Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma.

BACKGROUND: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells. METHODS: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 µM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling. RESULTS: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment. CONCLUSION: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

Alien emergent aquatic plants develop better ciprofloxacin tolerance and metabolic capacity than one native submerged species.

Antibiotic pollution and biological invasion pose significant risks to freshwater biodiversity and ecosystem health. However, few studies have compared the ecological adaptability and ciprofloxacin (CIPR) degradation potential between alien and native macrophytes. We examined growth, physiological response, and CIPR accumulation, translocation and metabolic abilities of two alien plants (Eichhornia crassipes and Myriophyllum aquaticum) and one native submerged species (Vallisneria natans) exposed to CIPR at 0, 1 and 10 mg/L. We found that E. crassipes and M. aquaticum's growth were unaffected by CIPR while V. natans was significantly hindered under the 10 mg/L treatment. CIPR significantly decreased the maximal quantum yield of PSII, actual quantum yield of PSII and relative electron transfer rate in E. crassipes and V. natans but didn't impact these photosynthetic characteristics in M. aquaticum. All the plants can accumulate, translocate and metabolize CIPR. M. aquaticum and E. crassipes in the 10 mg/L treatment group showed greater CIPR accumulation potential than V. natans indicated by higher CIPR contents in their roots. The oxidative cleavage of the piperazine ring acts as a key pathway for these aquatic plants to metabolize CIPR and the metabolites mainly distributed in plant roots. M. aquaticum and E. crassipes showed a higher production of CIPR metabolites compared to V. natans, with M. aquaticum exhibiting the strongest CIPR metabolic ability, as indicated by the most extensive structural breakdown of CIPR and the largest number of potential metabolic pathways. Taken together, alien species outperformed the native species in ecological adaptability, CIPR accumulation and metabolic capacity. These findings may shed light on the successful invasion mechanisms of alien aquatic species under antibiotic pressure and highlight the potential ecological impacts of alien species, particularly M. aquaticum. Additionally, the interaction of antibiotic contamination and invasion might further challenge the native submerged macrophytes and pose greater risks to freshwater ecosystems.

Application of phosphogypsum and phosphate-solubilizing fungi to Pb remediation: From simulation to in vivo incubation.

Phosphogypsum (PG) is the produced solid waste during phosphorus (P) extraction from phosphate rocks. PG is featured by its abundant PO43- and SO42-. This study investigated the utilization of PG as a material for lead (Pb) remediation, with the assistance of functional fungus. Aspergillus niger (A. niger) is a typical phosphate-solubilizing fungi (PSF), which has high ability to secret organic acids. Oxalic acid is its major secreted organic acid, which is often applied to enhance the P release from phosphate minerals. In this study, synthetic oxalic acid increased the immobilization rate of Pb2+ up to >99 % with the addition of PG. Then, it was observed that biogenic oxalic acid from A. niger can achieve comparable remediation effects. This was due to that PG could provide sufficient P for fungal growth, which allowed sustainable remediation. Subsequently, oxalic acid secreted by A. niger significantly increased the release of active P from PG, and then induced the formation of PPb minerals. In addition, other metabolites of A. niger (such as tyrosine-like substance) can also be complexed with Pb2+. Simultaneously, A. niger did not induce evidently elevation water-soluble fluorine (F) as PG contained abundant Ca2+. Moreover, this study elucidated that oversupply of PG promoted the formation of anglesite (Ksp = 1.6 × 10-8, relatively unstable), whereas the formation of lead oxalate (Ksp = 4.8 × 10-10, relatively stable) was reduced. This study hence shed a bright light on the sustainable utilization of PG for fungus-assisted remediation of heavy metals.

Using artificial intelligence methods to study the effectiveness of exercise in patients with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly affects children and adults worldwide, characterized by persistent inattention, hyperactivity, and impulsivity. Current research in this field faces challenges, particularly in accurate diagnosis and effective treatment strategies. The analysis of motor information, enriched by artificial intelligence methodologies, plays a vital role in deepening our understanding and improving the management of ADHD. The integration of AI techniques, such as machine learning and data analysis, into the study of ADHD-related motor behaviors, allows for a more nuanced understanding of the disorder. This approach facilitates the identification of patterns and anomalies in motor activity that are often characteristic of ADHD, thereby contributing to more precise diagnostics and tailored treatment strategies. Our approach focuses on utilizing AI techniques to deeply analyze patients' motor information and cognitive processes, aiming to improve ADHD diagnosis and treatment strategies. On the ADHD dataset, the model significantly improved accuracy to 98.21% and recall to 93.86%, especially excelling in EEG data processing with accuracy and recall rates of 96.62 and 95.21%, respectively, demonstrating precise capturing of ADHD characteristic behaviors and physiological responses. These results not only reveal the great potential of our model in improving ADHD diagnostic accuracy and developing personalized treatment plans, but also open up new research perspectives for understanding the complex neurological logic of ADHD. In addition, our study not only suggests innovative perspectives and approaches for ADHD treatment, but also provides a solid foundation for future research exploring similar complex neurological disorders, providing valuable data and insights. This is scientifically important for improving treatment outcomes and patients' quality of life, and points the way for future-oriented medical research and clinical practice.

