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.

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.

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.

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.

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.

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.

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.

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.

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.

Study of the effect of Lactobacillus crispatus FSCDJY67L3 on Helicobacter Pylori eradication: a double-blind randomized controlled clinical trial.

Helicobacter pylori (H. pylori) is a gram-negative bacterium exhibiting high pathogenicity. Traditional antibiotic treatments are considered ineffective as the H. pylori resistance has increased. Recently, a quadruple therapy strategy of probiotics and antibiotics to eliminate H. pylori was proposed. Probiotics play a therapeutic role as supplements in this process. The present research screened a probiotic strain (Lactobacillus crispatus FSCDJY67L3) that co-aggregates strongly with H. pylori. L. crispatus FSCDJY67L3 was demonstrated to significantly reduce H. pylori load (14C breath test) in clinical trials with H. pylori-positive patients. The Gastrointestinal Symptom Rating Scale (GSRS) score decreased, indicating improvement in the gastrointestinal discomfort of patients. Furthermore, L. crispatus FSCDJY67L3 showed no change in the structure of the intestinal flora of patients. Routine blood indices and blood biochemical indices related to liver and kidney function were also not affected in the patients. Therefore, L. crispatus FSCDJY67L3 may be used clinically as a supplement for the treatment of H. pylori. Clinical Trial Registration: https://www.chictr.org.cn/, Chinese Clinical Trial Registry (ChiCTR2100053710).

Herbicidal Activity of Secondary Metabolites Isolated from Streptomyces sp. NEAU-HV44 on Selected Weeds and Crops.

Streptomyces is an effective source of new natural bioherbicides. In this study, a novel isolated strain NEAU-HV44 showed strong inhibitory activity against Amaranthus retroflexus L. and was concluded to the genus Streptomyces. Strain NEAU-HV44 fermentation conditions were optimized to maximize the herbicidal activity. The supernatant of strain NEAU-HV44 could significantly control the growth of weeds (A. retroflexus L., Setaria viridis, Portulaca oleracea L., and Chenopodium album) and crops (maize, soybean, wheat, Chinese cabbage, cucumber, tomato, and romaine lettuce) with dose-dependent in preemergence. Notably, weeds were more sensitive to a low-concentration supernatant extract than crops in preemergence. In postemergence, the 2 mg mL-1 supernatant extract could significantly reduce the height and >50% biomass (fresh weight) of tested weeds. The supernatant extract could cause cell membrane destabilization and the cell death of weeds. In addition, the growth of tomato was also inhibited at a high concentration, but no obvious symptoms were observed on soybean and romaine lettuce after spraying the supernatant extract. Then two novel julichrome monomers, julichromes Q12 (1) and Q13 (2), and two known julichromes, julichrome Q3.3 (3) and julichrome Q3.5 (4), were isolated from the supernatant extract of strain NEAU-HV44 by bioactivity-guided approach. This is the first report of the herbicidal activity of julichromes. These four herbicidal compounds could inhibit the shoot and root growth of weeds at 0.2 mg mL-1, and compound 4 could completely inhibit the growth of P. oleracea L. Thus, julichromes (Q12, Q13, Q3.3, Q3.5 1-4) may be new bioherbicidal candidates.

Developments and Prospects of Farmland Application of Biogas Slurry in China-A Review.

Biogas slurry (BS) is an attractive agricultural waste resource which can be used to regulate soil microbial communities, enhance nutrient absorption capacity of crops, promote plant-soil interactions, and consequently, increase crop productivity. Presently, BS discharge is not environmentally friendly. It is therefore necessary to explore alternative efficient utilization of BS. The use of BS as fertilizer meets the requirements for sustainable and eco-friendly development in agriculture, but this has not been fully actualized. Hence, this paper reviewed the advantages of using BS in farmland as soil fertilization for the improvement of crop production and quality. This review also highlighted the potential of BS for the prevention and control of soil acidification, salinization, as well as improve microbial structure and soil enzyme activity. Moreover, this review reports on the current techniques, application methods, relevant engineering measures, environmental benefits, challenges, and prospects associated with BS utilization. Lastly, additional research efforts require for optimal utilization of BS in farmlands were elucidated.

Phenopyrrolizins A and B, Two Novel Pyrrolizine Alkaloids from Marine-Derived Actinomycetes Micromonospora sp. HU138.

