Transcriptome profiling reveals the impact of various levels of biochar application on the growth of flue-cured tobacco plants.

BACKGROUND: Biochar, a carbon-rich source and natural growth stimulant, is usually produced by the pyrolysis of agricultural biomass. It is widely used to enhance plant growth, enzyme activity, and crop productivity. However, there are no conclusive studies on how different levels of biochar application influence these systems. METHODS AND RESULTS: The present study elucidated the dose-dependent effects of biochar application on the physiological performance, enzyme activity, and dry matter accumulation of tobacco plants via field experiments. In addition, transcriptome analysis was performed on 60-day-old (early growth stage) and 100-day-old (late growth stage) tobacco leaves to determine the changes in transcript levels at the molecular level under various biochar application levels (0, 600, and 1800 kg/ha). The results demonstrated that optimum biochar application enhances plant growth, regulates enzymatic activity, and promotes biomass accumulation in tobacco plants, while higher biochar doses had adverse effects. Furthermore, transcriptome analysis revealed a total of 6561 differentially expressed genes (DEGs) that were up- or down-regulated in the groupwise comparison under different treatments. KEGG pathways analysis demonstrated that carbon fixation in photosynthetic organisms (ko00710), photosynthesis (ko00195), and starch and sucrose metabolism (ko00500) pathways were significantly up-regulated under the optimal biochar dosage (600 kg/ha) and down-regulated under the higher biochar dosage (1800 kg/ha). CONCLUSION: Collectively, these results indicate that biochar application at an optimal rate (600 kg/ha) could positively affect photosynthesis and carbon fixation, which in turn increased the synthesis and accumulation of sucrose and starch, thus promoting the growth and dry matter accumulation of tobacco plants. However, a higher biochar dosage (1800 kg/ha) disturbs the crucial source-sink balance of organic compounds and inhibits the growth of tobacco plants.

Self-Assembly Method for Synthesizing High-Dimensional EMOFs with High Stability and Laser Response.

Dimension and solvent molecules affect the performance of energetic metal-organic frameworks (EMOFs). High-dimensional EMOFs are usually characterized by high stability and low sensitivity due to their complex network structure. However, solvent molecules affect the detonation performance of EMOFs, and these molecules may be removed at low temperatures, resulting in structural collapse and affecting the stability of EMOFs. In this work, zero-dimensional (0D) Co(AFTO)2·(H2O)2 (EMOF 1) and Ni(AFTO)2·(H2O)2 (EMOF 2) with coordinated water molecules and [Co(AFTO)2]n·EtOH (EMOF 3) and [Ni(AFTO)2]n (EMOF 4) (AFTO = 5-(4-amino-furazan-3-yl)-1-hydroxytetrazole) with high-dimensional structure were synthesized using hydrothermal and self-assembly methods in ethanol, respectively. Structural and performance tests show that EMOF 3 and 4 exhibit remarkable thermal stability and low mechanical sensitivity. This method is a simple, effective, and green technique for synthesizing high-dimensional EMOFs with high stability through self-assembly in ethanol solution. In addition, EMOF 3 and 4 can be used as primary green laser explosives.

Impact of summer hypoxia on macrobenthic communities in a semi-enclosed bay: A long-term observation in the North Yellow sea of China.

The O2 content of the global ocean has been declining progressively over the past decades, mainly because of human activities and global warming. Despite this situation, the responses of macrobenthos under hypoxic conditions remain poorly understood. In this study, we conducted a long-term observation (2015-2022) to investigate the intricate impact of summer hypoxia on macrobenthic communities in a semi-enclosed bay of the North Yellow Sea. Comparative analyses revealed higher macrobenthos abundance (1956.8 ± 1507.5 ind./m2 vs. 871.8 ± 636.9 ind./m2) and biomass (8.2 ± 4.1 g/m2 vs. 5.6 ± 3.2 g/m2) at hypoxic sites compared to normoxic sites during hypoxic years. Notably, polychaete species demonstrated remarkable adaptability, dominating hypoxic sites, and shaping community structure. The decline in biodiversity underscored the vulnerability and diminished resilience of macrobenthic communities to hypoxic stressors. Stable isotope analysis provided valuable insights into food web structures. The average trophic level of macrobenthos measured 2.84 ± 0.70 at hypoxic sites, contrasting with the higher value of 3.14 ± 0.74 observed at normoxic sites, indicating the absence of predators at high trophic levels under hypoxic conditions. Moreover, trophic interactions were significantly altered, resulting in a simplified and more vulnerable macrobenthic trophic structure. The findings underscored the importance of comprehensive research to understand the complex responses of macrobenthic communities to hypoxia, thereby informing future conservation efforts in impacted ecosystems.

