Triiodothyronine (T3) suppresses hepatic tumorigenesis and development by inhibiting the phosphorylation of ERK.

The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild-type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras-Tg and Kras-Tg)]) systems were used to investigate the effect of T3 on p-ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p-ERK in hepatoma cells within 30 min. However, p-ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p-ERK in liver tissues of WT. In Hras-Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p-ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p-MEK. Especially, the inhibitory effect of T3 on p-ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p-MEK was further confirmed in Kras-Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.

ZLN005 alleviates PBDE-47 induced impairment of mitochondrial translation and neurotoxicity through PGC-1α/ERRα axis.

Recent studies are identified the mitochondria as critical targets of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) induced neurotoxicity. This study aimed at examining the impact of PBDE-47 exposure on mitochondrial translation, and its subsequent effect on PBDE-47 neurotoxicity. The Sprague-Dawley (SD) rat model and neuroendocrine pheochromocytoma (PC12) cells were adopted for the measurements of mitochondrial ATP levels, mitochondrial translation products, and expressions of important mitochondrial regulators, such as required meiotic nuclear division 1 (RMND1), estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). To delve into the role of PGC-1α/ERRα axis in mitochondrial translation, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) was employed. Both cellular and animal model results shown that PBDE-47 impeded PGC-1α/ERRα axis and mitochondrial translation. PBDE-47 suppressed mitochondrial function in rat hippocampus and PC12 cells by decreasing relative mitochondrial DNA (mtDNA) content, mitochondrial translation products, and mitochondrial ATP levels. Particularly, ZLN005 reversed PBDE-47 neurotoxicity by enhancing mitochondrial translation through activation of PGC-1α/ERRα axis, yet suppressing PGC-1α with siRNA attenuates its neuroprotective effect in vitro. In conclusion, this work highlights the importance of mitochondrial translation in PBDE-47 neurotoxicity by presenting results from cellular and animal models and suggests a potential therapeutic approach through activation of PGC-1α/ERRα axis. ENVIRONMENTAL IMPLICATION: PBDEs have attracted extensive attention because of their high lipophilicity, persistence, and detection levels in various environmental media. Increasing evidence has shown that neurodevelopmental disorders in children are associated with PBDE exposure. Several studies have also found that perinatal PBDE exposure can cause long-lasting neurobehavioral abnormalities in experimental animals. Our recent studies have also demonstrated the impact of PBDE-47 exposure on mitochondrial biogenesis and dynamics, leading to memory and neurobehavioral deficits. Therefore, we explore whether the pathological mechanism of PBDE-47-induced neurotoxicity involves the regulation of mitochondrial translation through the PGC-1α/ERRα axis.

N-Sulfonyl amidine polypeptides: new polymeric biomaterials with conformation transition responsive to tumor acidity.

Manipulation of pH responsiveness is a frequently employed tactic in the formulation of trigger-responsive nanomaterials. It offers an avenue for "smart" designs capitalizing on distinctive pH gradients across diverse tissues and intracellular compartments. However, an overwhelming majority of documented functional groups (>80%) exhibit responsiveness solely to the heightened acidic milieu of intracellular pH (about 4.5-5.5). This scenario diverges markedly from the moderately acidic extracellular pH (∼6.8) characteristic of tumor microenvironments. Consequently, systems predicated upon intracellular pH responsiveness are unlikely to confer discernible advantages concerning targeted penetration and cellular uptake at tumor sites. In this study, we elucidated the extracellular pH responsiveness intrinsic to N-sulfonyl amidine (SAi), delineating a method to synthesize an array of SAi-bearing polypeptides (SAi-polypeptides). Notably, we demonstrated the pH-dependent modulation of SAi-polypeptide conformations, made possible by the protonation/deprotonation equilibrium of SAi in response to minute fluctuations in pH from physiological conditions to the extracellular milieu of tumors. This dynamic pH-triggered transition of SAi-polypeptides from negatively charged to neutrally charged side chains at the pH outside tumor cells (∼6.8) facilitated a transition from coil to helix conformations, concomitant with the induction of cellular internalization upon arrival at tumor sites. Furthermore, the progressive acidification of the intracellular environment expedited drug release, culminating in significantly enhanced site-specific chemotherapeutic efficacy compared with free-drug counterparts. The distinct pH-responsive attributes of SAi could aid the design of tumor acidity-responsive applications, thereby furnishing invaluable insights into the realm of smart material design.

