Pulley Effect in the Capture of DNA Translocation through Solid-State Nanopores.

Nanopores are powerful single-molecule sensors for analyzing biomolecules such as DNA and proteins. Understanding the dynamics of DNA capture and translocation through nanopores is essential for optimizing their performance. In this study, we examine the effects of applied voltage and pore diameter on current blockage, translocation time, collision, and capture location by translocating λ-DNA through 5.7 and 16 nm solid-state nanopores. Ionic current changes are used to infer DNA conformations during translocation. We find that translocation time increases with pore diameter, which can be attributed to the decrease of the stall force. Linear and exponential decreases of collision frequency with voltage are observed in the 16 and 5.7 nm pores, respectively, indicating a free energy barrier in the small pore. Moreover, the results reveal a voltage-dependent bias in the capture location toward the DNA ends, which is explained by a "pulley effect" deforming the DNA as it approaches the pore. This study provides insights into the physics governing DNA capture and translocation, which can be useful for promoting single-file translocation to enhance nanopore sensing.

Analysis of the effect of cations on protein conformational stability using solid-state nanopores.

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ. As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na+ and Li+) on a model protein bovine serum albumin (BSA) conformation using SiNx nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li+ is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

Low levels of mouse sperm chromatin fragmentation delay embryo development.

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner. Mouse sperm were treated with varying concentrations of either H2O2 or MnCl2, and the DNA damage was assessed by pulse-field gel electrophoresis, and the alkaline and neutral comet assays. Oocytes were injected with either treated sperm and the resulting embryos analyzed with an embryoscope to detect subtle changes in embryonic development. We confirmed that H2O2 treatment induced primarily single-stranded DNA breaks and MnCl2 induced primarily double-stranded DNA breaks, indicating different mechanisms of damage. These sperm were injected into oocytes, and the development of the resulting embryos followed with an embryoscope equipped with time lapse recording. We found that aberrations in early embryonic development by day 2 with even the lowest levels of DNA damage and that the levels of embryonic aberrations correlated to the concentration of either H2O2 or MnCl2. Low levels of H2O2 caused significantly more aberrations in embryonic development than low levels of MnCl2 even though the levels of DNA damage as measured by comet assays were similar. These data demonstrate that even low levels of sperm DNA damage cause delays and arrests in embryonic development.

Deletion of Orc4 during oogenesis severely reduces polar body extrusion and blocks zygotic DNA replication†.

Origin recognition complex subunit 4 (ORC4) is a DNA-binding protein required for DNA replication. During oocyte maturation, after the last oocyte DNA replication step and before zygotic DNA replication, the oocyte undergoes two meiotic cell divisions in which half the DNA is ejected in much smaller polar bodies. We previously demonstrated that ORC4 forms a cytoplasmic cage around the DNA that is ejected in both polar body extrusion (PBE) events. Here, we used ZP3 activated Cre to delete exon 7 of Orc4 during oogenesis to test how it affected both predicted functions of ORC4: its recently discovered role in PBE and its well-known role in DNA synthesis. Orc4 deletion severely reduced PBE. Almost half of Orc4-depleted germinal vesicle (GV) oocytes cultured in vitro were arrested before anaphase I (48%), and only 25% produced normal first polar bodies. This supports the role of ORC4 in PBE and suggests that transcription of the full-length Orc4 during oogenesis is required for efficient PBE. Orc4 deletion also abolished zygotic DNA synthesis. Fewer Orc4-depleted oocytes developed to the metaphase II (MII) stage, and after activation these oocytes were arrested at the two-cell stage without undergoing DNA synthesis. This confirms that transcription of full-length Orc4 after the primary follicle stage is required for zygotic DNA replication. The data also suggest that MII oocytes do not have a replication licensing checkpoint as cytokinesis progressed without DNA synthesis. Together, the data confirm that oocyte ORC4 is important for both PBE and zygotic DNA synthesis.

Sperm degradation after vasectomy follows a sperm chromatin fragmentation-dependent mechanism causing DNA breaks in the toroid linker regions.

