Application of machine learning for high-throughput tumor marker screening.

High-throughput sequencing and multiomics technologies have allowed increasing numbers of biomarkers to be mined and used for disease diagnosis, risk stratification, efficacy assessment, and prognosis prediction. However, the large number and complexity of tumor markers make screening them a substantial challenge. Machine learning (ML) offers new and effective ways to solve the screening problem. ML goes beyond mere data processing and is instrumental in recognizing intricate patterns within data. ML also has a crucial role in modeling dynamic changes associated with diseases. Used together, ML techniques have been included in automatic pipelines for tumor marker screening, thereby enhancing the efficiency and accuracy of the screening process. In this review, we discuss the general processes and common ML algorithms, and highlight recent applications of ML in tumor marker screening of genomic, transcriptomic, proteomic, and metabolomic data of patients with various types of cancers. Finally, the challenges and future prospects of the application of ML in tumor therapy are discussed.

Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis.

BACKGROUND: Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. METHODS: The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. RESULTS: ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e-6). CONCLUSIONS: Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9.

TRIM3 inhibits colorectal cancer cell migration and lipid droplet formation by promoting FABP4 degradation.

This study is to investigate the regulation of TRIM3/FABP4 on colorectal cancer (CRC) cell migration and lipid metabolism. After transfection of HCT116, LoVo, or SW480 cells, the expression of FABP4, TRIM3, N-cadherin, Vimentin, E-cadherin, and lipid droplet (LD) formation-related genes was measured by qRT-PCR or western blot assays. Wound healing and Transwell assays were applied to detect CRC cell migration and invasion abilities. The levels of triglyceride (TG) and total cholesterol (TC) were measured and the formation of LDs was observed. Additionally, the relationship between FABP4 and TRIM3 was confirmed by Co-IP and ubiquitination assays. Furthermore, a liver metastasis model of CRC was established to explore the effect of FABP4 on CRC tumor metastasis in vivo. FABP4 was upregulated in CRC cells. Downregulation of FABP4 or upregulation of TRIM3 resulted in repressed cell migration and invasion, decreased TG and TC levels, and reduced numbers of LDs. In nude mice, knockdown of FABP4 reduced metastatic nodules in the liver. Mechanistically, TRIM3 combined FABP4 and decreased its protein expression by ubiquitination. Overexpressed FABP4 reversed the influence of TRIM3 upregulation on CRC cell migration and LD formation. In conclusion, underexpressed TRIM3 suppressed FABP4 ubiquitination and accelerated CRC cell migration and LD formation.

Current status of research on emergency surgery score in trauma patients: a bibliometric analysis.

Background: The use of a relevant emergency score can provide an accurate assessment of the patient's condition and prognosis. However, the status of related studies remains unclear. The current study analyzed the research status of emergency surgery score (ESS) of trauma patients by using bibliometric methods. Methods: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection (WOSCC) was searched using keywords "trauma" and "emergency surgery score". All records from the search results and cited references were exported to Excel, duplicate literature records were removed, information for the same author and organization in different signature forms were merged. The resulting literatures were analyzed by year of publication, citation, discipline, countries and research institutions, journals, authors, and use of keywords. The cooperation among countries, institutions, and authors was also examined. Results: A total of 2,175 document were retrieved. The number of published literature and the number of citations per year increased annually. The number of published documents (n=1,029) and research cooperation (centrality score, 0.44) in the United States were significantly ahead of those in other countries. The ten research institutions with the largest number of published documents were all from the United States, with much cooperation between research institutions and authors. There were many publications from China (n=108), but with few cooperations (centrality score, 0.22). The journals with the largest number of published articles were professional in the fields of trauma, emergency, and critical care. Keyword analysis showed that infection and shock were important issues besides surgery in the research related to ESS of trauma patients. Conclusions: Research related to ESS of trauma patients has been mainly conducted in the United States, and Chinese researchers should increase their level of cooperation.

Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.

Kruppel-like factor 5 enhances proliferation, lipid droplet formation and oxaliplatin resistance in colorectal cancer by promoting fatty acid binding protein 6 transcription.

