A functional study reveals CsNAC086 regulated the biosynthesis of flavonols in Camellia sinensis.

MAIN CONCLUSION: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171-550), while the conserved NAC domain (positions 1-170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars.

A modified separate vertical fixation by wires and titanium cables for comminuted inferior patella fracture: A technique note and finite element analysis.

PURPOSE: Comminuted inferior patellar pole fractures are challenging injuries and require adequate treatment due to the extension mechanism of the knee. METHODS: A modified separate vertical fixation by wires and Titanium cables was established according to a finite element biomechanical study. Between September 2018 and May 2021, 18 patients with inferior pole fractures of the patella were retrospectively enrolled in this study. RESULTS: The results of the finite element analysis showed the concentration of stress in the intermediate vertical wire and the cerclage wire. As a partial replacement for steel wires, Titanium cables provide less concentration of stress on the vertical wire (489.4 MPa vs 441.2 Mpa) and less cutting force on the bone (75.87 Mpa vs 53.27), which reduces the possibility of internal fixation failure and improves the stability of internal fixation. In the clinic study, No patients experienced non-union of the fracture, loss of fracture repositioning, malunion of wounds, or wire breakage. At the last follow-up, the average range of motion was 134.7°±11.2°, and the Lysholm Score was 90.7 ± 3.9. CONCLUSIONS: The separate vertical fixation by wires and titanium cables is an effective fixation method for treating displaced, comminuted inferior pole fractures, which attributes to early exercise and better function.

P14.5 functions to inhibit cell migration and can be used as a prognostic marker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with a high mortality rate. P14.5 is a member of the highly conserved YER057c/YIL051c/YjgF subfamily and is highly expressed in the liver. However, its low expression is associated with carcinogenesis in HCC. OBJECTIVE: This study aimed to investigate the role and prognostic significance of P14.5 in HCC. METHODS: The clinical significance of P14.5 in HCC was examined using ONCOMINE, UALCAN, Human Protein Atlas, and Kaplan-Meier plotter. The DNA methylation profile of the P14.5 promoter was examined in 103 HCC and paired precancerous tissues; the HCC cell lines HepG2, MHCC-97L, SMMC-7721, SK-Hep-1, and Huh7; and the normal hepatic cell line HL-7702 via MALDI-TOF mass spectrometry. In addition, in vitro experiments were performed to examine the effects of P14.5 overexpression on the proliferation and migration of SMMC-7721 cells. RESULTS: Low expression of P14.5 was correlated with shorter overall survival (OS) and disease-free survival (DFS) in HCC. Based on the results of MALDI-TOF mass spectrometry, no difference was observed in the methylation level between HCC cells and normal human hepatic cells and between HCC and paired precancerous tissues. Additionally, P14.5 overexpression promoted the proliferation and inhibited the migration of SMMC7721 cells in vitro. CONCLUSIONS: P14.5 may serve as a prognostic biomarker in HCC and plays a role in the migration and proliferation of HCC cells. Low expression of P14.5 during hepatocarcinogenesis is not attributed to DNA methylation.

Thrombin Improves Diabetic Wound Healing by ERK-Dependent and Independent Smad2/3 Linker Region Phosphorylation.

BACKGROUND: Impaired wound healing is one of the most noteworthy features and troublesome complications of diabetes mellitus, which arouses a rising global health concern without potent remedies. Thrombin is the major hemostatic agent applied at wound healing initiation and recently gained therapeutic credits in later phases. However, a rare investigation achieved prolonged use of thrombin and probed the detailed mechanism. OBJECTIVE: The objective of this study is to investigate the effects and mechanism of thrombin on diabetic skin wound healing. METHODS: The effect of thrombin on fibroblast proliferation, α-SMA, and Collagen I expression was firstly studied in vitro by Cell Counting Kit 8 (CCK8) and western blotting. Then, the specific phosphorylation site of SMAD2/3 and their ERK1/2 dependence during thrombin treatment were assessed by western blotting for mechanism exploration. After that, full-thickness wound defects were established in diabetic male SD rats and treated with thrombin in the presence or absence of PD98059 to observe the in vivo effects of thrombin and to confirm its ERK dependence. RESULTS: We found that thrombin promoted fibroblast proliferation and their α-SMA and Collagen I production. Mechanistically, thrombin induced phosphorylation of Smad2 linker region (Ser245/250/255) through ERK1/2 phosphorylation but promoted phosphorylation of Smad3 linker region (Ser204) independent of ERK1/2. Histological results showed that thrombin facilitated wound healing by promoting α-SMA and Collagen I expression, which was not abolished by inhibiting ERK phosphorylation. CONCLUSION: Collectively, this study validated the therapeutic efficacy of thrombin on diabetic wound healing and identified both ERK-dependent and -independent Smad2/3 linker region phosphorylation as the essential signaling events in this process.

