ABSTRACT
Background: Cancers arise from genetic and epigenetic abnormalities that affect oncogenes and tumor suppressor genes, compounded by gene mutations. The N6-methyladenosine (m6A) RNA modification, regulated by methylation regulators, has been implicated in tumor proliferation, differentiation, tumorigenesis, invasion, and metastasis. However, the role of m6A modification patterns in the tumor microenvironment of gastric cancer (GC) remains poorly understood. Materials and methods: In this study, we analyzed m6A modification patterns in 267 GC samples utilizing 31 m6A regulators. Using consensus clustering, we identified two unique subgroups of GC. Patients with GC were segregated into high- and low-infiltration cohorts to evaluate the infiltration proportions of the five prognostically significant immune cell types. Leveraging the differential genes in GC, we identified a "green" module via Weighted Gene Co-expression Network Analysis. A risk prediction model was established using the LASSO regression method. Results: The "green" module was connected to both the m6A RNA methylation cluster and immune infiltration patterns. Based on "Module Membership" and "Gene Significance", 37 hub genes were identified, and a risk prediction model incorporating nine hub genes was established. Furthermore, methylated RNA immunoprecipitation and RNA Immunoprecipitation assays revealed that YTHDF1 elevated the expression of DNMT3B, which synergistically promoted the initiation and development of GC. We elucidated the molecular mechanism underlying the regulation of DNMT3B by YTHDF1 and explored the crosstalk between m6A and 5mC modification. Conclusion: m6A RNA methylation regulators are instrumental in malignant progression and the dynamics of tumor microenvironment infiltration of GC. Assessing m6A modification patterns and tumor microenvironment infiltration characteristics in patients with GC holds promise as a valuable prognostic biomarker.
ABSTRACT
Deregulation of E3 ubiquitin ligases drives the proliferation and metastasis of various cancers; however, the underlying mechanisms remain unknown. This study aimed to investigate the role of tripartite motif-containing 22 (TRIM22), a poorly investigated E3 ubiquitin ligase in the TRIM family, as a tumor suppressor in breast cancer. High expression of TRIM22 in breast cancer correlated with better prognosis. Functional experiments demonstrated that TRIM22 significantly inhibited the proliferation and invasion of breast cancer cells. Label-free proteomics and biochemical analyses revealed that the copper chaperone for superoxide dismutase (CCS), an oncoprotein that is upregulated in breast cancer and promotes the growth and invasion of breast cancer cells, was a target of TRIM22 for degradation via K27-linked ubiquitination. Notably, the ability of the coiled-coil domain-defective mutants of TRIM22 to induce CCS ubiquitination and degradation diminished, with lysine 76 of the CCS serving as the ubiquitination site. Moreover, the TRIM22-mediated inhibition of the proliferation and invasion of breast cancer cells was restored by ectopic CCS expression. RNA-sequencing experiments using Gene Set Enrichment Analysis demonstrated that TRIM22 is involved in the JAK-STAT signaling pathway. TRIM22 overexpression also improved reactive oxygen species levels in breast cancer cells and inhibited STAT3 phosphorylation, which was restored via CCS overexpression or N-acetyl-l-cysteine treatment. Chromatin immunoprecipitation-quantitative polymerase chain reaction results showed that TRIM22 overexpression decreased the enrichment of phosphorylated STAT3 in FN1, VIM and JARID2 promoters. Clinically, low TRIM22 expression correlated with high CCS expression and decreased survival rates in patients with breast cancer. Moreover, TRIM22 upregulation was associated with a better prognosis in patients with breast cancer who received classical therapy. TRIM22 expression was downregulated in many cancer types, including colon, kidney, lung, and prostate cancers. To the best of our knowledge, the E3 ubiquitin ligase TRIM22 was first reported as a tumor suppressor that inhibits the proliferation and invasion of breast cancer cells through CCS ubiquitination and degradation. TRIM22 is a potential prognostic biomarker in patients with breast cancer.
