Transceptor NRT1.1 and receptor-kinase QSK1 complex controls PM H+-ATPase activity under low nitrate.

NRT1.1, a nitrate transceptor, plays an important role in nitrate binding, sensing, and nitrate-dependent lateral root (LR) morphology. However, little is known about NRT1.1-mediated nitrate signaling transduction through plasma membrane (PM)-localized proteins. Through in-depth phosphoproteome profiling using membranes of Arabidopsis roots, we identified receptor kinase QSK1 and plasma membrane H+-ATPase AHA2 as potential downstream components of NRT1.1 signaling in a mild low-nitrate (LN)-dependent manner. QSK1, as a functional kinase and molecular link, physically interacts with NRT1.1 and AHA2 at LN and specifically phosphorylates AHA2 at S899. Importantly, we found that LN, not high nitrate (HN), induces formation of the NRT1.1-QSK1-AHA2 complex in order to repress the proton efflux into the apoplast by increased phosphorylation of AHA2 at S899. Loss of either NRT1.1 or QSK1 thus results in a higher T947/S899 phosphorylation ratio on AHA2, leading to enhanced pump activity and longer LRs under LN. Our results uncover a regulatory mechanism in which NRT1.1, under LN conditions, promotes coreceptor QSK1 phosphorylation and enhances the NRT1.1-QSK1 complex formation to transduce LN sensing to the PM H+-ATPase AHA2, controlling the phosphorylation ratio of activating and inhibitory phosphorylation sites on AHA2. This then results in altered proton pump activity, apoplast acidification, and regulation of NRT1.1-mediated LR growth.

APP1/NTL9-CalS8 module ensures proper phloem differentiation by stabilizing callose accumulation and symplastic communication.

Phloem sieve elements (PSE), the primary conduits collaborating with neighboring phloem pole pericycle (PPP) cells to facilitate unloading in Arabidopsis roots, undergo a series of developmental stages before achieving maturation and functionality. However, the mechanism that maintains the proper progression of these differentiation stages remains largely unknown. We identified a gain-of-function mutant altered phloem pole pericycle 1 Dominant (app1D), producing a truncated, nuclear-localized active form of NAC with Transmembrane Motif 1-like (NTL9). This mutation leads to ectopic expression of its downstream target CALLOSE SYNTHASE 8 (CalS8), thereby inducing callose accumulation, impeding SE differentiation, impairing phloem transport, and inhibiting root growth. The app1D phenotype could be reproduced by blocking the symplastic channels of cells within APP1 expression domain in wild-type (WT) roots. The WT APP1 is primarily membrane-tethered and dormant in the root meristem cells but entries into the nucleus in several cells in PPP near the unloading region, and this import is inhibited by blocking the symplastic intercellular transport in differentiating SE. Our results suggest a potential maintenance mechanism involving an APP1-CalS8 module, which induces CalS8 expression and modulates symplastic communication, and the proper activation of this module is crucial for the successful differentiation of SE in the Arabidopsis root.

Comparison of the safety and effectiveness of the four-hook needle and hook wire for the preoperative positioning of localization ground glass nodules.

BACKGROUND: With the implementation of lung cancer screening programs, an increasing number of pulmonary nodules have been detected.Video-assisted thoracoscopic surgery (VATS) could provide adequate tissue specimens for pathological analysis, and has few postoperative complications.However, locating the nodules intraoperatively by palpation can be difficult for thoracic surgeons. The preoperative pulmonary nodule localization technique is a very effective method.We compared the safety and effectiveness of two methods for the preoperative localization of pulmonary ground glass nodules. METHODS: From October 2020 to April 2021, 133 patients who underwent CT-guided single pulmonary nodule localization were retrospectively reviewed. All patients underwent video-assisted thoracoscopic surgery (VATS) after successful localization. Statistical analysis was used to evaluate the localization accuracy, safety, information related to surgery and postoperative pathology information. The aim of this study was to evaluate the clinical effects of the two localization needles. RESULTS: The mean maximal transverse nodule diameters in the four-hook needle and hook wire groups were 8.97 ± 3.85 mm and 9.00 ± 3.19 mm, respectively (P = 0.967). The localization times in the four-hook needle and hook wire groups were 20.58 ± 2.65 min and 21.43 ± 3.06 min, respectively (P = 0.09). The dislodgement rate was significantly higher in the hook wire group than in the four-hook needle group (7.46% vs. 0, P = 0.024). The mean patient pain scores based on the visual analog scale in the four-hook needle and hook wire groups were 2.87 ± 0.67 and 6.10 ± 2.39, respectively (P = 0.000). All ground glass nodules (GGNs) were successfully resected by VATS. CONCLUSIONS: Preoperative pulmonary nodule localization with both a four-hook needle and hook wire is safe, convenient and effective.

