Knockdown of CPSF4 Inhibits Bladder Cancer Cell Growth by Upregulating NRF1.

Increasing studies have shown that nuclear respiratory factor 1 (NRF1) deficiency frequently occurs in many human diseases, and its activation can protect neurons and other cells from degenerative diseases and malignant tumors. However, how NRF1 is regulated in bladder cancer remains unknown. Our research aims to reveal the role of leavage and polyadenylation-specific factor 4 (CPSF4) on the growth inhibition effect of bladder cancer and clarify its relationship with NRF1. Here, cell proliferation assay, transwell migration assay and multicellular tumor spheroids (MCTS) formation assay in the bladder cancer cell lines were carried out to measure tumor cell growth. Western bolt assay was carried out to identify the relationship between NRF1 and CPSF4. Also, subcutaneous xenograft tumors in nude mice were established to further validate the inhibition effect of CPSF4 on bladder tumor and the regulation on NRF1. The results in vitro showed that knockdown of CPSF4 strongly reduced the proliferation and migration, and inhibited MCTS formation in 5637 and HT1376 cell lines, while an additional knockdown of increased NRF1 induced by CPSF4 knockdown partially abolished these effects. The results in vivo showed that knockdown of CPSF4 strongly reduced the volume and weight of subcutaneous tumor, and decreased the expression of Ki-67 in tumor tissue, while NRF1 knockdown partially reversed these effects induced by CPSF4 knockdown. Western bolt assay demonstrated that CPSF4 could negatively regulate NRF1. Our results indicated that knock-down of CPSF4 inhibited bladder cancer cell growth by upregulating NRF1, which might provide evidence of CPSF4 as a therapeutic target for bladder cancer.

Discovery of novel indazole derivatives as second-generation TRK inhibitors.

NTRK gene fusion leads to the activation of downstream signaling pathways, which is a oncogenic driver in various cancers. NTRK fusion-positive cancers can be treated with the first-generation TRK inhibitors, larotrectinib and entrectinib. Unfortunately, the patients eventually face the dilemma of no drugs available as the emergence of certain resistance mutations. The development of efficient and broad-spectrum second-generation TRK inhibitors is still of great significance. Here, we analyzed the binding modes of compounds 6, 10 with TRKA protein, respectively, a series of novel indazole TRK inhibitors were designed and synthesized using molecular hybridization strategy. Among them, the optimal compound B31 showed strong antiproliferative activities against Km-12, Ba/F3-TRKAG595R, and Ba/F3-TRKAG667C cell lines with IC50 values of 0.3, 4.7, and 9.9 nM, respectively. And the inhibitory effect against TRKAG667C (IC50 = 9.9 nM) was better than that of selitrectinib (IC50 = 113.1 nM). Further, compound B31 exhibited moderate kinase selectivity and excellent plasma stability (t1/2 > 480 min). In vivo pharmacokinetic studies in Sprague-Dawley rats showed that B31 had acceptable pharmacokinetic properties.

Impact of biological manure substitution on grain yield, nitrogen recovery efficiency, and soil biochemical properties.

Fertilization plays a crucial role in ensuring global food security and ecological balance. This study investigated the impact of substituting innovative biological manure for chemical fertilization on rice (Oryza sativa L) productivity and soil biochemical properties based on a three-year experiment. Our results suggested rice yield and straw weight were increased under manure addition treatment. Specifically, 70% of total nitrogen (N) fertilizer substituted by biological manure derived from straw, animal waste and microbiome, led to a substantial 13.6% increase in rice yield and a remarkable 34.2% boost in straw weight. In comparison to the conventional local farmer practice of applying 165 kg N ha-1, adopting 70% of total N plus biological manure demonstrated superior outcomes, particularly in enhancing yield components and spike morphology. Fertilization treatments led to elevated levels of soil microbial biomass carbon and N. However, a nuanced comparison with local practices indicated that applying biological manure alongside urea resulted in a slight reduction in N content in vegetative and economic organs, along with decreases of 10.4%, 11.2%, and 6.1% in N recovery efficiency (NRE), respectively. Prudent N management through the judicious application of partial biological manure fertilizer in rice systems could be imperative for sustaining productivity and soil fertility in southern China.

