A meta-analysis of MRI radiomics-based diagnosis for BI-RADS 4 breast lesions.

OBJECTIVE: The aim of this study is to conduct a systematic evaluation of the diagnostic efficacy of Breast Imaging Reporting and Data System (BI-RADS) 4 benign and malignant breast lesions using magnetic resonance imaging (MRI) radiomics. METHODS: A systematic search identified relevant studies. Eligible studies were screened, assessed for quality, and analyzed for diagnostic accuracy. Subgroup and sensitivity analyses explored heterogeneity, while publication bias, clinical relevance and threshold effect were evaluated. RESULTS: This study analyzed a total of 11 studies involving 1,915 lesions in 1,893 patients with BI-RADS 4 classification. The results showed that the combined sensitivity and specificity of MRI radiomics for diagnosing BI-RADS 4 lesions were 0.88 (95% CI 0.83-0.92) and 0.79 (95% CI 0.72-0.84). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 4.2 (95% CI 3.1-5.7), 0.15 (95% CI: 0.10-0.22), and 29.0 (95% CI 15-55). The summary receiver operating characteristic (SROC) analysis yielded an area under the curve (AUC) of 0.90 (95% CI 0.87-0.92), indicating good diagnostic performance. The study found no significant threshold effect or publication bias, and heterogeneity among studies was attributed to various factors like feature selection algorithm, radiomics algorithms, etc. Overall, the results suggest that MRI radiomics has the potential to improve the diagnostic accuracy of BI-RADS 4 lesions and enhance patient outcomes. CONCLUSION: MRI-based radiomics is highly effective in diagnosing BI-RADS 4 benign and malignant breast lesions, enabling improving patients' medical outcomes and quality of life.

Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.

Elimination of Pathogen Biofilms via Postbiotics from Lactic Acid Bacteria: A Promising Method in Food and Biomedicine.

Pathogenic biofilms provide a naturally favorable barrier for microbial growth and are closely related to the virulence of pathogens. Postbiotics from lactic acid bacteria (LAB) are secondary metabolites and cellular components obtained by inactivation of fermentation broth; they have a certain inhibitory effect on all stages of pathogen biofilms. Postbiotics from LAB have drawn attention because of their high stability, safety dose parameters, and long storage period, which give them a broad application prospect in the fields of food and medicine. The mechanisms of eliminating pathogen biofilms via postbiotics from LAB mainly affect the surface adhesion, self-aggregation, virulence, and QS of pathogens influencing interspecific and intraspecific communication. However, there are some factors (preparation process and lack of target) which can limit the antibiofilm impact of postbiotics. Therefore, by using a delivery carrier and optimizing process parameters, the effect of interfering factors can be eliminated. This review summarizes the concept and characteristics of postbiotics from LAB, focusing on their preparation technology and antibiofilm effect, and the applications and limitations of postbiotics in food processing and clinical treatment are also discussed.

Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy.

This study assesses the efficacy of an innovative therapeutic approach that combines GLP-1 and amylin analogues for weight reduction. Focusing on GLP-1 analogues from bullfrog (Rana catesbeiana), we designed ten bGLP-1 analogues with various modifications. Among them, bGLP-10 showed high potency in binding and activating GLP-1 receptors, with superior albumin affinity. In diet-induced obesity (DIO) mice fed a high-fat diet, bGLP-10 demonstrated significant superiority over semaglutide in reducing blood sugar and food intake at a dose of 10 nmol/kg (P < 0.001). Notably, in a chronic study involving DIO mice, the combination of bGLP-10 with the amylin analogue cagrilintide led to a more substantial weight loss (-38.4%, P < 0.001) compared to either the semaglutide-cagrilintide combination (-23.0%) or cagrilintide (-5.7%), bGLP-10 (-16.1%), and semaglutide (-10.9%) alone. Furthermore, the bGLP-10 and cagrilintide combination exhibited superior glucose control and liver lipid management compared to the semaglutide-cagrilintide combination (P < 0.001). These results highlight bGLP-10's potential in GLP-1 and amylin-based therapies and suggest exploring more GLP-1 analogues from natural sources for anti-obesity and anti-diabetic treatments.

Obesity Paradox in Patients with Acute Coronary Syndrome: Is Malnutrition the Answer?

