3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius.

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

Causal effect of education on bone mineral density: A Mendelian randomization study.

Education level may have some association with the incidence of osteoporosis, but it is elusive if this association is causal. This two-sample Mendelian randomization analysis focused on the causal effect of education level on femoral neck bone mineral density (FN-BMD), forearm BMD, lumbar spine BMD, and heel BMD. Twelve single nucleotide polymorphisms were used as instrumental variables. The results suggested that high education level was associated with improved FN-BMD (beta-estimate: 0.406, 95% confidence interval: 0.061 to 0.751, standard error: 0.176, P-value = .021). There were null association between education and other sites of bone mineral density. Our results found the causal effect of high education level on improved FN-BMD, and improved educational attainment may be beneficial to prevent osteoporosis.

Microstructural and chemical features of impact melts on Ryugu particle surfaces: Records of interplanetary dust hit on asteroid Ryugu.

The Hayabusa2 spacecraft delivered samples of the carbonaceous asteroid Ryugu to Earth. Some of the sample particles show evidence of micrometeoroid impacts, which occurred on the asteroid surface. Among those, particles A0067 and A0094 have flat surfaces on which a large number of microcraters and impact melt splashes are observed. Two impact melt splashes and one microcrater were analyzed to unveil the nature of the objects that impacted the asteroid surface. The melt splashes consist mainly of Mg-Fe-rich glassy silicates and Fe-Ni sulfides. The microcrater trapped an impact melt consisting mainly of Mg-Fe-rich glassy silicate, Fe-Ni sulfides, and minor silica-rich glass. These impact melts show a single compositional trend indicating mixing of Ryugu surface materials and impactors having chondritic chemical compositions. The relict impactor in one of the melt splashes shows mineralogical similarity with anhydrous chondritic interplanetary dust particles having a probable cometary origin. The chondritic micrometeoroids probably impacted the Ryugu surface during its residence in a near-Earth orbit.

ZnO-Au@ZIF-8 core-shell nanorod arrays for ppb-level NO2 detection.

ZnO-Au@ZIF-8 core-shell heterostructures were prepared by ZIF-8 encapsulation of sacrificial ZnO-Au nanorods. Because of the catalytic activity of the Au nanoparticles and the sieving effects of the ZIF-8, the ZnO-Au@ZIF-8 heterostructures showed an outstanding response of 1.8 to 5 ppb NO2, and exhibited higher selectivity, stability, anti-humidity and fast response and recovery properties. The combination of the gas-selective catalytic activity of noble metals with the MOF filter used in this work can be easily extended to synthesize other types of MOS@MOF sensors, opening a new avenue for the detection of hazardous gases.

Enhanced Optical Transmission through a Hybrid Bull's Eye Structure Integrated with a Silicon Hemisphere.

In this work, we demonstrate a novel structure that can generate extraordinary optical transmission with a silicon hemisphere placed on a conventional bull's eye structure. There is a single subwavelength aperture surrounded by concentric periodic grooves on a substrate. The extraordinary optical transmission in this work is realized by the coupling of the surface plasmon polaritons in the periodic grooves and the localized electromagnetic field generated by the Mie resonance in the silicon hemisphere. The maximum normalized-to-area transmission peak can reach up to 662 with a decreasing device area and size. The electromagnetic field distribution at different geometry parameters is analyzed to clarify the mechanisms of the work in this paper. Additionally, the use of dielectric material in the aperture can avoid ohmic losses of metal material compared with the conventional one, which may suggest that a wider range of bull's-eye-structure applications is possible.

A low-content CeOx dually promoted Ni3Fe@CNT electrocatalyst for overall water splitting.

