Influence of Chrysanthemum morifolium-maize intercropping pattern on yield, quality, soil condition, and rhizosphere soil microbial communities of C. morifolium.

Introduction: Chrysanthemum morifolium Ramat. is a perennial herb in the Compositae family, often employed in traditional Chinese medicine due to its medicinal value. The planting of C. morifolium faces the challenges of continuous cropping, and intercropping is able to somewhat overcome the obstacles of continuous cropping. Methods: In our study, we designed two different C. morifolium-maize intercropping patterns, including C. morifolium-maize narrow-wide row planting (IS) and C. morifolium-maize middle row planting (IM). Compared with monoculture, the agronomic traits, yield, active ingredients, soil physicochemical properties, soil enzyme activities, and rhizosphere soil microbial communities of C. morifolium and maize were measured under the two C. morifolium-maize intercropping patterns. Results: The findings indicated that (1) Intercropping elevated the agronomic traits, yield, and active ingredients of C. morifolium, especially in C. morifolium-maize narrow-wide row planting pattern, which indicating that interspecific distance played an important role in intercropping system; (2) Intercropping enhanced soil physicochemical properties and enzyme activities of C. morifolium and maize; (3) Intercropping altered rhizosphere soil microbial communities of C. morifolium and maize, making microbial interrelationships more complex. (4) Intercropping could recruit a large number of beneficial microorganisms enrich in the soil, including Bacillus, Sphingomonas, Burkholderia-Caballeronia-Paraburkholderia, Chaetomium, and Ceratorhiza, which may increase the content of AN, NN, AvK, ExCa, AvCu, AvZn and other nutrients in soil and promoted the growth and quality of C. morifolium. Discussion: In summary, intercropping with maize could promote the accumulation of beneficial microorganisms in the soil, thus improving the overall growing environment, and finally realizing the growth and improvement of C. morifolium.

Synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines and isocoumarins enabled by multi-component reagents system (MCRS).

The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

2-Aminopurine-based quencher-free DNA tweezers with fluorescence properties well tuned by surrounding bases.

Reversible structural changes in DNA nanomachines have great potential in the field of bioanalysis. Here, we demonstrate an assembly strategy for quencher-free and tunable DNA tweezers based on 2-aminopurine (2-AP), avoiding the tedious fluorescence labelling step. The conformational state of the tweezers could be controlled by specific oligonucleotides (fuel or anti-fuel). Taking advantage of the local environmental sensitivity of 2-AP, the structural changes of the tweezers were easily tracked, and multiple cyclic switching of the tweezers between the open and closed states was achieved. In addition, the influence of oligonucleotide structure on the fluorescence properties of 2-AP was deeply explored. We figured out that the fluorescence of 2-AP was highly quenched by the base-stacking of natural bases in DNA oligonucleotides. Moreover, by comprehensively regulating the type of bases surrounding the inserted 2-AP site, a sensitive fluorescence response towards dynamic change can be obtained. This principle of quencher-free nanodevices based on 2-AP provides a convenient method for monitoring the structural changes of DNA nanomachines.

Quantitative Measurement on Contrast-Enhanced CT Distinguishes Small Clear Cell Renal Cell Carcinoma From Benign Renal Tumors: A Multicenter Study.

