Ionones from cigar tobacco leaves.

Phytochemical studies on cigar tobacco leaves led to the isolation of 18 ionone-type compounds, including previously undescribed cigatobanes E (1) and F (2). Additionally, compounds vomifoliol acetate (3), dehydrovomifoliol (4), 8,9-dihydromegastigmane-4,6-diene-3-one (5), 7α,8α-epoxyblumenol B (6), 3-oxoactinidol (12), and loliolide acetate (15), 4ß-hydroxy-dihydroactinidiolide (17), were found in tobacco leaves for the first time. The structural elucidation of all compounds was accomplished through rigorous spectral analysis.

Integrating ICP-MS and Chemometrics for Profiling Inorganic Elements in Lianhua Qingwen Capsules and Evaluating Health Risk.

Lianhua Qingwen capsule (LHQWC) is composed of 13 traditional Chinese herbs. In this study, we employed inductively coupled plasma mass spectrometry (ICP-MS) to quantify the concentrations of 26 inorganic elements (Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Ag, Cd, Cs, Ba, Hg, Tl, Pb, U) across 22 batches of LHQWC. These results were complemented with Chemometrics analysis and health risk assessment of selected hazardous elements. Chemometric analysis revealed significant quality variations among the 22 batches of LHQWC, identifying U, Cs, Tl, Rb, Mn, As, Mg, and Al as characteristic elements influencing formulation consistency. Moreover, the health risk assessment indicated that while levels of Cu, As, Cd, Pb, Cr, and Hg in LHQWC were within acceptable limits, concerns arose regarding vanadium levels in certain batches. These findings underscore the necessity of comprehensive elemental analysis and health risk assessment to ensure the safety and quality of LHQWC. Our study provides valuable insights for both quality evaluation and regulatory considerations in the production of LHQWC and similar herbal formulations.

Comparative Analysis Between Directly Measured and Parent-Evaluated Executive Function: Predicting Children's Academic Achievement and Social Development in a One-Year Longitudinal Study.

Purpose: The purpose of this study was to examine differences between directly measured and parent-evaluated executive function in predicting children's academic achievement and social development, and to explore the mediating roles of peer status and social competence in the effects of executive function on social behavior. Patients and Methods: The study followed 106 first-grade children in an elementary school in China for one year. Regression and mediation analyses were conducted using SPSS 26.0 and AMOS 21.0 to test the hypotheses. Results: First, in a comparison of the predictive role of directly measured and parent-evaluated executive function, directly measured executive function played a more important role in predicting academic achievement, while parent-evaluated executive function played a greater role in predicting social development. Second, parent-evaluated executive function influenced social behavior primarily through social competence and peer status, with social competence playing a more significant mediating role than peer status. Conclusion: Compared with previous studies, the results of the present study provide more direct evidence for the relationship and differences between directly measured and parent-evaluated executive function, further suggesting that they have different efficacy and predictive goals, while the present study also describes the pathways through which executive function influences social behavior: the mediating role of peer status and social competence. This suggests that, on the one hand, educators or researchers need to choose appropriate measures of executive function for their own purposes and, on the other hand, in order to promote the development of children's social behavior, they need to focus on the development of children's executive function, social competence and peer relationships.

Enhancing biohydrogen production from xylose at low temperature (20 °C) using natural FeS2 Ore: Thermodynamic analysis and mechanistic insights.

This study investigates the efficacy of pyrite in enhancing biohydrogen production from xylose at low temperature (20 °C). Higher hydrogen yield rates (Rm) and reduced lag time (λ) were achieved across initial xylose concentrations ranging from 2-10 g/L. At an optimal xylose concentration of 5 g/L, pyrite reduced λ by 2.5 h and increased Rm from 1.3 to 2.7 mL h-1. These improvements are attributed to pyrite's ability to enhance the secretion of extracellular polymeric substance and flavins, facilitate NADH and NAD+ generation and transition, and favor biohydrogen production. Thermodynamic analyses and Gibbs free energy calculations further elucidated pyrite's role in the full reaction process and rate-limiting steps at low temperature. This study offers valuable insights into improving the efficiency of biohydrogen production at low temperature, with significant implications for energy conservation.

Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir-treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.

WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.

