A Novel Method for Rolling Bearing Fault Diagnosis Based on Gramian Angular Field and CNN-ViT.

Fault diagnosis is one of the important applications of edge computing in the Industrial Internet of Things (IIoT). To address the issue that traditional fault diagnosis methods often struggle to effectively extract fault features, this paper proposes a novel rolling bearing fault diagnosis method that integrates Gramian Angular Field (GAF), Convolutional Neural Network (CNN), and Vision Transformer (ViT). First, GAF is used to convert one-dimensional vibration signals from sensors into two-dimensional images, effectively retaining the fault features of the vibration signal. Then, the CNN branch is used to extract the local features of the image, which are combined with the global features extracted by the ViT branch to diagnose the bearing fault. The effectiveness of this method is validated with two datasets. Experimental results show that the proposed method achieves average accuracies of 99.79% and 99.63% on the CWRU and XJTU-SY rolling bearing fault datasets, respectively. Compared with several widely used fault diagnosis methods, the proposed method achieves higher accuracy for different fault classifications, providing reliable technical support for performing complex fault diagnosis on edge devices.

Rictor mediates p53 deactivation to facilitate the malignant transformation of hepatocytes and promote hepatocarcinogenesis.

BACKGROUND: Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear. METHODS: Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo. RESULTS: Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P < 0.05). In mice, xenograft tumors overexpressing miR-192 exhibited lower Rictor expression levels, leading to higher p53 activity, and these tumors displayed slower growth compared to untreated HCC cells. CONCLUSIONS: Rictor dynamically shuttles between the nucleus and cytoplasm during HCC development. Its pivotal oncogenic role involves binding and inhibiting p53wt activity within the nucleus in early hepatocarcinogenesis. Targeting Rictor presents a promising strategy for HCC based on p53 status.

Intricate role of intestinal microbe and metabolite in schizophrenia.

BACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia. METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms. RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms. CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

The predictive value of nontraditional lipid parameters for intracranial and extracranial atherosclerotic stenosis: a hospital-based observational study in China.

BACKGROUND: Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis. METHODS: The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed. RESULTS: Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), TG/HDL-C, remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli's index-I (CRI-I) and Castelli's index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P < 0.05). Compared with other nontraditional lipid parameters, regardless of adjusting for potential confounding factors, AIP had a greater OR value in ICAS (OR = 4.226, 95% CI: 1.681-10.625), ECAS (OR = 2.993, 95% CI: 1.119-8.003) and IECAS (OR = 4.502, 95% CI: 1.613-12.561). ROC curve analysis revealed that nontraditional lipid parameters had good predictive power for intracranial or extracranial atherosclerotic stenosis. CONCLUSIONS: This Chinese hospital-based study demonstrates that nontraditional lipid parameters (AIP, LCI, RC, CRI-II, AC, CRI-I and non-HDL-C) are effective predictors of intracranial and extracranial atherosclerotic stenosis, of which AIP may be a significant risk factor for predicting atherosclerotic arterial stenosis in the intracranial or extracranial regions.

Thoracic Endovascular Aortic Repair of Highly Tapered Type B Aortic Dissection with Proximal Tapered Stent Grafts and Distal Restrictive Stent Grafts.

