Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows.

Introduction: Peripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows. Methods: In this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal. Results: In comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines. Discussion: In summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Common Methods for Phylogenetic Tree Construction and Their Implementation in R.

A phylogenetic tree can reflect the evolutionary relationships between species or gene families, and they play a critical role in modern biological research. In this review, we summarize common methods for constructing phylogenetic trees, including distance methods, maximum parsimony, maximum likelihood, Bayesian inference, and tree-integration methods (supermatrix and supertree). Here we discuss the advantages, shortcomings, and applications of each method and offer relevant codes to construct phylogenetic trees from molecular data using packages and algorithms in R. This review aims to provide comprehensive guidance and reference for researchers seeking to construct phylogenetic trees while also promoting further development and innovation in this field. By offering a clear and concise overview of the different methods available, we hope to enable researchers to select the most appropriate approach for their specific research questions and datasets.

Antimicrobial Activity and Mechanisms of Punicalagin against Vibrio parahaemolyticus.

This study sought to explore the antimicrobial activity of punicalagin against V. parahaemolyticus and its potential modes of action. V. parahaemolyticus ATCC 17802 and RIMD 2210633Sm were exposed to punicalagin, and the energy production, membrane potential, and envelope permeability, as well as the interaction with cell biomolecules, were measured using a variety of fluorescent probes combined with electrophoresis and Raman spectroscopy. Punicalagin treatment disrupted the envelope integrity and induced a decrease in intracellular ATP and pH. The uptake of 1-N-phenyl-naphtylamine (NPN) demonstrated that punicalagin weakened the outer membrane. Punicalagin damaged the cytoplasmic membrane, as indicated by the membrane depolarization and the leakage of intracellular potassium ions, proteins, and nucleic acids. Electronic microscopy observation visualized the cell damage caused by punicalagin. Further, gel electrophoresis coupled with the Raman spectrum assay revealed that punicalagin affected the protein expression of V. parahaemolyticus, and there was no effect on the integrity of genomic DNA. Therefore, the cell envelope and proteins of V. parahaemolyticus were the assailable targets of punicalagin treatment. These findings suggested that punicalagin may be promising as a natural bacteriostatic agent to control the growth of V. parahaemolyticus.

Recent Advances and Outlook of Benzopyran Derivatives in the Discovery of Agricultural Chemicals.

Scaffold structures, new mechanisms of action, and targets present enormous challenges in the discovery of novel pesticides. The discovery of new scaffolds is the basis for the continuous development of modern agrochemicals. Identification of a good scaffold such as triazole, carbamate, methoxy acrylate, pyrazolamide, pyrido-pyrimidinone mesoionic, and bisamide often leads to the development of a new series of pesticides. In addition, pesticides with the same target, including the inhibitors of succinate dehydrogenase (SDH), oxysterol-binding-protein, and p-hydroxyphenyl pyruvate dioxygenase (HPPD), may have the same or similar scaffold structure. Recent years have witnessed significant progress in the discovery of new pesticides using natural products as scaffolds or bridges. In recent years, there have been increasing reports on the application of natural benzopyran compounds in the discovery of new pesticides, especially osthole and coumarin. A systematic and comprehensive review of benzopyran active compounds in the discovery of new agricultural chemicals is helpful to promote the discussion and development of benzopyran active compounds. Therefore, this work systematically reviewed the research and application of benzopyran derivatives in the discovery of agricultural chemicals, summarized the antiviral, herbicidal, antibacterial, fungicidal, insecticidal, nematicidal and acaricidal activities of benzopyran active compounds, and discussed the structural-activity relationship and mechanism of action. In addition, some active fragments were recommended to further optimize the chemical structure of benzopyran active compounds based on reference information.

Dexmedetomidine affects the NOX4/Nrf2 pathway to improve renal antioxidant capacity.

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins. KEY FINDINGS: The open-field experiments validated the successful establishment of the acute stress model. Acute stress-induced renal injury led to increased NADPH oxidase 4 (NOX4) protein expression and decreased expression levels of nuclear transcription factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). Following DEX treatment, there was a significant reduction in renal NOX4 expression. The DEX-treated group exhibited normalized renal biochemical results and less damage observed in pathological sections compared to the acute stress group. CONCLUSIONS: The findings suggest that DEX treatment during acute stress can impact the NOX4/Nrf2/HO-1/NQO1 signaling pathway and inhibit oxidative stress, thereby preventing acute stress-induced kidney injury. Additionally, DEX shows promise for clinical applications in stress syndromes.

