Disruption of the Hippo pathway promotes the proliferation of childhood acute lymphoblastic leukemia cells, inhibits apoptosis and chemosensitivity.

BACKGROUND: Despite advancements in chemotherapy and stem cell transplantation, the recurrence and chemoresistance of childhood acute lymphoblastic leukemia (cALL) remain a significant challenge, thus indicating the need for novel therapeutic targets. RESEARCH DESIGN AND METHODS: The protein levels of YAP1, p-YAP1, TAZ, and Cyr61 of cALL patients and healthy volunteers were measured by western blot analysis. Then the leukemic cell line SUP-B15 was transfected with sh-YAP1 and pcDNA3.1-YAP1 to knockdown or overexpress YAP1. The viability, chemosensitivity, apoptosis, migration, and invasion of SUP-B15 cells were determined by MTT, flow cytometry, and Transwell assay. RESULTS: The cALL patients had higher YAP1, TAZ, and Cyr61 protein expression and lower p-YAP1 protein expression in bone marrow tissues compared with healthy volunteers (p < 0.01). In SUP-B15 cells, YAP1 knockdown upregulated p-YAP1 protein expression (p < 0.01) and downregulated TAZ and Cyr61 protein expression (p < 0.01). In addition, knocking down YAP1 significantly inhibited cell viability, migration, and invasion, and induced apoptosis (p < 0.01). YAP1 knockdown also reduced the IC50 value following treatment with vincristine, daunorubicin, cyclophosphamide, and dexamethasone (p < 0.05). CONCLUSIONS: Disruption of the Hippo pathway attenuates the development of cALL by promoting cell proliferation while suppressing apoptosis and drug sensitivity.

Correlation analysis of bone marrow microvessel density and miRNA expression on drug resistance in patients with chronic myelogenous leukemia after tyrosine kinase inhibitor treatment.

OBJECTIVE: This study analyzed the relationship between bone marrow microvessel density (MVD) and the expression of four miRNAs with chronic myelogenous leukemia (CML) resistance after tyrosine kinase inhibitor (TKI) treatment. METHODS: 234 CML patients were divided into resistance and non-resistance groups in terms of the results of the 5-year follow-up. Patients were divided into the Optimum response group and the Warning/Failure group based on TKI response. MVD was determined by immunohistochemistry, and the expression levels of four miRNAs (miR-106a, miR-155, miR-146a, and miR-340) in bone marrow biopsy specimens were examined by qPCR. We evaluated the association of MVD with four miRNAs and them predictive value for CML resistance after TKI treatment. RESULTS: The MVD and the levels of miR-106a, miR-155, and miR-146a were significantly higher while the miR-340 level was lower in the resistance group than the non-resistance group. Besides, MVD had a significant correlation with the levels of miR-340 and miR-155. According to the results of survival analysis, MVD as well as miR-340 and miR-155 levels were observably correlated with 5-year survival of patients without TKI resistance. The results of the ROC curve indicated that the MVD, miR-106a, miR-340, and miR-155 had good predictive accuracy for CML resistance after TKI treatment. As for the results of multivariate analysis, disease stage, risk level (high risk), high MVD, low miR-340 expression, and high miR-155 expression were all independent risk factors for CML resistance. CONCLUSION: MVD and the expression of miR-340 and miR-155 are closely associated with CML resistance after TKI treatment.

The quantification of circular RNA 0007841 during induction therapy helps estimate the response and survival benefits to bortezomib-based regimen in multiple myeloma.

