Chemical Synthesis, Herbicidal Activity, Crop Safety, and Molecular Basis of -Fluoroalkoxy Substituted Sulfonylureas as Novel Acetohydroxyacid Synthase Inhibitors.

In the face of increasing resistance to the currently used commercial herbicides and the lack of success in identifying new herbicide targets, alternative herbicides need to be developed to control unwanted monocotyledon grasses in food crops. Here, a panel of 29 novel sulfonylurea-based compounds with fluoroalkoxy substitutions at the phenyl ring were designed and synthesized. Pot assays demonstrated that two of these compounds, and , have strong herbicidal activities against , , , and Steudel at a dosage of 15 g ha.

The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice.

Background: Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression.

Nomogram for predicting the biochemical recurrence of prostate cancer after neoadjuvant androgen deprivation therapy.

Background: A predictive model for biochemical recurrence (BCR) of prostate cancer (PCa) after neoadjuvant androgen deprivation therapy (nADT) has not been established. This study was aimed at determining multiparameter variables that could be used to construct a nomogram to predict the post-nADT BCR of PCa.

Methods: Overall, 43 radical prostatectomy specimens from PCa patients who had undergone nADT were collected.

Prognostic Value of Inflammation Biomarkers in Penile Squamous Cell Carcinoma Patients Without Distant Metastasis.

Background: To investigate the value of the presurgical inflammatory biomarkers including C-reactive protein (CRP), albumin (ALB), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), the modified GPS (mGPS), and the high-sensitivity modified GPS (Hs-mGPS) in penile squamous cell carcinoma (PSCC) without distant metastasis and develop a tool to predict the overall survival (OS) of PSCC patients.

Methods: We retrospectively enrolled 271 PSCC patients without distant metastasis from 2006 to 2021. Patients were divided into 2 cohorts by a 7:3 ratio-a training cohort (n = 191) and a validation cohort (n = 80).

mC-dependent cross-regulation between nuclear reader ALYREF and writer NSUN2 promotes urothelial bladder cancer malignancy through facilitating RABL6/TK1 mRNAs splicing and stabilization.

The significance of 5-methylcytosine (mC) methylation in human malignancies has become an increasing focus of investigation. Here, we show that mC regulators including writers, readers and erasers, are predominantly upregulated in urothelial carcinoma of the bladder (UCB) derived from Sun Yat-sen University Cancer Center and The Cancer Genome Atlas cohort. In addition, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) as a methyltransferase and Aly/REF export factor (ALYREF) as a nuclear mC reader, are frequently coexpressed in UCB.

Facile synthesis, crystal structure, quantum calculation, and biological evaluations of novel selenenyl sulfide compounds as potential agrochemicals.

Background: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS).

Results: All the target compounds were characterized by proton nuclear magnetic resonance ( H-NMR), carbon-13 ( C)-NMR, selenium-77 ( Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed.

Chemical preparation, degradation analysis, computational docking and biological activities of novel sulfonylureas with 2,5-disubstituted groups.

Based on the previous finding that a substitution at 5-position of the benzene ring is favorable to enhance the degradation rates of sulfonylurea herbicides, a total of 16 novel 2,5-disubsituted sulfonylurea compounds were chemically synthesized and fully characterized by means of H NMR, C NMR, HRMS and X-ray diffraction. By using HPLC analysis, the degradation behavior of M03, a compound belonging to this family, was studied and confirmed that chlorsulfuron itself is not a degraded product of the 2,5-disubstituted sulfonylureas. Inhibition constants against plant acetohydroxyacid synthase (AHAS) were determined for selected compounds, among which SU3 showed seven times stronger activity against the mutant W574L enzyme than chlorsulfuron.

Synthesis, herbicidal activity and soil degradation of novel 5-substituted sulfonylureas as AHAS inhibitors.

Background: Chlorsulfuron, metsulfuron-methyl and ethametsulfuron can damage sensitive crops in rotation pattern as a result of their long persistence in soil. To explore novel sulfonylurea (SU) herbicides with favorable soil degradation rates, four series of SUs were synthesized through a structure-based drug design (SBDD) strategy.

Results: The target compounds, especially Ia, Id and Ie, exhibited prospective herbicidal activity against dicotyledon oil seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), monocotyledon barnyard grass (Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) at a concentration of 15 a.

[Effects of Mulching and Slow-release Fertilizer Application Reduction on Soil Microbial Community Structure in Rapeseed Field Under Two Different Rainfall Conditions].