BACKGROUND: This study evaluated aortic remodeling in highly tapered type B aortic dissection (TBAD) patients who underwent thoracic endovascular aortic repair (TEVAR) with a proximal tapered stent graft plus a distal restrictive stent graft to maximize thoracic coverage while avoiding distal excessive oversizing. METHODS: Thirty-four patients presenting with highly tapered TABD were randomized to restricted TEVAR (r-TEVAR) and standard TEVAR groups. Highly tapered TBAD was defined as the maximal diameter of the true lumen at proximal and distal thoracic aorta landing zone tapers greater than 8 mm or taper ratio greater than 20%. Patients in the r-TEVAR group underwent proximal tapered stent grafts plus distal restrictive stent grafts, to match the taper ratio of the descending thoracic aorta (DTA) and extend the length of stent coverage. Patients in the standard TEVAR group underwent proximal tapered stent grafts implantation without distal restrictive stent grafts. Aortic remodeling was estimated by computed tomography angiography (CTA) during the follow-up. RESULTS: In total, 16 patients underwent r-TEVAR, and 18 patients underwent standard TEVAR. The taper ratio of the stent graft matched the DTA in the r-TEVAR group (24.7 ± 3.4% vs. 27.3 ± 4.2%, P = 0.068), but did not match that in the standard TEVAR group (13.5 ± 3.3% vs. 30.5 ± 9.6%, P < 0.001). The length of stent graft coverage in the r-TEVAR group was longer than that in the standard TEVAR group (220.4 ± 21.1 mm vs. 175.3 ± 17.8 mm, P < 0.001). Compared with the standard TEVAR group, the r-TEVAR group had better complete remodeling of the DTA at 6 months (40% vs. 5.6%, P = 0.03), 12 months (60% vs. 16.7%, P = 0.027), and 24 months (78.6% vs. 41.2%, P = 0.036) after the operation. There was no difference in the cumulative survival rate between the r-TEVAR and standard TEVAR groups (P = 0.166). CONCLUSIONS: The r-TEVAR with overlapping proximal tapered stent grafts and distal restrictive stent grafts can match the taper of highly tapered TABD, extend the length of stent graft coverage, and lead to better remodeling of the DTA than standard TEVAR.

Characterization of DinJ-YafQ toxin-antitoxin module in Tetragenococcus halophilus: activity, interplay, and evolution.

Tetragenococcus halophilus is a moderately halophilic lactic acid bacterium widely used in high-salt food fermentation because of its coping ability under various stress conditions. Bacterial toxin-antitoxin (TA) modules are widely distributed and play important roles in stress response, but those specific for genus Tetragenococcus have never been explored. Here, a bona fide TA module named DinJ1-YafQ1tha was characterized in T. halophilus. The toxin protein YafQ1tha acts as a ribonuclease, and its overexpression severely inhibits Escherichia coli growth. These toxic effects can be eliminated by introducing DinJ1tha, indicating that YafQ1tha activity is blocked by the formed DinJ1-YafQ1tha complex. In vivo and in vitro assays showed that DinJ1tha alone or DinJ1-YafQ1tha complex can repress the transcription of dinJ1-yafQ1tha operon by binding directly to the promoter sequence. In addition, dinJ1-yafQ1tha is involved in plasmid maintenance and stress response, and its transcriptional level is regulated by various stresses. These findings reveal the possible roles of DinJ1-YafQ1tha system in the stress adaptation processes of T. halophilus during fermentation. A single antitoxin DinJ2tha without a cognate toxin protein was also found. Its sequence shows low similarity to that of DinJ1tha, indicating that this antitoxin may have evolved from a different ancestor. Moreover, DinJ2tha can cross-interact with noncognate toxin YafQ1tha and cross-regulate with dinJ1-yafQ1tha operon. In summary, DinJ-YafQtha characterization may be helpful in investigating the key roles of TA systems in T. halophilus and serves as a foundation for further research. KEY POINTS: • dinJ1-yafQ1tha is the first functional TA module characterized in T. halophilus and upregulated significantly upon osmotic and acidic stress. • DinJ2tha can exhibit physical and transcriptional interplay with DinJ1-YafQ1tha. • dinJ2tha may be acquired from bacteria in distant affiliation and inserted into the T. halophilus genome through horizontal gene transfer.

Integrative transcriptomic and proteomic analysis reveals CD9/ITGA4/PI3K-Akt axis mediates trabecular meshwork cell apoptosis in human glaucoma.