Failure mechanical properties of lumbar intervertebral disc under high loading rate.

BACKGROUND: Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. METHOD: Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. RESULTS: For healthy samples, the stress-strain curve appears collapsed only at high rates of compression; for damaged samples, the stress-strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. CONCLUSION: Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.

Analysis of the relationship between color and natural pigments of tobacco leaves during curing.

Color is one of the most important indicators for the flue-cured tobacco quality. The color change of tobacco has a great relationship with the natural pigments in the tobacco. The relationship between color characteristics and the content of natural pigments in tobacco leaves during curing was investigated. The middle part of variety K326 tobacco was taken at each key time point during the curing process to determine the changes of color characteristics, moisture, pigment and polyphenol content. The results showed that moisture content of wet basis of tobacco gradually decreased from 72 to 18% during the curing process, the b* value increased and then decreased, and the a* value increased significantly. The lutein and ß-carotene content decreased to 63.83 µg/g and 28.3 µg/g, respectively. The total polyphenols content increased to 50.19 mg/g. Meanwhile, the a* value was significantly and positively correlated with polyphenols content and negatively correlated with pigments content. Cluster analysis showed that the samples were divided into three categories: samples with the curing time of 0 h, 24-72 h, and 84-132 h. These results demonstrated that the color change of tobacco during curing process can be divided into three stages from the perspective of chemical composition, which are strongly related to the degradation of pigments and the transformation of polyphenols.

Biochar derived from tobacco waste significantly reduces the accumulations of cadmium and copper in edible parts of two vegetables: an in-situ field study.

Biochar, as a soil amendment, can be applied to remediate heavy metal (HM) contaminated farmland. However, there is little research on the effect of tobacco biochar (TB) derived from tobacco waste on HM controlling in edible parts of vegetables. In this study, the impact of two TB levels on the plant growth, copper (Cu) and cadmium (Cd) accumulation in the edible parts of lettuce and chrysanthemum, and on Cu and Cd bioavailability of rhizosphere soil was investigated through in-situ field experiments. The results showed that TB has rich oxygen containing functional groups, high porosity, high nitrogen adsorption capacity. The addition of 5 t ha-1 and 10 t ha-1 TB significantly increased the shoot biomass of chrysanthemum, but had no effect on the growth of lettuce. Two levels of TB significantly increased the pH value, but decreased the available Cu and Cd concentrations of rhizosphere soil, thereby reducing the Cu and Cd accumulations in the edible parts of lettuce and chrysanthemum. The findings provided effective evidences that TB derived from tobacco waste is an efficient strategy for controlling Cu and Cd accumulation in the edible parts of vegetables to ensure agri-product safety production in HM-polluted farmland.

SIRT1, a target of miR-708-3p, alleviates fluoride-induced neuronal damage via remodeling mitochondrial network dynamics.

INTRODUCTION: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. OBJECTIVES: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. METHODS: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. RESULTS: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. CONCLUSION: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

[Effectiveness of Kirschner wire fixation and coracoclavicular ligament reconstruction with suture anchor in treatment of Cho type â ¡C distal clavicle fractures].