Oxaliplatin (OXA) is a standard agent for colorectal cancer (CRC) adjuvant chemotherapy. However, acquired and intrinsic OXA resistance is a primary challenge for CRC treatment. This study investigates the function of the Kruppel-like factor 5/fatty acid binding proteins 6 (KLF5/FABP6) axis in CRC proliferation, lipid droplet formation and OXA resistance. OXA-resistant CRC cell lines were constructed, and FABP6 and KLF5 expression was assessed in parental and OXA-resistant CRC cells. Subsequent to gain- and loss-of-function experiments, CRC cell proliferation was assessed by cell counting kit-8 (CCK-8) and clone formation assays, the intracellular lipid synthesis by oil red O staining and the protein expression of lipid metabolism genes by western blot. OXA resistance of CRC cells was assessed by CCK-8 assay. The binding of KLF5 to FABP6 was analyzed by the dual-luciferase reporter and ChIP assays. A tumorigenicity assay in nude mice was adopted to examine the impact of KLF5 on CRC tumor growth and OXA resistance in vivo . FABP6 and KLF5 expression was high in CRC cell lines. Downregulation of FABP6 or KLF5 restrained CRC cell proliferation and lipid droplet formation in vitro . FABP6 and KLF5 expression was elevated in OXA-resistant CRC cells. Downregulation of FABP6 or KLF5 repressed the OXA resistance of OXA-resistant CRC cells. Mechanistically, KLF5 facilitated the transcription of FABP6. FABP6 overexpression counteracted the suppressive effects of KLF5 downregulation on CRC cell growth, lipid droplet formation and OXA resistance. KLF5 downregulation restrained CRC tumor growth and OXA resistance in vivo . In conclusion, KLF5 knockdown reduced FABP6 transcription to protect against proliferation, lipid droplet formation and OXA resistance in CRC.

Surface adsorbed and lattice oxygen activated by the CeO2/Co3O4 interface for enhancive catalytic soot combustion: Experimental and theoretical investigations.

Metal oxide-oxide interface on supported catalyst has been rarely studied due to the complex interfacial structure and synthetic challenge. Herein, different Ag-supported CeO2/Co3O4 samples with various covered-state of CeO2 were prepared for catalytic soot oxidation. In comparison, catalytic activity was significantly improved by grafting CeO2 on Co3O4, in which the best performing Ag/CoCe-2 exhibited remarkable catalytic performance towards soot oxidation with a T50 of 290.5 â„ƒ under 10 % O2/N2. Catalyst characterization investigated by Scanning Electron Microscope (SEM), quasi in-situ X-ray Photoelectron Spectroscopy (XPS), in-situ Raman, etc. revealed that this outstanding promotion in catalytic activity can be principally ascribed to the formation of the CeO2/Co3O4 interface. An appropriate CeO2 dosage maximized the contact and interaction between Co3O4 and CeO2, resulting in the largest CeO2/Co3O4 interface featured with abundant generated superoxide species and activated surface lattice oxygen. Density functional theory (DFT) calculations were also carried out for the oxygen vacancy formation energy, Gibbs free energy, etc. In presence of the CeO2/Co3O4 interface, a charge density redistribution around the adsorbed reactants at oxygen vacancies could be formed, owing to the efficient charge transfer enhanced by the electron-appealing effect. The change in electronic structure favored reducing the oxygen vacancy formation energy and boosting the lattice oxygen activation induced by the hybridized Co-O-Ce bonds, finally lowering the adsorption and activation barriers for reactive species and accelerating the reaction kinetics.

Comprehensive Analysis of Ferroptosis- and Immune-Related Signatures to Improve the Prognosis and Diagnosis of Kidney Renal Clear Cell Carcinoma.

Background: Almost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC. Methods: ChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)-related biomarkers. Results: We finally identified five FI biomarkers (CCR4, CMTM3, IFITM1, MX2, and NR3C2) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors. Conclusion: Our present study suggested that these five FI-DEGs (CCR4, CMTM3, IFITM1, MX2, and NR3C2) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them.

Functionalized dual modification of covalent organic framework for efficient and rapid trace heavy metals removal from drinking water.

