Synthesis of Nucleotides Bearing the 2'-O-Trifluoromethyl Group and Their Application in RNA Analogs Preparation.

The integration of fluorine atoms into biologically active organic compounds has proved to be a vital technique in small molecule drugs. This technique can substantially enhance crucial properties, including metabolic stability, lipophilicity, and bioavailability, often with a mere addition of a single fluorine atom or a trifluoromethyl group. Over the past few decades, this concept has also been applied in nucleic acid chemistry. A commonly employed 2'-OH substitution is the introduction of a 2'-deoxy-2'-fluoro (2'-F) group. The strong electronegativity of fluorine prompts the modified siRNA to readily adopt a C3'-endo conformation, resulting in significant advantages in terms of binding affinity. To enrich the toolbox of chemical modification of oligonucleotides, the replacement of the 2'-OH with the 2'-O-trifluoromethyl group has been developed in RNA analog synthesis. Oligodeoxynucleotides containing the 2'-O-trifluoromethyl group can greatly increase the thermal stability of DNA/RNA duplexes depending on the position and amount of the modification. Moreover, 2'-O-trifluoromethylated oligodeoxynucleotide also exhibited a slightly higher resistance to snake venom phosphodiesterase than the unmodified oligodeoxynucleotide. The 2'-O-trifluoromethylated oligonucleotides can emerge as a label to study RNA structure and function as well, or to develop DNA/RNA-based diagnostics. Hence, it is necessary to report an effective method for the synthesis, deprotection, purification, and characterization of oligonucleotides bearing a 2'-O-trifluoromethyl group. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-N-benzoyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl adenosine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 2: Preparation of 4-N-acetyl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl cytidine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 3: Preparation of 2-N-isobutyryl-5'-O-dimethoxytrityl-2'-O-trifluoromethyl guanine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 4: Preparation of 5'-O-dimethoxytrityl-2'-O-2-trifluoromethyl uridine 3'-(2-cyanoethyl N,N-diisopropyl) phosphoramidite Basic Protocol 5: Solid-phase synthesis of 2'-O-trifluoromethylated RNA analogs Basic Protocol 6: Deprotection and purification of 2'-O-trifluoromethyl-RNAs.

A Convenient Method for the Synthesis of 2'-O-Cyanoethylated Nucleotides and Their Application in the Solid-Phase Synthesis of Related RNA Analogs.

Although small interfering RNA (siRNA) is a key player among gene inhibition therapeutics, there are many obstacles to the development of siRNA drugs due to inherent properties of oligonucleotides, including the unsatisfactory stability of unmodified siRNA, poor pharmacokinetic distribution, and the toxicity induced by off-target effects. To maximize treatment potency, chemical modification of siRNA has undoubtedly been the most successful strategy by far. Widely applied modifications include phosphorothioate linkages, 2'-O-methyl modifications, and 2'-fluoro modifications, among others. To extend the family of chemical modifications for oligonucleotides, 2'-O-cyanoethylated RNA analogs were developed through the replacement of the 2'-hydroxyl group with a 2'-O-cyanoethyl group (-OCH2 CH2 CN). This modification can provide several advantages over unmodified RNA, such as increased stability, improved binding affinity to complementary DNA or RNA strands, and resistance to degradation by cellular nucleases. The 2'-O-cyanoethyl-modified RNAs not only are applied in RNA silencing machinery but also act as research tools for studying RNA structure and function or for developing RNA-based diagnostics. Therefore, the efficient synthesis, deprotection, purification, and characterization of 2'-O-cyanoethylated RNAs deserves more attention. This protocol describes the chemical synthesis of 2'-O-cyanoethylated nucleotides and the solid-phase synthesis, deprotection, and purification of 2'-O-cyanoethylated RNAs. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-N-dimethylformamidyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl adenosine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 2: Preparation of 4-N-acetyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl cytidine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 3: Preparation of 2-N-dimethylformamidyl-5'-O-dimethoxytrityl-2'-O-cyanoethyl guanine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 4: Preparation of 5'-O-dimethoxytrityl-2'-O-2-cyanoethyl uridine 3'-(2-cyanoethyl N,N-diisopropyl)phosphoramidite Basic Protocol 5: Solid-phase synthesis of 2'-O-cyanoethylated RNA analogs Basic Protocol 6: Deprotection and purification of synthesized 2'-O-cyanoethyl-RNAs.