A Bibliometric Analysis: Current Perspectives and Potential Trends of Enzyme Thermostability from 1991-2022.

Thermostability is considered a crucial parameter to evaluate the viability of enzymes in industrial applications. Over the past 31 years, many studies have been reported on the thermostability of enzymes. However, there is no systematic bibliometric analysis of publications on the thermostability of enzymes. In this study, 16,035 publications related to the thermostability of enzymes were searched and collected, showing an increasing annual trend. China contributed the most publications, while the United States had the highest citation count. International Journal of Biological Macromolecules is the most productive journal in the research field. Moreover, Chinese acad sci and Khosro Khajeh are the most active institutions and prolific authors in the field, respectively. Analysis of references with the strongest citation bursts and keyword co-occurrences, magnetic nanoparticles, metal-organic frameworks, molecular dynamics, and rational design are current hot spots and significant future research directions. This study is the first comprehensive bibliometric analysis summarizing trends and developments in enzyme thermostability research. Our findings could provide scholars with an understanding of the fundamental knowledge framework of the field and identify recent potential hotspots and research trends that could facilitate the discovery of collaboration opportunities.

The OsSGS3-tasiRNA-OsARF3 module orchestrates abiotic-biotic stress response trade-off in rice.

Recurrent heat stress and pathogen invasion seriously threaten crop production, and abiotic stress often antagonizes biotic stress response against pathogens. However, the molecular mechanisms of trade-offs between thermotolerance and defense remain obscure. Here, we identify a rice thermo-sensitive mutant that displays a defect in floret development under high temperature with a mutation in SUPPRESSOR OF GENE SILENCING 3a (OsSGS3a). OsSGS3a interacts with its homolog OsSGS3b and modulates the biogenesis of trans-acting small interfering RNA (tasiRNA) targeting AUXIN RESPONSE FACTORS (ARFs). We find that OsSGS3a/b positively, while OsARF3a/b and OsARF3la/lb negatively modulate thermotolerance. Moreover, OsSGS3a negatively, while OsARF3a/b and OsARF3la/lb positively regulate disease resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) and the fungal pathogen Magnaporthe oryzae (M. oryzae). Taken together, our study uncovers a previously unknown trade-off mechanism that regulates distinct immunity and thermotolerance through the OsSGS3-tasiRNA-OsARF3 module, highlighting the regulation of abiotic-biotic stress response trade-off in plants.

Discovery of coumaric acid derivatives hinted by coastal marine source to seek for uric acid lowering agents.

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 µM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 µM in the hyperuricemic model mice (723.0 µM), comparable with Allopurinol (325.8 µM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.

Trends and hotspots for European Journal of Medicinal Chemistry: A bibliometric study.

