Homologous mapping yielded a comprehensive predicted protein-protein interaction network for peanut (Arachis hypogaea L.).

BACKGROUND: Protein-protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear. RESULTS: We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. 'Tifrunner' (282,619 pairs), A. hypogaea cv. 'Shitouqi' (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut. CONCLUSION: Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut.

A truncated B-box zinc finger transcription factor confers drought sensitivity in modern cultivated tomatoes.

Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18TT) that encodes a C-terminal truncated protein. While most wild tomato germplasms contain the BBX18CC allele and show more drought tolerant, modern cultivated tomatoes mostly carry BBX18TT allele and are more drought sensitive. Knockout of BBX18 leads to improved drought tolerance in transgenic plants of cultivated tomato. Ascorbate peroxidase 1 (APX1) is identified as a BBX18-interacting protein that acts as a positive regulator of drought resistance in tomato. Chromatin immunoprecipitation sequencing analyses reveal that BBX18 binds to a unique cis-acting element of the APX1 promoter and represses its gene expression. This study provides insights into the molecular mechanism underlying drought resistance mediated by the BBX18-APX1 module in plants.

Pd-Catalyzed Deacylative [4 + 1] Annulation of N-Arylimidoyl Chlorides with ß-Keto Esters Leading to 2-Fluoroalkyl Indoles.

A palladium-catalyzed [4 + 1] annulation of N-arylimidoyl chlorides with ß-keto esters has been developed. In the presence of Pd(OAc)2, PCy3, and K3PO4, a variety of fluoalkyl-containing N-arylimidoyl chlorides smoothly underwent the cascade C-H imidoylation/deacylative Heck-type reactions to afford biologically important 2-fluoroalkyl indoles in moderate to good yields.

BjuA03.BNT1 plays a positive role in resistance to clubroot disease in resynthesized Brassica juncea L.

Clubroot has become a major obstacle in rapeseed production. Breeding varieties resistant to clubroot is the most effective method for disease management. However, the clubroot-resistant germplasm of rapeseed remains limited. To tackle this challenge, we synthesized the clubroot-resistant mustard, CT19, via distant hybridization, and subsequently an F2 segregating population was created by intercrossing CT19 with a clubroot-susceptible germplasm CS15. A major-effect clubroot resistance QTL qCRa3-1 on chromosome A03 was identified through QTL scanning. Transcriptome analyses of CT19 and CS15 revealed that the mechanisms conferring resistance to Plasmodiophora brassica likely involved the regulation of flavonoid metabolism, fatty acid metabolism, and sulfur metabolism. By combining the results from transcriptome, QTL mapping, and gene sequencing, a candidate gene BjuA03.BNT1, encoding NLR (nucleotide-binding domain leucine-rich repeat-containing receptors) protein, was obtained. Intriguingly, comparing with CT19, a base T insertion was discovered in the BjuA03.BNT1 gene's coding sequence in CS15, resulting an alteration within the LRR conserved domain. Overexpression of BjuA03.BNT1 from CT19 notably enhanced the resistance to clubroot in Arabidopsis. Our investigations revealed that BjuA03.BNT1 regulated the resistance to clubroot by modulating fatty acid synthesis and the structure of cell wall. These results are highly relevant for molecular breeding to improve clubroot resistance in rapeseed.

Anti-Biofilm Effects of Z102-E of Lactiplantibacillus plantarum against Listeria monocytogenes and the Mechanism Revealed by Transcriptomic Analysis.

