Protons intercalation induced hydrogen bond network in δ-MnO2 cathode for high-performance aqueous zinc-ion batteries.

Birnessite-type MnO2 (δ-MnO2) exhibits great potential as a cathode material for aqueous zinc-ion batteries (AZIBs). However, the structural instability and sluggish reaction kinetics restrict its further application. Herein, a unique protons intercalation strategy was utilized to simultaneously modify the interlayer environment and transition metal layers of δ-MnO2. The intercalated protons directly form strong O  H bonds with the adjacent oxygens, while the increased H2O molecules also establish a hydrogen bond network (O  H···O) between H2O molecules or bond with adjacent oxygens. Based on the Grotthuss mechanism, these bondings ultimately enhance the stability of layered structures and facilitate the rapid diffusion of protons. Moreover, the introduction of protons induces numerous oxygen vacancies, reduces steric hindrance, and accelerates ion transport kinetics. Consequently, the protons intercalated δ-MnO2 (H-MnO2-x) demonstrates exceptional specific capacity of 401.7 mAh/g at 0.1 A/g and a fast-charging performance over 1000 cycles. Density functional theory analysis confirms the improved electronic conductivity and reduced diffusion energy barrier. Most importantly, electrochemical quartz crystal microbalance tests combining with ex-situ characterizations verify the inhibitory effect of the interlayer proton environment on basic zinc sulfate formation. Protons intercalation behavior provides a promising avenue for the development of MnO2 as well as other cathodes in AZIBs.

Chemical fuel-driven transient 2D supramolecular organic frameworks (SOFs): catalysis for green synthesis.

Mimicking the dissipative assemblies found in living systems fueled by bioenergy, we present a novel chemical fuel-driven transient 2D SOF, formed via the redox reaction-driven transient self-assembly of tetraphenylene-based structural units and cucurbit[8]uril (CB[8]). The system was initiated by adding sodium dithionite (SDT) as the fuel, leading to the formation of 2D SOFs through 2 : 1 host-guest complexation between the viologen cation radical and CB[8]. These 2D SOFs then spontaneously disassemble over time as the radicals are oxidized by air. The temporal assembly and lifetimes of these transient SOFs can be controlled by adjusting the concentrations of the fuel. Moreover, the resulting transient 2D SOFs exhibited remarkable potential as catalysts for the green synthesis of benzyl sulfones in water.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

Survival outcomes of segmentectomy and lobectomy for early stage non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The question of whether segmentectomy and lobectomy have similar survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC) is a matter of debate. METHODS: A cohort study and randomized controlled trial were included, comparing segmentectomy and lobectomy, by utilizing computerized access to the Pubmed, Web of Science, and Cochrane Library databases up until July 2022. The Cochrane Collaboration tool was used to evaluate the randomized controlled trials, while the Newcastle-Ottawa Scale (NOS) was used to evaluate the cohort studies. Sensitivity analyses were also carried out. RESULTS: The analysis incorporated 17 literature studies, including one randomized controlled trial and 16 cohort studies, and was divided into a segmentectomy group (n = 2081) and a lobectomy group (n = 2395) based on the type of surgery the patient underwent. Each study was followed up from 27 months to 130.8 months after surgery. Over survival (OS): HR = 1.14, 95%CI(0.97,1.32), P = 0.10; disease-free survival (DFS): HR = 1.13, 95%CI(0.91,1.41), P = 0.27; recurrence-free survival (RFS): HR = 0.95, 95%CI(0.81,1.12), P = 0.54. CONCLUSION: The results of the study suggest that the survival outcomes of the segmentectomy group were not inferior to that of the lobectomy group. Segmentectomy should therefore be considered as a treatment option for early stage NSCLC.

Molecular mechanism of Saikosaponin-d in the treatment of gastric cancer based on network pharmacology and in vitro experimental verification.