RATIONALE AND OBJECTIVES: To evaluate the potential of quantitative measurements on contrast-enhanced CT (CECT) in differentiating small (≤4 cm) clear cell renal cell carcinoma (ccRCC) from benign renal tumors, including fat-poor angiomyolipoma (fpAML) and renal oncocytoma (RO). MATERIALS AND METHODS: 244 patients with pathologically confirmed ccRCC (n = 184) and benign renal tumors (fpAML, n = 50; RO, n = 10) were randomly assigned into training cohort (n = 193) and test cohort 1 (n = 51), while external test cohort 2 (n = 50) was from another hospital. Quantitative parameters were obtained from CECT (unenhanced phase, UP; corticomedullary phase, CMP; nephrographic phase, NP; excretory phase, EP) by measuring attenuation of renal mass and cortex and subsequently calculated. Univariable and multivariable logistic regression analyses were performed to evaluate the association between these parameters and ccRCC. Finally, the constructed models were compared with radiologists' diagnoses. RESULTS: In univariable analysis, UP-related parameters, particularly UPC-T (cortex minus tumor attenuation on UP), demonstrated AUC of 0.766 in training cohort, 0.901 in test cohort 1, 0.805 in test cohort 2. The heterogeneity-related parameter SD (standard deviation) showed AUC of 0.781, 0.834, and 0.875 respectively. In multivariable analysis, model 1 incorporating UPC-T, NPC-T (cortex minus tumor attenuation on NP), CMPT-UPT (tumor attenuation on CMP minus UP), and SD yielded AUC of 0.866, 0.923, and 0.949 respectively. When compared with radiologists, multivariate models demonstrated higher accuracy (0.800-0.860) and sensitivity (0.794-0.971) than radiologists' assessments (accuracy: 0.700-0.720, sensitivity: 0.588-0.706). CONCLUSION: Quantitative measurements on CECT, particularly UP- and heterogeneity-related parameters, have potential to discriminate ccRCC and benign renal tumors (fpAML, RO).

DNA Polymerase-Steered Self-Propelled and Self-Enhanced DNA Walker for Rapid and Distinctly Amplified Electrochemical Sensing.

The development of a simple, rapid, easy-to-operate, and ultrasensitive DNA walker-based sensing system is challenging but would be very intriguing for the enormous applications in biological analysis and disease monitoring. Herein, a new self-propelled and self-enhanced DNA walking strategy was developed on the basis of a simple DNA polymerase-steered conversion from a typical alternate DNA assembly process. The sensing platform was fabricated easily by immobilizing only one hairpin probe (H1) and the sensing process was based on a simple one-step mixing with another hairpin-like DNA probe (H2) and DNA polymerase. The DNA polymerization could achieve target recycling and successive DNA walking steps. Interestingly, along with each DNA walking step, the new DNA walker sequence could be autonomously accumulated for a self-enhanced DNA walking effect. This provided a multilevel signal amplification ability for the ultrasensitive detection of the target with a low detection limit of 0.18 fM. Moreover, it could greatly reduce the reaction time with the sensing process finished within 1 h. The detection selectivity and the applicative potential in a complicated biological matrix were also demonstrated. Furthermore, the flexible control of sensing modes (self-enhanced DNA walking or the alternate DNA assembly) by using DNA polymerase or not offered a powerful means for sensing performance modulation. It thus opens a new avenue toward the development of a DNA walker-based sensing platform with both rapid and ultrasensitive features and might hold a huge potential for point-of-care diagnostic applications.

Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice.

The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Probiotics are commonly used after bariatric surgery. However, uncertainty remains regarding their effects. The purpose of this systematic review was to assess the effect of probiotics in patients with morbid obesity undergoing bariatric surgery. METHODS: PubMed, Cochrane Library, Embase, Science Direct, and Web of Science were searched from inception to April 4, 2023. No language restrictions were applied. Relevant randomized controlled trials and controlled clinical trials were included. We used the aggregated data extracted from the trials and assessed the heterogeneity. When severe heterogeneity was detected, a random effect model was used. All stages of the review were done by independent authors. RESULTS: We screened 2024 references and included 11 randomized controlled trials and controlled clinical trials. Compared with the protocol groups, probiotics showed significant effects on regulating aspartate amino transferase level (MD = -4.32 U/L; 95% CI [-7.10, -1.53], p = 0.002), triglycerides (MD = -20.16 mg/dL; 95% CI [-34.51, -5.82], p = 0.006), weight (MD = -1.99 kg; 95% CI [-3.97, -0.01], p = 0.05), vitamin B12 (MD = 2.24 pg/dL; 95% CI [-0.02, 4.51], p = 0.05), dietary energy (MD = -151.03 kcal; 95% CI [-215.68, -86.37], p < 0.00001), dietary protein (MD = -4.48 g/day, 95% CI [-8.76, -0.20], p = 0.04), dietary carbohydrate (MD = -34.25 g/day, 95% CI [-44.87, -23.62], p < 0.00001), and dietary fiber (MD = -2.17 g/day, 95% CI [-3.21, -1.14], p < 0.0001). There were no severe side effects related to probiotics. CONCLUSIONS: Our meta-analysis suggested that probiotics may delay the progression of liver function injury, improve lipid metabolism, reduce weight, and reduce food intake, although the effects on other indicators were insignificant. Probiotics may be helpful for patients undergoing bariatric surgery. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42023407970. No primary source of funding.

Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is among the most widespread metabolic disease globally, and its associated complications including insulin resistance and diabetes have become threatening conditions for human health. Previous studies on non-alcoholic fatty liver disease (NAFLD) were focused on the liver's lipid metabolism. However, growing evidence suggests that mitochondrial metabolism is involved in the pathogenesis of NAFLD to varying degrees in several ways, for instance in cellular division, oxidative stress, autophagy, and mitochondrial quality control. Ultimately, liver function gradually declines as a result of mitochondrial dysfunction. The liver is unable to transfer the excess lipid droplets outside the liver. Therefore, how to regulate hepatic mitochondrial function to treat NAFLD has become the focus of current research. This review provides details about the intrinsic link of NAFLD with mitochondrial metabolism and the mechanisms by which mitochondrial dysfunctions contribute to NAFLD progression. Given the crucial role of mitochondrial metabolism in NAFLD progression, the application potential of multiple mitochondrial function improvement modalities (including physical exercise, diabetic medications, small molecule agonists targeting Sirt3, and mitochondria-specific antioxidants) in the treatment of NAFLD was evaluated hoping to provide new insights into NAFLD treatment.

A DNA polymerase-powered self-propelled DNA walking strategy for one-step, amplified and dual-signal electrochemical target detection.

Developing a simple and easy-to-operate sensing platform for sensitive and reliable target analysis would provide enormous opportunities to boost the applications in clinical biomedicine and disease diagnosis. Herein, a DNA polymerase-powered self-propelled DNA walking strategy was developed to achieve one-step, dual-signal and amplified nucleic acid detection. The sensing platform was fabricated easily by immobilizing two hybrid probes on an electrode surface. Each hybrid probe consisted of a DNA hairpin and a redox reporter-labelled signal strand. The HIV-1 DNA fragment was used as a model target. It could trigger the DNA polymerization cascade between two hairpins assisted by DNA polymerase, accompanying the release of two signal strands from the electrode surface for the concurrent responses of two electrochemical signals of methylene blue and ferrocene. The simultaneous dual-signal and amplified responses facilitated the sensitive and reliable analysis of the target. The low detection limit toward the target nucleic acid could reach 0.1 fM whether by methylene blue or ferrocene responses. It could also achieve the selective discrimination toward mismatched sequences and the application for target detection in a serum sample. The distinct features of the current sensing strategy also include its autonomous one-step operation and no extra DNA reagent requirement for signal amplification except for a DNA polymerase. Thus, it provides an attractive means for biosensor fabrication directed toward the reliable and sensitive analysis of nucleic acids or more analytes.

Intramolecular Heterocyclization/Fluoromethylthiolation of Alkynes Enabled by a Multicomponent Reagent System.

The BnSRf (Rf = CF2H or CF3)/mCPBA/Tf2O system was found to be an effective multicomponent reagent system for the one-pot synthesis of di/trifluoromethylthiolated heterocycles from alkynes. The reaction was postulated to proceed via a cascade sequence involving the oxidation of BnSRf by mCPBA, activation of the in situ-generated sulfoxide by Tf2O, and intramolecular cyclization/fluoromethylthiolation of the alkyne substrates enabled by the formed electrophilic sulfonium salt to give di/trifluoromethylthiolated heterocycles.

Soluble Immune-Related Proteins as New Candidate Serum Biomarkers for the Diagnosis and Progression of Lymphangioleiomyomatosis.

