Search

Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Research into the pulmonary function of patients with transfusion-dependent thalassemia (TDT) is limited, with existing studies presenting conflicting results. We carried out a retrospective study involving 140 patients with TDT. The mean patient age was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (IQR: 2424.1–5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43 % (65 out of 140) of patients, primarily manifesting as diffusion dysfunction (26.43 %), followed by ventilatory dysfunction (5.0 %), and mixed pulmonary dysfunction (15.0 %). A serum ferritin level above 2500 ng/ml significantly correlated with the occurrence of these abnormalities(OR = 3.187, 95%CI:1.312–7.741, P = 0.010), while higher hemoglobin concentrations demonstrated a protective effect (OR = 0.966, 95%CI: 0.943–0.989, P = 0.004). Our study highlights diffusion dysfunction as the most prevalent type of pulmonary function abnormalities in TDT patients. Furthermore, it establishes a correlation between elevated serum ferritin levels and pulmonary dysfunction.

Urbanization accelerates habitat fragmentation and leads to the decline of biodiversity in cities. Urban greenway landscapes provide not only social functions but also important ecological services. In this study, taxonomic richness, abundance, diversity, and the distribution of soil meso- and microfauna were investigated in three different urban greenway landscapes to assess their environmental quality. Urban greenway landscapes that had a richer tree species composition, higher deciduous tree ratios, wider ecological greenspace, moderate soil temperature and moisture, and lower soil bulk density and less lead were conducive to the survival and development of the soil meso- and microfauna community. Different soil fauna groups had varied responses to different environmental conditions in urban greenway landscapes. Microarthropods were more sensitive to plant communities; in contrast, soil moisture was the most important abiotic driver for hygrophilous meso-micro fauna. Our study highlights the importance of deciduous trees for their rich litter input, and the wide ecological greenspace for its buffering effect on various disturbances, which promote the conservation of biodiversity in urban greenway landscapes.

Background: Hepatocellular carcinoma (HCC), which is characterized by its high malignancy, generally exhibits poor response to immunotherapy. As part of the tumor microenvironment, basement membranes (BMs) are involved in tumor development and immune activities. Presently, there is no integrated analysis linking the basement membrane with immune checkpoints, especially from the perspective of lncRNA. Methods: Based on transcriptome data from The Cancer Genome Atlas, BMs-related and immune checkpoint-related lncRNAs were identified. By applying univariable Cox regression and Machine learning (LASSO and SVM-RFE algorithm), a 10-lncRNA prognosis signature was constructed. The prognostic significance of this signature was assessed by survival analysis. GSEA, ssGSEA, and drug sensitivity analysis were conducted to investigate potential functional pathways, immune status, and clinical implications of guiding individual treatments in HCC. Finally, the promoting migration effect of LINC01224 was validated via in vitro experiments. Results: The multiple Cox regression, receiver operating characteristic curves, and stratified survival analysis of clinical subgroups exhibited the robust prognostic ability of the lncRNA signature. Results of the GSEA and drug sensitivity analysis revealed significant differences in potential functional pathways and response to drugs between the two risk groups. In addition, the risk level of HCC patients was distinctly correlated with immune cell infiltration status. More importantly, LINC01224 was independently associated with the OS of HCC patients (P

In coronavirus disease 2019 (COVID-19) patients, interleukin (IL)-6 is one of the leading factors causing death through cytokine release syndrome. Hence, identification of IL-6 downstream from clinical patients’ transcriptome is very valid for analyses of its mechanism. However, clinical study is conditional and time consuming to collect optional size of samples, as patients have the clinical heterogeneity. A possible solution is to deeply mine the relative existing data. Several transcriptome-based studies on other diseases or treatments have revealed different genes to be regulated by IL-6. Through our meta-analysis of these transcriptome datasets, 352 genes were suggested to be regulated by IL-6 in different biological conditions, some of which were related to virus infection and cardiovascular disease. Among them, 232 genes were not identified by current transcriptome studies from clinical research. ICAM1 and PFKFB3 were the most significantly upregulated genes in our meta-analysis and could be employed as biomarkers in patients with severe COVID-19. In general, a meta-analysis of transcriptome datasets could be an alternative way to analyze the immune response and complications of patients suffering from severe COVID-19 and other emergency diseases.