The study aimed to utilize network pharmacology combined with cell experiments to research the mechanism of action of Saikosaponin-d in the treatment of gastric cancer. Drug target genes were obtained from the PubChem database and the Swiss Target Prediction database. Additionally, target genes for gastric cancer were obtained from the GEO database and the Gene Cards database. The core targets were then identified and further analyzed through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GESA enrichment. The clinical relevance of the core targets was assessed using the GEPIA and HPA databases. Molecular docking of drug monomers and core target proteins was performed using Auto Duck Tools and Pymol software. Finally, in vitro cellular experiments including cell viability, apoptosis, cell scratch, transwell invasion, transwell migration, qRT-PCR, and Western blot were conducted to verify these findings of network pharmacology. The network pharmacology analysis predicted that the drug monomers interacted with 54 disease targets. Based on clinical relevance analysis, six core targets were selected: VEGFA, IL2, CASP3, BCL2L1, MMP2, and MMP1. Molecular docking results showed binding activity between the Saikosaponin-d monomer and these core targets. Saikosaponin-d could inhibit gastric cancer cell proliferation, induce apoptosis, and inhibit cell migration and invasion.

Ferulic Acid Dimers as Potential Antiviral Agents by Inhibiting TMV Self-Assembly.

A series of ferulic acid dimers were designed, synthesized, and evaluated for anti-TMV activity. Biological assays demonstrated that compounds A6, E3, and E5 displayed excellent inactivating against tobacco mosaic virus (TMV) with EC50 values of 62.8, 94.4, and 85.2 µg mL-1, respectively, which were superior to that of ningnanmycin (108.1 µg mL-1). Microscale thermophoresis indicated that compounds A6, E3, and E5 showed strong binding capacity to TMV coat protein with binding affinity values of 1.862, 3.439, and 2.926 µM, respectively. Molecular docking and molecular dynamics simulation revealed that compound A6 could firmly bind to the TMV coat protein through hydrogen and hydrophobic bonds. Transmission electron microscopy and self-assembly experiments indicated that compound A6 obviously destroyed the integrity of the TMV particles and blocked the virus from infecting the host. This study revealed that A6 can be used as a promising leading structure for the development of antiviral agents by inhibiting TMV self-assembly.

Preparation of Hybrid Magnetic Nanoparticles for Sensitive and Rapid Detection of Phorate Residue in Celery Using SERS Immunochromatography Assay.

Extensive use of pesticides in agricultural production has been causing serious health threats to humans and animals. Among them, phorate is a highly toxic organophosphorus insecticide that has been widely used in planting. Due to its harmful effects on human and animal health, it has been restricted for use in many countries. Analytical methods for the rapid and sensitive detection of phorate residues in agricultural products are urgently needed. In this study, a new method was developed by combining surface-enhanced Raman spectroscopy (SERS) and immunochromatography assay (ICA). Hybrid magnetic Fe3O4@Au@DTNB-Ab nanoprobes were prepared by modifying and growing Au nanoseeds on an Fe3O4 core. SERS activity of the nanoprobe was optimized by adjusting the concentration of the Au precursor. A rapid and sensitive assay was established by replacing the traditional colloidal gold-based ICA with hybrid SERS nanoprobes for SERS-ICA. After optimizing parameters including coating antibody concentrations and the composition and pH of the buffer solution, the limit of detection (LOD) for phorate could reach 1 ng/mL, with a linear range of 5~100 ng/mL. This LOD is remarkably lower than the maximum residue limit in vegetables and fruits set by the Chinese government. The feasibility of this method was further examined by conducting a spiking test with celery as the real sample. The result demonstrated that this method could serve as a promising platform for rapid and sensitive detection of phorate in agricultural products.

Bidentate Coordination Structure Facilitates High-Voltage and High-Utilization Aqueous Zn-I2 Batteries.

The zinc-iodine aqueous battery is a promising energy storage device, but the conventional two-electron reaction potential and energy density of the iodine cathode are far from meeting practical application requirements. Given that iodine is rich in redox reactions, activating the high-valence iodine cathode reaction has become a promising research direction for developing high-voltage zinc-iodine batteries. In this work, by designing a multifunctional electrolyte additive trimethylamine hydrochloride (TAH), a stable high-valence iodine cathode in four-electron-transfer I-/I2/I+ reactions with a high theoretical specific capacity is achieved through a unique amine group, Cl bidentate coordination structure of (TA)ICl. Characterization techniques such as synchrotron radiation, in-situ Raman spectra, and DFT calculations are used to verify the mechanism of the stable bidentate structure. This electrolyte additive stabilizes the zinc anode by promoting the desolvation process and shielding mechanism, enabling the zinc anode to cycle steadily at a maximum areal capacity of 57 mAh cm-2 with 97% zinc utilization rate. Finally, the four-electron-transfer aqueous Zn-I2 full cell achieves 5000 stable cycles at an N/P ratio of 2.5. The unique bidentate coordination structure contributes to the further development of high-valence and high capacity aqueous zinc-iodine batteries.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of ß-glucan by resetting TAMs.