Blended controlled-release nitrogen fertilizer increases rice post-anthesis nitrogen accumulation, translocation and nitrogen-use efficiency.

One-time application of blended controlled-release nitrogen fertilizer (CRN) has the potential to solve the difficulty of top-dressing fertilizer in the cultivation of rice and reduce the cost of CRN fertilizer application. However, its effects on rice dry matter and nitrogen (N) accumulation and translocation, yield and N-use efficiency (NUE) remain uncertain. Field experiments were carried out at three sites (Mingguang, Chaohu, and Guichi) in the Yangtze River Delta in China to compare the effects of the conventional split applications of urea and the blended CRN and on post-anthesis dry matter and N accumulation and translocation, yield, and NUE in rice at 0, 60, 120, 180, and 240 kg N ha-1. The results showed that at the equal N application rates, compared under the conventional N fertilizer treatment, the blended CRN application significantly increased the rice yield by an average of 0.9-6.9%, mainly due to increase the number of spikelets per panicle. The highest yield achieved with blended CRN treatment occurred at 200 kg N ha-1, with an NUE of 45.9%. Moreover, in comparison to the conventional N fertilizer, the blended CRN treatment increased pre-anthesis N translocation (Pre-NT) by 1.0-19.8%, and the contribution of pre-NT to grain N by 0.2-8.7%, and NUE by 3.2-28.4%. Meanwhile, the blended CRN treatment reduced labor costs by 1800 Yuan ha-1 and enhanced the economic gains by 21.5-68.8%. Therefore, one-time application of blended CRN ≤ 200 kg N ha-1 application rate improved rice yield, NUE, and economic profit compared to equivalent rates of split applied conventional N fertilizers.

Advances in miniature CRISPR-Cas proteins and their applications in gene editing.

The CRISPR-Cas system consists of Cas proteins and single-stranded RNAs that recruit Cas proteins and specifically target the nucleic acid. Some Cas proteins can accurately cleave the target nucleic acid under the guidance of the single-stranded RNAs. Due to its exceptionally high specificity, the CRISPR-Cas system is now widely used in various fields such as gene editing, transcription regulation, and molecular diagnosis. However, the huge size of the most frequently utilized Cas proteins (Cas9, Cas12a, and Cas13, which contain 950-1,400 amino acids) can limit their applicability, especially in eukaryotic gene editing, where larger Cas proteins are difficult to deliver into the target cells. Recently discovered miniature CRISPR-Cas proteins, consisting of only 400 to 800 amino acids, offer the possibility of overcoming this limitation. This article systematically reviews the latest research progress of several miniature CRISPR-Cas proteins (Cas12f, Cas12j, Cas12k, and Cas12m) and their practical applications in the field of gene editing.

Design, synthesis and evaluation of 2-phenylpyrimidine derivatives as novel antifungal agents targeting CYP51.

Invasive fungal infections, with high morbidity and mortality, have become one of the most serious threats to human health. There are a few kinds of clinical antifungal drugs but large amounts of them are used, so there is an urgent need for a new structural type of antifungal drug. In this study, we carried out three rounds of structural optimisation and modification of the compound YW-01, which was obtained from the preliminary screening of the group, by using the strategy of scaffold hopping. A series of novel phenylpyrimidine CYP51 inhibitors were designed and synthesised. In vitro antifungal testing showed that target compound C6 exhibited good efficacy against seven common clinically susceptible strains, which was significantly superior to the clinical first-line drug fluconazole. Subsequently in vitro tests on metabolic stability and cytotoxicity revealed that C6 was safe and stable for hepatic microsomal function. Finally, C6 warranted further exploration as a possible novel structural type of CYP51 inhibitor.