Lactic acid bacteria (LAB) are the most common probiotics, and they present excellent inhibitory effects on pathogenic bacteria. This study aimed to explore the anti-biofilm potential of the purified active substance of Lactiplantibacillus plantarum, named Z102-E. The effects of Z102-E on Listeria monocytogenes were investigated in detail, and a transcriptomic analysis was conducted to reveal the anti-biofilm mechanism. The results indicated that the sub-MIC of Z102-E (3.2, 1.6, and 0.8 mg/mL) decreased the bacterial growth and effectively reduced the self-aggregation, surface hydrophobicity, sugar utilization, motility, biofilm formation, AI-2 signal molecule, contents of extracellular polysaccharides, and extracellular protein of L. monocytogenes. Moreover, the inverted fluorescence microscopy observation confirmed the anti-biofilm effect of Z102-E. The transcriptomic analysis indicated that 117 genes were up-regulated and 214 were down-regulated. Z102-E regulated the expressions of genes related to L. monocytogenes quorum sensing, biofilm formation, etc. These findings suggested that Z102-E has great application potential as a natural bacteriostatic agent.

A flexible glucose biosensor modified by reduced-swelling and conductive zwitterionic hydrogel enzyme membrane.

This paper reports a flexible glucose biosensor which is modified by a reduced-swelling and conductive zwitterionic hydrogel enzyme membrane that contains two forms of chemical cross-links. One chemical cross-linking is induced by thermal initiators and forms the basal network of the hydrogel. Another cross-linking is achieved by the coordination interactions between the multivalent metal ion Al3+ and anionic group -COO- of zwitterionic poly-carboxy betaine (pCBMA), which significantly increase the cross-linking density of the zwitterionic hydrogel, improving the reduced-swelling property and reducing the pore size. The better reduced-swelling property and reduced diameters of pores within the zwitterionic hydrogel make less glucose oxidase (GOx) leakage, thus significantly improving the enzyme membrane's service life. By introducing the Al3+ and Cl-, the conductivity of the zwitterionic hydrogel is enhanced approximately 10.4-fold. According to the enhanced conductivity, the reduced-swelling property, and the high GOx loading capacity of the zwitterionic hydrogel, the sensitivity of the biosensor with GOx/pCBMA-Al3+ is significantly improved by 5 times and has a long service life. Finally, the proposed GOx/pCBMA-Al3+ biosensor was applied in non-invasive blood glucose detection on the human body, verifying the capability in practice.

Genome-Wide Identification of the Whirly Gene Family and Its Potential Function in Low Phosphate Stress in Soybean (Glycine max).

The Whirly (WHY) gene family, functioning as transcription factors, plays an essential role in the regulation of plant metabolic responses, which has been demonstrated across multiple species. However, the WHY gene family and its functions in soybean remains unclear. In this paper, we conducted genome-wide screening and identification to characterize the WHY gene family. Seven WHY members were identified and randomly distributed across six chromosomes. The phylogenetic evolutionary tree of WHY genes in soybean and other species was divided into five clades. An in-depth analysis revealed that segmental duplications significantly contributed to the expansion of GmWHYs, and the GmWHY gene members may have experienced evolutionary pressure for purifying selection in soybeans. The analysis of promoter Cis-elements in GmWHYs suggested their potential significance in addressing diverse stress conditions. The expression patterns of GmWHYs exhibited tissue-specific variations throughout the different stages of soybean development. Additionally, six GmWHY genes exhibited different responses to low phosphate stress. These findings will provide a theoretical basis and valuable reference for the future exploration of WHY gene function.

Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective Additive.

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.

Case report: Paralytic ileus resulted from nirmatrelvir/ritonavir-tacrolimus drug-drug interaction in a systemic lupus erythematosus patient with COVID-19.

Patients with systemic autoimmune rheumatic diseases are at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and effective antiviral treatments including nirmatrelvir/ritonavir can improve their outcomes. However, there might be potential drug-drug interactions when these patients take nirmatrelvir/ritonavir together with immunosuppressants with a narrow therapeutic window, such as tacrolimus and cyclosporine. We present a case of paralytic ileus resulting from tacrolimus toxicity mediated by the use of nirmatrelvir/ritonavir in a patient with systemic lupus erythematosus (SLE). A 37-year-old female SLE patient was prescribed nirmatrelvir/ritonavir without discontinuing tacrolimus. She presented to the emergency room with symptoms of paralytic ileus including persistent abdominal pain, nausea, and vomiting, which were verified to be associated with tacrolimus toxicity. The blood concentration of tacrolimus was measured >30 ng/mL. Urgent medical intervention was initiated, while tacrolimus was withheld. The residual concentration was brought within the appropriate range and tacrolimus was resumed 8 days later. Physicians must be aware of the potential DDIs when prescribing nirmatrelvir/ritonavir, especially to those taking immunosuppresants like tacrolimus.