Anti-CD40 antibodies (Abs) have been shown to induce antitumor T-cell responses. We reported that the engineered agonistic anti-CD40 Ab (5C11, IgG4 isotype) recognized human CD40 antigen expressed on a human B lymphoblastoid cell line as well as on splenic cells isolated from humanized CD40 mice. Of note, a single high dosage of 5C11 was able to prohibit tumor growth in parallel with an increase in the population of infiltrated CD8+ T cells. Furthermore, the antitumor effects of 5C11 were enhanced in the presence of ß-glucan along with an increase in the population of infiltrated CD8+ T cells. In addition, the numbers of CD86+ TAMs and neutrophils were elevated in the combination of 5C11 and ß-glucan compared with either 5C11 or ß-glucan alone. Furthermore, the abundance of Faecalibaculum, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and ß-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and ß-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and ß-glucan could be a promising therapeutic strategy for cancer patients.

Experimental Study on the Effect of Wetting-Drying Cycles on Crack Development and Radon Retardation of the Covering Soil in Uranium Mill Tailing Impoundments.

The majority of uranium mill tailing impoundments in the southern part of China are located in humid subtropical regions where persistent rainfall and rapid evaporation of water after rain often occur. Under the prolonged influence of alternating wet and dry conditions, the covering soil layer of uranium mill tailing impoundments develops cracks, leading to the issue of degradation or even failure of the radon retardation effect. A beach surface of uranium mill tailing impoundments in the southern part of China is selected as the research object. Through use of a self-made simulation test device, a degradation experiment of uranium mill tailing covering soil models under wetting-drying cycles was conducted indoors. The experimental results indicate that with a constant amplitude of wetting-drying cycles, microcracks characterized by a narrow width and high abundance were mainly generated in the early-to-mid-stage of wetting-drying cycles. The main cracks, characterized by their wide width and less abundance, were mainly formed in the mid-to-late stage of wetting-drying cycles. After seven wetting-drying cycles, the total length of cracks showed a "stair-step" increase and the surface crack ratio exhibited a trend of moving from rapid growth to stable growth and then to a slight decline. The cumulative damage degree showed a rapid increase to stable growth with an increase in the number of wetting-drying cycles. Grey relational analysis revealed that, compared to other surface crack indicators, radon exhalation rate was the most closely correlated with the surface crack ratio. With a constant amplitude of wetting-drying cycles, the radon exhalation rate underwent four stages as the number of wetting-drying cycles increased: stage I witnessed a rapid increase, stage II witnessed a rapid decrease, stage III witnessed a gradual increase, and stage IV witnessed a stable or even slight decrease. With a constant number of wetting-drying cycles, the radon exhalation rate correspondingly increased with the amplitude of wetting-drying cycles, particularly noticeable when the alternation amplitude was 30 ± 20%. From the early mid-stage to the late stage of wetting-drying cycles, the curves of the radon exhalation rate, surface crack ratio, and cumulative damage degree tended to be consistent, showing a gradual increase. The research provided in this study offers valuable insights into radon control measures and environmental assessments on the beach surface of uranium mill tailing impoundments.

Physiological, Biochemical, and Molecular Analyses Reveal Dark Heartwood Formation Mechanism in Acacia melanoxylon.

