Tabersonine Induces the Apoptosis of Human Hepatocellular Carcinoma In vitro and In vivo.

BACKGROUND: Tabersonine, a natural indole alkaloid derived from Apocynaceae plants, exhibits antiinflammatory and acetylcholinesterase inhibitory activities, among other pharmacological effects. However, its anti-tumor properties and the underlying molecular mechanisms remain underexplored. OBJECTIVE: The present study aims to investigate the anti-tumor effects of tabersonine and its mechanisms in inducing apoptosis in hepatocellular carcinoma. METHODS: The inhibitory effects of tabersonine on the viability and proliferation of liver cancer cells were evaluated using MTT assay and colony formation assay. AO/EB, Hoechst, and Annexin V-FITC/ PI staining techniques were employed to observe cell damage and apoptosis. JC-1 staining was used to detect changes in mitochondrial membrane potential. Western blot analysis was conducted to study the anti-tumor mechanism of tabersonine on liver cancer cells. Additionally, a xenograft model using mice hepatoma HepG2 cells was established to assess the anti-tumor potency of tabersonine in vivo. RESULTS AND DISCUSSION: Our findings revealed that tabersonine significantly inhibited cell viability and proliferation, inducing apoptosis in liver cancer cells. Treatment with tabersonine inhibited Akt phosphorylation, reduced mitochondrial membrane potential, promoted cytochrome c release from mitochondria to the cytoplasm, and increased the ratio of Bax to Bcl-2. These findings suggested that tabersonine induces apoptosis in liver cancer cells through the mitochondrial pathway. Furthermore, tabersonine treatment activated the death receptor pathway of apoptosis. In vivo studies demonstrated that tabersonine significantly inhibited xenograft tumor growth. CONCLUSION: Our study is the first to demonstrate that tabersonine induces apoptosis in HepG2 cells through both mitochondrial and death receptor apoptotic pathways, suggesting its potential as a therapeutic agent candidate for hepatic cancer.

A dual-energy CT reconstruction method based on anchor network from dual quarter scans.

Compared with conventional single-energy computed tomography (CT), dual-energy CT (DECT) provides better material differentiation but most DECT imaging systems require dual full-angle projection data at different X-ray spectra. Relaxing the requirement of data acquisition is an attractive research to promote the applications of DECT in wide range areas and reduce the radiation dose as low as reasonably achievable. In this work, we design a novel DECT imaging scheme with dual quarter scans and propose an efficient method to reconstruct the desired DECT images from the dual limited-angle projection data. We first study the characteristics of limited-angle artifacts under dual quarter scans scheme, and find that the negative and positive artifacts of DECT images are complementarily distributed in image domain because the corresponding X-rays of high- and low-energy scans are symmetric. Inspired by this finding, a fusion CT image is generated by integrating the limited-angle DECT images of dual quarter scans. This strategy enhances the true image information and suppresses the limited-angle artifacts, thereby restoring the image edges and inner structures. Utilizing the capability of neural network in the modeling of nonlinear problem, a novel Anchor network with single-entry double-out architecture is designed in this work to yield the desired DECT images from the generated fusion CT image. Experimental results on the simulated and real data verify the effectiveness of the proposed method. This work enables DECT on imaging configurations with half-scan and largely reduces scanning angles and radiation doses.

Expert consensus on perioperative integrated skincare for noninvasive energy-based device aesthetic procedures in clinical practice in China.

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.

Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis.

BACKGROUND: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. METHODS: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. RESULTS: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. CONCLUSION: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.

Evolution of high-molecular-mass hyaluronic acid is associated with subterranean lifestyle.

Hyaluronic acid is a major component of extracellular matrix which plays an important role in development, cellular response to injury and inflammation, cell migration, and cancer. The naked mole-rat (Heterocephalus glaber) contains abundant high-molecular-mass hyaluronic acid in its tissues, which contributes to this species' cancer resistance and possibly to its longevity. Here we report that abundant high-molecular-mass hyaluronic acid is found in a wide range of subterranean mammalian species, but not in phylogenetically related aboveground species. These subterranean mammalian species accumulate abundant high-molecular-mass hyaluronic acid by regulating the expression of genes involved in hyaluronic acid degradation and synthesis and contain unique mutations in these genes. The abundant high-molecular-mass hyaluronic acid may benefit the adaptation to subterranean environment by increasing skin elasticity and protecting from oxidative stress due to hypoxic conditions. Our work suggests that high-molecular-mass hyaluronic acid has evolved with subterranean lifestyle.