Vasectomy is a widely used surgical technique creating an obstructive azoospermia. Although sperm cannot be ejaculated, the testis maintains sperm production in vasectomized males. The continuous accumulation of sperm deposited in the epididymis and the vas deferens fraction necessarily need to be degraded and eliminated. While the elimination process is carried out by granulomas that form after vasectomy, the detailed mechanisms of sperm degradation are still not known. The aim was to assess whether sperm chromatin fragmentation (SCF), a mechanism that degrades the entire sperm genome at the toroid linker regions (TLRs), is activated after vasectomy in sperm cells. We vasectomized mice and evaluated the presence of TLR-specific double-strand breaks through pulsed-field gel electrophoresis and the Comet assay at 1, 2 and 3 weeks after surgery. Results for DNA damage (Olive tail moment) at single-cell level showed an increase of double-strand breaks after vasectomy for vas deferens sperm after 1, 2 and 3 weeks postvasectomy (21.78 ± 2.29; 19.71 ± 1.79 and 32.59 ± 1.81, respectively), compared to mock surgery (7.04 ± 1.03; 10.10 ± 1.29 and 8.64 ± 0.85, respectively; P < 0.001). Similar findings were obtained for cauda epididymis sperm (P < 0.001), but not for caput epididymis (P > 0.05). Pulsed-field gel electrophoresis showed the presence of double-stranded breaks between 15 and 145 kb, indicating that DNA breaks were produced mainly in the sperm TLRs. Results presented here suggest that SCF is a mechanism activated in vas deferens after vasectomy to degrade sperm DNA when they cannot be ejaculated, preventing their function.

Prevalence of anxiety and its associated factors among infertile patients after 'two-child' policy in Chongqing, China: a cross-sectional study.

BACKGROUND: With the prevalence of infertility increasing every year around the world, it has seriously impacted the individual quality of family and social life. Anxiety is one of the most prevalent anxiety disorders among infertile patients. After the two-child policy, whether it affected the prevalence of anxiety is controversial. This study aimed to determine the prevalence of anxiety and its potential risk factors among Chinese infertile women after the enforcement of 'two-child policy'. METHODS: This cross-sectional study included 693 infertile patients in a reproductive medical center in Chongqing, China, between February 2016 and December 2018. Data was collected by Self-filling questionnaires including basic demographic information and the Generalized Anxiety Disorder-7 (GAD-7). SPSS statistical software (IBM SPSS version 25) was used to analyse the obtained data. Descriptive analysis was used to describe basic information and anxiety scores, the chi-square test and binary logistic regression were used to analyse the relationship between anxiety and other variables. RESULTS: The prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients (FI), and 18.4% among second-child infertile patients (SI) respectively (P > 0.05). Binary logistic regression showed that patients with lower education levels were more likely to have anxiety (P < 0.01). Patients with middle salary incomes were more likely to have anxiety (OR = 1.860, 95% CI: 1.068-3.238). Oral contraception taking history (OR = 1.778, 95% CI: 1.186-2.667), and history of allergy (OR = 2.098, 95% CI: 1.219-3.612) were associated with anxiety. CONCLUSIONS: Under the full liberalization of the "two-child policy", the total prevalence of anxiety among Chinese infertile female is comparatively high. Low education levels, middle incomes, oral contraception taking and allergy history can be the related risk factors of anxiety. We promote that all infertile patients should be evaluated for the prevalence of anxiety, especially those with potential risks, and receive consultant or targeted treatment when needed.

Effect of Loading Devices on Muscle Activation in Squat and Lunge.

