Molluscicidal activity and biochemical impacts of borrelidins against an aquatic invasive snail Pomacea canaliculata for crop protection.

The invasive golden apple snail Pomacea canaliculata is one of the devastating threats to aquatic ecosystems and wetland agriculture worldwide. Macrolides from microbes display various advantages over other compounds in controlling snails. However, emergence of antibiotic-resistant phenotypes against certain macrolides in the field appeals for exploring more effectively molluscicidal macrolides. Here, two borrelidins, borrelidin BN1 and BN2, from the extract of a Streptomyces strain fermentation were evaluated for molluscicidal potential against P. canaliculata using both immersion and contact bioassay methods. Borrelidin BN1 (borrelidin A) presented a significant molluscicidal activity comparable to the chemical pesticide metaldehyde, and had a much lower median lethal concentration value (LC50, 522.984 µg·ml-1) than avermectin B1 at 72 h of contact-killing treatment. Snail growth was inhibited by borrelidin BN1 more than by metaldehyde at sublethal concentrations, consistent with responses of key biochemical parameters. Exposure to borrelidin BN1 decreased the activity of acetylcholinesterase (AChE), glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as the levels of energy reserves and sex steroids in snail tissues, while increased the activity of superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH) and the level of lipid peroxidation (LPO). Further application assay confirmed that borrelidin BN1 protected crop plant Zizania latifolia from P. canaliculata damage via suppressing snail population density. These findings suggest great potential of borrelidin BN1 as a molluscicide. Additionally, its higher activity than the stereoisomeric borrelidin BN2 (borrelidin F) implied better molluscicidal borrelidins could be acquired through structural optimization.

Construction of a Bifunctional Nanoelectrode for Intracellular Natural Product Delivery and Monitoring Anticancer Efficiency in Single Cells.

Natural products play a significant role in new drug discovery and anticancer therapy, making the evaluation of their anticancer efficiency crucial for clinical application. However, delivering natural products to single cells and in situ monitoring of induced signaling molecule fluctuation to evaluate anticancer efficiency remain significant challenges. Hence, we proposed a universal and straightforward strategy to construct a bifunctional nanoelectrode that integrates drug loading and monitoring of signal molecule fluctuations at the single-cell level. Platinum (Pt) nanoparticles/reduced graphene oxide (rGO) composites were first electrochemically deposited on the carbon fiber nanoelectrode (CFNE@Pt/rGO) to serve as electrocatalytic materials for the monitoring of natural-product-induced reactive oxygen species (ROS) generation. The GO/natural product complex, formed by π-π stacking and hydrophobic interactions, was further electrochemically reduced on the surface of CFNE@Pt/rGO to enable the CFNE drug-loading function. Using this bifunctional functional nanoelectrode, a series of natural products (such as capsaicin, curcumin, and chrysin) were delivered into single cancer cells, and their anticancer efficiency was evaluated by measuring ROS generation. The results showed that intracellular ROS production induced by chrysin was 1.5-fold greater than that of curcumin and 2.1-fold greater than that of capsaicin. This work proposes an effective tool to evaluate the anticancer efficiency of various natural products. Additionally, this nanotool can be expanded to monitor the fluctuation of other biomolecules (such as RNS, GSH, NADH, etc.) by replacing Pt nanoparticles with other electrocatalytic materials, which is significant for comprehensively exploring the anticancer efficiency of new drugs and for the clinical treatment of various diseases.

Platinum nanoparticles-based electrochemical H2O2 sensor for rapid antibiotic susceptibility testing.

With the increase of antimicrobial resistance, rapid antibiotic susceptibility testing (AST) to guide precise antibiotic administration has become increasingly important. However, current gold standard AST approaches tend to take up to 24-48 h. In this work, based on the nature of catalase-positive bacteria decomposing H2O2, we developed a rapid, portable, straightforward, and cost-effective phenotypic AST approach by detecting residual H2O2 using a Pt nanoparticles-based electrochemical sensor. The pulse current of the sensor exhibited a linear increase with rising H2O2 concentration, demonstrating a high sensitivity of ∼382.2 µA cm-2 mM-1. This approach showed superb diagnostic performance, with an area under the curve of 1 for 24 clinical samples of Escherichia coli and Staphylococcus aureus, with a total detection time of 60 and 45 min, respectively. Furthermore, the performance of the sensor showed no degradation even after 100 detections, promising a substantial reduction in AST costs. Overall, the proposed approach exhibited immense potential for diagnosing bacterial antibiotic resistance.