Characterization of wheat dough and Chinese steamed bread using mealworm powder formulated with medium-gluten and whole wheat flour.

BACKGROUND: Mealworm (Tenebrio molitor) larvae are nutritious edible insects and exhibit the potential to act as protein substitutes in food products. In this study, we added mealworm powder as a substitute to medium-gluten wheat and whole wheat flours to enhance the quality of baked products. We compared the pasting, farinograph and extensograph properties of medium-gluten wheat and whole wheat flours replaced with different concentrations of mealworm powder to explore the interactions between flour and mealworm powder. RESULTS: Mealworm powder changed the pasting characteristics of medium-gluten wheat and whole wheat flours. After adding 20% mealworm powder, the pasting temperature of the medium-gluten wheat flour remained unchanged (approximately 89.9 °C), while the pasting temperature of whole wheat flour increased from 88.83 to 90.27 °C. Water absorption of medium-gluten and whole wheat flours exhibited a decreasing trend with increasing mealworm powder concentrations. Mealworm powder substitution resulted in stronger medium-gluten dough but exerted an opposite effect on the farinograph properties of whole wheat dough. Mealworm powder substitution decreased the stretching resistance of medium-gluten dough but increased that of whole wheat dough. With an increase in the concentration of mealworm powder, the specific volume of medium-gluten wheat steamed bread significantly increased from 1.69 mL g-1 (M0) to 3.31 mL g-1 (M10) whereas that of whole wheat steamed bread increased from 1.64 mL g-1 (M0) to 2.34 mL g-1 (M15). The addition of mealworm powder increased the protein, dietary fiber, lipid and sodium contents of steamed bread samples. CONCLUSIONS: This study provides a reference for the rheological properties of medium-gluten wheat and whole wheat flours substituted with mealworm powder and supports the addition of insects as a protein source in food products. © 2023 Society of Chemical Industry.

CD8 + T-cell marker genes reveal different immune subtypes of oral lichen planus by integrating single-cell RNA-seq and bulk RNA-sequencing.

BACKGROUND: Oral lichen planus (OLP) is a local autoimmune disease induced by T-cell dysfunction that frequently affects middle-aged or elderly people, with a higher prevalence in women. CD8 + T cells, also known as killer T cells, play an important role in the progression and persistence of OLP. In order to identify different OLP subtypes associated with CD8 + T cell pathogenesis, consensus clustering was used. METHODS: In this study, we preprocessed and downscaled the OLP single-cell dataset GSE211630 cohort downloaded from Gene Expression Omnibus (GEO) to finally obtain the marker genes of CD8 + T cells. Based on the expression of marker genes, we classified OLP patients into CMGs subtypes using unsupervised clustering analysis. The gene expression profiles were analyzed by WGCNA using the "WGCNA" R package based on the clinical disease traits and typing results, and 108 CD8 + T-cell related OLP pathogenicity-related genes were obtained from the intersection. Patients were once again classified into gene subtypes based on intersection gene expression using unsupervised clustering analysis. RESULTS: After obtaining the intersecting genes of CD8 + T cells related to pathogenesis, OLP patients can be precisely classified into two different subtypes based on unsupervised clustering analysis, and subtype B has better immune infiltration results, providing clinicians with a reference for personalized treatment. CONCLUSIONS: Classification of OLP into different subtypes improve our current understanding of the underlying pathogenesis of OLP and provides new insights for future studies.