A key challenge in trace heavy metals removal from drinking water by adsorption technology is to achieve high adsorption capacity and rapid uptake speed of adsorbent. Herein, we report a functionalized double modified covalent organic framework (DMTD-COF-SH) bearing high-density sulfur and nitrogen chelating groups provided simultaneously by 2,5-dimercapto-1,3,4-thiadiazole (DMTD) and 1,2-ethanedithiol, which was prepared via a facile one-pot thiol-ene "click" reaction. PXRD, FTIR, XPS, SEM, BET and 13C MAS NMR confirmed their successful graft, and DMTD was found to be more easily grafted on the COF surface layer than 1,2-ethanedithiol. The as-prepared DMTD-COF-SH showed remarkable adsorption capacity and ultrafast uptake dynamics to trace heavy metals owing to the synergistic effects resulting from densely populated sulfur and nitrogen chelating groups within ordered COF mesopores and at the COF surface. On the basis of the drinking water treatment units standard NSF/ANSI 53-2020, when the adsorbent dosage was 10 mg/30 mL and 20 mg L-1 calcium ions coexisted, the lead concentration decreased from initial 150 µg L-1 to 2.89 µg L-1 within 10 s, far below the allowable limit of world health organization (WHO) drinking water standard (10 µg L-1), and the maximum adsorption capacity meeting the standard attained 14.22 mg g-1. The adsorbent also exhibited excellent stability, wide applicable pH range and outstanding adsorption performance for coexisting trace lead, mercury, cadmium, chromium (VI) and copper in tap water, indicating that the DMTD-COF-SH material has excellent application prospect for trace heavy metals removal from drinking water.

Association between air particulate matter pollution and blood cell counts of women preparing for pregnancy: Baseline analysis of a national birth cohort in China.

BACKGROUND: Limited evidence is known about whether long-term exposures to air borne particulate matters of 2.5 µm or less (PM2.5) impact human hematologic index for women preparing for pregnancy. No study assessed the effect of PM1, which is small enough to reach the blood circulation. OBJECTIVE: To evaluate whether exposure to PM1 and PM2.5 is associated with blood cell count of woman preparing for pregnancy. METHOD: Based on the baseline data of a national birth cohort in China, we analysed the white blood cell (WBC), red blood cells (RBC) and thrombocyte counts of 1,203,565 women who are aged 18-45 years, being Han ethnicity, had no chronic disease and preparing for pregnancy. We matched their home addresses and examination date with daily concentrations of PM1 and PM2.5 which were estimated by a machine learning method with remote sensing, meteorological and land use information. Generalized additive mixed model to examine the associations between exposure to one-year average exposure to PMs prior to the health examination and the blood cells counts, after adjustment for potential individual variables. RESULTS: A 10 µg/m3 PM1 increment was associated with -1.49% (95%CI: 1.56%, -1.42%) difference in WBC count; with 0.33% (95%CI: 0.30%, 0.36%) difference of RBC count; and with 1.08% (95%CI: 1.01%, 1.15%) difference of thrombocyte count. For PM2.5, the corresponding difference was -0.47% (95%CI: 0.54%, -0.39%) for WBC; was 0.06% (95%CI: 0.03%, 0.09%) for RBC; and was 1.10% (95%CI: 1.02%, 1.18%) for thrombocyte. Women working as workers, being overweight and with tobacco smoking exposure had higher associations between PMs and hematologic index than their counterparts (p < 0.05 for interaction test). CONCLUSION: Long-term exposure to PMs were associated with decrement in WBC, as well as increment in RBC and thrombocytes among Han Chinese women preparing for pregnancy. Measures such as using air purifiers and wearing a mask in polluted areas should be improved to prevent women from the impact of PMs.

Role of IL-6-IL-27 Complex in Host Antiviral Immune Response.