Microscopic and Transcriptomic Analyses to Elucidate Antifungal Mechanisms of Bacillus velezensis TCS001 Lipopeptides against Botrytis cinerea.

Botrytis cinerea is an important fungal pathogen that causes gray mold disease in plants. Previously, Bacillus velezensis TCS001 live culture presented broad-spectrum antifungal activity against various plant pathogenic fungi and oomycetes, particularly B. cinerea. Here, the bioactivity of lipopeptides produced by TCS001 against B. cinerea was investigated. The IC50 values of the crude lipopeptide extract (CLE) from TCS001 to suppress mycelial growth and conidial germination were 14.20 and 49.39 mg/L, respectively. SEM and TEM imaging revealed that CLE caused morphological deformities and ultrastructural changes in the mycelium. Transcriptomic analyses combined with ΔBcpsd mutant construction demonstrated that the CLE could confer antifungal activity via suppressing Bcpsd expression in the pathogen. In addition, the CLE activated the plant immune system by increasing the content of defense-related enzymes and the expression of marker genes in immunity signaling pathways in cucumber plants. Therefore, TCS001 CLE could be potentially developed into biopesticides for the biocontrol of gray mold disease.

Mechanisms of biodiversity loss under nitrogen enrichment: unveiling a shift from light competition to cation toxicity.

The primary mechanisms contributing to nitrogen (N) addition induced grassland biodiversity loss, namely light competition and soil cation toxicity, are often examined separately in various studies. However, their relative significance in governing biodiversity loss along N addition gradient remains unclear. We conducted a 4-yr field experiment with five N addition rates (0, 2, 10, 20, and 50 g N m-2 yr-1) and performed a meta-analysis using global data from 239 observations in N-fertilized grassland ecosystems. Results from our field experiment and meta-analysis indicate that both light competition and soil cation (e.g. Mn2+ and Al3+) toxicity contribute to plant diversity loss under N enrichment. The relative importance of these mechanisms varied with N enrichment intensity. Light competition played a more significant role in influencing species richness under low N addition (≤ 10 g m-2 yr-1), while cation toxicity became increasingly dominant in reducing biodiversity under high N addition (>10 g m-2 yr-1). Therefore, a transition from light competition to cation toxicity occurs with increasing N availability. These findings imply that the biodiversity loss along the N gradient is regulated by distinct mechanisms, necessitating the adoption of differential management strategies to mitigate diversity loss under varying intensities of N enrichment.

Soil Acidification Can Be Improved under Different Long-Term Fertilization Regimes in a Sweetpotato-Wheat Rotation System.

Soil acidification is a significant form of agricultural soil degradation, which is accelerated by irrational fertilizer application. Sweetpotato and wheat rotation has emerged as an important rotation system and an effective strategy to optimize nutrient cycling and enhance soil fertility in hilly areas, which is also a good option to improve soil acidification and raise soil quality. Studying the effects of different fertilization regimes on soil acidification provides crucial data for managing it effectively. An eight-year field experiment explored seven fertilizer treatments: without fertilization (CK), phosphorus (P) and potassium (K) fertilization (PK), nitrogen (N) and K fertilization (NK), NP fertilization (NP), NP with K chloride fertilization (NPK1), NP with K sulfate fertilization (NPK2), and NPK combined with organic fertilization (NPKM). This study focused on the soil acidity, buffering capacity, and related indicators. After eight years of continuous fertilization in the sweetpotato-wheat rotation, all the treatments accelerated the soil acidification. Notably, N fertilization reduced the soil pH by 1.30-1.84, whereas N-deficient soil showed minimal change. Organic fertilizer addition resulted in the slowest pH reduction among the N treatments. Both N-deficient (PK) and organic fertilizer addition (NPKM) significantly increased the soil cation exchange capacity (CEC) by 8.83% and 6.55%, respectively, compared to CK. Similar trends were observed for the soil-buffering capacity (pHBC). NPK2 increased the soil K+ content more effectively than NPK1. NPKM reduced the sodium and magnesium content compared to CK, with the highest magnesium content among the treatments at 1.60 cmol·kg-1. Regression tree analysis identified the N input and soil magnesium and calcium content as the primary factors influencing the pHBC changes. Structural equation modeling showed that the soil pH is mainly influenced by the soil ammonium N content and pHBC, with coefficients of -0.28 and 0.29, respectively. Changes in the soil pH in the sweetpotato-wheat rotation were primarily associated with the pHBC and N input, where the CEC content emerged as the main factor, modulated by magnesium and calcium. Long-term organic fertilization enhances the soil pHBC and CEC, slowing the magnesium reduction and mitigating soil acidification in agricultural settings.

