Development and experimental validation of an M2 macrophage and platelet-associated gene signature to predict prognosis and immunotherapy sensitivity in bladder cancer.

Platelets and M2 macrophages both play crucial roles in tumorigenesis, but their relationship and the prognosis value of the relative genes in bladder cancer (BLCA) remain obscure. In the present study, we found that platelets stimulated by BLCA cell lines could promote M2 macrophage polarization, and platelets were significantly associated with the infiltration of M2 macrophages in BLCA samples. Through the bioinformatic analyses, A2M, TGFB3, and MYLK, which were associated with platelets and M2 macrophages, were identified and verified in vitro and then included in the predictive model. A platelet and M2 macrophage-related gene signature was constructed to evaluate the prognosis and immunotherapeutic sensitivity, helping to guide personalized treatment and to disclose the underlying mechanisms.

A review focusing on mechanisms and ecological risks of enrichment and propagation of antibiotic resistance genes and mobile genetic elements by microplastic biofilms.

Microplastics (MPs) are emerging ubiquitous pollutants in aquatic environment and have received extensive global attention. In addition to the traditional studies related to the toxicity of MPs and their carrier effects, their unique surface-induced biofilm formation also increases the ecotoxicity potential of MPs from multiple perspectives. In this review, the ecological risks of MPs biofilms were summarized and assessed in detail from several aspects, including the formation and factors affecting the development of MPs biofilms, the selective enrichment and propagation mechanisms of current pollution status of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in MPs biofilms, the dominant bacterial communities in MPs biofilms, as well as the potential risks of ARGs and MGEs transferring from MPs biofilms to aquatic organisms. On this basis, this paper also put forward the inadequacy and prospects of the current research and revealed that the MGEs-mediated ARG propagation on MPs under actual environmental conditions and the ecological risk of the transmission of ARGs and MGEs to aquatic organisms and human beings are hot spots for future research. Relevant research from the perspective of MPs biofilm should be carried out as soon as possible to provide support for the ecological pollution prevention and control of MPs.

Microbial necromass in cropland soils: A global meta-analysis of management effects.

Microbial necromass is a large and persistent component of soil organic carbon (SOC), especially under croplands. The effects of cropland management on microbial necromass accumulation and its contribution to SOC have been measured in individual studies but have not yet been summarized on the global scale. We conducted a meta-analysis of 481-paired measurements from cropland soils to examine the management effects on microbial necromass and identify the optimal conditions for its accumulation. Nitrogen fertilization increased total microbial necromass C by 12%, cover crops by 14%, no or reduced tillage (NT/RT) by 20%, manure by 21%, and straw amendment by 21%. Microbial necromass accumulation was independent of biochar addition. NT/RT and straw amendment increased fungal necromass and its contribution to SOC more than bacterial necromass. Manure increased bacterial necromass higher than fungal, leading to decreased ratio of fungal-to-bacterial necromass. Greater microbial necromass increases after straw amendments were common under semi-arid and in cool climates in soils with pH <8, and were proportional to the amount of straw input. In contrast, NT/RT increased microbial necromass mainly under warm and humid climates. Manure application increased microbial necromass irrespective of soil properties and climate. Management effects were especially strong when applied during medium (3-10 years) to long (10+ years) periods to soils with larger initial SOC contents, but were absent in sandy soils. Close positive links between microbial biomass, necromass and SOC indicate the important role of stabilized microbial products for C accrual. Microbial necromass contribution to SOC increment (accumulation efficiency) under NT/RT, cover crops, manure and straw amendment ranged from 45% to 52%, which was 9%-16% larger than under N fertilization. In summary, long-term cropland management increases SOC by enhancing microbial necromass accumulation, and optimizing microbial necromass accumulation and its contribution to SOC sequestration requires site-specific management.

Ergothioneine attenuates varicocele-induced testicular damage by upregulating HSP90AA1 in rats.

This study investigates the therapeutic effect and the underlying mechanisms of ergothioneine (EGT) on the testicular damage caused by varicocele (VC) in vivo, in vitro, and in silico. This preclinical study combines a series of biological experiments and network pharmacology analyses. A total of 18 Sprague Dawley (SD) male rats were randomly and averagely divided into three groups: the sham-operated, VC model, and VC model with EGT treatment (VC + EGT) groups. The left renal vein of the VC model and the VC + EGT groups were half-ligated for 4 weeks. Meanwhile, the VC + EGT group was intragastrically administrated with EGT (10 mg/kg). GC1 and GC2 cells were exposed to H2 O2 with or without EGT treatment to re-verify the conclusion. The structure disorder of seminiferous tubules ameliorated the apoptosis decrease in the VC rats receiving EGT. EGT can also increase the sperm quality of the VC model rats (p < 0.05). The exposure to H2 O2 decreased proliferation and increased apoptosis of GC1 and GC2 cells, which was revisable by adding EGT to the plates (p < 0.05). The network pharmacology and molecular docking were conducted to explore the potential targets of EGT in VC, and HSP90AA1 was identified as the pivotal gene, which was validated by western blot, immunohistochemistry, and RT-qPCR both in vivo and in vitro (p < 0.05). Overall, EGT attenuates the testicular injury in the VC model both in vivo and in vitro by potentially potentiating the expression of HSP90AA1.