Preparation, characterization and biocompatibility of calcium peroxide-loaded polycaprolactone microparticles. / èšå·±å† é ¯åŒ è½½è¿‡æ°§åŒ–é’™å¾®ç²’çš„åˆ¶å¤‡ã€è¡¨å¾åŠå ¶ç”Ÿç‰©ç›¸å®¹æ€§ç ”ç©¶.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O2 and H2O2 after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O2 and H2O2 released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS: CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.

Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

OBJECTIVE: Over-proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of RA disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. METHODS: Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a CIA mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. RESULTS: Compared with healthy controls, ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1 (FTH1), GPX4 and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in healthy controls, the increase in antioxidation was slightly higher than oxidation. RNA-seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. CONCLUSIONS: In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease.

Preparation of a Chitosan-Lead Composite Carbon Aerogel and Its Catalytic Thermal Decomposition Performance on Ammonium Perchlorate.

Chitosan-lead (CS-Pb) carbon aerogels were prepared by ionic cross-linking and high-temperature carbonization using chitosan (CS) as the carbon precursor. The obtained carbon aerogels were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and X-ray photoelectron spectroscopy (XPS). The obtained aerogels have a 3D structure and a large surface area, which can effectively prevent the agglomeration phenomenon of metals. Differential thermal analysis (DTA) was used to analyze the catalytic performance of a carbon aerogel for ammonium perchlorate (AP). The results showed that the CS-Pb carbon aerogel reduced the peak temperature of AP pyrolysis from 703.9 to 627.7 K. According to the Kissinger method calculations, the Ea of AP decomposition decreased about 27.2 kJ/mol. The TG data at different warming rates were analyzed by the Flynne-Walle-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods, which are two of the isoconversion methods, and the activation energies of AP and AP+CS-Pb-3.5 were calculated. Between the conversion degrees (α) of 0.1 and 0.9, the Ea values obtained by the two isoconversion methods are similar and have a certain match. Also, the two isoconversion methods confirm Kissinger's calculation. Finally, thermogravimetry-mass spectrometry (TG-MS) was used to monitor the gases generated during the thermal decomposition of the AP+CS-Pb-3.5 system in real time.

Diversity of transcription activator-like effectors and pathogenicity in strains of Xanthomonas oryzae pv. oryzicola from Yunnan.

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice.

TSP1 is the essential domain of SEMA5A involved in pannus formation in rheumatoid arthritis.

OBJECTIVE: In this study, we explored the effect of semaphorin5A (SEMA5A) on RA pathogenesis and its specific TSP1 domain on pannus formation. METHODS: The expression of SEMA5A was detected in the synovium, the fibroblast-like synoviocytes (FLSs) and the SF of RA patients and healthy controls (HCs) by real-time quantitative PCR (q-PCR), immunohistochemistry staining, western blot and ELISA. SEMA5A-mAb intervention was performed to appraise the severity of joints in the CIA model. Transcriptome sequencing and bioinformatics analysis in SEMA5A-transfected FLSs from HCs were performed to screen differentially expressed genes after SEMA5A overexpression. An MTT assay in RA-FLSs, a chicken embryo allantoic membrane experiment and a tube formation experiment were used to clarify the influence of SEMA5A on cell proliferation and angiogenesis. Furthermore, a rescue experiment verified the function of the TSP1 domain of SEMA5A in the progress of RA with Sema5a-/- CIA mice. RESULTS: The expression of SEMA5A increased in RA compared with that in HCs. Simultaneously, SEMA5A-mAbs significantly attenuated joint injury and the inflammatory response in CIA models. In addition, transcriptome sequencing and angiogenesis-related experiments verified the ability of SEMA5A to promote FLS proliferation and angiogenesis. Moreover, TSP1 was proved to be an essential domain in SEMA5A-induced angiogenesis in vitro. Additionally, rescue of TSP1-deleted SEMA5A failed to reduce the severity of arthritis in a CIA model constructed with Sema5a -/- mice. CONCLUSION: In summary, upregulation of SEMA5A was first confirmed in pathological lesions of RA patients. Furthermore, treatment with SEMA5A-mAbs attenuated the progress of RA in the CIA model. Moreover, TSP1 was indicated as the key domain of SEMA5A in the promotion of pannus formation in RA.