[Application Value of Artificial Intelligence-assisted Three-dimensional Reconstruction in Planning Thoracoscopic Segmentectomy].

BACKGROUND: The three-dimensional (3D) can assist in planning lung segmentectomy. 3D reconstruction software based on artificial intelligence algorithm is gradually applied in clinic. The aim of this study was to evaluate the accuracy and safety of 3D reconstruction assisted planning of thoracoscopic segmentectomy. METHODS: A total of 90 patients admitted to Department of Thoracic Surgery of Lanzhou University Second Hospital were evaluated for thoracoscopic segmentectomy. Before operation, artificial intelligence 3D reconstruction software was used to make 3D lung images and conduct preoperative planning. Surgical videos were saved during the operation and perioperative data were recorded. Video recordings of 38 patients were selected to explore the effectiveness of artificial intelligence 3D reconstruction for surgical planning. The results of artificial intelligence 3D reconstruction and Mimics 21 software reconstruction were compared with the actual results in the operation, and the detection and classification ability of bronchus and blood vessels of the two reconstruction methods were compared. RESULTS: All the 90 patients underwent artificial intelligence 3D reconstruction planning, including 57 patients (63.3%) with single lung segmentectomy and 33 patients (36.7%) with combined sub-segmentectomy. The accuracy of artificial intelligence 3D reconstruction for lesion localization was 100.0%, and the accuracy of computed tomography (CT) was 94.4% (85/90). The detection accuracy of artificial intelligence 3D reconstruction and Mimics 21 software was 92.1% (35/38) and 89.5% (34/38), and the anatomic typing accuracy was 89.5% (34/38) and 84.2% (32/38), and the total accuracy was 76.3% (29/38) and 71.1% (27/38). In the comparative observation of 38 surgical videos and reconstructed images, the consistent rates of target segment planning, surgical approach, artery dissection, vein dissection and bronchial dissection for preoperative planning using artificial intelligence 3D reconstruction were 92.1% (35/38), 92.1% (35/38), 89.5% (34/38), 86.8% (33/38) and 94.7% (36/38). The overall planning operational consistency rate was 68.4% (26/38). CONCLUSIONS: It is accurate and safe to use artificial intelligence 3D reconstruction to assist planning thoracoscopic segmentectomy.

[Exploration of the Perturbation of PKIG in Lung Squamous Cell Carcinoma and the Role in Tumor Microenvironment Based on Bioinformatics Method].

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and patients have limited survival benefits from traditional treatments such as surgery, radiotherapy and chemotherapy. As a new treatment for lung cancer, immunotherapy has significantly prolonged the overall survival (OS) of patients. However, only some patients can benefit from it. We need to explore immunotherapy biomarkers more deeply to screen for advantages. METHODS: The original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, and the immunological and prognostic genes of lung squamous cell carcinoma (LUSC) were screened using R software and TIMER database. The expression of target genes was studied in TCGA and GEO databases, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and correlation analysis with tumor immune characteristics were performed by R software and TISIDB database. RESULTS: We screened out a gene related to immunity and prognosis, cAMP dependent protein kinase inhibitor γ (PKIG), which is significantly differentially expressed in LUSC and normal tissues, and has important reference value for the diagnosis and prognosis assessment of LUSC. PKIG differential genes are mainly concentrated in the regulation of humoral immune response and other processes. The expression of PKIG was positively correlated with the infiltration level of regulatory T cells (Tregs) (r=0.340, P<0.001). In addition, the expression level of PKIG was positively correlated with the expression of chemokines/chemokine receptors such as chemokine C-C motif ligand 2 (CCL2) (r=0.503, P<0.001), CXC chemokine ligand 12 (CXCL12) (r=0.386, P<0.001) and CXC-chemokine receptor 4 (CXCR4) (r=0.492, P<0.001), and immunoinhibitors such as programmed cell death protein 1 (PDCD1) (r=0.359, P<0.001), cytotoxic T-lymphocyte associated antigen 4 (CTLA4) (r=0.375, P<0.001) and T cell immunoglobulin and ITIM domains (TIGIT) (r=0.305, P<0.001) in LUSC. CONCLUSIONS: The immunological and prognostic gene PKIG in lung squamous cell carcinoma was screened through bioinformatics analysis. PKIG is highly correlated with LUSC prognosis and immune microenvironment, and is expected to be a potential biomolecular marker for LUSC immunotherapy.