Comprehensive prognostic assessment in kidney cancer: A multidimensional approach analyzing Fufang Sanling granules, genetic variants, and immune infiltration.

This study delves into the potential therapeutic benefits of Fufang Sanling Granules for kidney cancer, focusing on their active components and the underlying mechanisms of their interaction with cancer-related targets. By constructing a drug-active component-target network based on eight herbs, key active compounds such as kaempferol, quercetin, and linolenic acid were identified, suggesting their pivotal roles in modulating immune responses and cellular signaling pathways relevant to cancer progression. The research further identified 51 central drug-disease genes through comprehensive bioinformatics analyses, implicating their involvement in crucial biological processes and pathways. A novel risk score model, encompassing six genes with significant prognostic value for renal cancer, was established and validated, showcasing its effectiveness in predicting patient outcomes through mutation analysis and survival studies. The model's predictive power was further confirmed by its ability to stratify patients into distinct risk groups with significant survival differences, highlighting its potential as a prognostic tool. Additionally, the study explored the relationship between gene expression within the identified black module and the risk score, uncovering significant associations with the extracellular matrix and immune infiltration patterns. This reveals the complex interplay between the tumor microenvironment and cancer progression. The integration of the risk score with clinical parameters through a nomogram significantly improved the model's predictive accuracy, offering a more comprehensive tool for predicting kidney cancer prognosis. In summary, by combining detailed molecular analyses with clinical insights, this study presents a robust framework for understanding the therapeutic potential of Fufang Sanling Granules in kidney cancer. It not only sheds light on the active components and their interactions with cancer-related genes but also introduces a reliable risk score model, paving the way for personalized treatment strategies and improved patient management in the future.

Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

Dynamic N6 -methyladenosine RNA modification regulates peanut resistance to bacterial wilt.

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.

Tandem Sulfonylative Annulation/Halogenation of 1,7-Enynes with Sodium Sulfinate and TBAX for the Assembly of 4-Methylenechromanes.

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

Natural resistance-associated macrophage proteins are involved in tolerance to heavy metal Cd2+ toxicity and resistance to bacterial wilt of peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil and industrial crops. However, heavy-metal pollution and frequent soil diseases, poses a significant threat to the production of green and healthy peanuts. Herein, we investigated the effects of heavy metal Cd2+ toxicity to the peanuts, and screened out two peanut cultivars H108 and YZ 9102 with higher Cd2+-tolerance. RNA-seq revealed that Natural resistance-associated macrophage proteins (NRAMP)-like genes were involved in the Cd2+ stress tolerance in H108. Genome-wide identification revealed that 28, 13 and 9 Nramp-like genes existing in the A. hypogaea, A. duranensis and A. ipaensis, respectively. The 50 peanut NRAMP genes share conserved architectural characters, and they were classified into two groups. Expressions of AhNramps, particularly AhNramp4, AhNramp12, AhNramp19, and AhNramp25 could be greatly induced by not only cadmium toxicity, but also copper and zinc stresses. The expression profiles of AhNramp14, AhNramp16 and AhNramp25 showed significant differences in the H108 (resistance) and H107 (susceptible) under the infection of bacterial wilt. In addition, we found that the expression profiles of AhNramp14, AhNramp16, and AhNramp25 were greatly up- or down-regulated by the application of exogenous salicylic acid, methyl jasmonate, and abscisic acid. The AhNramp25, of which expression was affected by both heavy metal toxicity and bacterial wilt infection, were selected as strong candidate genes for peanut stress breeding. Our findings will provide an additional information required for further analysis of AhNramps involved in tolerance to heavy metal toxicity and resistance to bacterial wilt of peanut.