Cortical allograft strut augmented with platelet-rich plasma for the treatment of long bone non-union in lower limb- a pilot study.

BACKGROUND: The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb. METHOD: This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up. RESULTS: Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18-56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication. CONCLUSION: Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.

Gender-Related and Hemispheric Effects in Cortical Thickness-Based Hemispheric Brain Morphological Network.

OBJECTIVE: The current study examined gender-related differences in hemispheric asymmetries of graph metrics, calculated from a cortical thickness-based brain structural covariance network named hemispheric morphological network. METHODS: Using the T1-weighted magnetic resonance imaging scans of 285 participants (150 females, 135 males) retrieved from the Human Connectome Project (HCP), hemispheric morphological networks were constructed per participant. In these hemispheric morphologic networks, the degree of similarity between two different brain regions in terms of the distributed patterns of cortical thickness values (the Jensen-Shannon divergence) was defined as weight of network edge that connects two different brain regions. After the calculation and summation of global and local graph metrics (across the network sparsity levels K = 0.10-0.36), asymmetry indexes of these graph metrics were derived. RESULTS: Hemispheric morphological networks satisfied small-worldness and global efficiency for the network sparsity ranges of K = 0.10-0.36. Between-group comparisons (female versus male) of asymmetry indexes revealed opposite directionality of asymmetries (leftward versus rightward) for global metrics of normalized clustering coefficient, normalized characteristic path length, and global efficiency (all p < 0.05). For the local graph metrics, larger rightward asymmetries of cingulate-superior parietal gyri for nodal efficiency in male compared to female, larger leftward asymmetry of temporal pole for degree centrality in female compared to male, and opposite directionality of interhemispheric asymmetry of rectal gyrus for degree centrality between female (rightward) and male (leftward) were shown (all p < 0.05). CONCLUSION: Patterns of interhemispheric asymmetries for cingulate, superior parietal gyrus, temporal pole, and rectal gyrus are different between male and female for the similarities of the cortical thickness distribution with other brain regions. Accordingly, possible effect of gender-by-hemispheric interaction has to be considered in future studies of brain morphology and brain structural covariance networks.

Electrospun fibrous membranes featuring sustained release of ibuprofen reduce adhesion and improve neurological function following lumbar laminectomy.

Electrospun fibrous membranes provide suitable physical anti-adhesion barriers for reducing tissue anti-adhesion following surgery. However, often during the biodegradation process, these barriers trigger inflammation and cause a foreign body reaction with subsequent decrease in anti-adhesion efficacy. Here, a facile strategy comprising the incorporation of ibuprofen (IBU) into implantable membranes and its sustained release was proposed in order to improve anti-adhesion effects and neurological outcomes, namely to prevent failed back surgery syndrome (FBSS). The combination of free IBU and a newly synthetized polymeric prodrug of IBU, namely poly(hydroxyethyl methacrylate) with ester-linked IBU, was successfully used in order to reduce initial burst drug release and provide sustained drug release from fibrous membranes throughout several weeks. Such release profile was shown useful in preventing both acute and chronic inflammation in rats following laminectomy and membrane implantation. Moreover, histological analysis provided evidence of an excellent anti-adhesion effect, while associated neurological deficits were effectively reduced. Furthermore, the assessment of macrophage density, neovascularization, and related gene expression at the lesion site revealed that a sustained anti-inflammatory effect was achieved with the IBU-loaded proposed fibrous membranes. Results suggested that the COX2 pathway plays an important role in the development epidural fibrosis and arachnoiditis. Overall, this study provided evidence that precisely engineered IBU-loaded electrospun fibrous membranes may be useful in preventing FBSS and able to potentially impact the outcome of patients undergoing spine surgery.