European Journal of Medicinal Chemistry (EJMC) has been around for a long time and has gained broad interest from the various individuals working in the field. However, there is no bibliometric analysis on the publications of EJMC to thoroughly assess the scientific output and current status systematically. Therefore, the study was conducted to analyze the various publications of EJMC from 1987 to 2022 to improve their quality. A total of 13,386 papers were retrieved, with the number of publications increasing yearly. Based on the multiple indicators of bibliometrics, the highest impact countries, institutions, authors and representative literature were identified, and visualization networks were constructed using VOSviewer. Keyword co-occurrence analysis reveals a gradual shift from phenotypic drug discovery to target-based drug discovery in the EJMC theme change. Moreover, further discussion of the keyword clustering results is provided to support researchers in defining the scope of their research topics and planning their research directions. At this stage, there is a greater focus on developing antitumor and oxidative stress-related drugs than on the earlier anti-infective activities. In future studies, the main research directions are tumor multidrug resistance, oxidative stress, and dual inhibitors.

Non-coding RNAs fine-tune the balance between plant growth and abiotic stress tolerance.

To survive in adverse environmental conditions, plants have evolved sophisticated genetic and epigenetic regulatory mechanisms to balance their growth and abiotic stress tolerance. An increasing number of non-coding RNAs (ncRNAs), including small RNAs (sRNAs) and long non-coding RNAs (lncRNAs) have been identified as essential regulators which enable plants to coordinate multiple aspects of growth and responses to environmental stresses through modulating the expression of target genes at both the transcriptional and posttranscriptional levels. In this review, we summarize recent advances in understanding ncRNAs-mediated prioritization towards plant growth or tolerance to abiotic stresses, especially to cold, heat, drought and salt stresses. We highlight the diverse roles of evolutionally conserved microRNAs (miRNAs) and small interfering RNAs (siRNAs), and the underlying phytohormone-based signaling crosstalk in regulating the balance between plant growth and abiotic stress tolerance. We also review current discoveries regarding the potential roles of ncRNAs in stress memory in plants, which offer their descendants the potential for better fitness. Future ncRNAs-based breeding strategies are proposed to optimize the balance between growth and stress tolerance to maximize crop yield under the changing climate.

The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer.

Radiofrequency ablation (RFA) is a technology that uses radiofrequency thermal effect to induce coagulation necrosis of tumor tissue under the guidance of imaging. However, distant metastasis of tumor cells caused by tumor angiogenesis can lead to incomplete tumor clearing. In this study, LLC1 cell line was used for the construction of subcutaneous xenografts. Either 10 mg/kg or 20 mg/kg Fosbretabulin disodium (FBTD) was intragastrically administered every 2 days for a week. RFA was performed at the end of medication. The proportion of T cells was examined by flow cytometry. Serum IgG and IgA levels of mice were examined by ELISA. Expression of certain genes was estimated by qRT-PCR assay. In this study, we demonstrated that FBTD was able to significantly enhance RFA-induced immune function in tumor-bearing mice by upregulating RFA-induced CD8+ killer T cells. Consistently, 10 mg/kg or 20 mg/kg FBTD therapy upregulated the percentage of IFNγ+ and TNFα+ CD8+ tumor infiltrating lymphocytes in tumor-bearing mice compared to the RFA alone or FBTD alone group. Mechanistically, we reported that FBTD inhibited the RFA-induced PD-1 and PD-L1 upregulation in vivo. In conclusion, we demonstrated that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in this study.

Discovery of derivatives from Spartina alterniflora-sourced moiety as xanthine oxidase inhibitors to lower uric acid.

In this work, hit compounds Spartinin F1-F20 sharing the Spartina alterniflora-sourced ferulic acid backbone were synthesized and evaluated on inhibiting xanthine oxidase and lowering uric acid level. The top hit Spartinin F2 exhibited inhibition percentages at 10 µM dosage as high as 84.48 (higher than that of the positive control allopurinol) and low cyto-toxicity. Spartinin F2 inferred potential efficiency in lowering the serum UA level (from 631.6 µM to 295.0 µM), which was comparable with allopurinol (to 309.2 µM). Spartinin F2 was also beneficial for other serum indexes. The bioavailability of Spartinin F2 was 63.71% from the preliminary pharmacokinetics test and the molecular docking simulation indicated that except for retaining the hydrogen bonds with the key residues such as THR 1010 and LYS 771, the introduction of the π-sulfur interactions via the sulfonate might also be beneficial for developing more potent XO inhibitors.

