Multi-omics analysis reveals key regulatory defense pathways and genes involved in salt tolerance of rose plants.

Salinity stress causes serious damage to crops worldwide, limiting plant production. However, the metabolic and molecular mechanisms underlying the response to salt stress in rose (Rosa spp.) remain poorly studied. We therefore performed a multi-omics investigation of Rosa hybrida cv. Jardin de Granville (JDG) and Rosa damascena Mill. (DMS) under salt stress to determine the mechanisms underlying rose adaptability to salinity stress. Salt treatment of both JDG and DMS led to the buildup of reactive oxygen species (H2O2). Palisade tissue was more severely damaged in DMS than in JDG, while the relative electrolyte permeability was lower and the soluble protein content was higher in JDG than in DMS. Metabolome profiling revealed significant alterations in phenolic acid, lipids, and flavonoid metabolite levels in JDG and DMS under salt stress. Proteome analysis identified enrichment of flavone and flavonol pathways in JDG under salt stress. RNA sequencing showed that salt stress influenced primary metabolism in DMS, whereas it substantially affected secondary metabolism in JDG. Integrating these datasets revealed that the phenylpropane pathway, especially the flavonoid pathway, is strongly enhanced in rose under salt stress. Consistent with this, weighted gene coexpression network analysis (WGCNA) identified the key regulatory gene chalcone synthase 1 (CHS1), which is important in the phenylpropane pathway. Moreover, luciferase assays indicated that the bHLH74 transcription factor binds to the CHS1 promoter to block its transcription. These results clarify the role of the phenylpropane pathway, especially flavonoid and flavonol metabolism, in the response to salt stress in rose.

Discovery of LLC355 as an Autophagy-Tethering Compound for the Degradation of Discoidin Domain Receptor 1.

Discoidin domain receptor 1 (DDR1) is a potential target for cancer drug discovery. Although several DDR1 kinase inhibitors have been developed, recent studies have revealed the critical roles of the noncatalytic functions of DDR1 in tumor progression, metastasis, and immune exclusion. Degradation of DDR1 presents an opportunity to block its noncatalytic functions. Here, we report the discovery of the DDR1 degrader LLC355 by employing autophagosome-tethering compound technology. Compound LLC355 efficiently degraded DDR1 protein with a DC50 value of 150.8 nM in non-small cell lung cancer NCI-H23 cells. Mechanistic studies revealed compound LLC355 to induce DDR1 degradation via lysosome-mediated autophagy. Importantly, compound LLC355 potently suppressed cancer cell tumorigenicity, migration, and invasion and significantly outperformed the corresponding inhibitor 1. These results underline the therapeutic advantage of targeting the noncatalytic function of DDR1 over inhibition of its kinase activity.

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.

Multi-View Time-Series Hypergraph Neural Network for Action Recognition.

Recently, action recognition has attracted considerable attention in the field of computer vision. In dynamic circumstances and complicated backgrounds, there are some problems, such as object occlusion, insufficient light, and weak correlation of human body joints, resulting in skeleton-based human action recognition accuracy being very low. To address this issue, we propose a Multi-View Time-Series Hypergraph Neural Network (MV-TSHGNN) method. The framework is composed of two main parts: the construction of a multi-view time-series hypergraph structure and the learning process of multi-view time-series hypergraph convolutions. Specifically, given the multi-view video sequence frames, we first extract the joint features of actions from different views. Then, limb components and adjacent joints spatial hypergraphs based on the joints of different views at the same time are constructed respectively, temporal hypergraphs are constructed joints of the same view at continuous times, which are established high-order semantic relationships and cooperatively generate complementary action features. After that, we design a multi-view time-series hypergraph neural network to efficiently learn the features of spatial and temporal hypergraphs, and effectively improve the accuracy of skeleton-based action recognition. To evaluate the effectiveness and efficiency of MV-TSHGNN, we conduct experiments on NTU RGB+D, NTU RGB+D 120 and imitating traffic police gestures datasets. The experimental results indicate that our proposed method model achieves the new state-of-the-art performance.

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.

Exploring secondary aerosol formation associated with elemental carbon in the lower free troposphere.

