Gene associations of lipid traits, lipid-lowering drug-target genes and endometriosis.

RESEARCH QUESTION: Does the observed correlation between dyslipidaemia and endometriosis indicate a bidirectional causal association? DESIGN: Bidirectional Mendelian randomization was used to investigate the causal association between lipid traits and endometriosis. Drug-target Mendelian randomization was used to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets were significant, aggregate analyses, such as summary-data-based Mendelian randomization and colocalization methods, were introduced to validate the outcomes. Mediation analyses supplemented these evaluations. RESULTS: The bidirectional Mendelian randomization results suggested that genetically predicted triglyceride (OR 1.15, 95% CI 1.08-1.23), high-density lipoprotein cholesterol (OR 0.87, 95% CI 0.81-0.94), low-density lipoprotein cholesterol (OR 1.20, 95% CI 1.06-1.34) and apolipoprotein A (OR 0.90, 95% CI 0.83-0.96) concentrations were causally associated with endometriosis. Reverse Mendelian randomization results revealed that genetically proxied endometriosis was causally associated with triglyceride concentration (OR 1.02, 95% CI 1.01-1.02). In drug-target Mendelian randomization, genetic mimicry in proprotein convertase subtilisin/kexin type 9 (PCSK9) (OR 1.40, 95% CI 1.13-1.72), apolipoprotein B (APOB) (OR 1.49, 95% CI 1.21-1.86) and angiopoietin-related protein 3 (ANGPTL3) (OR 1.57, 95% CI 1.14-2.16) was significantly associated with the risk of endometriosis stages 1-2. CONCLUSION: There is a potential bidirectional causal association between endometriosis and dyslipidaemia. Genetic mimicry of PCSK9, APOB and ANGPTL3 is associated with the risk of early-stage endometriosis. The development of lipid-lowering drugs to treat endometriosis is of potential clinical interest.

Comparison of Alignment Accuracy and Clinical Outcomes between a CT-Based, Saw Cutting Robotic System and a CT-Free, Jig-guided Robotic System for Total Knee Arthroplasty.

OBJECTIVE: The different cutting mode of robot-assisted TKAs may influence the accuracy of alignment. The purpose of this study was to compare alignment accuracy and early clinical outcomes between a CT-based, saw cutting robotic system (MAKO) and a CT-free, jig-guided robotic system (ROSA) for total knee arthroplasty (TKA). METHODS: A total of 20 MAKO TKAs and 20 ROSA TKAs from June 2021 to June 2022 were retrospectively analyzed. Differences in the postoperative hip-knee-ankle (HKA) angle, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), posterior tibial slope (PTS) and 3° outlier frequency of the HKA, LDFA, MPTA and PTS were studied at 3 months and 1 year of follow-up. The operative time and total blood loss (TBL) were compared between these two groups. Clinical outcomes at 1 year after surgery, including range of motion (ROM), Western Ontario McMaster University Osteoarthritis Index (WOMAC) score, and Knee Society Score-2011 (KSS-2011), were also compared between these two groups. RESULTS: The baseline characteristics of the two groups were comparable. There were no significant differences in the mean deviations of postoperative HKA, LDFA, MPTA or PTS between the two groups at 3 months or 1 year (all ps > 0.05). Moreover, there was no significant difference in the percentage of 3° outliers for HKA, LDFA, MPTA, or PTS between the two groups at 3-month or 1-year follow-up (all ps > 0.05). The mean operation time of MAKO was longer than that of ROSA (112.7 ± 12.8 min vs 94.8 ± 23.0 min, p = 0.001), but the mean TBL (1356.7 ± 648.5 mL vs 1384.5 ± 676.3 mL) and transfusion rate (15.0% vs 5.0%) were not significantly different between the two groups (all ps > 0.05). No significant differences were found in postoperative ROM, WOMAC score or KSS score at 1 year (all ps > 0.05). CONCLUSION: The MAKO and ROSA had similar accuracy and precision in TKA alignment. The clinical outcomes at 1 year after surgery were also comparable.

Mutant p53 gains oncogenic functions through a chromosomal instability-induced cytosolic DNA response.