OBJECTIVE: Circular RNA_0007841 (Circ_0007841) facilitates multiple myeloma (MM) progression and resistance of the bortezomib by experimental studies, while its clinical implication in MM patients is still unclear. This study intended to evaluate the longitudinal change and prognostic role of circ_0007841 expression in MM patients receiving bortezomib-based induction therapy. METHODS: In this prospective study, bone marrow plasma cell (BMPC) samples were gained from 97 MM patients at diagnosis and after bortezomib-based induction therapy, and from 30 healthy controls (HCs) proposing BM donation. Then, circ_0007841 expression in BMPC samples was measured by reverse transcription-quantitative polymerase chain reaction. Additionally, MM patients were followed up for a median of 29.4 months. RESULTS: Circ_0007841 expression was increased in MM patients compared to HCs (P < 0.001), but it was decreased after bortezomib-based induction therapy in MM patients (P < 0.001). Moreover, circ_0007841 expression at diagnosis was associated with the presence of t (4; 14) (P = 0.034), while its expression after bortezomib-based induction therapy was linked with higher revised international staging system stage (P = 0.025) in MM patients. Interestingly, circ_0007841 expression after bortezomib-based induction therapy was lower in MM patients who achieved complete remissions (P = 0.001) and overall responses (P = 0.002) compared to those who did not. Prognostically, circ_0007841 expression after bortezomib-based induction therapy (over the median vs. below the median) independently predicted shorter progression-free survival (hazard ratio (HR): 2.497, P = 0.002) and overall survival (HR: 3.107, P = 0.008) in MM patients. CONCLUSION: Circ_0007841 quantification during induction therapy may reflect the response and survival benefits to bortezomib-based regimen in MM patients.

Stochastic model for cell population dynamics quantifies homeostasis in colonic crypts and its disruption in early tumorigenesis.

The questions of how healthy colonic crypts maintain their size, and how homeostasis is disrupted by driver mutations, are central to understanding colorectal tumorigenesis. We propose a three-type stochastic branching process, which accounts for stem, transit-amplifying (TA) and fully differentiated (FD) cells, to model the dynamics of cell populations residing in colonic crypts. Our model is simple in its formulation, allowing us to estimate all but one of the model parameters from the literature. Fitting the single remaining parameter, we find that model results agree well with data from healthy human colonic crypts, capturing the considerable variance in population sizes observed experimentally. Importantly, our model predicts a steady-state population in healthy colonic crypts for relevant parameter values. We show that APC and KRAS mutations, the most significant early alterations leading to colorectal cancer, result in increased steady-state populations in mutated crypts, in agreement with experimental results. Finally, our model predicts a simple condition for unbounded growth of cells in a crypt, corresponding to colorectal malignancy. This is predicted to occur when the division rate of TA cells exceeds their differentiation rate, with implications for therapeutic cancer prevention strategies.

Waiting times in a branching process model of colorectal cancer initiation.

We study a multi-stage model for the development of colorectal cancer from initially healthy tissue. The model incorporates a complex sequence of driver gene alterations, some of which result in immediate growth advantage, while others have initially neutral effects. We derive analytic estimates for the sizes of premalignant subpopulations, and use these results to compute the waiting times to premalignant and malignant genotypes. This work contributes to the quantitative understanding of colorectal tumor evolution and the lifetime risk of colorectal cancer.

Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice.

OBJECTIVE: To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice. MATERIALS AND METHODS: Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction were conducted to measure the protein and gene expression, while corresponding kits were used to detect the levels of oxidative stress indicators. RESULTS: PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC group, the histological NEC score was higher in the NEC + EX527 group but lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated, with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α, as well as the downregulation of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could be improved by PDTC, which could be further reversed by EX527. CONCLUSION: SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal permeability by mediating the NF-κB pathway, playing an important role in the alleviation of NEC.

Predicting binding affinities of emerging variants of SARS-CoV-2 using spike protein sequencing data: observations, caveats and recommendations.

Predicting protein properties from amino acid sequences is an important problem in biology and pharmacology. Protein-protein interactions among SARS-CoV-2 spike protein, human receptors and antibodies are key determinants of the potency of this virus and its ability to evade the human immune response. As a rapidly evolving virus, SARS-CoV-2 has already developed into many variants with considerable variation in virulence among these variants. Utilizing the proteomic data of SARS-CoV-2 to predict its viral characteristics will, therefore, greatly aid in disease control and prevention. In this paper, we review and compare recent successful prediction methods based on long short-term memory (LSTM), transformer, convolutional neural network (CNN) and a similarity-based topological regression (TR) model and offer recommendations about appropriate predictive methodology depending on the similarity between training and test datasets. We compare the effectiveness of these models in predicting the binding affinity and expression of SARS-CoV-2 spike protein sequences. We also explore how effective these predictive methods are when trained on laboratory-created data and are tasked with predicting the binding affinity of the in-the-wild SARS-CoV-2 spike protein sequences obtained from the GISAID datasets. We observe that TR is a better method when the sample size is small and test protein sequences are sufficiently similar to the training sequence. However, when the training sample size is sufficiently large and prediction requires extrapolation, LSTM embedding and CNN-based predictive model show superior performance.