Molecular phylogenetic analysis of the East Asian hemicultrine fishes (Teleostei: Cyprinidae: Xenocypridinae), with suggestions to their generic classification and redescription of the recently described species Hemiculter yungaoi Vasil'eva et al. 2022.

The hemicultrine fishes are a group of small-sized cyprinids, widely distributed but endemic to East Asian rivers and lakes. Till now, the taxonomic boundaries and relationships within this group remain poorly explored. In the present study, we study the phylogeny of this group, providing suggestions for classification of the hemicultrine group. Using two mitochondrial and three nuclear genes, and samples representing all genera, our results showed that the group consists of seven major lineages, of which four (Hemiculterella, Hainania, Pseudolaubuca, and Anabarilius) were monophyletic and three (Hemiculter, Toxabramis, and Pseudohemiculter) were not. Based on the phylogenetic tree, we redefined the genera. We revive the genus Siniichthys, which has three species, Siniichthys bleekeri, Siniichthys lucidus, and S. varpachovskii, that were previously treated as members of the genus Hemiculter but showed distant relationships to the genus Hemiculter in our phylogenetic tree. With the new results, a diagnostic key for clades of the hemicultrine group is provided. Furthermore, we provide more detailed information on diagnostic features of the recently described species Hemiculter yungaoi (Vasil'eva et al., 2022). This work will facilitate future systematic studies, pave the way for evolutionary studies, and provide valuable information for the urgent conservation of hemicultrine fishes.

Analysis of the Trends and Influencing Factors for Postoperative Cough in Patients with Esophageal Cancer Based on Patient-Reported Outcomes.

BACKGROUND: Cough is a common symptom that affects patients' recovery and quality of life after esophagectomy. This study sought to investigate trends in postoperative cough and the factors that influence cough. METHODS: A total of 208 of 225 patients were enrolled in this study. The Mandarin Chinese version of the Leicester Cough Questionnaire was administered the day before surgery and at three time points (1 week, 1 month, and 3 months) after esophagectomy to assess patient-reported outcomes. RESULTS: All patients' LCQ-MC scores after surgery were lower than presurgery (P < 0.05), with the lowest score found 1 week after esophagectomy. Factors associated with a cough 1 week after surgery included clinical stage of cancer (OR 0.782, 95% CI 0.647-0.944, P = 0.011), anastomotic position (OR 1.241, 95% CI 1.069-1.441, P = 0.005), duration of surgery (OR 0.759, 95% CI 0.577-0.998, P = 0.049), and subcarinal lymph node dissection (OR 0.682, 95% CI 0.563-0.825, P < 0.001). Factors associated with a cough one month after surgery included clinical stage (OR 0.782, 95% CI 0.650-0.940, P = 0.009), anastomotic position (OR 1.293, 95% CI 1.113-1.503, P = 0.001), and maintaining a semi-reclining position (OR 1.440, 95% CI 1.175-1.766, P < 0.001). Factors associated with a cough 3 months after surgery were clinical stage (OR 0.741, 95% CI 0.591-0.928, P = 0.009) and anastomotic position (OR 1.220, 95% CI 1.037-1.435, P = 0.016). CONCLUSIONS: This study showed that the factors influencing postoperative cough differed over time following esophagectomy. These results may warrant prospective intervention to better manage patients undergoing surgery for esophageal cancer to prevent postoperative cough.

A unified classification system for HIV-1 5' long terminal repeats.

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.

UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice.

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.

Progress in the application of nanoparticles for the treatment of fungal infections: A review.

The burden of fungal infections on human health is increasing worldwide. Aspergillus, Candida, and Cryptococcus are the top three human pathogenic fungi that are responsible for over 90% of infection-related deaths. Moreover, effective antifungal therapeutics are lacking, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proved not only to be more efficient antifungal therapeutic agents but also to overcome resistance against fungal medication. This review will examine the limitations of standard antifungal therapy as well as focus on the development of nanomaterials.

Oncological Outcomes of Transoral Laser Microsurgery for Early Stage Glottic Cancer with Involvement of the Anterior Commissure.