Glaucoma has been the leading cause of irreversible blindness worldwide. High intraocular pressure (IOP) is a high-risk factor of glaucoma, repression of which has been the important treatment of glaucoma in clinic. Trabecular meshwork is crucial for maintaining IOP in aqueous humour out-flow system. It is urgent to reveal the molecular mechanism of trabecular meshwork in glaucoma. Previous studies found that some pathways were related to glaucoma, such as extracellular matrix (ECM)-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and apoptosis. To identify novel molecules in glaucoma, we performed high-throughput transcriptome and proteome analysis to immortal human trabecular meshwork cells (iHTM) and glaucomatous human trabecular meshwork cells (GTM3 ), respectively. Twenty-six up-regulated genes/proteins and 59 down-regulated genes/proteins were identified as the high-risk factors based on differential analysis, including some known factors of glaucoma. Furthermore, a glaucoma-related protein-protein interaction (PPI) network was constructed for investigating the function roles of risk factors. Some genes were identified as potential regulator in the pathogenesis of glaucoma based on the topology analysis and module analysis to the network. Importantly, we identified and demonstrated that CD9 played key roles in glaucoma by biological experiment. CD9 is down-regulated in glaucoma, overexpression of CD9 can active integrin α4 (ITGA4), PI3K and Akt, which lead to the decreased apoptosis and attenuate glaucoma. All these results provide a novel molecular therapy of glaucoma.

Comparison of Anterior and Posterior Decompressions in Treatment of Traumatic Thoracolumbar Spinal Fractures Complicated with Spinal Cord Injury.

BACKGROUND For patients with thoracolumbar spinal fractures complicated with spinal cord injury, timely surgery is the first choice. We compared the effects of anterior and posterior decompressions in treatment of these patients. MATERIAL AND METHODS A total of 80 male patients with traumatic thoracolumbar spinal fractures and spinal cord injury were prospectively selected and divided into 2 groups. The control group underwent posterior decompression and internal fixation and the observation group underwent real-time anterior decompression. RESULTS The observation group had longer operative time and length of postoperative hospital stay, larger intraoperative blood loss, remarkably greater immediate postoperative anterior height and middle column height of the fractured vertebrae, and a notably smaller Cobb's angle than in the control group. The total ASIA score was significantly higher in the observation group than in the control group immediately after surgery and at 6 months and 1 year after surgery. The maximal urine flow, maximal detrusor pressure, and bladder compliance were also evidently higher in the observation group than in the control group during 1 year of follow-up. Compared with the control group, the International Index of Erectile Function-5 (IIEF-5) score in the observation group was significantly higher at 3 months, 6 months, and 1 year after surgery. CONCLUSIONS Compared with the posterior approach, anterior decompression in patients with thoracolumbar spinal fractures complicated with spinal cord injury can effectually enhance the surgical efficiency, and restore the physiological anatomy of the fractured vertebrae, thereby improving patient quality of life.

A Data-driven Adaptive Sampling Method Based on Edge Computing.

The rise of edge computing has promoted the development of the industrial internet of things (IIoT). Supported by edge computing technology, data acquisition can also support more complex and perfect application requirements in industrial field. Most of traditional sampling methods use constant sampling frequency and ignore the impact of changes of sampling objects during the data acquisition. For the problem of sampling distortion, edge data redundancy and energy consumption caused by constant sampling frequency of sensors in the IIoT, a data-driven adaptive sampling method based on edge computing is proposed in this paper. The method uses the latest data collected by the sensors at the edge node for linear fitting and adjusts the next sampling frequency according to the linear median jitter sum and adaptive sampling strategy. An edge data acquisition platform is established to verify the validity of the method. According to the experimental results, the proposed method is more effective than other adaptive sampling methods. Compared with constant sampling frequency, the proposed method can reduce the edge data redundancy and energy consumption by more than 13.92% and 12.86%, respectively.

Posteroanterior Lag Screws Versus Posterior Buttress Plate Fixation of Posterior Malleolar Fragments in Spiral Tibial Shaft Fracture.