Rational construction of low-cost and high-performance electrocatalysts for water splitting is crucial for the advancement of renewable hydrogen fuel. Hybridizing heterojunctions or noble metals is one typical strategy used to boost the electrocatalytic performance for either the oxygen evolution reaction (OER) or hydrogen evolution reaction (HER). Here, low-content CeOx (3.74 wt%) is introduced into Ni3Fe nanoparticle-encapsulated carbon nanotubes (Ni3Fe@CNTs/CeOx), with both the OER and HER activities boosted, as a bifunctional electrocatalyst for overall water splitting. The composite is derived by pyrolyzing a mixture of melamine/ternary NiFeCe-layered double hydroxide. The composite electrocatalyst requires low overpotentials of 195 and 125 mV at 10 mA cm-2 in 1.0 M KOH, respectively, which are superior to those of Ni3Fe@CNTs/NF (313 and 139 mV) and CeOx/NF (345 and 129 mV), and in particular, OER overpotentials of 320 and 370 mV at 50 and 100 mA cm-2, respectively. Moreover, the composite-assembled electrolyzer for overall water splitting requires a current density of 10 mA cm-2 at a decent cell voltage of 1.641 V. Furthermore, the enhancement is elucidated by the synergistic effect: the dual role of CeOx in boosting the OER and HER, the highly conductive carbonaceous CNTs, large electrochemically active surface area and low charge-transfer resistance. The results can offer an effective route for designing and preparing low-cost and high-efficiency electrocatalysts for electrocatalytic water splitting.

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu.

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (-OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss.

Composite Mesoporous Silica Nanoparticles with Dual-color Afterglow for Cross-correlation-based Living Cell Imaging.

Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Förster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.

Causal Roles of Sleep Duration in Osteoporosis and Cardiometabolic Diseases: A Mendelian Randomization Study.

Sleep duration suggests some association with osteoporosis and cardiometabolic diseases, but it is unknown if these associations are causal or confounded. In this two-sample Mendelian randomization (MR) study, we included the largest genome-wide association studies (GWASs) associated with sleep duration and the outcome measures of osteoporosis and cardiometabolic diseases. Finally, 25 single nucleotide polymorphisms (SNPs) associated with short sleep duration and 7 SNPs associated with long sleep duration obtained the genome-wide significance (P < 5 × 10-8) and were used as instrumental variables. Genetic predisposition to short sleep duration was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.199, 95% confidence interval CI: 0.081 to 0.317, standard error SE:0.060, P value = 0.001) and heart failure (beta-estimate: 0.145, 95% CI: 0.025 to 0.264, SE:0.061, P value = 0.017), which were both confirmed by the sensitivity analyses. Both short and long sleep duration may reduce the estimated bone mineral density (eBMD, beta-estimate: -0.086, 95% CI: -0.141 to -0.031, SE:0.028, P value = 0.002 for short sleep duration; beta-estimate: -0.080, 95% CI: -0.120 to -0.041, SE:0.020, P value < 0.0001 for long sleep duration). There was limited evidence of associations between sleep duration and fracture, type 2 diabetes, atrial fibrillation, fasting glucose, fasting insulin, or HbA1c. This study provides robust evidence that short sleep duration is causally associated with high risk of coronary artery disease and heart failure and suggests that short sleep duration should be avoided to prevent these two cardiovascular diseases. Short and long sleep duration show some MR association with reduced eBMD, which indicates that both short and long sleep duration may be prevented to reduce the incidence of osteoporosis.

Polymeric micelle-based nanoagents enable phototriggering combined chemotherapy and photothermal therapy with high sensitivity.

A new type of polymeric nanomicelle-based nanoagent (denoted as PT@MFH hereafter) capable of the highly sensitive release of the chemotherapeutic drug paclitaxel (PTX) upon exposure to a near-infrared (NIR) laser trigger was developed. Specifically, PTX and a photothermal polymer (T-DPPT) were encapsulated in the cavity of nanomicelles, which were constructed from an amphiphilic block copolymer (PCL-PEEP) with a lower critical solution temperature (LCST) of ∼54 °C. Owing to the unprecedented ability of the T-DPPT moiety to harvest near-infrared light, with a mass extinction coefficient at 808 nm of up to ∼80.8 L g-1 cm-1, and convert NIR light to heat, with a photothermal conversion efficiency (η) of up to ∼70%, local hyperthermia was promptly realized via irradiation from an 808 nm laser with extraordinarily low output power. This enabled remarkable contrast in the local temperature and drug release between the "silent" state (prior to phototriggering) and the "activated" state (after phototriggering). This NIR-light-activated local hyperthermia and drug release presented the basis for combined chemotherapy and photothermal therapy (PTT) in antitumor treatment and displayed superb therapeutic efficacy. This pattern together with the high spatial precision imparted by laser triggering jointly contributed to the maximum combined antitumor efficacy to the tumor, while exhibiting minimal side effects on the normal tissues, as preliminarily verified in the in vivo experiment regarding the ability of PT@MFH to efficiently inhibit tumor growth in tumor-bearing model mice.