Background: The goal of this study was to analyze serum from lymphangioleiomyomatosis (LAM) patients and healthy controls to identify novel biomarkers that could shed light on disease diagnosis and pathogenesis. Methods: From April 2017 to October 2019, qualified serum samples were obtained to explore differences in 59 immune proteins between 67 LAM patients and 49 healthy controls by the Luminex method. Results: We characterized 22 serum immune proteins that were differentially expressed in LAM patients compared with healthy people. Fifty-nine proteins were then classified into eight categories according to their biological function, and the results showed that LAM patients displayed significantly higher levels of growth factors (p = 0.006) and lower levels of costimulatory molecules (p = 0.008). LAG-3 was not only likely to have better predictive value than VEGF-D but also showed a significant difference between patients without elevated VEGF-D and healthy people. IL-18 was positively correlated with lung function and six-minute walk test (6MWT) distance and negatively correlated with St. George's Respiratory Questionnaire (SGRQ) score and pulmonary artery systolic pressure (PASP), which suggested that IL-18 was related to disease severity. PD-1 was significantly different between patients with pneumothorax and/or chylothorax and those without complications. Conclusion: We performed a large-scale serum immune factor analysis of LAM. Our study provides evidence that LAG-3 may be a novel candidate serum biomarker for the diagnosis of LAM. Future independent validation in prospective studies is warranted.

Fuhrman nuclear grade prediction of clear cell renal cell carcinoma: influence of volume of interest delineation strategies on machine learning-based dynamic enhanced CT radiomics analysis.

OBJECTIVE: To investigate the influence of different volume of interest (VOI) delineation strategies on machine learning-based predictive models for discrimination between low and high nuclear grade clear cell renal cell carcinoma (ccRCC) on dynamic contrast-enhanced CT. METHODS: This study retrospectively collected 177 patients with pathologically proven ccRCC (124 low-grade; 53 high-grade). Tumor VOI was manually segmented, followed by artificially introducing uncertainties as: (i) contour-focused VOI, (ii) margin erosion of 2 or 4 mm, and (iii) margin dilation (2, 4, or 6 mm) inclusive of perirenal fat, peritumoral renal parenchyma, or both. Radiomics features were extracted from four-phase CT images (unenhanced phase (UP), corticomedullary phase (CMP), nephrographic phase (NP), excretory phase (EP)). Different combinations of four-phasic features for each VOI delineation strategy were used to build 176 classification models. The best VOI delineation strategy and superior CT phase were identified and the top-ranked features were analyzed. RESULTS: Features extracted from UP and EP outperformed features from other single/combined phase(s). Shape features and first-order statistics features exhibited superior discrimination. The best performance (ACC 81%, SEN 67%, SPE 87%, AUC 0.87) was achieved with radiomics features extracted from UP and EP based on contour-focused VOI. CONCLUSION: Shape and first-order features extracted from UP + EP images are better feature representations. Contour-focused VOI erosion by 2 mm or dilation by 4 mm within peritumor renal parenchyma exerts limited impact on discriminative performance. It provides a reference for segmentation tolerance in radiomics-based modeling for ccRCC nuclear grading. KEY POINTS: • Lesion delineation uncertainties are tolerated within a VOI erosion range of 2 mm or dilation range of 4 mm within peritumor renal parenchyma for radiomics-based ccRCC nuclear grading. • Radiomics features extracted from unenhanced phase and excretory phase are superior to other single/combined phase(s) at differentiating high vs low nuclear grade ccRCC. • Shape features and first-order statistics features showed superior discriminative capability compared to texture features.

A Multiparametric MR-Based RadioFusionOmics Model with Robust Capabilities of Differentiating Glioblastoma Multiforme from Solitary Brain Metastasis.