The aim of this study is to compare the clinical outcomes of posteroanterior (PA) lag screws versus posterior buttress plate fixation in treatment of posterior malleolar fragments (PMFs) in spiral tibial shaft fracture, and provide guidance for surgeons selecting a treatment strategy. A total of 48 eligible patients with PMFs associated with spiral tibial shaft fracture surgically treated from March 2009 to January 2016 were included in the study. They were divided into the screw group (n = 24) and the plate group (n = 24). All operations were performed via a posterolateral approach by a senior orthopedic surgeon. The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analog scale (VAS), and assessment of ankle range of motion (ROM) were used for clinical evaluation. The radiographic evaluation of posttraumatic arthritis scale was determined by Bargon reference criteria. At the mean follow-up period of 29.5 ± 4.3 and 30.4 ± 4.1 months, respectively (p > .05), all patients in both groups had bone union without severe wound problems or complications. There were no significant differences in AOFAS (92.5 ± 5.3 vs 94.7 ± 5.6, p = .129) and VAS (2.4 ± 0.8 vs 2.2 ± 0.9, p = .196) scores between the groups at final follow-up. No significant differences were found between the groups in injured/contralateral ankle ROM or posttraumatic ankle arthritis scale postoperatively (p > .05). For PMFs in spiral tibial shaft fracture, PA lag screws or posterior buttress plate fixation via a posterolateral approach can achieve good and equivalent clinical and radiological outcomes with minimal complications.

Identification of a GntR family regulator BusRTha and its regulatory mechanism in the glycine betaine ABC transport system of Tetragenococcus halophilus.

Glycine betaine is one of the most effective compatible solutes of the halophilic lactic acid bacterium Tetragenococcus halophilus, the transportation of which is essential for its survival under salinity stress condition. In the current study, we attempted to define a glycine betaine ABC transporter system of T. halophilus, busATha, which plays an important role in adapting to salinity condition. The expression of busATha enhanced the growth of the recombinant strain under high salinity. BusRTha, a transcription regulator that represses the expression of busATha, was characterized, and the repression was abrogated under high salinity. The binding of the regulator was demonstrated through electrophoretic mobility shift assays, and the binding sites were characterized as 5'-AAA(T/G)TGAC(C/A)(G/A)T(C/A)C-3'. This is the first studied transcription regulator of T. halophilus, and our findings provide insights into the molecular mechanism of halophilic life and tools for further application of halophiles as chassis in industrial biotechnology.

Visual Outcome of Carotid Endarterectomy in Patients with Carotid Artery Stenosis.

BACKGROUND: Carotid endarterectomy (CEA) is deemed to restore the blood flow of the carotid and ophthalmic arteries in patients with carotid artery stenosis. However, specific changes in visual function before and after CEA are not well understood; hence, this observational study aimed to investigate the functional and structural changes in vision after CEA in those patients. METHODS: Patients with severe carotid artery stenosis (>70% with standard carotid duplex scanning or arteriography) scheduled to undergo CEA were consecutively recruited for the study between September 2015 and July 2016. All patients underwent a standardized ophthalmic examination, including intraocular pressure (IOP) measurement, slit-lamp examination, and fundus examination. Visual acuity, best corrected visual acuity (BCVA), and kinetic and static visual fields (VFs) were tested to evaluate subjective visual function. Flash and pattern visual evoked potentials (VEPs) and an electroretinogram (ERG) were measured for objective visual function. Retinal nerve fiber layer (RNFL) thickness was scanned using optical coherence tomography for structural evaluation. RESULTS: The study involved 15 patients (11 male and 4 female, corresponding to 30 eyes; mean age 62.8 ± 5.0 years). After CEA, both uncorrected visual acuity and BCVA improved, and IOP significantly decreased from 17.41 ± 2.59 to 15.95 ± 2.50 mm Hg (P = 0.0022). Kinetic VF range increased significantly (P = 0.0126) as did mean sensitivity from 18.8 ± 5.5 to 20.6 ± 4.3 dB (P = 0.0208), whereas mean defect decreased from 8.2 ± 5.3 to 6.5 ± 4.2 dB (P = 0.025). RNFL thickness was not significantly altered. Latency of the P2 wave on flash VEP reduced significantly after CEA (P = 0.0151), whereas the oscillatory potential amplitude of waveform 3 in the ERG significantly increased after CEA. CONCLUSIONS: Our results demonstrate that an improvement in carotid artery and ophthalmic artery blood flow after CEA does indeed enhance subjective and objective assessments of visual function in patients with carotid artery stenosis, including visual acuity, kinetic and static VF, P2 latency, and ocular pressure amplitude; however, it did not affect RNFL thickness.