Evolution of High-Molecular-Mass Hyaluronic Acid is Associated with Subterranean Lifestyle.

Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) which plays an important role in development, cellular response to injury and inflammation, cell migration, and cancer. The naked mole-rat (NMR, Heterocephalus glaber ) contains abundant high-molecular-mass HA (HMM-HA) in its tissues, which contributes to this species' cancer resistance and possibly longevity. Here we report that abundant HMM-HA is found in a wide range of subterranean mammalian species, but not in phylogenetically related aboveground species. These species accumulate abundant HMM-HA by regulating the expression of genes involved in HA degradation and synthesis and contain unique mutations in these genes. The abundant high molecular weight HA may benefit the adaptation to subterranean environment by increasing skin elasticity and protecting from oxidative stress due to hypoxic subterranean environment. HMM-HA may also be coopted to confer cancer resistance and longevity to subterranean mammals. Our work suggests that HMM-HA has evolved with subterranean lifestyle.

Direct Multi-Material Reconstruction via Iterative Proximal Adaptive Descent for Spectral CT Imaging.

Spectral computed tomography (spectral CT) is a promising medical imaging technology because of its ability to provide information on material characterization and quantification. However, with an increasing number of basis materials, the nonlinearity of measurements causes difficulty in decomposition. In addition, noise amplification and beam hardening further reduce image quality. Thus, improving the accuracy of material decomposition while suppressing noise is pivotal for spectral CT imaging. This paper proposes a one-step multi-material reconstruction model as well as an iterative proximal adaptive decent method. In this approach, a proximal step and a descent step with adaptive step size are designed under the forward-backward splitting framework. The convergence analysis of the algorithm is further discussed according to the convexity of the optimization objective function. For simulation experiments with different noise levels, the peak signal-to-noise ratio (PSNR) obtained by the proposed method increases approximately 23 dB, 14 dB, and 4 dB compared to those of other algorithms. Magnified areas of thorax data further demonstrated that the proposed method has a better ability to preserve details in tissues, bones, and lungs. Numerical experiments verify that the proposed method efficiently reconstructed the material maps, and reduced noise and beam hardening artifacts compared with the state-of-the-art methods.

Short-term clinical outcomes and five-year survival analysis of laparoscopic-assisted transanal natural orifice specimen extraction versus conventional laparoscopic surgery for sigmoid and rectal cancer: a single-center retrospective study.

Background: The cosmetic benefits of natural orifice specimen extraction (NOSE) are easily noticeable, but its principles of aseptic and tumor-free procedure have caused controversy. Methods: We conducted a retrospective analysis of the clinical data of patients who underwent laparoscopic-assisted transanal NOSE or conventional laparoscopic surgery (CLS) for sigmoid and rectal cancer at our hospital between January 2018 and December 2018. The study aimed to compare the general characteristics, perioperative indicators, postoperative complications, and five-year follow-up results between the two groups. Results: A total of 121 eligible patients were enrolled, with 52 underwent laparoscopic-assisted transanal NOSE and 69 underwent CLS. There were no significant differences observed between the two groups in terms of gender, age, body mass index (BMI), TNM stage, etc. (P > 0.05). However, the NOSE group exhibited significantly shorter total incision length and longer operation time compared to the CLS group (P < 0.05). There were no statistically significant differences observed between the two groups in terms of positive rate of bacterial culture, incidence rates of intraabdominal infections or anastomotic leakage (P > 0.05). Furthermore, during follow-up period there was no statistically significant difference observed between these two groups concerning overall survival rate and disease-free survival outcomes (P > 0.05). Conclusions: The management of surgical complications in CLS is exemplary, with NOSE presenting a sole advantage in terms of incision length albeit at the cost of prolonged operative time. Therefore, NOSE may be deemed appropriate for patients who place high emphasis on postoperative cosmetic outcomes.

MTHFR Polymorphism and Folic Acid Supplementation Influence Serum Homocysteine Levels in Psoriatic Patients Treated with Methotrexate.

