Changes in cuproptosis-related gene expression in periodontitis: An integrated bioinformatic analysis.

Periodontitis causes inflammatory destruction of tooth-supporting tissues; however, the complex mechanism underlying its etiology remains unclear. Cuproptosis is a type of cell death caused by an imbalance in intracellular copper homeostasis that leads to excess copper. However, changes in the expression and biological function of cuproptosis-related genes (CRGs) in periodontitis are not yet fully understood. This study investigated the comprehensive effects of differentially expressed CRGs (DE-CRGs) on periodontitis via bioinformatic analysis. Nine DE-CRGs were discovered using normal and periodontitis gingival samples, and single-cell RNA sequencing data were analyzed to identify them changes in diverse cell clusters. We then detected the correlation between DE-CRGs and immune infiltration, immune factors, mitochondrial dysfunction, diagnostic efficacy, and predicted drugs. Moreover, changes of DE-CRG in whole periodontitis tissue and a human gingival fibroblast cell line (HGF-1) were confirmed and copper content changes in HGF-1 cells were investigated. Most DE-CRG expression trends were reversed between the periodontal tissues and cell clusters, which may be related to the proportion of cell clusters changes caused periodontitis. Furthermore, most DE-CRG trends in periodontitis cell clusters were inconsistent with the effects of cuproptosis. In HGF-1 cells treated with Porphyromonas gingivalis lipopolysaccharide (Pg-LPS), the intracellular copper content increased by more than threefold, indicating that although some periodontitis cells had excess copper, the amount may not have been sufficient to trigger cuproptosis. Additionally, DE-CRGs were closely associated with multiple biological functions, antibiotic drugs, and natural herbal medicines. Our findings may provide an overview of DE-CRGs in the pathogenesis and treatment of periodontitis.

Comparative effectiveness of nipple-sparing mastectomy and breast-conserving surgery on long-term prognosis in breast cancer.

Background: The frequency of nipple-sparing mastectomy (NSM) surgery is presently increasing. Nonetheless, there is a paucity of long-term prognosis data on NSM. This study compared the long-standing prognosis of NSM in relation to breast-conserving surgery (BCS). Methods: Population-level data for 438,588 female breast cancer patients treated with NSM or BCS and postoperative radiation from 2000 to 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database; 321 patients from the Second Xiangya Hospital of Central South University were also included. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables to make valid comparisons. The Kaplan-Meier analysis, log-rank test, and Cox regression were applied to analyze the data. Results: There were no significant differences in long-term survival rates between patients who underwent NSM and those who underwent BCS+radiotherapy (BCS+RT), as indicated by the lack of significant differences in overall survival (OS) (p = 0.566) and breast cancer-specific survival (BCSS) (p = 0.431). Cox regression indicated that NSM and BCS+RT had comparable prognostic values (p = 0.286) after adjusting for other clinicopathological characteristics. For OS and BCSS, subgroup analysis showed that the majority of patients achieved an analogous prognosis whether they underwent NSM or BCS. The groups had comparable recurrence-free survival (RFS), with no significant difference found (p = 0.873). Conclusions: This study offers valuable insights into the long-term safety and comparative effectiveness of NSM and BCS in the treatment of breast cancer. These findings can assist clinicians in making informed decisions on a case-by-case basis.

Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression.

Background: Origin recognition complex 6 (ORC6) is one of the six highly conserved subunit proteins required for DNA replication and is essential for maintaining genome stability during cell division. Recent research shows that ORC6 regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment. Methods: Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of ORC6 in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of ORC6. To evaluate the potential prognostic impact and diagnostic significance of ORC6 expression, we carried out log-rank, univariate Cox regression, and receiver operating characteristic curve analysis. The ICGC-LIRI-JP cohort, CGGA-301 cohort, CGGA-325 cohort, CGGA-693 cohort, and GSE13041 cohort were used for external validation of the study findings. The associations between ORC6 expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to ORC6 expression, gene set enrichment analysis was performed. To clarify the expression and function of ORC6 in hepatocellular carcinoma (LIHC) and glioma, we conducted in vitro experiments. Results: Expression of ORC6 is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, ORC6 may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of ORC6 correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the ORC6 high-expression group benefited from immunotherapy. Inhibiting ORC6 expression suppressed the proliferative and migratory abilities of LIHC and glioma cells. Conclusion: High expression of ORC6 may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of ORC6 may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.

The Expression of the StNRAMP2 Gene Determined the Accumulation of Cadmium in Different Tissues of Potato.

