Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Maximum Entropy Modeling the Distribution Area of Morchella Dill. ex Pers. Species in China under Changing Climate.

Morchella is a kind of precious edible, medicinal fungi with a series of important effects, including anti-tumor and anti-oxidation effects. Based on the data of 18 environmental variables and the distribution sites of wild Morchella species, this study used a maximum entropy (MaxEnt) model to predict the changes in the geographic distribution of Morchella species in different historical periods (the Last Glacial Maximum (LGM), Mid Holocene (MH), current, 2050s and 2070s). The results revealed that the area under the curve (AUC) values of the receiver operating characteristic curves of different periods were all relatively high (>0.83), indicating that the results of the maximum entropy model are good. Species distribution modeling showed that the major factors influencing the geographical distribution of Morchella species were the precipitation of the driest quarter (Bio17), elevation, the mean temperature of the coldest quarter (Bio11) and the annual mean temperature (Bio1). The simulation of geographic distribution suggested that the current suitable habitat of Morchella was mainly located in Yunnan, Sichuan, Gansu, Shaanxi, Xinjiang Uygur Autonomous Region (XUAR) and other provinces in China. Compared with current times, the suitable area in Northwest and Northeast China decreased in the LGM and MH periods. As for the future periods, the suitable habitats all increased under the different scenarios compared with those in contemporary times, showing a trend of expansion to Northeast and Northwest China. These results could provide a theoretical basis for the protection, rational exploitation and utilization of wild Morchella resources under scenarios of climate change.

Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy.

The transforming growth factor (TGF)-ß signaling pathway controls many cellular processes, including proliferation, differentiation, and apoptosis. Abnormalities in the TGF-ß signaling pathway and its components are closely related to the occurrence of many human diseases, including cancer. Mothers against decapentaplegic homolog 4 (Smad4), also known as deleted in pancreatic cancer locus 4, is a typical tumor suppressor candidate gene locating at q21.1 of human chromosome 18 and the common mediator of the TGF-ß/Smad and bone morphogenetic protein/Smad signaling pathways. It is believed that Smad4 inactivation correlates with the development of tumors and stem cell fate decisions. Smad4 also interacts with cytokines, miRNAs, and other signaling pathways, jointly regulating cell behavior. However, the regulatory function of Smad4 in tumorigenesis, stem cells, and drug resistance is currently controversial. In addition, Smad4 represents an attractive therapeutic target for cancer. Elucidating the specific role of Smad4 is important for understanding the mechanism of tumorigenesis and cancer treatment. Here, we review the identification and characterization of Smad4, the canonical TGF-ß/Smad pathway, as well as the multiple roles of Smad4 in tumorigenesis, stem cells, and drug resistance. Furthermore, we provide novel insights into the prospects of Smad4-targeted cancer therapy and the challenges that it will face in the future.

The Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy.

Mitochondria are key cellular organelles and play vital roles in energy metabolism, apoptosis regulation and cellular homeostasis. Mitochondrial dynamics refers to the varying balance between mitochondrial fission and mitochondrial fusion that plays an important part in maintaining mitochondrial homeostasis and quality. Mitochondrial malfunction is involved in aging, metabolic disease, neurodegenerative disorders, and cancers. Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control. In past decades, numerous studies have identified a series of factors that regulate mitophagy and are also involved in carcinogenesis, cancer cell migration and death. Therefore, it has become critically important to analyze signal pathways that regulate mitophagy to identify potential therapeutic targets. Here, we review recent progresses in mitochondrial dynamics, the mechanisms of mitophagy regulation, and the implications for understanding carcinogenesis, metastasis, treatment, and drug resistance.

Isolation of CHS Gene from Brunfelsia acuminata Flowers and Its Regulation in Anthocyanin Biosysthesis.

Chalcone synthase gene (BaCHS) from Brunfelsia acuminata flowers was isolated using RT-PCR and RACE. The coding region of the gene is 1425-bp with an open reading frame of 1170-bp, 73-bp 5'UTR, and 172-bp 3'UTR. Its deduced protein does not have a signal peptide but does contain a cond_enzyme superfamily domain, and consists of 389 amino acids with a predicted molecular mass of 42,699 Da and a pI of 6.57. The deduced amino acid sequence of BaCHS shares 90%, 88%, 85%, 84% and 79% identity with CHS from Petunia hybrida, Nicotiana tabacum, Solanum lycopersicum, Capsicum annuum and Camellia sinensis, respectively. The striking color change from dark purple to light purple and ultimately lead to pure white resulted from a decline in anthocyanin content of the petals and was preceded by a decrease in the expression of BaCHS. Its gene expression was positively correlated with the contents of anthocyanin (p ≤ 0.01).