Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Confined water-encapsulated activated carbon for capturing short-chain perfluoroalkyl and polyfluoroalkyl substances from drinking water.

The global ecological crisis of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in drinking water has gradually shifted from long-chain to short-chain PFASs; however, the widespread established PFAS adsorption technology cannot cope with the impact of such hydrophilic pollutants given the inherent defects of solid-liquid mass transfer. Herein, we describe a reagent-free and low-cost strategy to reduce the energy state of short-chain PFASs in hydrophobic nanopores by employing an in situ constructed confined water structure in activated carbon (AC). Through direct (driving force) and indirect (assisted slip) effects, the confined water introduced a dual-drive mode in the confined water-encapsulated activated carbon (CW-AC) and completely eliminated the mass transfer barrier (3.27 to 5.66 kcal/mol), which caused the CW-AC to exhibit the highest adsorption capacity for various short-chain PFASs (C-F number: 3-6) among parent AC and other adsorbents reported. Meanwhile, benefiting from the chain length- and functional group-dependent confined water-binding pattern, the affinity of the CW-AC surpassed the traditional hydrophobicity dominance and shifted toward hydrophilic short-chain PFASs that easily escaped treatment. Importantly, the ability of CW-AC functionality to directly transfer to existing adsorption devices was verified, which could treat 21,000 bed volumes of environment-related high-load (~350 ng/L short-chain PFAS each) real drinking water to below the World Health Organization's standard. Overall, our results provide a green and cost-effective in situ upgrade scheme for existing adsorption devices to address the short-chain PFAS crisis.

HGCLAMIR: Hypergraph contrastive learning with attention mechanism and integrated multi-view representation for predicting miRNA-disease associations.

Existing studies have shown that the abnormal expression of microRNAs (miRNAs) usually leads to the occurrence and development of human diseases. Identifying disease-related miRNAs contributes to studying the pathogenesis of diseases at the molecular level. As traditional biological experiments are time-consuming and expensive, computational methods have been used as an effective complement to infer the potential associations between miRNAs and diseases. However, most of the existing computational methods still face three main challenges: (i) learning of high-order relations; (ii) insufficient representation learning ability; (iii) importance learning and integration of multi-view embedding representation. To this end, we developed a HyperGraph Contrastive Learning with view-aware Attention Mechanism and Integrated multi-view Representation (HGCLAMIR) model to discover potential miRNA-disease associations. First, hypergraph convolutional network (HGCN) was utilized to capture high-order complex relations from hypergraphs related to miRNAs and diseases. Then, we combined HGCN with contrastive learning to improve and enhance the embedded representation learning ability of HGCN. Moreover, we introduced view-aware attention mechanism to adaptively weight the embedded representations of different views, thereby obtaining the importance of multi-view latent representations. Next, we innovatively proposed integrated representation learning to integrate the embedded representation information of multiple views for obtaining more reasonable embedding information. Finally, the integrated representation information was fed into a neural network-based matrix completion method to perform miRNA-disease association prediction. Experimental results on the cross-validation set and independent test set indicated that HGCLAMIR can achieve better prediction performance than other baseline models. Furthermore, the results of case studies and enrichment analysis further demonstrated the accuracy of HGCLAMIR and unconfirmed potential associations had biological significance.

Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target.

YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, its biological functions in bladder cancer remains to be proven. We analysed variations in YARS1 expression and survival in bladder cancer using multiple data sets, including TCGA-BLCA, GSE13507 and bladder cancer-specific tissue microarrays. Furthermore, we explored the biological functions of YARS1 using transcriptome data. Our findings revealed a noteworthy correlation between YARS1 and immune infiltration in bladder cancer, as determined using the XCELL algorithm and single-cell analysis. In addition, we employed the TIDE algorithm to evaluate the responsiveness of different cohorts to immune checkpoint therapy. We investigated the regulatory associations between YARS1 and various aspects of bladder cancer, including senescence, ferroptosis and stemness. Finally, we established a ceRNA network that is directly linked to the overall prognosis, YARS1 can serve as a prognostic biomarker for bladder cancer; its interaction with MYC has implications for bladder cancer cell senescence, ferroptosis and stemness. Moreover, the identified ceRNA network has potential as a therapeutic target in bladder cancer.

