Brassinosteroids play diverse roles in plant growth and development. Plants deficient in brassinosteroid (BR) biosynthesis or defective in signal transduction show many abnormal developmental ...phenotypes, indicating the importance of both BR biosynthesis and the signaling pathway in regulating these biological processes. Recently, using genetics, proteomics, genomics, cell biology, and many other approaches, more components involved in the BR signaling pathway were identified. Furthermore, the physiological, cellular, and molecular mechanisms by which BRs regulate various aspects of plant development, are being discovered. These include root development, anther and pollen development and formation, stem elongation, vasculature differentiation, and cellulose biosynthesis, suggesting that the biological functions of BRs are far beyond promoting cell elongation. This review will focus on the up-to-date progresses about regulatory mechanisms of the BR signaling pathway and the physiological and molecular mechanisms whereby BRs regulate plant growth and development.
Background
The role of carbohydrate antigen 19‐9 (CA 19‐9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of ...the CA 19‐9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA.
Methods
A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19‐9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19‐9 response and the radiologic response was performed. The associations between CA 19‐9 response and imaging response, progression‐free survival (PFS), and overall survival (OS) were analyzed.
Results
Two hundred sixty‐seven patients (63.3%) had a CA 19‐9 response. A CA 19‐9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19‐9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio HR, 4.8 months; 95% confidence interval CI, 3.8–6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2–6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19‐9 nonresponder status, and radiologic nonresponder status in multivariable analysis.
Conclusions
CA 19‐9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19‐9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies.
Plain language summary
A decline in carbohydrate antigen 19‐9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.
Biomarkers for predicting treatment outcomes are an unmet need for patients with intrahepatic cholangiocarcinoma (iCCA) treated with systemic therapies. This article shows that the carbohydrate antigen 19‐9 response correlates with the radiologic response and outcome of patients with iCCA after treatment.
COVID-19 vaccination is essential. However, no study has reported adverse events (AEs) after ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease (ESRD) on hemodialysis (HD). This ...study investigated the AEs within 30-days after the first dose of ChAdOx1 nCoV19 (Oxford-AstraZeneca) in ESRD patients on HD. A total of 270 ESRD patients on HD were enrolled in this study. To determine the significance of vascular access thrombosis (VAT) post vaccination, we performed a self-controlled case study (SCCS) analysis. Of these patients, 38.5% had local AEs; local pain (29.6%), tenderness (28.9%), and induration (15.6%) were the most common. Further, 62.2% had systemic AEs; fatigue (41.1%), feverishness (20%), and lethargy (19.9%) were the most common. In addition, post-vaccination thirst affected 18.9% of the participants with female predominance. Younger age, female sex, and diabetes mellitus were risk factors for AEs. Five patients had severe AEs, including fever (n = 1), herpes zoster (HZ) reactivation (n = 1), and acute VAT (n = 3). However, the SCCS analysis revealed no association between vaccination and VAT; the incidence rate ratio (IRR)-person ratio was 0.56 (95% CI 0.13-2.33) and 0.78 (95% CI 0.20-2.93) IRR-event ratio 0.78 (95% CI 0.15-4.10) and 1.00 (95% CI 0.20-4.93) in the 0-3 months and 3-6 months period prior to vaccination, respectively. Though some ESRD patients on HD had local and systemic AEs after first-dose vaccination, the clinical significance of these symptoms was minor. Our study confirmed the safety profile of ChAdOx1 nCoV-19 in HD patients and presented a new viewpoint on vaccine-related AEs. The SCCS analysis did not find an elevated risk of VAT at 1 month following vaccination. Apart from VAT, other vaccine-related AEs, irrespective of local or systemic symptoms, had minor clinical significance on safety issues. Nonetheless, further coordinated, multi-center, or registry-based studies are needed to establish the causality.
Association mapping is a powerful approach for dissecting the genetic architecture of complex quantitative traits using high-density SNP markers in maize. Here, we expanded our association panel size ...from 368 to 513 inbred lines with 0.5 million high quality SNPs using a two-step data-imputation method which combines identity by descent (IBD) based projection and k-nearest neighbor (KNN) algorithm. Genome-wide association studies (GWAS) were carried out for 17 agronomic traits with a panel of 513 inbred lines applying both mixed linear model (MLM) and a new method, the Anderson-Darling (A-D) test. Ten loci for five traits were identified using the MLM method at the Bonferroni-corrected threshold -log10 (P) >5.74 (α=1). Many loci ranging from one to 34 loci (107 loci for plant height) were identified for 17 traits using the A-D test at the Bonferroni-corrected threshold -log10 (P) >7.05 (α=0.05) using 556809 SNPs. Many known loci and new candidate loci were only observed by the A-D test, a few of which were also detected in independent linkage analysis. This study indicates that combining IBD based projection and KNN algorithm is an efficient imputation method for inferring large missing genotype segments. In addition, we showed that the A-D test is a useful complement for GWAS analysis of complex quantitative traits. Especially for traits with abnormal phenotype distribution, controlled by moderate effect loci or rare variations, the A-D test balances false positives and statistical power. The candidate SNPs and associated genes also provide a rich resource for maize genetics and breeding.
Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme ...aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines
and formation of metastatic lung cancer foci
. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both
and
. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. SIGNIFICANCE: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non-small lung cancer and that blocking this interaction could be an effective cancer treatment.
In order to identify the moldy tea leaves in a fast and nondestructive way, a method involving wavelet coupled with k-nearest neighbor (WKNN) was proposed to select effective characteristic ...wavelengths in this paper. The hyperspectral imaging of 300 dried tea samples with 3 different mildew degrees (contrast check, mild moldy and severe moldy) were obtained using hyperspectral data acquisition device. Besides, food microbiological examination results showed that mold count and total numbers of colony increased with the increase of storage time, temperature and humidity. Roughness penalty smoothing (RPS) algorithm was used to preprocess the raw spectra. Afterwards, WKNN was applied to select the optimal wavelengths of spectral data by using db4, db6, sym5, sym7 as wavelet basis functions, respectively. In addition, five layers of wavelet decomposition were adopted based on different wavelet basis functions. Linear discriminant analysis (LDA) algorithm was used to build the classification models based on preprocessed spectra feature in characteristic wavelengths. The results showed that four optimal prediction models were optimal decomposition level in each wavelet basis function. In addition, the best performance model among all LDA models achieved an identification rate of 100% in the calibration set and 98.33% in the prediction set, in which db4 was used as wavelet basis function and the optimal wavelet decomposition level was 2. WKNN algorithm can effectively achieve the best wavelet decomposition layer and the best wavelengths. WKNN algorithm combined with NIR hyperspectral imaging technology can realize the effective wavelength extraction and classification of dried tea with different mildew degrees.
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•Wavelet coupled with k-nearest neighbor (WKNN) was proposed.•Mold count and total numbers of colony with different sample sets were carried out.•Hyperspectra imaging of dried tea samples with 3 different mildew degrees were obtained.•WKNN feature extraction algorithm is feasible and effective for building models.
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•Mn–Sb/TiO2 catalyst shows higher NH3-SCR activity and wider temperature window than Mn/TiO2 catalyst.•Mn–Sb/TiO2 catalyst has much better Na-resistance than Mn/TiO2 catalyst.•The ...addition of Sb on Mn/TiO2 catalyst can improve its low-temperature reducibility.•The addition of Sb on Mn/TiO2 catalyst can generate strong Lewis acid sites for NH3 adsorption.
Na has a serious deactivation effect on Mn/TiO2 catalyst for selective catalytic reduction of NO with NH3. In this study, it was found that Sb had a promotion effect on the Na resistance of MnOx/TiO2 catalyst. Then the promotion mechanism was investigated based on the characterization results of BET, XRD, H2-TPR, NH3-TPD, XPS and in situ DRIFT. The results of H2-TPR and NH3-TPD showed that the addition of Sb on MnOx/TiO2 could enhance the redox ability and surface acidity respectively, and the results of DRIFT indicated that the addition of Sb on MnOx/TiO2 could generate strong Lewis acid sites on the catalyst surface for NH3 adsorption. Therefore, the doping of Sb has a promotion effect on the Na resistance of Mn/TiO2 catalyst.
Retinal ganglion cells (RGCs) are the only output neurons that conduct visual signals from the eyes to the brain. RGC degeneration occurs in many retinal diseases leading to blindness and increasing ...evidence suggests that RGCs are susceptible to various injuries in a type-specific manner. Glutamate excitotoxicity is the pathological process by which neurons are damaged and killed by excessive stimulation of glutamate receptors and it plays a central role in the death of neurons in many CNS and retinal diseases. The purpose of this study is to characterize the susceptibility of genetically identified RGC types to the excitotoxicity induced by
-methyl-D-aspartate (NMDA). We show that the susceptibility of different types of RGCs to NMDA excitotoxicity varies significantly, in which the αRGCs are the most resistant type of RGCs to NMDA excitotoxicity while the J-RGCs are the most sensitive cells to NMDA excitotoxicity. These results strongly suggest that the differences in the genetic background of RGC types might provide valuable insights for understanding the selective susceptibility of RGCs to pathological insults and the development of a strategy to protect RGCs from death in disease conditions. In addition, our results show that RGCs lose dendrites before death and the sequence of the morphological and molecular events during RGC death suggests that the initial insult of NMDA excitotoxicity might set off a cascade of events independent of the primary insults. However, the kinetics of dendritic retraction in RGCs does not directly correlate to the susceptibility of type-specific RGC death.
Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long ...non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.
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