The F-box protein RhSAF destabilizes the gibberellic acid receptor RhGID1 to mediate ethylene-induced petal senescence in rose.

Roses are among the most popular ornamental plants cultivated worldwide for their great economic, symbolic, and cultural importance. Nevertheless, rapid petal senescence markedly reduces rose (Rosa hybrida) flower quality and value. Petal senescence is a developmental process tightly regulated by various phytohormones. Ethylene accelerates petal senescence, while gibberellic acid (GA) delays this process. However, the molecular mechanisms underlying the crosstalk between these phytohormones in the regulation of petal senescence remain largely unclear. Here, we identified SENESCENCE-ASSOCIATED F-BOX (RhSAF), an ethylene-induced F-box protein gene encoding a recognition subunit of the SCF-type E3 ligase. We demonstrated that RhSAF promotes degradation of the GA receptor GIBBERELLIN INSENSITIVE DWARF1 (RhGID1) to accelerate petal senescence. Silencing RhSAF expression delays petal senescence, while suppressing RhGID1 expression accelerates petal senescence. RhSAF physically interacts with RhGID1s and targets them for ubiquitin/26S proteasome-mediated degradation. Accordingly, ethylene-induced RhGID1C degradation and RhDELLA3 accumulation are compromised in RhSAF-RNAi lines. Our results demonstrate that ethylene antagonizes GA activity through RhGID1 degradation mediated by the E3 ligase RhSAF. These findings enhance our understanding of the phytohormone crosstalk regulating petal senescence and provide insights for improving flower longevity.

Substrates mimicking the blastocyst geometry revert pluripotent stem cell to naivety.

Naive pluripotent stem cells have the highest developmental potential but their in vivo existence in the blastocyst is transient. Here we report a blastocyst motif substrate for the in vitro reversion of mouse and human pluripotent stem cells to a naive state. The substrate features randomly varied microstructures, which we call motifs, mimicking the geometry of the blastocyst. Motifs representing mouse-blastocyst-scaled curvature ranging between 15 and 62 mm-1 were the most efficient in promoting reversion to naivety, as determined by time-resolved correlative analysis. In these substrates, apical constriction enhances E-cadherin/RAC1 signalling and activates the mechanosensitive nuclear transducer YAP, promoting the histone modification of pluripotency genes. This results in enhanced levels of pluripotency transcription factor NANOG, which persist even after cells are removed from the substrate. Pluripotent stem cells cultured in blastocyst motif substrates display a higher development potential in generating embryoid bodies and teratomas. These findings shed light on naivety-promoting substrate design and their large-scale implementation.

Multiomics analyses provide insights into the genomic basis of differentiation among four sweet osmanthus groups.

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers.

Poly (adenosine diphosphate-ribose) polymerase inhibitors in the treatment of triple-negative breast cancer with homologous repair deficiency.

Breast cancer (BC) is a highly heterogeneous disease, and the presence of germline breast cancer gene mutation (gBRCAm) is associated with a poor prognosis. Triple-negative breast cancer (TNBC) is a BC subtype, characterized by the absence of hormone and growth factor receptor expression, making therapeutic decisions difficult. Defects in the DNA damage response pathway due to mutation in breast cancer genes (BRCA 1/2) lead to homologous recombination deficiency (HRD). However, in HRD conditions, poly (adenosine diphosphate-ribose) polymerase (PARP) proteins repair DNA damage and lead to tumor cell survival. Biological understanding of HRD leads to the development of PARP inhibitors (PARPi), which trap PARP proteins and cause genomic instability and tumor cell lysis. HRD assessment can be an important biomarker in identifying gBRCAm patients with BC who could benefit from PARPi therapy. HRD can be identified by homologous recombination repair (HRR) gene-based assays, genomic-scarring assays and mutational signatures, transcription and protein expression profiles, and functional assays. However, gold standard methodologies that are robust and reliable to assess HRD are not available currently. Hence, there is a pressing need to develop accurate biomarkers identifying HRD tumors to guide targeted therapies such as PARPi in patients with BC. HRD assessment has shown fruitful outcomes in chemotherapy studies and preliminary evidence on PARPi intervention as monotherapy and combination therapy in HRD-stratified patients. Furthermore, ongoing trials are exploring the potential of PARPi in BC and clinically complex TNBC settings, where HRD testing is used as an adjunct to stratify patients based on BRCA mutations.