CONTEXT: Squats and lunges are common exercises frequently applied in muscle-strengthening and therapeutic exercises. The loading devices are often used to increase the training intensity. OBJECTIVE: To determine the effect of loading devices on muscle activation in squat and lunge and to compare the differences in muscle activation between squat and lunge. DESIGN: Cross-sectional cohort. PARTICIPANTS: Nineteen healthy, male, recreationally active individuals without a history of lower limb injury. INTERVENTIONS: Each participant performed 10 repetitions of a squat under 5 conditions: unloaded, barbell, dumbbell, loaded vest, and kettlebell, and 10 repetitions of a lunge under 4 conditions: unloaded, barbell, dumbbell, and loaded vest. MAIN OUTCOME MEASURES: The electromyography signals of quadriceps, hamstrings, tibialis anterior, gastrocnemius lateralis and medialis were measured. One-way repeated-measure analysis of variance was used to compare the difference among different loading conditions. Paired t test was used to compare the difference between squat and lunge. RESULTS: The muscle activation in the loaded conditions was significantly higher than that in nonloaded conditions in squat and lunge. Compared with the barbell, dumbbell, and loaded vest conditions, the semitendinosus showed significantly higher activation, and the tibialis anterior showed significantly lower activation in kettlebell condition in squat. No significant difference in muscle activation was found among barbell, dumbbell, and kettlebell conditions in lunge. In addition, quadriceps and hamstring activities were significantly higher in lunge than in squat. CONCLUSIONS: Muscle activation was affected by the loading devices in squat but not affected in lunge. Kettlebell squat could be suggested for targeting in strengthening medial hamstring. Progressive strengthening exercise could be recommended from squat to lunge based on sequential activation level.

Translocation of Rigid Rod-Shaped Virus through Various Solid-State Nanopores.

Nanopores have been used as a high throughput tool for characterizing individual biomolecules and nanoparticles. Here, we present the translocation of rigid rod-shaped tobacco mosaic virus (TMV) through solid-state nanopores. Interestingly, due to the high rigidity of TMV, three types of events with distinctive characteristics at the capture process and a strong current fluctuation during the translocation of TMV are observed. A kinetic model is then proposed to address the dynamics of the translocation, followed by corresponding dynamics simulations. The results reveal that TMV has to rotate to fit and pass the pore when it is captured by a nanopore with an angle larger than the maximum angle that allows it to pass through. Then, we investigate the dependence of the rotation of TMV on the conductance fluctuations at the blockade stage. The results show that the rotation of TMV during the passage through the pore affects the current signal significantly. This study gives a fundamental understanding of the dynamics of rod-shaped particles translocating through the nanopore and how the current responds to it. It opens a new possible way to characterize the rigidity of analytes by nanopores.

Strategies for obstacle crossing in older adults with high and low risk of falling.

[Purpose] Tripping is a frequent cause of falls among aging adults. Appropriate limb movements while negotiating obstacles are critical to trip avoidance. The aim of our study was to investigate the mechanics of obstacle crossing in older adults at low or high risk of falling. [Subjects and Methods] Twenty community-dwelling adults aged ≥55 years, were evaluated with the Tinetti Balance and Gait scale and classified as being at high or low risk of falling. Between-group comparisons of kinematics were evaluated for obstacle heights of 10%, 20%, and 30% of leg length. [Results] The high-risk group demonstrated greater toe-obstacle clearance of the leading leg. Increasing obstacle height led to increased maximal toe-obstacle clearance, toe-obstacle distance, and shortened swing phase of the leading limb. Adaptation of clearance height was greater for the trailing leg. Individuals at high risk of falling demonstrated less symmetry between the leading and trailing legs and a narrower step width, features that increase the likelihood of tripping. [Conclusion] Kinematic parameters of obstacle clearance, including the symmetry index described in our study, could provide clinicians with a quick screening tool to identify patients at risk of falling and to evaluate outcomes of training programs.

Effect of ankle kinesio taping on vertical jump with run-up and countermovement jump in athletes with ankle functional instability.

[Purpose] Limited research has been performed in spite of biomechanical evaluation of jump landing with kinesio taping. Therefore, the main objective of this study was to evaluate the effect of kinesio taping applied to athletes. In this study, the authors wished to investigate the effect of kinesio taping during a vertical jump with run-up and countermovement jump on ankle functional instability. [Subjects and Methods] Ten male athletes with ankle functional instability (FI) were recruited in this study from a college volleyball team. Each participant was requested to perform two tasks, the countermovement jump and vertical jump with run-up. Infrared high-speed cameras and force plates were used to assess the effect of ankle taping. [Results] The results showed that the peak ground reaction force in the sagittal plane during a vertical jump with run-up slowed down after kinesio taping and that the peak ankle plantar flexion moment in both types of jump also decreased. [Conclusion] In conclusion, this study proved the effect of kinesio taping on ankle functional instability, which was evaluated by measuring the vertical ground reaction force and peak plantar flexion moment. Its finding may allow us to provide some recommendations for athletes and trainers.

