Summary
Glycosylation of monolignols has been found to be widespread in land plants since the 1970s. However, whether monolignol glycosylation is crucial for cell wall lignification and how it exerts ...effects are still unknown. Here, we report the identification of a mutant ugt72b1 showing aggravated and ectopic lignification in floral stems along with arrested growth and anthocyanin accumulation. Histochemical assays and thioacidolysis analysis confirmed the enhanced lignification and increased lignin biosynthesis in the ugt72b1 mutant. The loss of UDP‐glycosyltransferase UGT72B1 function was responsible for the lignification phenotype, as demonstrated by complementation experiments. Enzyme activity analysis indicated that UGT72B1 could catalyze the glucose conjugation of monolignols, especially coniferyl alcohol and coniferyl aldehyde, which was confirmed by analyzing monolignol glucosides of UGT72B1 transgenic plants. Furthermore, the UGT72B1 gene was strongly expressed in young stem tissues, especially xylem tissues. However, UGT72B1 paralogs, such as UGT72B2 and UGT72B3, had weak enzyme activity toward monolignols and weak expression in stem tissues. Transcriptomic profiling showed that UGT72B1 knockout resulted in extensively increased transcript levels of genes involved in monolignol biosynthesis, lignin polymerization and cell wall‐related transcription factors, which was confirmed by quantitative real‐time PCR assays. These results provided evidence that monolignol glucosylation catalyzed by UGT72B1 was essential for normal cell wall lignification, thus offering insight into the molecular mechanism of cell wall development and cell wall lignification.
Significance Statement
Lignin provides mechanical support to plant stems and helps protect plants from pathogen attack. Although monolignol glucosides were reported in planta in the 1970s, whether they were important for cell wall lignification was unknown. Here we characterize a mutant in a UDP‐glycosyl transferase and show that monolignol glucosylation indeed plays an essential role in normal cell wall lignification.
The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is not only the core structural protein required for viral packaging, but also participates in the ...regulation of viral replication, and its post‐translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP ubiquitination is currently unknown. In this study, we first pinpointed TRIM6 as the E3 ubiquitin ligase responsible for NP ubiquitination, binding to NP's CTD via its RING and B‐box‐CCD domains. TRIM6 promotes the K29‐typed polyubiquitination of NP at K102, K347, and K361 residues, increasing its binding to viral genomic RNA. Consistently, functional experiments such as the use of the reverse genetic tool trVLP model and gene knockout of TRIM6 further confirmed that blocking the ubiquitination of NP by TRIM6 significantly inhibited the proliferation of SARS‐CoV‐2. Notably, the NP of coronavirus is relatively conserved, and the NP of SARS‐CoV can also be ubiquitinated by TRIM6, indicating that NP could be a broad‐spectrum anti‐coronavirus target. These findings shed light on the intricate interaction between SARS‐CoV‐2 and the host, potentially opening new opportunities for COVID‐19 therapeutic development.
Living organisms evolve complex genetic networks to interact with the environment. Due to the rapid development of synthetic biology, various modularized genetic parts and units have been identified ...from these networks. They have been employed to construct synthetic genetic circuits, including toggle switches, oscillators, feedback loops and Boolean logic gates. Building on these circuits, complex genetic machines with capabilities in programmable decision-making could be created. Consequently, these accomplishments have led to novel applications, such as dynamic and autonomous modulation of metabolic networks, directed evolution of biological units, remote and targeted diagnostics and therapies, as well as biological containment methods to prevent release of engineered microorganisms and genetic materials. Herein, we outline the principles in genetic circuit design that have initiated a new chapter in transforming concepts to realistic applications. The features of modularized building blocks and circuit architecture that facilitate realization of circuits for a variety of novel applications are discussed. Furthermore, recent advances and challenges in employing genetic circuits to impart microorganisms with distinct and programmable functionalities are highlighted. We envision that this review gives new insights into the design of synthetic genetic circuits and offers a guideline for the implementation of different circuits in various aspects of biotechnology and bioengineering.
