influence-of-step-width-manipulation-on-running-biomechanics

Influence of Step-Width Manipulation on Running Biomechanics

Step width is a critical factor influencing lower limb biomechanics during running, significantly affecting stability, performance, and injury risk. ...

Ningbo University

GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next, we also investigated the alterations of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) catalytic subunit (PKAca), cAMP response element-binding (CREB), and glutamate transporter 1 (GLT1) levels produced by GEBR-7b in the rats model of depression.

cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats.

Previous studies have revealed that neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62 rapidly activates brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor/mammalian target of rapamycin (mTOR) signaling and produces antidepressant-like actions in rodents. In addition, acute TLQP-62 infusion also markedly changes the AMPA receptor GluA1 subunit phosphorylation at Ser 845 (pGluA1 Ser845) in the PFC of mice, indicating that the GluA1 may contributes to the rapid antidepressant-like effects of TLQP-62. However, how to regulate the TrkB-mediated signaling and GluA1 changes in the prefrontal cortex (PFC) by TLQP-62 remains unclear. Herein, acute administration of TLQP-62 into PFC produced rapid-acting antidepressant-like effects in mice. Additionally, we confirmed that TLQP-62 ameliorated the depression-like behaviors induced by chronic social defeat stress (CSDS) in mice. Further investigation demonstrated that this effect of TLQP-62 was mediated by activation of TrkB and mTOR, which proceeded to decrease bicaudal C homolog 1 gene (BICC1) and increase synaptic protein expression, including GluA1 subunit and pGluA1 Ser845. Notably, we further found that beneficial effects of TLQP-62 on depression-like behaviors and TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC of mice were significantly abolished by TrkB antagonist ANA-12. In conclusion, our findings indicate that TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC may involve in the rapid-acting antidepressant-like actions of TLQP-62 in mice.

Mechanisms underlying the rapid-acting antidepressant-like effects of neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62.

Previous studies have suggested that rapid reductions in depression-like behaviors are observed in response to sub-anesthetic-doses of ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist. Neuropeptide VGF (non-acronymic) is a critical effector of depression-like behaviors and is thought to be involved in the antidepressant actions of ketamine that have been demonstrated. However, the mechanism underlying the involvement of VGF in the anti-depressant action of ketamine remains unclear. We found that single dose ketamine treatment reversed CSDS-induced depression-like behaviors and decrease of VGF in the PFC of mice. To investigate the involvement of VGF in the antidepressant-like effects of ketamine, a lentivirus vector for VGF was constructed to knockdown the expression of VGF in the prefrontal cortex (PFC) of mice. The biochemical and behavioral effects of this VGF knockdown were examined, using the open field, forced swim, and sucrose preference tests. Our results show that knockdown of VGF increased the immobility time and decreased the sucrose preference in mice. These effects were not improved by ketamine administration. In addition, we found that knockdown of VGF significantly decreased the expression of phosphorylation of tropomyosin receptor kinase B (TrkB), mammalian target of rapamycin (mTOR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 Ser845 and increased the expression of bicaudal C homolog 1 (BICC1) in the mouse PFC, and blocked the regulation of TrkB/mTOR/BICC1 signaling and GluA1 phosphorylation by ketamine. Our results indicate that the rapid onset antidepressant-like actions of ketamine require VGF to regulate TrkB/mTOR/BICC1 signaling and AMPA receptor GluA1 phosphorylation.

Essential roles of neuropeptide VGF regulated TrkB/mTOR/BICC1 signaling and phosphorylation of AMPA receptor subunit GluA1 in the rapid antidepressant-like actions of ketamine in mice.

The discovery of atomically precise nanoclusters is generally unpredictable, and the rational synthesis of nanoclusters guided by the theoretical design is still in its infancy. Here we present a de novo design of Au(SR) nanoclusters, from theoretical prediction to experimental synthesis and characterization of their physicochemical properties. The crystal structure of an Au(SR) nanocluster perfectly matches the simulated structural pattern with Au tetrahedral units along a two-dimensional growth. The Au(SR) nanocluster indeed differs from its structural isomer whose kernel is dissected in an Au tetrahedral manner along a one-dimensional growth. The structural isomerism in the Au(SR) nanoclusters further induces distinct differences in ultrafast electron dynamics and chirality. This work will not only promote the atomically precise synthesis of nanoclusters enlightened by theoretical science, but also open up exciting opportunities for underpinning the widespread applications of structural isomers with atomic precision.

De novo design of Au(SR) nanoclusters.

