Quinolone Antibiotics Inhibit the Rice Photosynthesis by Targeting Photosystem II Center Protein: Generational Differences and Mechanistic Insights.

Soil antibiotic pollution profoundly influences plant growth and photosynthetic performance, yet the main disturbed processes and the underlying mechanisms remain elusive. This study explored the photosynthetic toxicity of quinolone antibiotics across three generations on rice plants and clarified the mechanisms through experimental and computational studies. Marked variations across antibiotic generations were noted in their impact on rice photosynthesis with the level of inhibition intensifying from the second to the fourth generation. Omics analyses consistently targeted the light reaction phase of photosynthesis as the primary process impacted, emphasizing the particular vulnerability of photosystem II (PS II) to the antibiotic stress, as manifested by significant interruptions in the photon-mediated electron transport and O2 production. PS II center D2 protein (psbD) was identified as the primary target of the tested antibiotics, with the fourth-generation quinolones displaying the highest binding affinity to psbD. A predictive machine learning method was constructed to pinpoint antibiotic substructures that conferred enhanced affinity. As antibiotic generations evolve, the positive contribution of the carbonyl and carboxyl groups on the 4-quinolone core ring in the affinity interaction gradually intensified. This research illuminates the photosynthetic toxicities of antibiotics across generations, offering insights for the risk assessment of antibiotics and highlighting their potential threats to carbon fixation of agroecosystems.

ABA-importing transporter (AIT1) synergies enhances exogenous ABA minimize heavy metals accumulations in Arabidopsis.

Exogenous abscisic acid (ABA) presents a novel approach to mitigate heavy metal (HM) accumulation in plants, yet its efficacy against multiple HMs and potential enhancement methods remain underexplored. In this study, we demonstrated that the exogenous ABA application simultaneously decreased Zn, Cd and Ni accumulation by 22-25 %, 27-39 % and 60-62 %, respectively, in wild-type (WT) Arabidopsis. Conversely, ABA reduced Pb in shoots but increased its root concentration. ABA application also modulated the expression of HM uptake genes, inhibiting IRT1, NRAMP1, NRAMP4, and HMA3, and increasing ZIP1 and ZIP4 expressions. Further analysis revealed that overexpressing the ABA-importing transporter (AIT1) in plants intensified the reduction of Cd, Zn, and Ni, compared to WT. However, the inhibitory effect of exogenous ABA on Pb accumulation was mitigated in shoots with higher AIT1 expression. Furthermore, HMs-induced growth inhibition and the damage to photosynthesis were also alleviated with ABA treatment. Conclusively, AIT1's synergistic effect with ABA effectively reduces Cd, Zn and Ni accumulation, offering a synergistic approach to mitigate HM stress in plants.

Assessing the influence of college campus environments on mental health interventions for economically disadvantaged students

Objective: To explore the relationship between college students with financial difficulties, campus environment and mental health, and to explore whether physical activity can be used as a mediating variable to make campus environment affect mental health through it,so as to improve the mental health of college students. Methods:A total of 150 college students from five universities in Shanghai were selected by stratified random sampling.The basic information of the questionnaire was surveyed, the 3D accelerometer and GPS measured the intensity, time and trajectory of physical activity, the built environment factors were extracted by GIS, and the structural equation model was tested by AMOS 22.0. Results:Campus environment had a significant direct effect on the mental health of college students with financial difficulties, and the path coefficient was 0., respectively43, the order of its contribution is landscape elements,spatial configuration, building density, distance from sports venues, and the obvious direct and indirect effects on the mental health of college students with financial difficulties through physical activities, and the path coefficients are 032. 0.101;Campus environment and physical activities have a positive impact on the mental health of collegestudents with financial difficulties. Conclusion:Campus environment and physical activities have direct and indirect effects on the mental health of college students with financial difficulties. By revealing the impact path of college students with financial difficulties' mental health, it is of great practical significance for the construction of urban communities, the improvement of campus environment, the promotion of physical activities, and the improvement of mental health in the new era. (AU)

Photoaged microplastics enhanced the antibiotic resistance dissemination in WWTPs by altering the adsorption behavior of antibiotic resistance plasmids.