Mechanisms of Cr(VI) reduction by Bacillus sp. CRB-1, a novel Cr(VI)-reducing bacterium isolated from tannery activated sludge.

Cr(VI) reduction by microorganisms has been extensively reported, however, the mechanism of Cr(VI) reduction varies among different microorganisms. In this study, a Cr(VI)-reducing bacterium identified as Bacillus sp. was isolated from tannery activated sludge, strain CRB-1 was able to completely reduce 50 mg/L of Cr(VI) within 24 h under aerobic conditions and exhibited considerable Cr(VI) removal efficiency in the pH range from 7.0 to 9.0, temperature 24-42 °C. Cr(VI) reduction assays with resting cells, permeabilized cells, and subcellular fractions suggested that Cr(VI) reduction mainly occurred in the cytoplasm. According to qRT-PCR analysis, a chrA gene and a nitR2 gene were up-regulated under Cr(VI) stress. Heterologous expression of the chrA gene and the nitR2 gene indicated that ChrA was associated with Cr(VI) resistance, while NitR2 was responsible for Cr(VI) reduction. Furthermore, soluble end products were detected. On the basis of FTIR, it was speculated that the formation of soluble end products may be due to the complexation of EPS with Cr(III). Consequently, the Cr(VI)-reducing ability of strain CRB-1 and its chromate reductases enables CRB-1 a potential candidate for Cr(VI) bioremediation.

Genistein Inhibited Estradiol-Induced Vascular Endothelial Cell Injury by Downregulating the FAK/Focal Adhesion Pathway.

BACKGROUND/AIMS: In this study, we aimed to investigate the effects of genistein on the focal adhesion signaling pathway through its regulation of FAK. Genistein ultimately restored and alleviated estradiol-induced vascular endothelial injury. METHODS: Microarray analysis was used to select differentially expressed genes. MTT assay was performed to detect the cell activity, and ROS test and NO test were performed to detect the degree of damage to HUVECs (human umbilical vein endothelial cells). The relative mRNA expression levels and protein expression levels of FAK were tested by western blot and qRT-PCR. GO functional analysis and KEGG pathway analysis were applied to predict the possible relationship between functions and related pathways, and transwell assay was used to detect cell invasion and migration. RESULTS: FAK was highly expressed in the HUVECs treated with estradiol (HU-ESTs). Cell viability and NO level decreased, whereas ROS level increased in the HU-ESTs. Effective knockdown of FAK in HU-ESTs elevated cell viability and NO levels while suppressing ROS levels. In addition, inhibition of FAK greatly decreased cell invasion and migration, while the overexpression of FAK enhanced cell invasion and migration. KEGG further indicated focal adhesion pathways were activated. Genistein elevated HU-EST viability, and NO and ROS level increased in a concentration dependent manner. Transwell and western blot assays revealed that genistein could reduce the FAK expression levels and alleviate the damage to the HU-ESTs. CONCLUSION: FAK overexpression promoted invasion and migration of the HU-ESTs. However, genistein greatly suppressed FAK and estradiol-induced vascular endothelial cell injury.

Research on the Multiple Factors Influencing Human Identification Based on Pyroelectric Infrared Sensors.