Astragaloside IV inhibits epithelial-mesenchymal transition and pulmonary fibrosis via lncRNA-ATB/miR-200c/ZEB1 signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease involving multiple factors and genes. Astragaloside IV (ASV) is one of the main bioactive ingredients extracted from the root of Astragalus membranaceus, which plays an important role in anti-inflammatory, antioxidant and improve cardiopulmonary function. Epithelial-mesenchymal transition (EMT) is a key driver of the process of pulmonary fibrosis, and Zinc finger E-box-binding homeobox 1 (ZEB1) can promote pulmonary fibrosis in an EMT-dependent manner. Here, we found that ASV effectively inhibited the ZEB1 and EMT in both bleomycin (BLM)-induced rat pulmonary fibrosis and TGF-ß1-treated A549 cells. To further elucidate the molecular mechanisms underlying effects of ASV in IPF, we explored the truth using bioinformatics, plasmid construction, immunofluorescence staining, western blotting and other experiments. Dual luciferase reporter assay and bioinformatics proved that miR-200c not only acts as an upstream regulatory miRNA of ZEB1 but also has binding sites for the lncRNA-ATB. In A549 cell-based EMT models, ASV reduced the expression of lncRNA-ATB and upregulated miR-200c. Furthermore, overexpression of lncRNA-ATB and silencing of miR-200c reversed the down-regulation of ZEB1 and the inhibition of EMT processes by ASV. In addition, the intervention of ASV prevented lncRNA-ATB as a ceRNA from regulating the expression of ZEB1 through sponging miR-200c. Taken together, the results showed that ASV inhibited the EMT process through the lncRNA-ATB/miR-200c/ZEB1 signaling pathway, which provides a novel approach to the treatment of IPF.

Coordinated Lipid Mobilization during Seed Development and Germination in Peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil crops in the world due to its lipid-rich seeds. Lipid accumulation and degradation play crucial roles in peanut seed maturation and seedling establishment, respectively. Here, we utilized lipidomics and transcriptomics to comprehensively identify lipids and the associated functional genes that are important in the development and germination processes of a large-seed peanut variety. A total of 332 lipids were identified; triacylglycerols (TAGs) and diacylglycerols were the most abundant during seed maturation, constituting 70.43 and 16.11%, respectively, of the total lipids. Significant alterations in lipid profiles were observed throughout seed maturation and germination. Notably, TAG (18:1/18:1/18:2) and (18:1/18:2/18:2) peaked at 23386.63 and 23392.43 nmol/g, respectively, at the final stage of seed development. Levels of hydroxylated TAGs (HO-TAGs) increased significantly during the initial stage of germination. Accumulation patterns revealed an inverse relationship between free fatty acids and TAGs. Lipid degradation was determined to be regulated by diacylglycerol acyltransferase, triacylglycerol lipase, and associated transcription factors, predominantly yielding oleic acid, linoleic acid, and linolenic acid. Collectively, the results of this study provide valuable insights into lipid dynamics during the development and germination of large-seed peanuts, gene resources, and guiding future research into lipid accumulation in an economically important crop.

The workload change and depression among emergency medical staff after the open policy during COVID-19: a cross-sectional survey in Shandong, China.