Enzymatic Activation and Continuous Electrochemical Production of Methane from Dilute CO2 Sources with a Self-Healing Capsule.

Converting dilute CO2 source into value-added chemicals and fuels is a promising route to reduce fossil fuel consumption and greenhouse gas emission, but integrating electrocatalysis with CO2 capture still faced marked challenges. Herein, we show that a self-healing metal-organic macrocycle functionalized as an electrochemical catalyst to selectively produce methane from flue gas and air with the lowest applied potential so far (0.06 V vs reversible hydrogen electrode, RHE) through an enzymatic activation fashion. The capsule emulates the enzyme' pocket to abstract one in situ-formed CO2-adduct molecule with the commercial amino alcohols, forming an easy-to-reduce substrate-involving clathrate to combine the CO2 capture with electroreduction for a thorough CO2 reduction. We find that the self-healing system exhibited enzymatic kinetics for the first time with the Michaelis-Menten mechanism in the electrochemical reduction of CO2 and maintained a methane Faraday efficiency (FE) of 74.24% with a selectivity of over 99% for continuous operation over 200 h. A consecutive working lab at 50 mA·cm-2, in an eleven-for-one (10 h working and 1 h healing) electrolysis manner, gives a methane turnover number (TON) of more than 10,000 within 100 h. The integrated electrolysis with CO2 capture facilitates the thorough reduction of flue gas (ca. 13.0% of CO2) and first time of air (ca. 400 ppm of CO2 to 42.7 mL CH4 from 1.0 m3 air). The new self-healing strategy of molecular electrocatalyst with an enzymatic activation manner and anodic shifting of the applied potentials provided a departure from the existing electrochemical catalytic techniques.

Addressing Challenges in Ion-Selectivity Characterization in Nanopores.

Ion selectivity is the basis for designing smart nanopore/channel-based devices, e.g., ion separators and biosensors. Quantitative characterization of ion selectivities in nanopores often employs the Nernst or Goldman-Hodgkin-Katz (GHK) equation to interpret transmembrane potentials. However, the direction of the measured transmembrane potential drop is not specified in these equations, and selectivity values calculated using absolute values of transmembrane potentials do not directly reveal the ion for which the membrane is selective. Moreover, researchers arbitrarily choose whether to use the Nernst or GHK equation and overlook the significant differences between them, leading to ineffective quantitative comparisons between studies. This work addresses these challenges through (a) specifying the transmembrane potential (sign) and salt concentrations in terms of working and reference electrodes and the solutions in which they reside when using the Nernst and GHK equations, (b) reporting of both Nernst-selectivity and GHK-selectivity along with solution compositions and transmembrane potentials when comparing different nanopores/channels, and (c) performing simulations to define an ideal selectivity for nanochannels. Experimental and modeling studies provide significant insight into these fundamental equations and guidelines for the development of nanopore/channel-based devices.

Pore-Size-Dependent Role of Functional Elements at the Outer Surface and Inner Wall in Single-Nanochannel Biosensors.

Biological nanopores feature functional elements on the outer surfaces (FEOS) and inner walls (FEIW), enabling precise control over ions and molecules with exceptional sensitivity and specificity. This provides valuable inspiration to scientists for the development of intelligent artificial nanochannel-based platforms, with a wide range of potential applications, including biosensors. Much effort has been dedicated to investigating the distinct contribution of FEOS and FEIW of multichannel membrane biosensors. However, the intricate interactions among neighboring pores in multichannel biosensors have presented challenges. This underscores the untapped potential of single nanochannels as ideal candidates in this field. Here, we employed single nanochannel membranes with different pore sizes to investigate the distinct contributions of FEIW and FEOS to single-nanochannel biosensors, combined with numerical simulations. Our findings revealed that alterations in the negative charges of FEIW and FEOS, induced by target binding, have differential effects on ion transport, contingent upon the degree of nanoconfinement. In the case of smaller pores, such as 20 nm, the ion concentration polarization driven by FEIW can independently control ion transport through the surface's electric double layer. However, as the pore size increases to 40-60 nm, both FEIW and FEOS become essential for effective ion concentration polarization. When the pore size reaches 100 nm, both FEIW and FEOS are ineffective and thus unsuitable for biosensors. Simulations demonstrate that the observed phenomena can be attributed to the interactions between the charges of FEIW and FEOS within the overlapping electric double layer under confinement. These results underscore the critical role of pore size as a key parameter in governing the functionality of probes within or on nanopore-based biosensors as well as in the design of nanopore-based devices.