Two previously undescribed pyrrolizine alkaloids, named phenopyrrolizins A and B (1 and 2), were obtained from the fermentation broth of marine-derived Micromonospora sp. HU138. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR spectra as well as HRESIMS data. The structure of 1 was confirmed by single-crystal diffraction analysis and its racemization mechanism was proposed. The antifungal activity assay showed that 2 could inhibit the mycelial growth of Botrytis cinerea with the inhibitory rates of 18.9% and 35.9% at 20 µg/disc and 40 µg/disc, respectively.

Metabolic Engineering of Escherichia coli for Efficient Production of Pseudouridine.

Pseudouridine-incorporated mRNA vaccines can enhance protein expression and reduce immunogenicity, leading to a high demand for pseudouridine to be used in mRNA drug production. To achieve the low-cost production of pseudouridine, Escherichia coli was systematically modified to utilize inexpensive raw materials to efficiently produce pseudouridine. First, in the pyrimidine biosynthesis pathway, genes related to the precursor competing pathway and the negative regulator were deleted, which increased pseudouridine production. Second, two critical genes, pseudouridine-5'-phosphate glycosidase (psuG) and phosphatase genes from different bacteria, were screened and employed in various genetic constructs, and the pseudouridine yield of the optical strain increased to 599 mg/L. The accumulation of pseudouridine was further increased by the deletion of pseudouridine catabolism-related genes. Ultimately, the pseudouridine titer in a 5 L bioreactor reached 7.9 g/L, and the yield of pseudouridine on glucose was 0.15 g/g. Overall, a cell factory producing pseudouridine was successfully constructed and showed potential for industrial production.

Gallic acid improves the metformin effects on diabetic kidney disease in mice.

OBJECTIVES: Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. METHODS: Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). RESULTS: Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). CONCLUSION: Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Long-Term Organic Fertilization Strengthens the Soil Phosphorus Cycle and Phosphorus Availability by Regulating the pqqC- and phoD-Harboring Bacterial Communities.

The pqqC and phoD genes encode pyrroloquinoline quinone synthase and alkaline phosphomonoesterase (ALP), respectively. These genes play a crucial role in regulating the solubilization of inorganic phosphorus (Pi) and the mineralization of organic phosphorus (Po), making them valuable markers for P-mobilizing bacterial. However, there is limited understanding of how the interplay between soil P-mobilizing bacterial communities and abiotic factors influences P transformation and availability in the context of long-term fertilization scenarios. We used real-time polymerase chain reaction and high-throughput sequencing to explore the characteristics of soil P-mobilizing bacterial communities and their relationships with key physicochemical properties and P fractions under long-term fertilization scenarios. In a 38-year fertilization experiment, six fertilization treatments were selected. These treatments were sorted into three groups: the non-P-amended group, including no fertilization and mineral NK fertilizer; the sole mineral-P-amended group, including mineral NP and NPK fertilizer; and the organically amended group, including sole organic fertilizer and organic fertilizer plus mineral NPK fertilizer. The organically amended group significantly increased soil labile P (Ca2-P and enzyme-P) and Olsen-P content and proportion but decreased non-labile P (Ca10-P) proportion compared with the sole mineral-P-amended group, indicating enhanced P availability in the soil. Meanwhile, the organically amended group significantly increased soil ALP activity and pqqC and phoD gene abundances, indicating that organic fertilization promotes the activity and abundance of microorganisms involved in P mobilization processes. Interestingly, the organically amended group dramatically reshaped the community structure of P-mobilizing bacteria and increased the relative abundance of Acidiphilium, Panacagrimonas, Hansschlegelia, and Beijerinckia. These changes had a greater positive impact on ALP activity, labile P, and Olsen-P content compared to the abundance of P-mobilizing genes alone, indicating their importance in driving P mobilization processes. Structural equation modeling indicated that soil organic carbon and Po modulated the relationship between P-mobilizing bacterial communities and labile P and Olsen-P, highlighting the influence of SOC and Po on the functioning of P-mobilizing bacteria and their impact on P availability. Overall, our study demonstrates that organic fertilization has the potential to reshape the structure of P-mobilizing bacterial communities, leading to increased P mobilization and availability in the soil. These findings contribute to our understanding of the mechanisms underlying P cycling in agricultural systems and provide valuable insights for enhancing microbial P mobilization through organic fertilization.