Growing concerns have raised about the microplastic eco-coronas in the ultraviolet (UV) disinfection wastewater, which accelerated the pollution of antibiotic resistance genes (ARGs) in the aquatic environment. As the hotspot of gene exchange, microplastics (MPs), especially for the UV-aged MPs, could alter the spread of ARGs in the eco-coronas and affect the resistance of the environment through adsorbing antibiotic resistant plasmids (ARPs). However, the relationship between the MP adsorption for ARPs and ARG spreading characteristics in MP eco-corona remain unclear. Herein, this study explored the distribution of ARGs in the MP eco-corona through in situ investigations of the discharged wastewater, and the adsorption behaviors of MPs for ARPs by in vitro adsorption experiments and in silico calculations. Results showed that the adsorption capacity of MPs for ARPs was enhanced by 42.7-48.0 % and the adsorption behavior changed from monolayer to multilayer adsorption after UV-aging. It was related to the increased surface roughness and oxygen-containing functional groups of MPs under UV treatment. Moreover, the abundance of ARGs in MP eco-corona of UV-treated wastewater was 1.33-1.55 folds higher than that without UV treatment, promoting the proliferation of drug resistance. DFT and DLVO theoretical calculations indicated that the MP-ARP interactions were dominated by electrostatic physical adsorption, endowing the aged MPs with low potential oxygen-containing groups to increase the electrostatic interaction with ARPs. Besides, due to the desorption of ARPs on MPs driven by the electrostatic repulsion, the bioavailability of ARGs in the MP eco-coronas was increased with pH and decreased with salinity after the wastewater discharge. Overall, this study advanced the understanding of the adsorption behavior of MPs for ARPs and provided inspirations for the evaluation of the resistance spread in the aquatic environment mediated by MP eco-coronas.

NRT1.2 overexpression enhances the synergistic interplay between ABA-generating bacteria and biochars in reducing heavy metal accumulation in pak choi.

The agricultural sector faces severe challenges owing to heavy metal (HM) contamination of farmlands, requiring urgent preventive measures. To address this, we investigated the impact of the synergistic application of Azospirillum brasilense, a growth-promoting rhizobacterium producing abscisic acid (ABA), and biochar to minimize HM accumulation in pak choi, using three distinct expression levels of the ABA transporter NRT1.2 in pak choi and three different types of contaminated soils as experimental materials. The results revealed that pak choi with low, medium, and high NRT1.2 expression intensity, when subjected to bacterial strain-biochar treatment, exhibited an increasing trend in ABA content compared to the control. Correspondingly, the aboveground HM content decreased by 1-49 %, 22-52 %, and 15-96 %, whereas the fresh weight increased by 12-38 %, 88-126 %, and 152-340 %, respectively, showing a significant correlation with NRT1.2 expression. Pearson correlation analysis demonstrated that NRT1.2 expression intensity was inversely associated with the combined treatment's reduction in HM accumulation and positively correlated with the promotional effect. Simultaneously, soil discrepancies significantly affected the combined treatment, which was likely associated with variations in the active forms of HM in each soil. Consequently, when employing ABA-producing bacteria for mitigating crop HM accumulation, selecting plants with higher relative NRT1.2 expression intensity, combined with biochar, is recommended.

Oxyhaemoglobin saturation NIR-IIb imaging for assessing cancer metabolism and predicting the response to immunotherapy.

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2 imaging technique to visualize the sO2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2 imaging, the tumour-associated-vessel sO2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2 and PD-L1, allowing a more accurate prediction of immunotherapy response.

[Effects of Exogenous Plant Hormone Spraying on the Phytoremediation by Bidens pilosa L. in Cadmium-contaminated Soil].