Objective: To evaluate the effectiveness of Kirschner wire fixation and coracoclavicular ligament reconstruction with suture anchor in the treatment of Cho type ⅡC distal clavicle fractures. Methods: The data of 17 patients with Cho type ⅡC distal clavicular fractures, who were treated with Kirschner wire fixation and coracoclavicular ligament reconstruction with suture anchor between June 2019 and June 2021, was retrospectively analyzed. There were 11 males and 6 females with an average age of 38.7 years (range, 19-72 years). The fractures were caused by falling in 12 cases and traffic accident in 5 cases. All patients had fresh closed fractures. The interval from injury to operation was 1-5 days (mean, 2.6 days). The preoperative injury severity score (ISS) was 6-27 (mean, 10.2). The operation time, intraoperative blood loss, hospital stay, fracture healing, and postoperative complications were analyzed. The shoulder joint function was evaluated by disabilities of the arm, shoulder, and hand (DASH) score and Constant score at last follow-up. Results: All operations were completed successfully. The operation time was 20-50 minutes (mean, 31.6 minutes). The intraoperative blood loss was 30-100 mL (mean, 50.6 mL). The hospital stay was 4-9 days (mean, 5.3 days). All incisions healed by first intention. All patients were followed up 12-16 months (mean, 13 months). All clavicle fractures healed, and the healing time was 8-15 weeks (mean, 11 weeks). No complications such as fracture displacement or nonunion caused by internal fixation failure occurred. During the follow-up, skin irritation caused by the Kirschner wire withdrawal occurred in 3 cases. The Kirschner wires were removed after fracture healing in 17 patients. At last follow-up, the Constant score of shoulder joint was 90-100 (mean, 98.2). The DASH score was 0-10 (mean, 1.5). Conclusion: Kirschner wire fixation combined with coracoclavicular ligament reconstruction with suture anchor in the treatment of Cho type ⅡC distal clavicle fractures has less postoperative complications and slight complications. It is convenient to remove the internal fixator. The Kirschner wire does not fix the distal clavicle fracture through the acromion, which has little effect on shoulder joint function and can obtain good effectiveness.

Peroxiredoxin II regulates exosome secretion from dermal mesenchymal stem cells through the ISGylation signaling pathway.

BACKGROUND: Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. RESULTS: In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. CONCLUSIONS: Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. Video Abstract.

Melatonin protects against developmental PBDE-47 neurotoxicity by targeting the AMPK/mitophagy axis.

The neurotoxicity of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is closely linked to mitochondrial abnormalities while mitophagy is vital for mitochondrial homeostasis. However, whether PBDE-47 disrupts mitophagy contributing to impaired neurodevelopment remain elusive. Here, this study showed that neonatal PBDE-47 exposure caused learning and memory deficits in adult rats, accompanied with striatal mitochondrial abnormalities, neuronal apoptosis and the resultant neuronal loss. Mechanistically, PBDE-47 suppressed PINK1/Parkin-mediated mitophagy induction and degradation, inducing mitophagosome accumulation and mitochondrial dysfunction in vivo and in vitro. Additionally, stimulation of mitophagy by adenovirus-mediated Parkin or Autophagy-related protein 7 (Atg7) overexpression aggravated PBDE-47-induced mitophagosome accumulation, mitochondrial dysfunction, neuronal apoptosis and death. Conversely, suppression of mitophagy by the siRNA knockdown of Atg7 rescued PBDE-47-induced detrimental consequences. Importantly, melatonin, a hormone secreted rhythmically by the pineal, improved PBDE-47-caused neurotoxicity via preventing neuronal apoptosis and loss by restoring mitophagic activity and mitochondrial function. These neuroprotective effects of melatonin depended on activation of the AMP-activated protein kinase (AMPK)/Unc-51-like kinase 1 (ULK1) signaling. Collectively, these data indicate that PBDE-47 impairs mitophagy to perturb mitochondrial homeostasis, thus triggering apoptosis, leading to neuronal loss and consequent neurobehavioral deficits. Manipulation of the AMPK-mitophagy axis via melatonin could be a novel therapeutic strategy against developmental PBDE-47 neurotoxicity.

Polymeric Phthalocyanine-Based Nanosensitizers for Enhanced Photodynamic and Sonodynamic Therapies.