Restoring Impaired Fertility Through Diet: Observations of Switching From High-Fat Diet During Puberty to Normal Diet in Adulthood Among Obese Male Mice.

Background: Obesity is associated with a decrease in testicular function, yet the effects and mechanisms relative to different stages of sexual development remain unclear. The aim of this study is to determine whether high-fat diet-induced obesity impairs male fertility during puberty and in adulthood, and to ascertain its underlying mechanisms. This study aims to further reveal whether restoring to a normal diet can improve impaired fertility. Methods: Male mice were divided into 6 groups: the group N and H exposed to a normal diet or high-fat diet during puberty. The group NN or NH were further maintained a normal diet or exposed to high-fat diet in adulthood, the group HH or HN were further maintained high-fat diet or switched to normal diet in adulthood. Metabolic parameters, fertility parameters, testicular function parameters, TUNEL staining and testicular function-related proteins were evaluated, respectively. Results: The fertility of the mice in the high-fat diet group was impaired, which validated by declines in pregnancy rates and litter weight loss. Further analysis demonstrated the increased level of oxidative stress, the increased number of spermatogenic cell apoptosis and decreased number of sperm and decreased acrosome integrity. The expression of steroidogenic acute regulatory (StAR) and spermatogenesis related proteins (WT-1) decreased. Fertility among the HN group recovered, accompanied by the recovery of metabolism, fertility and testicular function parameters, StAR and WT-1 expression. Conclusions: The findings suggest that high-fat diet-induced obesity impairs male fertility during puberty and in adulthood. The loss of acrosome integrity, the increase of oxidative stress, the increase of cells apoptosis and the down-regulation of StAR and WT-1 may be the underlying mechanisms. Switching from high-fat diets during puberty to normal diets in adulthood can improve male fertility.

Environmental risk assessment of the potential "Chemical Time Bomb" of ion-adsorption type rare earth elements in urban areas.

Ion-adsorption type rare earth elements (REEs) located in tropical and subtropical zones have abundant movable and bioavailable ion-exchangeable REEs and could be an environmental hazard. However, our understanding of their environmental risk in urban areas is limited. We aimed to determine whether ion-adsorption type REEs in Guangzhou represent a kind of potential "Chemical Time Bomb" (CTB) and assess the environmental risk. We conducted a comprehensive survey of REEs in 181 samples including regolith (n = 70), surface water (n = 55), sediment (n = 25), vegetables (n = 22) and rhizosphere soil (n = 9), collected from five regions around Guangzhou, as a representative city of ion-adsorption type REEs in tropical and subtropical zones. The existing environmental risk was assessed by calculating the estimated daily intake (EDI) of REEs through vegetable consumption, and leaching simulation experiments were used to discuss the factors affecting the long-term stability of REEs. The average REEs concentrations (ΣREEs) in the regolith and sediment were 458.5 and 218.6 µg·g-1, respectively, which were higher than the background values of regolith (197.3 µg·g-1) and sediment (173.3 µg·g-1), and large proportions of ion-exchangeable REEs were observed in regolith and sediment, indicating that ion-adsorption type REEs in Guangzhou are a kind of potential CTB. The average ΣREEs in surface water (3.9 µg·L-1), rhizosphere soil (466.9 µg·g-1) and vegetables (25.0 µg·g-1·dw) suggest that REEs have migrated to the supergene environment even organisms. The average EDI (55.4 µg·kg-1·d-1) close to the safety limitation (70 µg·kg-1·d-1) suggests that the existing health risk is very worrisome. Human factors, including acid rain, mining and farming, probably ignite the CTB, causing the release of REEs to the urban environment on a large scale. This prospective study demonstrated that REEs exposure problems in urban areas of ion-adsorption type REEs should not be ignored.

Characterization and functional properties of conjugates of rice protein with exopolysaccharides from Arthrobacter ps-5 by Maillard reaction.

