Successive peptide ligation using a one‐pot method can improve the efficiency of protein chemical synthesis. Although one‐pot three‐segment ligation has enjoyed widespread application, a robust ...method for one‐pot four‐segment ligation had to date remained undeveloped. Herein we report a new one‐pot multisegment peptide ligation method that can be used to condense up to four segments with operational simplicity and high efficiency. Its practicality is demonstrated by the one‐pot four‐segment synthesis of a plant protein, crambin, and a human chemokine, hCCL21.
Pick up a peptide: Tfacm‐protected cysteine is readily activated by pH adjustment, enabling the development of a highly efficient one‐pot four‐segment ligation method. Two proteins, crambin and the chemokine hCCL21, are prepared using this rapid and high‐yielding synthetic route.
Summary
Sessile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS‐box ...transcription factor AGL16 acting as a negative regulator in stress response in Arabidopsis.
Loss‐of‐AGL16 confers resistance to salt stress in seed germination, root elongation and soil‐grown plants, while elevated AGL16 expression confers the opposite phenotypes compared with wild‐type. However, the sensitivity to abscisic acid (ABA) in seed germination is inversely correlated with AGL16 expression levels.
Transcriptomic comparison revealed that the improved salt resistance of agl16 mutants was largely attributed to enhanced expression of stress‐responsive transcriptional factors and the genes involved in ABA signalling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter of HKT1;1, HsfA6a and MYB102 and represses their expression. Genetic analyses with double mutants also support that HsfA6a and MYB102 are target genes of AGL16.
Taken together, our results show that AGL16 acts as a negative regulator transcriptionally suppressing key components in the stress response and may play a role in balancing stress response with growth.
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct ...disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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•First deep proteogenomic landscape of non-smoking lung adenocarcinoma in East Asia•Identified age, sex-related endogenous, and environmental carcinogen mutagenic processes•Proteome-informed classification distinguished clinical features within early stages•Protein networks identified tumorigenesis hallmarks, biomarkers, and druggable targets
Deep proteogenomic landscape of early stage lung adenocarcinoma in a cohort of mostly non-smokers reveals unique drivers and biomarkers, as well as gender-associated mutagenesis.
Summary
A novel technology for banana starch modification has been developed using dielectric barrier discharge (DBD) plasma, and the effect of DBD plasma treatment on the solubility and pasting ...behaviours of banana starch were evaluated. The solubility of treated starch significantly increased from 1.35 to 15.05 g 100 g−1 at 55 °C as the treatment intensity increased. Rapid viscosity analyser examination showed a dramatic change in the pasting behaviours of modified starch, and the peak viscosity decreased from 5242.0 to 153.0 (cP) as the treatment intensity increased. Evidence of nonpenetrative damage caused by plasma etching was shown by scanning electron microscope micrographs. The results of X‐ray diffraction and Fourier‐transform infrared spectroscopy analyses indicated that the DBD treatment changed the granular structure of banana starch.
Effect of DBD plasma on banana starch.
Long non-coding RNA (LncRNA) have been reported to be involved in the pathogenesis of neurodegenerative diseases, but whether it can serve as a biomarker for Alzheimer disease (AD) is not yet known.
...The present study selected four specific LncRNA (17A, 51A, BACE1 and BC200) as possible AD biomarker. RT-qPCR was performed to validate the LncRNA. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to study the potential of LncRNA as a biomarker in a population of 88 AD patients and 72 control individuals.
We found that the plasma LncRNA BACE1 level of AD patients was significantly higher than that of healthy controls (p = 0.006). Plasma level of LncRNA 17A, 51A and BC200 did not show a significant difference between two groups (p = 0.098, p = 0.204 and p = 0.232, respectively). ROC curve analysis showed that LncRNA BACE1 was the best candidate of these LncRNA (95% CI: 0.553-0.781, p = 0.003). In addition, no correlation was found for expression of these LncRNA in both control and AD groups with age or MMSE scale (p > 0.05).
Our present study compared the plasma level of four LncRNA between AD and non-AD patients, and found that the level of the BACE1 is increased in the plasma of AD patients and have a high specificity (88%) for AD, indicating BACE1 may be a potential candidate biomarker to predict AD.
Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic ...hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear.
We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10
) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis.
The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI.
This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.
Cu-based nanocatalysts have been widely used for CO2 hydrogenation, but their poor stability is the bottleneck for further industrial applications. A high-performance and long-lived Cu/SiO2 ...nanocatalyst was synthesized by an ammonia-evaporation method for CO2 hydrogenation. The conversion of CO2 reaches up to 28%, which is close to the equilibrium conversion of CO2 (30%), and the selectivity to methanol is 21.3%, which is much higher than the equilibrium selectivity (6.6%) at 320 °C and 3.0 MPa. Furthermore, after 120 h of evaluation, the conversion can be still maintained at a high value (27%), which is much better than a Cu/SiO2 catalyst prepared by traditional impregnation. The Cu+ species has been demonstrated to be the active component for the activation and conversion of CO2. The higher ratio of Cu+/(Cu0 + Cu+) and interaction between the metal and support deriving from copper phyllosilicate are mainly responsible for the high catalytic activity and excellent stability, respectively.
Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many ...health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin
in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and
in 6-OHDA-treated PC12 cells.
, we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our
findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either
or
.
We synthesized monodisperse Pd nanocrystals with exposed (111) and (100) facets through preferentially oriented facet growth technology. We then supported them on α-Al2O3 as catalysts for application ...in CO oxidative coupling to dimethyl oxalate (DMO) and find, for the first time, that the (111) facets of Pd nanocrystals are active planes for CO oxidative coupling to DMO. This conclusion is based on experiment results, reaction mechanism, and density functional theory calculation. Directed by this shape effect, a high-performance and long-lived nanocatalyst with much lower Pd load for CO oxidative coupling to DMO was successfully prepared by a new wet impregnation–solution chemical reduction method, which can well control the exposure of (111) facets and sizes of Pd nanocrystals.
The effects of blue (BL) and green light (GL) treatment during the dark period were examined in Camellia sinensis as a first step to understanding the spectral effects of artificial BL and GL on ...plant secondary metabolism and light signaling interactions. BL could induce the expression of CRY2/3, SPAs, HY5, and R2R3-MYBs to promote the accumulation of anthocyanins and catechins in tea plants. GL, on the other hand, could stimulate the accumulation of several functional substances (e.g., procyanidin B2/B3 and l-ascorbate) and temper these BL responses via down-regulation of CRY2/3 and PHOT2. Furthermore, the molecular events that triggered by BL and GL signals were partly overlapped with abiotic/biotic stress responses. We indicate the possibility of a targeted use of BL and GL to regulate the amount of functional metabolites to enhance tea quality and taste, and to potentially trigger defense mechanisms of tea plants.
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