Single-atom catalysts (SACs) often exhibit superb catalytic activity due to their high atom utilization. By comparing the adsorption energies of O2 and CO adsorbed on TM@C9N4, we expect that Co and Ni anchored at the cavity of C9N4 exhibit a higher catalytic activity for CO oxidation. For the entire reaction, the Eley-Rideal, New Eley-Rideal, Ter-molecular Eley-Rideal and Langmuir-Hinshelwood mechanisms are all taken into account. Depending on the reaction mechanisms, the catalysts Co@C9N4 and Ni@C9N4 show excellent activity, with a kinetic energy barrier ranging from 0.19 eV to 0.54 eV for the former, while the corresponding energy barrier is 0.26 eV to 0.44 eV for the latter. The superior stability and activity of Co/Ni@C9N4 can efficiently oxidize the large amounts of CO caused by inadequate combustion of coal and natural gas resources.

Single transition metal anchored CN sheets as an efficient catalyst for CO oxidation: a first-principles study.

With atomically precise gold nanoclusters acting as a starting unit, substituting one or more gold atoms of the nanocluster with other metals has become an effective strategy to create metal synergy for improving catalytic performances and other properties. However, so far detailed insight into how to design the gold-based nanoclusters to optimize the synergy is still lacking, as atomic-level exchange between the surface-gold (or core-gold) and the incoming heteroatoms is quite challenging without changing other parts. Here we report a Cd-driven reconstruction of Au(DMBT) (DMBT = 3,5-dimethylbenzenethiol), in which four Au(DMBT) staples are precisely replaced by two AuCd(DMBT) staples to form AuCd(DMBT) with the face-centered cubic inner core retained. With the dual modifications of the surface and electronic structure, the AuCd(DMBT) nanocluster exhibits distinct excitonic behaviors and superior photocatalytic performances compared to the parent Au(DMBT) nanocluster.

Cd-driven surface reconstruction and photodynamics in gold nanoclusters.

 Circular RNA can serve as a biomarker for early diagnosis of pancreatic cancer.  Analyzed the expression of various differentially expressed circular RNAs in the pancreatic cancer tissues by gene chip and identified the expression of hsa_circ_0013587 in pancreatic cancer cells, tissues and plasma by quantitative reverse transcription PCR (qRT-PCR).  Hsa_circ_0013587 was highly expressed in the pancreatic cancer tissues, cell lines and plasma samples from patients with pancreatic cancer. Notably, hsa_circ_0013587 was upregulated in pancreatic cancer patients with later clinical stages III-IV as compared with those detected in early clinical stages I-II.  A high expression of hsa_circ_0013587 may serve as a novel diagnostic and therapeutic biomarker for pancreatic cancer.

Increased levels of circulating circular RNA (hsa_circ_0013587) may serve as a novel biomarker for pancreatic cancer.

Accumulating evidence suggests that glutamate clearance plays a critical role in the pathophysiology and treatment of depression. Preclinical and clinical studies have demonstrated that ketamine provides an immediate and sustained antidepressant effect. However, the precise mechanism of its action remains to be elucidated. Glutamate transporter 1 (GLT1) participates in glutamate clearance; therefore, we hypothesized that GLT1 may play an important role in the antidepressant effect of ketamine. In this study, we determined that GLT1 inhibition blocks the antidepressant-like properties of ketamine and alters the phosphorylation of the mammalian target of rapamycin (mTOR) in the prefrontal cortex (PFC). Our results show that pretreatment with dihydrokainic acid (DHK), a GLT1 inhibitor, alleviated the antidepressant-like effect of ketamine, and decreased the level of phosphorylated mTOR (pmTOR) in mice (which is normally upregulated by ketamine). In addition, inhibition of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor and L-type voltage-dependent calcium channel (L-VDCC) significantly abolished the antidepressant-like effect of ketamine. Moreover, inhibition of L-VDCC significantly blocked the upregulation of GLT1 and BDNF in the PFC of mice. The inhibition of the AMPA receptor only significantly alleviated BDNF. Our results provide insight into the role of GLT1 as the critical presynaptic molecule participating in the pathophysiological mechanism of depression and contributing to the antidepressant-like effect of ketamine. In addition, our study confirms that both AMPA receptor and L-VDCC are crucial factors in the immediate antidepressant-like effect of ketamine.

The Regulation of Glutamate Transporter 1 in the Rapid Antidepressant-Like Effect of Ketamine in Mice.

Pancreatic cancer is a highly malignant tumor of the digestive system.

Exosomal circular RNA hsa_circ_0006220, and hsa_circ_0001666 as biomarkers in the diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.