Direct Oxidative Cyclization of 3-Arylpropionic Acids to 3,4-Dihydrocoumarins: Reinvestigation of the Reaction Mechanism.

Instigated by olfactory analysis of odorant molecules, the constitutions of 3,4-dihydrocoumarins prepared by PIFA-based oxidative cyclizations of 3-arylpropionic acids were revised by means of 2D NMR and X-ray analysis. Supported by computational analysis, the migratory mechanism of intermediate spirolactonic cations has been amended: 1,2-alkyl shifts instead of 1,2-carboxylic shifts were selectively obtained.

Fe-MOF/AuNP-based ratiometric electrochemical immunosensor for the detection of deoxynivalenol in grain products.

A ratiometric assay was designed to improve the sensitivity and reliability of electrochemical immunosensors for deoxynivalenol (DON) detection. The indicator signal caused by the Fe-based metal-organic framework nanocomposites loaded with gold nanoparticles and the internal reference signal from the [Fe(CN)6]3-/4- in the electrolyte came together at the immunosensor. When immunoreactivity occurred, the indicator signals decreased as the concentration of DON increased, while the internal reference signals increased slightly. The ratio of the indicator signal to the internal reference signal was available for reproducible and sensitive monitoring of DON. The prepared immunosensor showed excellent performance in the range from 0.5 to 5000 pg mL-1, and the detection limit was 0.0166 pg mL-1. The immunosensor achieved satisfactory detection toward DON in spiked and actual samples and has a promising application in the control of DON in grain products.

A novel isophorone-based NIR fluorescent and colormetric probe for Al3+ sensing and its application for living cells and plants imaging.

In this paper, an isophorone-based NIR fluorescent and colormetric probe BDDH for Al3+ was synthesized and characterized, it showed highly selectivity and sensitivity through significant fluorescence enhancement and visible color change towards Al3+. The job plot confirmed that the binding ratio of BDDH with Al3+ was 1:1. Furthermore, the limit of detection (LOD) of Al3+ was determined to be 4.01 × 10-8 M. Moreover, BDDH was successfully applicated in identification of Al3+ in the different water samples, cell imaging in alive MCF-7 cells and plant imaging in soybean roots.

Comparison of the gene expression profile of testicular tissue before and after sexual maturity in Qianbei Ma goats.

BACKGROUND: With long-term research on the reproductive ability of Qianbei Ma goat, we found that the puberty of the male goats comes at the age of 3 months and reaches sexual maturity at 4 months,the male goats are identified as physically mature at 9 months and able to mate. Compared with other kinds of breeds of goats, Qianbei Ma goat is featured with more faster growth and earlier sexual maturity.Therefore, in order to explore the laws of growth of Qianbei Ma goat before sexual maturity(3-month-old)and after sexual maturity (9-month-old). The testicular tissue was collected to explore their changes in morphology through HE staining, the serum was collected to detect the hormone content, and the mRNA expression profile of the testis was analyzed by transcriptomics. In this way, the effect of testicular development on the reproduction of Qianbei ma goats was further analyzed. RESULTS: The results showed that the area and diameter of spermatogenic tubules were larger at 9 months than 3 months, and the number of spermatocytes, interstitial cells, spermatogonia and secondary spermatocytes in the lumen of the tubules showed a similar trend. The appearance of spermatozoa at age 3 months indicated that puberty had begun in Qianbei Ma goats. The Elasa test for testosterone, luteinizing hormone, follicle stimulating hormone and anti-Müllerian hormone showed that the levels of these hormones in the serum at age 9 months were all highly significantly different than those at age 3 months (P < 0.01). There were 490 differentially expressed genes (DEGs) between the (|log2(fold change)| > 1 and p value < 0.05) 3-month-old and 9-month-old groups, of which 233 genes were upregulated and 257 genes were downregulated (3 months of age was used as the control group and 9 months of age was used as the experimental group). According to the GO and KEGG enrichment analyses of DEGs, PRSS58, ECM1, WFDC8 and LHCGR are involved in testicular development and androgen secretion, which contribute to the sexual maturation of Qianbei Ma goats. CONCLUSIONS: Potential biomarker genes and relevant pathways involved in the regulation of testicular development and spermatogenesis in Qianbei Ma goats were identified, providing a theoretical basis and data support for later studies on the influence of testicular development and spermatogenesis before and after sexual maturity in Qianbei Ma goats.