Effects of the type and direction of support surface perturbation on postural responses.

BACKGROUND: Postural control is organized around a task goal. The two most frequently used types of tasks for postural control research are translational (translation along the anterior-posterior axis) and rotational (rotation in sagittal plane) surface perturbations. These types of perturbations rotate the ankle joint, causing different magnitudes and directions of body sway. The purpose of this study was to investigate the effects of the type (translation vs. rotation) and direction (forward/toe up vs. backward/toe down) of the perturbation on postural responses. METHOD: Nineteen healthy subjects were tested with four perturbations, i.e., forward and backward translation and toe up and toe down rotation. The onset latency and magnitude of muscle activations, angular changes, and COM displacements were measured. In addition, the kinematic data were divided into two phases. The initial phase reflected the balance disturbance induced by the platform movement, and the reversal phase reflected the balance reaction. RESULTS: The results showed that, in the initial phase, rotational perturbation induced earlier ankle movement and faster and larger vertical COM displacement, while translational and forward/toe up perturbations induced larger head and trunk angular change and faster and larger horizontal COM displacement. In the reversal phase, balance reaction was attained by multi-joint movements. Translational and forward/toe up perturbations that induced larger upper body instability evoked faster muscle activation as well as faster and larger hip or knee joint movements. CONCLUSIONS: These findings provide insights into an appropriate support surface perturbation for the evaluation and training of balance.

Machine learning and experimental validation identified autophagy signature in hepatic fibrosis.

Background: The molecular mechanisms of hepatic fibrosis (HF), closely related to autophagy, remain unclear. This study aimed to investigate autophagy characteristics in HF. Methods: Gene expression profiles (GSE6764, GSE49541 and GSE84044) were downloaded, normalized, and merged. Autophagy-related differentially expressed genes (ARDEGs) were determined using the limma R package and the Wilcoxon rank sum test and then analyzed by GO, KEGG, GSEA and GSVA. The infiltration of immune cells, molecular subtypes and immune types of healthy control (HC) and HF were analyzed. Machine learning was carried out with two methods, by which, core genes were obtained. Models of liver fibrosis in vivo and in vitro were constructed to verify the expression of core genes and corresponding immune cells. Results: A total of 69 ARDEGs were identified. Series functional cluster analysis showed that ARDEGs were significantly enriched in autophagy and immunity. Activated CD4 T cells, CD56bright natural killer cells, CD56dim natural killer cells, eosinophils, macrophages, mast cells, neutrophils, and type 17 T helper (Th17) cells showed significant differences in infiltration between HC and HF groups. Among ARDEGs, three core genes were identified, that were ATG5, RB1CC1, and PARK2. Considerable changes in the infiltration of immune cells were observed at different expression levels of the three core genes, among which the expression of RB1CC1 was significantly associated with the infiltration of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. In the mouse liver fibrosis experiment, ATG5, RB1CC1, and PARK2 were at higher levels in HF group than those in HC group. Compared with HC group, HF group showed low positive area in F4/80, IL-17 and CD56, indicating decreased expression of macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell. Meanwhile, knocking down RB1CC1 was found to inhibit the activation of hepatic stellate cells and alleviate liver fibrosis. Conclusion: ATG5, RB1CC1, and PARK2 are promising autophagy-related therapeutic biomarkers for HF. This is the first study to identify RB1CC1 in HF, which may promote the progression of liver fibrosis by regulating macrophage, Th17 cell, natural killer cell and CD56dim natural killer cell.

Metagenomic next-generation sequencing for the identification of infections caused by Gram-negative pathogens and the prediction of antimicrobial resistance.