Inactivating TP53 mutations leads to a loss of function of p53, but can also often result in oncogenic gain-of-function (GOF) of mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities of TP53 mutations are well documented, but the mechanisms involved remain poorly understood. Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability (CIN), leading to a tumor cell-autonomous and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent cytosolic DNA response that activates downstream non-canonical nuclear factor kappa light chain enhancer of activated B cell (NC-NF-κB) signaling. Consequently, GOF mutp53-MCMs-CIN-cytosolic DNA-cGAS-STING-NC-NF-κB signaling promotes tumor cell metastasis and an immunosuppressive tumor microenvironment through antagonizing interferon signaling and regulating genes associated with pro-tumorigenic inflammation. Our findings have important implications for understanding not only the GOF activities of TP53 mutations but also the genome-guardian role of p53 and its inactivation during tumor development and progression.

Proteomics-based identification of proteins in tumor-derived exosomes as candidate biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death, with high morbidity worldwide. There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms. Exosomes are involved in intercellular communication and participate in multiple pathological processes, serving as an important part of the tumor microenvironment. AIM: To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC. METHODS: In this study, 10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited. We paired CRC tissues and adjacent normal intestinal tissues (> 5 cm) to form the experimental and control groups. Purified exosomes were extracted separately from each tissue sample. Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles, and differentially expressed proteins (DEPs) were screened by bioinformatics analysis. Promising exosomal proteins were verified using parallel reaction monitoring (PRM) analysis in 10 matched exosome samples. RESULTS: A total of 1393 proteins were identified in the CRC tissue group, 1304 proteins were identified in the adjacent tissue group, and 283 proteins were significantly differentially expressed between them. Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction, cell movement and migration, immune response, tumor growth and telomere metabolism, as well as ECM-receptor interaction, focal adhesion and mTOR signaling pathways. Six differentially expressed exosomal proteins (NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28) were validated by PRM analysis and evaluated by receiver operating characteristic curve (ROC) analysis. The area under the ROC curve was 0.93, 0.96, 0.97, 0.78, 0.75, and 0.88 (P < 0.05) for NHP2, OLFM4, TOP1, SAMP, TAGL, and TRIM28, respectively, indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues. CONCLUSION: In our study, comprehensive proteomic profiles were obtained for CRC tissue exosomes. Six exosomal proteins, NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28, may be promising diagnostic markers and effective therapeutic targets for CRC, but further experimental investigation is needed.

Observation of the efficacy of parathyroidectomy for secondary hyperparathyroidism in hemodialysis patients: a retrospective study.

PURPOSE: Parathyroidectomy (PTX) is commonly performed as a treatment for secondary hyperparathyroidism (SHPT) in patients with end-stage renal disease (ESRD). We aimed to evaluate the efficacy of PTX in patients with SHPT who underwent hemodialysis. METHODS: This retrospective study analyzed the clinical treatment of 80 hemodialysis patients with SHPT who underwent either total PTX with forearm auto transplantation (TPTX + AT) or subtotal parathyroidectomy (SPTX). We compared the changes in biochemical indices before and after surgery as well as the attenuation of intact parathyroid hormone (iPTH) in the TPTX and SPTX groups. We also evaluated clinical symptoms and quality of life using the Visual Analog Scale (VAS) and the Short Form-36 Questionnaire (SF-36) before and at 3, 6, and 12 months after surgery. RESULTS: Serum iPTH and serum phosphorus levels decreased significantly after surgery in 80 patients with SHPT (P < 0.05). Within one month of surgery, there was a difference in iPTH levels between the TPTX + AT and SPTH groups, but there was no difference over time. Patients experienced significant improvement in their clinical symptoms of restless leg syndrome, skin itching, bone pain, and joint pain at 1 week post operation (P < 0.001). Quality of life significantly improved after surgery, as assessed by SF-36 scores (P < 0.05). Hypocalcemia was the most common postoperative complication, occurring in 35% of patients. Within the first 12 months post surgery, 5 patients had a recurrence. CONCLUSION: PTX is effective in rapidly reducing iPTH levels, improving calcium and phosphorus metabolism disorders, and enhancing patients' quality of life by safely and effectively relieving clinical symptoms.

Kidney damage on fertility and pregnancy: A Mendelian randomization.