Acacia melanoxylon is highly valued for its commercial applications, with the heartwood exhibiting a range of colors from dark to light among its various clones. The underlying mechanisms contributing to this color variation, however, have not been fully elucidated. In an effort to understand the factors that influence the development of dark heartwood, a comparative analysis was conducted on the microstructure, substance composition, differential gene expression, and metabolite profiles in the sapwood (SW), transition zone (TZ), and heartwood (HW) of two distinct clones, SR14 and SR25. A microscopic examination revealed that heartwood color variations are associated with an increased substance content within the ray parenchyma cells. A substance analysis indicated that the levels of starches, sugars, and lignin were more abundant in SP compared to HW, while the concentrations of phenols, flavonoids, and terpenoids were found to be higher in HW than in SP. Notably, the dark heartwood of the SR25 clone exhibited greater quantities of phenols and flavonoids compared to the SR14 clone, suggesting that these compounds are pivotal to the color distinction of the heartwood. An integrated analysis of transcriptome and metabolomics data uncovered a significant accumulation of sinapyl alcohol, sinapoyl aldehyde, hesperetin, 2', 3, 4, 4', 6'-peptahydroxychalcone 4'-O-glucoside, homoeriodictyol, and (2S)-liquiritigenin in the heartwood of SR25, which correlates with the up-regulated expression of CCRs (evm.TU.Chr3.1751, evm.TU.Chr4.654_667, evm.TU.Chr4.675, evm.TU.Chr4.699, and evm.TU.Chr4.704), COMTs (evm.TU.Chr13.3082, evm.TU.Chr13.3086, and evm.TU.Chr7.1411), CADs (evm.TU.Chr10.2175, evm.TU.Chr1.3453, and evm.TU.Chr8.1600), and HCTs (evm.TU.Chr4.1122, evm.TU.Chr4.1123, evm.TU.Chr8.1758, and evm.TU.Chr9.2960) in the TZ of A. melanoxylon. Furthermore, a marked differential expression of transcription factors (TFs), including MYBs, AP2/ERFs, bHLHs, bZIPs, C2H2s, and WRKYs, were observed to be closely linked to the phenols and flavonoids metabolites, highlighting the potential role of multiple TFs in regulating the biosynthesis of these metabolites and, consequently, influencing the color variation in the heartwood. This study facilitates molecular breeding for the accumulation of metabolites influencing the heartwood color in A. melanoxylon, and offers new insights into the molecular mechanisms underlying heartwood formation in woody plants.

On the correlation among the students' epistemic cognition, academic emotions, and academic achievement in higher education.

Students' academic achievement relies on a variety of pedagogical, affective, and individual factors. The investigation of academic emotions and epistemic cognition has been a focal point in existing research. Previous studies have predominantly delved into the essence of students' epistemic cognition and academic emotions. Nonetheless, the correlation between the epistemic cognition, academic emotions, and academic success of Chinese undergraduate students remains inadequately explored. This research delves into the interconnectedness of these variables and examines which facets of epistemic cognition and academic emotions can forecast students' academic performance. A total of three hundred and eighty (380) Chinese undergraduate students were chosen via random sampling for this study. Their self-reported academic achievements were taken into account. Additionally, they completed questionnaires tailored to evaluate their epistemic cognition and academic emotions. The participants' scores underwent Pearson correlation and multiple regression analyses. The findings indicate that positive emotions correlate positively, while negative emotions correlate negatively with students' academic success. Furthermore, positive emotions and three categories of epistemic cognition were found to be predictors of students' academic accomplishments. In conclusion, it is deduced that both epistemic cognition and positive emotions play a role in enhancing students' academic success. The implications of these findings extend to educational psychologists, educators, and students, both theoretically and practically.

Establishment and evaluation of on-chip intestinal barrier biosystems based on microfluidic techniques.

As a booming engineering technology, the microfluidic chip has been widely applied for replicating the complexity of human intestinal micro-physiological ecosystems in vitro. Biosensors, 3D imaging, and multi-omics have been applied to engineer more sophisticated intestinal barrier-on-chip platforms, allowing the improved monitoring of physiological processes and enhancing chip performance. In this review, we report cutting-edge advances in the microfluidic techniques applied for the establishment and evaluation of intestinal barrier platforms. We discuss different design principles and microfabrication strategies for the establishment of microfluidic gut barrier models in vitro. Further, we comprehensively cover the complex cell types (e.g., epithelium, intestinal organoids, endothelium, microbes, and immune cells) and controllable extracellular microenvironment parameters (e.g., oxygen gradient, peristalsis, bioflow, and gut-organ axis) used to recapitulate the main structural and functional complexity of gut barriers. We also present the current multidisciplinary technologies and indicators used for evaluating the morphological structure and barrier integrity of established gut barrier models in vitro. Finally, we highlight the challenges and future perspectives for accelerating the broader applications of these platforms in disease simulation, drug development, and personalized medicine. Hence, this review provides a comprehensive guide for the development and evaluation of microfluidic-based gut barrier platforms.