Discovery of a Potent Thieno[2,3-d]pyrimidine-2,4-dione-Based Protoporphyrinogen IX Oxidase Inhibitor through an In Silico Structure-Guided Optimization Approach.

A key objective for herbicide research is to develop new compounds with improved bioactivity. Protoporphyrinogen IX oxidase (PPO) is an essential target for herbicide discovery. Here, we report using an in silico structure-guided optimization approach of our previous lead compound 1 and designed and synthesized a new series of compounds 2-6. Systematic bioassays led to the discovery of a highly potent compound 6g, 1-methyl-3-(2,2,7-trifluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, which exhibited an excellent and wide spectrum of weed control at the rates of 30-75 g ai/ha by the postemergence application and is relatively safe on maize at 75 g ai/ha. Additionally, the Ki value of 6g to Nicotiana tabacum PPO (NtPPO) was found to be 2.5 nM, showing 3-, 12-, and 18-fold higher potency relative to compound 1 (Ki = 7.4 nM), trifludimoxazin (Ki = 31 nM), and flumioxazin (Ki = 46 nM), respectively. Furthermore, molecular simulations further suggested that the thieno[2,3-d]pyrimidine-2,4-dione moiety of 6g could form a more favorable π-π stacking interaction with the Phe392 of NtPPO than the heterocyclic moiety of compound 1. This study provides an effective strategy to obtain enzyme inhibitors with improved performance through molecular simulation and structure-guided optimization.

[Radial growth of dominant coniferous species and their responses to climate changes in the Altay Mountains, China]. / é˜¿å°”æ³°å±±ä¸»è¦é’ˆå¶æ ‘ç§æ ‘æœ¨å¾„å‘ç”Ÿé•¿åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Based on the standard method of dendrochronology, we examined the tree-ring width index of two dominant tree species in the Altay Mountains, China, including Picea obovata and Larix sibirica. We analyzed the basal area increments (BAI) of those two species and the relationships between their radial growth and the climatic factors, which were compared in similar habitats. The results showed that the BAI of P. obovata was greater than L. sibirica, but the radial growth rate of L. sibirica was greater. In recent 60 years, the radial growth of P. obovata negatively correlated with high temperature in the fast growing stage of previous year, while the high temperature in June of current year promoted the radial growth of L. sibirica. There was a significantly negative correlation between radial growth of L. sibirica with temperature in January of current year. The sensitivity of tree growth to climate showed an obvious increase after an abrupt climate change under the background of recent warming and wetting trend in mid-1980s. Results of the moving correlation analysis showed that the response of the radial growth of P. obovata and L. sibirica to temperature and precipitation were enhanced under the background of climate change in the study area.

Discovery of N-Phenylaminomethylthioacetylpyrimidine-2,4-diones as Protoporphyrinogen IX Oxidase Inhibitors through a Reaction Intermediate Derivation Approach.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an effective target for green herbicide discovery. In this work, we reported the unexpected discovery of a novel series of N-phenylaminomethylthioacetylpyrimidine-2,4-diones (2-6) as promising PPO inhibitors based on investigating the reaction intermediates of our initially designed N-phenyluracil thiazolidinone (1). An efficient one-pot procedure that gave 41 target compounds in good to high yields was developed. Systematic Nicotiana tabacum PPO (NtPPO) inhibitory and herbicidal activity evaluations led to identifying some compounds with improved NtPPO inhibition potency than saflufenacil and good post-emergence herbicidal activity at 37.5-150 g of ai/ha. Among these analogues, ethyl 2-((((2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)phenyl)amino)methyl)thio)acetate (2c) (Ki = 11 nM), exhibited excellent weed control at 37.5-150 g of ai/ha and was safe for rice at 150 g of ai/ha, indicating that compound 2c has the potential to be developed as a new herbicide for weed management in paddy fields. Additionally, our molecular simulation and metabolism studies showed that the side chains of compound 2c could form a hydrogen-bond-mediated seven-membered ring system; substituting a methyl group at R1 could reinforce the hydrogen bond of the ring system and reduce the metabolic rate of target compounds in planta.