BACKGROUND: Low fertility and adverse pregnancy outcomes are commonly observed in women with chronic kidney disease (CKD). However, a causal relationship between low fertility and adverse pregnancy outcomes with CKD remains unclear. Besides, whether mild kidney dysfunction can affect fertility and pregnancy still needs exploration. Hence, this study aimed to investigate the causal effect of kidney damage on fertility and pregnancy using Mendelian randomization (MR). METHODS: We first used two-sample MR to examine the effects of kidney damage on fertility and pregnancy. Next, we introduced the Bayesian model averaging MR analysis to detect major causal relationships and render the results robust. The genetic instruments and outcome data were derived from various large genome-wide association studies. RESULTS: Adverse pregnancy outcomes: Our analyses supported a suggestive causal effect of CKD and estimated glomerular filtration rate (eGFR) rapid on stillbirth, with CKD having an odds ratio (OR) of 1.020 [95% confidence interval (CI) 1.002 to 1.038] and eGFR rapid having an OR of 1.026 (95% CI 1.004-1.048). We also discovered a suggestive causal effect of eGFR on spontaneous abortion, with an OR of 2.63 (95% CI 1.269 to 5.450). Moreover, increased urinary albumin-to-creatinine ratio (UACR) was regarded as a potential risk factor for pre-eclampsia (OR = 1.936; 95% CI 1.065 to 3.517) and gestational hypertension (OR = 1.700; 95% CI 1.002 to 2.886). Fertility assessment: The results indicated that eGFR and UACR had a suggestive causal relationship with the anti-Müllerian hormone level (eGFR beta: 1.004; UACR beta: 0.405). CONCLUSIONS: Our study used MR to demonstrate a suggestive causal relationship between kidney damage and fertility and pregnancy. We reported that mild kidney dysfunction might be a risk factor for reduced fertility and adverse pregnancy outcomes. Dynamic renal detection may help preserve fertility and reduce the risk of pregnancy loss.

Change-Point Detection for Multi-Way Tensor-Based Frameworks.

Graph-based change-point detection methods are often applied due to their advantages for using high-dimensional data. Most applications focus on extracting effective information of objects while ignoring their main features. However, in some applications, one may be interested in detecting objects with different features, such as color. Therefore, we propose a general graph-based change-point detection method under the multi-way tensor framework, aimed at detecting objects with different features that change in the distribution of one or more slices. Furthermore, considering that recorded tensor sequences may be vulnerable to natural disturbances, such as lighting in images or videos, we propose an improved method incorporating histogram equalization techniques to improve detection efficiency. Finally, through simulations and real data analysis, we show that the proposed methods achieve higher efficiency in detecting change-points.

Demographic and radiographic factors for knee symptoms and range of motion in patients with knee osteoarthritis: a cross-sectional study in Beijing, China.

BACKGROUND: Knee osteoarthritis (KOA) causes not only pain, stiffness, and dysfunction of the knee, but also the reduction of the joint range of motion (ROM). This study explored the demographic and radiographic factors for knee symptoms and ROM in patients with symptomatic KOA. METHODS: The demographic variables, Kellgren-Lawrence (KL) grade, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of patients with symptomatic KOA recruited in Beijing were collected. The knee ROM of all patients were also measured. We analyzed the influencing factors for WOMAC and ROM using a generalize linear model, respectively. RESULTS: This study included a total of 2034 patients with symptomatic KOA, including 530 males (26.1%) and 1504 females (73.0%), with a mean age of 59.17 (± 10.22) years. Patients with advanced age, overweight or obesity, a family history of KOA, a moderate-to-heavy manual labor job and use of nonsteroidal anti-inflammatory drugs (NSAIDs) had significantly higher WOMAC and lower ROM (all P < 0.05). The more the comorbidities, the higher the WOMAC (all P < 0.05). Patients with higher education had better ROM than those with only an elementary education(ß = 4.905, P < 0.05). Compared with those KL = 0/1, the WOMAC of patients whose KL = 4 were higher (ß = 0.069, P < 0.05), but the WOMAC of those KL = 2 were lower (ß = -0.068, P < 0.05). ROM decreased with the increase of KL grade (all P < 0.05). CONCLUSIONS: KOA patients with advanced age, overweight or obesity, a family history of KOA in first-degree relatives, a moderate-to-heavy manual labor job tended to have more severe clinical symptoms and worse ROM. Patients with more severe imaging lesions tend to have poorer ROM. Symptom management measures and regular ROM screening should be taken early to these people.

microRNA-627-5p inhibits colorectal cancer cell proliferation, migration and invasion by targeting Wnt2.