To explore the effect of exogenous plant hormone spraying on the absorption of heavy metals by hyperaccumulated plants, Bidens pilosa L. was selected as the tested plant owing to the large biomass, short growth cycle, and high accumulation efficiency. Here, the effect of foliar spraying 6-benzylaminopurine (6-BA), salicylic acid (SA), and 24-epi-brassinosteroid (24-EBR) on the remediation of cadmium (Cd)-contaminated soil by B. pilosa L. was examined. The results showed:① the efficiency of the remediation in Cd-contaminated soil by B. pilosa L. was effectively enhanced after the spraying of all three kinds of exogenous plant hormones with appropriate concentrations. The spraying of the three exogenous plant hormones could promote the cadmium concentration in the leaves of B. pilosa L. to increase by 4.21%, 31.79%, and 14.89%; promote the translocation factor (TF) to increase by 9.67%, 18.83%, and 17.85%; promote the phytoextraction rates (PR) to increase by 15.36%, 32.33%, and 64.38%, respectively. ② The growth of B. pilosa L. was significantly promoted after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The spraying of the three exogenous plant hormones could promote plant growth under cadmium stress, and the dry weight of the plant root, stem, and leaf was increased by 37.53%, 74.50%, and 104.02%, respectively. ③ The photosynthesis of B. pilosa L. was significantly enhanced after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The chlorophyll concentration of the plant was significantly increased after foliar spraying with plant hormones, and the concentration of chlorophyll a was increased by 79.31%, 92.27%, and 51.12%; the photochemical quenching coefficient (qP) was increased by 11.32%, 89.16%, and 78.43%; and the non-photochemical quenching coefficient (NPQ) was increased by 51.71%, 241.12%, and 27.85%, respectively, after foliar spraying with appropriate concentrations of 6-BA, SA, and 24-EBR. ④ The antioxidant capacity of B. pilosa L. was significantly strengthened after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The malondialdehyde (MDA) concentration of the plant was reduced by 62.41%, 68.67%, and 46.76% after the application of 6-BA, SA, and 24-EBR, respectively. Meanwhile, superoxide dismutase (SOD) was increased by 68.33%, 10.28%, and 6.17%, and catalase (CAT) was increased by 31.43%, 37.87%, and 37.31%, respectively. Generally, the spraying of exogenous 6-BA, SA, and 24-EBR with the appropriate concentration under Cd stress could significantly increase the biomass of B. pilosa L. and promote the accumulation of heavy metals in the plant, improve the photosynthetic ability of the plant, reduce the oxidative damage of the plant under heavy metal stress, enhance the antioxidant capacity, and improve the absorption and tolerance of plants to Cd. It also could promote the transfer of Cd from roots to shoots, improve the phytoextraction rates of Cd from the plant, and effectively strengthen the phytoremediation efficiency. Among them, 30 mg·L-1 SA foliar spraying had the best effect.

ABA-metabolizing bacteria and rhamnolipids as valuable allies for enhancing phytoremediation efficiency in heavy metal-contaminated soils.

Microbial-assisted phytoremediation has great potential to improve the efficiency of phytoremediation in heavy metal (HM)-contaminated soils. In this study, the synergistic effects of rhamnolipids and the abscisic acid (ABA)-metabolizing bacterium Rhodococcus qingshengii on the phytoremediation efficiency of Indian mustard (Brassica juncea) in HM-contaminated soils were investigated. The Cd, Zn, and Pb contents in plants treated with a combination of rhamnolipids and R. qingshengii were 48.4-77.1 %, 14.6-40.4 %, and 16.1-20.0 % higher, respectively, than in those treated with R. qingshengii alone, and 42.8-59.2 %, 13.1-48.2 %, and 7.3-67.5 % higher, respectively, than in those treated with rhamnolipids alone. In addition, the bioconcentration factors of each metal were improved, and the biomass further increased by 36.6-65.7 % compared to that of single treatments. Pearson's correlation analysis showed that rhamnolipids and R. qingshengii enhanced the accumulation of HMs in B. juncea by activating the available forms of HMs in the soil and regulating the ABA and indole-3-acetic acid in plants, respectively. The structural equation model indicated that R. qingshengii had a larger path coefficient than rhamnolipids in terms of HM content and plant biomass, suggesting that R. qingshengii may have a greater contribution to promoting the extraction of HMs from the soil under synergistic conditions. In conclusion, the combination of rhamnolipids and R. qingshengii has great potential to enhance the phytoremediation efficiency of hyperaccumulating plants in HM-contaminated soils.

Polystyrene microplastic attenuated the toxic effects of florfenicol on rice (Oryza sativa L.) seedlings in hydroponics: From the perspective of oxidative response, phototoxicity and molecular metabolism.