Characteristics of tree-ring density at different stem heights and their climatic responses.

Taking windfall woods of Picea schrenkiana in the southern mountainous area of the Ili Prefecture as the research object, tree-ring density chronologies were developed from the discs for maximum density (MXD), minimum density (MID), mean earlywood density (EWD), and mean latewood density (LWD) at five different stem heights (1.3, 5, 10, 15 and 20 m) to examine the climatic responses of tree-ring density by correlation analysis with local meteorological data. The results showed that there was a good coherence among the four types of tree-ring density chronologies for the same stem height, which was relatively significant for the data from 10, 15 and 20 m. The LWD had good coherence among different stem heights, while the climatic responses of tree-ring density at different stem heights varied. The MXD and LWD at 15 m were sensitive to mean tempera-ture from July to September in the previous year and from May to September in the current year. It might underestimate the response of P. schrenkiana to temperature if we sample tree-ring at 1.3 m.

Design, Synthesis, and Molecular Mechanism Studies of N-Phenylisoxazoline-thiadiazolo[3,4-a]pyridazine Hybrids as Protoporphyrinogen IX Oxidase Inhibitors.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for green agrochemical discovery. Herein, a novel N-phenylisoxazoline-thiadiazolo[3,4-a]pyridazine herbicidal active scaffold was designed by the scaffold hybridization strategy. Systematic structural optimization enabled the discovery of a series of derivatives with excellent weed control at 9.375-150 g ai/ha by the post-emergent application. Some derivatives exhibited improved Nicotiana tabacum PPO (NtPPO)-inhibitory activity than fluthiacet-methyl. Of these, 2b, with Ki = 21.8 nM, displayed higher weed control than fluthiacet-methyl at the rate of 12-75 g ai/ha, and selective to maize at 75 g ai/ha. In planta, 2b was converted into a bioactive metabolite 5 (Ki = 4.6 nM), which exhibited 4.6-fold more potency than 2b in inhibiting the activity of NtPPO. Molecular dynamics simulation explained that 5 formed stronger π-π interaction with Phe392 than that of 2b. This work not only provides a promising lead compound for weed control in maize fields but is also helpful to understand the molecular mechanism and basis of the designed hybrids.

Representation of features as images with neighborhood dependencies for compatibility with convolutional neural networks.

Deep learning with Convolutional Neural Networks has shown great promise in image-based classification and enhancement but is often unsuitable for predictive modeling using features without spatial correlations. We present a feature representation approach termed REFINED (REpresentation of Features as Images with NEighborhood Dependencies) to arrange high-dimensional vectors in a compact image form conducible for CNN-based deep learning. We consider the similarities between features to generate a concise feature map in the form of a two-dimensional image by minimizing the pairwise distance values following a Bayesian Metric Multidimensional Scaling Approach. We hypothesize that this approach enables embedded feature extraction and, integrated with CNN-based deep learning, can boost the predictive accuracy. We illustrate the superior predictive capabilities of the proposed framework as compared to state-of-the-art methodologies in drug sensitivity prediction scenarios using synthetic datasets, drug chemical descriptors as predictors from NCI60, and both transcriptomic information and drug descriptors as predictors from GDSC.

Hole Transfer Layer Engineering for CdTe Nanocrystal Photovoltaics with Improved Efficiency.

Interface engineering has led to significant progress in solution-processed CdTe nanocrystal (NC) solar cells in recent years. High performance solar cells can be fabricated by introducing a hole transfer layer (HTL) between CdTe and a back contact electrode to reduce carrier recombination by forming interfacial dipole effect at the interface. Here, we report the usage of a commercial product 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro) as a hole transfer layer to facilitate the hole collecting for CdTe nanocrystal solar cells. It is found that heat treatment on the hole transfer layer has significant influence on the NC solar cells performance. The Jsc, Voc, and power conversion efficiency (PCE) of NC solar cells are simultaneously increased due to the decreased contact resistance and enhanced built-in electric field. We demonstrate solar cells that achieve a high PCE of 8.34% for solution-processed CdTe NC solar cells with an inverted structure by further optimizing the HTL annealing temperature, which is among the highest value in CdTe NC solar cells with the inverted structure.