Two new aromatic tenvermectins from mutant Streptomyces avermitilis HU02-06.

Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.

Butein inhibits oral squamous cell carcinoma growth via promoting MCL-1 ubiquitination.

Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.

Progressive enhanced photodynamic therapy and enhanced chemotherapy fighting against malignant tumors with sequential drug release.

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.

Biochar and Manure Co-Application Increases Rice Yield in Low Productive Acid Soil by Increasing Soil pH, Organic Carbon, and Nutrient Retention and Availability.

In recent years, overuse of chemical fertilization has led to soil acidification and decreased rice yield productivity in southern China. Biochar and manure co-application remediation may have positive effects on rice yield and improve acid paddy soil fertility. This study was conducted to understand the effects of co-application of wood biochar and pig manure on rice yield and acid paddy soil quality (0-40 cm soil layers) in a 5-year field experiment. The experiment consisted of six treatments: no biochar and no fertilizer (CK); biochar only (BC); mineral fertilizer (N); mineral fertilizer combined with biochar (N + BC); manure (25% manure N replacing fertilizer N) combined with mineral fertilizer (MN); and manure combined with mineral fertilizer and biochar (MN + BC). Total nitrogen application for each treatment was the same at 270 kg nitrogen ha-1y-1, and 30 t ha-1 biochar was added to the soil only in the first year. After five years, compared with N treatments, N + BC, MN, and MN + BC treatments increased the rice yield rate to 2.8%, 4.3%, and 6.3%, respectively, by improving soil organic matter, total nitrogen, and available phosphate under a 0-40 cm soil layer. MN + BC had the strongest resistance to soil acidification among all the treatments. The interaction between fertilizers and biochar application was significant (p < 0.05) in rice yield, soil electrical conductivity (10-20 cm), and soil available phosphate (20-40 cm). Principal component analysis indicated that the effect of manure on soil property was stronger than that of biochar in the 0-40 cm soil layer. The overall rice yield and soil fertility decreased in the order of biochar + mineral fertilizer + manure > mineral fertilizer + manure > biochar + mineral fertilizer > mineral fertilizer > biochar > control. These results suggest that biochar and manure co-application is a long-term viable strategy for improving acid soil productivity due to its improvements in soil pH, organic carbon, nutrient retention, and availability.

Digital Circulating Tumor Cells Quantification.

Circulating tumor cells (CTCs) are an emerging but vital biomarker for cancer management. An efficient methodology for accurately quantifying CTCs remains challenging due to their rareness. Here, we develop a digital CTC detection strategy using partitioning instead of enrichment to quantify CTCs. By utilizing the characteristics of droplet microfluidics that can rapidly generate a large number of parallel independent reactors, combined with Poisson distribution, we realize the quantification of CTCs in the blood directly. The limit of detection of our digital CTCs quantification assay is five cells per 5 mL of whole blood. By simultaneously detecting multiple genetic mutations, our approach achieves highly sensitive and specific detection of CTCs in peripheral blood from NSCLC patients (AUC = 1). Our digital platform offers a potential approach and strategy for the quantification of CTCs, which could contribute to the advancement of cancer medical management.

Erianin promotes apoptosis and inhibits Akt-mediated aerobic glycolysis of cancer cells.

Highly activated aerobic glycolysis provides the metabolic requirements for tumor cell growth and proliferation. Erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has been reported to exert antitumor activity in multiple cancers. However, whether Erianin exerts inhibitory effects on aerobic glycolysis and the inherent mechanism remain poorly defined in non-small cell lung cancer (NSCLC). Here, we showed that Erianin inhibited the cell viability and proliferation, and induced apoptosis in NSCLC cells. Moreover, Erianin overtly suppressed aerobic glycolysis via decreasing HK2 expression. Mechanistically, Erianin dose-dependently curbed the Akt-GSK3ß signaling pathway phosphorylation activation, which afterwards downregulated HK2 expression. Meanwhile, Erianin inhibited HCC827 tumor growth in vivo. Taken together, our results suggest that the natural product Erianin can suppress aerobic glycolysis and exert potent anticancer effects via the Akt-GSK3ß signaling pathway in NSCLC cells.