Antibiotics and microplastics (MPs) are two emerging pollutants in agroecosystems, however the effects of co-exposure to antibiotics and MPs remain unclear. The toxicity of florfenicol (FF) and polystyrene microplastics (PS-MPs) on rice seedlings was investigated. FF and PS-MPs caused colloidal agglomeration, which changed the environmental behavior of FF. FF inhibited rice growth and altered antioxidant enzyme (superoxide dismutase, peroxidase, and catalase) activities, leading to membrane lipid peroxidation; impaired photosynthetic systems, decreased photosynthetic pigments (Chlorophyll a, Chlorophyll b, and carotene), chlorophyll precursors (Proto IX, Mg-Proto IX, and Pchlide), photosynthetic and respiratory rates. The key photosynthesis related genes (PsaA, PsaB, PsbA, PsbB, PsbC, and PsbD) were significantly down-regulated. The ultrastructure of mesophyll cells was destroyed with chloroplast swelling, membrane surface blurring, irregular thylakoid lamellar structure, and number of peroxisomes increased. PS-MPs mitigated FF toxicity, and the IBR index values showed that 10 mg∙L-1 PS-MPs were more effective. Metabolomic analysis revealed that the abundance of metabolites and metabolic pathways were altered by FF, was greater than the combined "MPs-FF" contamination. The metabolism of amino acids, sugars, and organic acids were severely interfered. Among these, 15 metabolic pathways were significantly altered, with the most significant effects on phenylalanine metabolism and the citric acid cycle (p < 0.05).

N fertilizers promote abscisic acid-catabolizing bacteria to enhance heavy metal phytoremediation from metalliferous soils.

Bacterial-assisted phytoextraction is an attractive strategy to enhance the phytoremediation efficiency of heavy metal (HM)-contaminated soils. In the present study, we investigated the synergistic effects of N fertilizers and abscisic acid (ABA)-catabolizing bacteria on the HM (Cd, Zn, and Pb) phytoremediation efficiency of Brassica juncea L. (B. juncea). Compared with Rhodococcus qingshengii (R. qingshengii) alone, urea, ammonium­nitrogen (NH4+-N), and nitrate­nitrogen (NO3--N) fertilizers combined with R. qingshengii increased HM concentrations in B. juncea by 13.8 %-48.2 %, 44.2 %-54.4 %, and 59.4 %-113.6 %, respectively, and enhanced the biomass of B. juncea by 7.7 %-38.8 %, 10.9 %-29.5 %, and 19.9 %-46.8 %, respectively. Consequently, the bioconcentration factor increased by 3.4 %-30.9 % and the phytoextraction rate increased by 18.5 %-98.7 %. Treatment with NO3--N showed the most significant effect. In structural equation modeling, R. qingshengii inoculation showed greater path coefficients with soil pH and ABA and indoleacetic acid concentrations of B. juncea than N fertilization, indicating that R. qingshengii contributed more to HM extraction efficiency than N fertilizers. Additionally, differences in the extraction rates of Cd, Zn, and Pb from B. juncea were reduced following N fertilization. In summary, synergistic R. qingshengii inoculation and N fertilization have substantial potential to enhance phytoremediation efficiency. Combined application of R. qingshengii and NO3--N fertilizers is recommended.

Synergistic interplay between ABA-generating bacteria and biochar in the reduction of heavy metal accumulation in radish, pakchoi, and tomato.

Heavy metal (HM) contamination is an environmental concern that threatens the agricultural product safety and human health. To address this concern, we developed a novel strategy involving the synergistic application of Azospirillum brasilense, a growth-promoting rhizobacterium which produces abscisic acid (ABA), and biochar to minimize HM accumulation in the edible parts of vegetable crops. Compared to A. brasilense or biochar alone, the concentrations of Cd, Ni, Pb, and Zn in radish (Raphanus sativus L.), pakchoi (Brassica chinensis L.), and tomato (Lycopersicon esculentum L.) decreased by 18-63% and 14-56%, respectively. Additionally, the synergistic treatment led to a 14-63% decrease in the bioconcentration factor. The biomass of the edible parts of the three crops increased by 65-278% after synergistic treatment, surpassing the effects of single treatments. Furthermore, the synergistic application enhanced the SPAD values by 1-45% compared to single treatments. The MDA concentrations in stressed plants decreased by 16-39% with the bacteria-biochar co-treatment compared to single treatments. Co-treatment also resulted in increased soluble protein and sugar concentrations by 8-174%, and improvements in flavonoids, total phenols, ascorbic acid, and DPPH levels by 2-50%. Pearson correlation analysis and structural equation modeling revealed that the synergistic effect was attributed to the enhanced growth of A. brasilense facilitated by biochar and the improved availability of HMs in soils. Notably, although ABA concentrations were not as high as those achieved with A. brasilense alone, they were maintained at relatively high levels. Overall, the synergistic application of A. brasilense-biochar might have remarkable potential for reducing the accumulation of HMs while promoting growth and improving nutritional and antioxidant qualities in tuberous, leafy, and fruit crops.