Precise Regulation in Chain-Edge Structural Microenvironments of 1D Covalent Organic Frameworks for Photocatalysis.

Covalent organic frameworks (COFs) constitute a promising research topic for photocatalytic reactions, but the rules and conformational relationships of 1D COFs are poorly defined. Herein, the chain edge structure is designed by precise modulation at the atomic level, and the 1D COFs bonded by C, O, and S elements is directionally prepared for oxygen-tolerant photoinduced electron transfer-atom transfer radical polymerization (PET-ATRP) reactions. It is demonstrated that heteroatom-type chain edge structures (─O─, ─S─) lead to a decrease in intra-plane conjugation, which restricts the effective transport of photogenerated electrons along the direction of the 1D strip. In contrast, the all-carbon type chain edge structure (─C─) with higher intra-plane conjugation not only reduces the energy loss of photoexcited electrons but also enhances the carrier density, which exhibits the optimal photopolymerization performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance. This work offers valuable guidance in the exploitation of 1D COFs for high photocatalytic performance.

Bacterial isolation and genome analysis of a novel Klebsiella quasipneumoniae phage in southwest China's karst area.

BACKGROUND: Southwest China is one of the largest karst regions in the world. Karst environment is relatively fragile and vulnerable to human activities. Due to the discharge of sewage and domestic garbage, the karst system may be polluted by pathogenic bacteria. The detection of bacterial distribution and identification of phage capable of infecting them is an important approach for environmental assessment and resource acquisition. METHODS: Bacteria and phages were isolated from karst water in southwest China using the plate scribing and double plate method, respectively. Isolated phage was defined by transmission electron microscopy, one-step growth curve and optimal multiplicity of infection (MOI). Genomic sequencing, phylogenetic analysis, comparative genomic and proteomic analysis were performed. RESULTS: A Klebsiella quasipneumoniae phage was isolated from 32 isolates and named KL01. KL01 is morphologically identified as Caudoviricetes with an optimal MOI of 0.1, an incubation period of 10 min, and a lysis period of 60 min. The genome length of KL01 is about 45 kb, the GC content is 42.5%, and it contains 59 open reading frames. The highest average nucleotide similarity between KL01 and a known Klebsiella phage 6939 was 83.04%. CONCLUSIONS: KL01 is a novel phage, belonging to the Autophagoviridae, which has strong lytic ability. This study indicates that there were not only some potential potentially pathogenic bacteria in the karst environment, but also phage resources for exploration and application.

Tailoring Cu-Based Electrocatalysts for Enhanced Electrochemical CO2 Reduction to Alcohols: Structure-Selectivity Relationship.

The use of CO2 as a feedstock for the production of carbon-based fuels and value-added chemicals offers a promising route toward carbon neutrality. In this study, two Cu-based electrocatalysts, namely, Cu24/N-C and Cu2/N-C, are successfully prepared by thermal treatment of Cu24 metal-organic polyhedron-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocrystals (Cu24/ZIF-8) and Cu2 dinuclear compound-loaded ZIF-8 nanocrystals (Cu2/ZIF-8), respectively. Extensive structural and compositional analyses were conducted to confirm the formation of Cu nanocluster-loaded N-doped porous carbon supports in both Cu24/N-C and Cu2/N-C and Cu nanoparticles encapsulated by graphitic carbons in Cu2/N-C as well. These two Cu-based electrocatalysts exhibited different behaviors in the electrochemical CO2 reduction reaction (CO2RR). The Cu24/N-C electrocatalyst showed high selectivity for CO production, while Cu2/N-C showed a preference for alcohol generation. The excellent stability of Cu2/N-C over a 30 h continuous electrochemical reduction further highlights its potential for practical applications. The difference in electrocatalytic performance observed in the two catalysts for CO2RR was attributed to distinct catalytic sites associated with Cu nanoclusters and nanoparticles. This research reveals the significance of their structures and compositions for the development of highly selective electrocatalysts for CO2 reduction.