Photodynamic therapy and sonodynamic therapy are two highly promising modalities for cancer treatment. The latter holds an additional advantage in deep-tumor therapy owing to the deep penetration of the ultrasonic radiation. The therapeutic efficacy depends highly on the photo/ultrasound-responsive properties of the sensitizers as well as their tumor-localization property and pharmacokinetics. A novel nanosensitizer system based on a polymeric phthalocyanine (pPC-TK) is reported herein in which the phthalocyanine units are connected with cleavable thioketal linkers. Such polymer could self-assemble in water forming nanoparticles with a hydrodynamic diameter of 48 nm. The degradable and flexible thioketal linkers could effectively inhibit the π-π stacking of the phthalocyanine units, rendering the resulting nanoparticles an efficient generator of reactive oxygen species upon light or ultrasonic irradiation. The nanosensitizer could be internalized into cancer cells readily, inducing cell death by efficient photodynamic and sonodynamic effects. The potency is significantly higher than that of the monomeric phthalocyanine (PC-4COOH). The nanosensitizer could also effectively inhibit the growth of tumor in liver tumor-bearing mice by these two therapies without causing noticeable side effects. More importantly, it could also retard the growth of a deep-located orthotopic liver tumor in vivo by sonodynamic therapy.

Secondary Structure in Overcoming Photosensitizers' Aggregation: α-Helical Polypeptides for Enhanced Photodynamic Therapy.

Aggregation caused quenching (ACQ) effect can severely inhibit the application of hydrophobic photosensitizers (PSs) bearing planar and rigid structures. Most of the reported cases utilized random-coiled polymers for the in vivo delivery of PSs, which would inevitably aggravate ACQ effect due to the flexible chains. In this work, the role of polymers' secondary structures (especially α-helical conformation) in overcoming the PSs' aggregation is systemically investigated based on the design of α-helical polypeptides bearing tetraphenylporphyrin (TPP) side chains. Atomistic molecular dynamics simulation, fluorescence quantum yield, and reactive oxygen species (ROS) generation yield are evaluated to demonstrate that α-helical polypeptide backbones can significantly boost both fluorescence quantum yield and ROS by suppressing the π-π stacking interaction between TPP units. The enhanced in vitro and in vivo phototoxicity for helical polypeptides also reveal functions of secondary structures in inhibiting ACQ and improving the membrane activity. Successful in vivo photodynamic therapy (PDT) results in mice bearing H22 tumors showed great potentials for further clinical applications.

Heavy metals immobilization of ternary geopolymer based on nickel slag, lithium slag and metakaolin.

To solve heavy metals leaching problem in the utilization of various industrial solid wastes, this work investigated the heavy metals immobilization of ternary geopolymer prepared by nickel slag (NS), lithium slag (LS), and metakaolin (MK). Compressive strength was measured to determine the optimum and appropriate mix proportions. The leaching characteristics of typical heavy metals (Cu (Ⅱ), Pb (Ⅱ), and Cr (Ⅲ)) in acid, alkali, and salt environments were revealed by Inductively Coupled Plasma (ICP). The heavy metals immobilization mechanism was explored by Mercury Intrusion Porosimetry (MIP), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) tests. The experimental results show that the group with a mass ratio of NS, LS and MK of 1:1:8 exhibits the highest compressive strength, which reaches 69.1 MPa at 28 d. The ternary geopolymer possesses a desirable capacity for immobilizing inherent heavy metals, where the immobilization rates of Cu and Pb reach 96.69 %, and that of Cr reaches 99.97 %. The leaching concentrations of Cr and Pb increase when the samples are exposed to acidic and alkaline environments. Cu and Pb are mainly physically encapsulated in geopolymer. Additionally, immobilization of Cr mainly involves physical encapsulation and chemical bonding.

Fluoride impairs mitochondrial translation by targeting miR-221-3p/c-Fos/RMND1 axis contributing to neurodevelopment defects.

