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 genomic profiling of small bowel adenocarcinoma by tissue and plasma biopsy.

Small bowel adenocarcinoma (SBA) is a rare and aggressive malignancy with limited treatment options and poor prognosis. The molecular landscape and immunological characteristics of SBA are poorly understood. Here, we performed comprehensive mutation profiling of tissue and plasma biopsies from 143 and 42 patients with SBA. Analysis showed that SBA had a distinct mutation spectrum from left- and right-sided colorectal carcinoma. Plasma biopsy had high concordance with tissue biopsy for single nucleotide variants and structural variants, but low concordance for copy number variations, which showed that plasma biopsy can be an alternative to tissue biopsy. Moreover, we analyzed the association of TMB with clinical and molecular features, and found that TMB was significantly higher in tumors with DNA damage response alterations. Our findings provide valuable insights into the molecular and immunological features of SBA and demonstrate the potential of plasma biopsy as a non-invasive method for SBA diagnosis and treatment.

Superconductivity and Charge-Density-Wave-Like Transition in Th2Cu4As5.

We report the synthesis, crystal structure, and physical properties of a novel ternary compound, Th2Cu4As5. The material crystallizes in a tetragonal structure with lattice parameters a = 4.0639(3) Å and c = 24.8221(17) Å. Its structure can be described as an alternating stacking of fluorite-type Th2As2 layers with antifluorite-type double-layered Cu4As3 slabs. The measurement of electrical resistivity, magnetic susceptibility, and specific heat reveals that Th2Cu4As5 undergoes bulk superconducting transition at 4.2 K. Additionally, all these physical quantities exhibit anomalies at 48 K, accompanied by a sign change in the Hall coefficient, suggesting a charge-density-wave-like (CDW) phase transition. Drawing from both experimental data and band calculations, we propose that the superconducting and CDW-like phase transitions are, respectively, associated with the Cu4As3 slabs and the As plane in the Th2As2 layers.

Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2.

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis.

BACKGROUND: Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. METHODS: In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. RESULTS: Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-ß treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-ß-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-ß/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-ß/Smad signaling pathway in NSCLC cells. CONCLUSION: In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-ß/Smad signaling pathway and represents a novel therapeutic target for NSCLC.

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.

Performance of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of invasive pulmonary filamentous fungi infections in non-neutropenic patients.

The diagnosis of invasive pulmonary fungal disease depends on histopathology and mycological culture; there are few studies on touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of pulmonary filamentous fungi infections. The purpose of the present study was to explore the detection accuracy of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the filamentous fungi, and it aims to provide a basis for initiating antifungal therapy before obtaining microbiological evidence. We retrospectively analyzed the diagnosis and treatment of 44 non-neutropenic patients with invasive pulmonary filamentous fungi confirmed by glactomannan assay, histopathology, and culture from February 2017 to December 2023. The diagnostic positive rate and sensitivity of rapid on-site evaluation for these filamentous fungi identification, including diagnostic turnaround time, were calculated. Compared with the final diagnosis, the sensitivity of rapid on-site evaluation was 81.8%, and the sensitivity of histopathology, culture of bronchoalveolar lavage fluid, and glactomannan assay of bronchoalveolar lavage fluid was 86.4%, 52.3%, and 68.2%, respectively. The average turnaround time of detecting filamentous fungi by rapid on-site evaluation was 0.17 ± 0.03 hours, which was significantly faster than histopathology, glactomannan assay, and mycological culture. A total of 29 (76.3%) patients received earlier antifungal therapy based on ROSE diagnosis and demonstrated clinical improvement. Rapid on-site evaluation showed good sensitivity and accuracy that can be comparable to histopathology in identification of pulmonary filamentous fungi. Importantly, it contributed to the triage of biopsies for further microbial culture or molecular detection based on the preliminary diagnosis, and the decision on early antifungal therapy before microbiological evidence is available.

The causes of species richness patterns among clades.

Two major types of species richness patterns are spatial (e.g. the latitudinal diversity gradient) and clade-based (e.g. the dominance of angiosperms among plants). Studies have debated whether clade-based richness patterns are explained primarily by larger clades having faster rates of species accumulation (speciation minus extinction over time; diversification-rate hypothesis) or by simply being older (clade-age hypothesis). However, these studies typically compared named clades of the same taxonomic rank, such as phyla and families. This study design is potentially biased against the clade-age hypothesis, since clades of the same rank may be more similar in age than randomly selected clades. Here, we analyse the causes of clade-based richness patterns across the tree of life using a large-scale, time-calibrated, species-level phylogeny and random sampling of clades. We find that within major groups of organisms (animals, plants, fungi, bacteria, archaeans), richness patterns are most strongly related to clade age. Nevertheless, weaker relationships with diversification rates are present in animals and plants. These overall results contrast with similar large-scale analyses across life based on named clades, which showed little effect of clade age on richness. More broadly, these results help support the overall importance of time for explaining diverse types of species richness patterns.

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.

High-performance Ag-TiO2 nanoparticle composite catalyst synthesized by pulsed laser ablation in liquid: properties, mechanism and preparation studies.

Precious metal doping can effectively improves the catalytic performance of TiO2. In this study, pulsed laser ablation in liquid (PLAL) is employed to integrate preparation with doping and control composite nanoparticle products by adjusting the laser action time to synthesise Ag-TiO2 composite nanoparticles with high catalytic performance. The generation and evolution of Ag-TiO2 nanoparticles are investigated by analysing particle size, microscopic morphology, crystalline phase, and other characteristics. The generation and doped-morphology evolution of composite nanoparticles are simulated based on thermodynamics, and the optimisation of Ag-doped structure on the composite nanomaterials is investigated based on density functional theory. The effect of Ag-TiO2 structural properties on its performance is examined under different catalytic conditions to determine optimal degradation conditions. In this study, the effect of laser ablation time on the doped structure during PLAL is analysed, which is of further research significance in exploring the structural evolution law of laser and composite nanoparticles, multi-variate catalytic performance testing, reduction of photogenerated carrier complexation rate, and expansion of its spectral absorption range, thereby providing the basis for practical production.