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Using 3 cyprinid fish species zebra fish, rare minnow, and juvenile grass carp, we conducted assays of lethal reaction and ventilatory response to analyze sensitivity of the fish to 4 heavy metals. Our results showed that the 96 h LC50 of Hg(2+) to zebra fish, juvenile grass carp, and rare minnow were 0.14 mg L(-1), 0.23 mg L(-1), and 0.10 mg L(-1), respectively; of Cu(2+)0.17 mg L(-1), 0.09 mg L(-1), and 0.12 mg L(-1) respectively; of Cd(2+)6.5 mg L(-1), 18.47 mg L(-1), 5.36 mg L(-1), respectively; and of Zn(2+)44.48 mg L(-1), 31.37 mg L(-1), and 12.74 mg L(-1), respectively. Under a 1-h exposure, the ventilatory response to the different heavy metals varied. Ventilatory frequency (Vf) and amplitude (Va) increased in zebra fish, juvenile grass carp, and rare minnows exposed to Hg(2+) and Cu(2+) (P<0.05), and the Vf and Va of the 3 species rose initially and then declined when exposed to Cd(2+). Zn(2+) had markedly different toxic effects than the other heavy metals, whose Vf and Va gradually decreased with increasing exposure concentration (P<0.05). The rare minnow was the most highly susceptible of the 3 fish species to the heavy metals, with threshold effect concentrations (TEC) of 0.019 mg L(-1), 0.046 mg L(-1), 2.142 mg L(-1), and 0.633 mg L(-1) for Hg(2+), Cu(2+), Cd(2+), and Zn(2+), respectively. Therefore, it is feasible to use ventilatory parameters as a biomarker for evaluating the pollution toxicity of metals and to recognize early warning signs by using rare minnows as a sensor.

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

Tumor vaccines have become crucial in cancer immunotherapy, but, only a limited number of phase III clinical trials have demonstrated clinical efficacy. The crux of this issue is the inability of tumor vaccines to effectively harmonize the tumor microenvironment with its intricate interplay. One factor that can hinder the effectiveness of vaccines is the natural immunosuppressive element present in the tumor microenvironment. This element can lead to low rates of T-cell response specific to antigens and the development of acquired resistance. Conversely, anticancer vaccines alter the tumor microenvironment in conflicting manners, inducing both immune activation and immunological evasion. Hence, comprehending the correlation between tumor vaccines and the tumor microenvironment would establish a foundation for forthcoming tumor treatment. Our review explores the realm of research pertaining to tumor vaccinations and the tumor microenvironment. Our objective is to investigate the correlation between tumor vaccines and the tumor microenvironment within this domain. We then focus our review on the dominant international paradigms in this research field and visually illustrates the historical progression and emergent patterns observed in the past. From January 1, 1999 to February 7, 2023, 1420 articles on the interplay between tumor vaccines and the tumor microenvironment were published, according to The Clarivate Web of Science (WOS) database used in our review. A bibliometric review was designed for this collection and consisted of an evaluation. The evaluation encompassed various discernible attributes, including the year of publication, the journals in which the articles were published, the authors involved, the affiliated institutions, the geographical locations of the institutions, the references cited, and the keywords employed. Between the years 1999 and 2022, publications saw a significant increase, from 3 to 265 annually. With 72 papers published, Frontiers in Immunology had the most manuscripts published. The Cancer Research publication garnered the highest number of citations, amounting to 2874 citations. The United States exerts significant dominance in the subject, with the National Cancer Institute being recognized as a prominent institution in terms of both productivity and influence. Furthermore, Elizabeth M. Jaffee was recognized as the field's most prolific and influential author with 24 publications and 1,756 citations. The co-occurrence cluster analysis was conducted on the top 197 keywords, resulting in the identification of five distinct clusters. The most recent high-frequency keywords, namely immune therapy, dendritic cell, tumor microenvironment, cancer, and vaccine, signify the emerging frontiers in the interaction between tumor vaccines and the tumor microenvironment. Our review uncovers insights into contemporary trends, global patterns of collaboration, fundamental knowledge, research areas of high interest, and emerging frontiers in the field of TME-targeted vaccines.

Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear. Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-κB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR). TLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth . Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing. TLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1/NGFR axis represents a novel potential therapeutic target for CRPC.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and its current diagnostic and therapeutic methods still face severe challenges in terms of specificity, efficacy, and toxicity. The emergence of nanotechnology provides a powerful platform to overcome these obstacles. Through the design of sophisticated nanocarriers, targeted delivery and controlled release of therapeutic agents, as well as the synergy of multiple treatment modalities, can be achieved, thereby significantly improving efficacy and reducing side effects. Meanwhile, nanotechnology shows great potential in developing highly sensitive diagnostic tools and theranostic platforms, laying the foundation for early detection and precise treatment of PCa. Although challenges such as scalability and safety remain to be addressed before clinical translation, nanotechnology is undoubtedly reshaping the landscape of PCa management and driving the field towards personalized medicine. This review aims to provide a systematic overview of significant advancements in nanotechnology for the diagnosis and treatment of PCa over the past three years. It focuses on innovative research in novel nanocarrier design, targeting strategies, and the construction of integrated diagnostic and therapeutic platforms. Furthermore, current challenges and future directions for clinical translation are discussed, with the aim of offering valuable insights and references for researchers and clinicians in this field.

