Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Enhancement Effect Induced by the Second Metal to Promote Ozone Catalytic Oxidation of VOCs.

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.

Newly recognized orbital malformations in kabuki syndrome: A case report.

Kabuki syndrome (KS) is a rare congenital disorder with distinctive characteristics. Herein, we describe a KS patient carrying a novel mutation in the KMT2D gene, c.11785C > T (p.Gln3929*). The patient presented with typical eyelid deformities, including eversion of the lateral lower eyelids, long palpebral fissures, hypertelorism, and medial epicanthus. Orbital computed tomography revealed orbital bone malformation with temporally and inferiorly displaced zygomatic bone. The bilateral orbits were shallow with an enlarged angle between the lateral walls. Zygomatic and maxillary bone dysplasia were also observed. Orbital bone anomalies are thought to be one of the characteristics of KS.

Cost-Effectiveness Analysis of Camrelizumab Plus Rivoceranib Versus Sorafenib as a First-Line Therapy for Unresectable Hepatocellular Carcinoma in the Chinese Health Care System.

BACKGROUND AND OBJECTIVES: Camrelizumab plus rivoceranib showed significant clinical benefits in progression-free survival and overall survival compared to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to assess its cost effectiveness from the perspective of Chinese health care system. METHODS: A Markov state-transition model was developed based on the Phase 3 randomized CARES-310 clinical trial data. Health state utility values were obtained from the CARES-310 clinical trial, and direct medical costs were derived from the relevant literature and local charges. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to assess the uncertainty of the model. RESULTS: In the base-case analysis, the incremental effectiveness and cost of camrelizumab plus rivoceranib versus sorafenib were 0.41 QALYs and $13,684.84, respectively, resulting in an ICER of $33,619.98/QALY, lower than the willingness-to-pay threshold of China ($35,864.61/QALY). Subgroup analyses revealed that the ICERs of camrelizumab plus rivoceranib versus sorafenib were $35,920.01 and $29,717.98 in patients with ALBI grade 1 and grade 2, respectively. One-way sensitivity analyses indicated that the cost of camrelizumab, the proportion of patients receiving subsequent treatment in the camrelizumab plus rivoceranib group, and the cost of rivoceranib were the most significant factors in the base-case analysis. Probabilistic sensitivity analysis suggested that the probabilities of cost effectiveness of camrelizumab plus rivoceranib were 61.27%, 51.46%, and 82.78% for any grade, and ALBI grade 1 and grade 2, respectively. CONCLUSIONS: Camrelizumab plus rivoceranib was more cost effective than sorafenib as first-line therapy for unresectable HCC in the Chinese setting.

The scaling of elemental stoichiometry and growth rate over the course of bamboo ontogeny.

Stoichiometric rules may explain the allometric scaling among biological traits and body size, a fundamental law of nature. However, testing the scaling of elemental stoichiometry and growth to size over the course of plant ontogeny is challenging. Here, we used a fast-growing bamboo species to examine how the concentrations and contents of carbon (C), nitrogen (N) and phosphorus (P), relative growth rate (G), and nutrient productivity scale with whole-plant mass (M) at the culm elongation and maturation stages. The whole-plant C content vs M and N content vs P content scaled isometrically, and the N or P content vs M scaled as a general 3/4 power function across both growth stages. The scaling exponents of G vs M and N (and P) productivity in newly grown mass vs M relationships across the whole growth stages decreased as a -1 power function. These findings reveal the previously undocumented generality of stoichiometric allometries over the course of plant ontogeny and provide new insights for understanding the origin of ubiquitous quarter-power scaling laws in the biosphere.

Design, Synthesis, Structure-Activity Relationship, and Three-Dimensional Quantitative Structure-Activity Relationship of Fusarium Acid Derivatives and Analogues as Potential Fungicides.