Inhibition of keloid by 32P isotope radiotherapy through suppressing TGF-ß/Smad signaling pathway.

BACKGROUND: Keloid seriously affects the appearance, and is accompanied by some symptoms including pain, burning, itching. Radioactive nuclides such as 32P have been proved to be effective in inhibiting the formation of keloid, but the mechanism remains unclear. METHODS: The keloid animal model was established through keloid tissues implantation. Hematoxylin-Eosin (HE) and Masson staining were performed to investigate histological changes and collagen deposition. The mRNA and protein expression were assessed using RT-PCR and western blotting, respectively. Cell apoptosis and cycle were evaluated through flow cytometry. RESULTS: Both 32P isotope injection and skin path significantly reduced the size of keloid, and inhibited TGF-ß/Smad signaling pathway. SRI-011381, the agonist of TGF-ß/Smad signaling pathway, markedly reversed the influence of 32P isotope on cell proliferation, cell apoptosis, cell cycle of LNCaP cells and TGF-ß/Smad signaling pathway. CONCLUSIONS: 32P isotope injection and skin path greatly reduced the size of keloid, and the TGF-ß/Smad signaling pathway was remarkably inhibited by 32P isotope treatment. The regulation of dermal fibroblast by 32P isotope was reversed by SRI-011381. 32P isotope might inhibit keloid through suppressing TGF-ß/Smad signaling pathway. Our study provides a novel therapeutic strategy for the treatment of keloid.

Clinical efficacy of iodine-125 (125I) seed implantation in patients with iodine-refractory differentiated thyroid cancer.

Patients with radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) are resistant to radioactive iodine-131(131I) treatment, and the clinical treatment for these patients is complex. The implantation of iodine-125 (125I) seeds in the lesion has been successfully applied to treat malignant tumors, but there are few reports on using 125I particles in the treatment of RAIR-DTC. This retrospective study collected data of 92 patients with RAIR-DTC. Patients treated with sorafenib were included in a control group (50 cases with 72 lesions) and patients treated with 125I implantation were included in an observation group (42 cases with 68 lesions). The results showed that compared with those in the control group, the lesion volume was lower and the VVR was higher in the observation group (P<0.05). The Tg and Tg-Ab levels 6 months after treatment were lower than those before treatment in both groups, and the post-treatment Tg and Tg-Ab levels of the observation group were lower than those of the control group (P<0.05). The efficacy, disease control rate, and objective remission rate were not significantly different between the observation group and the control group (P>0.05). Overall survival of patients in the observation group was longer than that in the control group, χ2 = 4.430, P = 0.035. The incidence of total adverse reactions in the observation group was lower than that in the control group (P<0.05). In conclusion, 125I seed implantation is effective in RAIR-DTC treatment as it can prolong the overall survival of patients while maintaining a safe profile.

Validation the role of desmocollin-2 in osteosarcoma based on single cell and bulk RNA seq and experimental analyses.

Background: The aetiology of osteosarcoma (OS) remains unclear. Desmocollin-2 (DSC2) mediates intercellular adhesion and is involved in tumour progression. Therefore, we aim to investigate the potential role of DSC2 in OS. Methods: We analyzed the expression, prognostic value and immune infiltration of DSC2 in OS via single cell and bulk RNA seq data. Besides, the expression and function of DSC2 in OS were further verified by in vitro experiment. Results: We preliminarily determined that DSC2 was high expressed in OS, which was a risk factor for survival and had a strong relationship with immune cell infiltration. What's more, in vitro experiments also demonstrated that DSC2 was high expressed in OS cells, and silencing DSC2 would suppress proliferation, migration and invasion of OS cells. Conclusions: DSC2 may serve as an oncogene, which exerts a crucial role in tumor progression, predicting prognosis and immune cell infiltration in OS.

RAMP1 as a novel prognostic biomarker in pan-cancer and osteosarcoma.