Evidence suggests that fluoride-induced neurodevelopment damage is linked to mitochondrial disorder, yet the detailed mechanism remains unclear. A cohort of Sprague-Dawley rats developmentally exposed to sodium fluoride (NaF) was established to simulate actual exposure of human beings. Using high-input proteomics and small RNA sequencing technology in rat hippocampus, we found mitochondrial translation as the most striking enriched biological process after NaF treatment, which involves the differentially expressed Required Meiotic Nuclear Division 1 homolog (RMND1) and neural-specific miR-221-3p. Further experiments in vivo and in vitro neuroendocrine pheochromocytoma (PC12) cells demonstrated that NaF impaired mitochondrial translation and function, as shown by declined mitochondrial membrane potential and inhibited expression of mitochondrial translation factors, mitochondrial translation products, and OXPHOS complexes, which was concomitant with decreased RMND1 and transcription factor c-Fos in mRNA and proteins as well as elevated miR-221-3p. Notably, RMND1 overexpression alleviated the NaF-elicited mitochondrial translation impairment by up-regulating translation factors, but not vice versa. Interestingly, ChIP-qPCR confirmed that c-Fos specifically controls the RMND1 transcription through direct binding with Rmnd1 promotor. Interference of gene expression verified c-Fos as an upstream positive regulator of RMND1, implicating in fluoride-caused mitochondrial translation impairment. Furthermore, dual-luciferase reporter assay evidenced that miR-221-3p targets c-Fos by binding its 3' untranslated region. By modulating the miR-221-3p expression, we identified miR-221-3p as a critical negative regulator of c-Fos. More importantly, we proved that miR-221-3p inhibitor improved mitochondrial translation and mitochondrial function to combat NaF neurotoxicity via activating the c-Fos/RMND1 axis, whereas miR-221-3p mimic tended towards opposite effects. Collectively, our data suggest fluoride impairs mitochondrial translation by dysregulating the miR-221-3p/c-Fos/RMND1 axis to trigger mitochondrial dysfunction, leading to neuronal death and neurodevelopment defects.

PBDE-47 induces impairment of mitochondrial biogenesis and subsequent neurotoxicity through miR-128-3p/PGC-1α axis.

The potential adverse effects of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) on neurons are extensively studied, and mitochondria are identified as critical targets. This study aimed to investigate whether PBDE-47 impairs mitochondrial biogenesis via the miR-128-3p/PGC-1α axis to trigger mitochondrial dysfunction-related neuronal damage. In vitro neuroendocrine pheochromocytoma (PC12) cells and in vivo Sprague Dawley rat model were adopted. In this study, biochemical methods were used to examine mitochondrial ATP content, cell viability, and expressions of key mitochondrial biogenesis regulators, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Mimics and inhibitors of miR-128-3p were employed to explore its role in PBDE-47-induced neurotoxicity. Both in vivo and in vitro evidences suggested that PBDE-47 suppressed PGC-1α/NRF1/TFAM signaling pathways and mitochondrial DNA (mtDNA) encoding proteins synthesis. PBDE-47 also suppressed the relative mtDNA content, mRNA levels of mtDNA-encoded subunits, and mitochondrial ATP levels in vitro. Specifically, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) alleviated PBDE-47-induced neuronal death through the improvement of mitochondrial function by activating PGC-1α/NRF1/TFAM signaling pathways. Mechanistically, PBDE-47 dramatically upregulated miR-128-3p expression. Furthermore, miR-128-3p inhibition enhanced PGC-1α/NRF1/TFAM signaling and abolished PBDE-47-induced impairment of mitochondrial biogenesis. In summary, this study provides in vitro evidence to reveal the role of mitochondrial biogenesis in PBDE-47-induced mitochondrial dysfunction and related neurotoxicity and suggests that miR-128-3p/PGC-1α axis may be a therapeutic target for PBDE-47 neurotoxicity.

Perioperative Protocol of Ankle Fracture and Distal Radius Fracture Based on Enhanced Recovery after Surgery Program: A Multicenter Prospective Clinical Controlled study.

Background: The enhanced recovery after surgery (ERAS) program is aimed to shorten patients' recovery process and improve clinical outcomes. This study aimed to compare the outcomes between the ERAS program and the traditional pathway among patients with ankle fracture and distal radius fracture. Methods: This is a multicenter prospective clinical controlled study consisting of 323 consecutive adults with ankle fracture from 12 centers and 323 consecutive adults with distal radial fracture from 13 centers scheduled for open reduction and internal fixation between January 2017 and December 2018. According to the perioperative protocol, patients were divided into two groups: the ERAS group and the traditional group. The primary outcome was the patients' satisfaction of the whole treatment on discharge and at 6 months postoperatively. The secondary outcomes include delapsed time between admission and surgery, length of hospital stay, postoperative complications, functional score, and the MOS item short form health survey-36. Results: Data describing 772 patients with ankle fracture and 658 patients with distal radius fracture were collected, of which 323 patients with ankle fracture and 323 patients with distal radial fracture were included for analysis. The patients in the ERAS group showed higher satisfaction levels on discharge and at 6 months postoperatively than in the traditional group (P < 0.001). In the subgroup analysis, patients with distal radial fracture in the ERAS group were more satisfied with the treatment (P=0.001). Furthermore, patients with ankle fracture had less time in bed (P < 0.001) and shorter hospital stay (P < 0.001) and patients with distal radial fracture received surgery quickly after being admitted into the ward in the ERAS group than in the traditional group (P=0.001). Conclusions: Perioperative protocol based on the ERAS program was associated with high satisfaction levels, less time in bed, and short hospital stay without increased complication rate and decreased functional outcomes.

