Publications by authors named "Q Li"

Introduction: Fetal-originated osteoarthritis is relative to poor cartilage quality and may exhibit transgenerational genetic effects. Previous findings revealed prenatal dexamethasone exposure (PDE) induced poor cartilage quality in offspring.

Objectives: This study focused on further exploring molecular mechanism, heritability, and early intervention of fetal-originated osteoarthritis.

Methods: Pregnant rats (F0) were segregated into control and PDE groups depending upon whether dexamethasone was administered on gestational days (GDs) 9-20. Some female offspring were bred with healthy males during postnatal week (PW) 8 to attain the F2 and F3 generations. The F3-generation rats were administrated with glucosamine intragastrically at PW12 for 6 weeks. The knee cartilages of male and female rats at different time points were harvested to assay their morphologies and functions. Furthermore, primary chondrocytes from the F3-generation rats were isolated to confirm the mechanism and intervention target of glucosamine.

Results: Compared with the control, female and male rats in each generation of PDE group showed thinner cartilage thicknesses; shallower and uneven staining; fewer chondrocytes; higher Osteoarthritis Research Society International scores; and lower mRNA and protein expression of SP1, TGFβR1, Smad2, SOX9, ACAN and COL2A1. After F3-generation rats were treated with glucosamine, all of the above changes could be reversed. In primary chondrocytes isolated from the F3-generation rats of PDE group, glucosamine promoted SP1 expression and binding to TGFβR1 promoter to increase the expression of TGFβR1, p-Smad2, SOX9, ACAN and COL2A1, but these were prevented by SB431542 (a potent and selective inhibitor of TGFβR1).

Conclusions: PDE induced chondrodysplasia in offspring and stably inherited in F3-generation rats, which was related to decreased expression of SP1/TGFβR1/Smad2/SOX9 pathway to reduce the cartilage matrix synthesis, without major sex-based variations. Glucosamine could alleviate the poor genetic cartilage quality in offspring induced by PDE by up-regulating SP1/TGFβR1 signaling, which was prevented by a TGFβR1 inhibitor. This study elucidated the molecular mechanism and therapeutic target (TGFβR1) of genetic chondrodysplasia caused by PDE, which provides a research basis for precisely treating fetal-originated osteoarthritis.

Recently, Bi-activated phosphors have been widely researched for phosphor-converted light-emitting diode (pc-LED) applications. Herein, novel full-spectrum ABO:Bi (A = Gd, La; B = Sb, Nb) phosphors with a luminescence-tunable performance were achieved by a chemical substitution strategy. In the LaSbO host material, a new luminescent center was introduced, with Gd replacing La. The photoluminescence (PL) spectra show a large blue shift from 520 to 445 nm, thus achieving regulation from green to blue lights. Moreover, a series of solid solution-phase phosphors LaSbNbO:Bi were prepared by replacing Sb with Nb, and a PL spectral tunability from green (520 nm) to orange-red (592 nm) was realized. Temperature-dependent PL spectra show that LaGdSbO:Bi phosphors have excellent thermal stability. Upon 350 nm excitation, the PL intensity of LaGdSbO:Bi phosphors at 150 °C remained at more than 93% at room temperature. With Gd doping, the thermal stability gradually improved, and LaGdSbO:0.03Bi represents splendid antithermal quenching (135.2% at 150 °C). Finally, a full-visible spectrum for pc-LED with a high color-rendering index (Ra = 94.4) was obtained. These results indicated that chemical substitution is an effective strategy to adjust the PL of Bi, which is of great significance in white-light illumination and accurate plant lighting.

Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients.

Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score.

Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively.

Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X-related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1 mutation in knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

Replicating natural postures of human arms is essential to generate human-like behaviors in robotic applications for humans nearby. However, how to realize this requirement in interactive scenarios remains a challenge due to the kinematic redundancy and unknown postural control strategy of human arms. Inspired by the physiological characteristics that the musculoskeletal system is coordinated to minimize muscle effort in human behaviors, this paper aims to address the issue by solving a muscle effort minimization problem. It adopts a high-fidelity human arm musculoskeletal model (HAMM) and considers the implicit constraint (desired hand pose) and the inequality constraints (range of joint motion). The constrained minimization is in general nonconvex, consequently sensitive to initial guesses in iterative procedures. So, it is impracticable to solve it directly with existing gradient-based deterministic approaches or standard evolutionary algorithms. As the main contribution, a hybrid inverse kinematics algorithm was proposed for the HAMM with 7 independent and 13 mimic joints to obtain the feasible arm postures satisfying the minimization constraints. Using the arm swivel angle that parametrizes the kinematic redundancy of the HAMM, geometrically equidistant initial guess candidates can be generated over the 1-dimension feasible posture manifold. As another contribution, we present a two-phase global minimization algorithm to handle the nonconvexity of the constrained minimization. It consists of a local-search phase on the null-space of the geometric Jacobian matrix and a global-search phase with an initial guess resampling strategy. The proposed approach was validated by replicating the natural arm postures of 5 right-handed subjects in daily tasks.