In order to investigate the effects of furrow and ridge rainwater harvesting, straw mulching, and reduced and slow-release fertilizer on soil microbial community structure of rapeseed, a two-year field study was conducted in rainy (2016-2017) and drought (2017-2018) seasons, which included three cultivation patterns:1 conventional flat planting, 2 straw mulching, and 3 ridge-furrow rainfall harvesting system and four fertilization patterns:1 conventional fertilization (100% of the amount), 2 reduced slow-release fertilizer Ⅰ (80% of the amount), 3 reduced slow-release fertilizer Ⅱ (60% of the amount), and 4 no fertilizer. The results indicated that it was rainy in 2016-2017, with seasonal drought during the nutritional growth stage in 2017-2018. The two technologies (straw mulching+80% slow-release fertilizer, J80 and ridge-furrow rainfall harvesting system+80% slow-release fertilizer, M80) were beneficial to boost the soil microbial activity.

Discovery of (5-(Benzylthio)-4-(3-(trifluoromethyl)phenyl)-4-1,2,4-triazol-3-yl) Methanols as Potent Phytoene Desaturase Inhibitors through Virtual Screening and Structure Optimization.

Phytoene desaturase (PDS) is not only an important enzyme in the biosynthesis of carotenoids but also a promising target for herbicide discovery. However, in recent years, no expected PDS inhibitors with new scaffolds have been reported. Hence, a solution for developing PDS inhibitors is to search for new compounds with novel chemotypes based on the PDS protein structure.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

Background: The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients.

Methods: PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated.

Chemical synthesis, biological activities, and molecular simulations of novel sulfonylurea compounds bearing ortho-alkoxy substitutions.

A series of 51 novel sulfonylurea compounds with ortho-alkoxy substituent at phenyl ring were chemically synthesized and spectroscopically characterized. The biological activities of the target compounds were evaluated using the enzyme inhibition against acetohydroxyacid synthase (AHAS; EC 2.2.

Alkaline Soil Degradation and Crop Safety of 5-Substituted Chlorsulfuron Derivatives.

Sulfonylurea herbicides can lead to serious weed resistance due to their long degradation times and large-scale applications. This is especially true for chlorsulfuron, a widely used acetolactate synthase inhibitor used around the world. Its persistence in soil often affects the growth of crop seedlings in the following crop rotation, and leads to serious environmental pollution all over the world.

Synthesis, Herbicidal Activity, Crop Safety and Soil Degradation of Pyrimidine- and Triazine-Substituted Chlorsulfuron Derivatives.

Chlrosulfuron, a classical sulfonylurea herbicide that exhibits good safety for wheat but causes a certain degree of damage to subsequent corn in a wheat-corn rotation mode, has been suspended field application in China since 2014. Our previous study found that diethylamino-substituted chlorsulfuron derivatives accelerated the degradation rate in soil. In order to obtain sulfonylurea herbicides with good crop safety for both wheat and corn, while maintaining high herbicidal activities, a series of pyrimidine- and triazine-based diethylamino-substituted chlorsulfuron derivatives (-) were systematically evaluated.

CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer.

Background: This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa.

Method: A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation.

Degradation of 5-Dialkylamino-Substituted Chlorsulfuron Derivatives in Alkaline Soil.

Sulfonylurea herbicides are widely used as acetolactate synthase (ALS) inhibitors due to their super-efficient activity. However, some sulfonylurea herbicides show toxicity under crop rotation due to their long degradation time, for example, chlorsulfuron. Our research goal is to obtain chlorsulfuron-derived herbicides with controllable degradation time, good crop safety and high herbicidal activities.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018.

Ghrelin improves cognition via activation of the cAMP- CREB signalling pathway in depressed male C57BL/6J mice.

Background: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway.

Discovery of Alkoxy Substituted Novel Sulfonylurea Compounds That Display Strong Herbicidal Activity against Monocotyledon Grasses.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.

Pelvic Lymph Node Dissection in Penile Cancer With Inguinal Lymph Node Extranodal Extension: A Multicenter Experience.

The aim of this study is to determine the necessary extent of penile lymph node dissection (PLND) in penile cancer patients with inguinal lymph node extracapsular extension (ILN-ENE). Penile cancer patients who underwent PLND in 15 centers from January 2006 to April 2020 were retrospectively analyzed. PLND was performed in patients with ILN-ENE.

Burden of Outpatient Visits Attributable to Ambient Temperature in Qingdao, China.

Climate change has been referred to as one of the greatest threats to human health, with reports citing likely increases in extreme meteorological events. In this study, we estimated the relationships between temperature and outpatients at a major hospital in Qingdao, China, during 2015-2017, and assessed the morbidity burden. The results showed that both low and high temperatures were associated with an increased risk of outpatient visits.

Prognostic significance of tumor-infiltrating immune cells in muscle-invasive bladder cancer.

Background: Muscle-invasive bladder cancer (MIBC) is a lethal disease with poor treatment response and a high death rate. Immune cells infiltrating the tumor tissues have been shown to play a vital role in tumorigenesis and tumor progression, but their prognostic significance in MIBC remains unclear.

Objectives: To explore the landscape and prognostic significance of tumor-infiltrating immune cells (TIICs) in MIBC, and to develop a model to improve the prognostic predictions of MIBC.