in order to produce better shunting and filtration. The research in this paper provides a reference for the design of high-efficiency bionic filters.

Yolk-porous shell biphasic bioceramic granules enhancing bone regeneration and repair beyond homogenous hybrid.

Bioactive stimulation and spatiotemporal evolution of porous scaffolds with time are crucial for bone regeneration rate in bone repair process. Granule-type bioceramic scaffolds have attracted significant interest in biomedical applications in recent years. However, the major limitation of such porous architecture is that the low initial porosity is disadvantageous for enhancing new bone tissue ingrowth. Here we reported that the yolk-shell-structured biphasic bioceramic granules with adjustable shell microstructures were favorable for controllable ion release in vitro, superior to the granules with the conventional homogenous hybrid structures. Also, we illustrated a significant difference in biodegradation of the granules in vivo, and especially the porous-shell granules exhibited appreciable new bone tissue ingrowth with time. The underlying fundamental mechanisms governing the new bone tissue ingrowth behavior of the yolk-shell granule scaffolds were elucidated based on microCT analyses and histological observation. It was underscored that during biodegradation in vivo, the highly bioactive ions in yolk layer were continuously released due to the porous structures of the sparingly dissolvable shell layer, thereby resulting in hollow shell and rapid new bone tissue ingrowth. Hence, these results demonstrate that the slight tailoring in microstructure and component distribution of biphasic composites is beneficial for adjusting the bone regeneration, and may help us to precisely control bone repair efficiency for a variety of clinical conditions.