Metabolomics and proteomics reveal the toxicological mechanisms of florfenicol stress on wheat (Triticum aestivum L.) seedlings.

Although the ecological impacts of antibiotics have received attention worldwide, research on the toxicity of florfenicol is still limited. We conducted a metabolomic and proteomic study on wheat (Triticum aestivum L.) seedlings to reveal the toxicological mechanism of florfenicol. The growth of the wheat seedlings was found to be inhibited by florfenicol. Antioxidant enzyme activities (superoxide dismutase, peroxidase and catalase), malondialdehyde content and membrane permeability increased with increasing florfenicol concentration. The contents of chlorophyll and chlorophyll synthesis precursor substances (Proto IX, Mg-proto IX and Pchlide), photosynthetic and respiration rates, and chlorophyll fluorescence parameters decreased, indicating that photosynthesis was inhibited. The ultrastructure of chloroplasts was destroyed, as evidenced by the blurred membrane surface, irregular grana arrangement, irregular thylakoid lamella structure, and increased plastoglobuli number. Proteome analysis revealed that up-regulated proteins were highly involved in protein refolding, translation, oxidation-reduction, tricarboxylic acid cycle (TCA cycle), reactive oxygen species metabolic process, cellular oxidant detoxification, and response to oxidative stress. The down-regulated proteins were mainly enriched in photosynthesis-related pathways. In the metabolome analysis, the content of most of the metabolites in wheat leaves, such as carbohydrates and amino acids increased significantly (p < 0.05). Combined pathway analysis showed that florfenicol stress stimulated the TCA cycle pathway and downregulated the photosynthesis pathway.

[Role and Mechanism of Low Molecular-Weight-Organic Acids in Enhanced Phytoremediation of Heavy Metal Contaminated Soil].

Phytoremediation is an environmentally friendly technology to remove heavy metals from polluted soil by using the physical and chemical roles of plants. This can effectively reduce the production of secondary pollutants and is economically feasible. Low molecular-weight-organic acids (LMWOAs) are biodegradable and environmentally friendly and have strong application potential in the phytoremediation of heavy metal-contaminated soils. The role and mechanism of LMWOAs in phytoremediation was elaborated on in this study with the aim to:① regulate the development of roots, stems, and leaves; increase plant biomass; and enhance plant enrichment of heavy metals; ② improve photosynthesis, enhance plant resistance, and promote tolerance to heavy metals; ③ change the properties of rhizosphere soil, improve rhizosphere microbial activity, and promote the absorption of heavy metals; and ④ change the form of heavy metals, reduce the toxicity of heavy metals, and improve transport efficiency. Moreover, the advantages, disadvantages, and application of LMWOAs in enhanced phytoremediation of heavy metal-contaminated soil were explored in this study. Finally, the research direction of LMWOAs in the phytoremediation of heavy metal-contaminated soils was proposed, which will have practical scientific significance for the research and application of LMWOAs in future phytoremediation.

The addition of exogenous low-molecular-weight organic acids improved phytoremediation by Bidens pilosa L. in Cd-contaminated soil.

Enhancing the uptake and enrichment of heavy metals in plants is one of the important means to strengthen phytoremediation. In the present study, citric acid (CA), tartaric acid (TA), and malic acid (MA) were applied to enhance phytoremediation by Bidens pilosa L. in Cd-contaminated soil. The results showed that by the addition of appropriate concentrations of CA, TA, and MA, the values of the bioconcentration factor increased by 77.98%, 78.33%, and 64.49%, respectively, the translocation factor values increased by 16.45%, 12.61%, and 5.73%, respectively, and the values of the phytoextraction rates increased by 169.21%, 71.28%, and 63.11%, respectively. The minimum fluorescence values of leaves decreased by 31.62%, 0.28%, and 17.95%, while the potential efficiency of the PSII values of leaves increased 117.87%, 2.25%, and 13.18%, respectively, when CA, TA, and MA with suitable concentration were added. Redundancy analysis showed that CA and MA in plants were significantly positively correlated with plant growth, photosynthesis, and other indicators, whereas TA showed a negative correlation with most indicators. Moreover, CA addition could significantly increase the abundances of Azotobacter, Pseudomonas, and other growth-promoting bacteria, and the abundance values of Actinophytocola and Ensifer were improved in TA treatments. Therefore, our results demonstrated that low-molecular-weight organic acids could enhance phytoremediation, and exogenous CA could significantly improve the phytoremediation of Cd-contaminated soil by Bidens pilosa L.