Receptor activity modifying protein 1 (RAMP1) facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane, but its role in osteosarcoma (OS) remains unclear. We evaluated the RAMP1 expression and prognostic value across different cancers, studying tumor immune infiltration. The prognostic value was analyzed using the GSE39058 and TARGET datasets. Differential gene expression was evaluated. a protein-protein interaction network was constructed, and gene set enrichment analysis was performed. The function of RAMP1 in the tumor microenvironment was analyzed, and its expression in OS cell lines was validated using quantitative real-time PCR. High RAMP1 expression correlated with poor prognosis relative to low RAMP1 expression (p < 0.05). Low RAMP1 expression correlated with an abundance of CD4+ memory-activated T cells. whereas a high expression level correlated with a high proportion of gamma-delta T cells (γδ T cells). Differentially expressed genes from TARGET was enriched in olfactory transduction pathways (normalized enrichment scores [NES] = 1.6998, p < 0.0001). RAMP1 expression negatively correlated with CD44 expression but positively correlated with TNFSF9 expression. The RAMP1 gene is substantially expressed in OS cells compared to the normal osteoblast cell line hFOB1.19. Thus, RAMP1 may be a prognostic biomarker and potential therapeutic target in OS.

A change point-based analysis procedure for improving the success rate of decision-making in clinical trials with delayed treatment effects.

A delayed treatment effect is a commonly observed phenomenon in tumor immunotherapy clinical trials. It can cause a loss of statistical power and complicate the interpretation of the analytical findings. This phenomenon also poses challenges for interim analysis in the context of phase II/III seamless design or group sequential design. It shows potential to lead researchers to make incorrect go/no-go decisions. Despite its significance, rare research has explored the impact of delayed treatment effects on the decision success rate of the interim analysis and the methods to compensate for this loss. In this study, we propose an analysis procedure based on change points for improving the decision success rate at the interim analysis in the presence of delayed treatment effects. This procedure primarily involves three steps: I. detecting and testing the number and locations of change points; II. estimating treatment efficacy; and III. making go/no-go decisions. Simulation results demonstrate that when there is a delayed treatment effect with a single change point, using the proposed analysis procedure significantly improves the decision success rate while controlling the type I error rate. Moreover, the proposed method exhibits very little disparity compared to the unadjusted method when the proportional hazards assumption holds. Therefore, the proposed analysis procedure provides a feasible approach for decision-making at the interim analysis when delayed treatment effects are present.

Changes in the Physical Properties and Volatile Odor Characteristics of Shiitake Mushrooms (Lentinula edodes) in Far Infrared Radiation Drying.

The effects of far infrared radiation drying (FID) on physical properties (drying kinetics, color, shrinkage ratio, rehydration ratio, and microstructural characterization) and volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms were evaluated in this study. During the FID, the drying time decreased with the increase in drying temperature, and it had a less significant effect in the lower temperature range. The increase in drying temperature led to increasing shrinkage and collapse in the microstructure, resulting in a decreased rehydration rate and highlighting the influence of microstructure characteristics on macroscopic properties. Higher drying temperatures employed in the FID process were found to be associated with a decreasing L* value and an increasing ΔE value. The application of principal component analysis can effectively distinguish the significant effect of FID on the volatile odor profiles of shiitake mushrooms. Compared to raw shiitake mushrooms, FID treatment has endowed samples with a greater variety of volatile compounds. After processing with FID, there have been increases in volatile components such as sulfur compounds, acids, nitrogen compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons have shown decreases.

The clinical-histologic and prognostic characteristics in patients with a second primary non-small-cell lung cancer after a lobectomy.

OBJECTIVES: The goal of this study was to investigate whether an operation can offer survival benefits for patients with a second primary non-small-cell lung cancer (NSCLC) after a lobectomy for a first primary NSCLC and to analyse the characteristics affecting the survival of those patients. METHODS: We performed survival analyses of patients with a second primary NSCLC based on the Surveillance, Epidemiology and End Results program and used propensity score matching to reduce the potential bias and analyse the data. In addition, the primary observational end point was overall survival (OS), and the secondary observational end point was histologic migration. RESULTS: The data from 944 patients were used to perform the main analysis. A total of 36.2% of patients experienced a shift in tumour histologic type between 2 diagnoses of primary NSCLC, and this shift significantly affected OS (P = 0.0065). The median survival time in patients with surgical resection and those without an operation was 52.0 months versus 33.0 months, respectively. Patients with surgical resection at the secondary diagnosis had better survival than those without surgery (5-year OS rate: 48.0% vs 34.0%, P < 0.001). In addition, compared with a pneumonectomy and a sublobar resection, a lobectomy was the optimal surgical procedure for patients diagnosed with a second primary NSCLC after adjusting for other confounders (adjusted hazard ratio: 0.68, P < 0.01). However, in the subgroup analysis, lobar and sublobar resections could provide similar survival benefits for patients with tumour size ≤20 mm (P = 0.5). CONCLUSIONS: The operation, especially a lobectomy, can prolong OS in patients with a second primary NSCLC. Besides, sublobar resection can be performed in selected patients with tumour size ≤20 mm. Moreover, histologic migration may impact the survival of those patients with a secondary primary NSCLC.

Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety.

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it.

Predictive value of 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity in the prognosis of gastric cancer.

OBJECTIVE: We aimed to investigate the predictive value of pre-treatment 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity for gastric cancer prognosis. METHODS: Seventy-one patients with gastric cancer were included. All patients underwent 18F-FDG PET/CT whole-body scans prior to treatment and had pathologically confirmed gastric adenocarcinomas. Each metabolic parameter, including SUVmax, SUVmean, MTV, and TLG, was collected from the primary lesions of gastric cancer in all patients, and the slope of the linear regression between the MTV corresponding to different SUVmax thresholds (40% × SUVmax, 80% × SUVmax) of the primary lesions was calculated. The absolute value of the slope was regarded as the metabolic heterogeneity of the primary lesions, expressed as the heterogeneity index HI-1, and the coefficient of variance of the SUVmean of the primary lesions was regarded as HI-2. Patient prognosis was assessed by PFS and OS, and a nomogram of the prognostic prediction model was constructed, after which the clinical utility of the model was assessed using DCA. RESULTS: A total of 71 patients with gastric cancer, including 57 (80.3%) males and 14 (19.7%) females, had a mean age of 61 ± 10 years; disease progression occurred in 27 (38.0%) patients and death occurred in 24 (33.8%) patients. Multivariate Cox regression analysis showed that HI-1 alone was a common independent risk factor for PFS (HR: 1.183; 95% CI: 1.010-1.387, P < 0.05) and OS (HR: 1.214; 95% CI: 1.016-1.450, P < 0.05) in patients with gastric cancer. A nomogram created based on the results of Cox regression analysis increased the net clinical benefit for patients. Considering disease progression as a positive event, patients were divided into low-, intermediate-, and high-risk groups, and Kaplan-Meier survival analysis showed that there were significant differences in PFS among the three groups. When death was considered a positive event and patients were included in the low- and high-risk groups, there were significant differences in OS between the two groups. CONCLUSION: The heterogeneity index HI-1 of primary gastric cancer lesions is an independent risk factor for patient prognosis. A nomogram of prognostic prediction models constructed for each independent factor can increase the net clinical benefit and stratify the risk level of patients, providing a reference for guiding individualized patient treatment.

Mechanistic exploration of Yiqi Liangxue Shengji prescription on restenosis after balloon injury by integrating metabolomics with network pharmacology.

CONTEXT: Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI). OBJECTIVE: To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC-MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated. RESULTS: Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 µm vs. 14.32 ± 1.37 µm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA. DISCUSSION AND CONCLUSIONS: This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.

Factors influencing postoperative anxiety and depression following Iodine-131 treatment in patients with differentiated thyroid cancer: A cross-sectional study.

BACKGROUND: Differentiated thyroid cancer (DTC) often seriously impacts patients' lives. Radionuclide Iodine-131 (131I) is widely used in treating patients with DTC. However, most patients know little about radionuclide therapy, and the treatment needs to be performed in a special isolation ward, which can cause anxiety and depression. AIM: To explore anxiety and depression status and their influencing factors after 131I treatment in patients with DTC. METHODS: A questionnaire survey was conducted among postoperative patients with DTC who received 131I treatment at our hospital from June 2020 to December 2022. General patient data were collected using a self-administered demographic characteristics questionnaire. The self-rating depression scale and self-rating anxiety scale were used to determine whether patients were worried about their symptoms and the degree of anxiety and depression. The patients were cate-gorized into anxiety, non-anxiety, depression, and non-depression groups. Single-variable and multiple-variable analyses were used to determine the risk factors for anxiety and depression in patients with thyroid cancer after surgery. RESULTS: A total of 144 patients were included in this study. The baseline mean score of self-rating anxiety and depression scales were 50.06 ± 16.10 and 50.96 ± 16.55, respectively. Notably, 48.62% (70/144) had anxiety and 47.22% (68/144) of the patients had depression. Sex, age, education level, marital status, household income, underlying diseases, and medication compliance significantly differed among groups (P < 0.05). Furthermore, multivariate logistic regression analysis showed that education level, per capita monthly household income, and medication compliance level affected anxiety (P = 0.015, 0.001, and 0.001 respectively. Patient's sex, marital status, and underlying diseases affected depression (P = 0.007, 0.001, and 0.009, respectively). CONCLUSION: Nursing interventions aiming at reducing the risk of anxiety and depression should target unmarried female patients with low education level, low family income, underlying diseases, and poor adherence to medications.