BACKGROUND: Sorafenib is currently the first choice for the treatment of patients with advanced hepatocellular carcinoma, but its therapeutic effect is still limited. OBJECTIVES: This study aims to examine whether WEE family kinase inhibitors can enhance the anticancer effect of sorafenib. METHODS: We analyzed the expression levels of PKMYT1 kinase and WEE1 kinase in HCC, studied the inhibitory effect of PKMYT1 kinase inhibitor RP-6306, WEE1 kinase inhibitor adavosertib combined with sorafenib on the proliferation of HCC cells, and detected the effect of drug combination on CDK1 phosphorylation. RESULTS: We found that PKMYT1 and WEE1 were upregulated in HCC and were detrimental to patient survival. Cell experiments showed that both RP-6306 and adavosertib (1-100 µM) inhibited the proliferation of HCC cell lines in a dose-dependent manner alone, and the combination of the two drugs had a synergistic effect. In HCC cell lines, sorafenib combined with RP-6306 or adavosertib showed a synergistic antiproliferation effect and less toxicity to normal cells. Sorafenib combined with RP-6306 and adavosertib further inhibited the proliferation of HCC cells and caused complete dephosphorylation of CDK1. CONCLUSION: Taken together, our findings provide experimental evidence for the future use of sorafenib in combination with RP-6306 or adavosertib for the treatment of HCC.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Impacts of regional socioeconomic statuses and global events on solid waste research reflected in six waste-focused journals.

The research pertaining to solid waste is undergoing extensive advancement, thereby necessitating a consolidation and analysis of its research trajectories. The existing biblio-studies on solid waste research (SWR) lack thorough analyses of the factors influencing its trends. This article presents an innovative categorization framework that categorizes publications from six SWR journals utilizing Source Latent Dirichlet Allocation. First analyse changes in publication numbers across main categories, subcategories, journals, and regions, providing a macro-level study of SWR. Temporal analysis of keywords supplements a micro-level study of SWR, which highlights that emerging technologies with low Technology Readiness Level receive significant attention, while studies on widespread technologies are diminishing. Additionally, this study demonstrates the substantial influence of socioeconomic factors and previous SWR publications on current and future SWR trends. Finally, the article confirms the impact of global events on SWR trends by examining the structural breakpoints of SWR and their correlation with global events.

Aging Increases Global Annual Food Greenhouse Gas Emissions up to 300 Million Tonnes by 2100.

The dietary preferences of the elderly population exhibit distinct variations from the overall averages in most countries, gaining increasing significance due to aging demographics worldwide. These dietary preferences play a crucial role in shaping global food systems, which will result in changed environmental impacts in the future such as greenhouse gas (GHG) emissions. We present a quantitative evaluation of the influence of population aging on the changes in GHG emissions from global food systems. To achieve this, we developed regional dietary coefficients (DCs) of the elderly based on the Global Dietary Database (GDD). We then reconciled the GDD with the dataset from the Food and Agriculture Organization of the United Nations (FAO) to calculate the food GHG emissions of the average population in each of the countries. By applying the DCs, we estimated the national food GHG emissions and obtained the variations between the emissions from aged and average populations. We employed a modified version of the regional integrated model of climate and the economy model (RICE) to forecast the emission trends in different countries based on FAO and GDD data. This integrated approach allowed us to evaluate the dynamic relationships among aging demographics, food consumption patterns, and economic developments within regions. Our results indicate that the annual aging-embodied global food GHG emissions will reach 288 million tonnes of CO2 equivalent (Mt CO2e) by 2100. This estimation is crucial for policymakers, entrepreneurs, and researchers as it provides insights into a potential future environmental challenge and emphasizes the importance of sustainable food production and consumption strategies to GHG emission mitigations associated with aging dietary patterns.

Categorization of leaching behaviors of elements from commercially treated incineration bottom ash in Singapore.

Leaching of potentially hazardous substances, especially the heavy metals from Incineration Bottom Ash (IBA) is a major problem in its recyclable usage. To address this concern, treatment of IBA is indispensable before it can be reused. IBA subjected to laboratory-scale treatment typically yields clearer conclusions in terms of leaching behaviors, benefiting from the controlled laboratory environment. However, the leaching behaviors of commercially treated IBA appear to be more ambiguous due to the complex and comprehensive nature of industrial-scale treatments, where multiple treatment techniques are involved concurrently. Furthermore, treatment efficiencies vary among different plants. In this study, three types of commercially treated IBA were sampled from leading waste treatment companies in Singapore. Characterization and leaching tests were performed on the treated IBAs in both standardized and modified manners to simulate various scenarios. Besides deionized water, artificial seawater was used as a leachant in leaching tests for simulating seawater intrusion. The results reveal the promoting effect of seawater on the leaching levels of several elements from three types of treated IBA, which may require special attention for IBA application and landfill near the coast. Furthermore, the elements examined in these three types of commercially treated IBA generally comply with the non-hazardous waste acceptance criteria outlined in Council Decision, 2003/33/EC (2003), except Sb. By combining two leaching tests, the elements were categorized into different types of leaching behavior, making it possible to prepare and respond to the concerning leaching scenarios in future engineering applications.