Discovery of novel 3-(1H-pyrazol-4-yl)-1H-indazole derivatives as potent type II TRK inhibitors against acquired resistance.

Tropomyosin receptor kinase (TRK) is a promising target for treating NTRK fusion cancers. The solvent front and xDFG mutations induced by larotrectinib and entrectinib result in acquired resistance in advanced-stage patients. In this study, we report a highly potent and selective type II TRK inhibitor, 40l, developed using a structure-based design strategy. Compound 40l significantly suppressed Km-12, Ba/F3-TRKAG595R, and Ba/F3-TRKAG667C cell proliferation. In biochemical and cellular assays, 40l showed better inhibitory activity against TRKAG667C than that by the positive control, selitrectinib. Additionally, it induced apoptosis of Ba/F3-TRKAG595R and Ba/F3-TRKAG667C cells in a dose-dependent manner. Furthermore, 40l showed good selectivity for a panel of 41 kinases. In vitro assays indicated that 40l possessed outstanding plasma stability and moderate liver microsomal stability. Based on the above results, compound 40l could be further optimized to overcome the solvent front and xDFG TRK mutations.

Design, synthesis, and biological evaluation of diaminopyrimidine derivatives as novel focal adhesion kinase inhibitors.

Focal adhesion kinase (FAK) is a cytoplasmic non-receptor protein tyrosine kinase that belongs to the family of focal adhesion complexes and is responsible for the development of various tumors. Herein, 24 diaminopyrimidine derivatives were designed and synthesized based on TAE-226. Several compounds with good activity were further evaluated regarding their antiproliferative activities against two cancer cells with high FAK expression. Compound A12 showed potent anticancer activity against A549 and MDA-MB-231 cell lines with IC50 values of 130 nM and 94 nM, respectively. In vitro metabolic stability and cytochrome P450 (CYP) inhibition assays showed that A12 exhibited favorable stability and weak inhibitory activity on CYP isoforms. Preliminary evaluation of kinase selectivity showed that A12 was a multi-kinase inhibitor. The acute toxicity in vivo indicated that A12 possessed acceptable safety. Compound A12 was also selected for molecular docking studies and the prediction of molecular properties and drug-like properties. These results indicated that compound A12 could be used as a potential lead compound targeting FAK for further development.

Discovery of the First Potent, Selective, and In Vivo Efficacious Polo-like Kinase 4 Proteolysis Targeting Chimera Degrader for the Treatment of TRIM37-Amplified Breast Cancer.

Polo-like kinase 4 (PLK4) is a master regulator of centriole replication and has been proposed as a therapeutic target for multiple cancers, especially TRIM37-amplified breast cancer. The development of novel and effective therapeutic strategies for TRIM37-amplified breast cancer therapy is challenging and extremely desirable. Herein, a structure-activity relationship (SAR) study with an emphasis on exploring different linker lengths and compositions was performed to report the discovery and characterization of SP27 as the first selective PLK4 proteolysis targeting chimera (PROTAC) degrader. SP27 exhibited effective PLK4 degradation, more potent inhibition of cell growth, and more efficient precision-therapeutic effect in the TRIM37-amplified MCF-7 cell line than conventional inhibitor CZS-035. Moreover, SP27 showed 149% bioavailability after intraperitoneal administration in PK studies and potent antitumor efficacy in vivo. The discovery of SP27 demonstrated the practicality and importance of PLK4 PROTAC and paved the way for studying PLK4-dependent biological functions and treat TRIM37-amplified breast cancer.

Phase-tailored assembly and encoding of dissipative soliton molecules.