This letter proposes a method using convolutional neural networks (CNNs) for airport detection on optical satellite images. To efficiently build a deep CNN with limited satellite image samples, a ...transfer learning approach had been employed by sharing the common image features of the natural images. To decrease the computing cost, an efficient region proposal method had been proposed based on the prior knowledge of the line segments distribution in an airport. The transfer learning ability on deep CNN for airport detection on satellite images had been first evaluated in this letter. The proposed method was tested on an image data set, including 170 different airports and 30 nonairports. The detection rate could reach 88.8% in experiments with seconds' computation time, which showed a great improvement over other the state-of-the-art methods.
Scope
Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The ...study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association.
Methods and results
This study includes 5405 participants with T2D who provided at least one 24‐h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio HR: 1.10; 95% confidence interval CI: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A, C‐reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD.
Conclusion
Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.
In this prospective cohort study of individuals with type 2 diabetes (T2D), higher ultraprocessed food (UPF) intakes are associated with increased risks of overall cardiovascular disease (CVD), coronary heart disease, and heart failure. The higher risk of overall CVD associated with higher UPF consumption possibly goes through pathways that include renal function, lipid metabolism, inflammation, and body weight. Our study supports the need to stress the importance of decreasing UPF intake in dietary guidelines for T2D patients.
The discovery of complete ammonia oxidizers (comammox) refutes the century-old paradigm that nitrification requires the activity of two types of microbes. Determining the distribution and abundance ...of comammox in various environments is important for revealing the ecology of microbial nitrification within the global nitrogen cycle. In this study, the ubiquity and diversity of comammox were analyzed for samples from different types of environments, including soil, sediment, sludge, and water. The results of a two-step PCR using highly degenerate primers (THDP-PCR) and quantitative real-time PCR (qPCR) supported the relatively high abundance of comammox in nearly half of all samples tested, sometimes even outnumbering canonical ammonia-oxidizing bacteria (AOB). In addition, a relatively high proportion of comammox in tap and coastal water samples was confirmed via analysis of metagenomic data sets in public databases. The diversity of comammox was estimated by comammox-specific partial nested PCR amplification of the ammonia monooxygenase subunit A (
) gene, and phylogenetic analysis of comammox AmoA clearly showed a split of clade A into clades A.1 and A.2, with the proportions of clades A.1, A.2, and B differing among the various environmental samples. Moreover, compared to the
genes of AOB and ammonia-oxidizing archaea (AOA), the comammox
gene exhibited higher diversity indices. The ubiquitous distribution and high diversity of comammox indicate that they are likely overlooked contributors to nitrification in various ecosystems.
The discovery of complete ammonia oxidizers (comammox), which oxidize ammonia to nitrate via nitrite, refutes the century-old paradigm that nitrification requires the activity of two types of microbes and redefines a key process in the biogeochemical nitrogen cycle. Understanding the functional relationships between comammox and other nitrifiers is important for ecological studies on the nitrogen cycle. Therefore, the diversity and contribution of comammox should be considered during ecological analyses of nitrifying microorganisms. In this study, a ubiquitous and highly diverse distribution of comammox was observed in various environmental samples, similar to the distribution of canonical ammonia-oxidizing bacteria. The proportion of comammox was relatively high in coastal water and sediment samples, whereas it was nearly undetectable in open-ocean samples. The ubiquitous distribution and high diversity of comammox indicate that these microorganisms might be important contributors to nitrification.