The variability of element carbon (EC) mixed with secondary species significantly complicates the assessment of its environmental impact, reflecting the complexity and diversity of EC-containing particles' composition and morphology during their ascent and regional transport. While the catalytic role of EC in secondary aerosol formation is recognized, the effects of heterogeneous chemistry on secondary species formation within diverse EC particle types are not thoroughly understood, particularly in the troposphere. Alpine sites offer a prime environment to explore EC properties post-transport from the ground to the free troposphere. Consequently, we conducted a comprehensive study on the genesis of secondary aerosols in EC-containing particles at Mt. Hua (altitude: 2069 m) from 1 May to 10 July, using a single particle aerosol mass spectrometer (SPAMS). Our analysis identified six major EC particle types, with EC-K, EC-SN, and EC-NaK particles accounting for 27.6 %, 27.0 %, and 19.6 % of the EC particle population, respectively. The concentration-weighted trajectory (CWT) indicated that the lower free troposphere over Mt. Hua is significantly affected by anthropogenic emissions at ground-level, predominantly from northwestern and eastern China. Atmospheric interactions are crucial in generating high sulfate levels in EC-SN and EC-OC particles (> 70 %) and notable nitrate levels in EC-K, EC-BB, and EC-Fe particles (> 80 %). The observed high chloride content in EC-OC particles (56 ± 32 %) might enhance chlorine's reactivity with organic compounds via heterogeneous reactions within the troposphere. Distinct diurnal cycles for sulfate and nitrate are mainly driven by varying transport dynamics and formation processes, showing minimal dependency on EC particle types. Enhanced nocturnal oxalate conversion in EC-Fe particles is likely due to the aqueous oxidation of precursors, with Fe-catalyzed Fenton reactions enhancing OH radical production. This investigation provides critical insights into EC's role in secondary aerosol development during its transport in the lower free troposphere.

Effects of seasonal precipitation regimes on microbial biomass and extracellular enzyme activity during shrub foliar litter decomposition in a subtropical forest.

Elucidating the mechanisms underlying microbial biomass and extracellular enzyme activity responses to the seasonal precipitation regime during foliar litter decomposition is highly important for understanding the material cycle of forest ecosystems in the context of global climate change; however, the specific underlying mechanisms remain unclear. Hence, a precipitation manipulation experiment involving a control (CK) and treatments with decreased precipitation in the dry season and extremely increased precipitation in the wet season (IE) and decreased precipitation in the dry season and proportionally increased precipitation in the wet season (IP) was conducted in a subtropical evergreen broad-leaved forest in China from October 2020 to October 2021. The moisture, microbial biomass, and extracellular enzyme activities of foliar litter from two dominant shrub species, Phyllostachys violascens and Alangium chinense, were measured at six stages during the dry and wet seasons. The results showed that (1) both IE and IP significantly decreased the microbial biomass carbon and microbial biomass nitrogen content and the activities of ß-1,4-glucosidase, ß-1,4-N-acetylglucosaminidase, acid phosphatase and cellulase in the dry season, while the opposite effects were observed in the wet season. (2) Compared with those of IE, the effects of IP on foliar litter microbial biomass and extracellular enzyme activity were more significant. (3) The results from the partial least squares model indicated that extracellular enzyme activity during foliar litter decomposition was strongly controlled by the foliar litter water content, microbial biomass nitrogen, the ratio of total carbon to total phosphorus, foliar litter total carbon, and foliar litter total nitrogen. These results provide an important theoretical basis for elucidating the microbial mechanisms driving litter decomposition in a subtropical forest under global climate change scenarios.

Multi-omics 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. Multi-omic 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 multi-seasonal 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, 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 multi-season flowering of osmanthus and other flowers.

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVE: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

Effectiveness of Maze IV procedure versus thoracoscopic ablation for atrial fibrillation: a propensity score-matched analysis.

Background: Thoracoscopic ablation (TA) has emerged as a promising treatment for atrial fibrillation (AF), with the Cox-Maze IV Procedure (CMP-IV) as the current gold-standard intervention. This study aims to evaluate and compare the outcomes of TA and CMP-IV in treating AF. Methods: Patients with AF underwent either CMP-IV or TA through a left-side chest approach. The CMP-IV entailed bi-atrium ablation, whereas the TA involved creating three circular plus three linear ablations in the left atrium. We analyzed baseline characteristics, perioperative outcomes and recurrence rates using propensity score matching (PSM) at a 1:1 ratio, to ensure comparability between the two treatment groups. Results: A total of 459 patients underwent either CMP-IV (n=93) or TA via left chest (n=366) and 174 patients were deemed eligible for 1:1 PSM. The TA group experienced significantly shorter intensive care unit (ICU) and hospital stays. The mean follow-up period was 31.5±22.1 months. Pre- and post-matching analysis showed that CMP-IV had a higher rate of freedom from recurrence compared to TA, particularly in non-paroxysmal AF patients. Multivariable Cox regression analysis revealed that CMP-IV was associated with a reduced risk of recurrence, while an increased left atrial size emerged as an independent predictor of postoperative recurrence, regardless of the use of CMP-IV or TA. Conclusions: Our study suggests that while the therapeutic efficacy of TA for "lone" AF may fall short of the classic CMP-IV, its less invasive nature results in significantly shorter ICU and hospital stays. To enhance patient outcomes following TA, it is essential to improve the quality of ablation, refine the ablation route, and focus on careful patient selection.