ABSTRACT
The metastasis-associated protein (MTA) family plays a crucial role in the development of breast cancer, a common malignancy with a high incidence rate among women. However, the mechanism by which each member of the MTA family contributes to breast cancer progression is poorly understood. In this study, we aimed to investigate the roles of MTA1, MTA3, and tripartite motif-containing 21 (TRIM21) in the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stem cell-like properties of breast cancer cells in vivo and in vitro. The molecular mechanisms of the feedback loop between MTA1 and MTA3/TRIM21 regulated by estrogen were explored using Chromatin immunoprecipitation (ChIP), luciferase reporter, immunoprecipitation (IP), and ubiquitination assays. These findings demonstrated that MTA1 acts as a driver to promote the progression of breast cancer by repressing the transcription of tumor suppressor genes, including TRIM21 and MTA3. Conversely, MTA3 inhibited MTA1 transcription and TRIM21 regulated MTA1 protein stability in breast cancer. Estrogen disrupted the balance between MTA1 and MTA3, as well as between MTA1 and TRIM21, thereby affecting stemness and the EMT processes in breast cancer. These findings suggest that MTA1 plays a vital role in stem cell fate and the hierarchical regulatory network of EMT through negative feedback loops with MTA3 or TRIM21 in response to estrogen, supporting MTA1, MTA3, and TRIM21 as potential prognostic biomarkers and MTA1 as a treatment target for future breast cancer therapies.
Subject(s)
Breast Neoplasms , Epithelial-Mesenchymal Transition , Estrogens , Histone Deacetylases , Neoplastic Stem Cells , Repressor Proteins , Trans-Activators , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Female , Repressor Proteins/metabolism , Repressor Proteins/genetics , Trans-Activators/metabolism , Trans-Activators/genetics , Estrogens/pharmacology , Estrogens/metabolism , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Animals , Gene Expression Regulation, Neoplastic/drug effects , Mice , Cell Proliferation/drug effects , Cell Line, Tumor , Feedback, Physiological/drug effects , Ribonucleoproteins/metabolism , Ribonucleoproteins/genetics , Mice, Nude , MCF-7 Cells , Mice, Inbred BALB C , Neoplasm ProteinsABSTRACT
Surface Plasmon Resonance (SPR) technology, as a powerful analytical tool, plays a crucial role in the preparation, performance evaluation, and biomedical applications of nanoparticles due to its real-time, label-free, and highly sensitive detection capabilities. In the nanoparticle preparation process, SPR technology can monitor synthesis reactions and surface modifications in real-time, optimizing preparation techniques and conditions. SPR enables precise measurement of interactions between nanoparticles and biomolecules, including binding affinities and kinetic parameters, thereby assessing nanoparticle performance. In biomedical applications, SPR technology is extensively used in the study of drug delivery systems, biomarker detection for disease diagnosis, and nanoparticle-biomolecule interactions. This paper reviews the latest advancements in SPR technology for nanoparticle preparation, performance evaluation, and biomedical applications, discussing its advantages and challenges in biomedical applications, and forecasting future development directions.
Subject(s)
Nanoparticles , Surface Plasmon Resonance , Surface Plasmon Resonance/methods , Nanoparticles/chemistry , Humans , Drug Delivery Systems/methodsABSTRACT
Antral follicle size is a useful predictive marker of the competency of enclosed oocytes for yielding an embryo following in vitro maturation and fertilization. However, the molecular mechanisms underpinning oocyte developmental potential during bovine antral follicle growth are still unclear. Here, we used a modified single-cell multi-omics approach to analyze the transcriptome, DNA methylome and chromatin accessibility in parallel for oocytes and cumulus cells collected from bovine antral follicles of different sizes. Transcriptome profiling identified three types of oocytes (Small, Medium and Large) that underwent different developmental trajectories, with Large oocytes exhibiting the largest average follicle size and characteristics resembling metaphase-II oocytes. Differential expression analysis and real-time PCR assay showed that most replication-dependent histone genes were highly expressed in Large oocytes. The joint analysis of multi-omics data revealed that the transcription of 20 differentially expressed genes in Large oocytes was associated with both DNA methylation and chromatin accessibility. In addition, oocyte-cumulus interaction analysis showed that inflammation, DNA damage, and p53 signaling pathways were active in Small oocytes, which had the smallest average follicle sizes. We further confirmed that p53 pathway inhibition in in vitro maturation experiments using oocytes obtained from small antral follicles could improve the quality of oocytes and increased the blastocyte rate after in vitro fertilization and culture. Our work provides new insights into the intricate orchestration of bovine oocyte fate determination during antral folliculogenesis, which is instrumental for optimizing in vitro maturation techniques to optimize oocyte quality.