PEDF inhibits LPS-induced acute lung injury in rats and promotes lung epithelial cell survival by upregulating PPAR-γ.

BACKGROUND: The progression of acute lung injury (ALI) involves numerous pathological factors and complex mechanisms, and cause the destruction of epithelial and endothelial barriers. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-inflammatory factor. The purpose of this study was to investigate the effect of PEDF on lipopolysaccharide (LPS)-induced ALI in rats. METHODS: In vivo, pathological and injury related factors examination were performed on rat lung to investigate the effect of PEDF on ALI. In vitro, the effect of PEDF on inflammatory injury and apoptosis of lung epithelial type II RLE-6TN cell was evaluated, and the expression of inflammatory factors and related pathway proteins and PPAR-γ (in the presence or absence of PPAR-γ inhibitors) were analyzed. RESULTS: In vivo results showed that PEDF inhibited the inflammatory factor expression (TNF-α, IL-6 and IL-1ß) and progression of ALI and reduced lung cell apoptosis in rats. In vitro results showed that PEDF could effectively inhibit LPS-stimulated inflammatory damage and apoptosis of RLE-6TN cells. PEDF inhibited the RLE-6TN cell injury by enhancing the expression of PPAR-γ. CONCLUSIONS: PEDF is an anti-inflammatory factor, which can inhibit apoptosis of lung epithelial cells by upregulating the expression of PPAR-γ and reducing LPS-induced ALI in rats.

Construction and experimental validation of a B cell senescence-related gene signature to evaluate prognosis and immunotherapeutic sensitivity in bladder cancer.

Senescent B cells exhibit reduced antibody production and enhanced proinflammatory cytokine and chemokine secretion, exerting non-negligible functions in antitumor immunity. This study aims to clarify the prognosis value of B cell senescence-related genes in bladder cancer (BLCA). Twelve B cell senescence-related genes were identified based on previous studies and the single-cell RNA sequencing of a BLCA sample from Gene Expression Omnibus (GEO). The Cancer Genome Atlas BLCA cohort was used as the training dataset. Three cohorts from GEO, 35 clinical samples from the local hospital, and in vitro cell experiments were used for validation. The unsupervised clustering based on the 12 genes was associated with the prognosis and the tumor immunity. Through least absolute shrinkage and selection operator regression and random forest algorithm, G protein subunit gamma 11 (GNG11) and inhibitor of DNA binding 1 (ID1) of the 12 genes were determined as significant prognosis predictors and then included in the multivariate Cox regression model. The model was a reliable and robust prognosis biomarker across multiple large-scale cohorts (pooled HR = 1.76, 95% CI = 1.41-2.20). The tight association between the model and BLCA malignant degree was demonstrated in the local cohort (P < 0.01). The model could also predict the immunotherapeutic sensitivity, which was confirmed by the tumor immune dysfunction and exclusion algorithm (P < 0.0001) and IMvigor210 cohort (P < 0.0001). At last, in vitro cell experiments in IM-9 and GM12878 B cells indicated that GNG11 and ID1 were involved in the cellular aging process. Collectively, a B cell senescence-related gene signature was constructed to evaluate the prognosis and immunotherapeutic response in BLCA, providing novel insights into the biological mechanisms.

12(S)-hydroxyeicosatetraenoic acid is significantly increased in diabetic kidney disease and associated with renal function decline.

AIMS: 12(S)-hydroxyeicosatetraenoic (12(S)-HETE), an alternate arachidonic acid metabolite, has been recently examined in metabolic disease. However, the role of 12(S)-HETE in diabetic kidney disease (DKD) remains unclear. We studied for the first time the relationship of serum 12(S)-HETE and DKD and renal function parameters in a Chinese population. MATERIALS AND METHODS: We recruited 275 subjects who were diagnosed with type 2 diabetes (T2DM) for more than 10 years, including 149 DKD patients and 126 T2DM patients without DKD. Serum 12(S)-HETE was measured using the enzyme-linked immunosorbent assay. RESULTS: Serum 12(S)-HETE was significantly higher in DKD patients than controls [384.69 (77.54, 1003.05) pg/ml and 17.77 (8.11, 75.13) pg/ml, respectively, p < 0.0001]. Compared to controls, 12(S)-HETE was significantly increased in both macroalbuminuria and microalbuminuria groups (p < 0.0001). Further, the macroalbuminuria group also had a higher serum 12(S)-HETE level compared to the microalbuminuria group (p = 0.0063). Moreover, serum 12(S)-HETE was positively correlated with the albuminuria level (r = 0.5833, p < 0.0001), serum creatinine (r = 0.2725, p < 0.0001), and was negatively associated with the estimated glomerular filtration rate (r = -0.2085, p = 0.0005). Further, receiver operating characteristic analysis (ROC) revealed that 12(S)-HETE had a good performance of distinguishing DKD from controls (AUC 0.828) with a sensitivity of 0.913 and a specificity of 0.711. CONCLUSION: Our findings revealed that serum 12(S)-HETE significantly associated with DKD and disease severity, suggesting that serum 12(S)-HETE may be used as a potential biomarker for the early diagnosis of DKD.

