RNADisease v4.0: an updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction.

Numerous studies have shown that RNA plays an important role in the occurrence and development of diseases, and RNA-disease associations are not limited to noncoding RNAs in mammals but also exist for protein-coding RNAs. Furthermore, RNA-associated diseases are found across species including plants and nonmammals. To better analyze diseases at the RNA level and facilitate researchers in exploring the pathogenic mechanism of diseases, we decided to update and change MNDR v3.0 to RNADisease v4.0, a repository for RNA-disease association (http://www.rnadisease.org/ or http://www.rna-society.org/mndr/). Compared to the previous version, new features include: (i) expanded data sources and categories of species, RNA types, and diseases; (ii) the addition of a comprehensive analysis of RNAs from thousands of high-throughput sequencing data of cancer samples and normal samples; (iii) the addition of an RNA-disease enrichment tool and (iv) the addition of four RNA-disease prediction tools. In summary, RNADisease v4.0 provides a comprehensive and concise data resource of RNA-disease associations which contains a total of 3 428 058 RNA-disease entries covering 18 RNA types, 117 species and 4090 diseases to meet the needs of biological research and lay the foundation for future therapeutic applications of diseases.

Simultaneous separation and determination of seven biphenyl cyclooctene lignans in Schisandra chinensis and its preparations by micellar electrokinetic chromatography with dual organic solvent system.

INTRODUCTION: Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. OBJECTIVE: The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. METHODS: The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S. chinensis and its preparations. RESULTS: In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9 µg/mL and from 2.6 to 3.0 µg/mL, respectively. The recovery rate was between 99.1% and 102.5%. CONCLUSION: The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S. chinensis and its preparations.

Efficacy of Autologous Hematopoietic Stem Cell Transplantation versus Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation for Follicular Lymphoma: Systematic Review and Meta-Analysis.

BACKGROUND: The effect of autologous hematopoietic stem cell transplantation (auto-HSCT) versus conventional chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the survival of patients with advanced follicular lymphoma (FL) is uncertain. OBJECTIVES: To elucidate this, FL and HSCT were used as keywords to search in PubMed, Embase, Web of Science, and Cochrane Library databases. METHOD: After data extraction and quality evaluation, a total of 13 studies were included, seven of which compared auto-HSCT with conventional chemotherapy and the other six compared allo-HSCT with auto-HSCT to the survival of FL patients. RESULTS: The results showed that auto-HSCT improved overall survival (OS), progression-free survival, and event-free survival of FL patients compared with conventional chemotherapy without auto-HSCT. Compared with allo-HSCT, the patients receiving auto-HSCT had longer OS and lower non-recurrent mortality. CONCLUSIONS: Auto-HSCT can provide a survival advantage for patients with FL compared with conventional chemotherapy and allo-HSCT did not result in a survival benefit.

Active projection nonlinear γ correction method for fringe projection profilometry.

In fringe projection profilometry (FPP), the luminance nonlinearity generated by the superimposed γ effect of the projector and camera can lead to distortion of the intensity of the sinusoidal phase-shift fringe, resulting in a reduction of measurement precision and resolution. Traditional phase error compensation and γ-correction methods need to focus on the projector's optimal performance. However, commercial projectors often have huge apertures and are, therefore, unable to project a perfectly focused sinusoidal fringe image. This paper proposes an easy-to-implement active projection error correction method with high precision that is insensitive to projector defocus. After calibrating the projector to establish the nonlinear γ-response model of the optical measurement system, inverse γ compensation is performed. By generating and projecting a set of precorrected sinusoidal fringes, the camera can capture the high-quality sinusoidal fringe image and decrease the phase measurement error caused by the nonlinear γ effect of the FPP system. Computer simulations and experiments verify the effectiveness and feasibility of the proposed method for estimating and correcting the nonlinear γ distortion of the FPP system. The experimental results show that using the proposed active projection method to compensate for the error of the three-step phase-shift algorithm can achieve a high-precision measurement, and the influence of the system's nonlinear γ effect on the measurement accuracy is significantly suppressed.

Optimization of cationic polymer-mediated transfection for RNA interference.