BACKGROUND: microRNA-627-5p (miR-627-5p) dysregulation has been observed in several cancer types, such as hepatocellular carcinoma, oral squamous cell carcinoma, glioblastoma multiforme, and gastric cancer. The biological function of miR-627-5p in colorectal cancer (CRC) growth and metastasis is yet unclear. AIM: To investigate the effects of miR-627-5p on the malignant biological properties of colorectal malignant tumour cells by targeting Wnt2. METHODS: The levels of miR-627-5p in colorectal tumour tissues were assessed in Gene Expression Omnibus datasets. In order to identify Wnt2 transcript expression in CRC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used. Luciferase reporter tests were used to explore whether miR-627-5p might potentially target Wnt2. Wnt2 transcript and protein levels were detected in CRC cells with high miR-627-5p expression. To learn more about how miR-627-5p affects CRC development, migration, apoptosis, and invasion, functional experiments were conducted. Cotransfection with the overexpression vector of Wnt2 and miR-627-5p mimics was utilized to verify whether overexpression of Wnt2 could cancel the impact of miR-627-5p in CRC. Western blot and qRT-PCR were conducted to investigate the effects of miR-627-5p on the Wnt/ß-catenin signalling pathway. RESULTS: miR-627-5p was notably decreased in colorectal tumour tissues, while the gene level of Wnt2 was notably upregulated. A dual luciferase reporter assay revealed that miR-627-5p specifically targets the 3'-untranslated regions of Wnt2 and miR-627-5p upregulation markedly reduced the protein and gene expression of Wnt2 in CRC cells. In vitro gain-of-function assays displayed that miR-627-5p overexpression decreased CRC cells' capabilities to invade, move, and remain viable while increasing apoptosis. Wnt2 overexpression could reverse the suppressive functions of miR-627-5p. Moreover, upregulation of miR-627-5p suppressed the transcript and protein levels of the downstream target factors in the canonical Wnt/ß-catenin signalling, such as c-myc, CD44, ß-catenin, and cyclinD1. CONCLUSION: miR-627-5p acts as a critical inhibitory factor in CRC, possibly by directly targeting Wnt2 and negatively modulating the Wnt/ß-catenin signalling, revealing that miR-627-5p could be a possible treatment target for CRC.

Research focus and theme trend on fulminant myocarditis: A bibliometric analysis.

Aims: This study intends to explore the research focus and trends of fulminant myocarditis (FM) to have a better understanding of the topic. Materials and methods: The data were downloaded from the Web of Science (WoS) database using the topic (TS) advanced search strategy. Many instruments were used to extract, analyze, and visualize the data, such as Microsoft Excel, HistCite Pro, GunnMap, BibExcel, and VOSviewer. Results: From 1985 to 2022, 726 documents were indexed in the WoS. The United States and Columbia University were the most productive country and institutions. Keywords co-occurrence was carried out and four research themes were identified. In addition, the top three prolific authors, the first three highly cited authors, and the core authors of the author co-citation network were identified. The topics that they kept an eye on were analyzed, and the research areas of key authors were similar to the results of keyword co-occurrence. The hot topics of FM were related to the mechanical circulatory support, etiology, diagnosis, and the disease or therapy associated with FM. Conclusion: This study carried out a systematic analysis of the documents related to FM from 1985 to 2022, which can provide a guideline for researchers to understand the theme trend to promote future research to be carried out.

Comprehensive proteomic signature and identification of CDKN2A as a promising prognostic biomarker and therapeutic target of colorectal cancer.