Introduction: In the middle of December 2022, the Chinese government adjusted the lockdown policy on coronavirus disease 2019 (COVID-19), a large number of infected patients flooded into the emergency department. The emergency medical staff encountered significant working and mental stress while fighting the COVID-19 pandemic. We aimed to investigate the workload change, and the prevalence and associated factors for depression symptoms among emergency medical staff after the policy adjustment. Methods: We conducted a cross-sectional online survey of emergency medical staff who fought against COVID-19 in Shandong Province during January 16 to 31, 2023. The respondents' sociodemographic and work information were collected, and they were asked to complete the 9-item Patient Health Questionnaire (PHQ-9) then. Univariate and multivariate logistic regression analyses were applied to identify the potential associated factors for major depression. Results: Nine hundred and sixteen emergency medical personnel from 108 hospitals responded to this survey. The respondents' weekly working hours (53.65 ± 17.36 vs 49.68 ± 14.84) and monthly night shifts (7.25 ± 3.85 vs 6.80 ± 3.77) increased after the open policy. About 54.3% of the respondents scored more than 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. In univariate analysis, being doctors, living with family members aged ≤16 or ≥ 65 years old, COVID-19 infection and increased weekly working hours after the open policy were significantly associated with a PHQ-9 score ≥ 10 points. In the multivariate analysis, only increased weekly working hours showed significant association with scoring ≥10 points. Conclusion: Emergency medical staff' workload had increased after the open policy announcement, which was strongly associated with a higher PHQ-9 scores, indicating a very high risk for major depression. Emergency medical staff working as doctors or with an intermediate title from grade-A tertiary hospitals had higher PHQ-9 scores, while COVID-19 infection and weekly working hours of 60 or more after the open policy were associated with higher PHQ-9 scores for those from grade-B tertiary hospitals. Hospital administrators should reinforce the importance of targeted emergency medical staff support during future outbreaks.

Hazardous risk of antibiotic resistance genes: Host occurrence, distribution, mobility and vertical transmission from different environments to corn silage.

Antibiotic resistance genes (ARGs) are one of the emerging contaminants posing a great deal of hazardous risk to public health. This study employed metagenomics and deciphered the potential risk of the antibiotic resistome and their vertical transfer to ensiled whole-crop corn silage harvested from six climate zones: 1. Warm temperate-fully humid-hot summer (Cfa), 2. Arid-desert-cold arid (BWk), 3. Snow-desert-cold summer (Dwc), 4. Snow-desert-hot summer (Dwa), 5. Arid-steppe-cold arid (BSk), and 6. Equatorial-desert (Aw) based on the Köppen-Geiger climate classification in China. The findings demonstrate a high diversity of ARGs, which is related to the drug classes of tetracycline, ciprofloxacin, lincosamide, fosfomycin, and beta lactam. Resistome variations are mostly related to variations in microbial composition and fermentation characteristics of the silages from different climate zones, which are indirectly influenced by environmental conditions. The most dominating ARGs in corn silage were tetM, acrA, H-NS, lnuA, emrR, and KpnG, which is primarily hosted by Klebsiella and Lactobacilli. There were 5 high-risk ARGs (tetM, bacA, SHV-1, dfrA17, and QnrS1) in silage from different climate zones, and the tetM was the most prevalent high-risk ARG. However, throughout the ensiling process, the abundance of ARGs, and mobile ARGs were reduced. The resistome contamination in silage from Tibet (Dwc) with high altitude and harsh environment was relatively low due to the low variety and abundance of ARGs, the low abundance of mobile ARGs and high-risk ARGs. In addition, most of the bacteria responsible for the silage fermentation were also found to be the hosts to the ARGs, although their abundance decreased after 90 d of silage fermentation. Hence, we alert the existence of ARGs-related biosafety risk in silages and call for more attention to the silage ARGs, their hosts, and mobile genetic elements in order to curtail their possible risk to public health.

Synthesis of Trifluoromethylated Dibenzoxepines via Palladium-Catalyzed Tandem C-O Bond Formation/C-H Arylation.

A palladium-catalyzed cyclization reaction of phenols with trifluoromethyl-containing ortho-bromo-ß-chlorostyrenes has been developed. In the presence of palladium(II) acetate, tricyclohexylphosphine, and cesium carbonate, a variety of 6-trifluoromethyldibenzo[b,d]oxepines were prepared in moderate to good yields through the tandem O-alkenylation of general phenols and subsequent C-H arylation.