ABSTRACT
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
Subject(s)
Adjuvants, Immunologic , Disease Models, Animal , Mycobacterium tuberculosis , Tuberculosis Vaccines , Animals , Adjuvants, Immunologic/administration & dosage , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/administration & dosage , Mycobacterium tuberculosis/immunology , Mice , Female , Antigens, Bacterial/immunology , Acyltransferases/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/administration & dosage , Bacterial Proteins/immunology , Tuberculosis/immunology , Tuberculosis/prevention & control , Latent Tuberculosis/immunology , Mice, Inbred BALB C , Administration, IntranasalABSTRACT
Flexible composite film has gained increasing attention in the fields of wearable devices and portable electronic products. In this work, a novel core-shell structure of cellulose nanofibers/BaTiO3@TiO2 (CNF/BTO@TiO2) was synthesized with the assistant of the biological macromolecule material of cellulose nanofiber (CNF), in which the CNF can improve the stability and dispersibility of BaTiO3 (BTO) in the aqueous phase and elevate the integrity of the core-shell structure. The core-shell structure can reduce the agglomeration of fillers in polyvinylidene fluoride (PVDF) and improve the structural defects of the composite film. Meanwhile, the core-shell structure can promote the polarization of the electric dipole and the formation of ß phase in PVDF due to the generated interface spatial polarization between the shell of TiO2 and the core of BTO. When the content of the core-shell structure was 5 wt%, the ß phase content reaches 61.89 %, and the piezoelectric coefficient of composite film reaches 84.29 pm/V. Thus the maximum output open-circuit voltage (VOC) and short-circuit current (ISC) of the piezoelectric composite film is as high as 13.10 V and 464.3 nA. In addition, its excellent pressure sensing capability allows for its application in various flexible electronic devices.
Subject(s)
Barium Compounds , Cellulose , Nanofibers , Polyvinyls , Titanium , Titanium/chemistry , Nanofibers/chemistry , Polyvinyls/chemistry , Barium Compounds/chemistry , Cellulose/chemistry , Electricity , Fluorocarbon PolymersABSTRACT
Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.
Subject(s)
Diet, High-Fat , Disease Models, Animal , Gastrointestinal Microbiome , Honey , Mice, Inbred C57BL , Polyphenols , Renal Insufficiency, Chronic , Animals , Gastrointestinal Microbiome/drug effects , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/microbiology , Mice , Diet, High-Fat/adverse effects , Male , Polyphenols/pharmacology , Kidney/drug effects , Fatty Acids, Volatile/metabolismABSTRACT
Spherical movable tensegrity robots, resorting to the intrinsic hallmark of being lightweight and resilient, have exhibited tremendous potential in exploring unpredictable terrains and extreme environments where traditional robots often struggle. The geometry of spherical tensegrities is suitable for rolling locomotion, which guarantees the system to react to changing demands, navigate unexplored terrain, and perform missions even after suffering massive damage. The objective of this article is to enrich the type of spherical movable tensegrity robots with multiple kinematic gait patterns and to gain superior motion paths that are in conformity with the intrinsic features of structural rolling locomotion. Aiming at this purpose, three 12-rod spherical tensegrities with multi-gait patterns are investigated, and the dynamic simulation on independent (or evolutionary) gait patterns is conducted and testified on ADAMS. The routing spaces and the blind zones formed by single kinematic gait are compared to assess the suitability of the assigned kinematic gait pattern. Accordingly, we develop a trajectory planning method with the embedding of the steering control strategy into a modified rapidly exploring random tree (MRRT) algorithm to produce qualified marching routes. In the meantime, two momentous evaluation indictors, applicable to multi-gaits tensegrities, are introduced in searching the corresponding optimal gait patterns that conform to specified needs. The techniques are illustrated and validated in simulation with comparisons on several prototypes of tensegrity robots, indicating that the proposed method is a viable means of attaining marching routes on rolling locomotion of spherical movable tensegrity robots.
ABSTRACT
The aim of the present study was to explore the association between N6methyladenosine (m6A) modification regulatory generelated long noncoding (lnc)RNA RP1228H13.5 and cancer prognosis through bioinformatics analysis, as well as the impact of RP1228H13.5 on cell biologyrelated behaviors and specific molecular mechanisms. Bioinformatics analysis was used to construct a risk model consisting of nine genes. This model can reflect the survival time and differentiation degree of cancer. Subsequently, a competing endogenous RNA network consisting of 3 m6Arelated lncRNAs, six microRNAs (miRs) and 201 mRNAs was constructed. A cell assay confirmed that RP1228H13.5 is significantly upregulated in liver cancer cells, which can promote liver cancer cell proliferation, migration and invasion, and inhibit liver cancer cell apoptosis. The specific molecular mechanism may be the regulation of the expression of zinc finger protein interacting with K protein 1 (ZIK1) by targeting the downstream hsamiR205. Further experiments found that the m6A methyltransferase 14, N6adenosinemethyltransferase subunit mediates the regulation of miR2055p expression by RP1228H13.5. m6A methylation regulatory factorrelated lncRNA has an important role in cancer. The targeting of hsamiR205 by RP1228H13.5 to regulate ZIK1 may serve as a potential mechanism in the occurrence and development of liver cancer.