In research related to fungicides, the development of compounds from natural products with high antifungal activity has attracted considerable attention. Fusaric acid (FA), an alkaloid isolated from the metabolites of Fusarium oxysporum, is an important precursor for developing pharmacologically active herbicides. In our previous work, we reported that FA has a wide range of inhibitory activities against 14 plant pathogenic fungi. In particular, it exhibited excellent antifugal effects on Colletotrichum higginsianum (EC50 = 31.7 µg/mL). Herein, to explore the practical application in the agricultural field, the design and synthesis of three series of FA derivatives and their inhibitory activities against plant pathogenic fungi were examined. Results demonstrated that the optimized FA derivatives had excellent inhibitory activities against C. higginsianum, Helminthosporium (Harpophora maydis), and Pyricularia grisea. In particular, the inhibitory activities were considerably improved when the 5-butyl groups of FA were substituted. The EC50 of C. higginsianum and P. grisea was only 1.2 and 12.0 µg/mL when 5-butylalkyl groups were substituted with 5-([1,1'-biphenyl]-4-yl) and 5-phenyl, respectively. Moreover, the safety index of target compounds, which was obtained from the treatment index of medicines, on rice seeds was evaluated. Finally, 16 leading compounds (H4, H22-H24, H27, H29, H30-H34, H37, H45, H50, H52, and H53) were obtained; they had considerable potential for additional modification and optimization as agricultural fungicides. Moreover, three-dimensional quantitative structure-activity relationship models were developed for obtaining a systematic structure-activity relationship profile to explore the possibility of more potent FA derivatives as novel fungicides.

International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease.

Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions.

Employing Mobile Learning in Music Education.

This study sought to evaluate the effectiveness of introducing digital software in music education to improve academic performance and solfeggio class attendance. To assess academic performance, a test consisting of 25 theoretical questions and 25 practical tasks was developed. The Bologna model was used as an assessment system. The groups were compared by calculating the Student's t-test in terms of the "Test Score" and "Missed Classes" parameters. The collected data revealed that the mean score for the experimental group was 87.50 out of 100, while in the control group, it was much lower, namely 65.37. Likewise, the control group was characterized by satisfactory (D) performance in mastering solfeggio, with the mean score ranging between 64 and 73, whereas experimental group participants had an average of 82-89. The statistical data processing results showed that the six-month use of the ChordIQ app contributed to more effective mastering of solfeggio by amateur musicians. At the same time, the difference between the groups turned out to be significant in both cases, so the research hypothesis was confirmed for both of them (p < 0.05). Overall, the results showed that ChordIQ is a useful mobile app teaching the user music in an exciting and interactive way. The findings collected can be used to update traditional solfeggio curricula, conduct scientific studies in the field of interactive music education, as well as create new dedicated software.

Safety and efficacy of immunotherapy rechallenge following checkpoint inhibitor-related pneumonitis in advanced lung cancer patients: a retrospective multi-center cohort study.

Background: Checkpoint inhibitor-related pneumonitis (CIP) induced by immune checkpoint inhibitors (ICIs) is one of the most fatal immune-related adverse events (irAE). However, only limited data are available on rechallenge with ICIs after CIP. We evaluated the efficacy and safety of rechallenge after CIP in patients with advanced lung cancer to identify the potential populations that would benefit. Methods: We conducted a multicenter retrospective study of advanced lung cancer patients who received further ICI treatment (rechallenge) or did not undergo re-administration after grade ≥1 CIP between May 2017 and May 2021. Progression-free survival (PFS) and overall survival (OS) were estimated from first or second ICI initiation to disease progression (PFS1 and PFS2, respectively), death, or last follow-up (OS1 and OS2, respectively). The recurrence of CIP and new irAEs in these patients after ICI rechallenge were calculated. Results: Among 107 patients afflicted with CIP, 45 (42.1%) received ICI rechallenge. Multivariate analysis showed that severe grade (grades ≥3) and ground-glass opacity of pneumonitis lesions were negatively associated with rechallenge. Following rechallenge, 9 (20.0%) patients developed recurrent pneumonitis, and 11 (24.4%) developed a new irAE. Severe grade of CIP and poor performance status at initial CIP as well as levels of interleukin (IL)-6 and C-reactive protein (CRP), and absolute white blood cell and neutrophil counts at the time of ICI rechallenge were associated with a higher recurrence rate. The median (95% confidence interval) PFS1 and PFS2 were 17.9 (9.9-24.2) and 15.5 (5.5-25.6) months, respectively. The median (95% confidence interval) OS1 and OS2 were 23.5 (16.5-30.5) and 18.4 (10.1-26.7) months, respectively. Lower OS2 was observed in patients with severe grade of CIP and poor performance status at the initial CIP, recurrence of CIP, and in patients with high levels of CRP and IL-6 at rechallenge. Only IL-6 was found to affect OS2 on multivariate analysis. Conclusions: ICI rechallenge following CIP may be a promising treatment for patients with advanced lung cancer, particularly in those with low-grade of CIP and good performance status at initial CIP, and low levels of IL-6 and CRP at the time of initial challenge. Prospective studies are needed for further verification.

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor-related pneumonitis.