A Dual-Targeting Liposome Enhances Triple-Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation.

Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus.

Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD's pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.

Comparison of Urine and Genital Samples for Detecting Human Papillomavirus (HPV) in Clinical Patients.

Background: Human papillomavirus (HPV) is the main cause of cervical cancer. The aim of the present study was to investigate HPV DNA detection and genotyping on paired genital and urine samples and to evaluate if urine samples could be used to monitor HPV infection. Methods: Study subjects were recruited from one local hospital in Guangdong of China from September 1, 2011, to June 30, 2012. They were invited to participate if they have taken an HPV genotyping assay for clinical diagnosis of the genital-urinary disease or for a health check-up 3-5 days ago. DNA was extracted from paired genital and urine samples; genotyping was performed with the GenoArray assay. Results: A total of 250 patients were recruited, which included 203 females and 47 males. Our results showed that the overall agreement on HPV status between the paired samples was 77.1% (155/201, 95% CI: 0.713-0.829) for females, with a kappa value of 0.523 (95% CI: 0.469-0.632), while the agreement was extremely low in the paired male samples. As to individual genotyping, the greatest agreement was found for HPV16 type-specific identification in females (96.02%, 0.933-0.987), followed by the other 12 high oncogenic risk (HR-HPV) types, while the agreement for low-risk HPV detection is poor (κ < 0.6). Agreement between paired samples showed that HPV detection had a significantly greater concordance in the samples obtained in females than males (p = 0.002). Moreover, the agreement for low-risk HPV detection was significantly lower as compared to HR-HPV detection (48.1% vs. 62.3%, p = 0.044). Conclusion: Despite reduced sensitivity, HPV detection in urine closely represents the same trend that is seen with genital sampling. Urine appears to be an appropriate surrogate sample for HPV DNA detection in women with very limited access to healthcare, while the utility of urine for HPV DNA detection in males is less certain.

Small-molecule natural plants for reversing liver fibrosis based on modulation of hepatic stellate cells activation: An update.

BACKGROUND: Liver fibrosis (LF) is a trauma repair process carried out by the liver in response to various acute and chronic liver injuries. Its primary pathological characteristics are excessive proliferation and improper dismissal of the extracellular matrix, and if left untreated, it will progress into cirrhosis, liver cancer, and other diseases. Hepatic stellate cells (HSCs) activation is intimately associated to the onset of LF, and it is anticipated that addressing HSCs proliferation can reverse LF. Plant-based small-molecule medications have anti-LF properties, and their mechanisms of action involve suppression of extracellular matrix abnormally accumulating as well as anti-inflammation and anti-oxidative stress. New targeting HSC agents will therefore be needed to provide a potential curative response. PURPOSE: The most recent HSC routes and small molecule natural plants that target HSC described domestically and internationally in recent years were examined in this review. METHODS: The data was looked up using resources including ScienceDirect, CNKI, Web of Science, and PubMed. Keyword searches for information on hepatic stellate cells included "liver fibrosis", "natural plant", "hepatic stellate cells", "adverse reaction", "toxicity", etc. RESULTS: We discovered that plant monomers can target and control various pathways to prevent the activation and proliferation of HSC and promote the apoptosis of HSC in order to achieve the anti-LF effect in this work by compiling the plant monomers that influence many common pathways of HSC in recent years. It demonstrates the wide-ranging potential of plant monomers targeting different routes to combat LF, with a view to supplying new concepts and new strategies for natural plant therapy of LF as well as research and development of novel pharmaceuticals. The investigation of kaempferol, physalin B, and other plant monomers additionally motivated researchers to focus on the structure-activity link between the main chemicals and LF. CONCLUSION: The creation of novel pharmaceuticals can benefit greatly from the use of natural components. They are often harmless for people, non-target creatures, and the environment because they are found in nature, and they can be employed as the starting chemicals for the creation of novel medications. Natural plants are valuable resources for creating new medications with fresh action targets because they feature original and distinctive action mechanisms.