Series of AzTO-Based Energetic Materials: Effect of Different π-π Stacking Modes on Their Thermal Stability and Sensitivity.

π-Stacking is common in materials, but different π-π stacking modes remarkably affect the properties and performances of materials. In particular, weak interactions, π-stacking and hydrogen bonding, often have a great impact on the stability and sensitivity of high-energetic compounds. Therefore, several of energetic materials based on 1,1'-dihydroxyazotetrazole (1) with a nearly flat structure, such as the salts of aminoguanidine (2), 1,3-diaminoguanidine (3), imidazole (4), pyrazole (5) and triaminoguanidine (6), and a cocrystal of 2-methylimidazole (7), were designed and synthesized. Based on single-crystal diffraction data, thermal decomposition behaviors, and the mechanical sensitivity test, the compounds of 4, 5, and 7 with face-to-face π-π stacking display outstanding thermal stability and insensitivity.

Photoregulation of Gene Expression with Amantadine-Modified Caged siRNAs through Host-Guest Interactions.

RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expression and functions. In this study, a series of photolabile siRNAs with amantadine modification have been rationally designed and developed through host-guest interactions between amantadine and ß-cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or RNA-induced silencing complex processing. These caged siRNAs with amantadine modification at the 5' end of antisense-strand RNA were efficiently inactivated through the host-guest interactions between amantadine and ß-cyclodextrin. Photomodulation of the gene silencing activity of these amantadine-modified caged siRNAs targeting both exogenous and endogenous genes was successfully achieved, which indicates that host-guest interactions could be a new strategy for developing new caged siRNAs for gene photoregulation with low leaking activity.

Dextran-Conjugated Caged siRNA Nanoparticles for Photochemical Regulation of RNAi-Induced Gene Silencing in Cells and Mice.

RNA interference (RNAi)-based gene therapy is a precision therapeutic approach for highly efficient sequence-specific gene silencing in vivo or in vitro. Caged RNAs featuring dextran conjugation of antisense and sense RNA strands using photolabile linker were rationally designed and self-assembled to form caged siRNA nanoparticles (Dex- p-siRNA) for photoregulation of target gene expression. The dextran-conjugated caged siRNA nanoparticles showed significant serum nuclease-resistance due to the formation of dextran-siRNA nanoparticles. Photomodulation of exogenous GFP and endogenous mitotic kinesin-5 ( Eg5) gene expression in cells was achieved using the prepared caged Dex- p-siRNA nanoparticles. The caged Dex- p-siRNA nanoparticles targeting GFP successfully photoregulated GFP expression in tumor-bearing mice via intratumoral injection. Caged siRNA nanoparticles with high serum stability not only show great promise for photoregulation of exogenous and endogenous gene expression for both in vitro and in vivo applications, but also provide a novel and convenient way to spatiotemporally control RNAi-induced gene silencing.

Synthesis of site-specifically phosphate-caged siRNAs and evaluation of their RNAi activity and stability.

A complete set of new photolabile nucleoside phosphoramidites were synthesized, then site-specifically incorporated into sense or antisense strands of siRNA for phosphate caging. Single caging modification was made along siRNA strands and their photomodulation of gene silencing were examined by using the firefly luciferase reporter gene. Several key phosphate positions were then identified. Furthermore, multiple caging modifications at these key positions led to significantly enhanced photomodulation of gene silencing activity, suggesting a synergistic effect. The caging group on both the terminally phosphate-caged siRNA and the single-stranded caged RNA has comparatively high stability, whereas hydrolysis of the caged group from the internally caged siRNA was observed, irrespective of the presence of Mg(2+). Molecular dynamic simulations demonstrated that enhanced hydrolysis of the caging group on internally phosphate-caged siRNAs was due to easy fragmentation of the caging group upon formation of the pentavalent intermediate of the phosphotriester with attack by water. The caging group in the terminally phosphate-caged siRNA or single-stranded caged RNA prefers to form π-π stacks with nearby nucleobases. In addition to providing explanations for previous observations, this study sheds further light on the design of caged oligonucleotides and indicates the direction of future development of nucleic acid drugs with phosphate modifications.