Background: Checkpoint inhibitor-related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined. Methods: We conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase's characteristics. Results: There were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005). Conclusions: The general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.

Deep Learning Analysis Using 18F-FDG PET/CT to Predict Occult Lymph Node Metastasis in Patients With Clinical N0 Lung Adenocarcinoma.

Introduction: The aim of this work was to determine the feasibility of using a deep learning approach to predict occult lymph node metastasis (OLM) based on preoperative FDG-PET/CT images in patients with clinical node-negative (cN0) lung adenocarcinoma. Materials and Methods: Dataset 1 (for training and internal validation) included 376 consecutive patients with cN0 lung adenocarcinoma from our hospital between May 2012 and May 2021. Dataset 2 (for prospective test) used 58 consecutive patients with cN0 lung adenocarcinoma from June 2021 to February 2022 at the same center. Three deep learning models: PET alone, CT alone, and combined model, were developed for the prediction of OLM. The performance of the models was evaluated on internal validation and prospective test in terms of accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve (AUCs). Results: The combined model incorporating PET and CT showed the best performance, achieved an AUC of 0.81 [95% confidence interval (CI): 0.61, 1.00] in the prediction of OLM in internal validation set (n = 60) and an AUC of 0.87 (95% CI: 0.75, 0.99) in the prospective test set (n = 58). The model achieved 87.50% sensitivity, 80.00% specificity, and 81.00% accuracy in the internal validation set and achieved 75.00% sensitivity, 88.46% specificity, and 86.60% accuracy in the prospective test set. Conclusion: This study presented a deep learning approach to enable the prediction of occult nodal involvement based on the PET/CT images before surgery in cN0 lung adenocarcinoma, which would help clinicians select patients who would be suitable for sublobar resection.

Environmentally Benign and User-Friendly In Situ Generation of Nitrile Imines from Hydrazones for 1,3-Dipolar Cycloaddition.

Nitrile imines are highly reactive and versatile dipoles and conventionally generated in situ from unstable hydrazonyl halides under basic conditions. Herein, we report the first green and user-friendly protocol for in situ generation of nitrile imines from Oxone-KBr oxidation of hydrazones and base-promoted dehydrobromination. The nitrile imines were demonstrated for 1,3-dipolar cycloaddition with various dipolarophiles, including alkene and alkyne groups. With its green nature, ease of operation, and air and moisture tolerance, we expect our method will find wide applications in organic synthesis.

The Treatment Status of Patients in NSCLC With RET Fusion Under the Prelude of Selective RET-TKI Application in China: A Multicenter Retrospective Research.

Background: Rearranged during transfection (RET) fusion is a kind of uncommon mutation (about 1%) in non-small cell lung cancer (NSCLC). Although selective tyrosine kinase inhibitors (TKI) (selpercatinib and pralsetinib) have been available, there are no real-world data about the difference in the efficacy between RET-TKI and other regimens in China. Methods: We conducted a multicenter retrospective analysis of 49 patients with RET-fusion-positive NSCLC. The characteristics and the clinical outcomes with RET-TKI, multi-kinase inhibitor (MKI), systematic chemotherapy, and immune-checkpoint inhibitor (ICI)-based regimens were evaluated. Results: Of the 92 treatments in patients included, RET-TKI was administered 24 times (26.1%), systematic chemotherapy was 35 times (38.0%), ICI-based regimens was 26 times (28.3%), and MKI was 7 times (7.6%). RET-TKI had a higher objective response rate than the chemotherapy and ICI-based regimens (63.6% vs. 14.3% vs. 21.0%, p < 0.001). The median progress-free survival (mPFS) of RET-TKI, chemotherapy, immunotherapy, and MKI was 16.9 (95% CI: 1.8-32.0) months, 11.9 (95% CI: 7.7-16.1) months, 6.7 (95% CI: 2.9-10.5) months, and 2.8 (95% CI: 1.1-4.4) months, respectively. The mPFS of RET-TKI was longer than MKI and immunotherapy (p < 0.001), while without difference with chemotherapy (p = 0.096). Moreover, chemotherapy had longer mPFS than MKI (p < 0.001). In subgroup analysis, patients with brain metastases in RET-TKI treatment had worse mPFS than the one of patients without brain metastases (6.1 (95% CI: 0.0-13.9) months and 8.5 (95% CI: 6.3-10.6) months, p = 0.012). For patients having chemotherapy with or without angiogenesis inhibitors, the mPFS was 12.0 (95% CI: 11.05-13.02) months and 9.1 (95% CI: 8.31-9.89) months (p = 0.468). In the group of ICI-based regimens, the expression level of PD-L1 did not affect the mPFS of ICI [PD-L1 (+) vs. PD-L1 (-): 4.7 (95% CI: 1.8-9.0) months vs. 7.6 (95% CI: 1.1-14.0) months, p = 0.910]. For overall patients, ECOG PS score, therapy lines, and therapeutic regimens were the independent factors affecting the prognosis. Conclusions: In RET-fusion-positive NSCLC, RET-TKI is the best choice for a better response rate and PFS. In addition, chemotherapy which may bring a good PFS, is still a good choice for this group of patients.

microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene.