Influence of site-specific factors on antibiotic resistance in agricultural soils of Yangtze River Delta: An integrated study of multi-factor modeling.

Agricultural soils are important reservoirs for antibiotic resistance genes (ARGs), which is closely linked to soil microorganisms. Environmental factors and co-existed pollutants may function as promoters or inhibitors for ARG proliferation to influence the agriculture green development. However, research focusing on the interaction of potential environmental drivers and ARGs is still lacking in agricultural soils. Here, we explored the microbial profile in 241 soil samples in Yangtze River Delta, and analyzed the relationship of microbial structures, ARGs, and typical site-specific factors. We found that the abundance of most ARGs was negatively correlated with the ratio of fungi and bacteria (F/B), whereas positively correlated with the ratio of gram-positive and gram-negative microbes (G+/G-). The co-occurrence network revealed significant associations among 18 site-specific factors, including 6 meteorological factors, 5 soil physicochemical properties, 5 co-existed organic pollutants, and 2 co-existed heavy metals. Random forest analysis demonstrated that F/B was mainly influenced by soil organic matters and co-existed polychlorinated biphenyls, while G+/G- was predominately regulated by soil total phosphorus and moisture content, which possibly resulting in their difference relationship with ARG abundance. Besides, the contribution of meteorological factors (>30%) in the explanation for F/B and G+/G- structures was the highest among all the site-specific factors. Together with path analysis showing meteorological factors probably affecting the ARG abundance through direct positive ways or indirect paths via physicochemical properties, microbial structure, and co-existed organic pollutants, we considered meteorological factors as the potential promoters for ARG proliferation. Collectively, these results increase our understanding of agricultural soils as hotspots of ARGs, and highlight the underappreciated role of meteorological factors as potential promoters for soil ARGs, providing reference for us to regulate ARG pollution scientifically to improve the development of green agriculture.

Fibroblast Activation Protein-α Responsive Peptide Assembling Prodrug Nanoparticles for Remodeling the Immunosuppressive Microenvironment and Boosting Cancer Immunotherapy.

Checkpoint blockade immunotherapy has broad application prospects in the clinical treatment of malignant tumors. However, the low response rate of the checkpoint blockade is due to low tumor immunogenicity and immunosuppression within the tumor microenvironment. Herein, the authors design an amphiphilic bifunctional PD-1/PD-L1 peptide antagonist PCP, and co-deliver doxorubicin (DOX) and R848 through co-assembly of a multi-agent prodrug (PCP@R848/DOX), which can be specifically cleaved by fibroblast activation protein-α (FAP-α) in the tumor stroma. Upon reaching the tumor tissue, the PCP@R848/DOX prodrug nanostructure is disassembled by FAP-α. The localized release of DOX and R848 triggers immunogenic cell death (ICD) and reprograms tumor-associated macrophages (TAMs) to elicit antitumor immunity. Furthermore, sustained release of PD-1 or PD-L1 peptide antagonists mediates the PD-L1 pathway blockade for further propagated activation of cytotoxic T lymphocytes. Notably, a tumor microenvironment activatable prodrug nanoparticle is presented for triple-modality cancer therapy that functions by simultaneously activating ICD and altering the phenotype of TAMs when combined with PD-1 blockade therapy, which efficiently elicits a strong systemic antitumor immune response. This strategy may emerge as a new paradigm in the treatment of cancer by combination immunotherapy.

Novel Peptide-Based Magnetic Nanoparticle for Mesenchymal Circulating Tumor Cells Detection.

The monitoring of circulating tumor cells (CTCs) has recently served as a promising approach for assessing prognosis and evaluating cancer treatment. We have already developed a CTCs enrichment platform by EpCAM recognition peptide-functionalized magnetic nanoparticles (EP@MNPs). However, considering heterogeneous CTCs generated through epithelial-mesenchymal transition (EMT), mesenchymal CTCs would be missed with this method. Notably, N-cadherin, overexpressed on mesenchymal CTCs, can facilitate the migration of cancer cells. Hence, we screened a novel peptide targeting N-cadherin, NP, and developed a new CTCs isolation approach via NP@MNPs to complement EpCAM methods' deficiencies. NP@MNPs had a high capture efficiency (about 85%) of mesenchymal CTCs from spiked human blood. Subsequently, CTCs were captured and sequenced at the single-cell level via NP@MNPs and EP@MNPs, RNA profiles of which showed that epithelial and mesenchymal subgroups could be distinguished. Here, a novel CTCs isolation platform laid the foundation for mesenchymal CTCs isolation and subsequent molecular analysis.

