Purpose
The aim of this study was to compare long-term outcomes after anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) repair and reconstruction at 5–10 years after surgery.
...Methods
Forty-five patients who underwent surgical repair or reconstruction of both ATFL and CFL were retrospectively investigated in this study. American Orthopedic Foot and Ankle Society (AOFAS), Karlsson Score, and Tegner activity scale were used to evaluate the ankle function at a follow-up of 5–10 years. Ultrasound examination was used to evaluate the ATFL and CFL, and MRI was used to evaluate the cartilage.
Results
At final follow-up, no patient had recurrent ankle instability. There were no significant differences in AOFAS (92.6 ± 6.5 vs 89.6 ± 3.4; n.s.) or Karlsson Score (93 ± 8.2 vs 90.6 ± 5.0; n.s.) between the reconstruction group (twenty patients) and the repair group (twenty-five patients) postoperatively. There were also no significant differences in activity level as measured by the Tegner activity score (6 (range 4 to 8) vs 6 (range 5 to 7); n.s.). Five patients in the reconstruction group complained of some tightness of the ankles. Ultrasound showed the reconstructed ligaments maintained good continuity and were thicker than the repaired ligaments.
Conclusion
Patients in both the repair and the reconstruction cohort had high patient satisfaction with the outcomes and high function and activity levels that indicated recreational sports participation over a long period.
Level of evidence
III.
The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an ...abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy.
Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear ...whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions.
Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found that viral genes not only participated in most microbial metabolic pathways but also formed branched pathways in microbial metabolisms. The metabolic compensation of hosts mediated by viruses may help hosts to adapt to extreme environments and may be essential for host survival.
ATP-binding cassette transporter A7 (ABCA7) is highly expressed in the brain. Recent genome-wide association studies (GWAS) identify ABCA7 single nt polymorphisms (SNPs) that increase Alzheimer's ...disease (AD) risk. It is now important to understand the true function of ABCA7 in the AD context. We have begun to address this using in vitro and in vivo AD models. Our initial studies showed that transient overexpression of ABCA7 in Chinese hamster ovary cells stably expressing human amyloid precursor protein (APP) resulted in an approximate 50% inhibition in the production of the AD-related amyloid-β (Aβ) peptide as compared with mock-transfected cells. This increased ABCA7 expression was also associated with alterations in other markers of APP processing and an accumulation of cellular APP. To probe for a function of ABCA7 in vivo, we crossed Abca7(-/-) mice with J20 mice, an amyloidogenic transgenic AD mouse model B6.Cg-Tg(PDGFB-APPSwInd)20Lms/J expressing a mutant form of human APP bearing both the Swedish (K670N/M671L) and Indiana (V717F) familial AD mutations. We found that ABCA7 loss doubled insoluble Aβ levels and amyloid plaques in the brain. This did not appear to be related to changes in APP processing (C-terminal fragment analysis), which led us to assess other mechanism by which ABCA7 may modulate Aβ homoeostasis. As we have shown that microglia express high levels of ABCA7, we examined a role for ABCA7 in the phagocytic clearance of Aβ. Our data indicated that the capacity for bone marrow-derived macrophages derived from Abca7(-/-) mice to phagocytose Aβ was reduced by 51% compared with wild-type (WT) mice. This suggests ABCA7 plays a role in the regulation of Aβ homoeostasis in the brain and that this may be related to Aβ clearance by microglia.
Growing evidence suggests the importance of microRNAs （miRNAs） in stress signaling pathways. Transforming growth factor-β （TGF-β） is a potent cytokine that promotes the development of skeletal muscle ...fibrosis after acute contusion. However, how miRNAs are involved in TGF-β signaling and confer the robustness of TGF-β-induced fibrotic response remains to be fully elucidated. Here, we demonstrated that miR-146a-5p （miR-146） levels were reduced in a fibrotic mouse model after acute muscle contusion. It was also found that TGF-β treatment decreased the expression of miR-146 in vitro in a dose- and time-dependent manner. In addition, overexpression of Smad3 and Samd4, two key players in TGF-β signaling, suppressed the expression of miR-146 in muscle cells. Overexpression of miR-146 inhibited the expressions of fibrosis markers both in vitro and in vivo. Moreover, increase in the expression of miR-146 in muscle cells was able to attenuate the effect of TGF-β on the expressions of fibrosis markers. Mechanistic analysis revealed that Smad4 is a direct target of miR-146 in muscle cells. Furthermore, the anti-fibrotic effect of miR-146 could be blocked by overexpression of Smad4 in vivo. These results suggest that Smad4 is down-regulated by miR-146 in skeletal muscle. Taken together, our results indicate that the anti-fibrotic miR-146 is a component of TGF-β signaling. It is down-regulated by Smad protein, and can inhibit the expression of Smad4. Our study suggests that miR-146 might have a therapeutic potential to reduce skeletal muscle fibrosis after injury.
Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. ...Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR). Inhibition of glycolysis completely compromises the tumor-promoting effect of YBX1 on tumor growth. Mechanistically, YBX1 regulates the expression of c-Myc and HIF1α, which further upregulate glycolytic enzymes to facilitate glycolysis. Moreover,
study further confirms that genetic silencing of YBX1 markedly attenuates tumor growth and this tumor-suppressive effect is largely dependent on reduced glycolysis. Taken together, these results, as a proof of principle, provide a novel insight into the oncogenic role of YBX1 in glycolysis and suggest the potential therapeutic strategy by targeting YBX1 in bladder cancer.
We have designed an all-dielectric device based on permittivity-asymmetric rectangular blocks on meta-surfaces, yielding multiple Fano resonances with high sensitivity and high figure of merit (FOM) ...in the near-infrared regime. By introducing different materials to break the permittivity-symmetry, three sharp Fano peaks are generated with high Q-factors arising from the interference between the sub-radiant modes and the magnetic dipole resonance modes. Combining the field distributions and the multipole decomposition in Cartesian coordinates, the resonance modes are analyzed to be magnetic quadrupoles (MQs) and magnetic dipoles (MDs). Furthermore, the dependence on materials and geometric parameters has been studied. The maximal sensitivity, FOM and Q-factor reach 394 nm/RIU, 4925 and 14437, respectively. This proposed structure provides a good alternative to geometry-asymmetric meta-surface structures and may be used for multichannel sensing, nonlinear optical devices, and laser.
Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and ...accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.
The construction of a household integrated energy system will reduce greenhouse gas emissions and promote sustainable development. Firstly, a household energy system is proposed, which consists of a ...photovoltaic, wind turbine, electrolysis cell, hydrogen storage tank, and hydrogen‐fired gas turbine. The proposed system is modelled as a bi‐objective optimization problem in which the minimum daily system economic cost, and the minimum loss of energy supply probability. Secondly, a novel multi‐objective egret swarm optimization algorithm with strong search capability and fast convergence is proposed. Thirdly, a household load corresponding to a typical day in spring is chosen as the study case. The optimization results show that the daily system economic cost with the optimal number of devices is 97.48 RMB, and the loss of energy supply probability is 8.33% at the lowest. Finally, to validate the efficiency of the proposed method, the proposed method is compared with NSGA‐II (a widely used multi‐objective evolutionary algorithm). The comparison indicates that the proposed method has a better diversity due to the random searchability. As a consequence, the proposed method can be used in the optimization capacity design of the integrated energy system.
The capacity design method of a household integrated energy system is proposed, which is modeled as a bi‐objective optimization problem. Then, a novel multi‐objective egret swarm optimization algorithm with strong search capability and fast convergence is applied. The result indicates that the proposed method has a better diversity due to the random searchability.
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