OBJECTIVES: Accumulating research have reported that microRNAs (miRNAs) play important roles in Retinoblastoma (RB). Nonetheless, the function and underlying mechanism of miR-181a-5p in RB remain ambiguous. METHODS: The relative expression levels of miR-181a-5p and NRAS mRNA were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). RB cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) and 5'-Bromo-2'-deoxyuridine (BrdU) assays. Transwell assays and flow cytometry were performed to detect the migration, invasion, and apoptosis of RB cells. The interaction between miR-181a-5p and NRAS was explored using luciferase experiments, western blotting, and qRT-PCR. RESULTS: miR-181a-5p expression was found to be decreased in RB tissues and cell lines, and its expression was correlated with unfavorable pathological features of the patients. In vitro experiments revealed that miR-181a-5p reduced RB cell proliferation, migration, and invasion while enhancing apoptosis. Further research confirmed that NRAS is a direct target of miR-181a-5p. miR-181a-5p inhibited NRAS expression at both the mRNA and protein levels. Co-transfection of pcDNA-NRAS or NRAS small interfering RNA (siRNA) reversed the effects of miR-181a-5p mimics or miR-181a-5p inhibitors on RB cells. CONCLUSION: miR-181a-5p was significantly downregulated during the development of RB, and it suppressed the malignant behaviors of RB cells by targeting NRAS.

Serum neurofilament light chain or glial fibrillary acidic protein in the diagnosis and prognosis of brain metastases.

INTRODUCTION: Brain metastases (BM) remains the most cumbersome disease burden in patients with lung cancer. This study aimed to investigate whether serum brain injury biomarkers can indicate BM, to further establish related diagnostic models, or to predict prognosis of BM. MATERIALS AND METHODS: This was a prospective study of patients diagnosed with lung cancer with BM (BM group), with lung cancer without BM (NBM group), and healthy participants (control group). Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were detected at baseline. We identified and integrated the risk factors of BM to establish diagnostic models. RESULTS: A total of 158 patients were included (n = 37, 57, and 64 in the BM, NBM, and control groups, respectively). Serum biomarker levels were significantly higher in the NBM group than in the control group. Higher serum NfL and GFAP concentrations were associated with BM (odds ratios, 3.06 and 1.79, respectively). NfL (area under curve [AUC] = 0.77, p < 0.001) and GFAP (AUC = 0.64, p = 0.02) had diagnostic value for BM. The final diagnostic model included NfL level, age, Karnofsky Performance Status. The model had an AUC value of 0.83 (95% confidence interval [CI] 0.75-0.92). High NfL concentration was correlated with poor overall survival of patients with BM (hazard ratio, 3.31; 95% CI 1.22-9.04; p = 0.019). CONCLUSION: Serum NfL and GFAP could be potential diagnostic biomarkers for BM in patients with lung cancer. We established a model that can provide individual diagnoses of BM. Higher NfL level may be associated with poor prognosis of patients with BM.

[Application of sulfylated calcium alginate composite hydrogel loaded with zinc-based zeolite imidazole for the treatment of periodontitis].