Subject(s)
Adenine/analogs & derivatives , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , MicroRNAs/genetics , Liver Neoplasms/genetics , Methyltransferases/genetics , RNA, Long Noncoding/genetics , Microtubule-Associated ProteinsABSTRACT
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
ABSTRACT
BACKGROUND: Sarcopenia is a senile syndrome of age-related muscle loss. It is thought to affect the development of chronic kidney disease and has a serious impact on the quality of life of the elder adults. Little is known about the association between sarcopenia and new-onset chronic kidney disease in middle-aged and elder adults. Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a longitudinal analysis to investigate the association between sarcopenia status and new-onset chronic kidney disease in middle-aged and elder adults in China. METHODS: The study population consisted of 3676 participants aged 45 or older selected from 2011 CHARLS database who had no history of chronic kidney disease at the baseline and completed the follow-up in 2015. A multivariate cox regression model was employed to examine the association between sarcopenia and the incidence of new-onset chronic kidney disease. RESULTS: Followed up for 4 years, a total of 873 (22.5%) new cases of chronic kidney disease occurred. Among them, participants diagnosed with sarcopenia (HR1.45; 95% CI 1.15-1.83) were more likely to develop new-onset chronic kidney disease than those without sarcopenia. Similarly, patients with sarcopenia were more likely to develop new-onset chronic kidney disease than those with possible sarcopenia (HR 1.27; 95%CI 1.00-1.60). Subgroup analysis revealed that elder adults aged between 60 and 75 years old (HR 1.666; 95%CI 1.20-22.28), with hypertension (HR 1.57; 95%CI 1.02-2.40), people with sarcopenia had a significantly higher risk of developing new-onset chronic kidney disease than those without sarcopenia (all P < 0.05). CONCLUSION: Middle-aged and elder adults diagnosed with sarcopenia have a higher risk of developing new-onset chronic kidney disease.
Subject(s)
Renal Insufficiency, Chronic , Sarcopenia , Humans , Middle Aged , Aged , Retirement , Longitudinal Studies , Quality of Life , ChinaABSTRACT
This study developed an efficient and stable landfill leachate treatment process, which was based on the combination of biochar catalytic ozonation and activated sludge technology for intensive treatment of landfill leachate, aiming to achieve the standard discharge of leachate. The focus is to investigate the effect of manganese loading on the physicochemical properties of biochar and the mechanism of its catalytic ozonation. It was found that more surface functional groups (CO, Mn-O, etc.) and defects (ID/IG = 1.27) were exposed via the change of original carbon structure by loading Mn, which is conducive to the generation of lattice oxygen. Meanwhile, generating different valence states of Mn metal can improve the redox properties and electron migration rate, and encourage the production of reactive oxygen species (ROS) during the reaction process and enhance the catalytic efficiency. The synergistic action of microorganisms, especially denitrifying bacteria, was found to play a key role in the degradation of nitrogenous pollutants during the activated sludge process. The concentration of NH+4-N was reduced from the initial 1087.03 ± 9.56 mg/L to 9.05 ± 1.91 mg/L, while COD was reduced from 2290 ± 14.14 mg/L to 86.5 ± 2.12 mg/L, with corresponding removal rates of 99.17% and 99.20%, respectively. This method offers high efficiency and stability, achieving discharge standards for leachate (GB16889-2008). The synergy between Mn-loaded biochar and microorganisms in the activated sludge is key to effective treatment. This study offers a new approach to solving the challenge of waste leachate treatment.