TSPO-induced degradation of the ethylene receptor RhETR3 promotes salt tolerance in rose (Rosa hybrida).

The gaseous plant hormone ethylene regulates plant development, growth, and responses to stress. In particular, ethylene affects tolerance to salinity; however, the underlying mechanisms of ethylene signaling and salt tolerance are not fully understood. Here, we demonstrate that salt stress induces the degradation of the ethylene receptor ETHYLENE RESPONSE 3 (RhETR3) in rose (Rosa hybrid). Furthermore, the TspO/MBR (Tryptophan-rich sensory protein/mitochondrial benzodiazepine receptor) domain-containing membrane protein RhTSPO interacted with RhETR3 to promote its degradation in response to salt stress. Salt tolerance is enhanced in RhETR3-silenced rose plants but decreased in RhTSPO-silenced plants. The improved salt tolerance of RhETR3-silenced rose plants is partly due to the increased expression of ACC SYNTHASE1 (ACS1) and ACS2, which results in an increase in ethylene production, leading to the activation of ETHYLENE RESPONSE FACTOR98 (RhERF98) expression and, ultimately accelerating H2O2 scavenging under salinity conditions. Additionally, overexpression of RhETR3 increased the salt sensitivity of rose plants. Co-overexpression with RhTSPO alleviated this sensitivity. Together, our findings suggest that RhETR3 degradation is a key intersection hub for the ethylene signalling-mediated regulation of salt stress.

Longterm erythromycin treatment alters the airway and gut microbiota：Data from COPD 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.

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.

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.

Insights into anthropogenic impact on atmospheric inorganic aerosols in the largest city of the Tibetan Plateau through multidimensional isotope analysis.

Particulate inorganic nitrogen aerosols (PIN) significantly influence air pollution and pose health risks worldwide. Despite extensive observations on ammonium (pNH4+) and nitrate (pNO3-) aerosols in various regions, their key sources and mechanisms in the Tibetan Plateau remain poorly understood. To bridge this gap, this study conducted a sampling campaign in Lhasa, the Tibetan Plateau's largest city, with a focus on analyzing the multiple isotopic signatures (δ15N, ∆17O). These isotopes were integrated into a Bayesian mixing model to quantify the source contributions and oxidation pathways for pNH4+ and pNO3-. Our results showed that traffic was the largest contributor to pNH4+ (31.8 %), followed by livestock (25.4 %), waste (21.8 %), and fertilizer (21.0 %), underscoring the impact of vehicular emissions on urban NH3 levels in Lhasa. For pNO3-, coal combustion emerged as the largest contributor (27.3 %), succeeded by biomass burning (26.3 %), traffic emission (25.3 %), and soil emission (21.1 %). In addition, the ∆17O-based model indicated a dominant role of NO2 + OH (52.9 %) in pNO3- production in Lhasa, which was similar to previous observations. However, it should be noted that the NO3 + volatile organic component (VOC) contributed up to 18.5 % to pNO3- production, which was four times higher than the Tibetan Plateau's background regions. Taken together, the multidimensional isotope analysis performed in this study elucidates the pronounced influence of anthropogenic activities on PIN in the atmospheric environment of Lhasa.

Targeting EGFR degradation by autophagosome degraders.

Several generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed for the treatment of non-small cell lung cancer (NSCLC) in clinic. However, emerging drug resistance mediated by new EGFR mutations or activations by pass, leads to malignant progression of NSCLC. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome the drug resistance acquired by mutant EGFR, newly potent and selective degraders are still need to be developed for clinical applications. Herein, we developed autophagosome-tethering compounds (ATTECs) in which EGFR can be anchored to microtubule-associated protein-1 light chain-3B (LC3B) on the autophagosome with the assistance of the LC3 ligand GW5074. A series of EGFR-ATTECs have been designed and synthesized. Biological evaluations showed that these compounds could degrade EGFR and exhibited moderate inhibitory effects on certain NSCLC cell lines. The ATTEC 12c potently induced the degradation of EGFR with a DC50 value of 0.98 µM and a Dmax value of 81% in HCC827 cells. Mechanistic exploration revealed that the lysosomal pathway was mainly involved in this degradation. Compound 12c also exhibited promising inhibitory activity, as well as degradation efficiency in vivo. Our study highlights that EGFR-ATTECs could be developed as a new expandable EGFR degradation tool and also reveals a novel potential therapeutic strategy to prevent drug resistance acquired EGFR mutations.

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.