The response to immune checkpoint inhibitors (ICIs) monotherapy remains unsatisfactory in patients with NSCLC. Thus, combining ICIs with other potential modalities is of great significance to enhance ...the response of single drug alone. Here, we identified that HIF-1α inhibition was capable of promoting anti-tumor immunity in NSCLC. We applied NSCLC cell lines and mouse models to evaluate the synergy of combined HIF-1α inhibition and PD-1 blockade on tumor growth and the function of tumor infiltrating lymphocytes (TILs). Public datasets were utilized to investigate patients' prognosis based on expressions of HIF-1α and LOXL2 as well as EMT-associated markers and CD8+ TILs. Moreover, we explored the correlation between HIF-1α and LOXL2 levels and CD8+ TILs in tumor samples from patients with NSCLC by immunohistochemistry, as well as their association to patients’ survival. In vitro, PX-478, an HIF-1α inhibitor, promoted tumor cell apoptosis induced by T cells when combined with ICIs. Furthermore, mice treated with PX-478 and anti-PD-1 antibodies exhibited a marked delay in tumor growth and prolonged survival, which correlated with increased TILs and granzyme B secretion. Besides, patients with high HIF-1α expression exhibited high levels of EMT-related markers and low TILs, indicating an immunosuppressive phenotype. Mechanistically, we observed that HIF-1α inhibition suppressed the EMT phenotypes induced by hypoxia and further alleviated tumor immunosuppression, which was related to blockage of HIF-1α/LOXL2 signaling pathway. In summary, we identified that HIF-1α inhibition could synergize with anti-PD-1 to impair tumor growth in vitro and in vivo. Our data suggest that HIF-1α inhibitors represent a promising treatment to enhance anti-tumor immunity and provide preclinical rationale to evaluate the combination of ICIs with HIF-1α inhibition clinically in NSCLC.
•Attenuating hypoxia-induced EMT phenotypes may increase tumor infiltrated activating T cells.•Downregulation of EMT by HIF-1α inhibition was associated with suppression of the HIF-1α-LOXL2 signaling pathway.•The combination of HIF-1α inhibition and ICIs can induce significant tumor regression and improve efficacy of immunotherapy.
Recently, metal-organic frameworks (MOFs) have been extensively investigated as fluorescence chemsensors due to their tunable porosity, framework structure and photoluminescence properties. In this ...paper, a well-known Zr(
iv
)-based MOF, UiO-66-NH
2
was demonstrated to have capability for detection of
l
-lysine (Lys) and
l
-arginine (Arg) selectively from common essential amino acids in aqueous media
via
a fluorescence turn-on mechanism. Further investigation reveals its high sensitivity and strong anti-interference properties. Moreover, the possible mechanism for sensing Lys and Arg was explored by FT-IR and
1
H-NMR, and the results indicate that the enhancement of the fluorescence could be ascribed to the adsorption of Lys/Arg and the hydrogen bonding interactions between Lys/Arg and the amino group of UiO-66-NH
2
. The difference of the sensing capacity and sensitivity between UiO-66 and UiO-66-NH
2
revealed that the amino group plays an essential role in the sensing performance. This work presents a unique example of the functional group dependent sensing properties of MOFs.
The amino group of UiO-66-NH
2
was demonstrated to play an important role in selective fluorescence turn-on sensing of lysine and arginine.
The neuropeptide natalisin (NTL) has been determined to play essential roles in reproduction in two Diptera and one Coleoptera species. Whether NTL has similar or even different functions in ...Lepidoptera remains to be determined. Here, we cloned the NTL transcript in the common cutworm moth Spodoptera litura. This transcript encodes a 438-amino acid protein. Twelve putative Sl-NTL neuropeptides were defined by cleavage sites. These NTL peptides share a DDPFWxxRamide C-terminal motif. The expressions of Sl-NTL is low during the egg and larval stages, which increased to a higher level during the pupal stage, and then reached the maximum during the adult stage. Moreover, the expression pattern during the pupal stage is similar between sexes while during the adult stage, it is dimorphic. To explore the function of Sl-NTL and assess its potential as a target for pest control, we knocked down the expression of Sl-NTL in both sexes by using bacteria-mediated RNAi. This technique significantly down regulated (reduced up to 83%) the expression of Sl-NTL in both sexes. Knocking down Sl-NTL expression did not significantly affect its development, survival and morphology but significantly reduced adults' reproductive behavior (including female calling, male courtship, mating and remating patterns and rates) and reproductive output (offspring gain reduced more than 70%).
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