Transfection efficiency was estimated to optimize the conditions for RNA interference (RNAi), including transfection time, validity, and nucleic acid concentration and type, using the EZ Trans Cell Reagent, a cationic polymer. An shRNA against GFP was designed and transfected into cells using the EZ transfection reagent. The shRNA significantly decreased the expression of GFP. In addition, pre-diluted transfection reagent at room temperature and small nucleic acids increased the transfection efficiency, which peaked at 24 h. Compared with circular nucleic acids, linear nucleic acids showed higher transfection efficiency and a higher genome integration rate. We optimized cationic polymer-mediated RNAi conditions, and our data will be useful for future RNAi studies.

Isostructural and Multivalent Anion Substitution toward Improved Phosphate Cathode Materials for Sodium-Ion Batteries.

Polyanion-type phosphate materials are highly promising cathode candidates for next-generation batteries due to their excellent structural stability during cycling; however, their poor conductivity has impeded their development. Isostructural and multivalent anion substitution combined with carbon coating is proposed to greatly improve the electrochemical properties of phosphate cathode in sodium-ion batteries (SIBs). Specifically, multivalent tetrahedral SiO4 4- substitute for PO4 3- in Na3 V2 (PO4 )3 (NVP) lattice, preparing the optimal Na3.1 V2 (PO4 )2.9 (SiO4 )0.1 with high-rate capability (delivering a high capacity of 82.5 mAh g-1 even at 20 C) and outstanding cyclic stability (≈98% capacity retention after 500 cycles at 1 C). Theoretical calculation and experimental analyses reveal that the anion-substituted Na3.1 V2 (PO4 )2.9 (SiO4 )0.1 reduces the bandgap of NVP lattice and enhanced its structural stability, Na+ -diffusion kinetics and electronic conductivity. This strategy of multivalent and isostructural anion substitution chemistry provides a new insight to develop advanced phosphate cathodes.

Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells.

Toll-like receptors (TLRs) are important sensors that recognize pathogen-associated molecular patterns. Generally, TLR9 is known to recognize bacterial or viral DNA but not viral RNA and initiate an immune response. Herein, we demonstrate that infection with dengue virus (DENV), an RNA virus, activates TLR9 in human dendritic cells (DCs). DENV infection induces release of mitochondrial DNA (mtDNA) into the cytosol and activates TLR9 signaling pathways, leading to production of interferons (IFNs). The DENV-induced mtDNA release involves reactive oxygen species generation and inflammasome activation. DENV infection disrupts the association between transcription factor A mitochondria (TFAM) and mtDNA and activates the mitochondrial permeability transition pores. The side-by-side comparison of TLR9 and cyclic GMP-AMP synthase (cGAS) knockdown reveals that both cGAS and TLR9 comparably contribute to DENV-induced immune activation. The significance of TLR9 in DENV-induced immune response is also confirmed in examination with the bone marrow-derived DCs prepared from Tlr9-knockout mice. Our study unravels a previously unrecognized phenomenon in which infection with an RNA virus, DENV, activates TLR9 signaling by inducing mtDNA release in human DCs.

Excision of preauricular sinus with abscess drainage in children.

PURPOSE: To introduce a feasible approach for excising a preauricular sinus with abscess in children. MATERIALS AND METHODS: Patients under 14 years old with a preauricular sinus abscess and volunteering for surgery were involved in this study. RESULTS: Neither recurrence nor local deformity was found in these patients with a follow-up of 3 to 72 months. CONCLUSIONS: Excising the preauricular sinus with abscess in children is a feasible approach to treatment.

Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection.

The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV), herpes simplex virus (HSV), influenza virus, dengue virus (DENV), and human immunodeficiency virus (HIV). This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases.

Up-regulation of galectin-9 induces cell migration in human dendritic cells infected with dengue virus.