Cadmium (Cd) is a toxic metal that threatens human health when enriched in crops. NRAMPs are a family of natural macrophage proteins reported to play a key role in Cd transport in plants. In order to explore the gene regulation mechanism of potato under Cd stress and the role of NRAMPs family in it, this study analyzed the gene expression differences of two different Cd accumulation levels in potato after 7 days of 50 mg/kg Cd stress and screened out the key genes that may play a major role in the differential accumulation of Cd in different varieties. Additionally, StNRAMP2 was selected for verification. Further verification showed that the StNRAMP2 gene plays an important role in the accumulation of Cd in potato. Interestingly, silencing StNRAMP2 increased Cd accumulation in tubers but significantly decreased Cd accumulation in other sites, suggesting a critical role of StNRAMP2 in Cd uptake and transport in potatoes. To further confirm this conclusion, we performed heterologous expression experiments in which overexpression of StNRAMP2 gene in tomato resulted in a threefold increase in Cd content, which further confirmed the important role of StNRAMP2 in the process of Cd accumulation compared with wild-type plants. In addition, we found that the addition of Cd to the soil increased the activity of the plant antioxidant enzyme system, and silencing StNRAMP2 partially reversed this effect. This suggests that the StNRAMP2 gene plays an important role in plant stress tolerance, and future studies could further explore the role of this gene in other environmental stresses. In conclusion, the results of this study improve the understanding of the mechanism of Cd accumulation in potato and provide experimental basis for remediation of Cd pollution.

Different composites inhibit Cd accumulation in grains under the rice-oilseed rape rotation mode of karst area: A field study.

Ensuring the safe production of food and oil crops in soils with elevated cadmium (Cd) content in karst regions is crucial. We tested a field experiment to examine the long-term remediation effects of compound microorganisms (CM), strong anion exchange adsorbent (SAX), processed oyster shell (POS), and composite humic acids (CHA) on Cd contamination in paddy fields under a rice-oilseed rape rotation system. In comparison to the control group (CK), the application of amendments significantly increased soil pH, cation exchange capacity (CEC), and soil organic matter (SOM) content while markedly decreasing the content of available Cd (ACd). During the rice cultivation season, Cd was predominantly concentrated in the roots. Relative to the control (CK), the Cd content in each organ was significantly reduced. The Cd content in brown rice decreased by 19.18-85.45%. The Cd content in brown rice following different treatments exhibited the order of CM > POS > CHA > SAX, which was lower than the Chinese Food Safety Standard (GB 2762-2017) (0.20 mg/kg). Intriguingly, during the oilseed rape cultivation season, we discovered that oilseed rape possesses potential phytoremediation capabilities, with Cd mainly accumulating in roots and stems. Notably, CHA treatment alone significantly decreased the Cd content in oilseed rape grains to 0.156 mg/kg. CHA treatment also maintained soil pH and SOM content, consistently reduced soil ACd content, and stabilized Cd content in RSF within the rice-oilseed rape rotation system. Importantly, CHA treatment not only enhances crop production but also has a low total cost (1255.230 US$/hm2). Our research demonstrated that CHA provides a consistent and stable remediation effect on Cd-contaminated rice fields within the crop rotation system, as evidenced by the analysis of Cd reduction efficiency, crop yield, soil environmental change, and total cost. These findings offer valuable guidance for sustainable soil utilization and safe production of grain and oil crops in the context of high Cd concentrations in karst mountainous regions.

Discovery of cadmium-tolerant biomacromolecule (StCAX1/4 transportproteins) in potato and its potential regulatory relationship with WRKY transcription factors.

The cation/H+ exchanger (CAX) involved in Ca2+, Mg2+ and Mn2+ transport is a special class of vacuolar transporters that play an important role in maintaining ion homeostasis in plant cells. However, it has been rarely reported whether CAX proteins have unique tolerance to cadmium stress. In our research, the cadmium-resistant potato variety "Yunshu 505" was taken as the object, through biological etc. methods, explored 1: response mode of StCAXs to cadmium stress; 2: the evolutionary characteristics and Cd ion binding sites of StCAXs; and 3: possible upstream regulatory pathways of StCAXs. The results showed that cadmium stress significantly induced the expression of StCAX1/4, and there were specific mutations in the evolution process, thus the possible main binding site of Cd ion (EDEE/DH/GxxxxxS/EEEE) was speculated. StCAX1/4 interacts with several proteins, and be regulated by transcription factors, especially the WRKY6. This synergistic regulation through WRKY6 may be an important pathway through which StCAX1/4 imparts high cadmium tolerance to potato. These results provide certain support for understanding the binding sites and specific evolutionary mechanisms of key amino acid residues of cadmium ion in StCAXs, also provide new clues for the identification and regulatory model of potato CAX key positive stress-responsive proteins under cadmium stress.