Unraveling the Nature of Spin Coupling in a Metal-Free Diradical: Theoretical Distinction of Ferromagnetic and Antiferromagnetic Interactions.

Metal-free diradicals based on polycyclic aromatic hydrocarbons are promising candidates for organic spintronics due to their stable magnetism and tunable spin coupling. However, distinguishing and elucidating the origins of ferromagnetic and antiferromagnetic interactions in these systems remain challenging. Here, we investigate the 2-OS diradical molecule sandwiched between gold electrodes using a combined density functional theory and hierarchical equations of motion approach. We find that the dihedral angle between the radical moieties controls the nature and strength of the intramolecular spin coupling, transitioning smoothly from antiferromagnetic to ferromagnetic as the angle increases. Distinct features in the inelastic electron tunneling spectra are identified that can discern the two coupling regimes, including spin excitation steps whose energies directly reveal the exchange coupling constant. Mechanical stretching of the junction is predicted to modulate the spectral line shapes by adjusting the hybridization of the molecular radicals with the electrodes. Our work elucidates the electronic origin of tunable spin interactions in 2-OS and provides spectroscopic fingerprints for characterizing magnetism in metal-free diradicals.

Inhibition of Notch3/Hey1 ameliorates peribiliary hypoxia by preventing hypertrophic hepatic arteriopathy in biliary atresia progression.

Emerging evidence indicates the presence of vascular abnormalities and ischemia in biliary atresia (BA), although specific mechanisms remain undefined. This study examined both human and experimental BA. Structural and hemodynamic features of hepatic arteries were investigated by Doppler ultrasound, indocyanine green angiography, microscopic histology, and invasive arterial pressure measurement. Opal multiplex immunohistochemistry, western blot, and RT-PCR were applied to assess Notch3 expression and the phenotype of hepatic arterial smooth muscle cells (HASMCs). We established animal models of Notch3 inhibition, overexpression, and knockout to evaluate the differences in overall survival, hepatic artery morphology, peribiliary hypoxia, and HASMC phenotype. Hypertrophic hepatic arteriopathy was evidenced by an increased wall-to-lumen ratio and clinically manifested as hepatic arterial hypertension, decreased hepatic artery perfusion, and formation of hepatic subcapsular vascular plexuses (HSVPs). We observed a correlation between overactivation of Notch3 and phenotypic disruption of HASMCs with the exacerbation of peribiliary hypoxia. Notch3 signaling mediated the phenotype alteration of HASMCs, resulting in arterial wall thickening and impaired oxygen supply in the portal microenvironment. Inhibition of Notch3/Hey1 ameliorates portal hypoxia by restoring the balance of contractile/synthetic HASMCs, thereby preventing hypertrophic arteriopathy in BA.

P-limitation regulates the accumulation of soil aggregates organic carbon during the restoration of Pinus tabuliformis forest.

Artificial forest restoration is widely recognized as a crucial approach to enhance the potential of soil carbon sequestration. Nevertheless, there is still limited understanding regarding the dynamics of aggregate organic carbon (OC) and the underlying mechanisms driving these dynamics after artificial forest restoration. To address this gap, we studied Pinus tabuliformis forests and adjacent farmland in three recovery periods (13, 24 and 33 years) in the Loess Plateau region. Samples of undisturbed soil from the surface layer were collected and divided into three aggregate sizes: >2 mm (large aggregate), 0.25-2 mm (medium aggregate), and <0.25 mm (small aggregate). The aim was to examine the distribution of OC and changes in enzyme activity within each aggregate size. The findings revealed a significant increase in OC content for all aggregate sizes following the restoration of Pinus tabuliformis forests. After 33 years of recovery, the OC of large aggregates, medium aggregates and micro-aggregates increased by (30.23 ± 9.85)%, (36.71 ± 21.60)% and (37.88 ± 16.07)% respectively compared with that of farmland. Moreover, the restoration of Pinus tabuliformis forests lead to increased activity of hydrolytic enzymes and decreased activity of oxidative enzymes. It is noteworthy that the regulation of carbon in all aggregates is influenced by soil P-limitation. In large aggregates, P-limitation promotes the enhancement of hydrolytic enzyme activity, thereby facilitate OC accumulation. Conversely, in medium and small aggregates, P-limitation inhibits the increase in oxidative enzyme activity, resulting in OC accumulation. The results emphasize the importance of P-limitation in regulating OC accumulation during the restoration of Pinus tabulaeformis forest, in which large aggregates play a leading role.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