Galectin-9 (Gal-9) exerts immunosuppressive effects by inducing apoptosis in T cells that produce interferon-γ and interleukin (IL)-17. However, Gal-9 can be pro-inflammatory in lipopolysaccharide-stimulated monocytes. Using microarray analysis, we observed that Gal-9 was up-regulated in human dendritic cells (DCs) after dengue virus (DV) infection. The investigation into the immunomodulatory effects and mechanisms of Gal-9 in DCs exposed to DV revealed that DV infection specifically increased mRNA and protein levels of Gal-9 but not those of Gal-1 or Gal-3. Blocking p38, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase (ERK), inhibited DV-induced expression of Gal-9. Reduction in Gal-9 by small interference RNA treatment suppressed DV-stimulated migration of DCs towards the chemoattractants CCL19 and CCL21. In addition, DV-induced IL-12p40 production was reduced after knockdown of Gal-9 in DCs. Furthermore, Gal-9 deficiency suppressed DV-induced activation of nuclear factor-κB. Inhibition of DV-induced DC migration under conditions of Gal-9 deficiency was mediated through suppressing ERK activation but not by regulating the expression of CCR7, the receptor for CCL19 and CCL21. Both the reduction in IL-12 production and the suppression of ERK activity might account for the inhibition of DV-induced DC migration after knockdown of Gal-9. In summary, this study reveals the roles of Gal-9 in DV-induced migration of DCs. The findings indicate that Gal-9 might be a therapeutic target for preventing immunopathogenesis induced by DV infection.

No effect of autistic traits on social attention: evidence based on single-cue and conflicting-cues scenarios.

Individuals often use others' gaze and head directions to direct their attention. To investigate the influence of autistic traits on social attention, we conducted two experiments comparing groups with high and low autistic traits in single-cue (Experiment 1) and conflicting-cue (Experiment 2) scenarios. Our findings indicate that individuals responded more rapidly to the direction of a single social cue or the consensus of multiple cues. However, we did not observe significant differences in social attention between individuals with high and low autistic traits. Notably, as the stimulus onset asynchrony (SOA) increased, individuals with low autistic traits exhibited greater improvements in reaction speed compared to those with high autistic traits. This suggests that individuals with low autistic traits excel at leveraging temporal information to optimize their behavioral readiness over time, hinting at potential variations in cognitive flexibility related to autistic traits.

[Research Progress of CAR-T Cell Immunotherapy in B-Cell Non-Hodgkin's Lymphoma--Review].

Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant advantages for high-risk and relapsed/refractory B cell non-Hodgkin's lymphoma (B-NHL) patients. Currently, a variety of anti-CD19 CAR-T cells have been approved by the FDA for the treatment of B-NHL, such as axicabtagene ciloleucel, tisagenlecucel, lisocababtagene maraleucel and brexucabtagene autoleucel. In addition, many studies are actively exploring and developing different targeted CAR-T cells, which show great potential in B-NHL. This review briefly summarized the latest research progress on the application of CAR-T in common B-NHL.

[Research Progress of Targeted Therapy for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma --Review].

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a relatively inert B lymphocyte proliferative disease. In recent years with the launch of new drugs, chemotherapy has been gradually replaced by targeted therapy, which significantly prolongs the survival of patients and reduces the side effects of treatment. At present, BTK inhibitors, PI3K inhibitors, spleen tyrosine kinase (SYK) inhibitors and BCL-2 inhibitors are the most studied targeted therapeutic drugs for CLL/SLL. This article reviews the research progress of different types of targeted therapeutic drugs in the treatment of CLL/SLL.

Muscle activation patterns and gait changes in unilateral knee osteoarthritis patients: a comparative study with healthy controls.

The objective of this study was to investigate the differences in muscle activation and kinematic parameters between patients with unilateral knee osteoarthritis (OA) and healthy individuals. Additionally, the study aimed to determine the correlation between muscle activation and kinematic parameters with knee OA symptoms. Participants with unilateral knee OA (n = 32) and healthy individuals (n = 32) completed the gait test. Electromyography (EMG) and motion capture were employed to collect muscle activation data and kinematic parameters. Spearman's correlation coefficient was used to analysis the correlation between BMI, symptomatic side EMG parameters, kinematic parameters, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Furthermore, a multiple linear regression analysis of WOMAC pain was also conducted. The peak root mean square, integrated electromyography, and co-activation index (CCI) were increased bilaterally in the unilateral knee OA group compared to the healthy group. Furthermore, these values were higher on the symptomatic side than on the asymptomatic side. Compared with the healthy group, the knee OA group had lower gait speed, decreased stride length and cadence on bilateral sides, longer total stance time and double-stance time, and shorter single stance time and swing time. The maximum knee flexion angle of the swing phase on the symptomatic side of the knee OA group was smaller than that on the asymptomatic side and healthy group. Changes in EMG and gait parameters on the symptomatic side correlated with WOMAC scores. The main factors influencing WOMAC pain were the CCI values of the lateral femoral and biceps femoris muscles and gait speed. Muscle activation and kinematic parameters in the lower limbs of patients with unilateral knee OA were altered bilaterally during walking. These alterations on the symptomatic side were associated with knee OA-related pain. ChiCTR2200064958. Date of registration: 2022-10-24. Key Points • Unilateral symptomatic knee OA leads to bilateral alterations in muscle activation and gait parameters. • Symptomatic muscle activation and gait parameter changes in knee OA patients are associated with knee OA symptoms. • Correcting abnormal muscle activation conditions and gait training may reduce knee OA-related pain.