A new mitochondria-targeted fluorescent probe for exogenous and endogenous superoxide anion imaging in living cells and pneumonia tissue.

As a precursor of all reactive oxygen species (ROS), superoxide anions play an important role in organisms. However, excessive superoxide anions can cause various diseases. Thus, it is highly urgent to develop efficient tools for in situ superoxide anion detection. In this work, a novel boric acid-based, mitochondria-targeted fluorescent probe Mito-YX for superoxide anion detection was designed by regulating its intramolecular charge transfer (ICT) effect. The probe exhibited turn-on fluorescence enhancement within 4 min of reaction with the superoxide anion. In addition, Mito-YX also exhibited high selectivity and a low detection limit down to 0.24 µM with good mitochondrial targeting characteristics, which provided a necessary basis for in vivo detection of superoxide anions. What is more, Mito-YX was successfully applied for the in situ monitoring of superoxide anions in living MCF-7 cells, RAW 264.7 cells and a mouse model of lung inflammation stimulated by LPS. This work provided an important and promising tool for rapid in situ diagnosis and research of the progression of pneumonia.

The risk factors for the failure of hook wire localization of ground glass nodules prior to thoracoscopic surgery.

OBJECTIVES: To retrospectively analyse the potential influencing factors of CT-guided hook wire localization failure prior to thoracoscopic resection surgery of ground glass nodules (GGNs), and determine the main risk elements for localization failure. METHODS: In all, 372 patients were included in this study, with 21 patients showing localization failure. The related parameters of patients, GGNs, and localization were analysed through univariate and multiple logistic regression analysis to determine the risk factors of localization failure. RESULTS: Univariate logistic regression analysis indicated that trans-fissure (odds ratio [OR] 4.896, 95% confidence interval [CI] 1.489-13.939); trans-emphysema (OR 3.538, 95% CI 1.343-8.827); localization time (OR 0.956, 95% CI 0.898-1.019); multi-nodule localization (OR 2.597, 95% CI 1.050-6.361); and pneumothorax (OR 10.326, 95% CI 3.414-44.684) were risk factors for localization failure, and the p-values of these factors were < 0.05. However, according to the results of multivariate analysis, pneumothorax (OR 5.998, 95% CI 1.680-28.342) was an exclusive risk factor for the failure of preoperative localization of GGNs. CONCLUSION: CT-guided hook wire localization of GGNs prior to thoracoscopic surgery is often known to fail; however, the incidence is low. Pneumothorax is an independent risk factor for failure in the localization process.

Quantitative CT comparison between COVID-19 and mycoplasma pneumonia suspected as COVID-19: a longitudinal study.

OBJECTIVE: The purpose of this study was to compare imaging features between COVID-19 and mycoplasma pneumonia (MP). MATERIALS AND METHODS: The data of patients with mild COVID-19 and MP who underwent chest computed tomography (CT) examination from February 1, 2020 to April 17, 2020 were retrospectively analyzed. The Pneumonia-CT-LKM-PP model based on a deep learning algorithm was used to automatically quantify the number, volume, and involved lobes of pulmonary lesions, and longitudinal changes in quantitative parameters were assessed in three CT follow-ups. RESULTS: A total of 10 patients with mild COVID-19 and 13 patients with MP were included in this study. There was no difference in lymphocyte counts at baseline between the two groups (1.43 ± 0.45 vs. 1.44 ± 0.50, p = 0.279). C-reactive protein levels were significantly higher in MP group than in COVID-19 group (p < 0.05). The number, volume, and involved lobes of pulmonary lesions reached a peak in 7-14 days in the COVID-19 group, but there was no peak or declining trend over time in the MP group (p < 0.05). CONCLUSION: Based on the longitudinal changes of quantitative CT, pulmonary lesions peaked at 7-14 days in patients with COVID-19, and this may be useful to distinguish COVID-19 from MP and evaluate curative effects and prognosis.