OBJECTIVES: To assess the value of carbon dioxide transoral laser microsurgery (CO2 TOLMS) for early-stage glottic cancer with special regard to involvement of the anterior commissure (AC). STUDY DESIGN: Single-center retrospective cohort study. SETTING: Grade-A tertiary hospital. METHODS: A retrospective analysis of patients with early-stage (Tis-T2) glottic cancer who underwent CO2 TOLMS. All patients had at least 2 years of follow-up. The univariate and multivariate survival analyses were used to identify the risk factors for recurrence and the Kaplan-Meier method was used to analyze OS and DSS rates. RESULTS: A total of 102 patients were included in the study. Eleven patients (10.78%) had recurrence. The univariate analysis showed that the recurrence was associated with the AC classification, T staging, tumor size, and tobacco use (P < .05). However, on multivariate analysis, the AC classification was the only independent risk factor for recurrence (P < .001, HR = 3.179). AC classification were distributed as follows: 59 (57.84%) AC0, 29 (28.43%) AC1, 8 (7.84%) AC2, and 6 (5.88%) AC3, 2-year/5-year OS and DSS rates were progressively reduced in the AC0, AC1, AC2, and AC3 groups (P < .001). At the same T staging, the OS rates incrementally decreased as the level of involvement of the AC became higher (P = .004). CONCLUSION: CO2 TOLMS is an effective treatment for early-stage glottic cancer. AC involvement is an independent risk factors for recurrence and poor prognosis. The AC classification system may be better at grading the prognosis of patients with early-stage glottic cancer and has prognostic value independent of T staging.

M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events.

Endogenous retroviruses (ERVs) are ancient retroviral remnants integrated in host genomes, and commonly deleted through unequal homologous recombination, leaving solitary long terminal repeats (solo-LTRs). This study, analysing the genomes of 362 bird species and their reptilian and mammalian outgroups, reveals an unusually higher level of solo-LTRs formation in birds, indicating evolutionary forces might have purged ERVs during evolution. Strikingly in the order Passeriformes, and especially the parvorder Passerida, endogenous retrovirus K (ERVK) solo-LTRs showed bursts of formation and recurrent accumulations coinciding with speciation events over past 22 million years. Moreover, our results indicate that the ongoing expansion of ERVK solo-LTRs in these bird species, marked by high transcriptional activity of ERVK retroviral genes in reproductive organs, caused variation of solo-LTRs between individual zebra finches. We experimentally demonstrated that cis-regulatory activity of recently evolved ERVK solo-LTRs may significantly increase the expression level of ITGA2 in the brain of zebra finches compared to chickens. These findings suggest that ERVK solo-LTRs expansion may introduce novel genomic sequences acting as cis-regulatory elements and contribute to adaptive evolution. Overall, our results underscore that the residual sequences of ancient retroviruses could influence the adaptive diversification of species by regulating host gene expression.

Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA.

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

Decomposition of exotic versus native aquatic plant litter in a lake littoral zone: Stoichiometry and life form analyses.

The decomposition rates and stoichiometric characteristics of many aquatic plants remain unclear, and our understanding of material flow and nutrient cycles within freshwater ecosystems is limited. In this study, an in-situ experiment involving 23 aquatic plants (16 native and 7 exotic species) was carried out via the litter bag method for 63 days, during which time the mass loss and nutrient content (carbon (C), nitrogen (N), and phosphorus (P)) of plants were measured. Floating-leaved plants exhibited the highest decomposition rate (0.038 ± 0.002 day-1), followed by submerged plants and free-floating plants (0.029 ± 0.002 day-1), and emergent plants had the lowest decomposition rate (0.019 ± 0.001 day-1). Mass loss by aquatic plants correlated with stoichiometric characteristics; the decomposition rate increased with an increasing P content and with a decreasing C content, C:N ratio, and C:P ratio. Notably, the decomposition rate of submerged exotic plants (0.044 ± 0.002 day-1) significantly exceeded that of native plants (0.026 ± 0.004 day-1), while the decomposition rate of emergent exotic plants was 55 ± 4 % higher than that of native plants. The decomposition rates of floating-leaved and free-floating plants did not significantly differ between the native and exotic species. During decomposition, emergent plants displayed an increase in C content and a decrease in N content, contrary to patterns observed in other life forms. The P content decreased for submerged (128 ± 7 %), emergent (90 ± 5 %), floating-leaved (104 ± 6 %), and free-floating plants (32 ± 6 %). Exotic plants released more C and P but accumulated more N than did native plants. In conclusion, the decomposition of aquatic plants is closely linked to litter quality and influences nutrient cycling in freshwater ecosystems. Given these findings, the invasion of the littoral zone by submerged and emergent exotic plants deserves further attention.

The expansion of oligopeptide transporters in Melampsora larici-populina may reflect its adaptation to a phytoparasitic lifestyle.