This study aimed to evaluate the diagnostic potential of a novel RFO model in differentiating GBM and SBM with multiparametric MR sequences collected from 244 (131 GBM and 113 SBM) patients. Three basic volume of interests (VOIs) were delineated on the conventional axial MR images (T1WI, T2WI, T2_FLAIR, and CE_T1WI), including volumetric non-enhanced tumor (nET), enhanced tumor (ET), and peritumoral edema (pTE). Using the RFO model, radiomics features extracted from different multiparametric MRI sequence(s) and VOI(s) were fused and the best sequence and VOI, or possible combinations, were determined. A multi-disciplinary team (MDT)-like fusion was performed to integrate predictions from the high-performing models for the final discrimination of GBM vs. SBM. Image features extracted from the volumetric ET (VOIET) had dominant predictive performances over features from other VOI combinations. Fusion of VOIET features from the T1WI and T2_FLAIR sequences via the RFO model achieved a discrimination accuracy of AUC = 0.925, accuracy = 0.855, sensitivity = 0.856, and specificity = 0.853, on the independent testing cohort 1, and AUC = 0.859, accuracy = 0.836, sensitivity = 0.708, and specificity = 0.919 on the independent testing cohort 2, which significantly outperformed three experienced radiologists (p = 0.03, 0.01, 0.02, and 0.01, and p = 0.02, 0.01, 0.45, and 0.02, respectively) and the MDT-decision result of three experienced experts (p = 0.03, 0.02, 0.03, and 0.02, and p = 0.03, 0.02, 0.44, and 0.03, respectively).

Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids.

(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.

Multiphase Contrast-Enhanced CT-Based Machine Learning Models to Predict the Fuhrman Nuclear Grade of Clear Cell Renal Cell Carcinoma.

OBJECTIVE: To investigate the predictive performance of different machine learning models for the discrimination of low and high nuclear grade clear cell renal cell carcinoma (ccRCC) by using multiphase computed tomography (CT)-based radiomic features. MATERIALS AND METHODS: A total of 137 consecutive patients with pathologically proven ccRCC (including 96 low-grade [grade 1 or 2] and 41 high-grade [grade 3 or 4] ccRCC) from January 2011 to January 2019 were enrolled in this retrospective study. Target region of interest (ROI) delineation followed by texture extraction was performed on a representative slice with the largest section of the tumor on the four-phase (unenhanced phase [UP], corticomedullary phase [CMP], nephrographic phase [NP] and excretory phase [EP]) CT images. Fifteen concatenations of the four-phase features were fed into 176 classification models (built with 8 classifiers and 22 feature selection methods), the classification performances of the 2640 resultant discriminative models were compared, and the top-ranked features were analyzed. RESULTS: Image features extracted from the unenhanced phase (UP) CT images demonstrated a dominant classification performance over features from the other three phases. The discriminative model "Bagging + CMIM" achieved the highest classification AUC of 0.75. The top-ranked features from the UP included one shape-based feature and five first-order statistical features. CONCLUSION: Image features extracted from the UP are more effective than other CT phases in differentiating low and high nuclear grade ccRCC based on machine learning-based classification modeling.

Risk factors for right ventricular dysfunction in patients with lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by diffuse cystic lesions of the lung. The present study was designed to evaluate the right ventricular (RV) function in LAM patients via single-beat real-time three-dimensional echocardiography (RT-3DE) and to investigate the factors affecting RV function in LAM patients. According to tricuspid regurgitation velocity (TRV), forty-five female LAM patients [(44.07 ± 10.22) years old] were divided into TRV ≤ 2.8 m/s group (n = 29) and TRV > 2.8 m/s group (n = 16). Relative echocardiography parameters were assessed by conventional transthoracic echocardiography, Doppler tissue imaging (DTI) and RT-3DE, respectively. Pulmonary function tests and the six-minute walk tests (SMWT) were also performed for LAM patients. We found that most of RV functional parameters in LAM patients were worse than that in control patients, although left ventricular dysfunction was not significantly observed. Correlation analysis showed that 3D echocardiographic RV ejection fraction (RVEF) was negatively correlated with pulmonary vascular resistance (PVR), TRV, and the decrease of oxygen saturation (SpO2) post SMWT, and positively correlated with Forced expiratory volume in the first second/forced vital capacity, carbon monoxide diffusion predicted value, SMWT distance, and resting SpO2 in LAM patients. Multivariate stepwise linear regression analysis showed that PVR and SpO2 before SMWT were independent influence factors of RVEF in LAM patients. In this study, we found that RV dysfunction was presented in LAM patients, although left ventricular dysfunction was not significantly obvious. The main influence factors of RVEF were PVR and hypoxia. RT-3DE is a low-cost and noninvasive way to evaluate RV function in LAM patients.

Clear cell renal cell carcinoma: the value of sex-specific abdominal visceral fat measured on CT for prediction of Fuhrman nuclear grade.