PURPOSE: To explore the feasibility of adhesive thiomer calcium alginate composite hydrogel (ZIF-8@CHA-SH) containing metal-organic framework for the treatment of periodontitis in rats. METHODS: Preparation and characterization of ZIF-8@CHA-SH were performed, and the morphology and chemical composition were observed. The antibacterial properties were detected by plate coating method and scanning electron microscope. CCK-8 and live/dead cell fluorescence staining were used to evaluate the toxicity of ZIF-8@CHA-SH on gingival fibroblasts. The anti-inflammatory and tissue repair promoting effects of ZIF-8@CHA-SH were verified by animal experiments. GraphPad Prism 7.0 software was used for statistical analysis. RESULTS: The successful synthesis of ZIF-8@CHA-SH was proved by scanning electron microscopy, energy spectrum analysis, Fourier transform infrared spectroscopy and X-ray diffraction. ZIF-8@CHA-SH had excellent antibacterial ability, and the antibacterial rates against Escherichia coli, Staphylococcus aureus and Streptococcus mutans were (99.88±0.12)%, (99.81±0.32)% and (95.53±3.08)%, respectively（P<0.001）. The cell viability rate of ZIF-8@CHA-SH was (91.64±3.66)% after 5 days of co-culture with human gingival fibroblasts (P=0.6). In vivo experiments showed that ZIF-8@CHA-SH could reduce the infiltration of inflammatory cells and the expression of pro-inflammatory factor IL-6 in rats with periodontitis. CONCLUSIONS: ZIF-8@CHA-SH has excellent biological performance, which can effectively treat periodontitis caused by bacteria, and provids a new strategy for the treatment of periodontal diseases in the future.

microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene

Abstract Objectives Accumulating research have reported that microRNAs (miRNAs) play important roles in Retinoblastoma (RB). Nonetheless, the function and underlying mechanism of miR-181a-5p in RB remain ambiguous. Methods The relative expression levels of miR-181a-5p and NRAS mRNA were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). RB cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) and 5′-Bromo-2′-deoxyuridine (BrdU) assays. Transwell assays and flow cytometry were performed to detect the migration, invasion, and apoptosis of RB cells. The interaction between miR-181a-5p and NRAS was explored using luciferase experiments, western blotting, and qRT-PCR. Results miR-181a-5p expression was found to be decreased in RB tissues and cell lines, and its expression was correlated with unfavorable pathological features of the patients. In vitro experiments revealed that miR-181a-5p reduced RB cell proliferation, migration, and invasion while enhancing apoptosis. Further research confirmed that NRAS is a direct target of miR-181a-5p. miR-181a-5p inhibited NRAS expression at both the mRNA and protein levels. Co-transfection of pcDNA-NRAS or NRAS small interfering RNA (siRNA) reversed the effects of miR-181a-5p mimics or miR-181a-5p inhibitors on RB cells. Conclusion miR-181a-5p was significantly downregulated during the development of RB, and it suppressed the malignant behaviors of RB cells by targeting NRAS.

Development and Validation of a 18F-FDG PET-Based Radiomic Model for Evaluating Hypermetabolic Mediastinal-Hilar Lymph Nodes in Non-Small-Cell Lung Cancer.

BACKGROUND: Accurate evaluation of lymph node (LN) status is critical for determining the treatment options in patients with non-small cell lung cancer (NSCLC). This study aimed to develop and validate a 18F-FDG PET-based radiomic model for the identification of metastatic LNs from the hypermetabolic mediastinal-hilar LNs in NSCLC. METHODS: We retrospectively reviewed 259 patients with hypermetabolic LNs who underwent pretreatment 18F-FDG PET/CT and were pathologically confirmed as NSCLC from two centers. Two hundred twenty-eight LNs were allocated to a training cohort (LN = 159) and an internal validation cohort (LN = 69) from one center (7:3 ratio), and 60 LNs were enrolled to an external validation cohort from the other. Radiomic features were extracted from LNs of PET images. A PET radiomics signature was constructed by multivariable logistic regression after using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation. The PET radiomics signature (model 1) and independent predictors from CT image features and clinical data (model 2) were incorporated into a combined model (model 3). A nomogram was plotted for the complex model, and the performance of the nomogram was assessed by its discrimination, calibration, and clinical usefulness. RESULTS: The area under the curve (AUC) values of model 1 were 0.820, 0.785, and 0.808 in the training, internal, and external validation cohorts, respectively, showing good diagnostic efficacy for lymph node metastasis (LNM). Furthermore, model 2 was able to discriminate metastatic LNs in the training (AUC 0.780), internal (AUC 0.794), and external validation cohorts (AUC 0.802), respectively. Model 3 showed optimal diagnostic performance among the three cohorts, with an AUC of 0.874, 0.845, and 0.841, respectively. The nomogram based on the model 3 showed good discrimination and calibration. CONCLUSIONS: Our study revealed that PET radiomics signature, especially when integrated with CT imaging features, showed the ability to identify true and false positives of mediastinal-hilar LNM detected by PET/CT in patients with NSCLC, which would help clinicians to make individual treatment decisions.

N-acetyl cysteine ameliorates aortic fibrosis by promoting M2 macrophage polarization in aging mice.

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear.Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice.Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined.Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis.Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.