The IL family of cytokines participates in immune response and regulation. We previously found that soluble IL-6 receptor plays an important role in the host antiviral response. In this study, we detected the IL-6-IL-27 complex in serum and throat swab samples from patients infected with influenza A virus. A plasmid expressing the IL-6-IL-27 complex was constructed to explore its biological function. The results indicated that the IL-6-IL-27 complex has a stronger antiviral effect than the individual subunits of IL-6, IL-27A, and EBV-induced gene 3. Furthermore, the activity of the IL-6-IL-27 complex is mainly mediated by the IL-27A subunit and the IL-27 receptor α. The IL-6-IL-27 complex can positively regulate virus-triggered expression of IFN and IFN-stimulated genes by interacting with adaptor protein mitochondrial antiviral signaling protein, potentiating the ubiquitination of TNF receptor-associated factors 3 and 6 and NF-κB nuclear translocation. The secreted IL-6-IL-27 complex can induce the phosphorylation of STAT1 and STAT3 and shows antiviral activity. Our results demonstrate a previously unrecognized mechanism by which IL-6, IL-27A, and EBV-induced gene 3 form a large complex both intracellularly and extracellularly, and this complex acts in the host antiviral response.

Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6.

The antiviral innate immune responses are crucial steps during host defense and must be strictly regulated, but the molecular mechanisms of control remain unclear. In this study, we report increased expression of human ATPase Na+/K+ transporting subunit ß 1(ATP1B1) after DNA and RNA virus infections. We found that the expression of ATP1B1 can inhibit viral replication and increase the levels of IFNs, IFN-stimulated genes, and inflammatory cytokines. Knockdown of ATP1B1 by specific short hairpin RNA had the opposite effects. Upon viral infection, ATP1B1 was induced, interacted with TRAF3 and TRAF6, and potentiated the ubiquitination of these proteins, leading to increased phosphorylation of downstream molecules, including TGF-ß-activated kinase 1 (TAK1) and TANK-binding kinase 1 (TBK1). These results reveal a previously unrecognized role of ATP1B1 in antiviral innate immunity and suggest a novel mechanism for the induction of IFNs and proinflammatory cytokines during viral infection.

Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin­resistant SKOV3/DDP ovarian cancer cells.

Advanced and recurrent ovarian cancer has a poor prognosis and is frequently resistant to numerous therapeutics; thus, safe and effective drugs are needed to combat this disease. Previous studies have demonstrated that triptolide (TPL) exhibits anticancer and sensitization effects against cisplatin (DDP)­resistant ovarian cancer both in vitro and in vivo by inducing apoptosis; however, the involvement of autophagy induced by TPL in resistant ovarian carcinoma remains unclear. In the present study, the results revealed that TPL induced autophagy to facilitate SKOV3/DDP ovarian cancer cell death. The xenograft experiment revealed that the autophagy inhibitor CQ significantly reduced TPL­mediated chemosensitization and tumor growth inhibition. Mechanically, TPL­induced autophagy in SKOV3/DDP cells was associated with the induction of ROS generation and inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription­3 (STAT3) pathway. The inhibitory effect of TPL on the JAK2/STAT3 pathway could be restored in the presence of the antioxidant NAC. Furthermore, it was further determined that TPL disrupted the interaction between Mcl­1 and Beclin1, which was prevented by the JAK2/STAT3 signaling activator IL­6. Overall, the present results revealed a novel molecular mechanism whereby TPL induced lethal autophagy through the ROS­JAK2/STAT3 signaling cascade in SKOV3/DDP cells. The present study has provided the groundwork for future application of TPL in the treatment of ovarian cancer.

Association between airborne particulate matter and renal function: An analysis of 2.5 million young adults.

BACKGROUND: Limited studies have examined the impact of airborne particulate matter of 2.5 µm or less (PM2.5) on renal function. No study has examined the effect of PM1, which is small enough to reach the blood circulation. We examined whether exposure to PM1 or PM2.5 affected renal function of young Han Chinese. METHOD: We included 2,546,047 young adults who were aged 18 to 45 years, being Han ethnicity and had no chronic disease from a Chinese national birth cohort. Serum creatinine (Scr) of each participant was measured during the baseline examination. Estimated glomerular filtration rate (eGFR) were calculated for each participant using the latest Chronic Kidney Disease Epidemiology Collaboration equation. One-year average exposure to PM1 and PM2.5 prior to the health examination for each participant were estimated using machine learning models with satellite remote sensing information. Generalized additive mixed models were used to estimate associations between PM1 or PM2.5 and renal function after adjusting for detailed individual variables. RESULTS: A 10 µg/m3 increment in PM1 exposure was associated with -0.95% (95%CI: -1.04%, -0.87%) difference of eGFR in females and -0.37% (95%CI: -0.44%, -0.31%) in males. For PM2.5, the corresponding difference of eGFR was -0.99% (95%CI: -1.05%, -0.93%) in females and -0.48% (95%CI: -0.53%, -0.43%) in males, respectively. Associations between eGFR and PM were higher in females compared to males (p < 0.05 for interaction test). Association with PM1 were weaker than that with other fractions included in PM2.5. Participants who worked as farmers, were of normal weight, were not exposed to tobacco smoking, did not drink alcohol, had higher associations between eGFR and PM than their counterparts (p < 0.05 for interaction test). CONCLUSION: Exposure to PM1 and PM2.5 was associated with reduced renal function among Han Chinese at reproductive age.