Radiomics approach to distinguish between benign and malignant soft tissue tumors on magnetic resonance imaging.

Objective: To build a radiomics signature based on MRI images and evaluate its capability for preoperatively identifying the benign and malignant Soft tissue neoplasms (STTs). Materials and methods: 193 patients (99 malignant STTs and 94 benign STTs) were at random segmented into a training cohort (69 malignant STTs and 65 benign STTs) and a validation cohort (30 malignant STTs and 29 benign STTs) with a portion of 7:3. Radiomics features were extracted from T2 with fat saturation and T1 with fat saturation and gadolinium contrast images. Radiomics signature was developed by the least absolute shrinkage and selection operator (LASSO) logistic regression model. The receiver that operated characteristics curve (ROC) analysis was used to assess radiomics signature's prediction performance. Inner validation was performed on an autonomous cohort that contained 40 patients. Results: A radiomics was developed by a total of 16 radiomics features (5 original shape features and 11 were wavelet features) achieved favorable predictive efficacy. Malignant STTs showed higher radiomics score than benign STTs in both training cohort and validation cohort. A good prediction performance was shown by the radiomics signature in both training cohorts and validation cohorts. The training cohorts and validation cohorts had an area under curves (AUCs) of 0.885 and 0.841, respectively. Conclusions: A radiomics signature based on MRI images can be a trustworthy imaging biomarker for identification of the benign and malignant STTs, which could help guide treatment strategies.

The effect of multiple factors on changes in organic-inorganic fractions of condensable particulate matter during coal combustion.

Condensable particulate matter (CPM) from coal combustion is the focus of current pollutant emission studies, and CPM can be divided into inorganic and organic fractions according to the component characteristics. At present, the effects of different factors in the combustion process on the organic and inorganic components of CPM have not been discussed systematically. Here, we conducted combustion experiments collected the generated CPM on a well-controlled drip tube furnace, and investigated the effects of different factors on the generation of organic and inorganic components of CPM by varying the furnace wall insulation temperature, the ratio of gas supply components and the water vapor content in the flue gas. The results showed that the increase in combustion temperature (1300-1500 °C) and oxygen concentration (15-25%) reduced the total CPM generation by 9.8% and 19.98%, respectively, and the intervention of water vapor increased the ability of the whole CPM sampling device to capture ultrafine condensable particles. The generation of CPM organic components decreased with the enhancement of combustion temperature and oxygen content on combustion characteristics, and alkanes shifted to low carbon content. The amount of CPM inorganic components increased with the increase of water vapor content in the flue gas, and this change was dominated by SO42-. The above results provide a feasible idea for the next step of the precise reduction of CPM components.

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, which is a key step in the synthesis of porphyrins in vivo. PPO inhibitors use protoporphyrinogen oxidase as the target and block the biosynthesis process of porphyrin by inhibiting the activity of the enzyme, eventually leading to plant death. In this paper, phenyl triazolinone was used as the parent structure, and the five-membered heterocycle with good herbicidal activity was introduced by using the principle of substructure splicing. According to the principle of bioisosterism, the sulfur atoms on the thiophene ring were replaced with oxygen atoms. Finally, 33 phenyl triazolinones and their derivatives were designed and synthesized, and their characterizations and biological activities were investigated. The in vitro PPO inhibitory activity and greenhouse herbicidal activity of 33 target compounds were determined, and compound D4 with better activity was screened out. The crop safety determination, field weeding effect determination, weeding spectrum determination, and crop metabolism study were carried out. The results showed that compound D4 showed good safety to corn, soybean, wheat, and peanut but poor selectivity to cotton. The field weeding effect of this compound is comparable to that of the commercial herbicide sulfentrazone. The herbicidal spectrum experiment showed that compound D4 had a wide herbicidal spectrum and a good growth inhibition effect on dicotyledonous weeds. Molecular docking results showed that compound D4 forms a hydrogen bond with amino acid residue Arg-98 in the tobacco mitochondria (mtPPO)-active pocket and forms two π-π stacking interactions with Phe-392. This indicates that compound D4 has stronger PPO inhibitory activity. This indicates that compound D4 has wide prospects for development.