Facile "Synergistic Inner-Outer Activation" Strategy for Nano-Engineering of Nature-Skin-Derived Wearable Daytime Radiation Cooling Materials.

Natural skin-derived products, as traditional wearable materials are widely used in people's daily life due to the products' excellent origins. Herein, a versatile daytime-radiation cooling wearable natural skin (RC-skin) consisting of the collagen micro-nano fibers with the on-demand double-layer radiation cooling structure is nano-engineered through the proposed facile "synergistic inner-outer activation" strategy. The bottom layer (inner strategy) of the RC-skin is fabricated by filling the skin with the Mg11 (HPO3 )8 (OH)6 nanoparticles by soaking. The superstratum (outer strategy) is constituted by a composite coating with an irregular microporous structure. The RC-skin harvests the inherent advantages of natural building blocks including sufficient hydrophobicity, excellent mechanical properties, and friction resistance. Owing to the subtle double-layer structure design, the solar reflectance and the average emissivity in the mid-infrared band of RC-skin are ≈92.7% and ≈95%, respectively. Therefore, the RC-skin's temperature in the sub-ambient is reduced by ≈7.5 °C. Various outdoor practical application experiments further substantiate that RC-skin has superior radiation cooling performances. Collectively, RC-skin has broad-application prospects for intelligent wearing, low-carbon travel, building materials, and intelligent thermoelectric power generation, and this study also provides novel strategies for developing natural-skin-derived functional materials.

A Nomogram Based on Atelectasis/Obstructive Pneumonitis Could Predict the Metastasis of Lymph Nodes and Postoperative Survival of Pathological N0 Classification in Non-small Cell Lung Cancer Patients.

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. METHODS: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan-Meier survival analysis were also used in this study. RESULTS: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694-0.704). Moreover, the Cox proportional hazards analysis and Kaplan-Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. CONCLUSION: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC.

Identification and verification of a BMPs-related gene signature for osteosarcoma prognosis prediction.

BACKGROUND: This study aimed to get a deeper insight into new osteosarcoma (OS) signature based on bone morphogenetic proteins (BMPs)-related genes and to confirm the prognostic pattern to speculate on the overall survival among OS patients. METHODS: Firstly, pathway analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were managed to search for possible prognostic mechanisms attached to the OS-specific differentially expressed BMPs-related genes (DEBRGs). Secondly, univariate and multivariate Cox analysis was executed to filter the prognostic DEBRGs and establish the polygenic model for risk prediction in OS patients with the least absolute shrinkage and selection operator (LASSO) regression analysis. The receiver operating characteristic (ROC) curve weighed the model's accuracy. Thirdly, the GEO database (GSE21257) was operated for independent validation. The nomogram was initiated using multivariable Cox regression. Immune infiltration of the OS sample was calculated. Finally, the three discovered hallmark genes' mRNA and protein expressions were verified. RESULTS: A total of 46 DEBRGs were found in the OS and control samples, and three prognostic DEBRGs (DLX2, TERT, and EVX1) were screened under the LASSO regression analyses. Multivariate and univariate Cox regression analysis were devised to forge the OS risk model. Both the TARGET training and validation sets indicated that the prognostic biomarker-based risk score model performed well based on ROC curves. In high- and low-risk groups, immune cells, including memory B, activated mast, resting mast, plasma, and activated memory CD4 + T cells, and the immune, stromal, and ESTIMATE scores showed significant differences. The nomogram that predicts survival was established with good performance according to clinical features of OS patients and risk scores. Finally, the expression of three crucial BMP-related genes in OS cell lines was investigated using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). CONCLUSION: The new BMP-related prognostic signature linked to OS can be a new tool to identify biomarkers to detect the disease early and a potential candidate to better treat OS in the future.