Self-assembly of particle-like dissipative solitons, in the presence of mutual interactions, emphasizes the vibrant concept of soliton molecules in varieties of laser resonators. Controllable manipulation of the molecular patterns, held by the degrees of freedom of internal motions, still remains challenging to explore more efficient and subtle tailoring approaches for the increasing demands. Here, we report a new phase-tailored quaternary encoding format based on the controllable internal assembly of dissipative soliton molecules. Artificial manipulation of the energy exchange of soliton-molecular elements stimulates the deterministic harnessing of the assemblies of internal dynamics. Self-assembled soliton molecules are tailored into four phase-defined regimes, thus constituting the phase-tailored quaternary encoding format. Such phase-tailored streams are endowed with great robustness and are resistant to significant timing jitter. All these results experimentally demonstrate the programmable phase tailoring and exemplify the application of the phase-tailored quaternary encoding, prospectively promoting high-capacity all-optical storage.

The optimum economic nitrogen rate of blended controlled-release nitrogen fertilizer for rice in the Chanoyu watershed in the Yangtze River Delta, China.

Introduction: The application of controlled-release nitrogen fertilizer (CRN) has become an important production method to achieve high crop yield and ecological safety. However, the rate of urea-blended CRN for rice is usually determined by conventional urea, and the actual rate is still unclear. Methods: A five-year field experiment was carried out in the Chaohu watershed in the Yangtze River Delta to study rice yield, N fertilizer utilization efficiency (NUE), ammonia (NH3) volatilization and economic benefit under the four urea-blended CRN treatments with a 4:3:3 ratio applied at one time (60, 120, 180, 240 kg/hm2, CRN60, CRN120, CRN180, CRN240), four conventional N fertilizer treatments (N60, N120, N180, N240) and a control without N fertilizer (N0). Results and Discussion: The results showed that the N released from the blended CRNs could well satisfy the N demand of rice growth. Similar to the conventional N fertilizer treatments, a quadratic equation was used to model the relationship between rice yield and N rate under the blended CRN treatments. The blended CRN treatments increased rice yield by 0.9-8.2% and NUE by 6.9-14.8%, respectively, compared with the conventional N fertilizer treatments at the same N application rate. The increase in NUE in response to applied blended CRN was related to the reduction in NH3 volatilization. Based on the quadratic equation, the five-year average NUE under the blended CRN treatment was 42.0% when rice yield reached the maximum, which was 28.9% higher than that under the conventional N fertilizer treatment. Among all treatments, CRN180 had the highest yield and net benefit in 2019. Considering the yield output, environmental loss, labor and fertilizer costs, the optimum economic N rate under the blended CRN treatment in the Chaohu watershed was 180-214 kg/hm2, compared with 212-278 kg/hm2 under the conventional N fertilizer treatment. The findings suggest that blended CRN improved rice yield, NUE and economic income while decreasing NH3 volatilization and negative environmental outcomes.

Design, synthesis and biological evaluation of novel indolin-2-one derivatives as potent second-generation TRKs inhibitors.

Tropomyosin receptor kinases (TRKs) are effective targets for anti-cancer drug discovery. The first-generation type I TRKs inhibitors, larotrectinib and entrectinib, exhibit durable disease control in the clinic. The emergence of acquired resistance mediated by secondary mutations in the TRKs domain significantly reduces the therapeutic efficacy of these two drugs, indicating an unmet clinical need. In this study, we designed a potent and orally bioavailable TRK inhibitor, compound 24b, using a molecular hybridization strategy. Compound 24b exhibited significant inhibitory potency against multiple TRK mutants in both biochemical and cellular assays. Furthermore, compound 24b induced apoptosis of Ba/F3-TRKAG595R and Ba/F3-TRKAG667C cells in a dose-dependent manner. Additionally, compound 24b exhibited moderate kinase selectivity. In vitro stability revealed that compound 24b showed excellent plasma stability (t1/2 > 289.1 min) and moderate liver microsomal stability (t1/2 = 44.3 min). Pharmacokinetic studies have revealed that compound 24b is an orally bioavailable TRK inhibitor with a good oral bioavailability of 116.07%. These results indicate that compound 24b be used as a lead molecule for further modifications to overcome drug-resistant mutants of TRK.

