HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.

Effect of the Innovative Running Shoes With the Special Midsole Structure on the Female Runners' Lower Limb Biomechanics.

The study aimed to research the effects of innovative running shoes (a high heel-to-toe drop and special structure of midsole) on the biomechanics of the lower limbs and perceptual sensitivity in female runners. Fifteen healthy female runners were recruited to run through a 145-m runway with planted force plates at one peculiar speed (3.6 m/s ± 5%) with two kinds of shoe conditions (innovative running shoes vs. normal running shoes) while getting biomechanical data. The perception of shoe characteristics was assessed simultaneously through a 15-cm visual analog scale. The statistical parametric mapping technique calculated the time-series parameters. Regarding 0D parameters, the ankle dorsiflexion angle of innovative running shoes at touchdown was higher, and the peak dorsiflexion angle, range of motion, peak dorsiflexion velocity, and plantarflexion moment on the metatarsophalangeal joint of innovative running shoes during running were significantly smaller than those of normal running shoes (all p < 0.001). In addition, the braking phase and the time of peak vertical force 1 of innovative running shoes were found to be longer than those of normal running shoes (both p < 0.05). Meanwhile, the average vertical loading rate 1, peak vertical loading rate 1, peak braking force, and peak vertical force 1 in the innovative running shoes were lower than those of the normal running shoes during running (both p < 0.01). The statistical parametric mapping analysis exhibited a higher ankle dorsiflexion angle (0-4%, p < 0.05), a smaller knee internal rotation angle (0-6%, p < 0.05) (63-72%, p < 0.05), a decreased vertical ground reaction force (11-17%, p = 0.009), and braking anteroposterior ground reaction force (22-27%, p = 0.043) for innovative running shoes than normal running shoes. Runners were able to perceive the cushioning of innovative running shoes was better than that of normal running shoes. These findings suggested combining the high offset and structure of the midsole would benefit the industrial utilization of shoe producers in light of reducing the risk of running injuries for female runners.

Pharmaceutical Activation of Nrf2 Accelerates Diabetic Wound Healing by Exosomes from Bone Marrow Mesenchymal Stem Cells.

Background and Objectives: Despite advances in wound treatments, chronic diabetic wounds remain a significant medical challenge. Exosomes from mesenchymal stem cells (MSCs) and small molecule activators of nuclear factor erythroid 2-related factor 2 (Nrf2) have emerged as potential therapies for nonhealing diabetic wounds. This study aimed to evaluate the effects of exosomes from bone marrow-derived MSCs (BMSCs) alone, or in combination with a small molecule activator of Nrf2 on diabetic wound healing. Methods and Results: BMSCs and endothelial progenitor cells (EPCs) were isolated from the femur and tibia bone marrow of Sprague-Dawley (SD) rats and culture-expanded. Exosomes were harvested from the BMSC culture supernatants through ultracentrifugation. The effects of the exosomes and Nrf2 knockdown, alone or in combination, on EPC tube formation were evaluated. Streptozotocin-induced diabetic rats bearing a fresh full-thickness round wound were treated with the exosomes alone, or in combination with a lentiviral shRNA targeting Nrf2 (Lenti-sh-Nrf2) or tert-butylhydroquinone (tBHQ), a small molecule activator of Nrf2. Two weeks later, wound closure, re-epithelization, collagen deposition, neovascularization, and local inflammation were evaluated. BMSC exosomes promoted while Nrf2 knockdown inhibited EPC tube formation. BMSC exosomes accelerated wound closure, re-epithelization, collagen deposition, and neovascularization, and reduced wound inflammation in diabetic rats. These regenerative and anti-inflammatory effects of the exosomes were inhibited by Lenti-sh-Nrf2 but enhanced by tBHQ administration. Conclusions: BMSC exosomes in combination with a small molecule Nrf2 activator hold promise as a new therapeutic option for chronic diabetic wounds.

Effect of the Construction of Carbon Fiber Plate Insert to Midsole on Running Performance.