Effect of oxygen concentrations and branched-chain amino acids on the growth and development of sub-seafloor fungus, Schizophyllum commune 20R-7-F01.

Fungi have been reported to be the dominant eukaryotic group in anoxic sub-seafloor sediments, but how fungi subsist in the anoxic sub-marine sedimental environment is rarely understood. Our previous study demonstrated that the fungus, Schizophyllum commune 20R-7-F01 isolated from a ~2 km sediment below the seafloor, can grow and produce primordia in the complete absence of oxygen with enhanced production of branched-chain amino acids (BCAAs), but the primordia cannot be developed into fruit bodies without oxygen. Here, we present the individual and synergistic effects of oxygen and BCAAs on the fruit-body development of this strain. It was found that the fungus required a minimum oxygen concentration of 0.5% pO2 to generate primordia and 1% pO2 to convert primordia into mature fruit body. However, if BCAAs (20 mM) were added to the medium, the primordium could be developed into fruit body at a lower oxygen concentration up to 0.5% pO2 where genes fst4 and c2h2 playing an important role in compensating oxygen deficiency. Moreover, under hypoxic conditions, the fungus showed an increase in mitochondrial number and initiation of auto-phagocytosis. These findings suggest that the fruit-body formation of S. commune may have multiple mechanisms, including energy and amino acid metabolism in response to oxygen concentrations.

Protein Phosphorylation in Plant Cell Signaling.

Owing to their sessile nature, plants have evolved sophisticated sensory mechanisms to respond quickly and precisely to the changing environment. The extracellular stimuli are perceived and integrated by diverse receptors, such as receptor-like protein kinases (RLKs) and receptor-like proteins (RLPs), and then transmitted to the nucleus by complex cellular signaling networks, which play vital roles in biological processes including plant growth, development, reproduction, and stress responses. The posttranslational modifications (PTMs) are important regulators for the diversification of protein functions in plant cell signaling. Protein phosphorylation is an important and well-characterized form of the PTMs, which influences the functions of many receptors and key components in cellular signaling. Protein phosphorylation in plants predominantly occurs on serine (Ser) and threonine (Thr) residues, which is dynamically and reversibly catalyzed by protein kinases and protein phosphatases, respectively. In this review, we focus on the function of protein phosphorylation in plant cell signaling, especially plant hormone signaling, and highlight the roles of protein phosphorylation in plant abiotic stress responses.

Roles of small RNAs in crop disease resistance.

Small RNAs (sRNAs) are a class of short, non-coding regulatory RNAs that have emerged as critical components of defense regulatory networks across plant kingdoms. Many sRNA-based technologies, such as host-induced gene silencing (HIGS), spray-induced gene silencing (SIGS), virus-induced gene silencing (VIGS), artificial microRNA (amiRNA) and synthetic trans-acting siRNA (syn-tasiRNA)-mediated RNA interference (RNAi), have been developed as disease control strategies in both monocot and dicot plants, particularly in crops. This review aims to highlight our current understanding of the roles of sRNAs including miRNAs, heterochromatic siRNAs (hc-siRNAs), phased, secondary siRNAs (phasiRNAs) and natural antisense siRNAs (nat-siRNAs) in disease resistance, and sRNAs-mediated trade-offs between defense and growth in crops. In particular, we focus on the diverse functions of sRNAs in defense responses to bacterial and fungal pathogens, oomycete and virus in crops. Further, we highlight the application of sRNA-based technologies in protecting crops from pathogens. Further research perspectives are proposed to develop new sRNAs-based efficient strategies to breed non-genetically modified (GMO), disease-tolerant crops for sustainable agriculture.

The anaerobic survival mechanism of Schizophyllum commune 20R-7-F01, isolated from deep sediment 2 km below the seafloor.