Effects of Partial Replacement of Nitrogen Fertilizer with Organic Fertilizer on Rice Growth, Nitrogen Utilization Efficiency and Soil Properties in the Yangtze River Basin.

Cake fertilizer and dairy manure were used as experimental materials to carry out a 9-year (2012-2020) field experiment in the main rice production areas in the Yangtze River basin. Different fertilization modes were used (no fertilization, CK; chemical fertilizer application alone, HY; reduced fertilization with chemical fertilizer application, RF; cake fertilizer replacement of nitrogen fertilizer, CFR; and dairy manure replacement of nitrogen fertilizer, DMR). Changes in the total rice yield, yield components, absorption of nitrogen, soil pH, organic matter, total nitrogen, and soil bulk density under different fertilization treatments were analyzed. The results show that organic fertilizer replacement leads to a stable and high rice yield. The 9-year average rice yields of the CFR and DMR treatments were 60.0% and 61.5% higher than that of CK. The nitrogen uptake of the CFR and DMR treatments was also higher than that of the other treatments. The nitrogen recovery efficiency in the current season could be increased by 16.37-22.89%, and after 9 years of testing, the soil total nitrogen contents of CFR and DMR increased by 0.23-0.85 g·kg-1 compared to the other treatments. The available P and K contents of DMR increased by 30.17 mg·kg-1 and 22.02 mg·kg-1 compared with HY, respectively. The soil bulk density was reduced by 0.08 g·cm-3. Generally, the effects of dairy manure replacement were better than those of cake fertilizer. This is an important method that can be used to fertilize the soil and foster sustainable soil utilization in the rice-growing area of the Yangtze River Basin, as a long-term partial replacement for chemical nitrogen fertilizer.

Discovery of CZS-241: A Potent, Selective, and Orally Available Polo-Like Kinase 4 Inhibitor for the Treatment of Chronic Myeloid Leukemia.

Recent studies demonstrate that PLK4 has emerged as a therapeutic target for the treatment of multiple cancers owing to its indispensable role in cell division. Herein, starting from previously identified effective compound CZS-034, based on rational drug design strategies, tyrosine kinase receptor A (TRKA) selectivity- and metabolic stability-guided structure-activity relationship (SAR) exploration were carried out to discover a highly potent (IC50 = 2.6 nM) and selective (SF = 1054.4 over TRKA) PLK4 inhibitor B43 (CZS-241) with acceptable human liver microsome stability (t1/2 = 31.5 min). Moreover, compound B43 effectively inhibited leukemia cells in 29 tested cell lines, especially chronic myeloid leukemia (CML) cell lines K562 and KU-812. Pharmacokinetic characteristics revealed that compound B43 possessed over 4 h of half-life and 70.8% bioavailability in mice. In the K562 cells xenograft mouse model, a 20 mg/kg/day dosage treatment obviously suppressed tumor progression. As a potential and novel PLK4-targeted candidate drug for CML, compound B43 is undergoing extensive preclinical safety evaluation.

Leveraging single-cell Raman spectroscopy and single-cell sorting for the detection and identification of yeast infections.