Identification of novel single nucleotide variants in the drug resistance mechanism of Mycobacterium tuberculosis isolates by whole-genome analysis.

BACKGROUND: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium. METHODS: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool. RESULTS: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins. CONCLUSION: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.

Fluorescence Sensing of Eclampsia Biomarkers via the Immunosorbent Atom Transfer Radical Polymerization Assay.

Accurate and quantitative detection of pre-eclampsia markers is crucial in reducing pregnancy mortality rates. This study introduces a novel approach utilizing a fluorescent biosensor by the immunosorbent atom transfer radical polymerization (immuno-ATRP) assay to detect the pre-eclampsia protein marker CD81. The critical step used in this sensor is the novel signal amplification strategy of fluorescein polymerization mediated by ferritin-enhanced controlled radical polymerization, which combines with a traditional enzyme-linked immunosorbent assay (ELISA) to further reduce the detection limit of the CD81 protein concentration. The fluorescence intensity was linear versus logarithmic CD81 protein concentration from 0.1 to 10,000 pg mL-1, and the detection limit was 0.067 pg mL-1. Surprisingly, in 30% normal human serum (NHS), the sensor can also detect target protein over 0.1-10,000 pg mL-1, with 0.083 pg mL-1 for the detection limit. Moreover, the proposed biosensor is designed to be cost-effective, making it accessible, particularly in resource-limited settings where expensive detection techniques may not be available. The affordability of this method enables widespread screening and monitoring of preeclampsia, ultimately benefiting many pregnant women by improving their healthcare outcomes. In short, developing of a low-cost and susceptible direct detection method for preeclampsia protein markers, such as CD81, through the use of the immuno-ATRP assay, has significant implications for reducing pregnancy mortality. This method holds promise for early detection, precise treatment, and improved management of preeclampsia, thereby contributing to better maternal and fetal health.

Identification and validation of stable reference genes for RT-qPCR analyses of Kobresia littledalei seedlings.

BACKGROUND: Kobreisa littledalei, belonging to the Cyperaceae family is the first Kobresia species with a reference genome and the most dominant species in Qinghai-Tibet Plateau alpine meadows. It has several resistance genes which could be used to breed improved crop varieties. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) is a popular and accurate gene expression analysis method. Its reliability depends on the expression levels of reference genes, which vary by species, tissues and environments. However, K.littledalei lacks a stable and normalized reference gene for RT-qPCR analysis. RESULTS: The stability of 13 potential reference genes was tested and the stable reference genes were selected for RT-qPCR normalization for the expression analysis in the different tissues of K. littledalei under two abiotic stresses (salt and drought) and two hormonal treatments (abscisic acid (ABA) and gibberellin (GA)). Five algorithms were used to assess the stability of putative reference genes. The results showed a variation amongst the methods, and the same reference genes showed tissue expression differences under the same conditions. The stability of combining two reference genes was better than a single one. The expression levels of ACTIN were stable in leaves and stems under normal conditions, in leaves under drought stress and in roots under ABA treatment. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression was stable in the roots under the control conditions and salt stress and in stems exposed to drought stress. Expression levels of superoxide dismutase (SOD) were stable in stems of ABA-treated plants and in the roots under drought stress. Moreover, RPL6 expression was stable in the leaves and stems under salt stress and in the stems of the GA-treated plants. EF1-alpha expression was stable in leaves under ABA and GA treatments. The expression levels of 28 S were stable in the roots under GA treatment. In general, ACTIN and GAPDH could be employed as housekeeping genes for K. littledalei under different treatments. CONCLUSION: This study identified the best RT-qPCR reference genes for different K. littledalei tissues under five experimental conditions. ACTIN and GAPDH genes can be employed as the ideal housekeeping genes for expression analysis under different conditions. This is the first study to investigate the stable reference genes for normalized gene expression analysis of K. littledalei under different conditions. The results could aid molecular biology and gene function research on Kobresia and other related species.

Incorporating ReS2 Nanosheet into ZnIn2S4 Nanoflower as Synergistic Z-Scheme Photocatalyst for Highly Effective and Stable Visible-Light-Driven Photocatalytic Hydrogen Evolution and Degradation.