Genetic Architecture of Circulating Very-Long-Chain (C24:0 and C22:0) Ceramide Concentrations.

OBJECTIVE: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations. METHODS: Heritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment. RESULTS: The multivariable-adjusted heritability for C22:0 and C24:0 ceramides was 0.42 (standard error [SE], 0.07; p=1.8E-9) and 0.25 (SE, 0.08; p=0.00025), respectively. Nineteen single nucleotide polymorphisms (SNPs), all on chromosome 20, significantly associated with C22:0 concentrations; the closest gene to these variants was SPTLC3. The lead SNP (rs4814175) significantly associated with 3% lower plasma C22:0 concentrations (p=2.83E-11). Nine SNPs, all on chromosome 20 and close to SPTLC3, were significantly associated with C24:0 ceramide concentrations. All 9 were also significantly related to plasma C22:0 levels. The lead SNP (rs168622) was significantly associated with 10% lower plasma C24:0 ceramide concentrations (p=9.94E-09). CONCLUSION: SNPs near the SPTLC3 gene, which encodes serine palmitoyltransferase long chain base subunit 3 (SPTLC3; part of the enzyme that catalyzes the rate-limiting step of de novo sphingolipid synthesis) were associated with plasma C22:0 and C24:0 ceramide concentrations. These results are biologically plausible and suggest that SPTLC3 may be a potential therapeutic target for C24:0 and C22:0 ceramide modulation.

Climatic change in southern Kazakhstan since 1850 C.E. inferred from tree rings.

Although global warming is an indisputable fact, there is still uncertainty about how climate change will occur at regional levels. Kazakhstan is the largest landlocked country in the world. To best manage this country's limited water resources, socio-economic development and environmental protection, a solid understanding of regional climate change impacts is needed. In this study, tree-ring width and δ13C chronologies were established based on 99 tree-ring samples of Schrenk spruce (Picea schrenkiana Fisch. et Mey.) collected in Almaty, Kazakhstan. Climate response analysis between the tree-ring chronologies and climate data indicates that summer mean temperature is the strongest climate signal recorded by tree-ring δ13C. We reconstructed temperature change in southern Kazakhstan since 1850 C.E. using the tree-ring δ13Ccorr chronology. The results show that the temperatures in southern Kazakhstan have risen at a rate of about 0.27 °C per decade over the past 166 years. However, the rate has increased by as much as 0.44 °C per decade over the past 30 years. Analyses of temperature and precipitation data show that the climate has alternated between warm-dry and cold-humid periods over the past 166 years. The extreme droughts of 1879, 1917 and 1945 were caused by the combination of continuously high temperatures and reduced precipitation.

Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial.

BACKGROUND: Cerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP. METHODS: Eligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18F-FDG-PET/CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0. RESULTS: Forty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation. CONCLUSIONS: Our clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800016554. Registered 08 June 2018-retrospectively registered. The public title was "Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy."

Discovery of Novel N-Isoxazolinylphenyltriazinones as Promising Protoporphyrinogen IX Oxidase Inhibitors.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a promising target for herbicide discovery. Search for new compounds with novel chemotypes is a key objective for agrochemists. Here, we describe the discovery and systematic SAR-based structure optimization of novel N-isoxazolinylphenyltriazinones 5-9 as PPO inhibitors. The in vivo herbicidal activity and in vitro Nicotiana tabacum PPO (NtPPO) inhibitory activity were explored in detail. A number of the new synthetic compounds displayed strong PPO inhibitory activity with Ki values in the nanomolar range. Some compounds exhibited excellent and broad-spectrum weed control at the rate of 9.375-37.5 g ai/ha by postemergence application and showed improved monocotyledonous weed control compared to saflufenacil. Most promisingly, ethyl 3-(2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate, 5a, with a Ki value of 4.9 nM, displayed over 2- and 6-fold higher potency than saflufenacil (Ki = 10 nM) and trifludimoxazin (Ki = 31 nM), respectively. Moreover, 5a showed excellent and broad-spectrum weed control against 32 kinds of weeds at 37.5-75 g ai/ha. Rice exhibited relative tolerance to 5a at 150 g ai/ha by postemergence application, indicating that 5a could be a potential herbicide candidate for weed control in paddy fields.