OBJECTIVE: The aim of this study was to evaluate the efficacy of metagenomic next-generation sequencing (mNGS) for the identification of Gram-negative bacteria (GNB) infections and the prediction of antimicrobial resistance. METHODS: A retrospective analysis was conducted on 182 patients with diagnosis of GNB infections who underwent mNGS and conventional microbiological tests (CMTs). RESULTS: The detection rate of mNGS was 96.15%, higher than CMTs (45.05%) with a significant difference (χ 2 = 114.46, P < .01). The pathogen spectrum identified by mNGS was significantly wider than CMTs. Interestingly, the detection rate of mNGS was substantially higher than that of CMTs (70.33% vs 23.08%, P < .01) in patients with but not without antibiotic exposure. There was a significant positive correlation between mapped reads and pro-inflammatory cytokines (interleukin-6 and interleukin-8). However, mNGS failed to predict antimicrobial resistance in 5 of 12 patients compared to phenotype antimicrobial susceptibility testing results. CONCLUSIONS: Metagenomic next-generation sequencing has a higher detection rate, a wider pathogen spectrum, and is less affected by prior antibiotic exposure than CMTs in identifying Gram-negative pathogens. The mapped reads may reflect a pro-inflammatory state in GNB-infected patients. Inferring actual resistance phenotypes from metagenomic data remains a great challenge.

Silicon nitride nanopores for nanoparticle sensing.

In recent years, nanopore has attracted broad attention as an essential technique for DNA sequencing and nanoparticle sensing. This work presented a fundamental study of nanoparticle translocation through silicon nitride nanopores. Since particles with rather high charge to mass ratio, such as DNA and proteins, have been widely studied, there was still little information about the translocation behavior of nanoparticles with low charge/mass ratio. However, these nanoparticles include viruses and colloids are important potential sample for nanopore sensing technique. In order to screen nanoparticles' size, concentration, surface property by apply silicon nitride nanopores, and fulfill specific recognition which could be applied in laboratory medicine and environmental monitoring, optimal experimental conditions needed to be confirmed. In this paper, polystyrene (PS) bead was used as an example to provide reference towards this condition. The effects of nanopore/nanoparticle diameter ratio and bias voltage on sensing results were analyzed in this work. We found that lower precision accuracy might be demonstrated by the larger pore (120 nm) while the translocation velocity tended to be slowed down. By increasing the bias voltage could favor the detection productiveness. In spite of the intense interest, the baseline fluctuations and vague event bounds aggravated are far from understood.

Effects of leg dominance on performance of ballet turns (pirouettes) by experienced and novice dancers.

Turns (pirouettes) are an important movement in ballet and may be affected by "lateral bias". This study investigated physiological differences exhibited by experienced and novice dancers, respectively, when performing pirouette with dominant and non-dominant leg supports, respectively. Thirteen novice and 13 experienced dancers performed turns on dominant or non-dominant legs. The maximum ankle plantarflexion, knee extension and hip extension were measured during the single-leg support phase. The inclination angle of rotation axis is the angle between instantaneous rotation axis and global vertical axis in the early single-leg support phase. Both groups exhibited a greater hip extension, knee extension, and ankle plantarflexion when performing a turn on the non-dominant leg. For experienced dancers, the inclination angle of rotation axis during the pre-swing phase was generally smaller for dominant leg support than non-dominant leg. However, no significant difference was found in inclination angle of rotation axis of novice dancers. For experienced dancers, an improved performance is obtained when using the dominant leg for support. By contrast, for novice dancers, the performance is independent of choice of support leg. The significant lateral bias in experienced dancers indicates the possible influence of training. That is, repetitive rehearsal on the preferred leg strengthens the impact of side dominance in experienced dancers.

Clinical Efficacy and Diagnostic Value of Metagenomic Next-Generation Sequencing for Pathogen Detection in Patients with Suspected Infectious Diseases: A Retrospective Study from a Large Tertiary Hospital.