Target-regulated photoactivities of CdS/Ni-MOF heterojunction with [Ru(bpy)2dppz]2+ intercalator: a bisphenol A photoelectrochemical aptasensor.

Bisphenol A (BPA), an important endocrine disrupting compound, has infiltrated human daily lives through electronic devices, food containers, and children's toys. Developing of novel BPA assay methods with high sensitivity holds tremendous importance in valuing the pollution state. Here, we constructed an ultrasensitive photoelectrochemical (PEC) aptasensor for BPA determination by regulating photoactivities of CdS/Ni-based metal-organic framework (CdS/Ni-MOF) with [Ru(bpy)2dppz]2+ sensitizer. CdS/Ni-MOF spheres exhibited excellent photocatalytic performance, serving as a potential sensing platform for the construction of target recognition process. [Ru(bpy)2dppz]2+ were embedded into DNA double-stranded structure, functioning as sensitizer for modulating the signal response of the developed PEC aptasensor. The proposed PEC sensor exhibited outstanding analytical performances, including a wide linear range (0.1 to 1000.0 nM), low detection limit (0.026 nM, at 3σ/m), excellent selectivity, and high stability. This work provides a perspective for the design of ideal photosensitive materials and signal amplification strategies and extends their application in environment analysis.

A New Biocontrol Agent Bacillus velezensis SF334 against Rubber Tree Fungal Leaf Anthracnose and Its Genome Analysis of Versatile Plant Probiotic Traits.

Natural rubber is an important national strategic and industrial raw material. The leaf anthracnose of rubber trees caused by the Colletotrichum species is one of the important factors restricting the yields of natural rubber. In this study, we isolated and identified strain Bacillus velezensis SF334, which exhibited significant antagonistic activity against both C. australisinense and C. siamense, the dominant species of Colletotrichum causing rubber tree leaf anthracnose in the Hainan province of China, from a pool of 223 bacterial strains. The cell suspensions of SF334 had a significant prevention effect for the leaf anthracnose of rubber trees, with an efficacy of 79.67% against C. siamense and 71.8% against C. australisinense. We demonstrated that SF334 can lead to the lysis of C. australisinense and C. siamense mycelia by causing mycelial expansion, resulting in mycelial rupture and subsequent death. B. velezensis SF334 also harbors some plant probiotic traits, such as secreting siderophore, protease, cellulase, pectinase, and the auxin of indole-3-acetic acid (IAA), and it has broad-spectrum antifungal activity against some important plant pathogenic fungi. The genome combined with comparative genomic analyses indicated that SF334 possesses most genes of the central metabolic and gene clusters of secondary metabolites in B. velezensis strains. To our knowledge, this is the first time a Bacillus velezensis strain has been reported as a promising biocontrol agent against the leaf anthracnose of rubber trees caused by C. siamense and C. australisinense. The results suggest that B. velezensis could be a potential candidate agent for the leaf anthracnose of rubber trees.

Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients.

This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine ß2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood ß2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood ß2 microglobulin was statistically significant at month 6 and months 12-30 (P < .05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine ß2 microglobulin fluctuated from 0.5 (0.3-1.1) to 0.8 (0.5-1.35) mg/L at months 18-30, which was higher than 0.41 (0.18-1.1) mg/L at month 0 (P < .05). The abnormal concentration proportion of urine ß2 microglobulin fluctuated from 72.7% to 81.3% at months 18-30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood ß2 microglobulin, urine ß2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = -0.008, r3 = -0.165, P > .05). Long-term TDF antiviral regimen in low-risk of kidney injury HIV-infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine ß2 microglobulin levels may be helpful in screening for renal dysfunction.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Role of regulatory non-coding RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Tolerability and effectiveness of albuvirtide combined with dolutegravir for hospitalized people living with HIV/AIDS.