BACKGROUND: The carcinogenesis of colorectal cancer (CRC) involves many different molecules and multiple pathways, and the specific mechanism has not been elucidated until now. Existing studies on the proteomic signature profiles of CRC are relatively limited. Therefore, we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues. AIM: To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC. METHODS: Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021. Data independent acquisition (DIA) quantitative proteomic analysis was performed using high-performance liquid chromatography-mass spectrometry/mass spectrometry (nano-UHPLC-MS/MS) to identify differentially expressed proteins, among which those with a P adj value (t test, BH correction) < 0.05 and an absolute fold change (|log2FC|) > 2 were identified as potential markers. Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays, and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC. RESULTS: Significantly differential protein expression was observed between cancer tissues and normal tissues. Compared with normal tissues, 1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj < 0.05 and |log2FC| > 2, and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis, including ribosome biogenesis in eukaryotes, focal adhesion, extracellular matrix-receptor interactions and other tumor metabolism processes. Moreover, cyclin-dependent kinase inhibitor 2A (CDKN2A) expression was markedly upregulated in CRC, as validated by immunohistochemistry (0.228 vs 0.364, P = 0.0044), and was significantly enriched in tumor proliferation and signal transduction pathways such as the cell cycle and p53 signaling pathways. High CDKN2A expression was significantly correlated with poor prognosis (P = 0.021). These results demonstrated that CDKN2A functions as a driver of CRC. CONCLUSION: Our study provides a comprehensive proteomic signature of CRC and highlights CDKN2A as a potential powerful prognostic marker and precision therapeutic target.

Catalpol attenuates polycystic ovarian syndrome by regulating sirtuin 1 mediated NF-κB signaling pathway.

Oxidative stress plays a central role in polycystic ovary syndrome (PCOS). Catalpol (CAT) is the active ingredient of Rehmannia glutinosa Libosch which has therapeutic effect on PCOS. However, little is known about the mechanism of CAT in PCOS. PCOS rats were induced by subcutaneous injection of dehydroepiandrosteronec for four weeks and then were treated with CAT (50 mg/kg) or carboxyl methyl cellulose (the solvent of CAT) or normal saline for another 4 weeks. Histopathological observation of ovarian tissues, the levels of testosterone, estradiol and progesterone in rat plasma samples, the oxidative stress related-indexes and the expressions of NF-κB pathway-related proteins were determined. KGN cell (human ovarian granulosa cell line) was used as PCOS cell model and was transfected with siSIRT1 in the presence of CAT. The viability, proliferation and apoptosis of cells and the levels of SIRT1 and NF-κB pathway-related proteins were measured. CAT lessened the anthropometric indices and improved ovarian damage in PCOS model rats, and reduced the levels of testosterone, estradiol, progesterone and MDA, increased GSH content, and elevated the activities of catalase, GSH-Px and SOD in ovarian tissues of PCOS model rats. CAT up-regulated SIRT1 level and inhibited the activation of NF-κB signaling pathway in PCOS rat model and KGN cells. Silencing SIRT1 increased the viability and proliferation, whilst decreased the apoptosis of CAT-treated KGN cells. Silencing SIRT1 counteracted the effect of CAT on the level of oxidative stress-related factors and NF-κB signaling pathway in KGN cells. CAT attenuated PCOS by regulating SIRT1 mediated NF-κB signaling pathway.

Associations of Musical Activities and Positive Affect With Fear of Childbirth: A Structural Equation Modeling Approach.

Background: Fear of childbirth is a prevalent issue among women, with a wide range of interventions to dispel it. Here we explored a novel and beneficial intervention and one possible influence mechanism of it. Methods: The cross-sectional study recruited 1,053 pregnant women from one tertiary-grade A class hospital between March to August 2021. The questionnaire included demographic characteristics, a self-made musical activities questionnaire, the Positive affect subscale, and the Childbirth Attitudes Questionnaire. We parceled the eight musical activities into three items by item parceling methodology. The associations of musical activities and positive affect with fear of childbirth were evaluated by a structural equation modeling approach. Results: Our analyses demonstrated the effectiveness of musical activities, which was notably correlated with the increase in positive affect (ß = 0.309, P < 0.01). On the contrary, positive affect predicted a decrease in fear of childbirth (ß = -0.085, P = 0.019). Additionally, positive affect mediated the effect of musical activities on fear of childbirth (ß = -0.026, P = 0.030). However, the direct effect of musical activities on fear of childbirth was not found (ß = 0.029, P = 0.514). Conclusions: Relying on musical activities alone may not be adequate to alleviate the fear of childbirth, and positive affect played a pivotal role between musical activities and fear of childbirth. The results showed that musical activities would be an effective non-pharmaceutical way to alleviate the fear of childbirth and positive affect can not be ignorant in future childbirth fear reduction programs.

Circulating miR-627-5p and miR-199a-5p are promising diagnostic biomarkers of colorectal neoplasia.