Inspired by natural photosynthesis, the visible-light-driven Z-scheme system is very effective and promising for boosting photocatalytic hydrogen production and pollutant degradation. Here, a synergistic Z-scheme photocatalyst is constructed by coupling ReS2 nanosheet and ZnIn2S4 nanoflower and the experimental evidence for this direct Z-scheme heterostructure is provided by X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and electron paramagnetic resonance. Consequently, such a unique nanostructure makes this Z-scheme heterostructure exhibit 23.7 times higher photocatalytic hydrogen production than that of ZnIn2S4 nanoflower. Moreover, the ZnIn2S4/ReS2 photocatalyst is also very stable for photocatalytic hydrogen evolution, almost without activity decay even storing for two weeks. Besides, this Z-scheme heterostructure also exhibits superior photocatalytic degradation rates of methylene blue (1.7 × 10-2 min-1) and mitoxantrone (4.2 × 10-3 min-1) than that of ZnIn2S4 photocatalyst. The ultraviolet-visible absorption spectra, transient photocurrent spectra, open-circuit potential measurement, and electrochemical impedance spectroscopy reveal that the superior photocatalytic performance of ZnIn2S4/ReS2 heterostructure is mostly attributed to its broad and strong visible-light absorption, effective separation of charge carrier, and improved redox ability. This work provides a promising nanostructure design of a visible-light-driven Z-scheme heterostructure to simultaneously promote photocatalytic reduction and oxidation activity.

The transcription factor RhMYB17 regulates the homeotic transformation of floral organs in rose (Rosa hybrida) under cold stress.

Low temperatures affect flower development in rose (Rosa hybrida), increasing petaloid stamen number and reducing normal stamen number. We identified the low-temperature-responsive R2R3-MYB transcription factor RhMYB17, which is homologous to Arabidopsis MYB17 by similarity of protein sequences. RhMYB17 was up-regulated at low temperatures, and RhMYB17 transcripts accumulated in floral buds. Transient silencing of RhMYB17 by virus-induced gene silencing decreased petaloid stamen number and increased normal stamen number. According to the ABCDE model of floral organ identity, class A genes APETALA 1 (AP1) and AP2 contribute to sepal and petal formation. Transcription factor binding analysis identified RhMYB17 binding sites in the promoters of rose APETALA 2 (RhAP2) and APETALA 2-LIKE (RhAP2L). Yeast one-hybrid assays, dual-luciferase reporter assays, and electrophoretic mobility shift assays confirmed that RhMYB17 directly binds to the promoters of RhAP2 and RhAP2L, thereby activating their expression. RNA sequencing further demonstrated that RhMYB17 plays a pivotal role in regulating the expression of class A genes, and indirectly influences the expression of the class C gene. This study reveals a novel mechanism for the homeotic transformation of floral organs in response to low temperatures.

Protein function annotation and virulence factor identification of Klebsiella pneumoniae genome by multiple machine learning models.

Klebsiella pneumoniae is a type of Gram-negative bacterium which can cause a range of infections in human. In recent years, an increasing number of strains of K. pneumoniae resistant to multiple antibiotics have emerged, posing a significant threat to public health. The protein function of this bacterium is not well known, thus a systematic investigation of K. pneumoniae proteome is in urgent need. In this study, the protein functions of this bacteria were re-annotated, and their function groups were analyzed. Moreover, three machine learning models were built to identify novel virulence factors. Results showed that the functions of 16 uncharacterized proteins were first annotated by sequence alignment. In addition, K. pneumoniae proteins share a high proportion of homology with Haemophilus influenzae and a low homology proportion with Chlamydia pneumoniae. By sequence analysis, 10 proteins were identified as potential drug targets for this bacterium. Our model achieved a high accuracy of 0.901 in the benchmark dataset. By applying our models to K. pneumoniae, we identified 39 virulence factors in this pathogen. Our findings could provide novel clues for the treatment of K. pneumoniae infection.

Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.

Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer.

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC50 up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment.

Rapid hydrolysis of NO2 at High Ionic Strengths of Deliquesced Aerosol Particles.

Nitrogen dioxide (NO2) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO2 hydrolysis. We find that high ionic strengths (I) enhance the reaction rate constants (kI) by more than an order of magnitude compared to that at infinite dilution (kI=0), yielding log10(kI/kI=0) = 0.04I or rate enhancement factor = 100.04I. A state-of-the-art air quality model shows that the enhanced NO2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.