BACKGROUND: Obesity paradox has been reported in patients with cardiovascular disease, showing an inverse association between obesity as defined by BMI (in kg/m2) and prognosis. Nutritional status is associated with systemic inflammatory response and affects cardiovascular disease outcomes. OBJECTIVES: This study sought to examine the influence of obesity and malnutrition on the prognosis of patients with acute coronary syndrome (ACS). METHODS: This study included consecutive patients diagnosed with ACS and underwent coronary angiogram between January 2009 and February 2023. At baseline, patients were categorized according to their BMI as follows: underweight (<18), normal weight (18-24.9), overweight (25.0-29.9), and obese (>30.0). We assessed the nutritional status by Prognostic Nutritional Index (PNI). Malnutrition was defined as a PNI value of <38. RESULTS: Of the 21,651 patients with ACS, 582 (2.7%) deaths from any cause were observed over 28.7 months. Compared with the patient's state of normal weight, overweight, and obesity were associated with decreased risk of all-cause mortality. Malnutrition was independently associated with poor survival (hazards ratio: 2.64; 95% CI: 2.24, 3.12; P < 0.001). In malnourished patients, overweight and obesity showed a 39% and 72% reduction in the incidence of all-cause mortality, respectively. However, in nourished patients, no significant reduction in the incidence of all-cause mortality was observed (all P > 0.05). CONCLUSIONS: Obesity paradox appears to occur in patients with ACS. Malnutrition may be a significant independent risk factor for prognosis in patients with ACS. The obesity paradox is influenced by the status of malnutrition.

Rapid, sensitive, and user-friendly detection of Pseudomonas aeruginosa using the RPA/CRISPR/Cas12a system.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening bacterium known for its rapid development of antibiotic resistance, posing significant challenges in clinical treatment, biosecurity, food safety, and environmental monitoring. Early and accurate identification of P. aeruginosa is crucial for effective intervention. METHODS: The lasB gene of P. aeruginosa was selected as the target for the detection. RPA primers for recombinase polymerase amplification (RPA) and crRNA for CRISPR/Cas12a detection were meticulously designed to target specific regions within the lasB gene. The specificity of the RPA/CRISPR/Cas12a detection platform was assessed using 15 strains. The detection limit of RPA/CRISPR/Cas12a detection platform was determined by utilizing a pseudo-dilution series of the P. aeruginosa DNA. The practical applicability of the RPA/CRISPR/Cas12a detection platform was validated by comparing it with qPCR on 150 samples (35 processed meat product samples, 55 cold seasoned vegetable dishes, 60 bottled water samples). RESULTS: The RPA/CRISPR/Cas12a detection platform demonstrates high specificity, with no cross-reactivity with non-P. aeruginosa strains. This assay exhibits remarkable sensitivity, with a limit of detection (LOD) of 100 copies/µL for fluorescence assay and 101 copies/µL for the LFTS method. Furthermore, the performance of the RPA/CRISPR/Cas12a detection platform is comparable to that of the well-established qPCR method, while offering advantages such as shorter reaction time, simplified operation, and reduced equipment requirements. CONCLUSIONS: The RPA/CRISPR/Cas12a detection platform presents a straightforward, accurate, and sensitive approach for early P. aeruginosa detection and holds great promise for diverse applications requiring rapid and reliable identification.

Metagenome reveals the possible mechanism that microbial strains promote methanogenesis during anaerobic digestion of food waste.

For better understanding the mechanism of microbial strains promoting methane production, four strains Hungatella xylanolytica A5, Bacillus licheniformis B1, Paraclostridium benzoelyticum C2 and Advenella faeciporci E1 were inoculated into anaerobic digestion systems. After bioaugmentation, the cumulative methane production of A5, B1, C2 and E1 groups elevated by 11.68%, 8.20%, 18.21% and 15.67% compared to CK group, respectively. The metagenomic analysis revealed that the species diversity and uniformity of the experimental groups was improved, and hydrolytic acidifying bacteria, represented by Clostridiaceae, Anaerolineaceae and Oscillospiraceae, and methanogens, such as Methanotrichaceae and Methanobacteriaceae, were enriched. Meanwhile, the abundance of key genes in carbohydrate, pyruvate and methane metabolism was increased in the inoculated groups, providing reasonable reasons for more methane production. The strengthening mechanism of microbial strains in this study offered a theoretical foundation for selecting a suitable bioaugmentation strategy to solve the problems of slow start-up and low methane production in anaerobic digestion.

Prognostic PET [11C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

BACKGROUND: Positron Emission Tomography (PET) with combined [18F]-FDG and [11C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS: Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [11C]-acetate and [18F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution. RESULTS: HAL-treated mice showed lower [11C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUVTLR): 2.14[2.05-2.21] vs 3.11[2.75-5.43], p = 0.02) but not [18F]-FDG (HAL-treated vs. Control, SUVTLR: 3.73[3.12-4.35] vs 3.86[3.7-5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [11C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [11C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06-0.42, p < 0.0001). CONCLUSIONS: [11C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.

