Licochalcone A-Inspired Chalcones: Synthesis and Their Antiproliferative Potential in Prostate Cancer Cells.

Prostate cancer remains a significant global health concern, prompting ongoing exploration of novel therapeutic agents. Licochalcone A, a natural product in the chalcone family isolated from licorice root, is characterized by its enone structure and demonstrates antiproliferative activity in the micromolar range across various cell lines, including prostate cancer. Building on our prior success in enhancing curcumin's antiproliferative potency by replacing the substituted phenol with a 1-alkyl-1H-imizadol-2-yl moiety, we applied a similar approach to design a new class of licochalcone A-inspired chalcones.

IDRWalker: A Random Walk Based Tool for Generating Intrinsically Disordered Regions in Large Protein Complexes.

Intrinsically disordered regions (IDRs), which may be functionally important, are common in proteins. However, the structures of IDRs are often missing due to their highly dynamic nature. In the study of IDRs, integrative modeling combining computational simulations and experimental data is a common approach, for which initial structures of the IDRs need to be built.

Molecular mechanism of specific HLA-A mRNA recognition by the RNA-binding-protein hMEX3B to promote tumor immune escape.

Immunotherapy, including immune checkpoint inhibitors and adoptive cell transfer, has obtained great progress, but their efficiencies vary among patients due to the genetic and epigenetic differences. Human MEX3B (hMEX3B) protein is an RNA-binding protein that contains two KH domains at the N-terminus and a RING domain at its C-terminus, which has the activity of E3 ubiquitin ligase and is essential for RNA degradation. Current evidence suggests that hMEX3B is involved in many important biological processes, including tumor immune evasion and HLA-A regulation, but the sequence of substrate RNA recognized by hMEX3B and the functional molecular mechanisms are unclear.

Fecal calprotectin as a non-invasive marker for the prediction of post-necrotizing enterocolitis stricture.

Purpose: This study aimed to evaluate the clinical utility of fecal calprotectin (FC) levels during the necrotizing enterocolitis (NEC) episode to predict the onset of post-NEC intestinal stricture.

Methods: The medical records of patients with NEC treated from April 2020 to April 2022 were recorded for this study. FC was quantified at the acute phase of NEC.

Tricyclic Diterpenoids Selectively Suppress Androgen Receptor-Positive Prostate Cancer Cells.

Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential -terminal AR antagonist, this study aims to explore the structure-activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation.

Modeling the effects of phosphorylation on phase separation of the FUS low-complexity domain.

Aggregation of the RNA-binding protein fused in sarcoma (FUS) is a hallmark of neurodegenerative diseases. Phosphorylation of Ser/Thr in the FUS low-complexity domain (FUS-LC) may regulate phase separation of FUS and prevent pathological aggregation in cells. However, many details of this process remain elusive to date.

Core Structure-Activity Relationship Studies of 5,7,20--Trimethylsilybins in Prostate Cancer Cell Models.

Silibinin, also known as silybin, is isolated from milk thistle (). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use.

Targeted to detect amino acids in complex mixtures using NMR spectroscopy.

Nuclear magnetic resonance spectroscopy of fluorine-19 nucleus ( -NMR) emerges as a powerful tool because of the high sensitivity due to its high natural abundance, broad spectral range, and the simplicity of a spin-half system. However, it is still seldom utilized in the chemistry classroom or research. This article thus aims to demonstrate the power of NMR by investigating the kinetics when a reacts with individual amino acids (AA) and eventually utilizing the approach to identify and quantify various AAs from a complex mixture such as a metabolomics sample.

Multi-scale analysis of nickel ion tolerance mechanism for thermophilic Sulfobacillus thermosulfidooxidans in bioleaching.

Bioleaching is intensively investigated for recovering valuable metals such as Li, Co, Ni and Cu. Nickel ion stress threatens the health of microorganisms when Ni starts to accumulate in the leachate during the bioleaching of materials that are rich in Ni, such as spent lithium-ion batteries. The possible mechanisms underlying the response of S.

Strategies for anti-oxidative stress and anti-acid stress in bioleaching of LiCoO using an acidophilic microbial consortium.

High metal ion concentrations and low pH cause severely inhibit the activity of an acidophilic microbial consortium (AMC) in bioleaching. This work investigated the effects of exogenous spermine on biofilm formation and the bioleaching efficiency of LiCoO by AMC in 9K medium. After the addition of 1 mM spermine, the activities of glutathione peroxidase and catalase increased, while the amount of HO, intracellular reactive oxygen species (ROS) and malondialdehyde in AMC decreased.

Forecasting Network Interface Flow Using a Broad Learning System Based on the Sparrow Search Algorithm.

In this paper, we propose a broad learning system based on the sparrow search algorithm. Firstly, in order to avoid the complicated manual parameter tuning process and obtain the best combination of hyperparameters, the sparrow search algorithm is used to optimize the shrinkage coefficient (r) and regularization coefficient (λ) in the broad learning system to improve the prediction accuracy of the model. Second, using the broad learning system to build a network interface flow forecasting model.