Polygonatum sibiricum Saponin Prevents Immune Dysfunction and Strengthens Intestinal Mucosal Barrier Function in Cyclophosphamide-Induced Immunosuppressed BALB/c Mice.

The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-α, IFN-γ, IL-4, IL-6, IL-ß, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-α, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6/MyD88/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.

Risk factors for venous thromboembolism following knee arthroscopy: A systematic review and meta-analysis of observational studies.

Objectives: To evaluate the risk factors for increased risk of venous thrombosis after arthroscopic knee surgery. Methods: PubMed, EMBASE and Cochrane Library were searched from their inception to April 4, 2023. Observational studies investigated venous thrombosis following arthroscopic knee surgery were included. The Newcastle Ottawa Scale (NOS) was used to evaluate the methodological quality of included studies. The odd ratios (ORs) and 95% confidence intervals (CIs) pertaining to each risk factor were synthesized through a random effects model by STATA 14 software. Results: The protocol this meta-analysis has been registered on PROSPERO (CRD42023410283). A total of 22 observational studies were included in the systematic review, all of which were of moderate or high methodological quality. The results of the meta-analysis revealed that several factors were significantly associated with an elevated risk of venous thrombosis following arthroscopic knee surgery. These factors included age (mean age ≥30 years) [OR = 1.08, 95%CI (1.04, 1.13), P = 0.001], overweight or obesity [OR = 1.31, 95%CI (1.13, 1.52), P＜0.001], oral contraceptive use [OR = 1.90, 95%CI (1.52, 2.37), P＜0.001], and smoking history [OR = 1.35, 95%CI (1.06, 1.71), P = 0.014]. Furthermore, the subgroup analysis indicated that patients with an average age over 50 years [OR = 3.18, 95%CI (1.17, 8.66), P = 0.001] and those who underwent surgery with a tourniquet for ≥90 min [OR = 4.79, 95%CI (1.55, 14.81), P = 0.007] were at a significantly increased risk of venous thrombosis after knee arthroscopy. Conclusion: Age, obesity, oral contraceptives, smoking history, and prolonged tourniquet use may increase the risk of venous thrombosis after arthroscopic knee surgery. The incidence of venous thrombosis after knee arthroscopy is on a downward trend, but due to its severity, increasing awareness of risk factors and implementing effective prophylaxis are important tasks for clinicians to prevent the risk of venous thrombosis after knee arthroscopy.

Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway.

Retinal inflammation is a pivotal characteristic observed in various retinal degenerative disorders, notably age-related macular degeneration (AMD), primarily orchestrated by the activation of microglia. Targeting the inhibition of microglial activation has emerged as a therapeutic focal point. Quercetin (Qu), ubiquitously present in dietary sources and tea, has garnered attention for its anti-neuroinflammatory properties. However, the impact of Qu on retinal inflammation and the associated mechanistic pathways remains incompletely elucidated. In this study, retinal inflammation was induced in adult male C57BL/6 J mice through intraperitoneal administration of LPS. The results revealed that Qu pre-treatment induces a phenotypic shift in microglia from M1 phenotype to M2 phenotype. Furthermore, Qu attenuated retinal inflammation and stabilized the integrity of the blood-retina barrier (BRB). In vitro experiments revealed that Qu impedes microglial activation, proliferation, and migration, primarily via modulation the ERK/STAT3 signaling pathway. Notably, these actions of Qu significantly contributed to the preservation of photoreceptors. Consequently, Qu pre-treatment holds promise as an effective strategy for controlling retinal inflammation and preserving visual function.

Electrolyte Engineering Empowers Li||CFx Batteries to Achieve High Energy Density and Low Self-Discharge at Harsh Conditions.