Analysis of the multiple factors affecting human identification ability based on pyroelectric infrared technology is a complex problem. First, we examine various sensed pyroelectric waveforms of the human body thermal infrared signal and reveal a mechanism for affecting human identification. Then, we find that the mechanism is decided by the distance, human target, pyroelectric infrared (PIR) sensor, the body type, human moving velocity, signal modulation mask, and Fresnel lens. The mapping relationship between the sensed waveform and multiple influencing factors is established, and a group of mathematical models are deduced which fuse the macro factors and micro factors. Finally, the experimental results show the macro-factors indirectly affect the recognition ability of human based on the pyroelectric technology. At the same time, the correctness and effectiveness of the mathematical models is also verified, which make it easier to obtain more pyroelectric infrared information about the human body for discriminating human targets.

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.

The tumor suppressor p53 is one of the most frequently mutated genes in hepatocellular carcinoma (HCC). Previous studies demonstrated that CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in tumor cells. However, the research on the application of CP-31398 to liver cancer has not been reported. Here, we investigated the effects of CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In tumor xenografts developed by PLC/PRF/5 cells, the inhibition of tumor growth by CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that CP-31398 inhibited the growth of p53-mutated liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that CP-31398 blocked the growth of xenografts tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.

CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.

Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis.

OBJECTIVE: The aim of this paper is to review the anti-inflammatory cytokines IL-4 and IL-13 and their receptor signals; we discuss new insight into their possible roles in systemic sclerosis (SSc) and their overlapping function in SSc. INTRODUCTION: SSc is a connective tissue disease characterized by fibrosis. The exact etiology of SSc is unknown, and no therapy has been proved effective in modifying its course. Recently the roles of IL-4 and IL-13 in the development of SSc have been extensively considered. The possible roles of IL-4 and IL-13, especially their overlapping function, in SSc are not well documented. METHODS: A literature survey was performed using a PubMed database search to gather complete information regarding IL-4 and IL-13 and their role in inflammation. RESULTS AND CONCLUSIONS: The participation of complex pathways of IL-4 and IL-13 in the process of inflammation and fibrosis action in SSc is still not very clear, and some pathogenesis of regulation found in vitro needs to be further proved. There is still more work which could be done to achieve useful developments with therapeutic benefit in SSc.

The epidemiology of alcohol consumption and multiple sclerosis: a review.

Alcohol consumption is accounted for a large proportion in patients with multiple sclerosis (MS) and may be a modifiable lifestyle factor that affects the risk of developing the disease. The epidemiological studies about the association between MS and alcohol consumption have got corresponding studies during the last decade. It has been suggested that alcohol consumption was associated with mood disorders, disability and even onset of MS, but a common theme is lacking. To make an understanding of the effect of alcohol consumption on MS, the related epidemiological evidence and potential mechanisms are reviewed.

Design, construction and mechanical testing of digital 3D anatomical data-based PCL-HA bone tissue engineering scaffold.

The study aims to investigate the techniques of design and construction of CT 3D reconstructional data-based polycaprolactone (PCL)-hydroxyapatite (HA) scaffold. Femoral and lumbar spinal specimens of eight male New Zealand white rabbits were performed CT and laser scanning data-based 3D printing scaffold processing using PCL-HA powder. Each group was performed eight scaffolds. The CAD-based 3D printed porous cylindrical stents were 16 piece × 3 groups, including the orthogonal scaffold, the Pozi-hole scaffold and the triangular hole scaffold. The gross forms, fiber scaffold diameters and porosities of the scaffolds were measured, and the mechanical testing was performed towards eight pieces of the three kinds of cylindrical scaffolds, respectively. The loading force, deformation, maximum-affordable pressure and deformation value were recorded. The pore-connection rate of each scaffold was 100 % within each group, there was no significant difference in the gross parameters and micro-structural parameters of each scaffold when compared with the design values (P > 0.05). There was no significant difference in the loading force, deformation and deformation value under the maximum-affordable pressure of the three different cylinder scaffolds when the load was above 320 N. The combination of CT and CAD reverse technology could accomplish the design and manufacturing of complex bone tissue engineering scaffolds, with no significant difference in the impacts of the microstructures towards the physical properties of different porous scaffolds under large load.