Biomechanical model of minimally invasive hallux valgus surgery.

Hallux valgus is a common foot deformity characterized by outward tilting and twisting of the big toe, often accompanied by a medial prominence at the base. Minimally invasive surgical techniques are widely utilized for treating metatarsus adductus due to their advantages of smaller incisions, faster recovery, and early weight-bearing. However, due to individual variations and limited sample size, the biomechanical effects of different Kirschner wire fixation methods and the underlying mechanisms of postoperative metatarsalgia remain unclear. In this study, a finite element method was employed to develop a biomechanical model of metatarsus adductus. The influence of various Kirschner wire entry points and angles on foot loading characteristics was investigated. Six different Kirschner wire fixation models, including two entry methods (along the adjacent fracture line and proximal-biased entry at the midshaft of the metatarsal) with different entry angles, were analyzed. Mechanical parameters such as metatarsal stress distribution, plantar pressure distribution, and displacement of the first metatarsal osteotomy plane were assessed. This research aims to enhance understanding of minimally invasive surgery and its fixation methods for metatarsus adductus. By providing scientific support and reliable evidence, it seeks to contribute to the development of minimally invasive surgical techniques and the improvement of clinical practice in metatarsus adductus surgery. Ultimately, the goal is to reduce complications, increase surgical success rates, and enhance patient satisfaction.

Daily Step Counts in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Physical inactivity is an essential factor in the prognosis of patients with chronic kidney disease (CKD). Daily step count is a straightforward measure to assess physical activity levels. Understanding the step counts among different CKD stages is essential to change sedentary behavior. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the daily step counts in patients with CKD at a different stage. DESIGN: A systematic review and meta-analysis. DATA SOURCES: The literature search was performed in PubMed, Embase, and Web of Science from inception to November 3rd, 2021. REVIEW METHODS: Observational studies (cross-sectional, case-control, or cohort studies) reported specific values of step counts in CKD patients by the wearable device were included. A random-effects model was used to pool the data. Subgroup analysis explored differences in outcomes by stage of CKD. Heterogeneity between studies was assessed using the χ2 test of Cochrane's Q statistic. A contour-enhanced funnel plot was conducted to investigate publication bias. Univariate and multivariate meta-regression was conducted to examine possible sources of heterogeneity. RESULTS: Twenty-eight articles were identified and used for quantitative analysis. The result showed that the daily step count in patients with CKD was 4642.47 (95% CI: 4274.18-5010.76), and significantly lower than the healthy population. Subgroup analysis revealed that the step counts decreased before dialysis, dropped to a freezing point at the hemodialysis phase, and increased after kidney transplantation. Meta-regression analysis showed that daily step counts were relatively higher in the Americas or younger than 60 or kidney transplant recipients. CONCLUSION: The status of daily step counts in patients with CKD decreases with CKD severity and increases after kidney transplantation. Although studies have begun to focus on strategies to improve step counts in patients with CKD, future studies should focus more on step counts in pre-dialysis patients and changing their physically inactive lifestyle early to alleviate deteriorating renal function. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291551, identifier: CRD42021291551.

Non-canonical phosphorylation of Bmf by p38 MAPK promotes its apoptotic activity in anoikis.

Bmf contributes to the onset of anoikis by translocating from cytoskeleton to mitochondria when cells lose attachment to the extracellular matrix. However, the structural details of Bmf cytoskeleton tethering and the control of Bmf release upon loss of anchorage remained unknown. Here we showed that cell detachment induced rapid and sustained activation of p38 MAPK in mammary epithelial cell lines. Inhibition of p38 signaling or Bmf knockdown rescued anoikis. Activated p38 MAPK could directly phosphorylate Bmf at multiple sites including a non-proline-directed site threonine 72 (T72). Crystallographic studies revealed that Bmf T72 directly participated in DLC2 binding and its phosphorylation would block Bmf/DLC2 interaction through steric hindrance. Finally, we showed that phosphomimetic mutation of T72 enhanced Bmf apoptotic activity in vitro and in a knock-in mouse model. This work unraveled a novel regulatory mechanism of Bmf activity during anoikis and provided structural basis for Bmf cytoskeleton tethering and dissociation.

LncRNA SAMMSON Mediates Adaptive Resistance to RAF Inhibition in BRAF-Mutant Melanoma Cells.