Rock fragments significantly affect the carbon and nitrogen distribution in the surface soil - Evidences from large number samples of soil rock fragment interfaces in a boreal forest watershed.

Rock fragments are widely distributed in soils. The material cycling and the physico-chemical processes of soil ecosystems are both inevitably spatially affected by rock fragments. However, the effect of rock fragments on the spatial distribution characteristics of soil carbon and nitrogen is still not well studied and understood. We carried out a study on the effect of rock fragments on the spatial distribution of soil carbon and nitrogen by mass sampling at the interfaces of rock fragments in a boreal forest watershed ecosystem of northest China. We found that the carbon and nitrogen content of rock fragments interface soil (SRIS) was significantly lower than that of general soil (GS). The content of total soil carbon (TC) and total soil nitrogen (TN) in 0-20 cm SRIS accounted for 73 % and 43 % of those in the GS, respectively. The content of TN in 20-40 cm SRIS was about 43 % of that in the GS. The results of Random Forest Model and Pearson correlation analysis (P < 0.01) indicated that the soil water content (SWC) and soil machinery composition (SMC) contributed most to the variabilities of soil carbon and nitrogen. We also found significant differences in SMC between GS and SRIS. Such evidences suggested that the presence of rock fragments was expected to promote the loss of soil carbon and nitrogen，and consequently influence soil carbon and nitrogen distribution nearby them. Our findings help improve the understanding of the impact of rock fragments on soil carbon and nitrogen distribution and provide new insights into the participation of rock fragments in the material-energy cycle of ecosystems.

Subject-Independent Emotion Recognition Based on EEG Frequency Band Features and Self-Adaptive Graph Construction.

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high correlation with emotion production. However, traditional emotion recognition methods cannot satisfactorily solve the problem of individual differences in subjects and data heterogeneity in EEG, and subject-independent emotion recognition based on EEG signals has attracted extensive attention from researchers. In this paper, we propose a subject-independent emotion recognition model based on adaptive extraction of layer structure based on frequency bands (BFE-Net), which is adaptive in extracting EEG map features through the multi-graphic layer construction module to obtain a frequency band-based multi-graphic layer emotion representation. To evaluate the performance of the model in subject-independent emotion recognition studies, extensive experiments are conducted on two public datasets including SEED and SEED-IV. The experimental results show that in most experimental settings, our model has a more advanced performance than the existing studies of the same type. In addition, the visualization of brain connectivity patterns reveals that some of the findings are consistent with previous neuroscientific validations, further validating the model in subject-independent emotion recognition studies.

Deubiquitylase OTUD3 regulates integrated stress response to suppress progression and sorafenib resistance of liver cancer.

The integrated stress response (ISR) is activated in response to intrinsic and extrinsic stimuli, playing a role in tumor progression and drug resistance. The regulatory role and mechanism of ISR in liver cancer, however, remain largely unexplored. Here, we demonstrate that OTU domain-containing protein 3 (OTUD3) is a deubiquitylase of eukaryotic initiation factor 2α (eIF2α), antagonizing ISR and suppressing liver cancer. OTUD3 decreases interactions between eIF2α and the kinase EIF2ΑK3 by removing K27-linked polyubiquitylation on eIF2α. OTUD3 deficiency in mice leads to enhanced ISR and accelerated progression of N-nitrosodiethylamine-induced hepatocellular carcinoma. Additionally, decreased OTUD3 expression associated with elevated eIF2α phosphorylation correlates with the progression of human liver cancer. Moreover, ISR activation due to decreased OTUD3 expression renders liver cancer cells resistant to sorafenib, while the combined use of the ISR inhibitor ISRIB significantly improves their sensitivity to sorafenib. Collectively, these findings illuminate the regulatory mechanism of ISR in liver cancer and provide a potential strategy to counteract sorafenib resistance.