BACKGROUND: Early detection of colorectal neoplasms, including colorectal cancers (CRCs) and advanced colorectal adenomas (AAs), is crucial to improve patient survival. Circulating microRNAs (miRNAs) in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers, but their potential for screening colorectal neoplasms remains ambiguous. AIM: To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms. METHODS: The study was divided into three phases: (1) Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods; (2) an independent set of serum samples from 60 CRC patients, 60 AA patients and 30 healthy controls (HCs) was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs, and their diagnostic power was detected by receiver operating characteristic (ROC) analysis; and (3) the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues. RESULTS: Based on bioinformatics analysis, miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study. Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs. The diagnostic power of miR-672-5p yielded an area under the curve (AUC) value of 0.90, and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs. A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA. Additionally, the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines, suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived. Furthermore, in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells. CONCLUSION: Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.

DFT Investigations of Aun Nano-Clusters Supported on TiO2 Nanotubes: Structures and Electronic Properties.

TiO2 nanotubes (TiO2NTs) are beneficial for photogenerated electron separation in photocatalysis. In order to improve the utilization rate of TiO2NTs in the visible light region, an effective method is to use Aun cluster deposition-modified TiO2NTs. It is of great significance to investigate the mechanism of Aun clusters supported on TiO2NTs to strengthen its visible-light response. In this work, the structures, electronic properties, Mulliken atomic charge, density of states, band structure, and deformation density of Aun (n = 1, 8, 13) clusters supported on TiO2NTs were investigated by DMOL3. Based on published research results, the most stable adsorption configurations of Aun (n = 1, 8, 13) clusters supported with TiO2NTs were obtained. The adsorption energy increased as the number of Au adatoms increased linearly. The Aun clusters supported on TiO2NTs carry a negative charge. The band gaps of the three most stable structures of each adsorption system decreased compared to TiO2NTs; the valence top and the conduction bottom of the Fermi level come mainly from the contribution of 5d and 6s-Au. The electronic properties of the 5d and 6s impurity orbitals cause valence widening and band gap narrowing.

Identification of circ_0000375 and circ_0011536 as novel diagnostic biomarkers of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) imposes a tremendous burden on human health, with high morbidity and mortality. Circular ribonucleic acids (circRNAs), a new type of noncoding RNA, are considered to participate in cancer pathogenesis as microRNA (miRNA) sponges. However, the dysregulation and biological functions of circRNAs in CRC remain to be explored. AIM: To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis. METHODS: CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus (GEO) database. Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates. Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues, serums and cell lines. Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs. Then, functional experiments, including cell counting kit-8, wound healing and Transwell invasion assays, were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines. Furthermore, candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis. The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets. A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs. Based on the target miRNAs and downstream genes, functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis. RESULTS: Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095, clinical CRC tissue and serum samples and CRC cell lines. The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum, respectively. Moreover, the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery, suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis. Circ_0000375 and circ_0011536 overexpression inhibited the proliferation, migration and invasion of CRC cells. Furthermore, miR-1182 and miR-1246, which were overexpressed in CRC tissues in GSE41655, GSE49246 and GSE115513, were verified as target miRNAs of circ_0000375 and circ_0011536, respectively, by luciferase reporter assays. The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways, such as the Wnt signaling pathway. CONCLUSION: Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression, serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.

Modified Medial Collateral Ligament Indentation Technique in Total Knee Arthroplasty with Severe Type II Valgus Deformity.

OBJECTIVE: To explore the feasibility and clinical efficacy of a modified medial collateral ligament indentation technique in total knee arthroplasty (TKA) with severe type II valgus deformity. METHODS: Consecutive patients with Krackow type II valgus deformity >20° who underwent a primary unilateral TKA between May 2008 and June 2017 were studied retrospectively. A medial collateral ligament indentation technique was performed in 20 patients (MCLI group), and 23 patients received the routine lateral structures release technique (LSR group). Radiological parameters, such as the valgus angle (VA), and functional outcomes including the use of constraint implants, Knee Society Score (KSS), Knee Society Function score (KSF), and thickness of the polyethylene insert were compared between the two groups. RESULTS: A total of 43 consecutive patients had a minimum 2-year follow-up. The preoperative VA was comparable between the MCLI (23.5° ± 5.8°) and LSR groups (21.3° ± 3.2°, P = 0.134), as was the postoperative VA (1.1° ± 2.1° and 2.5° ± 3.0°, respectively, P = 0.084). The mean KSS and KSF scores in the MCLI group were 30.2 ± 4.8 and 38.8 ± 4.8, respectively, before surgery, and they increased to 91.3 ± 2.6 and 86.5 ± 2.4 at the last follow-up. The scores in the LSR group were 31.5 ± 7.5 and 36.5 ± 7.8 before surgery and 92.4 ± 3.5 and 88.5 ± 3.6 at the last follow-up. While no statistically significant differences in pre- or postoperative functional scores were found between the two groups, the MCLI group had thinner polyethylene inserts (9.5 ± 1.1 mm vs 12.9 ± 1.5 mm) and less use of constrained condylar inserts (15% vs 69.6%). During follow-up, the MCLI group had fewer complications. CONCLUSION: A modified MCLI technique can achieve good outcomes in TKA with type II valgus deformity of >20°. It can maintain a normal joint line level, reduce the use of constrained condylar knee prostheses, and is a reliable choice for severe genu valgum.