Given its exceptional theoretical energy density (over 2000 Wh kg-1), lithium||carbon fluoride (Li||CFx) battery has garnered global attention. N-methylpyrrolidone (NMP)-based electrolyte is regarded as one promising candidate for tremendously enhancing the energy density of Li||CFx battery, provided self-discharge challenges can be resolved. This study successfully achieves a low self-discharge (LSD) and desirable electrochemical performance in Li||CFx batteries at high temperatures by utilizing NMP as the solvent and incorporating additional ingredients, including vinylene carbonate additive, as well as the dual-salt systems formed by LiBF4 with three different Li salts, namely lithium bis(oxalato)borate, lithium difluoro(oxalato)borate, and LiNO3. The experimental results unfold that the proposed methods not only minimize aluminum current collector corrosion, but also effectively passivate the Li metal anode. Among them, LiNO3 exhibits the most pronounced effect that achieves an energy density of ≈2400 Wh kg-1 at a current density of 10 mA g-1 at 30 °C, nearly 0% capacity-fade rate after 300 h of storage at 60 °C, and the capability to maintain a stable open-circuit voltage over 4000 h. This work provides a distinctive perspective on how to realize both high energy density and LSD rates at high temperature of Li||CFx battery.

Hospital­acquired pneumonia caused by Kodamaea ohmeri during extracorporeal membrane oxygenation treatment: A case report and literature review.

Kodamaea ohmeri (K. ohmeri) is an ascosporogenic species of yeast that belongs to the genus Ascosporogenous and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by K. ohmeri during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. K. ohmeri is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat K. ohmeri infections. It is important to raise awareness of rare fungal infections and actively treat them.

Nitrogen fertilization application strategies improve yield of the rice cultivars with different yield types by regulating phytohormones.

Rice (Oryza sativa L.) is the most important food crop worldwide, and its sustainable development is essential to ensure global food security. Panicle morphological and physiological characteristics plays an important role in rice yield formation. However, under different nitrogen (N) fertilization strategies, it is not clear whether the morphological and physiological state of panicles at panicle development stage affects the formation of yield. To understand how the panicle differentiation and development, and grain yield are affected by the N fertilization strategies, and clarify the relationship between related traits and yield in the process of panicle development in different cultivars. In this study consisted of no N fertilizer and four N fertilization strategies, a panicle weight type (PWT) rice cultivar, Dongfu 114 (DF114) and a panicle number type (PNT) rice cultivar, Longdao 11 (LD11) were grown in the field. The results showed that N fertilization strategies could improve the nitrogen use efficiency and yield of rice, but the response of different rice varieties to N fertilizer strategies was different. Different from the DF114, the further increase of panicle N fertilizer ratio could not further improve the yield of LD11, and the highest grain yield of DF114 and LD11 was obtained under N4 and N3 conditions, respectively. In addition, this study found that N fertilizer strategies can affect the content of phytohormones in rice at the panicle differentiation stage, and then regulate the differentiation and development of rice panicles to affect yield. It is of great significance to optimize the application mode of N fertilizer according to the characteristics of varieties to improve rice yield and ensure food security.

Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Design, synthesis and biological activity determination of novel phenylpyrazole protoporphyrinogen oxidase inhibitor herbicides.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is the last common enzyme in the biosynthetic pathway in the synthesis of heme and chlorophyll. The high-frequency use of PPO inhibitor herbicides has led to the gradual exposure of pesticide damage and resistance problems. In order to solve this kind of problem, there is an urgent need to develop new PPO inhibitor herbicides. In this paper, 16 phenylpyrazole derivatives were designed by the principle of active substructure splicing through the electron isosterism of five-membered heterocycles. Greenhouse herbicidal activity experiments and in vitro PPO activity experiments showed that the inhibitory effect of compound 9 on weed growth was comparable to that of pyraflufen-ethyl. Crop safety experiments and cumulative concentration experiments in crops showed that when the spraying concentration was 300 g ai/ha, wheat, corn, rice and other cereal crops were more tolerant to compound 9, among which wheat showed high tolerance, which was comparable to the crop safety of pyraflufen-ethyl. Herbicidal spectrum experiments showed that compound 9 had inhibitory activity against most weeds. Molecular docking results showed that compound 9 formed one hydrogen bond interaction with amino acid residue ARG-98 and two π-π stacking interactions with amino acid residue PHE-392, indicating that compound 9 had better herbicidal activity than pyraflufen-ethyl. It shows that compound 9 is expected to be a lead compound of phenylpyrazole PPO inhibitor herbicide and used as a herbicide in wheat field.