Percutaneous vertebroplasty compared with conservative treatment in patients with chronic painful osteoporotic spinal fractures.

The efficacy of percutaneous vertebroplasty (PVP) for patients with chronic painful osteoporotic compression fractures remains unknown. The purpose of this study was to compare the efficacy of PVP and conservative treatment (CT) for pain relief and functional outcome in patients with chronic compression fractures and persistent pain. Ninety-six patients with chronic compression fractures confirmed by MRI and persistent severe pain for 3 months or longer were prospectively randomly assigned to undergo PVP (n=46, Group A) or CT (n=50, Group B). The primary outcome was pain relief and functional outcome at 1 week, 1 month, 3 months, 6 months and 1 year. A total of 89 patients (46 in Group A and 43 in Group B) completed the 1 year follow-up assessment. Pain relief and functional outcomes were significantly better in Group A than in Group B, as determined by visual analogue scale scores, Oswestry Disability Index scores, and Roland Morris Disability scores at 1 week, 1 month, 3 months, 6 months and 1 year (all p<0.001). The final clinical follow-up assessment indicated complete pain relief in 39 Group A patients and 15 Group B patients (p<0.001). PVP for patients with chronic compression fractures and persistent severe pain was associated with better pain relief and improved functional outcomes at 1 year compared to CT.

Polymorphisms in the MDM2 gene and risk of malignant bone tumors: a meta-analysis.

There are several studies published to assess the associations of murine double minute 2 (MDM2) genetic polymorphisms with risk of malignant bone tumors, but they reported contradictory results and failed to confirm a strong and consistent association. To assess the evidence regarding the associations of MDM2 genetic polymorphisms with the risk of malignant bone tumors, we conducted a meta-analysis of epidemiological studies. The pooled odds ratio (OR) with its 95% confidence intervals (95% CI) was used to assess these possible associations. Four studies with a total of 3,958 individuals were finally included the meta-analysis. Meta-analysis of two studies on MDM2 SNP309 polymorphism showed that MDM2 SNP309 polymorphism was associated with an increased risk of malignant bone tumors (G versus T: OR = 1.72, 95% CI 1.35-2.20, P < 0.001; GG versus TT: OR = 2.64, 95% CI 1.59-4.39, P < 0.001; GG/GT versus TT: OR = 1.87, 95% CI 1.33-2.62, P < 0.001; GG versus TT/GT: OR = 2.20, 95% CI 1.38-3.51, P = 0.001). Meta-analysis of those two studies on MDM2 rs1690916 polymorphism showed that MDM2 rs1690916 minor allele A was associated with decreased risk of malignant bone tumors (OR = 0.60, 95% CI 0.46-0.77, P < 0.001). Meta-analyses of available data show that there are significant associations of MDM2 SNP309 polymorphism and MDM2 rs1690916 polymorphism with malignant bone tumors.

[Comparison of effectiveness between minimally invasive plating osteosynthesis and expandable intramedullary nailing technique in treatment of middle third humeral shaft fractures].