Modeling tuberculosis transmission flow in China, 2010-2012.

BACKGROUND: China has the third largest number of TB cases in the world, and the average annual floating population in China is more than 200 million, the increasing floating population across regions has a tremendous potential for spreading infectious diseases, however, the role of increasing massive floating population in tuberculosis transmission is yet unclear in China. METHODS: 29,667 tuberculosis flow data were derived from the new smear-positive pulmonary tuberculosis cases in China. Spatial variation of TB transmission was measured by geodetector q-statistic and spatial interaction model was used to model the tuberculosis flow and the regional socioeconomic factors. RESULTS: Tuberculosis transmission flow presented spatial heterogeneity. The Pearl River Delta in southern China and the Yangtze River Delta along China's east coast presented as the largest destination and concentration areas of tuberculosis inflows. Socioeconomic factors were determinants of tuberculosis flow. Some impact factors showed different spatial associations with tuberculosis transmission flow. A 10% increase in per capita GDP was associated with 10.2% in 2010 or 2.1% in 2012 decrease in tuberculosis outflows from the provinces of origin, and 1.2% in 2010 or 0.5% increase in tuberculosis inflows to the destinations and 18.9% increase in intraprovincial flow in 2012. Per capita net income of rural households and per capita disposable income of urban households were positively associated with tuberculosis flows. A 10% increase in per capita net income corresponded to 14.0% in 2010 or 3.6% in 2012 increase in outflows from the origin, 44.2% in 2010 or 12.8% increase in inflows to the destinations and 47.9% increase in intraprovincial flows in 2012. Tuberculosis incidence had positive impacts on tuberculosis flows. A 10% increase in the number of tuberculosis cases corresponded to 2.2% in 2010 or 1.1% in 2012 increase in tuberculosis inflows to the destinations, 5.2% in 2010 or 2.0% in 2012 increase in outflows from the origins, 11.5% in 2010 or 2.2% in 2012 increase in intraprovincial flows. CONCLUSIONS: Tuberculosis flows had clear spatial stratified heterogeneity and spatial autocorrelation, regional socio-economic characteristics had diverse and statistically significant effects on tuberculosis flows in the origin and destination, and income factor played an important role among the determinants.

Enterovibrio qingdaonensis sp. nov. and Enterovibrio gelatinilyticus sp. nov., two marine bacteria isolated from surface seawater of Qingdao offshore.

Two Gram-stain-negative, facultatively anaerobic, motile, and rod-shaped marine bacteria, designated strains ZSDZ35T and ZSDZ42T, were isolated from surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA genes and whole genome data placed ZSDZ35T and ZSDZ42T within the genus Enterovibrio. Strain ZSDZ35T was most closely related to Enterovibrio nigricans DSM 22720T with 97.55% sequence similarity, whereas ZSDZ42T was most closely related to Enterovibrio calviensis DSM 14347T with 98.97% sequence similarity. Strain ZSDZ35T grew with 0-8% (w/v) NaCl (optimum 4%), at 16-37 °C (optimum 28 °C) and pH 6.0-9.0 (optimum pH 8.0); whereas strain ZSDZ42T grew with 1-7% (w/v) NaCl (5%), at 4-28 °C (8 °C) and pH 6.0-9.0 (pH 7.0). Both strains shared the same major fatty acid components of summed feature 3 (C16:1ω7c or/and C16:1ω6c), summed feature 8 (C18:1ω7c and C18:1ω6c) and C16:0, with different proportions. The DNA G + C contents of strains ZSDZ35T and ZSDZ42T were 47.2% and 46.7%, respectively. Based on the results of polyphasic analyses, ZSDZ35T and ZSDZ42T are considered to represent novel species, for which the names Enterovibrio qingdaonensis sp. nov. (type strain, ZSDZ35T = MCCC 1K06293T = KCTC 82887T) and Enterovibrio gelatinilyticus sp. nov. (type strain, ZSDZ42T = MCCC 1K06294T = KCTC 82886T) are proposed, respectively.

Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models.

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

Air pollution's numerical, spatial, and temporal heterogeneous impacts on childhood hand, foot and mouth disease: a multi-model county-level study from China.

BACKGROUND: While stationary links between childhood hand, foot and mouth disease (HFMD) and air pollution are known, a comprehensive study on their heterogeneous relationships (nonstationarity), jointly considering numerical, temporal and spatial dimensions, has not been reported. METHODS: Monthly HFMD incidence and air pollution data were collected at the county level from Sichuan-Chongqing, China (2009-2011), alongside meteorological and social environmental covariates. Key influential factors were identified using random forest (RF) under the stationary assumption. Factors' numerically, temporally, and spatially heterogeneous relationships with HFMD were assessed using generalized additive model (GAM) and geographically and temporally weighted regression (GTWR). RESULTS: Our findings highlighted the relatively higher stationary contributions of fine particulate matter (PM2.5) and ozone (O3) to HFMD incidence across Sichuan-Chongqing counties. We further uncovered heterogeneous impacts of PM2.5 and O3 from three nonstationary perspectives. Numerically, PM2.5 showed an inverse 'V'-shaped relationship with HFMD incidence, while O3 exhibited a complex pattern, with increased HFMD incidence at low PM2.5 and moderate O3 concentrations. Temporally, PM2.5's impact peaked in autumn and was weakest in spring, whereas O3's effect was strongest in summer. Spatially, hotspot mapping revealed high-risk clusters for PM2.5 impact across all seasons, with notable geographical variations, and for O3 in spring, summer, and autumn, concentrated in specific regions of Sichuan-Chongqing. CONCLUSIONS: This study underscores the nuanced and three-perspective heterogeneous influences of air pollution on HFMD in small areas, emphasizing the need for differentiated, localized, and time-sensitive prevention and control strategies to enhance the precision of dynamic early warnings and predictive models for HFMD and other infectious diseases, particularly in the fields of environmental and spatial epidemiology.

Heat shock protein family A member 8 is a prognostic marker for bladder cancer: Evidences based on experiments and machine learning.

Heat shock protein member 8 (HSPA8) is one of the most abundant chaperones in eukaryotic cells, but its biological roles in bladder cancer (BC) are largely unclear. First, we observed that HSPA8 was abundant in both cell lines and tissues of BC, and the HSPA8-high group had poorer T stages and overall survival (OS) than the HSPA8-low group in the TCGA patients. Next, when we knocked down HSPA8 in BC cells, the growth and migration abilities were significantly decreased, the apoptosis rates were significantly increased, and the Ki67 fluorescence intensity was decreased in BC cells. Moreover, caspase 3 was significantly decreased with overexpression of HSPA8 in BC cells. After that, a machine learning prognostic model was created based on the expression of HSPA8 by applying LASSO Cox regression in TCGA and GEO patients. The model indicated that the low-risk (LR) group with BC had better tumour stages, lymphovascular invasion, and OS than the high-risk (HR) group. Additionally, the risk score was demonstrated to be an independent risk factor for the prognosis of BC by univariate and multivariate Cox analyses. Moreover, the HR group showed a greater rate of TP53 mutations and was mostly enriched in the ECM-receptor interaction pathway than the LR group. Importantly, lower CD8+ T-cell and NK cell infiltration, higher immune exclusion scores, higher expression of PD-L1 and CTLA4 and poorer immune checkpoint therapy effects were found in the HR group. These findings demonstrated how crucial HSPA8 plays a role in determining the prognosis of bladder cancer.

Ultra-fast Redox Pulse for Stable Electrochemiluminescence on AuNP-Based Biosensors and Mechanism Investigation.