[Screening and Identification of the Peptides Specifically Binding to 
Human Non-small Cell Lung Cancer NCI-H1299 Cells].

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and one of the malignant tumor with the highest mortality. As the main part of the optical molecular imaging probe, peptide can realize the early screening and diagnosis of tumor and improve the survival rate of patients. The aim of this study was to screen the small-molecule peptide that highly binds to NSCLC NCI-H1299 cells using in vivo phage display technology and to identify their binding specificity by in vitro experiment. METHODS: To prepare a tumor-bearing nude mouse model of NCI-H1299 cells, after 3 rounds of in vivo screening with Ph.D.-C7CTM Peptide Library, phage clones were randomly picked, using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) to identify the affinity of phage clones to NCI-H1299 cells. The positive monoclonal phages DNA was extracted and sequenced to obtain the amino acid sequence of the peptides. The peptides with the highest repetition rate was chemically synthesized and labeled with fluorescein (FITC) to prepare optical molecular probe. We preliminary identified the specificity of the probe binding to lung cancer cells by in vitro experiment. RESULTS: After three rounds of in vivo screening, the phages enrichment rate was 341.3 times compared with the first round. Immunohistochemical staining showed that with the increase of screening times, the phages binding to tumor tissues continued to increase, and the binding amount was significantly higher than normal tissues; ELISA results showed that 20 clones among the 30 randomly selected phage clones were positive. After sequencing, the peptide with the highest repetition rate was synthesized and named NSP1; Methyl thiazolyl tetrazolium assay (MTT) and would healing assay showed that NSP1 will not affect cell proliferation and migration. Flow cytometry and immunofluorescence showed specific binding of NSP1 to NCI-H1299 cells. CONCLUSIONS: We successfully obtained the peptide NSP1 that specifically binds to lung cancer NCI-H1299 cells by in vivo phage display, which provide a theoretical basis for NSCLC early diagnosis and targeted therapy.

A scoring system based on clinical features for the prediction of sporadic renal angiomyolipoma rupture and hemorrhage.

The purpose of this study is to analyze the risk factors of sporadic renal hamartoma and establish a risk scoring system, and to intervene in patients with high-risk sporadic renal hamartoma who are prone to rupture and bleeding as soon as possible.Retrospective univariate and multivariate logistic analyzes were conducted for clinical data of 332 sporadic renal hamartoma patients to screen out independent risk factors of tumor rupture. Score of each independent risk factor was calculated. (Calculation formula: the risk coefficient of each factor = the beta regression coefficient of each factor/the minimum value of the beta regression coefficient of all factors, the value of the smallest beta regression coefficient corresponding to all the factors was assigned 1 point. The score of each factor was equal to the risk coefficient of each variable was taken as an integer value by rounding.) The total score was equal to the sum of all factors. Then the area under the receiver operating characteristics (AUC) curve was compared between high risk factors and scoring system. Finally, the scoring system was evaluated by the area under the curve (AUC) and the Hosmer-Lemeshow method in an independent cohort of 130 patients.Factors such as symptoms at presentation, tumor size, tumor blood supply, and tumor growth pattern were significant predictors of sporadic renal angiomyolipoma rupture in both the univariate and multivariate analyses; these predictors were included in the scoring system to predict sporadic renal angiomyolipoma rupture. There were no significant differences in AUCs between high risk factors and scoring system (z = 0.6434, P = .583, AUC = 0.913, and 0.903 for high risk factors and scoring system, respectively). The sporadic renal angiomyolipoma patients who scored >6 points were prone to rupture. AUROC of the scoring system in the validation set was 0.854(95%CI:0.779, 0.928). Using the Hosmer-Lemeshow method, the value of X was 2.916, P = .893, suggesting the scoring system fitted well.A scoring system based on clinical features is simple and effective in predicting sporadic angiolipoma rupture and hemorrhage. When the score is higher than 6 points, the probability of hamartoma rupture and hemorrhage is significantly increased and early intervention is needed.

NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1.

Intracellular viral RNAs are recognized by the RIG-I-like receptors (RLRs), which signal through the mitochondrial antiviral signaling protein MAVS. MAVS recruits and activates TBK1 kinase, which further phosphorylates and activates the transcription factor IRF3, leading to the induction of type I IFN and downstream antiviral genes. We identified human nucleus accumbens-associated 1 (NAC1), a member of the BTB/POZ family, as a bridge for MAVS and TBK1 that positively regulates the RLR-mediated induction of type I IFN. Overexpression or knockdown of NAC1 could, respectively, enhance or impair Sendai virus-triggered activation of TBK1 and IRF3, as well as induction of IFN-ß. NAC1 also significantly boosted host antiviral responses against multiple RNA viruses. NAC1 was able to interact with MAVS and TBK1 upon viral infection. The BTB/POZ domain (aa 1-133) of NAC1 interacted with MAVS, and the remainder of NAC1 bound to TBK1. Furthermore, NAC1 could promote the recruitment of TBK1 to MAVS. In contrast, knockdown of NAC1 attenuated the interaction between TBK1 and MAVS. Collectively, our study characterizes NAC1 as an important component of RLR-mediated innate immune responses and uncovers a previously unrecognized function of the BTB/POZ family proteins.

Quantification of Cadmium in Rice by Surface-enhanced Raman Spectroscopy Based on a Ratiometric Indicator and Conical Holed Enhancing Substrates.

A surface-enhanced Raman spectroscopy (SERS) based method was developed for the quantification of Cd2+ in rice. Gold nano-particles (AuNPs) modified with trimercaptotriazine served as a ratiometric SERS probe for the detection of Cd2+. A conical holed substrate was used to further enhance SERS signals, and hence to improve the sensitivity. A calibration model based on the spectral shape deformation quantitative theory was employed to mitigate the influence of variations in the number and distribution of "hot spots". The proposed SERS method was applied to quantitative analysis of Cd2+ in three types of rice, and achieved satisfactory quantitative results with accuracy comparable to that of the reference method-inductively coupled plasma mass spectrometry. The limit of detection of the proposed method was estimated to be 8 µg kg-1. The proposed SERS method has the potential to become a fast screening method for the detection of Cd2+ in rice.

Antitumor evaluation and multiple analysis on different extracted fractions of the root of Cynanchum auriculatum Royle ex Wight.

The root of Cynanchum auriculatum (C. auriculatum) Royle ex Wight has been shown to possess various pharmacological effects and has recently attracted much attention with respect to its potential role in antitumor activity. The C-21 steroidal glycosides are commonly accepted as the major active ingredients of C. auriculatum. In this study, the antitumor abilities of different extracted fractions of the root bark and the root tuber of C. auriculatum were investigated by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human cancer cell lines HepG2 and SMMC-7721. The results showed that the chloroform and ethyl acetate fractions of the root tuber suppressed tumor cell growth strongly. To identify and characterize the chemical constituents of different active fractions, an ultra high performance liquid chromatography with triple-quadrupole tandem mass spectrometry method was developed for the simultaneous quantitation of eight C-21 steroidal glycosides. The analysis revealed that the C-21 steroidal glycosides were concentrated in the chloroform and ethyl acetate fractions, and the total contents of different fractions in the root tuber were significantly higher than those of corresponding ones in the root bark. Furthermore, the C-21 steroidal glycosides based on different types of aglucones were prone in different medicinal parts of C. auriculatum.