Invasive fungal infection serves as a great threat to human health. Discrimination between fungal and bacterial infections at the earliest stage is vital for effective clinic practice; however, traditional culture-dependent microscopic diagnosis of fungal infection usually requires several days, meanwhile, culture-independent immunological and molecular methods are limited by the detectable type of pathogens and the issues with high false-positive rates. In this study, we proposed a novel culture-independent phenotyping method based on single-cell Raman spectroscopy for the rapid discrimination between fungal and bacterial infections. Three Raman biomarkers, including cytochrome c, peptidoglycan, and nucleic acid, were identified through hierarchical clustering analysis of Raman spectra across 12 types of most common yeast and bacterial pathogens. Compared to those of bacterial pathogens, the single cells of yeast pathogens demonstrated significantly stronger Raman peaks for cytochrome c, but weaker signals for peptidoglycan and nucleic acid. A two-step protocol combining the three biomarkers was established and able to differentiate fungal infections from bacterial infections with an overall accuracy of 94.9%. Our approach was also used to detect ten raw urinary tract infection samples. Successful identification of fungi was achieved within half an hour after sample obtainment. We further demonstrated the accurate fungal species taxonomy achieved with Raman-assisted cell ejection. Our findings demonstrate that Raman-based fungal identification is a novel, facile, reliable, and with a breadth of coverage approach, that has a great potential to be adopted in routine clinical practice to reduce the turn-around time of invasive fungal disease (IFD) diagnostics.

Design, synthesis, and biological evaluation of a potent PLK4 inhibitor WY29 with 1H-pyrazolo[3,4-d]pyrimidine scaffold.

Centriole duplication occurs once per cell cycle and is regulated by Polo-like kinase 4 (PLK4). Overexpression of PLK4 in somatic cells can lead to the excessive formation of centrioles, directly causing chromosome segregation errors and tumorigenesis. In this study, we described our efforts to develop a series of PLK4 inhibitors with 1H-pyrazolo[3,4-d]pyrimidine core, and further structure- and receptor-based design and optimization resulted in a potent inhibitor WY29 (IC50 = 0.027 µM), which exhibited good selectivity to other PLK family members (PLK1-3). At the cellular level, compound WY29 showed excellent antiproliferative activity against three breast cancer cell lines (MCF-7, BT474, and MDA-MB-231) while weak inhibitory activity was found on normal cell line HUVECs. In addition, the in vitro preliminary drug-like properties evaluation of compound WY29 showed outstanding stability in human plasma and liver microsomes, and weak inhibitory activity against the major subtypes of human cytochrome P450. Also, the drug-like properties prediction of compound WY29 displayed remarkable drug-like properties (drug-likeness mode score: 1.06). In conclusion, these results support the further development of compound WY29 as a lead compound for PLK4-targeted anticancer drug discovery.

Design, synthesis, and biological evaluation of aminopyridine derivatives as novel tropomyosin receptor kinase inhibitors.

Tropomyosin receptor kinase (TRK) is a successful target for the treatment of various cancers caused by NTRK gene fusions. Herein, based on a rational drug design strategy, we designed and synthesized 35 aminopyrimidine derivatives that were shown to be TRKA inhibitors in the enzyme assay, among which compounds C3, C4, and C6 showed potent inhibitory activities against TRKA with IC50 values of 6.5, 5.0, and 7.0 nM, respectively. In vitro antiproliferative activity study showed that compound C3 significantly inhibited the proliferation of KM-12 cells but had weak inhibitory effect on MCF-7 cells and HUVEC cells. The preliminary druggability evaluation showed that compound C3 exhibited favorable liver microsomal and plasma stabilities and had weak or no inhibitory activity against cytochrome P450 isoforms at 10 µM. Compounds C3, C4, and C6 were also selected for ADME (absorption, distribution, metabolism, and elimination) properties prediction and molecular docking studies. Inhibition experiments showed that compound C3 was not selective for TRK subtypes. All results indicated that compound C3 was a useful candidate for the development of TRK inhibitors.

Amendment with controlled release urea increases leaf morpho-physiological traits, grain yield and NUE in a double-cropping rice system in southern China.