Purpose: Metagenomic next-generation sequencing (mNGS) is a powerful yet unbiased method to identify pathogens in suspected infections. However, little is known about its clinical effectiveness. The present study aimed to assess the efficacy of mNGS in routine clinical practice. Patients and Methods: In this single-center retrospective cohort study, 518 patients with suspected infectious diseases were assessed for inclusion. Among them, each patient had undergone mNGS testing; 407 patients had undergone both microbial culture and mNGS testing. The result of mNGS testing was compared to microbial culture performed concurrently. The diagnostic performance of mNGS was evaluated using the comprehensive clinical diagnosis as the reference standard. Results: There was a significant difference in the positive detection rates of pathogens between mNGS and culture (331/407, 81.3% vs 79/407, 19.4%, P < 0.001). The sensitivity of mNGS was much higher than the culture method (79.5% vs 21.3%, P < 0.001), especially in sample types of sputum and bronchoalveolar lavage fluid (BALF). Notably, the sensitivity of blood mNGS was relatively lower than other sample types (67.4% vs 88.9-93.8%). Pathogen cfDNA load based on standardized stringently mapped read number at the species level of microorganisms (SDSMRN) was significantly lower in blood than in other sample types from the same patient (P = 0.0003). Importantly, mNGS directly led to a change of treatment regimen in 142 (27.4%) cases, including antibiotic escalation (15.3%), antibiotic de-escalation (9.1%), and early definitive diagnosis to initiate appropriate treatment (3.1%). Conclusion: Our in-house mNGS platform significantly improved the sensitivity for the diagnosis of infectious diseases. mNGS has the potential to improve clinical outcomes by optimizing antimicrobial therapy.

Changes in biomechanics and muscle activation in injured ballet dancers during a jump-land task with turnout (Sissonne Fermée).

Large impact loading with abnormal muscle activity and motion patterns may contribute to lower extremity injuries in ballet dancers. Yet, few studies investigated the influence of injury on the ballet movement. The purpose of this study was to find the neuromuscular and biomechanical characteristics in dancers with and without ankle injury during a jump-landing Sissonne Fermée task. Twenty-two ballet dancers were recruited and divided into the injured group (n = 11) and the uninjured group (n = 11). They performed a ballet movement called "Sissonne Fermée" with reflective markers and electrodes attached to their lower extremities. Ground reaction force, joint kinematics, and muscle activity were measured. The injured dancers had greater peak ankle eversion but smaller hindfoot-to-tibial eversion angles. Also, the injured dancers had greater activity of the hamstring of the dominant leg and tibialis anterior of the non-dominant leg during the pre-landing phase. The injured dancers had greater tibialis anterior activity of the dominant leg but less muscle activity in the medial gastrocnemius of the non-dominant leg during the post-landing phase. The injured dancers had a greater co-contraction index in the non-dominant ankle and a lower loading rate. The higher co-contraction indices showed that the injured dancers required more muscle effort to control ankle stability. Furthermore, the injured dancers used a "load avoidance strategy" to protect themselves from re-injury. Neuromuscular control training of the ankle joint for ballet dancers to prevent injury is necessary.

Functional Aspects of Sperm Chromatin Organization.

Sperm nuclei present a highly organized and condensed chromatin due to the interchange of histones by protamines during spermiogenesis. This high DNA condensation leads to almost inert chromatin, with the impossibility of conducting gene transcription as in most other somatic cells. The major chromosomal structure responsible for DNA condensation is the formation of protamine-DNA toroids containing 25-50 kilobases of DNA. These toroids are connected by toroid linker regions (TLR), which attach them to the nuclear matrix, as matrix attachment regions (MAR) do in somatic cells. Despite this high degree of condensation, evidence shows that sperm chromatin contains vulnerable elements that can be degraded even in fully condensed chromatin, which may correspond to chromatin regions that transfer functionality to the zygote at fertilization. This chapter covers an updated review of our model for sperm chromatin structure and its potential functional elements that affect embryo development.

Six-Week Remodeled Bike Pedal Training Improves Dynamic Control of Lateral Shuffling in Athletes With Functional Ankle Instability.