Using phlebotomy to remove a difficult peripherally inserted central catheter insertion and removal in very low birth weight infants: case report of a rare complication.

Background: A peripherally inserted central catheter (PICC) is an important way to supply long-term intravenous infusion or parenteral nutrition for premature infants, especially very low birth weight (VLBW) infants. PICC removal difficulties occur mostly during use. It is rare to have difficulty removing a PICC due to reverse folding during catheterization. We presented a case to explore the nursing experience of caring for a VLBW infant with difficult PICC removal. Case Description: A 30-week, 1,240-g infant, suffered a difficult PICC removal during the catheterization adjustment process. The X-ray images showed that the tip of the catheter was bent at the elbow joint and formed three abnormal bends in the blood vessel. The result was that the catheter was removed by a multidisciplinary team, and the reasons for the difficulty were analyzed. We used multidisciplinary team collaboration to solve a clinical problem. First, we analyzed the possible causes of a difficult removal by consulting PICC nurses, vascular interventional surgeons, and venous specialist nurses. Second, we used nonsurgical treatment methods to try to solve the problem. Finally, the catheter was completely removed using phlebotomy. Healing of wound and the growth of blood vessel are both well. Conclusions: In neonates, PICC may have obstacles in insertion and removal, methods such as posture changes, wet and hot compresses, and local massage can help. Multidisciplinary cooperation can improve the success rate of removal with minimal trauma. Individualized analysis of causes and measures are key steps to solve the difficulty of PICC insertion and removal.

RIscoper 2.0: A deep learning tool to extract RNA biomedical relation sentences from literature.

RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.

Dopa and tetrahydrobiopterin (BH4) supplementation are recommended therapies for the dopa-responsive dystonia caused by GTP cyclohydrolase 1 (GCH1, also known as GTPCH) deficits. However, the efficacy and mechanisms of these therapies have not been intensively studied yet. In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1KI/KI, which manifested infancy-onset motor deficits and growth retardation similar to the patients. First, dopa supplementation supported Gch1KI/KI mouse survival to adulthood, but residual motor deficits and dwarfism remained. Interestingly, RNAseq analysis indicated that while the genes participating in BH4 biosynthesis and regeneration were significantly increased in the liver, no significant changes were observed in the brain. Second, BH4 supplementation alone restored the growth of Gch1KI/KI pups only in early postnatal developmental stage. High doses of BH4 supplementation indeed restored the total brain BH4 levels, but brain dopamine deficiency remained. While total brain TH levels were relatively increased in the BH4 treated Gch1KI/KI mice, the TH in the striatum were still almost undetectable, suggesting differential BH4 requirements among brain regions. Last, the growth of Gch1KI/KI mice under combined therapy outperformed dopa or BH4 therapy alone. Notably, dopamine was abnormally high in more than half, but not all, of the treated Gch1KI/KI mice, suggesting the existence of variable synergetic effects of dopa and BH4 supplementation. Our results provide not only experimental evidence but also novel mechanistic insights into the efficacy and limitations of dopa and BH4 therapies for GTPCH deficiency.

Lumbrokinase Extracted from Earthworms Synergizes with Bevacizumab and Chemotherapeutics in Treating Non-Small Cell Lung Cancer by Targeted Inactivation of BPTF/VEGF and NF-κB/COX-2 Signaling.