Electrochemical Monitoring of Sphingosine-1-phosphate-Induced ATP Release Using a Microsensor Based on an Entropy-Driven Bipedal DNA Walker.

Neuropathic pain is a chronic and severe syndrome for which effective therapy is insufficient and the release of ATP from microglia induced by sphingosine-1-phosphate (S1P) plays a vital role in neuropathic pain. Therefore, there is an urgent demand to develop highly sensitive and selective ATP biosensors for quantitative monitoring of low-concentration ATP in the complex nervous system, which helps in understanding the mechanism involved in neuropathic pain. Herein, we developed an electrochemical microsensor based on an entropy-driven bipedal DNA walker. First, the microsensor specifically recognized ATP via ATP aptamers, initiating the entropy-driven bipedal DNA walker. Subsequently, the bipedal DNA walker autonomously traversed the microelectrode interface, introducing methylene blue to the electrode surface and achieving cascade signal amplification. This microsensor showed excellent selectivity, stability, and a low limit of detection at 1.13 nM. The S1P-induced ATP release from BV2 cells was successfully monitored, and it was observed that dicumarol could inhibit this release, suggesting dicumarol as a potential treatment for neuropathic pain. The microsensor's small size exhibited significant potential for monitoring ATP level changes in neuropathic pain in vivo, which provides a new strategy for in situ and quantitative monitoring of nonelectroactive biomolecules associated with neurological diseases.

Amendment of straw with decomposing inoculants benefits the ecosystem carbon budget and carbon footprint in a subtropical wheat cropping field.

The incorporation of straw with decomposing inoculants into soils has been widely recommended to sustain agricultural productivity. However, comprehensive analyses assessing the effects of straw combined with decomposing inoculants on greenhouse gas (GHG) emissions, net primary production (NPP), the net ecosystem carbon budget (NECB), and the carbon footprint (CF) in farmland ecosystems are scant. Here, we carried out a 2-year field study in a wheat cropping system with six treatments: rice straw (S), a straw-decomposing Bacillus subtilis inoculant (K), a straw-decomposing Aspergillus oryzae inoculant (Q), a combination of straw and Bacillus subtilis inoculant (SK), a combination of straw and Aspergillus oryzae inoculant (SQ), and a control with no rice straw or decomposing inoculant (Control). We found that all the treatments resulted in a positive NECB ranging between 838 and 5065 kg C ha-1. Relative to the Control, the S treatment increased CO2 emissions by 16%, while considerably enhancing the NECB by 349%. This difference might be attributed to the straw C input and an increase in plant productivity (NPP, 30%). More importantly, in comparison to that in S, the NECB in SK and SQ significantly increased by 27-35% due to the positive response of NPP to the decomposing inoculants. Although the combination of straw and decomposing inoculants yielded a 3% increase in indirect GHG emissions, it also exhibited the lowest CF (0.18 kg CO2-eq kg-1 of grain). This result was attributed to the synergistic effects of straw and decomposing inoculants, which reduced direct N2O emissions and increased wheat productivity. Overall, the findings of the present study suggested that the combined amendment of straw and decomposing inoculants is an environmentally sustainable management practice in wheat cropping systems that can generate win-win scenarios through improvements in soil C stock, crop productivity, and GHG mitigation.

Identification of Lydicamycins as Main Antioomycete Compounds from the Biocontrol Agent Streptomyces sp. NEAU-S7GS2.

Oomycetes are well-known phytopathogens that seriously threaten many important crops worldwide. In this study, the endophytic actinobacterium Streptomyces sp. NEAU-S7GS2 demonstrated significant antagonistic activity against Phytophthora and Pythium and showed a potent biocontrol effect on suppression of soybean phytophthora root rot and pepper phytophthora blight. Two compounds were subsequently isolated as the main active components by bioassay-guided fractionation and identified as lydicamycins A and B. These two compounds showed high antioomycete activity against Phytophthora and Pythium with EC50 values of 0.73-2.67 µg/mL, which are equal to or lower than those of commercialized drug metalaxyl. In vivo bioassay using detached leaves demonstrated that lydicamycin A had a better control efficiency against soybean phytophthora root rot than metalaxyl. Taken together, these results suggest that the biocontrol agent Streptomyces sp. NEAU-S7GS2 and lydicamycins have the potential to be developed as promising pesticides to control diseases caused by oomycetes.