Differentiation of isomeric chalcone and dihydroflavone using liquid chromatography coupled with hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS): An application for flavonoids-focused characterization of Snow chrysanthemum.

Although the co-occurrences of isomeric chalcones and dihydroflavones widely appear in medicinal plants, the differentiation of such isomerism seldom succeeds using MS/MS, attributing to totally identical MS/MS spectra. Here, efforts were paid to pursue an eligible tool allowing to address the technical challenge. Being inspired by that one more proton signal is observed in 1H NMR spectrum of isoliquiritigenin than liquiritigenin when employing DMSO­d6 as solvent, hydrogen-deuterium exchange (HDX)-MS/MS was evaluated towards differentiating isomeric chalcones and dihydroflavones through replacing H2O with D2O to prepare the mobile phase. As a result, differences were observed for either MS1 or MS2 spectrum when comparing two pairs of isomers, such as liquiritigenin vs. isoliquiritigenin and liquiritin vs. isoliquiritin, because the isomeric precursor and fragment ion species owned different amounts of hydroxyl protons and those reactive protons could be partially or completely substituted by deuterium protons at the exposure in D2O to result in n × 1.006 mass increments. Moreover, utmost four hydrogen/deuterium exchanges occurred for a single glucosyl moiety. Thereafter, HDX-MS/MS was applied to characterize the flavonoids of Snow chrysanthemum, a precious edible herbal medicine that is rich in isomeric chalcones and dihydroflavones. Through paying special attention to the deuterium labeling styles of (de)protonated molecules as well as those featured fragment ions, five pairs of isomeric chalcones and dihydroflavones were confirmatively differentiated, in addition to that 28 flavonoids were structurally annotated by applying those well-defined mass fragmentation rules. Hence, this study offered an in-depth insight towards the flavonoids-focused characterization of Snow chrysanthemum, and more importantly, HDX-MS/MS is a superior tool to differentiate, but not limited to, isomeric chalcones and dihydroflavones.

DEHP induces apoptosis and autophagy of the thyroid via Rap1 signaling pathway: In vivo and in vitro study.

OBJECTIVE: DEHP has thyroid toxicity and affects thyroid function. However, the mechanism is unclear. METHODS: The offspring of SD rats were gavaged with different doses of DEHP from in utero to 8 or 12 weeks old. We observed the thyroid morphology with HE and autophagosomes with TEM. The THs levels were tested with ELISA. The apoptosis level was tested by flow cytometry. The levels of apoptosis-related genes, autophagy-related genes and Rap1 pathway genes, were measured with qRT-PCR and Western blot. We established an MEHP-treated Nthy-ori 3-1 cell model and inhibited the Rap1 to verify the mechanism. RESULTS: DEHP could cause pathological damage and ultrastructure damage of thyroids in offspring rats. After DEHP exposure, the THs levels were altered, the apoptosis levels increased, and autophagosomes appeared. DEHP significantly affected the levels of apoptosis-related genes and autophagy-related genes. DEHP also affected the levels of Rap1 pathway, which was correlated with the levels of apoptosis and autophagy. After inhibiting Rap1 in Nthy-ori 3-1 cells, the THs levels were altered. Rap1 pathway was inhibited and the levels of apoptosis and autophagy were down-regulated. CONCLUSION: DEHP could induce the apoptosis and autophagy of the thyroid, and Rap1 signaling pathway may play a significant role.

Assessment of Right Atrial Function Measured with Cardiac MRI Feature Tracking for Predicting Outcomes in Patients with Dilated Cardiomyopathy.