Biodegradation of 2-ethylhexyl-4-methoxycinnamate in river sediments and its impact on microbial communities.

Numerous studies have evaluated the toxicity and endocrine disrupting properties of organic UV filters for aquatic organisms, but little is known about their biodegradation in river sediments and their impact on microorganisms. We have set up the sterile and microbiological systems in the laboratory, adding 2-ethylhexyl-4-methoxycinnamate (EHMC), one of organic UV filters included in the list of high yield chemicals, at concentrations of 2, 20 and 200 µg/L, and characterized the microbial community composition and diversity in sediments. Monitoring of EHMC degradation within 30 days revealed that the half-life in the microbial system (3.49 days) was much shorter than that in the sterile system (7.55 days). Two potential degradation products, 4-mercaptobenzoic acid and 3-methoxyphenol were identified in the microbial system. Furthermore, high-throughput 16s and 18s rRNA gene sequencing showed that Proteobacteria dominated the sediment bacterial assemblages followed by Chloroflexi, Acidobacteria, Bacteroidetes and Nitrospirae; Eukaryota_uncultured fungus dominated the sediment fungal assemblages. Correlation analysis demonstrated that two bacterium genera (Anaerolineaceae_uncultured and Burkholderiaceae_uncultured) were significantly correlated with the biodegradation of EHMC. These results illustrate the biodegradability of EHMC in river sediments and its potential impact on microbial communities, which can provide useful information for eliminating the pollution of organic UV filters in natural river systems and assessing their potential ecological risks.

A Low-Power CMOS Wireless Acoustic Sensing Platform for Remote Surveillance Applications.

A low-power wireless acoustic sensing platform for remote surveillance applications based on a 180 nm CMOS technology is proposed in this paper. The audio signal, which is acquired by a microphone, is first amplified and filtered. Then, the analog signal is converted to a digital signal by a 10-bit analog-to-digital converter (ADC). A digital automatic gain control module is integrated to obtain an optimal input of the ADC. The digital signal is modulated and transmitted at the 433 MHz ISM band after being repacked and encoded. To save power for portable applications, the chip switches to standby mode when no audio is detected. The wireless sensing platform occupies a chip area of 1.76 mm 2 . The supply voltage is 2.5 V for the power amplifier and 1.8 V for other circuits. The measured maximum output power is 5.7 dBm and the transmission distance is over 500 m for real application scenarios. The chip consumes 25.1 mW power in normal work mode and 0.058 mW in standby mode. Compared to existing wireless acoustic sensors, the proposed wireless acoustic sensing platform can achieve features such as compactness, power efficiency, and reliability.

Effect of cadmium and polystyrene nanoplastics on the growth, antioxidant content, ionome, and metabolism of dandelion seedlings.

Cadmium is the most prevalent heavy metal pollutant in the environment and can be readily combined with micro/nanoplastics (M/NPs) to change their bioavailability. In the present study, we comprehensively investigated the effect of polystyrene (PS) NPs on dandelion plants grown under Cd stress. Cd exposure significantly inhibited the growth of dandelion seedlings, resulting in a decrease in seedling elongation from 26.47% to 28.83%, a reduction in biomass from 29.76% to 54.14%, and an exacerbation of lipid peroxidation and oxidative stress. The interaction between PS NPs and Cd resulted in the formation of larger aggregates, with the Cd bioavailability reduced by 12.56%. PS NPs affect ion absorption by regulating reactive oxygen production and increasing superoxide dismutase activity, thereby mitigating the adverse effects of Cd. PSCd aggregates induced significant changes in the metabolic profiles of dandelions, affecting various carbohydrates related to alcohols, organic acids, sugar metabolism, and bioactive components related to flavonoids and phenolic acids. Furthermore, based on a structural equation model, exposure to PSCd activated oxidative stress and nutrient absorption, thereby affecting plant growth and Cd accumulation. Overall, our study provides valuable insights into the effects of PS NPs on Cd bioavailability, accumulation, and plant growth, which are crucial for understanding the food safety of medicinal plants in a coexistence environment.