A novel sandwich-type biosensor denoted as "MIP-analyte-Ab" was constructed on a glassy carbon electrode modified with gold nanoparticles (AuNPs@GCE), which is dedicated to explore a general solution for electrochemical tests in a relatively high potential range on Au electrodes. In particular, parasitic reactions of Au oxidation severely hindered the electrochemiluminescence (ECL) reactions of the Ru(bpy)32+/tripropylamine (TPrA) system. In this work, we designed an ultra-fast redox pulse to alleviate reversible oxidation of Au with a potential range of -0.5 to 0.9 V. Stable ECL signals were generated in the last 3 ms of each run (RSD = 5.86%), and interesting mechanisms were revealed. The ultra-high-frequency sampler indicated that free diffusion of TPrA•+ was the rate-determining step at 0.9 V, and it followed a totally different route with ECL at 1.3 V. Furthermore, we proposed a particular ECL reaction route at 0.9 V with C5 desosamine of the analyte, azithromycin, involved for the first time, based on results of radical identification. We believe that our work paved the way for the application of Au-based sandwich-type biosensors in environmental monitoring.

Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.

BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs. METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts. RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo . CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.

Coordination of hydraulic and leaf-level gas exchange traits during water-deficit acclimation in apple rootstocks.

Water deficit episodes impact apple (Malus domestica) productivity through challenging the trees' water status, the influence of extreme high temperature climate has become increasingly prominent in recent years. Rootstocks can bestow specific properties on the fruit trees such as the resistance to drought stress. However, the related hydraulic mechanisms in response to water deficit have not been fully understood. Herein, five rootstocks (SH6, GM256, M9, M26, and MM106) were examined under water limitation. The hydraulic conductance of root (Kroot), shoots (Kshoot), and stems (Kstem-shoot) in the five rootstocks reduced slightly during drought stress. Whereas the leaf water potential and photosynthesis of five rootstocks decreased dramatically when they were exposed to drought stress. Additionally, the Kshoot and Kstem-shoot were strongly correlated with the total plant leaf area. Aquaporins (AQPs) involved in the symplastic water transport pathway, the PIP2:1, TIP1:1, and TIP2:2 mRNA levels of all genotypic rootstocks showed significant regulation under drought stress. We examined the relationships among photosynthesis, apoplastic, and symplastic water movement pathways to achieve a comprehensive understanding of rootstocks' hydraulic strategy for improving drought adaptation. The PIP2:1 and TIP2:1 in leaves were more sensitive to root hydraulic conductance in response to drought stress. Furthermore, the coordinated relationship existed in leaf-specific conductance of shoot (Kl -shoot) and transpiration rate (Tr) under drought stress in the rootstocks. Overall, the drought resistance in the five dwarfing rootstocks is associated with the rapid re-establishment of water-related traits, and the effect of the canopy on the drought resistance in apple rootstocks merits much more attention.

Microbial Transformation of Dissolved Organic Sulfur during the Oxic Process in 47 Full-Scale Municipal Wastewater Treatment Plants.

Dissolved organic sulfur (DOS) is a significant part of effluent organic matter of wastewater treatment plants (WWTPs) and poses a potential ecological risk for receiving waters. However, the oxic process is a critical unit of biological wastewater treatment for microorganisms performing organic matter removal, wherein DOS transformation and its mechanism are poorly understood. This study investigated the transformation of DOS during the oxic process in 47 full-scale municipal WWTPs across China from molecular and microbial aspects. Surprisingly, evident differences in DOS variations (ΔDOS) separated sampled WWTPs into two groups: 28 WWTPs with decreased DOS concentrations in effluents (ΔDOS < 0) and 19 WWTPs with increased DOS (ΔDOS > 0). These two groups also presented differences in DOS molecular characteristics: higher nitrogen/carbon (N/C) ratios (0.030) and more peptide-like DOS (8.2%) occurred in WWTPs with ΔDOS > 0, implying that peptide-like DOS generated from microbes contributed to increased DOS in effluents. Specific microbe-DOS correlations (Spearman correlation, p < 0.05) indicated that increased effluent DOS might be explained by peptide-like DOS preferentially being produced during copiotrophic bacterial growth and accumulating due to less active cofactor metabolisms. Considering the potential environmental issues accompanying DOS discharge from WWTPs with ΔDOS > 0, our study highlights the importance of focusing on the transformation and control of DOS in the oxic process.