Background Right atrial (RA) function strain is increasingly acknowledged as an important predictor of adverse events in patients with diverse cardiovascular conditions. However, the prognostic value of RA strain in patients with dilated cardiomyopathy (DCM) remains uncertain. Purpose To evaluate the prognostic value of RA strain derived from cardiac MRI (CMR) feature tracking (FT) in patients with DCM. Materials and Methods This multicenter, retrospective study included consecutive adult patients with DCM who underwent CMR between June 2010 and May 2022. RA strain parameters were obtained using CMR FT. The primary end points were sudden or cardiac death or heart transplant. Cox regression analysis was used to determine the association of variables with outcomes. Incremental prognostic value was evaluated using C indexes and likelihood ratio tests. Results A total of 526 patients with DCM (mean age, 51 years ± 15 [SD]; 381 male) were included. During a median follow-up of 41 months, 79 patients with DCM reached the primary end points. At univariable analysis, RA conduit strain was associated with the primary end points (hazard ratio [HR], 0.82 [95% CI: 0.76, 0.87]; P < .001). In multivariable Cox analysis, RA conduit strain was an independent predictor for the primary end points (HR, 0.83 [95% CI: 0.77, 0.90]; P < .001). A model combining RA conduit strain with other clinical and conventional imaging risk factors (C statistic, 0.80; likelihood ratio, 92.54) showed improved discrimination and calibration for the primary end points compared with models with clinical variables (C statistic, 0.71; likelihood ratio, 37.12; both P < .001) or clinical and imaging variables (C statistic, 0.75; likelihood ratio, 64.69; both P < .001). Conclusion CMR FT-derived RA conduit strain was an independent predictor of adverse outcomes among patients with DCM, providing incremental prognostic value when combined in a model with clinical and conventional CMR risk factors. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Peripheral immune cell traits and Parkinson's disease: A Mendelian randomization study.

BACKGROUND: The peripheral immune system is altered in Parkinson's disease (PD), but the causal relationship between the two remains controversial. In this study, we aimed to estimate the causal relationship between peripheral immune features and PD using a two-sample Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) data of peripheral blood immune signatures from European populations were used for exposure and PD summary statistics were used as results. We conducted a two-sample MR study using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods to evaluate the causal association between these factors. MR-Egger and MR-PRESSO were used for sensitivity analysis to test and correct horizontal pleiotropy. RESULTS: A total of 731 immune traits were analyzed for association with PD using three MR methods. After adjustment for FDR, we observed four peripheral immunological features associated with PD using the IVW method, including expression of CX3CR1 on monocytes [OR: 0.85, 95% CI: (0.81, 0.91), P = 6.56E-07] and CX3CR1 on CD14+CD16+ monocytes [OR: 0.87, 95% CI: (0.82, 0.93), P = 9.95E-06]. CONCLUSIONS: Our study further revealed the important role of monocytes in PD and indicated that CX3CR1 expression on monocytes is associated with a reduced risk of PD.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Regulation of Disease-Resistance Genes against CWMV Infection by NbHAG1-Mediated H3K36ac.

Post-translational modification of proteins plays a critical role in plant-pathogen interactions. Here, we demonstrate in Nicotiana benthamiana that knockout of NbHAG1 promotes Chinese wheat mosaic virus (CWMV) infection, whereas NbHAG1 overexpression inhibits infection. Transcriptome sequencing indicated that a series of disease resistance-related genes were up-regulated after overexpression of NbHAG1. In addition, cleavage under targets and tagmentation (Cut&Tag)-qPCR results demonstrated that NbHAG1 may activate the transcription of its downstream disease-resistance genes by facilitating the acetylation level of H3K36ac. Therefore, we suggest that NbHAG1 is an important positive regulator of resistance to CWMV infestation.

Ultrasensitive protein and exosome analysis based on a rolling circle amplification assisted-CRISPR/Cas12a strategy.

CRISPR/Cas12a system has attracted extensive concern in biosensing due to its high specificity and programmability. Nevertheless, existing Cas12a-based assays mainly focus on nucleic acid detection and have limitations in non-nucleic acid biomarker analysis. To broaden the application prospect of the CRISPR/Cas technology, a cascade Cas12a biosensing platform is reported by combining dual-functionalized gold nanoparticles (FGNPs)-assisted rolling circle amplification (RCA) and Cas12a trans-cleavage activity (GAR-Cas) for ultrasensitive protein and exosome analysis. FGNPs serve as a critical component in the transduction of protein or exosome recognition information into nucleic acid amplification events to produce Cas12a activators. In the GAR-Cas assay, by integrating the triple cascade amplification of FGNPs-assisted transduction, RCA, and Cas12a signal amplification, ultralow abundance of target molecules can arouse numerous concatemers to activate Cas12a trans-cleavage activity to release intense fluorescence, allowing the ultrasensitive detection of as low as 1 fg/mL (∼41 aM) cTnI and 5 exosomes per µL. Furthermore, the presented strategy can be applied to detect exosome levels from clinical samples, showing excellent performance in distinguishing cancer patients from healthy individuals. The GAR-Cas sensing platform exhibits great potential in clinical diagnosis and enlarges biosensing toolboxes based on CRISPR/Cas technology for non-nucleic acid target analysis.

Strategy strengthens structural identification through hyphenating full collision energy ramp-MS2 and full exciting energy ramp-MS3 spectra: An application for metabolites identification of rosmarinic acid.