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, is still poorly understood. In this study, we explored the anti-tumor role and the responsive molecular mechanisms of lumbrokinase in suppressing tumor angiogenesis and chemoresistance development in NSCLC and its clinical potential in combination with bevacizumab and chemotherapeutics. Lumbrokinase was found to inhibit cell proliferation in a concentration-dependent manner and caused metastasis suppression and apoptosis induction to varying degrees in NSCLC cells. Lumbrokinase enhanced the anti-angiogenesis efficiency of bevacizumab by down-regulating BPTF expression, decreasing its anchoring at the VEGF promoter region and subsequent VEGF expression and secretion. Furthermore, lumbrokinase treatment reduced IC50 values of chemotherapeutics and improved their cytotoxicity in parental and chemo-resistant NSCLC cells via inactivating the NF-κB pathway, inhibiting the expression of COX-2 and subsequent secretion of PGE2. LPS-induced NF-κB activation reversed its inhibition on NSCLC cell proliferation and its synergy with chemotherapeutic cytotoxicity, while COX-2 inhibitor celecoxib treatment boosted such effects. Lumbrokinase combined with bevacizumab, paclitaxel, or vincristine inhibited the xenograft growth of NSCLC cells in mice more significantly than a single treatment. In conclusion, lumbrokinase inhibited NSCLC survival and sensitized NSCLC cells to bevacizumab or chemotherapeutics treatment by targeted down-regulation of BPTF/VEGF signaling and inactivation of NF-κB/COX-2 signaling, respectively. The combinational applications of lumbrokinase with bevacizumab or chemotherapeutics are expected to be developed as promising candidate therapeutic strategies to improve the efficacy of the original monotherapy in anti-NSCLC.

Quantification of Measurable Residual Disease Detection by Next-Generation Sequencing-Based Clonality Testing in B-Cell and Plasma Cell Neoplasms.

Next-generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in post-treatment settings can be crucial for relapse risk stratification in patients with B-cell and plasma cell neoplasms. Prior studies have focused on validation of various technical aspects of the MRD assays, but more studies are warranted to establish the performance characteristics and enable standardization and broad utilization in routine clinical practice. Here, the authors describe an NGS-based IGH MRD quantification assay, incorporating a spike-in calibrator for monitoring B-cell and plasma cell neoplasms based on their unique IGH rearrangement status. Comparison of MRD status (positive or undetectable) by NGS and flow cytometry (FC) assays showed high concordance (91%, 471/519 cases) and overall good linear correlation in MRD quantitation, particularly for chronic lymphocytic leukemia and B-lymphoblastic leukemia/lymphoma (R = 0.85). Quantitative correlation was lower for plasma cell neoplasms, where underestimation by FC is a known limitation. No significant effects on sequencing efficiency by the spike-in calibrator were observed, with excellent inter- and intra-assay reproducibility within the authors' laboratory, and in comparison to an external laboratory, using the same assay and protocols. Assays performed both at internal and external laboratories showed highly concordant MRD detection (100%) and quantitation (R = 0.97). Overall, this NGS-based MRD assay showed highly reproducible results with quantitation that correlated well with FC MRD assessment, particularly for B-cell neoplasms.

Preparation and Properties of Photoresponsive Pendimethalin@Silica-cinnamamide/γ-CD Microspheres for Pesticide Controlled Release.

Photocontrolled pesticide delivery systems have broad prospects for application in agriculture. Here, a novel photoresponsive herbicide delivery system was fabricated by functionalizing silica microsphere surfaces with cinnamamide and encapsulating the silica-cinnamamide with γ-cyclodextrin (γ-CD) to form a double-layered microsphere shell loaded with pendimethalin (pendimethalin@silica-cinnamamide/γ-CD). The microspheres showed remarkable loading capacity for pendimethalin (approximately 30.25% w/w) and displayed excellent photoresponsiveness and controlled release. The cumulative drug release rate exceeded 80% over 72 h under UV or sunlight irradiation. The herbicidal activity of the microspheres against Echinochloa crusgalli (L.) Beauv. was almost the same as that of pendimethalin under UV or sunlight. A bioactivity survey confirmed that the pendimethalin@silica-cinnamamide/γ-CD microspheres exhibited longer duration weed control than commercial pendimethalin. Allium cepa chromosomal aberration assays demonstrated that the microspheres showed lower genotoxicity than pendimethalin. These advantages indicate that pendimethalin@silica-cinnamamide/γ-CD microspheres constitute an environmentally friendly herbicidal formulation.