BACKGROUND: Remodeled bicycle pedal training with multidirectional challenges through muscle strengthening and neuromuscular facilitation may increase dynamic postural control and performance during lateral shuffling for athletes with functional ankle instability (FAI). HYPOTHESIS: The 6-week remodeled bicycle pedal training is effective on the ankle joint control and muscle activation, and especially that of the ankle evertor muscle co-contraction to improve dynamic postural control during lateral shuffling for athletes with FAI. STUDY DESIGN: Laboratory randomized controlled trial. LEVEL OF EVIDENCE: Level 2. METHODS: Fourteen healthy athletes (healthy group) and 26 athletes with FAI aged 18 to 30 years were included in the study. The athletes with FAI were randomly assigned to either the training group (FAI-T group) or the nontraining group (FAI-NT group). The athletes in the FAI-T group underwent 6 weeks of remodeled bicycle pedal training, whereas those in the FAI-NT group did not undergo any intervention. Muscle co-contraction index and muscle activation in the initial contact (IC) and propulsion phases, and ankle joint angle in the IC and propulsion phases were measured during lateral shuffling before and after 6 weeks of training. RESULTS: After remodeled bicycle pedal training, the FAI-T group demonstrated greater muscle activation in the hamstring (P = 0.01), greater muscle coactivation of the tibialis anterior (TA) and the peroneus longus (P = 0.01), and greater ankle eversion angle in the IC phase. Significantly greater muscle activation of the TA (P = 0.01), greater coactivation of quadriceps and hamstring (P = 0.03), and a smaller ankle inversion angle (P = 0.04) in the propulsion phase were observed in the FAI-T group after training compared with those in the FAI-NT group. CONCLUSION: Remodeled bicycle pedal training facilitates the TA and peroneus longus activation and the coactivation of the quadriceps and hamstring muscles during lateral shuffling and resulted in enhanced ankle and knee joint stability. In addition, a better ankle movement strategy during a dynamic task can be achieved via a 6-week remodeled pedal training program. CLINICAL RELEVANCE: This remodeled bicycle pedal training can be effective for rehabilitating athletes with FAI to recover lateral dynamic movement capability.

[Effects of 89SrCl2 treatment on CD4+ CD25+ regulatory T cells and its Foxp3 mRNA expression in cancer patients with bone metastases].

OBJECTIVE: To study the influence of 89SrCl2 on CD4+ CD25+ regulatory T cells and its Foxp3 mRNA expression in cancer patients with bone metastases. METHODS: Peripheral blood samples were collected from 57 patients with bone metastases cancer and 25 healthy controls, the amount of CD4+ CD25+ regulatory T cells in peripheral blood was determined by flow cytometry, the expression level of Foxp3 mRNA in these regulatory T cells was detected by RT-PCR. RESULTS: The percentage of CD4+ CD25+ regulatory T cells in CD4+ cells was (11.3 +/- 5.5) % in the patients with bone metastases, which was significantly more than that (5.6 +/- 1.5)% in healthy control (P < 0.01). After the treatment of 89SrCl2, it was decreased to (10.4 +/- 5.2)%, and the decrease was statistically significant (P < 0.05). The expression level of Foxp3 mRNA was decreased significantly from 0.348 +/- 0.028 to 0.296 +/- 0.029 by the treatment of 89SrCl2 (P < 0.05). In addition, the amount of CD4+ CD25+ T cells in the patients obtaining 89SrCl2 therapeutic effects was (9.3 +/- 4.2) %, which was lower than that in those patients without effects (12.9 +/- 5.3)% (P < 0.01). The relative expression level of Foxp3 mRNA was 0.254 +/- 0.025 in the patients obtaining therapeutic effects, which was also significantly less than that (0.397 +/- 0.029) in those patients without any effects (P < 0.01). CONCLUSION: Foxp3 gene play a pivotal role in the regulation of CD4+ CD25+ T cells. The treatment of 89SrCl2 could decrease the amount of CD4+ CD25+ T cells and down-regulate Foxp3 mRNA expression of these cells in bone metastases cancer patients.