Identification of the Major Effector StSROs in Potato: A Potential StWRKY-SRO6 Regulatory Pathway Enhances Plant Tolerance to Cadmium Stress.

SIMILAR TO RCD-ONE (SRO) family members and transcription factors (TFs) often improve plant antioxidant capacity through interaction and co-regulation and participate in plant resistance to drought and high-salt stress. However, whether SROs are involved in the response to heavy metal stress, especially SRO genes with a specific response and tolerance characteristics to cadmium (Cd) stress, remains unclear. We first identified six SRO genes in the potato genome by PARP and RST domains. Special and conserved StSROs were found, and the spatio temporal tissue-specific expression patterns and co-expression network diagrams of StSROs under the stress of 5 heavy metals were constructed. Second, we identified StSRO6 as a major effector gene (StSRO6-MEG) and StSRO5 as a secondary effector gene (StSRO5-SEG) through a comprehensive analysis. Interestingly, they may hold true for various physiological or stress responses in plants. In addition, using systematic genomics and comparative omics techniques, the key gene StSRO6 that affects the difference in Cd accumulation was discovered, cloned in the low-Cd accumulation "Yunshu 505", and transformed into the yeast mutant ycf1 for overexpression. The results proved that StSRO6 could confer Cd tolerance. Finally, through transient expression and in vitro culture tests, we hypothesized that StSROs 5/6 are regulated by the transcription factor StWRKY6 and mediates the reactive oxygen species (ROS) system to confer Cd tolerance. These findings offer a new perspective for understanding the mechanisms underlying Cd tolerance in plants, and simultaneously provide clues for the development of biological agents for preventing and controlling Cd migration and transformation.

Plant Resistance to Fungal Pathogens: Bibliometric Analysis and Visualization.

Plants are susceptible to fungal pathogen infection, threatening plant growth and development. Researchers worldwide have conducted extensive studies to address this issue and have published numerous articles on the subject, but they lack a scientometric evaluation. This study analyzed international research on the topic "Plant resistance to fungal pathogens" between 2008 and 2021, using the core database of the Web of Science (WoS). By searching the subject words "Plants", "Disease Resistance", and "Fungal Pathogens", we received 6687 articles. Bibliometric visualization software analyzes the most published countries, institutions, journals, authors, the most cited articles, and the most common keywords. The results show that the number of articles in the database has increased year by year, with the United States and China occupying the core positions, accounting for 46.16% of the total published articles worldwide. The United States Department of Agriculture (USDA) is the main publishing organization. Wang Guoliang is the author with the most published articles, and the Frontiers in Plant Science ranks first in published articles. The research on plant anti-fungal pathogens is booming, and international exchanges and cooperation need to be further strengthened. This paper summarizes five possible research ideas, from fungal pathogens, gene editing technology, extraction of secondary metabolites from plants as anti-fungal agents, identification of related signal pathways, fungal molecular databases, and development of nanomaterials, to provide data for related research.

Prognosis comparison between intraoperative radiotherapy and whole-breast external beam radiotherapy for T1-2 stage breast cancer without lymph node metastasis treated with breast-conserving surgery: A case-control study after propensity score matching.