In this paper, to investigate the independent effect of the construction of the forefoot carbon-fiber plate inserted to the midsole on running biomechanics and finite element simulation, fifteen male marathon runners were arranged to run across a runway with embedded force plates at two specific running speeds (fast-speed: 4.81 ± 0.32 m/s, slow-speed: 3.97 ± 0.19 m/s) with two different experimental shoes (a segmented forefoot plate construction (SFC), and a full forefoot plate construction (FFC)), simulating the different pressure distributions, energy return, and stiffness during bending in the forefoot region between the SFC and FFC inserted to midsole. Kinetics and joint mechanics were analyzed. The results showed that the footwear with SFC significantly increased the peak metatarsophalangeal joint (MTPJ) plantarflexion velocity and positive work at the knee joint compared to the footwear with FFC. The results about finite element simulation showed a reduced maximum pressure on the midsole; meanwhile, not significantly affected was the longitudinal bending stiffness and energy return with the SFC compared to the FFC. The results can be used for the design of marathon running shoes, because changing the full carbon fiber plate to segment carbon fiber plate induced some biomechanical transformation but did not significantly affect the running performance, what is more, reducing the peak pressure of the carbon plate to the midsole by cutting the forefoot area of the carbon fiber plate could be beneficial from a long-distance running perspective for manufacturers.

Dynamics of Initial Hydrogen Spillover from a Single Atom Platinum Active Site to the Cu(111) Host Surface: The Impact of Substrate Electron-Hole Pairs.

The initial impulsive diffusion of hot hydrogen atoms resulted from the dissociative chemisorption of H2 at atomically dispersed Pt atoms embedded in Cu(111) is investigated using ab initio molecular dynamics. Upon dissociation, one of the two hydrogen atoms tends to roam away from the dissociation site while the other remains trapped. It is shown that the fraction of diffusion and the average diffusion length increase with the incident energy and H2 vibrational excitation, due apparently to the increased initial kinetic energy of the hot atoms. Most importantly, the strong interaction with surface electron-hole pairs, modeled using an electronic friction model, is shown to play an important role in rapid energy dissipation and significant retardation of the impulsive diffusion.

Erratum to "Analysis of Bone Mineral Density/Content of Paratroopers and Hoopsters".

[This corrects the article DOI: 10.1155/2018/6030624.].

Analysis of Bone Mineral Density/Content of Paratroopers and Hoopsters.

The different mechanical stimulus affects the bone mass and bone strength. The aim of this study was to investigate the effect of landing posture of the hoopster and paratrooper on the bone mass. In this study, 39 male participants were recruited including 13 paratroopers, 13 hoopsters, and 13 common students (control groups). Bone area (BA), BMD and BMC of calcaneus, and 1-5th of the metatarsus, hip, and lumbar spine (L1-L4) were measured by the dual-energy X-ray absorptiometry. Also, the vertical ground reaction forces (GRFs) of hoopsters and paratroopers were measured by the landing of 1.2 m 3D force platform. BA of hoopsters at the calcaneus, lumbar spine, and hip were significantly higher than the control group. The lumbar spine, hip, calcaneus, the 1st and 2nd metatarsals, BMC of paratroopers, and control groups were significantly lower than hoopsters. BMD of the lumbar spine, hip, and right and left femoral necks in hoopsters were significantly higher than the other participants. BMC and BMD of lower limber showed no significant difference between paratroopers and the control group. Besides, peak GRFs of paratroopers (11.06 times of BW) were significantly higher than hoopsters (6.49 times of BW). The higher GRF in the landing train is not always in accordance with higher BMD and BMC. Variable loads in hoopsters can improve bone remodeling and play an important role in bone expansions for trabecular bones. This will be considered by the method of training to prevent bone loss.

Dlf1, a WRKY transcription factor, is involved in the control of flowering time and plant height in rice.

Flowering time and plant height are important agronomic traits for crop production. In this study, we characterized a semi-dwarf and late flowering (dlf1) mutation of rice that has pleiotropic effects on these traits. The dlf1 mutation was caused by a T-DNA insertion and the cloned Dlf1 gene was found to encode a WRKY transcription factor (OsWRKY11). The dlf1 mutant contains a T-DNA insertion at the promoter region, leading to enhanced accumulation of Dlf1 transcripts, resulting in a semidominant mutation. The dlf1 mutation suppressed the transcription of Ehd2/RID1/OsId1 and its downstream flowering-time genes including Hd1, Ehd1 and Hd3a under both long-day (LD) and short-day (SD) conditions. Knock-down of Dlf1 expression exhibited early flowering at LD condition related to the wild-type plants. Accumulation of Dlf1 mRNA was observed in most tissues, and two splicing forms of Dlf1 cDNAs were obtained (OsWRKY11.1 and OsWRKY11.2). These two proteins showed transactivation activity in yeast cells. Dlf1 protein was found to be localized in the nucleus. Enhanced expression of OsWRKY11.2 or its 5' truncated gene showed similar phenotypes to the dlf1 mutant, suggesting that it might function as a negative regulator. We conclude that Dlf1 acts as a transactivator to downregulate Ehd2/RID1/OsId1 in the signal transduction pathway of flowering and plays an important role in the regulation of plant height in rice.