A photoelectrochemical cytosensor based on a Bi2S3-MoS2 heterojunction-modified reduced oxide graphene honeycomb film for sensitive detection of circulating tumor cells.

A novel photoelectrochemical (PEC) cytosensor for the ultrasensitive detection of circulating tumor cells (CTCs) was developed. The bio-inspired reduced graphene oxide (rGO) honeycomb film photoelectrode was fabricated via a "breath figure" method, followed by the self-assembly of a Bi2S3-MoS2 heterojunction. The resulting Bi2S3-MoS2 heterojunction-modified rGO honeycomb film was employed as a sensing matrix for the first time. Compared to the smooth rGO film, the significant enhanced photocurrent of the photoelectrode under visible light was attributed to its improved visible light absorption, increased surface area and enhanced separation efficiency of photo-generated electron-hole pairs, which met the requirements of the PEC sensor for detecting larger targets. By virtue of the photocurrent decrease due to the steric hindrance of MCF-7 cells, which were captured by an aptamer immobilized on the surface of the photoelectrode, a cytosensor for detecting CTCs was achieved, showing a wide linear range of 10-1 × 105 cells per mL and a low detection limit of 2 cells per mL. Furthermore, MCF-7 cells in human serum were determined by this PEC biosensor, exhibiting great potential in the clinical detection of CTCs.

Nanoparticles loaded withß-Lapachone and Fe3+exhibit enhanced chemodynamic therapy by producing H2O2through cascaded amplification.

The rapid, irreversible change of active Fe2+to inactive Fe3+after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here,ß-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated asß-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.

Multilayer nanodrug delivery system with spatiotemporal drug release improves tumor microenvironment for synergistic anticancer therapy.

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Biogas Slurry Significantly Improved Degraded Farmland Soil Quality and Promoted Capsicum spp. Production.

This study reports on the effects of pretreated biogas slurry on degraded farm soil properties, microflora and the production of Capsicum spp. The responses of soil properties, microorganisms and Capsicum spp. production to biogas slurry pretreated soil were determined. The biogas slurry pretreatment of degraded soil increases the total nitrogen (0.15-0.32 g/kg), total phosphorus (0.13-0.75 g/kg), available phosphorus (102.62-190.68 mg/kg), available potassium (78.94-140.31 mg/kg), organic carbon content (0.67-3.32 g/kg) and pH value of the soil, while the population, diversity and distribution of soil bacteria and fungi were significantly affected. Interestingly, soil ammonium nitrogen, soil pH and soil nitrate nitrogen were highly correlated with the population of bacteria and fungi present in the pretreated soil. The soil with biogas slurry pretreatment of 495 m3/hm2 favored the seedling survival rate, flowering rate and fruit-bearing rate of Capsicum spp. and significantly reduced the rate of rigid seedlings. In this study, the application of 495 m3/hm2 biogas slurry to pretreat degraded soil has achieved the multiple goals of biogas slurry valorization, soil biofertilization and preventing and controlling plant diseases caused by soil-borne pathogenic microorganisms. These findings are of significant importance for the safe and environmentally friendly application of biogas slurry for soil pretreatment.

Development of fecal microbial diagnostic marker sets of colorectal cancer using natural language processing method.

BACKGROUND: Cancer screening and early detection greatly increase the chances of successful treatment. However, most cancer types lack effective early screening biomarkers. In recent years, natural language processing (NLP)-based text-mining methods have proven effective in searching the scientific literature and identifying promising associations between potential biomarkers and disease, but unfortunately few are widely used. METHODS: In this study, we used an NLP-enabled text-mining system, MarkerGenie, to identify potential stool bacterial markers for early detection and screening of colorectal cancer. After filtering markers based on text-mining results, we validated bacterial markers using multiplex digital droplet polymerase chain reaction (ddPCR). Classifiers were built based on ddPCR results, and sensitivity, specificity, and area under the curve (AUC) were used to evaluate the performance. RESULTS: A total of 7 of the 14 bacterial markers showed significantly increased abundance in the stools of colorectal cancer patients. A five-bacteria classifier for colorectal cancer diagnosis was built, and achieved an AUC of 0.852, with a sensitivity of 0.692 and specificity of 0.935. When combined with the fecal immunochemical test (FIT), our classifier achieved an AUC of 0.959 and increased the sensitivity of FIT (0.929 vs. 0.872) at a specificity of 0.900. CONCLUSIONS: Our study provides a valuable case example of the use of NLP-based marker mining for biomarker identification.