IGF1 receptor-targeted black TiO nanoprobes for MRI-guided synergetic photothermal-chemotherapy in drug resistant pancreatic tumor.

Rare renal well-differentiated neuroendocrine tumors: clinical and imaging characteristics in a series of three cases.

 Pancreatic ductal adenocarcinoma (PDAC) is an insidious, rapidly progressing malignancy of the gastrointestinal tract. Due to its dense fibrous stroma and complex tumor microenvironment, neither of which is sensitive to radiotherapy, pancreatic adenocarcinoma is one of the malignancies with the poorest prognosis. Therefore, detailed elucidation of the inhibitory microenvironment of PDAC is essential for the development of novel therapeutic strategies.  We analyzed the association between cancer-associated fibroblasts (CAFs) and resistance to ferroptosis in PDAC using conditioned CAF medium and co-culture of pancreatic cancer cells. Abnormal cysteine metabolism was observed in CAFs using non-targeted metabolomics analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The regulatory effects of cysteine were investigated in PDAC cells through measurement of cell cloning, cell death, cell function, and EdU assays. The effects of exogenous cysteine intake were examined in a mouse xenograft model and the effects of the cysteine pathway on ferroptosis in PDAC were investigated by western blotting, measurement of glutathione and reactive oxygen species levels, among others.  It was found that CAFs played a critical role in PDAC metabolism by secreting cysteine, which could increase tumor resistance to ferroptosis. A previously unrecognized function of the sulfur transfer pathway in CAFs was identified, which increased the extracellular supply of cysteine to support glutathione synthesis and thus inducing ferroptosis resistance. Cysteine secretion by CAFs was found to be mediated by the TGF-β/SMAD3/ATF4 signaling axis.  Taken together, the findings demonstrate a novel metabolic relationship between CAFs and cancer cells, in which cysteine generated by CAFs acts as a substrate in the prevention of oxidative damage in PDAC and thus suggests new therapeutic targets for PDAC.

Cancer-associated fibroblasts reprogram cysteine metabolism to increase tumor resistance to ferroptosis in pancreatic cancer.

This research investigates the biomechanical impact of the split-step technique on forehand and backhand lunges in badminton, aiming to enhance players' on-court movement efficiency. Despite the importance of agile positioning in badminton, the specific contributions of the split-step to the biomechanical impact of lunging footwork still need to be determined.

Biomechanical Effects of the Badminton Split-Step on Forecourt Lunging Footwork.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell FeO@TiO nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form FeO@TiO@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.

VISTA antibody-loaded FeO@TiO nanoparticles for sonodynamic therapy-synergistic immune checkpoint therapy of pancreatic cancer.

Patients with severe Coronavirus Disease 2019 (COVID-19) can experience protein loss due to the inflammatory response and energy consumption, impairing immune function. The presence of excessive visceral and heart fat leads to chronic long-term inflammation that can adversely affect immune function and, thus, outcomes for these patients. We aimed to explore the roles of prognostic nutrition index (PNI) and quantitative fat assessment based on computed tomography (CT) scans in predicting the outcomes of patients with severe COVID-19.

Subcutaneous adipose tissue measured by computed tomography could be an independent predictor for early outcomes of patients with severe COVID-19.

Biomechanical asymmetries between children's left and right feet can affect stability and coordination, especially during dynamic movements. This study aimed to examine plantar pressure distribution, foot balance, and center of pressure (COP) trajectories in children during walking, running, and turning activities to understand how different movements influence these asymmetries. Fifteen children participated in the study, using a FootScan plantar pressure plate to capture detailed pressure and balance data. The parameters, including time-varying forces, COP, and Foot Balance Index (FBI), were analyzed through a one-dimensional Statistical Parametric Mapping (SPM1d) package. Results showed that asymmetries in COP and FBI became more pronounced, particularly during the tasks of running and directional turns. Regional plantar pressure analysis also revealed a more significant load on specific foot areas during these dynamic movements, indicating an increased reliance on one foot for stability and control. These findings suggest that early identification of asymmetrical loading patterns may be vital in promoting a balanced gait and preventing potential foot health issues in children. This study contributes to understanding pediatric foot biomechanics and provides insights for developing targeted interventions to support healthy physical development in children.

Liu Xu

Faculty of Sports Science

Ningbo University

Influence of Step-Width Manipulation on Running Biomechanics

Liu Xu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Faculty of Sports Science

Ningbo University

Influence of Step-Width Manipulation on Running Biomechanics

Faculty of Sports Science