Subject(s)
Charcoal , Ozone , Water Pollutants, Chemical , Ozone/chemistry , Manganese , Water Pollutants, Chemical/chemistry , SewageABSTRACT
Injectable materials have attracted great attention in the manufacture of in situ forming hydrogels for biomedical applications. In this study, a facile method to prepare methacrylic anhydride (MA)-modified sodium carboxymethyl cellulose (CMC) as an injectable material for the fabrication of hydrogels with controllable properties is reported. The chemical structure of the series of MA-grafted CMC (CMCMAs) with different MA contents was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopy, and the properties of CMCMAs were characterized. Then, the CMCMAs gel (CMCMAs-G) was fabricated by crosslinking of MA under blue light irradiation. The gelation performances, swelling behaviors, transmittance, surface porous structures and mechanical properties of CMCMAs-G can be controlled by varying the content of MA grafted on the CMC. The compressive strength of CMCMAs-G was measured by mechanical compressibility tests and up to 180 kPa. Furthermore, the in vitro cytocompatibility evaluation results suggest that the obtained CMCMAs-G exhibit good compatibility for cell proliferation. Hence, our strategy provides a facile approach for the preparation of light-sensitive and an injectable CMC-derived polymer to fabricate hydrogels for biomedical applications.
Subject(s)
Carboxymethylcellulose Sodium , Hydrogels , Hydrogels/chemistry , Carboxymethylcellulose Sodium/chemistry , Methacrylates , Magnetic Resonance Spectroscopy , SodiumABSTRACT
Caspase-11 detection of intracellular lipopolysaccharide mediates non-canonical pyroptosis, which could result in inflammatory damage and organ lesions in various diseases such as sepsis. Our research found that lactate from the microenvironment of acetaminophen-induced acute liver injury increased Caspase-11 levels, enhanced gasdermin D activation and accelerated macrophage pyroptosis, which lead to exacerbation of liver injury. Further experiments unveiled that lactate inhibits Caspase-11 ubiquitination by reducing its binding to NEDD4, a negative regulator of Caspase-11. We also identified that lactates regulated NEDD4 K33 lactylation, which inhibits protein interactions between Caspase-11 and NEDD4. Moreover, restraining lactylation reduces non-canonical pyroptosis in macrophages and ameliorates liver injury. Our work links lactate to the exquisite regulation of the non-canonical inflammasome, and provides a basis for targeting lactylation signaling to combat Caspase-11-mediated non-canonical pyroptosis and acetaminophen-induced liver injury.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Pyroptosis , Humans , Acetaminophen/toxicity , Caspases, Initiator/metabolism , Caspases/metabolism , Lactic AcidABSTRACT
Constructed wetlands (CWs) are widely used to treat wastewater, while innovative studies are needed to support resource conservation, enhance multi-functionality, and improve the effectiveness of effluent usage. This study assessed the potential of CW's multiple functions by combining low-rank coal (lignite) and industrial waste (steel slag) in different configurations as CW substrates. The results of scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and metagenomic sequencing showed that the experimental treatment with lignite and steel slag mixtures had the highest multi-functionality, including efficient nutrient removal and carbon sequestration, as well as hydroponic crop production. Lignite and steel slag were mixed to form lignite-steel slag particle clusters, where Ca2+ dissolved on the surface of steel slag was combined with PO43- in wastewater to form Ca3(PO4)2 precipitation for phosphorus removal. A biofilm grew on the surface of lignite in this cluster, and OH- released from steel slag promoted lignite to release fulvic acid, which provided a carbon source for heterotrophic microorganisms and promoted denitrification. Moreover, fulvic acid enhanced carbon sequestration in CWs by increasing the biomass of Phragmites australis. The effluent from lignite-steel slag CW increased cherry tomato yield and quality while saving N and P applications. These results provide new ideas for the "green" and economic development of CW technology.