BACKGROUND: Hyperhomocysteinemia has been reported in psoriasis. We investigated the effect of methylenetetrahydrofolate reductase (MTHFR), polymorphism and folic acid supplementation on serum homocysteine levels in psoriasis. METHODS: Serum homocysteine levels were detected at baseline and at week 12 in 201 patients who were genotyped with MTHFR rs1801133 without and 93 psoriatic patients with folate supplement. RESULTS: TT genotype carriers of MTHFR rs1801133 had significantly higher serum homocysteine levels at baseline and at week 12, a better PASI 75 response rate at week 8, and a higher PASI 90 response rate at week 12 than the CT and CC genotype carriers. Multiple regression analysis demonstrated that serum homocysteine concentration at baseline was significantly associated with sex, weight, PASI score at baseline, and the rs1801133 genotype. The significant upregulation of serum homocysteine levels after treatment with methotrexate (MTX) was only observed in male CT and CC genotype carriers and female CC genotype carriers. In contrast, folic acid supplementation significantly decreased serum homocysteine levels after MTX treatment but only in male psoriatic patients. CONCLUSIONS: The effect of MTX on serum homocysteine levels was associated with the polymorphism of MTHFR rs1801133 and sex. Folic acid supplementation only decreased serum homocysteine levels in male psoriatic patients.

SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1.

SMYD2, as an oncogene, has been involved in multiple types of cancer, but the potential role of SMYD2 in gastrointestinal stromal tumors (GIST) remains enigmatic and requires further investigation. Hence, this study was conducted with the main objective of analyzing the effect of SMYD2 on GIST. GIST and adjacent normal tissues were collected from 46 patients with GIST where the expression of EZH2, SMYD2, and TET1 was determined, followed by the analysis of their interactions. The functional role of SMYD2 in cell biological functions was determined using a loss-of-function assay in GIST-T1 cells. Nude mouse xenograft experiments were performed to verify the role of the SMYD2/EZH2/TET1 axis in GIST in vivo. EZH2 was upregulated in GIST tissues and cell lines, which was positively correlated with SMYD2 expression and inversely correlated with TET1 expression in GIST tissues. EZH2 silencing due to SMYD2 inhibition reduced GIST-T1 cell proliferation and accelerated cell senescence. EZH2 repressed TET1 expression by promoting H3K27me3 methylation in the TET1 promoter region. TET1 inhibition reversed the effect of EZH2 silencing on the biological functions of GIST-T1 cells. In vivo data further revealed the promoting effect of SMYD2 on the progression of GIST by regulating the EZH2/TET1 axis. Overall, this study demonstrates that SMYD2 can increase EZH2 expression while suppressing TET1 expression, thus accelerating GIST, and creating new treatment opportunities for GIST.

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis.

Aims: To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population. Methods: This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed. Results: The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04). Conclusions: This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Sex-differential downregulation of methotrexate on plasma viscosity and whole blood viscosity in psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. CONCLUSION: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

[Clinical Study of Artificial Intelligence-assisted Diagnosis System in Predicting the 
Invasive Subtypes of Early-stage Lung Adenocarcinoma Appearing as Pulmonary Nodules].

BACKGROUND: Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early­stage lung adenocarcinoma appearing as pulmonary nodules. METHODS: Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed. RESULTS: In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively. CONCLUSIONS: Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early­stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.

Total variation combining nonlocal means filtration for image reconstruction in X-ray computed tomography.

BACKGROUND: Image reconstruction for realistic medical images under incomplete observation is still one of the core tasks for computed tomography (CT). However, the stair-case artifacts of Total variation (TV) based ones have restricted the usage of the reconstructed images. OBJECTIVE: This work aims to propose and test an accurate and efficient algorithm to improve reconstruction quality under the idea of synergy between local and nonlocal regularizations. METHODS: The total variation combining the nonlocal means filtration is proposed and the alternating direction method of multipliers is utilized to develop an efficient algorithm. The first order approximation of linear expansion at intermediate point is applied to overcome the computation of the huge CT system matrix. RESULTS: The proposed method improves root mean squared error by 25.6% compared to the recent block-matching sparsity regularization (BMSR) on simulation dataset of 19 views. The structure similarities of image of the new method is higher than 0.95, while that of BMSR is about 0.92. Moreover, on real rabbit dataset of 20 views, the peak signal-to-noise ratio (PSNR) of the new method is 36.84, while using other methods PSNR are lower than 35.81. CONCLUSIONS: The proposed method shows advantages on noise suppression and detail preservations over the competing algorithms used in CT image reconstruction.