Treatment options for hospitalized people living with HIV/AIDS (PLWHA) with opportunistic infections and comorbidities are limited in China. Albuvirtide (ABT), a new peptide drug, is a long-acting HIV fusion inhibitor with limited drug-drug interactions and fast onset time. This single-center, retrospective cohort study investigated the effectiveness and safety of ABT plus dolutegravir (DTG) therapy in a real-world setting. We performed a chart review on the electronic patient records for hospitalized PLWHA using ABT plus DTG between April and December 2020. The clinical outcomes were retrospectively analyzed. Among 151 PLWHA (mean age 47.6 ± 15.9 years), 140 (93%) had at least 1 episode of bacterial and/or fungal infections and 64 (42%) had other comorbidities including syphilis, hepatitis B, and/or hypertension. ABT plus DTG was given to 87 treatment-naïve (TN) and 64 treatment-experienced (TE) PLWHA. Regardless of treatment history, mean HIV-1 RNA levels significantly decreased from 4.32 log10copies/mL to 2.24 log10copies/mL, 2.10 log10copies/mL and 1.89 log10copies/mL after 2, 4 and 8 weeks of treatment, respectively (P < .0001). Compared with baseline mean CD4 + T-cell counts of 122.72 cells/µL, it increased to 207.87 cells/µL (P = .0067) and 218.69 cells/µL (P = .0812) after 4 and 8 weeks of treatment. Except for limited laboratory abnormalities such as hyperuricemia, increased creatinine level, and hyperglycemia observed after treatment, no other clinical adverse events were considered related to ABT plus DTG. Data suggests that ABT plus DTG is safe and effective for critically-ill hospitalized PLWHA. In view of the rapid viral load suppression and restoration of CD4 + count within 8 weeks of treatment, its clinical application warrants further investigation.

Three new isoquinoline alkaloids from the fermentation of Aspergillus sp. 0338 and their anti-MRSA activities.

There is growing evidence that bioactive substances produced by microbial endophytes have applicability in medicine, agriculture and industry. To enrich the bioactive substances, in our search for new bioactive metabolites from fungi Aspergillus, the phytochemical reinvestigation on the Aspergillus sp. 0338 was carried out, and this led to the isolation of three new (1-3) and five known alkaloids (4-8). Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1-3 were evaluated for their anti-MRSA activities. The results revealed that compounds 1-3 exhibited good inhibitions with IZD of 15.2 ± 1.8, 14.6 ± 2.0, and 13.4 ± 2.2 mm, respectively.

Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma.

Background: Cuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients. Methods: RNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB). Results: We have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.

Antagonistic transcriptome profile reveals potential mechanisms of action on Xanthomonas oryzae pv. oryzicola by the cell-free supernatants of Bacillus velezensis 504, a versatile plant probiotic bacterium.

Bacterial leaf streak (BLS) of rice is a severe disease caused by the bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) that has gradually become the fourth major disease on rice in some rice-growing regions in southern China. Previously, we isolated a Bacillus velezensis strain 504 that exhibited apparent antagonistic activity against the Xoc wild-type strain RS105, and found that B. velezensis 504 was a potential biocontrol agent for BLS. However, the underlying mechanisms of antagonism and biocontrol are not completely understood. Here we mine the genomic data of B. velezensis 504, and the comparative transcriptomic data of Xoc RS105 treated by the cell-free supernatants (CFSs) of B. velezensis 504 to define differentially expressed genes (DEGs). We show that B. velezensis 504 shares over 89% conserved genes with FZB42 and SQR9, two representative model strains of B. velezensis, but 504 is more closely related to FZB42 than SQR9, as well as B. velezensis 504 possesses the secondary metabolite gene clusters encoding the essential anti-Xoc agents difficidin and bacilysin. We conclude that approximately 77% of Xoc RS105 coding sequences are differentially expressed by the CFSs of B. velezensis 504, which significantly downregulates genes involved in signal transduction, oxidative phosphorylation, transmembrane transport, cell motility, cell division, DNA translation, and five physiological metabolisms, as well as depresses an additional set of virulence-associated genes encoding the type III secretion, type II secretion system, type VI secretion system, type IV pilus, lipopolysaccharides and exopolysaccharides. We also show that B. velezensis 504 is a potential biocontrol agent for bacterial blight of rice exhibiting relative control efficiencies over 70% on two susceptible cultivars, and can efficiently antagonize against some important plant pathogenic fungi including Colletotrichum siamense and C. australisinense that are thought to be the two dominant pathogenic species causing leaf anthracnose of rubber tree in Hainan province of China. B. velezensis 504 also harbors some characteristics of plant growth-promoting rhizobacterium such as secreting protease and siderophore, and stimulating plant growth. This study reveals the potential biocontrol mechanisms of B. velezensis against BLS, and also suggests that B. velezensis 504 is a versatile plant probiotic bacterium.