Drivers' Decelerating Behaviors in Expressway Accident Segments under Different Speed Limit Schemes.

Traffic accidents occurring on expressways tend to give rise to traffic bottlenecks. To ensure the vehicles safely and smoothly pass through the accident segments, speed limits are generally taken to regulate the vehicles' movements. This study aims to explore the decelerating behaviors of drivers under different speed limit schemes. We designed traffic accident scenarios under four speed limit schemes using the driving simulator. A total of 60 subjects drove the simulator passing the accident segments according to their habits. The vehicles' kinematic data and the subjects' operating data were recorded. To further analyze the drivers' decelerating behaviors in different speed limit scenarios, driving experience was also taken into account. The results show that the speed limit schemes have significant effects on drivers' decelerating behaviors. The more speed limit signs there are, the smoother the decelerating process will be. Driving experience significantly affects some of the decelerating parameters, including the location of deceleration starting point, average deceleration, and locations of decelerating to the initial and final speed limits. These results provide a theoretical basis for traffic safety and driving behavior management.

Runtime verification in uncertain environment based on probabilistic model learning.

Runtime verification (RV) is a lightweight approach to detecting temporal errors of system at runtime. It confines the verification on observed trajectory which avoids state explosion problem. To predict the future violation, some work proposed the predictive RV which uses the information from models or static analysis. But for software whose models and codes cannot be obtained, or systems running under uncertain environment, these predictive methods cannot take effect. Meanwhile, RV in general takes multi-valued logic as the specification languages, for example the true, false and inconclusive in three-valued semantics. They cannot give accurate quantitative description of correctness when inconclusive is encountered. We in this paper present a RV method which learns probabilistic model of system and environment from history traces and then generates probabilistic runtime monitor to quantitatively predict the satisfaction of temporal property at each runtime state. In this approach, Hidden Markov Model (HMM) is firstly learned and then transformed to Discrete Time Markov Chain (DTMC). To construct incremental monitor, the monitored LTL property is translated into Deterministic Rabin Automaton (DRA). The final probabilistic monitor is obtained by generating the product of DTMC and DRA, and computing the probabilities for each state. With such a method, one can give early warning once the probability of correctness is lower than a pre-defined threshold, and have the chance to do adjustment in advance. The method has been implemented and experimented on real UAS (Unmanned Aerial Vehicle) simulation platform.

Research on the Hot Deformation Behavior of the Casting NiTi Alloy.

The hot deformation behavior and processing maps of the casting NiTi alloy were studied at the deformation temperature of 650-1050 °C and the strain rate of 5 × 10-3-1 s-1 by Gleeble-3800 thermal simulating tester. The variation of the strain rate sensitivity exponent m and the activation energy Q under different deformation conditions (T = 650-1050 °C, ε˙ = 0.005-1 s-1) were obtained. The formability of the NiTi alloy was the best from 800 °C to 950 °C. The constitutive equation of the casting NiTi alloy was constructed by the Arrhenius model. The processing map of the casting NiTi alloy was plotted according to the dynamic material model (DMM) based on the Prasad instability criterion. The optimal processing areas were at 800-950 °C and 0.005-0.05 s-1. The microstructure of the casting NiTi alloy was analyzed by TEM, SEM and EBSD. The softening mechanisms of the casting NiTi alloy were mainly dynamic recrystallization of the Ti2Ni phase and the nucleation and growth of fine martensite.