BACKGROUND: Understanding of mechanisms that underpin high-yielding cropping systems is essential for optimizing management practices. Currently, the contribution of plant traits such as leaf area, chlorophyll content and intercepted photosynthetically active radiation (PARi ) to yield and nitrogen use efficiency (NUE) are not fully understood. In addition, the understanding of how canopy traits are affected by nitrogen (N) management practices is unclear. The present study aimed to determine the effect of amendment with controlled release urea (CR), common urea or no urea on NUE and plant eco-physiological characteristics in a 2-year field study in a double rice cropping system. RESULTS: Regulation of N release through amendment with CR significantly increased grain yield, NUE and leaf morpho-physiological attributes. CR coupled with common urea (at comparable total N rates) increased leaf area index (LAI), relative chlorophyll content index (CCI) and PARi , leading to higher grain yield and NUE (increased 24.4% and 25.3% in early and late rice, respectively) compared to local farming practice. Structural equation model (SEM) analysis showed that differences in N application, between CR and common urea, directly accounted for differences observed in soil nutrient, PARi and NUE rather than yield components. Additionally, compared to traditional yield determinants, LAI and PARi (between booting and filling stage) are capable of predicting and explaining grain yield by 0.69 and 0.92 of R2 in early and late rice, respectively. CONCLUSION: Leaf morpho-physiological traits are important for developing N management practices to increase NUE and improve food security for paddy agriculture in southern China. © 2022 Society of Chemical Industry.

Responses of Rhizosphere Bacterial and Fungal Communities to the Long-Term Continuous Monoculture of Water Oat.

As an cultivated aquatic vegetable, the long-term continuous monocropping of water oat results in the frequent occurrence of diseases, the deterioration of ecological system and decreased quality of water oat. In this study, real-time quantitative PCR (qPCR) and Illumina high-throughput sequencing were used to determine the dynamic changes in bacterial and fungal communities in rhizosphere soil under continuous cropping of water oat for 1, 5, 10, 15 and 20 years (Y1, Y5, Y10, Y15 and Y20), and soil properties and enzyme activities were also determined. Results showed that the contents of soil organic carbon (SOC), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP) and the activities of four soil enzymes increased in Y5 and Y10 and then decreased in Y15 and Y20. Spearman correlation analysis identified SOC, TN, AP and AN as the main factors that affect the four enzyme activities. The qPCR results showed that there was no significant difference in bacterial abundance between the different planting years, while the fungal abundance first increased and then decreased. The long-term continuous planting of water oat (Y15 and Y20) significantly reduced the operational taxonomic unit numbers and the Shannon, Chao1, and ACE indices of rhizosphere bacteria and fungi. The bacterial and fungal community compositions were markedly affected by the continuous planting year. The relative abundances of Bacteroidetes and Firmicutes decreased significantly in Y10 and Bacteroidetes increased significantly in Y15. Relative abundances of dominated Mortierellomycota and Ascomycota phyla increased with the continuous cropping years, while Rozellomycota presented the opposite trend. The AK, AN, and SOC were the main factors that changed the bacterial community, while AK and AP significantly shifted the fungal community. Thus, long-term continuous planting of water oat resulted in the deterioration of soil nutrients and microbial communities. The results provided a reference for the remediation of soil under continuous water oat planting and sustainable development of water oat industry.

High-precision distributed detection of rail defects by tracking the acoustic propagation waves.

Nowadays, early defect detection plays a significant role for the railway safety warning. However, the existing methods cannot satisfy the requirements of real-time and high-precision detection. Here, a high-precision, distributed and on-line method for detecting rail defect is proposed and demonstrated. When a train goes through defects, the instantaneous elastic waves will be excited by the wheel-rail interaction, which will further propagate along railway tracks bidirectionally. Through mounting the backscattering enhanced optical fiber on the railway as sensors, the fiber optic distributed acoustic sensing system can record the propagation trace precisely. Further, the acoustic propagation fitting method is applied onto the propagation data to detect and locate defects along the long-distance railway. Especially, the dual-frequency joint-processing algorithm is proposed to improve the location accuracy. The field test proves that multiple defects along the railway can be successfully identified and located with a standard deviation of 0.314m. To the best of our knowledge, this work is the first report of distributed rail defect detection, which will bring a breakthrough for high-precision structural damage detection in the infrastructures such as the railway, pipeline and tunnel.