A Microfluidic Chip for Efficient Circulating Tumor Cells Enrichment, Screening, and Single-Cell RNA Sequencing.

Single-cell RNA sequencing on circulating tumor cells (CTCs) proves useful to study mechanisms of tumor heterogeneity, metastasis, and drug resistance. Currently, single-cell RNA sequencing of CTCs usually takes three prerequisite steps: enrichment of CTCs from whole blood, characterization of captured cells by immunostaining and microscopic imaging, and single-cell isolation through micromanipulation. However, multiple pipetting and transferring steps can easily cause the loss of rare CTCs. To address this issue, a novel integrated microfluidic chip for sequential enrichment, isolation, and characterization of CTCs at single-cell level, is developed. And, single CTC lysis is achieved on the same chip. The microfluidic chip includes functions of blood clot filtration, single-cell isolation, identification, and target single-cell lysate collection. By spiking tumor cells into whole blood, it is validated that this microfluidic chip can effectively conduct single-cell CTCs RNA sequencing. The approach lays a solid foundation for the analysis of RNA expression profiling of single-cell CTCs.

[Effect of Porous Fillers Properties on Biofilm Growth].

As an important part of biological aerated filters (BAFs), porous fillers are key to the effectiveness of BAF wastewater treatment. At present, there are many types of fillers, but the influence of the surface physical and chemical properties on biofilm formation is unclear, and how to compare and select the best biological filler remains a difficult problem in BAF engineering applications. In this study, the physical and chemical characteristics of several porous biological fillers that are commonly used in BAFs were studied, and the correlation between their physical/chemical properties and the biofilm attachment and enzyme activity of the biofilm on the filler was investigated. The results showed that the sponge filler could easily absorb sludge, but also clogged easily and the overall biofilm activity was not high. The three-dimensional hollow filler had a low surface-adsorbed biomass, but the specific surface area was large and the surface attachment growth biofilm activity was relatively strong. Ceramsite had a good hydrophilicity and high surface roughness, and the zeta potential was the most positive. Moreover, microorganisms easily attached and grew, it had the strongest sludge adhesion performance, and the best biofilm activity. According to a redundancy analysis (RDA), the main factor affecting the biomass on the surface of the fillers was the zeta potential, whereas the main factors affecting the surface sludge activity of the fillers was the clearance rate. According to the removal load of NH4+-N by six groups of reactors, the removal load of NH4+-N by ceramsite was the largest [68 g·(m3·d)-1], and was followed by volcanic rocks [67 g·(m3·d)-1]. Combined with the above factors, ceramsite was determined to be the most suitable filler for BAF.

The Phytophthora infestans AVR2 Effector Escapes R2 Recognition Through Effector Disordering.

Intrinsic disorder is a common structural characteristic of proteins and a central player in the biochemical processes of species. However, the role of intrinsic disorder in the evolution of plant-pathogen interactions is rarely investigated. Here, we explored the role of intrinsic disorder in the development of the pathogenicity in the RXLR AVR2 effector of Phytophthora infestans. We found AVR2 exhibited high nucleotide diversity generated by point mutation, early-termination, altered start codon, deletion/insertion, and intragenic recombination and is predicted to be an intrinsically disordered protein. AVR2 amino acid sequences conferring a virulent phenotype had a higher disorder tendency in both the N- and C-terminal regions compared with sequences conferring an avirulent phenotype. In addition, we also found virulent AVR2 mutants gained one or two short linear interaction motifs, the critical components of disordered proteins required for protein-protein interactions. Furthermore, virulent AVR2 mutants were predicted to be unstable and have a short protein half-life. Taken together, these results support the notion that intrinsic disorder is important for the effector function of pathogens and demonstrate that SLiM-mediated protein-protein interaction in the C-terminal effector domain might contribute greatly to the evasion of resistance-protein detection in P. infestans.