Framelet tensor sparsity with block matching for spectral CT reconstruction.

PURPOSE: Spectral computed tomography (CT) based on the photon-counting detection system has the capability to produce energy-discriminative attenuation maps of objects with a single scan. However, the insufficiency of photons collected into the narrow energy bins results in high quantum noise levels causing low image quality. This work aims to improve spectral CT image quality by developing a novel regularization based on framelet tensor prior. METHODS: First, similar patches are extracted from highly correlated interchannel images in spectral and spatial domains, and stacked to form a third-order tensor after vectorization along the energy channels. Second, the framelet tensor nuclear norm (FTNN) is introduced and applied to construct the regularization to exploit the sparsity embedded in nonlocal similarity of spectral images, and thus the reconstruction problem is modeled as a constrained optimization. Third, an iterative algorithm is proposed by utilizing the alternating direction method of multipliers framework in which efficient solvers are developed for each subproblem. RESULTS: Both numerical simulations and real data verifications were performed to evaluate and validate the proposed FTNN-based method. Compared to the analytic, TV-based, and the state-of-the-art tensor-based methods, the proposed method achieves higher numerical accuracy on both reconstructed CT images and decomposed material maps in the mouse data indicating the capability in noise suppression and detail preservation of the proposed method. CONCLUSIONS: A framelet tensor sparsity-based iterative algorithm is proposed for spectral reconstruction. The qualitative and quantitative comparisons show a promising improvement of image quality, indicating its promising potential in spectral CT imaging.

Gene losses may contribute to subterranean adaptations in naked mole-rat and blind mole-rat.

BACKGROUND: Naked mole-rats (Heterocephalus glaber, NMRs) and blind mole-rats (Spalax galili, BMRs) are representative subterranean rodents that have evolved many extraordinary traits, including hypoxia tolerance, longevity, and cancer resistance. Although multiple candidate loci responsible for these traits have been uncovered by genomic studies, many of them are limited to functional changes to amino acid sequence and little is known about the contributions of other genetic events. To address this issue, we focused on gene losses (unitary pseudogenes) and systematically analyzed gene losses in NMRs and BMRs, aiming to elucidate the potential roles of pseudogenes in their adaptation to subterranean lifestyle. RESULTS: We obtained the pseudogene repertoires in NMRs and BMRs, as well as their respective aboveground relatives, guinea pigs and rats, on a genome-wide scale. As a result, 167, 139, 341, and 112 pseudogenes were identified in NMRs, BMRs, guinea pigs, and rats, respectively. Functional enrichment analysis identified 4 shared and 2 species-specific enriched functional groups (EFGs) in subterranean lineages. Notably, the pseudogenes in these EFGs might be associated with either regressive (e.g., visual system) or adaptive (e.g., altered DNA damage response) traits. In addition, several pseudogenes including TNNI3K and PDE5A might be associated with specific cardiac features observed in subterranean lineages. Interestingly, we observed 20 convergent gene losses in NMRs and BMRs. Given that the functional investigations of these genes are generally scarce, we provided functional evidence that independent loss of TRIM17 in NMRs and BMRs might be beneficial for neuronal survival under hypoxia, supporting the positive role of eliminating TRIM17 function in hypoxia adaptation. Our results also suggested that pseudogenes, together with positively selected genes, reinforced subterranean adaptations cooperatively. CONCLUSIONS: Our study provides new insights into the molecular underpinnings of subterranean adaptations and highlights the importance of gene losses in mammalian evolution.

The difference of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio.

BACKGROUND: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. OBJECTIVE: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). METHODS: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. RESULTS: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. CONCLUSION: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. TRIAL REGISTRATION: ChiCTR2000036192.

Transposon-triggered innate immune response confers cancer resistance to the blind mole rat.

Blind mole rats (BMRs) are small rodents, characterized by an exceptionally long lifespan (>21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). Cells and tissues of BMRs express very low levels of DNA methyltransferase 1. Following cell hyperplasia, the BMR genome DNA loses methylation, resulting in the activation of RTEs. Upregulated RTEs form cytoplasmic RNA-DNA hybrids, which activate the cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and humans. We propose that RTEs were co-opted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of the innate immune response. Activation of RTEs is a double-edged sword, serving as a tumor suppressor but contributing to aging in late life via the induction of sterile inflammation.