The acquisition of nutrients from host plants by phytopathogenic fungi is critically important for their invasion success. Melampsora larici-populina, an obligate biotrophic pathogenic fungus, causes the poplar leaf rust disease and can severely damage host poplar plants. Previously, we found that oligopeptide transporters (OPTs) have undergone a convergent expansion, which might reflect adaptation to a phytoparasitic lifestyle. Here, we used various methods to evaluate this hypothesis, including conserved motif identification, positive selection signal mining, expression pattern clustering analysis, and neutral selection tests. The motif composition of the five clades in the OPT family differed, and positive selection was observed during clade differentiation. This suggests that OPTs in these five clades may be functionally differentiated, which would increase the range of transported substrates and promote the absorption of more types of nitrogen compounds from the hosts. According to clustering analysis of gene expression patterns, the expression of most genes from the two expanded clades (clade 2 and 4) was up-regulated during the infection of poplar trees, indicating that the expansion of OPTs likely occurred to promote the uptake of oligopeptides from host poplar plants. The MellpOPT4g gene was determined to be under significant balancing selection based on the neutral selection tests, suggesting that it plays a role in the pathogenic process. In conclusion, these three observations provide preliminary evidence supporting our hypothesis, as they indicate that the expansion of OPTs in M. larici-populina has aided the ability of this pathogen to acquire nutrients from host plants.

Genomic insights into the seawater adaptation in Cyprinidae.

BACKGROUND: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. RESULTS: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. CONCLUSIONS: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer.

BACKGROUND: The cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer. METHODS: The single-cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty-four genes from SECRETORY_PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP-counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan-carcinoma analysis were used to examine the performance of prognostic model. RESULTS: Eighteen prognostic genes from SECRETORY_PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor-related pathways, such as PATHWAYS_IN_CANCER and B_CELL_RECEPTOR_SIGNALING_PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four-gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high- and low-RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan-carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy. CONCLUSIONS: Based on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer.

Circ1811 suppresses gastric cancer progression by regulating the miR-632/DAPK1 axis.

Compelling evidence has identified circRNAs as crucial regulators in initiation and progression of various cancers, including gastric cancer (GC). However, the function and regulatory mechanisms of circRNAs in GC remain largely unknown. In this study, attention is paid to a novel circular RNA circ1811, which exerts significant downregulated expression in GC tissues compared with adjacent non-cancerous tissues. The expression of circ1811 in GC tumor tissues is negatively correlated with the extent of lymphatic metastasis in GC patients. Overexpression of circ1811 inhibited GC cell proliferation, migration and invasion while promoting apoptosis, whereas knockdown of circ1811 led to the opposite effects. AGO2 RIP and dual luciferase reporter assays indicated that circ1811 directly sponges miR-632 to upregulate the expression of DAPK1. Collectively, circ1811 acts as a tumor-suppressor for GC progression by regulating the miR-632/DAPK1 axis. Our findings suggest the potential of circ1811 as ideal biomarker and therapeutic target for GC.

The genus Dioscorea L. (Dioscoreaceae), a review of traditional uses, phytochemistry, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Dioscorea, a member of the Dioscoreaceae family, comprises approximately 600 species and is widely distributed across temperate and tropical regions such as Asia, South Africa, and North America. The traditional medicinal uses of Dioscorea have been documented in Asian and African pharmacological systems. In Asia, this genus is traditionally used to treat respiratory illnesses, rheumatism, diabetes, diarrhea, dysentery, and other conditions. In Africa, this genus has been used to treat human immunodeficiency virus and ring worms. However, the traditional medicinal practices in North America rarely mention the use of this genus. AIM OF THE STUDY: The aim of this review is to comprehensively review the genus Dioscorea, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. The research also aims to highlight the valuable bioactive compounds within Dioscorea and emphasize the need for further investigations into acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors to contribute to the discovery of novel pharmaceuticals. MATERIALS AND METHODS: A search for available information on Dioscorea was conducted using scientific databases, including PubMed, ISI-WOS, Scopus, and Google Scholar, as well as recent academic publications from reputable publishers and other literature sources. The search was not limited by language and spanned the literature published between 1950 and 2022. RESULTS: This article provides a comprehensive review of the Dioscorea genus, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. Extensive research has been conducted on this genus, resulting in the isolation and examination of over 1000 compounds, including steroids, terpenoids, and flavonoids, to determine their biological activities. These activities include anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, hypoglycemic, and hypolipidemic effects. However, some studies have indicated the potential toxicity of high doses of Dioscorea, highlighting the need for further investigations to assess the safety of this genus. Additionally, this review explores potential avenues for future research and discusses the challenges associated with a comprehensive understanding of the Dioscorea genus. CONCLUSIONS: Based on the existing literature, it can be concluded that Dioscorea is a valuable source of bioactive compounds that have the potential to treat various disorders. Future research should prioritize the investigation of acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors. This review provides a comprehensive analysis of the Dioscorea genus, emphasizing its potential to enable a deeper exploration of the biological activity mechanisms of these plants and contribute to the discovery of novel pharmaceuticals.