Subject(s)
Wastewater , Wetlands , Steel/chemistry , Coal , Waste Disposal, Fluid/methods , Phosphorus/chemistryABSTRACT
BACKGROUND: Bone mineral density (BMD) is important for the outcome of cervical spine surgery. As the gold standard of assessing BMD, dual-energy X-ray absorptiometry scans are often not ordered or go unreviewed in patients' charts. As the supplement, MRI-based vertebral bone quality (VBQ) was found to accurately predict osteopenia/osteoporosis and postoperative complications in lumbar spine. However, discussion of the efficiency of VBQ in cervical spine is lacking. And measurement methods of VBQ in cervical spine are diverse and not universally acknowledged like lumbar spine. We aimed to compare the predictive performance of three kinds of different Cervical-VBQ (C-VBQ) scores for bone mineral density assessment in patients undergoing cervical spine surgery. HU value of cervical spine was set as a reference. METHODS: Adult patients receiving cervical spine surgery for degenerative diseases were retrospectively included between Jan 2015 and Dec 2022 in our hospital. The VBQ scores and HU value were measured from preoperative MRI and CT. The correlation between HU value/C-VBQs (named C-VBQ1/2/3 according to different calculating methods) and DEXA T-score was analyzed using univariate linear correlation and Pearson's correlation. We evaluated the predictive performance of those two parameters and achieved the most appropriate cutoff value by comparing the receiver operating characteristic (ROC) curves. RESULTS: 106 patients (34 patients with T ≥ - 1.0 vs 72 patients with T < - 1.0) were included (mean age: 51.95 ± 10.94, 48 men). According to Pearson correlation analysis, C-VBQ1/2/3 and HU value were all significantly correlated to DEXA T-score (Correlation Coefficient (r): C-VBQ1: - 0.393, C-VBQ2: - 0.368, C-VBQ3: - 0.395, HU value: 0.417, p < 0.001). The area under the ROC curve (AUC) was calculated (C-VBQ1: 0.717, C-VBQ2: 0.717, C-VBQ3: 0.727, HU value: 0.746). The AUC of the combination of C-VBQ3 and HU value was 0.786. At last, the most appropriate cutoff value was determined (C-VBQ1: 3.175, C-VBQ2: 3.005, C-VBQ3: 2.99, HU value: 299.85 HU). CONCLUSIONS: Different MRI-based C-VBQ scores could all be potential and alternative tools for opportunistically screening patients with osteopenia and osteoporosis before cervical spine surgery. Among them, C-VBQ calculated in ASIC2-C7/SIT1-CSF performed better. We advised patients with C-VBQ higher than cutoff value to accept further BMD examination.
Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Adult , Male , Humans , Bone Density , Retrospective Studies , Tomography, X-Ray Computed/methods , Absorptiometry, Photon/methods , Lumbar Vertebrae , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Magnetic Resonance ImagingABSTRACT
Cold stress is a non-biological stressor that adversely affects tobacco yield and leaf quality. Plant photoreceptor proteins, which function as dual light-temperature sensors, play a vital role in temperature changes, making them crucial for responses to non-biological stressors. However, the regulatory mechanisms of PhyA in tobacco remain poorly understood. Therefore, in this study, we aimed to clone the NtPhyA gene from tobacco and generate overexpression (OE-NtPhyA) and mutant (KO-NtPhyA) constructs of NtPhyA. By assessing the physiological and biochemical responses of the mutants under cold stress and performing transcriptome sequencing, we determined the signalling mechanism of NtPhyA under cold stress. Comparative analysis with wild-type (WT) NtPhyA revealed that KO-NtPhyA exhibited increased seed germination rates and reduced wilting under cold stress. In additional, the degree of damage to leaf cells, cell membranes, and stomatal structures was mitigated, and the levels of reactive oxygen species (ROS) were significantly decreased. Antioxidant enzyme activity, net photosynthetic rate, and Fv/Fm were significantly enhanced in KO-NtPhyA, whereas the opposite effects were observed in OE-NtPhyA. These findings indicate that KO-NtPhyA augments tobacco tolerance to cold stress, implying a negative regulatory role of NtPhyA in tobacco during cold stress. Transcriptome analysis revealed that NtPhyA governs the expression of a cascade of genes involved in the response to oxygen-containing compounds, hydrogen peroxide (H2O2), ROS, temperature stimuli, photosystem II oxygen-evolving complex assembly, water channel activity, calcium channel activity, and carbohydrate transport. Collectively, our findings indicate that NtPhyA activates downstream gene expression to enhance the resilience of tobacco to cold stress.
Subject(s)
Cold-Shock Response , Nicotiana , Reactive Oxygen Species/metabolism , Nicotiana/metabolism , Hydrogen Peroxide/metabolism , Plants, Genetically Modified/genetics , Antioxidants/metabolism , Oxygen/metabolism , Gene Expression Regulation, Plant , Stress, Physiological/genetics , Plant Proteins/metabolismABSTRACT
BACKGROUND: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, p < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, p < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, p < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, p < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, p < 0.05). An increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, p < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, p = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, p = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, p = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, p < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, p < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, p < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, p < 0.01). Furthermore, increased HER-2 expression was an independent risk factor for recurrence-free survival (RFS) in patients (p < 0.01, HR = 3.421); Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.