The study examined the potential nutritive value of rice protein (RP) through Maillard reaction. Structures and properties of synthetic conjugates of RP and exopolysaccharide (EPS) from Arthrobacter ps-5 were investigated systematically. Fluorescence characteristics and high molecular weight compounds appeared in Maillard reaction products (MRPs). Moreover, EPS or its degradation products in the form of covalent bond cross-linked with RP were identified, where -NH2 disappeared and C=O, C=N and C-N increased. Determination of free -SH residues suggested mutual conversion between disulfide bonds and sulfhydryl groups occurred during Maillard reaction. HPLC analysis identified conjugates with different molecular weight, where melanoprotein was formed by covalent bonds. As RP conjugated with EPS, the molecules spread out and changed the spatial structure. Functional properties of MRPs, including solubility, foaming activity, emulsifying ability and resistance to oxidation, were greatly improved. The study has discovered an efficient method for increasing the application value of plant protein.

Overexpression of hsa_circ_0094742 inhibits IL-1ß-induced decline in CHON-001 cell viability by targeting microRNA-127-5p.

Osteoarthritis (OA) is a public health problem that affects 240 million people globally; however, the current treatment options for OA are not effective. Therefore, there is still an urgent need to identify novel strategies to reduce the incidence and progression of OA. The circular RNA hsa_circ_0094742 was reported to be downregulated in patients with OA. However, the underlying mechanism remains unclear. The levels of hsa_circ_0094742 in CHON-001 were detected by reverse transcription quantitative polymerase chain reaction. Moreover, Cell Counting Kit-8 assay and Ki67 staining were used to determine the cell viability. The protein expression of biomarkers was detected by western blot analysis. In addition, the putative downstream target of hsa_circ_0094742 was predicted using the Circinteractome and TargetScan online databases. The putative targeting relationship was verified by dual luciferase reporter assay and fluorescence in situ hybridization. Next, cell apoptosis was determined by Annexin V/PI staining. hsa_circ_0094742 overexpression (OE) inhibited interleukin (IL)-1ß-induced decline in the viability of CHON-001 cells and primary human chondrocytes. Furthermore, IL-1ß-induced alterations in aggrecan, matrix metallopeptidase 13, X-linked inhibitor of apoptosis protein (XIAP), Bax and active caspase 3 were reversed by hsa_circ_0094742 OE. Luciferase reporter assay indicated that miR-127-5p was the downstream target of hsa_circ_0094742, and latexin was the target of miR-127-5p. hsa_circ_0094742 OE inhibited IL-1ß-induced decline in CHON-001 cell viability by targeting miRNA-127-5p. The findings of the present study revealed the biological rational of the use of hsa_circ_0094742 OE as an anti-IL-1ß effector in human chondrocytes. These findings may prompt further research on hsa_circ_0094742 as a potent circRNA target for the treatment of OA.

Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress-Induced Blood-Testis Barrier Damage.

BACKGROUND/AIMS: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males. METHODS: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence. RESULTS: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs). CONCLUSION: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.

Cyclophilin D participates in the inhibitory effect of high-fat diet on the expression of steroidogenic acute regulatory protein.

OBJECTIVE: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD. METHODS: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif-/- ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays. RESULTS: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif-/- mice with HFD. CONCLUSIONS: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.

MiR-671 ameliorates the progression of osteoarthritis in vitro and in vivo.

OBJECTIVES: Expression of miR-671 was reported to be downregulated in articular cartilage of patients with OA compared to healthy individuals, indicating it may serve as potential biomarker for OA. However, the mechanism by which miR-671 regulates the progression of OA remains unclear. Here, we aimed to investigate the role of miR-671 in cartilage from patients with OA. METHODS: The expression of miR-671 and inflammation mediators in cartilage from patients with OA was analyzed by RT-PCR. In vitro, chondrocytes CHON-001 were stimulated with IL-1ß for 24 h for OA model establishment. Protein expression of MMP-13, aggrecan, and collagen II was measured by western blot. In vivo, the severity of OA in mice was determined by histological analysis. RESULTS: We found that the level of miR-671 was downregulated in OA tissues, plasma and IL-1ß treated CHON-001 cells, compared with control. MiR-671 mimics ameliorated IL-1ß-induced proliferation inhibition and apoptosis stimulation, as well as decreased protein levels of collagen II and aggrecan in CHON-001 cells. In vivo study showed miR-671 mimics alleviated the progression of OA in mice. CONCLUSION: These results indicated miR-671 play an important role during the pathogenesis of OA. Therefore, miR-671 may serve as a potential therapeutic target for the treatment of OA.