OBJECTIVE: To explore whether sex-specific abdominal visceral fat composition on CT can predict the Fuhrman nuclear grade of clear cell renal cell carcinoma (ccRCC). METHODS: One hundred seventy-one patients (123 males and 48 females) from four hospitals (multicentre group) and 159 patients (109 males and 50 females) from the cancer imaging archive (TCIA-KIRC group) with pathologically proven ccRCC (multicentre: 124 low grade and 47 high grade; TCIA-KIRC: 79 low grade and 80 high grade) were retrospectively included. Abdominal fat was segmented into subcutaneous fat area (SFA) and visceral fat area (VFA) on CT using ImageJ. The total fat area (TFA) and relative VFA (rVFA) were then calculated. Clinical characteristics (age, sex, waist circumference and maximum tumour diameter) were also assessed. Univariate and multivariate logistic regression analyses were performed to identify the association between general or sex-specific visceral fat composition and Fuhrman grade. RESULTS: Females with high-grade ccRCC from the multicentre group had a higher rVFA (42.4 vs 31.3, p = 0.001) than those with low-grade ccRCC after adjusting for age. There was no significant difference in males. The rVFA remained a stable and independent predictor for females high-grade ccRCC in both the univariate (multicentre: OR 1.205, 95% CI 1.074-1.352, p = 0.001; TCIA-KIRC: OR 1.171, 95% CI 1.016-1.349, p = 0.029) and multivariate (multicentre: OR 1.095, 95% CI 1.024-1.170, p = 0.003; TCIA-KIRC: OR 1.103, 95% CI 1.024-1.187, p = 0.010) models. CONCLUSIONS: Sex-specific visceral fat composition has different values for predicting high-grade ccRCC and could be used as an independent predictor for females with high-grade ccRCC. KEY POINTS: • Visceral fat measurement (rVFA) as an independent predictor for high-grade ccRCC had good predictive power in females, but not in males. • Sex-specific visceral fat composition was significantly associated with high-grade ccRCC in females only. • The rVFA could be considered one of the risk factors for high-grade ccRCC for females.

miR-223 induces retinal ganglion cells apoptosis and inflammation via decreasing HSP-70 in vitro and in vivo.

PURPOSE: Glaucoma is an eye disease characterized by the loss of peripheral vision, high pressure in the eye, optic nerve damage, and the loss of peripheral vision due to loss of retinal ganglion cells (RGCs). A number of miRNA have been detected in the pathogenesis of glaucoma. The paper was to focus on the miR-223 in RGCs apoptosis and inflammation, and investigated the possible mechanisms in vitro and in vivo. MATERIALS AND METHODS: After miR-223 inhibitor and mimics transfected into RGCs, the expression of miR-223 was detected by QRT-PCR, cell proliferation were performed by CCK-8 and EdU assays, cell apoptosis were measured by flow cytometer and TUNEL assays, apoptosis and inflammation -related proteins were detected by western blot, and whether miR-223 target to HSP-70 was detected by Luciferease reporter assay. Moreover, the effects si-HSP-70 on RGCs or RGCs transfected with miR-223 inhibitor were detected. In vivo study. New Zealand White rabbits (20 females) were used to detect the effect of miR-223 on the rabbit glaucoma model induced by injection of carbomer. RESULTS: CCK-8 and EdU assays demonstrated that miR-223 mimics decreased RGCs proliferation. FITC-Annexin V/PI Apoptosis and TUNEL assays showed that miR-223 mimics induced RGCs apoptosis. Western blot revealed that miR-223 mimics enhanced the expression of relative apoptosis and inflammation factors. Further, we demonstrated that miR-223 could inhibit cell proliferation, induce cell apoptosis as well as inflammation by targeting HSP-70 in RGCs. Moreover, the results were confirmed in rabbit glaucoma model. CONCLUSIONS: In summary, miR-223 plays a vital role in RGCs by regulating HSP-70 expression, and the new therapeutic strategy might potentially contribute to benefit glaucoma treatment.

Identification of driver genes and somatic mutations in cell-free DNA of patients with pulmonary lymphangioleiomyomatosis.

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.