Deciphering a Prognostic Signature Based on Soluble Mediators Defines the Immune Landscape and Predicts Prognosis in HNSCC.

BACKGROUND: The study on Head and Neck Squamous Cell Carcinoma (HNSCC), a prevalent and aggressive form of head and neck cancer, focuses on the often-overlooked role of soluble mediators. The objective is to leverage a transcriptome-based risk analysis utilizing soluble mediator-related genes (SMRGs) to provide novel insights into prognosis and immunotherapy efficacy in HNSCC patients. METHODS: We analyzed the expression and prognostic significance of 10,859 SMRGs using 502 HNSCC and 44 normal samples from the TCGA-HNSC cohort in The Cancer Genome Atlas (TCGA). The samples were divided into training and test sets in a 7:3 ratio, with an additional external validation using 40 tumor samples from the International Cancer Genome Consortium (ICGC). Key differentially expressed genes (DEGs) with prognostic significance were identified through univariate and Lasso-Cox regression analyses. A prognostic model based on 20 SMRGs was developed using Lasso and multivariate Cox regression. We assessed the clinical outcomes and immune status in high-risk (HR) and low-risk (LR) HNSCC patients utilizing the BEST databases and single-sample Gene Set Enrichment Analysis (ssGSEA). RESULTS: The 20 SMRGs were crucial in predicting the prognosis of HNSCC, with the SMRG signature emerging as an independent prognostic indicator. Patients classified in the HR group exhibited poorer outcomes compared to those in the LR group. A nomogram, integrating clinical characteristics and risk scores, demonstrated substantial prognostic value. Immunotherapy appeared to be more effective in the LR group, possibly attributed to enhanced immune infiltration and expression of immune checkpoints. CONCLUSIONS: The model based on soluble mediator-associated genes offers a fresh perspective for assessing the pre-immune efficacy and showcases robust predictive capabilities. This innovative approach holds significant promise in advancing the field of precision immuno-oncology research, providing valuable insights for personalized treatment strategies in HNSCC.

Identification of Fusarium oxysporum Causing Leaf Blight on Dendrobium chrysotoxum in Yunnan Province, China.

Leaf-blight disease caused by the Fusarium oxysporum is an emerging problem in Dendrobium chrysotoxum production in China. Symptoms of leaf blight were observed on seedlings of D. chrysotoxum cultivated in a nursery in Ruili City, Yunnan Province, China. In this study, we isolated the Fusarium sp. associated with leaf-blight disease of D. chrysotoxum from the diseased seedlings. A pathogenicity test was performed to fulfill Koch's postulates to confirm the pathogenicity of isolated strains and identified using morphological and molecular techniques. The results revealed that all four isolated Fusarium sp. isolates (DHRL-01~04) produced typical blight symptoms followed by marginal necrosis of leaves on the D. chrysotoxum plants. On the PDA medium, the fungal colony appeared as a white to purplish color with cottony mycelium growth. Microconidia are oval-shaped, whereas macroconidia are sickle-shaped, tapering at both ends with 2-4 septations. The phylogenetic trees were construed based on internal transcribed spacer (ITS), translation elongation factor (EF-1α), and RNA polymerase subunit genes RPB1 and RPB2 genes, respectively, and blasted against the NCBI database for species confirmation. Based on the NCBI database's blast results, the isolates showed that more than 99% identify with Fusarium oxysporum. To our knowledge, this is the first comprehensive report on the identification of Fusarium oxysporum as the causal agent of Dendrobium chrysotoxum leaf blight in Yunnan Province, China, based on morphological and molecular characteristics.