Association of TIMP4 gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China.

BACKGROUND: In clinical treatment, the use of steroid hormones is an important etiological factor of non-traumatic osteonecrosis of the femoral head (ONFH) risk. As an endogenous inhibitor of matrix metalloproteinases (MMPs) in the extracellular matrix, the expression of tissue inhibitors of metalloprotease-4 (TIMP4) plays an essential role in cartilage and bone tissue damage and remodeling, vasculitis formation, intravascular thrombosis, and lipid metabolism. METHODS: This study aimed to detect the association between TIMP4 polymorphism and steroid-induced ONFH. We genotyped seven single-nucleotide polymorphisms (SNPs) in TIMP4 genes and analyzed the association with steroid-induced ONFH from 286 steroid-induced ONFH patients and 309 normal individuals. RESULTS: We performed allelic model analysis and found that the minor alleles of five SNPs (rs99365, rs308952, rs3817004, rs2279750, and rs3755724) were associated with decreased steroid-induced ONFH (p = 0.02, p = 0.03, p = 0.04, p = 0.01, p = 0.04, respectively). rs2279750 showed a significant association with decreased risk of steroid-induced ONFH in the Dominant and Log-additive models (p = 0.042, p = 0.028, respectively), and rs9935, rs30892, and rs3817004 were associated with decreased risk in the Log-additive model (p = 0.038, p = 0.044, p = 0.042, respectively). In further stratification analysis, TIMP4 gene variants showed a significant association with steroid-induced ONFH in gender under the genotypes. Haplotype analysis also revealed that "TCAGAC" and "CCGGAA" sequences have protective effect on steroid-induced ONFH. CONCLUSION: Our results indicate that five TIMP4 SNPs (rs99365, rs308952, rs3817004 rs2279750, and rs3755724) are significantly associated with decreased risk of steroid-induced ONFH in the population of northern China.

MMP-14 single-nucleotide polymorphisms are related to steroid-induced osteonecrosis of the femoral head in the population of northern China.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a refractory disease which frequently occurs in young and middle-aged people. Recent studies indicated that MMP-14 played an important role in the development of chondrocytes, metabolism of osteoblasts as well as fate decision of hypertrophic chondrocytes. The aim of this study was to investigate the association between polymorphisms of MMP-14 and steroid-induced osteonecrosis of the femoral head in the Chinese population. METHODS: We selected 7 SNPs (rs3751488, rs1003349, rs1042703, rs2236302, rs1042704, rs2236303, and rs2236304) on gene MMP-14. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. RESULTS: We discovered that the genotype "G/G" of rs2236302 was associated with ONFH risk in the MMP-14 in the codominant model (OR = 8.62, 95% CI = 1.07-69.46, p = 0.038) and recessive model (OR = 8.86, 95% CI = 1.10-71.31, p = 0.013). CONCLUSIONS: We have confirmed that the susceptive SNPs (rs2236302) of MMP-14 from the MMPs/TIMPs system exhibit a significant association with increased risk of steroid-induced ONFH in the population of northern China.

Cyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates hepatic steatosis.

Physiological opening of the mitochondrial permeability transition pore (mPTP) is indispensable for maintaining mitochondrial function and cell homeostasis, but the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated by an increase of CypD expression induced hepatic mitochondrial dysfunction. Notably, such mitochondrial perturbation occurred before detectable triglyceride accumulation in the liver of high-fat diet-fed mice. Moreover, either genetic knockout or pharmacological inhibition of CypD could ameliorate mitochondrial dysfunction, including excess mPTP opening and stress, and down-regulate the transcription of sterol regulatory element-binding protein-1c, a key factor of lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of CypD-infected mice was aggravated relative to the control group. Blocking p38 mitogen-activated protein kinase or liver-specific Ire1α knockout could resist CypD-induced sterol regulatory element-binding protein-1c expression and steatosis. Importantly, CypD inhibitor applied prior to or after the onset of triglyceride deposition substantially prevented or ameliorated fatty liver. CONCLUSION: CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen-activated protein kinase activation, and results in enhanced sterol regulatory element-binding protein-1c transcription and hepatic steatosis. (Hepatology 2018;68:62-77).