Study of nonlinear viscoelastic mechanical properties of degenerated intervertebral discs / Estudio de las propiedades mecánicas viscoelásticas no lineales de discos intervertebrales degenerados

SUMMARY: Biomechanical factors are important factors in inducing intervertebral disc degeneration, in this paper, the nonlinear viscoelastic mechanical properties of degenerated intervertebral discs were analyzed experimentally. Firstly, the loading and unloading curves of intervertebral discs before and after degeneration at different strain rates were compared to analyze the changes of their apparent viscoelastic mechanical properties; The internal stress/strain distribution of the disc before and after degeneration was then tested by combining digital image technology and fiber grating technology. The results show that the intervertebral disc is strain-rate- dependent whether before or after degeneration; The modulus of elasticity and peak stress of the degenerated disc are significantly reduced, with the modulus of elasticity dropping to 50 % of the normal value and the peak stress decreasing by about 55 %; Degeneration will not change the distribution of the overall internal displacement of the intervertebral disc, but has a greater impact on the superficial and middle AF; The stress in the center of the nucleus pulposus decreases, and the stress in the outer AF increases after degeneration. Degeneration has a great impact on the nonlinear viscoelastic mechanical properties of intervertebral disc, which has reference value for the mechanism, treatment and prevention of clinical degenerative diseases.

RESUMEN: Los factores biomecánicos son importantes en la inducción de la degeneración del disco intervertebral. En este estudio se analizaron experimentalmente las propiedades mecánicas viscoelásticas no lineales de los discos intervertebrales degenerados. En primer lugar se compararon las curvas de carga y descarga de los discos intervertebrales, antes y después de la degeneración, a diferentes velocidades de deformación para analizar los cambios aparentes de sus propiedades mecánicas viscoelásticas. La distribución interna de tensión/deformación del disco antes y después de la degeneración se probó luego combinando tecnología de imagen digital y tecnología de rejilla de fibra. Los resultados mostraron que el disco intervertebral depende de la velocidad de deformación antes o después de la degeneración; El módulo de elasticidad y la tensión máxima del disco degenerado se reducen significativamente, cayendo el módulo de elasticidad al 50 % del valor normal y la tensión máxima disminuyendo en aproximadamente un 55 %; La degeneración no cambiará la distribución del desplazamiento interno general del disco intervertebral, pero tiene un mayor impacto en la FA superficial y media; El estrés en el centro del núcleo pulposo disminuye y el estrés en el FA externo aumenta después de la degeneración. La degeneración tiene un gran impacto en las propiedades mecánicas viscoelásticas no lineales del disco intervertebral, que tiene valor de referencia para el mecanismo, tratamiento y prevención de enfermedades clínicas degenerativas.

[Reconstruction of anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon in the treatment of chronic lateral ankle instability].