OBJECTIVE: To compare the effectiveness of two minimally invasive methods: minimally invasive plating osteosynthesis (MIPO) and expandable intramedullary nailing technique in treatment of middle third humeral shaft fractures. METHODS: The clinical data were retrospectively analyzed and compared from 33 cases with middle third humeral shaft fractures between May 2004 and December 2008. All the patients were divided into 2 groups: 14 patients were treated with MIPO technique (group A) and 19 with expandable intramedullary nailing technique (group B). In group A, there were 10 males and 4 females with an average age of 35 years (range, 21-51 years). The disease cause was traffic accident in 5 cases, tumbling in 6 cases, machine related trauma in 2 cases, crushed by a heavy object in 1 case. Six fractures were classified as AO type A, 6 as type B, and 2 as type C. The time from injury to operation was 3 to 11 days with an average of 5.9 days. In group B, there were 12 males and 7 females with an average age of 40 years (range, 19-68 years). The disease cause was traffic accident in 7 cases, tumbling in 8 cases, falling from height in 3 cases, crush injury in 1 case. Ten fractures were classified as AO type A, 8 as type B, and 1 as type C. The time from injury to operation was 2 to 6 days with an average of 4.2 days. There was no significant difference in general data between 2 groups (P > 0.05). RESULTS: The operation time was (104.6 +/- 25.8) minutes in group A and (85.0 +/- 35.7) minutes in group B, showing no significant difference (P > 0.05). Incision healed by first intention without iatrogenic radial nerve palsy in 2 groups. The patients were followed up 21.4 months on average (range, 12-37 months) in group A and 20.5 months on average (range, 22-35 months) in group B. The X-ray films showed bony healing in all patients. The fracture union time was (16.4 +/- 6.1) weeks in group A and (15.0 +/- 2.5) weeks in group B, showing no significant difference (P > 0.05). The University of California Los Angeles (UCLA) End-Result scores were 34.1 +/- 1.1 in group A and 31.8 +/- 2.6 in group B and the Mayo Elbow Performance scores were 100 in group A and 97.6 +/- 3.9 in group B; all showing significant differences (P < 0.05). CONCLUSION: Good clinical outcomes could be obtained when middle third humeral shaft fractures are treated by either MIPO or expandable intramedullary nailing techniques. However, MIPO technique could offer better shoulder and elbow functional results.

Dynamic activity classification based on automatic adaptation of postural orientation.

We propose a dynamic activity classification system with tri-axial accelerometer sensor using adaptation of user's postural orientation. In general, the sensor module is worn at a fixed position such as waist, head, wrist, thigh, and so on. However, in reality, the tilt of the attached sensor could be changed from time to time in actions such as sitting down, standing up, lying, walking or running. Moreover, most of the users want to wear the sensor at their own favorite positions instead of a recommended position. In these cases, the activity detection methods based on fixed tilt value may produce serious problem in their performance. Therefore, we propose a user adapted activity classification method which enables users to freely wear the sensor everywhere on their torso. In order to decide tilt values corresponding user's postural orientation, we focused on tilt-free activities such as walking and running. While walking, the algorithm tries to modify the predefined reference tilt values for the three axes, X, Y and Z. From an experiment, we have achieved 88% of the activity classification accuracy even though the tilt angle is changed while wearing sensors.

Toward real time detection of the basic living activity in home using a wearable sensor and smart home sensors.

As the elderly people living alone are enormously increasing recently, we need the system inferring activities of daily living (ADL) for maintaining healthy life and recognizing emergency. The system should be constructed with sensors, which are used to associate with people's living while remaining as non intrusive views as possible. To do this, the proposed system use a triaxial accelerometer sensor and environment sensors indicating contact with subject in home. Particularly, in order to robustly infer ADLs, we present component ADL, which is decided with conjunction of human motion together, not just only contacted object identification. It is an important component in inferring ADL. In special, component ADL decision firstly refines misclassified initial activities, which improves the accuracy of recognizing ADL. Preliminary experiments results for proposed system provides overall recognition rate of over 97% over 8 component ADLs, which can be effectively applicable to recognize the final ADLs.

An effective method for component activity classification supporting location awareness and user identification.

We present an effective method for component activity classification supporting location awareness and user identification at the same time. The system is comprised of three modules: Pressure Sensing Module (PSM), Activity Detecting Module (ADM), and Receiving Station (RS). The ADM having a unique id is a wearable module putting on one's waist-belt, which classifies component activity such as sitting chair, lying bed, sitting sofa, etc. utilizing both user's interaction with household furniture and atomic activities like lie, sit, and stand. We limit transmission range of RF chip in PSM to around 1 m so that we can find the most adjacent furniture to the ADM. It makes possible to find the user's relative location to the PSM, so we can aware of both who and where the acting person is while recognizing his/her activities. We obtained 92.5% of average precision of the activity classification.

Semantic tagging for medical knowledge tracking.

We propose a semantic tagger that provides high level concept information for phrases in clinical documents, which enriches medical information tracking system that support decision making or quality assurance of medical treatment. In this paper, we have tried to deal with patient records written by doctors rather than well-formed documents such as Medline abstracts. In addition, annotating clinical text on phrases semantically rather than syntactically has been attempted, which are at higher level granularity than words that have been the target for most tagging work.