RBS1, an RNA binding protein, interacts with SPIN1 and is involved in flowering time control in rice.

The rice U-box/ARM E3 ubiquitin ligase SPL11 negatively regulates programmed cell death (PCD) and disease resistance, and controls flowering time through interacting with the novel RNA/DNA binding KH domain protein SPIN1. Overexpression of Spin1 causes late flowering in transgenic rice under short-day (SD) and long-day (LD) conditions. In this study, we characterized the function of the RNA-binding and SPIN1-interacting 1 (RBS1) protein in flowering time regulation. Rbs1 was identified in a yeast-two-hybrid screen using the full-length Spin1 cDNA as a bait and encodes an RNA binding protein with three RNA recognition motifs. The protein binds RNA in vitro and interacts with SPIN1 in the nucleus. Rbs1 overexpression causes delayed flowering under SD and LD conditions in rice. Expression analyses of flowering marker genes show that Rbs1 overexpression represses the expression of Hd3a under SD and LD conditions. Rbs1 is upregulated in both Spin1 overexpression plants and in the spl11 mutant. Interestingly, Spin1 expression is increased but Spl11 expression is repressed in the Rbs1 overexpression plants. Western blot analysis revealed that the SPIN1 protein level is increased in the Rbs1 overexpression plants and that the RBS1 protein level is also up-regulated in the Spin1 overexpression plants. These results suggest that RBS1 is a new negative regulator of flowering time that itself is positively regulated by SPIN1 but negatively regulated by SPL11 in rice.

[Infrared spectrum analysis of admixture decoction of herba ephedrae with semen armeniacae amarum].

The infrared spectra of decoction of herba ephedra and semen armeniacae amarum and the mixed decoction of herba ephedra + semen armeniacae amarum were tested. The change in the the mixed decoction was discussed to study the relationship between herba ephedra and semen armeniacae amarum after decoction. The results showed that some absorption peaks of herba ephedra and semen armeniacae amarum were retained in the mixed decoction of herba ephedra + semen armeniacae amarum, such as 1402 and 1076 cm(-1), but some absorption peaks that never appear in the two ingredient spectra increased such as 1394 and 682 cm(-1). New absorption peaks were generated in the mixed decoction of herba ephedra + semen armeniacae amarum, such as 688 and 1187 cm(-1). It can be showed that there were differences in the chemistry environment of the various chemical groups in the three decoctions introduced above, with the variation in absorption peak position, and the biochemical structure of the material changed, possibly with some new chemical compositions created. Medical ingredients in the mixed decoction of herba ephedra + semen armeniacae amarum were not simply the addition of herba ephedra and semen armeniacae amarum based on studies of infrared spectrum of decoction, and the new notion of prescription spectroscopy was proposed.

Biomechanical and clinical study on screw hook fixation after direct repair of lumbar spondylolysis.

OBJECTIVE: To evaluate the biomechanical effect and clinical results of hook screw fixation after direct repair of lumbar spondylous defects in the pars interarticularis. METHODS: L(2)-L(6) spines of 8 fresh-frozen and thawed calf cadavers were used for mechanical testing. Bilateral spondylous defects were created in the L(4)vertebra. The intervertebral rotation ranges between L(4) and L(5) were scanned and computerized in various states of motion, such as flexion/extension, lateral bending and torsional loadings applied on the intact spine and the spondylous spine when the spondylous spine was fixed with modified Scott's fixation, hook screw fixation and Buck's fixation sequentially and respectively. Between July 2002 and February 2004, 14 young male patients (aged 15-31 years) suffering from symptomatic lumbar spondylolysis were treated with TSRH hook screw fixation after direct repair of the defects. MacNab criteria were used to assess their pre-and post-operative status. RESULTS: Each fixation technique could significantly increase the intervertebral rotational stiffness and made the stiffness return to nearly the intact level. Hook screw technique provided more rotational stability than the others. Hook screw and Buck's techniques provided more flexion/extension stability than modified Scott's technique. Neither complication nor instrumental failure was observed in this study. The mean follow-up period was 21 months. All the patients except one acquired union during the follow-up period. Thirteen patients had a "good" or "excellent" result according to MacNab criteria. CONCLUSIONS: Hook screw fixation shows biomechanical advantages and is safe and effective for young patients with lumbar spondylolysis.