"MS/MS spectrum to structure" analysis is the most challenging task for MS/MS-relied qualitative characterization. The conventional database- and computation-assisted strategies cannot reach confirmative identification, notably for isomers. Hence, an advanced strategy was proposed here through tackling the two determinant obstacles such as the transformation from elemental compositions to fragment ion structures and the linkage style amongst substructures. As typical conjugated structures, esters were measured for strategy illustration, and metabolite identification of a famous natural antioxidant namely rosmarinic acid (RosA) in rat was undertaken for applicability justification. Through programming online energy-resolved (ER)-MS for the first collision cell of Qtrap-MS device, full collision energy ramp (FCER)-MS2 spectrum was configured for [M-H]- ion of each ester to provide optimal collision energies (OCEs) for all concerned diagnostic fragment ions (DFIs), i.e. a-, b-, c-, y-, and z-type ions. The linear correlations between masses and OCEs were built for each ion type to facilitate DFIs recognition from chaotic MS2 spectrum. To identify 1st-generation fragment ions, full exciting energy ramp (FEER)-MS3 spectra were configured for key DFIs via programming the second ER-MS in the latter collision chamber. FEER-MS3 spectrum of 1st-generation fragment ion for ester was demonstrated to be identical with FEER-MS2 spectrum of certain hydrolysis product when sharing the same structure. After applying the advanced strategy to recognize DFIs and identify 1st-generation fragment ions, a total of forty metabolites (M1-M40), resulted from hydrolysis, methylation, sulfation, and glucuronidation, were unambiguously identified for RosA after oral administration. Together, the advanced bottom-up strategy hyphenating FCER-MS2 and FEER-MS3 spectra, is meaningful to strengthen "MS/MS spectrum to structure" analysis through recognizing and identifying fragment ions.

Enhanced Thermal Boundary Conductance across GaN/SiC Interfaces with AlN Transition Layers.

Heat dissipation plays a crucial role in the performance and reliability of high-power GaN-based electronics. While AlN transition layers are commonly employed in the heteroepitaxial growth of GaN-on-SiC substrates, concerns have been raised about their impact on thermal transport across GaN/SiC interfaces. In this study, we present experimental measurements of the thermal boundary conductance (TBC) across GaN/SiC interfaces with varying thicknesses of the AlN transition layer (ranging from 0 to 73 nm) at different temperatures. Our findings reveal that the addition of an AlN transition layer leads to a notable increase in the TBC of the GaN/SiC interface, particularly at elevated temperatures. Structural characterization techniques are employed to understand the influence of the AlN transition layer on the crystalline quality of the GaN layer and its potential effects on interfacial thermal transport. To gain further insights into the trend of TBC, we conduct molecular dynamics simulations using high-fidelity deep learning-based interatomic potentials, which reproduce the experimentally observed enhancement in TBC even for atomically perfect interfaces. These results suggest that the enhanced TBC facilitated by the AlN intermediate layer could result from a combination of improved crystalline quality at the interface and the "phonon bridge" effect provided by AlN that enhances the overlap between the vibrational spectra of GaN and SiC.

Joint analysis of proteome, transcriptome, and multi-trait analysis to identify novel Parkinson's disease risk genes.

Genome-wide association studies (GWAS) have identified multiple risk variants for Parkinson's disease (PD). Nevertheless, how the risk variants confer the risk of PD remains largely unknown. We conducted a proteome-wide association study (PWAS) and summary-data-based mendelian randomization (SMR) analysis by integrating PD GWAS with proteome and protein quantitative trait loci (pQTL) data from human brain, plasma and CSF. We also performed a large transcriptome-wide association study (TWAS) and Fine-mapping of causal gene sets (FOCUS), leveraging joint-tissue imputation (JTI) prediction models of 22 tissues to identify and prioritize putatively causal genes. We further conducted PWAS, SMR, TWAS, and FOCUS using a multi-trait analysis of GWAS (MTAG) to identify additional PD risk genes to boost statistical power. In this large-scale study, we identified 16 genes whose genetically regulated protein abundance levels were associated with Parkinson's disease risk. We undertook a large-scale analysis of PD and correlated traits, through TWAS and FOCUS studies, and discovered 26 casual genes related to PD that had not been reported in previous TWAS. 5 genes (CD38, GPNMB, RAB29, TMEM175, TTC19) showed significant associations with PD at both the proteome-wide and transcriptome-wide levels. Our study provides new insights into the etiology and underlying genetic architecture of PD.