Background: External beam radiotherapy (EBRT), an adjuvant to breast-conserving surgery (BCS), requires a long treatment period, is costly, and is associated with numerous complications. Large sample studies with long follow-up periods are lacking regarding whether intraoperative radiotherapy (IORT), an emerging radiotherapy modality, can replace EBRT for patients with T1-2 early stage breast cancer without lymph node metastasis treated with BCS. Methods: We identified 270,842 patients with T1-2N0M0 breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. A total of 10,992 patients were matched by propensity score matching (PSM). According to the radiotherapy method, the patients were divided into the IORT and EBRT groups. Overall survival (OS) and breast cancer-specific survival (BCSS) rates were analyzed and compared between the IORT and EBRT groups by Kaplan-Meier analysis. Bilateral P < 0.05 was considered to indicate significance. Results: After PSM, the survival analysis showed no significant differences in OS or BCSS rates between the IORT and EBRT groups. In the subgroup analysis, the IORT population diagnosed from 2010 to 2013 (HRs = 0.675, 95% CI 0.467-0.976, P = 0.037) or with T2 stage (HRs = 0.449, 95% CI 0.261-0.772, P = 0.004) had better OS rates, but in the overall population, the OS and BCSS rates were better in patients with T1 stage than in patients with T2 stage (P < 0.0001), and the proportion of chemotherapy was significantly higher in T2 stage than in T1 stage. Patients who had EBRT with unknown estrogen receptor had better OS rates (HRs = 3.392, 95% CI 1.368-8.407, P = 0.008). In addition, the IORT group had better BCSS rates for married (HRs = 0.403, 95% CI 0.184-0.881, P = 0.023), grade III (HRs = 0.405, 95% CI 0.173-0.952, P = 0.038), and chemotherapy-receiving (HRs = 0.327, 95% CI 0.116-0.917, P = 0.034) patients with breast cancer compared to the EBRT group. Conclusion: Intraoperative radiotherapy results of non-inferior OS and BCSS rates, compared to those of EBRT, in patients with early stage breast cancer without lymph node metastasis treated with BCS, and IORT may provide substantial benefits to patients as an effective alternative to standard treatment. This finding provides new insights into radiotherapy strategies for early stage breast cancer.

Chemotherapy significantly improves long-term survival of small lesion node negative metaplastic breast carcinoma in T1c population rather than T1a and T1b.

Metaplastic breast carcinoma (MpBC) is considered a highly aggressive disease, the outcome of chemotherapy on small lesions (T1abcN0M0) MpBC patients remain unclear. We identified 890 female MpBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. After propensity score matching (PSM), 584 patients were matched. Survival probability was compared among T1a, T1b, and T1c patients and between patients with and without chemotherapy using Kaplan-Meier analysis and Cox proportional hazard analysis. Significance was set at two-sided P < 0.05. We classified 49, 166, and 675 patients as T1a, T1b, and T1c MpBC, respectively. The chemotherapy group included 404 patients (45.4%). Following PSM, survival analysis indicated that the patients who underwent chemotherapy had higher OS (P = 0.0002) and BCSS (P = 0.0276) in the T1c substage, but no significant difference was detected in T1a or T1b patients. In this population-based study, small lesion MpBC showed a favorable prognosis. Chemotherapy improved the prognosis of T1c MpBC patients but not T1a and T1b patients to a beneficial extent. Our findings may offer novel insight into a therapeutic strategy for MpBC.

Specifically Targeted Transport of Plasma Membrane Transporters: From Potential Mechanisms for Regulating Cell Health or Disease to Applications.

Normal substrate transport and signal transmission are the premise to ensure the health of biological somatic cells. Therefore, a comprehensive understanding of the molecular mechanism of intercellular substrate transport is of great significance for clinical treatment. In order to better understand the membrane protein through its interaction with receptors, to help maintain a healthy cell and the molecular mechanisms of disease, in this paper, we seek to clarify, first of all, the recognition mechanism for different types of membrane protein receptors; pathogen invasion using the transport pathway involved in the membrane; and the latest specific target sites of various kinds of membrane transport carriers; to provide an explanation and summary of the system. Secondly, the downstream receptor proteins and specific substrates of different membrane transporters were classified systematically; the functional differences of different subclasses and their relationship with intracellular transport disorders were analyzed to further explore the potential relationship between cell transport disorders and diseases. Finally, the paper summarizes the use of membrane transporter-specific targets for drug design and development from the latest research results; it points out the transporter-related results in disease treatment; the application prospects and the direction for drug development and disease treatment providing a new train of thought; also for disease-specific targeted therapy, it provides a certain reference value.

OPT gene family analysis of potato (Solanum tuberosum) responding to heavy metal stress: Comparative omics and co-expression networks revealed the underlying core templates and specific response patterns.

Oligopeptides transporter (OPT) can maintain intracellular metal homeostat, however, their evolutionary characteristics, as well as their expression patterns in heavy metal exposure, remain unclear. Compared with previous OPT family identification, we identified 94 OPT genes (including 21 in potato) in potato and 4 other plants by HMMER program based on OPT domain (PF03169) for the first time. Secondly, conserved and special OPTs were found through comprehensive analysis. Thirdly, spatio-temporal tissue specific expression patterns and co-expression frameworks of potato OPT genes under different heavy metal stress were constructed. These data can provide excellent gene resources for food security and soil remediation.