Microbial communities are an important component of aquatic ecosystems. They play active roles in the biogeochemical cycles of organic matter and nutrients to maintain the health and stability of aquatic ecosystems. In the present study, the shifts in microbial communities in overlying water of 15 shallow lakes with different trophic states in Hubei Province (China) were assessed using Illumina MiSeq sequencing technology. The results revealed that the proteobacteria to be the most abundant phylum in lakes with different trophic states. Mesotrophic lakes were found to be similar to moderately eutrophic lakes in terms of the microbial community composition, the interrelation between microbial communities, and expression level of metabolic pathways. In mesotrophic and moderately eutrophic lakes, Bacillus and Pseudomonas were the dominant genera in overlying water. In lakes with less eutrophication, the microbial diversity tended to be higher. Lightly eutrophic lakes had the most microbial species; however, the interaction between microorganisms was the weakest in these lakes and the internal steady-state balance of the lakes was most susceptible to being broken. These results indicate that lightly eutrophication may be one of the most unstable transition states in the eutrophication process. Particulate organic matter, chlorophyll-a, and ammonium nitrogen were the main drivers affecting the distribution of microbial communities in the overlying water of lakes with different trophic states. In addition, the correlation between microbial communities and lake trophic states was analyzed based on the bacterial eutrophic index (BEI). An obvious positive correlation was noted between BEI and the trophic level index (TLI), indicating that microbial communities could play a role as biological factors in the evaluation of lake trophic states along with other known physicochemical indicators.

In this research, the effect of the mode-coupling branches/channels on harmonic amplitudes in single-mode classical Rayleigh-Taylor instability for arbitrary Atwood numbers in the weakly nonlinear stage is investigated by employing the tracking technology of the mode coupling up to the fifth order. When the effect of the mode-coupling channels is not taken into account (i.e., this effect is automatically merged in the derivation process), our results are the same as the first five-order results from the prediction of previous literatures within the framework of tenth-order perturbation theory (Liu et al., 2012). In the progress of the mode coupling, the tracking technology of the channel parameters equal to constant 1 is used and all the mode-coupling channels are distinctly extracted. It is found that the nth-harmonic amplitude with mth order mainly depends on fm,n factor. However, this factor comes from different mode-coupling branches which are either constant or variable with Atwood numbers A. For the channels with A, they can either strengthen or inhibit the growth of the relevant harmonic. For some channels, they are closed all the time for some fixed A.

In this work, the distribution of organic phosphorus (Po) species in sediment profiles of five shallow lakes was analyzed and its effect on the photo-release of dissolved phosphate (Pi) was investigated during sediment resuspension under simulated sunlight irradiation. The results show that Po was highly enriched in the surface sediment and gradually decreased as sediment depths increased: 33.10 ± 2.55–96.71 ± 7.60 mg/kg, 33.55 ± 2.34–142.86 ± 5.73 mg/kg, 57.50 ± 3.46–149.68 ± 7.67 mg/kg, 55.18 ± 4.67–168.73 ± 8.31 mg/kg, 98.75 ± 7.56–275.74 ± 10.70 mg/kg for Lake Hou, Lake Tuan, Lake Tangling, Lake Guozheng and Lake Miao, respectively. The photo-release amount of dissolved Pi in the resuspension composed of surface sediments was also higher than that of deep sediment during sediment resuspension under the simulated sunlight irradiation for 9 h. The potential reasons for these results are: (1) difference in morphology and composition of sediments at different depths: the mean particle size of sediment decreased first and then increased as sediment depths increased; (2) difference in composition of Po species with depths in the sediment profiles: more photolytic Po species existed in surface sediments confirmed by sequential extraction and 31P NMR analysis; and (3) more OH production in the resuspension composed of surface sediment under simulated sunlight irradiation, which directly influence the photo-release of dissolved Pi from photodegradation of organic phosphorus. All of these results indicate that the distribution of organic phosphorus species in the sediment profiles plays an important role in P cycle and its photodegradation during sediment resuspension may be one of the potential pathways for phosphate supplement in shallow lakes. Keywords: Sediment, Organic phosphorus, Photo-release, 31P NMR, Phosphate