Two-dimensional tetragonal AlOX (X = Cl, Br, or I) monolayers with promising photocatalytic performance: first-principles investigations.

It is of great significance to search for new two-dimensional materials with excellent photocatalytic water splitting properties. Here, the AlOX (X = Cl, Br, or I) monolayers were constructed to explore their electronic and optical properties as a potential photocatalyst and mechanism of high photocatalytic activity by first principles calculations, for the first time. The results show that the AlOX (X = Cl, Br, or I) monolayers are all dynamically and thermodynamically stable. It is found that the AlOI monolayer exhibits visible optical absorption with a 538 nm absorption band edge, due to its direct band gap of 2.22 eV. Moreover, an appropriate band edge potential ensures its excellent reduction-oxidation (redox) ability. The asymmetry of crystals along different directions results in a noncoplanar HOMO and LUMO as well as an anisotropy effective mass and favors the separation of photogenerated carriers. These findings present the potential of the AlOX (X = Cl, Br, or I) monolayers as photocatalysts.

Long-Term Erythromycin Treatment Alters the Airway and Gut Microbiota: Data from Chronic Obstructive Pulmonary Disease Patients and Mice with Emphysema.

INTRODUCTION: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. METHODS: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. RESULTS: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. CONCLUSION: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

A MRI radiomics-based model for prediction of pelvic lymph node metastasis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. METHODS: This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. RESULTS: In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: -0.0493-2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. CONCLUSIONS: This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.

Evaluation of the National Cancer Institute (NCI) Pathway to Independence Award (K99/R00) Program.

The National Cancer Institute (NCI) K99/R00 award is intended to help postdoctoral scholars transition in a timely manner to research independence and to foster their development of an impactful cancer research program that is competitive for subsequent independent funding. Here we analyzed factors that impact peer review outcomes and evaluated whether NCI K99/R00 awardees have achieved the goals of the K99/R00 funding mechanism. Our analysis of the K99/R00 review criterion scores demonstrates that while all review criterion scores are positively correlated with the overall impact score, the Research Plan criterion is the strongest predictor of the overall impact score and funding outcomes. In addition, our analysis shows the NCI K99/R00 award facilitated the successful transition of postdoctoral scholars to research independence and enhanced the likelihood of K99/R00 awardees to secure subsequent R01-equivalent NIH grant support although not in an accelerated fashion as originally intended. An NCI K99/R00 award was not determined to be a prerequisite to obtain a faculty position, but for some awardees, it was an asset in that transition. Our results suggest that the NCI K99/R00 award is an important component for training and retention of the next generation of independent cancer researchers and to increasing the percentage of women and promoting the diversity of the cancer research workforce.

Fermentation enrichment, structural characterization and immunostimulatory effects of ß-glucan from Quinoa.

We developed an efficient mixed-strain co-fermentation method to increase the yield of quinoa ß-glucan (Q+). Using a 1:1 mass ratio of highly active dry yeast and Streptococcus thermophilus, solid-to-liquid ratio of 1:12 (g/mL), inoculum size of 3.8 % (mass fraction), fermentation at 32 °C for 27 h, we achieved the highest ß-glucan yield of (11.13 ± 0.80)%, representing remarkable 100.18 % increase in yield compared to quinoa ß-glucan(Q-) extracted using hot water. The structure of Q+ and Q- were confirmed through Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopies. Q+ contained 41.66 % ß-glucan, 3.93 % protein, 2.12 % uronic acid; Q- contained 37.21 % ß-glucan, 11.49 % protein, and 1.73 % uronic acid. The average molecular weight of Q+(75.37 kDa) was lower than that of Q- (94.47 kDa). Both Q+ and Q- promote RAW264.7 cell proliferation without displaying toxicity. They stimulate RAW264.7 cells through the NF-κB and MAPK signaling pathways, primarily inducing NO and pro-inflammatory cytokines by upregulating CD40 expression. Notably, Q+ exhibited stronger immunostimulatory activity compared to Q-. In summary, the fermentation enrichment method yields higher content of quinoa ß-glucan with increased purity and stronger immunostimulatory properties. Further study of its bioimmunological activity and structure-activity relationship may contribute to the development of new immunostimulants.