The long noncoding RNA (lncRNA) SAMMSON is required for human melanoma cell growth and survival. However, whether SAMMSON regulates the response of mutant BRAF melanoma cells to RAF inhibitors remains unknown. In this work, we showed that SAMMSON is rapidly induced upon inhibition of ERK signaling, and SAMMSON overexpression conferred resistance to vemurafenib-induced cytotoxicity in melanoma cells. SOX10 mediated transcriptional induction of SAMMSON by vemurafenib, and SOX10 sumoylation at K55 was essential for this function. In addition, depletion of SAMMSON activated p53 signaling, which is dependent on the SAMMSON-interacting protein CARF. Depletion of SAMMSON sensitized mutant BRAF melanoma cells to RAF inhibitors in vitro and in vivo, while CARF knockdown reversed the enhanced sensitivity. In summary, these findings suggest that SAMMSON may function as a new mediator of adaptive resistance to RAF inhibitors in melanoma by modulating CARF-p53 signaling. SIGNIFICANCE: This study highlights the role of a SAMMSON/CARF/p53 signaling axis in modulating the adaptive resistance of mutant BRAF melanoma to RAF inhibitors.

CIC Is a Mediator of the ERK1/2-DUSP6 Negative Feedback Loop.

DUSP6 functions as an important negative feedback component of the MAPK/ERK signaling pathway. Although DUSP6 expression is tightly regulated by ERK1/2 signaling, the molecular mechanism of this regulation remains partially understood. In this work, we show that the transcriptional repressor CIC functions downstream of the ERK1/2 signaling to negatively regulate DUSP6 expression. CIC directly represses DUSP6 transcription by binding to three cis-regulatory elements (CREs) in DUSP6 promoter. p90RSK, a downstream target of ERK1/2, phosphorylates CIC at S173 and S301 sites, which creates a 14-3-3 recognition motif, resulting in 14-3-3-mediated nuclear export of CIC and derepression of DUSP6. Finally, we demonstrate that the oncogenic CIC-DUX4 fusion protein acts as a transcriptional activator of DUSP6 and its nuclear/cytoplasmic distribution remains regulated by ERK1/2 signaling. These results complete an ERK1/2/p90RSK/CIC/DUSP6 negative feedback circuit and elucidate the molecular mechanism of how RTK/MAPK signaling harnesses the transcriptional repressor activity of CIC in mammalian cells.

Publisher Correction: ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma.

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: The National Basic Research Program (2015CB553602 to J.L.), the National Natural Science Foundation of China (31570777, 91649106, 31770917 to J.L.) and Tianjin Applied Basic and Frontier Tech Major Project (12JCZDJC34400 to J.L.) and Tianjin Higher Education Sci-Tech Development Project (20112D05 to J.L.).

ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma.

In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for its transcription activity. Finally, depletion of SOX10 sensitizes mutant BRAF melanoma cells to RAF inhibitors in vitro and in vivo. Thus, our work discovers a novel phosphorylation-dependent regulatory mechanism of SOX10 transcription activity and completes an ERK1/2/SOX10/FOXD3/ERBB3 axis that mediates adaptive resistance to RAF inhibitors in mutant BRAF melanoma cells.

Facile Preparation of Doxorubicin-Loaded and Folic Acid-Conjugated Carbon Nanotubes@Poly(N-vinyl pyrrole) for Targeted Synergistic Chemo-Photothermal Cancer Treatment.

We developed a bifunctional nanoplatform for targeted synergistic chemo-photothermal cancer treatment. The nanoplatform was constructed through a facile method in which poly(N-vinyl pyrrole) (PVPy) was coated on cut multiwalled carbon nanotubes (c-MWNTs); FA-PEG-SH was then linked by thiol-ene click reaction to improve the active targeting ability, water dispersibility, and biocompatibility and to extend the circulation time in blood. The PVPy shell not only enhanced the photothermal effect of c-MWNTs significantly but also provided a surface that could tailor targeting molecules and drugs. The resulting MWNT@PVPy-S-PEG-FA possessed high drug-loading ratio as well as pH-sensitive unloading capacity for a broad-spectrum anticancer agent, doxorubicin. Owing to its outstanding efficiency in photothermal conversion and ability in targeted drug delivery, the material could potentially be used as an efficient chemo-photothermal therapeutic nanoagent to treat cancer.