Comparative physiological, biochemical, metabolomic, and transcriptomic analyses reveal the formation mechanism of heartwood for Acacia melanoxylon.

Acacia melanoxylon is well known as a valuable commercial tree species owing to its high-quality heartwood (HW) products. However, the metabolism and regulatory mechanism of heartwood during wood development remain largely unclear. In this study, both microscopic observation and content determination proved that total amount of starches decreased and phenolics and flavonoids increased gradually from sapwood (SW) to HW. We also obtained the metabolite profiles of 10 metabolites related to phenolics and flavonoids during HW formation by metabolomics. Additionally, we collected a comprehensive overview of genes associated with the biosynthesis of sugars, terpenoids, phenolics, and flavonoids using RNA-seq. A total of ninety-one genes related to HW formation were identified. The transcripts related to plant hormones, programmed cell death (PCD), and dehydration were increased in transition zone (TZ) than in SW. The results of RT-PCR showed that the relative expression level of genes and transcription factors was also high in the TZ, regardless of the horizontal or vertical direction of the trunk. Therefore, the HW formation took place in the TZ for A. melanoxylon from molecular level, and potentially connected to plant hormones, PCD, and cell dehydration. Besides, the increased expression of sugar and terpenoid biosynthesis-related genes in TZ further confirmed the close connection between terpenoid biosynthesis and carbohydrate metabolites of A. melanoxylon. Furthermore, the integrated analysis of metabolism data and RNA-seq data showed the key transcription factors (TFs) regulating flavonoids and phenolics accumulation in HW, including negative correlation TFs (WRKY, MYB) and positive correlation TFs (AP2, bZIP, CBF, PB1, and TCP). And, the genes and metabolites from phenylpropanoid and flavonoid metabolism and biosynthesis were up-regulated and largely accumulated in TZ and HW, respectively. The findings of this research provide a basis for comprehending the buildup of metabolites and the molecular regulatory processes of HW formation in A. melanoxylon.

Risk factors for anxiety and its impacts on acute exacerbation in older patients with chronic obstructive pulmonary disease.

Background: Anxiety is common in patients with chronic obstructive pulmonary disease (COPD), especially in older patients with the definition of age over 60 years old. Few studies have focused on anxiety in older COPD patients. This study aimed to analyze the risk factors of anxiety in older COPD patients and the impacts of anxiety on future acute exacerbation. Methods: The general information, questionnaire data, previous acute exacerbation and pulmonary function were collected. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the anxiety of older COPD patients. The patients were followed up for one year, the number and the degrees of acute exacerbations of COPD were recorded. Results: A total of 424 older COPD patients were included in the analysis. 19.81% (N = 84) had anxiety symptoms, and 80.19% (N = 340) had no anxiety symptoms. There were increased pack-years, more comorbidities, and more previous acute exacerbations in older COPD patients with anxiety compared to those without anxiety (P < 0.05). Meanwhile, a higher modified Medical Research Council (mMRC), a higher COPD assessment test (CAT) score and a shorter six-minute walking distance (6MWD) were found in older COPD patients with anxiety (P < 0.05). The BODE index, mMRC, CAT score, comorbidities and acute exacerbations were associated with anxiety. Eventually, anxiety will increase the risk of future acute exacerbation in older COPD patients (OR = 4.250, 95% CI: 2.369-7.626). Conclusion: Older COPD patients with anxiety had worsening symptoms, more comorbidities and frequent acute exacerbation. Meanwhile, anxiety may increase the risk of acute exacerbation in the future. Therefore, interventions should be provided to reduce the risk of anxiety in older COPD patients at an early stage.