Fungi dominated the eukaryotic group in the anaerobic sedimentary environment below the ocean floor where they play an essential ecological role. However, the adaptive mechanism of fungi to these anaerobic environments is still unclear. Here, we reported the anaerobic adaptive mechanism of Schizophyllum commune 20R-7-F01, isolated from deep coal-bearing sediment down to ~2 km below the seafloor, through biochemical, metabolomic and transcriptome analyses. The fungus grows well, but the morphology changes obviously and the fruit body develops incompletely under complete hypoxia. Compared with aerobic conditions, the fungus has enhanced branched-chain amino acid biosynthesis and ethanol fermentation under anaerobic conditions, and genes related to these metabolisms have been significantly up-regulated. Additionally, the fungus shows novel strategies for synthesizing ethanol by utilizing both glycolysis and ethanol fermentation pathways. These findings suggest that the subseafloor fungi may adopt multiple mechanisms to cope with lack of oxygen.

A computed tomography-based nomogram to predict pneumothorax caused by preoperative localization of ground glass nodules using hook wire.

OBJECTIVE: To develop and validate a CT-based nomogram to predict the occurrence of loculated pneumothorax due to hook wire placement. METHODS: Patients (n = 177) were divided into pneumothorax (n = 72) and non-pneumothorax (n = 105) groups. Multivariable logistic regression analysis was applied to build a clinical prediction model using significant predictors identified by univariate analysis of imaging features and clinical factors. Receiver operating characteristic (ROC) was applied to evaluate the discrimination of the nomogram, which was calibrated using calibration curve. RESULTS: Based on the results of multivariable regression analysis, transfissure approach [odds ratio (OR): 757.94; 95% confidence interval CI (21.20-27099.30) p < 0.0001], transemphysema [OR: 116.73; 95% CI (12.34-1104.04) p < 0.0001], localization of multiple nodules [OR: 8.04; 95% CI (2.09-30.89) p = 0.002], and depth of nodule [OR: 0.77; 95% CI (0.71-0.85) p < 0.0001] were independent risk factors for pneumothorax and were included in the predictive model (p < 0.05). The area under the ROC curve value for the nomogram was 0.95 [95% CI (0.92-0.98)] and the calibration curve indicated good consistency between risk predicted using the model and actual risk. CONCLUSION: A CT-based nomogram combining imaging features and clinical factors can predict the probability of pneumothorax before localization of ground-glass nodules. The nomogram is a decision-making tool to prevent pneumothorax and determine whether to proceed with further treatment. ADVANCES IN KNOWLEDGE: A nomogram composed of transfissure, transemphysema, multiple nodule localization, and depth of nodule has been developed to predict the probability of pneumothorax before localization of GGNs.

Small DNA Methylation, Big Player in Plant Abiotic Stress Responses and Memory.

DNA methylation is a conserved epigenetic mark that plays important roles in maintaining genome stability and regulating gene expression. As sessile organisms, plants have evolved sophisticated regulatory systems to endure or respond to diverse adverse abiotic environmental challenges, i.e., abiotic stresses, such as extreme temperatures (cold and heat), drought and salinity. Plant stress responses are often accompanied by changes in chromatin modifications at diverse responsive loci, such as 5-methylcytosine (5mC) and N 6-methyladenine (6mA) DNA methylation. Some abiotic stress responses are memorized for several hours or days through mitotic cell divisions and quickly reset to baseline levels after normal conditions are restored, which is referred to as somatic memory. In some cases, stress-induced chromatin marks are meiotically heritable and can impart the memory of stress exposure from parent plants to at least the next stress-free offspring generation through the mechanisms of transgenerational epigenetic inheritance, which may offer the descendants the potential to be adaptive for better fitness. In this review, we briefly summarize recent achievements regarding the establishment, maintenance and reset of DNA methylation, and highlight the diverse roles of DNA methylation in plant responses to abiotic stresses. Further, we discuss the potential role of DNA methylation in abiotic stress-induced somatic memory and transgenerational inheritance. Future research directions are proposed to develop stress-tolerant engineered crops to reduce the negative effects of abiotic stresses.