[Principal component extraction used for the interpretation of RS-FTIR spectra].

A method for interpretation of remote sensing FTIR spectra was set up based on ANN model. Considering long training time and over-fitting problem of ANN, two methods, partial least squares (PLS) and principal component analysis (PCA), were utilized to extract principal components of spectra, process time decrease from about 30 minutes to a few seconds. Meanwhile, the idea of calibration transfer was used to overcome the limitation of calibration model in remote sensing FTIR spectra analysis. With the optimization of ANN model, four-component mixtures of acetone, benzene, chloroform and methanol were predicted in a remote sensing and real-time way while the calibration model was built with EPA data. The best performance was yielded with PLS-ANN model, and the root mean square error (RMSE) of acetone, benzene, chloroform and methanol were 0.043, 0.031, 0.034 and 0.051 respectively, which confirm the real-time, correct and quick analysis of remote sensing FTIR in air monitoring.

[The calibration of instrument response function during passive FTIR measurement].

In order to obtain infrared spectral radiance distribution of some infrared sources, such as spectral radiant flux density, spectral radiant intensity, spectral radiance and spectral irradiance, the instrument response function under different conditions must be known. In the present paper, the calibration of instrument response function during passive FTIR measurement has been discussed. The experimental results illustrate that under different experimental conditions, the instrument response function varies not only with the temperature of the blackbody but also with the signal amplitude received by the infrared instrument. So, during passive FTIR measurement, the temperature and the emission signal amplitude of the source must be observed carefully in order to get satisfactory instrument response function.

Reconstruction of air contaminant concentration distribution in a two-dimensional plane by computed tomography and remote sensing FTIR spectroscopy.

This research combined open path FTIR (OP-FTIR) technique and computed tomography (CT) to reconstruct air contaminant concentration distribution in a two-dimensional plane. Remote sensing FTIR instrument was used to scan radial beam geometry and obtain path integrated concentration (PIC) data of acetone gas in the measuring plane. Smooth basis function minimization (SBFM) algorithm was adopted to reconstruct gaseous concentration distribution. For the purpose of finding out the preferable number of Gaussians used in SBFM algorithm, single-Gaussian, double-Gaussian, and three-Gaussian models were used respectively. Experimental results showed that the reconstruction result of acetone concentration distribution by SBFM algorithm with double-Gaussian model agreed with real distribution more qualitatively and quantitatively than single-Gaussian and three-Gaussian. Also, it has been proved that simulated annealing algorithm used in the optimization process of SBFM reconstruction was feasible and effective. Although computed tomography and remote sensing FTIR technique (CT-RS-FTIR) is still at the laboratory study stage, with further improvement of SBFM algorithm and beam geometry, it promises to be used in air pollution monitoring widely.

Path concentration distribution of toluene using remote sensing FTIR and one-dimensional reconstruction method.

A one-dimensional mapping technique coupled with Open-Path remote sensing FTIR was presented in this article. This technique was applied to one of the air toxic volatile organic compounds (VOCs)-toluene. The Path Integrated Concentrations (PICs) of toluene in different path lengths along one beam path were fitted by polynomial fitting method with degrees from 3 to 7. The 6th degree polynomial fitting showed the best fitting result. Moreover, the methods of reconstructing path concentration distribution along the beam path by applying a Gaussian model and the derivative of 6th degree polynomial fitting function were established in this article. The reconstructed concentrations of toluene along the beam path by the two methods were experimentally close. Results showed that the concentration peaks were at 1.05 and 2.40 m from the instrument by applying the Gaussian model with the maximum concentration of 0.85 and 3.19 ppm, and at 0.99 and 2.49 m from the instrument with the maximum concentration of 0.78 and 2.80 ppm by applying the 6th polynomial fitting function. It was obvious that the reconstruction results by these two methods were very close. This approach could be appreciated for its fast calculation, exact peak location orientation and concentration flow tendency mapping. In can be concluded that this method can provide the path concentration distributions of much more releasing gases in a briefly and intuitionistic way. The remote sensing FTIR coupled with these mathematical reconstruction techniques can be applied to the real world environmental and industrial hygiene monitoring, thus works as an alert system for the VOCs pollution.