OBJECTIVE: To explore the clinical efficacy of reconstruction the anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon for the treatment of chronic lateral ankle instability. METHODS: The clinical data of 42 patients with chronic lateral ankle instability treated by anatomical reconstruction of anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon from July 2016 to July 2019 was retrospectively analyzed. Including 30 males and 12 females, age ranged from 25 to 46 years old with an average of (37.6±12.4) years. There were 15 cases of left foot and 27 cases of right foot, the time from injury to operation was 3 to 12 months with a mean of (7.4±2.8) months. And 14 patients had tenderness in lateral collateral ligament area, 28 patients complained of multiple ankle sprains while walking on the flat ground. At 12 months after operation, the talar tilt angle and visual analogue scale(VAS)were observed, ankle joint varus stress and anterior drawer test were performed to check the mechanical stability of the ankle joint, American Orhopaedic Foot and Ankle Society(AOFAS) was used to score the ankle and hindfoot functions and evaluate the curative effect. RESULTS: Forty patients were followed up for 12 to 48 months with an average of (28.3±10.0) months, 2 cases were lost. The VAS decreased from(4.50±0.93) scores before surgery to (1.10±0.30) scores at 12 months after surgery;the talar tilt angle was reduced from (12.26±1.13)° before operation to (4.60±0.45)° at 12 months after operation;the AOFAS score increased from (65.10±7.50)scores before surgery to (84.40±3.95) scores at 12 months after surgery;all the differences were statically significant(P<0.05). According to the AOFAS score, 27 cases got excellent results, 7 good, 5 fair, and 1 poor. One patient had the symptoms of sural nerve injury after operation, and the symptoms were relieved after oral Mecobalamin for 3 months. The remaining patients had no complications such as nerve injury, infection, and skin necrosis. There was no instability of ankle joint, and both ankle varus stress test and drawer test were negative. CONCLUSION: Autologous peroneal brevis tendon with double bone channel pass through the tendon (modified Chrisman-Snook operation) can anatomically reconstruct the anterior talofibular ligament and the calcaneofibular ligament, restore the stability of the patient's ankle joint, reduce postoperative complications, and restore ankle joint function well.

Ensemble feature selection for stable biomarker identification and cancer classification from microarray expression data.

Microarray technology facilitates the simultaneous measurement of expression of tens of thousands of genes and enables us to study cancers and tumors at the molecular level. Because microarray data are typically characterized by small sample size and high dimensionality, accurate and stable feature selection is thus of fundamental importance to the diagnostic accuracy and deep understanding of disease mechanism. Hence, we in this study present an ensemble feature selection framework to improve the discrimination and stability of finally selected features. Specifically, we utilize sampling techniques to obtain multiple sampled datasets, from each of which we use a base feature selector to select a subset of features. Afterwards, we develop two aggregation strategies to combine multiple feature subsets into one set. Finally, comparative experiments are conducted on four publicly available microarray datasets covering both binary and multi-class cases in terms of classification accuracy and three stability metrics. Results show that the proposed method obtains better stability scores and achieves comparable to and even better classification performance than its competitors.

Protective effects of low-temperature plasma on cisplatin-induced nephrotoxicity.

The application of atmospheric pressure low-temperature plasma (LTP) in medical treatment has received extensive attention owing to its redox regulatory and anti-inflammatory properties. Nephrotoxicity due to oxidative stress and inflammation is the main adverse effect of cisplatin. In the present study, rats with cisplatin-induced nephrotoxicity were treated with LTP to investigate its potential protective effect. The results showed that LTP treatment has multiple protective effects on cisplatin-induced nephrotoxicity. It significantly improved clinical indicators such as survival rate, water intake, food intake, body weight, and mobility, as well as physiological indexes such as reduced renal index and levels of serum urea, creatinine, and total bilirubin; pathological indicators such as reduced tubular injury, inflammatory infiltration, tubulointerstitial fibrosis, and apoptosis; cell survival indicators such as decreased protein levels of Caspase-3 and Bax and increased Bcl-2; anti-oxidation status such as reduced malondialdehyde content and increased activities of catalase, superoxide dismutase, and glutathione peroxidase; and reduced inflammatory factors such as TNF-α in kidney tissues. Specially, LTP treatment did not influence the anticancer effect of cisplatin as observed in the solid tumor mouse model established by subcutaneously inoculating H22 cells. Moreover, LTP did not influence the physiological and pathological indicators of normal rats, suggesting its biological safety. In conclusion, LTP can protect against cisplatin-induced nephrotoxicity through its anti-oxidation, anti-inflammation, and anti-apoptosis effects, without influencing the anticancer effect of cisplatin.