Talin-1 (TLN1), encoded by the TLN1 gene, is a focal adhesion-related protein capable of binding various proteins in the cytoskeleton. It is also expressed at high levels in many cancers wherein it influences cellular adhesion and the activation of integrins. TLN1 is also capable of promoting tumor cell invasivity, proliferation, and metastatic progression, in addition to being a relevant biomarker and therapeutic target in certain cancers. The present review offers a comprehensive overview of current knowledge regarding TLN1 with respect to its structural properties, functions, and role in tumor development.

The tumor microenvironment (TME) is crucial for tumor growth and progression, within which cancer-associated fibroblasts (CAFs) play a central role in regulating cancer cell proliferation, metastasis, and therapy resistance through various mechanisms. Although early-stage prostate cancer (PCa) has a high cure rate, advanced disease often becomes difficult to manage due to resistance to standard therapies such as androgen deprivation therapy (ADT). Therefore, a deep understanding of the interaction mechanisms between CAFs and PCa cells is essential for developing novel therapeutic strategies targeting resistant advanced PCa. This review systematically summarizes key signaling pathways and molecular mechanisms through which CAFs promote PCa progression, as recently discovered, evaluates the potential of CAFs as prognostic biomarkers, and discusses novel CAF-based therapeutic targets and intervention strategies for PCa.

Background Tropomyosin 3 (TPM3), one of the four tropomyosin genes, is predominantly expressed in eukaryotic cells. As a crucial regulatory protein, TPM3 associates with actin within thin myofilaments, thereby playing an essential role in the regulation of muscle contraction. Beyond its fundamental function in muscle physiology, TPM3 is implicated in oncogenesis. Objective This review elucidates the molecular mechanisms underpinning TPM3 gene fusions, delineates the tumor types associated with these fusions, and examines their clinical implications. Findings Gene fusions such as TPM3—NTRK1, TPM3—ALK, and TPM3—ROS1 have been identified as oncogenic drivers in various cancers. These fusions promote constitutive activation of tyrosine kinases, disrupt normal cellular signaling, and consequently accelerate tumorigenesis. Malignancies harboring TPM3 fusions encompass several tumor categories. With the advent of tyrosine kinase inhibitors (TKIs) targeting NTRK1, ALK, and ROS1 fusions, these rearrangements have gained significant therapeutic relevance. However, resistance mechanisms and tumor heterogeneity pose ongoing challenges to targeted therapy. Conclusion By synthesizing current evidence, this review aims to provide insights into the diagnostic, prognostic, and therapeutic landscape of TPM3—related gene fusions, fostering advancements in precision oncology.

Non-Newtonian weighted fracturing fluids are used to carry out hydraulic fracturing operations into the deep and ultra-deep earth for oil and gas extraction, though their flow and friction drag characteristics are largely unknown. This study aims to understand the abovementioned characteristics. An engineering-oriented cost-effective numerical scheme is deployed, incorporating LES with a generalized Newtonian fluid constitutive equation, for predicting the non-Newtonian pipe flow and friction drag coefficient Cf. The weighted fracturing fluid is described as a power-law fluid, i.e., viscosity μ(γ˙)=Kγ˙n−1, where both K and n are coefficients related to fluid rheology, and γ˙ is the shear rate. The influences of fluid density ρ, mean velocity U and pipe diameter D, as well as K and n on Cf were documented and compared with a water pipe flow. It was found that Cf = f1 (K, n, ρ, U, D) may be reduced to Cf = f2 (Reg), where the scaling factor Reg = ρU2−nDn/(K8n−1) is the generalized Reynolds number. This scaling law can reasonably well predict the friction drag variation in the pipe flow of non-Newtonian weighted fracturing fluids throughout a range of interests and engineering applications.

BackgroundThe seasonal variations in macroinvertebrate communities in tropical, temperate and subarctic regions have been observed and well documented to date, but similar studies conducted in subtropical rivers at the regional scale are relatively rare. In this paper, the macroinvertebrate communities from the main tributaries in the Three Gorges Reservoir Catchment (TGRC) were investigated as a function of the four seasons to explore the temporal variations in macroinvertebrate communities and further tests the temporal stability of certain metrics that are based on macroinvertebrates under a routine bioassessment framework.ResultsThe taxa richness reached the highest point in spring, followed by winter, autumn and summer. The taxa Chironomidae, Heptageniidae, Corbiculidae and Baetidae dominated the communities across seasons. The temporal variations in communities were mainly reflected in the changes in taxa proportions between seasons. The percentages of the taxa Heptageniidae and Baetidae were the highest in autumn (normal discharge period) and lowest in summer (high discharge period). The abundance of macroinvertebrates was the lowest in summer, increased in autumn and winter, and then decreased in spring. Natural fluctuations of aquatic ecosystems (temporal effects) resulted in variations that were apparent in macroinvertebrate-based metrics, such as EPT%, Baetidae%, Caenidae%, Ephemerellidae% and Hydropsychidae%.ConclusionsThe results of our study demonstrated that the macroinvertebrate communities in the main tributaries of the TGRC varied as a function of seasons. This variation was fundamentally similar to the seasonal patterns in subarctic and temperate streams. Different hydro-morphological characteristics and water quality during the high discharge period (summer), low discharge period (winter) and normal discharge period (spring and autumn) strongly affected the distribution patterns of macroinvertebrate communities. Discharge variation among seasons resulted in seasonal fluctuations in the density of macroinvertebrates. In the TGRC, autumn was the important hatching period for mayflies (Ephemeroptera). The variations in metrics related to macroinvertebrates indicated that temporal effects should not be neglected under a biomonitoring framework in future studies.