Effects of cadmium sulfide nanoparticles on sulfate bioreduction and oxidative stress in Desulfovibrio desulfuricans.

Sulfate-containing wastewater has a serious threat to the environment and human health. Microbial technology has great potential for the treatment of sulfate-containing wastewater. It was found that nano-photocatalysts could be used as extracellular electron donors to promote the growth and metabolic activity of non-photosynthetic microorganisms.

Multi-Center Analysis of Predictive Factors of Enteral Autonomy and Risk Factors of Complications of Pediatric Intestinal Failure in China.

Objectives: The aim of this study was to identify predictors for enteral autonomy and intestinal failure (IF)-related complications and evaluate the outcomes of a multi-center pediatric cohort in China.

Methods: The medical records of pediatric patients with IF treated at four medical centers in China from January 1, 2012 to November 31, 2020 were retrospectively reviewed. Enteral autonomy was defined as sustained growth and cessation of parenteral nutrition for >90 days.

5-Substituted 3, 3', 4', 7-tetramethoxyflavonoids - A novel class of potent DNA triplex specific binding ligands.

Herein, we present a class of potent triplex DNA binding ligands derived from the natural product quercetin, which is the first of its kind that has ever been reported in the literature. The binding of 5-substituted quercetin derivatives (3, 3', 4', 7-tetramethoxyflavonoids) to triplex and duplex DNA was investigated using several biophysical tools, including thermal denaturation monitored by UV, circular dichroism, differential scanning calorimetry, and isothermal titration calorimetry. Experimental data reveal that several 5-substituted 3, 3', 4', 7-tetramethoxyflavonoids have remarkable effects on binding to DNA triple helices, and they do not influence the double-helical DNA structures.

3--Carbamoyl-5,7,20--trimethylsilybins: Synthesis and Preliminary Antiproliferative Evaluation.

To search for novel androgen receptor (AR) modulators for the potential treatment of castration-resistant prostate cancer (CRPC), naturally occurring silibinin was sought after as a lead compound because it possesses a moderate potency towards AR-positive prostate cancer cells and its chemical scaffold is dissimilar to all currently marketed AR antagonists. On the basis of the structure-activity relationships that we have explored, this study aims to incorporate carbamoyl groups to the alcoholic hydroxyl groups of silibinin to improve its capability in selectively suppressing AR-positive prostate cancer cell proliferation together with water solubility. To this end, a feasible approach was developed to regioselectively introduce a carbamoyl group to the secondary alcoholic hydroxyl group at C-3 without causing the undesired oxidation at C2-C3, providing an avenue for achieving 3--carbamoyl-5,7,20--trimethylsilybins.

Risk factors for the occurrence and recurrence of acute cerebellar ataxia: a retrospective observational study.

Objective: There is little evidence to support a correlation between abdominal surgery and acute cerebellar ataxia (ACA). We reviewed the records of children with ACA treated at our institution to analyze risk factors for ACA.

Methods: Clinical data of 442 children with ACA treated at Children's Hospital of Nanjing Medical University between November 2015 and June 2019 were retrospectively analyzed.

Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome.

Background: Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood.

Methods: Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study.

An amide mimic of desTHPdactylolide: Total synthesis and antiproliferative evaluation.

(-)-Zampanolide is a unique microtubule stabilizing agent (MSA) with covalent-binding mechanism and low nanomolar anitproliferative potency towards multi-drug resistant cancer cells. MSAs have a special connection with prostate cancer by inhibiting androgen receptor nuclear translocation. Zampanolide and the structurally related dactylolide have thus been sought after by us as lead compounds for development of anti-prostate cancer agents.

Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel.

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components.

New Zampanolide Mimics: Design, Synthesis, and Antiproliferative Evaluation.

Zampanolide is a promising microtubule-stabilizing agent (MSA) with a unique chemical structure. It is superior to the current clinically used MSAs due to the covalent nature of its binding to -tubulin and high cytotoxic potency toward multidrug-resistant cancer cells. However, its further development as a viable drug candidate is hindered by its limited availability.

Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

Hirschsprung disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one-third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC.

[Water Purification Effect and Saline-alkali Tolerance Improvement Mechanism of in the Estuary Area].

The pollution load of nitrogen and phosphorus in pollutants entering the sea is high, which seriously affects the water quality of coastal water. It is necessary to strengthen land-sea coordination. However, affected by the seawater encroachment, the salt and alkali content of the water in the estuary area is high and the variation range is large, which leads to difficulty in plant growth.

PP2Cδ inhibits p300-mediated p53 acetylation via ATM/BRCA1 pathway to impede DNA damage response in breast cancer.

Although nuclear type 2C protein phosphatase (PP2Cδ) has been demonstrated to be pro-oncogenic with an important role in tumorigenesis, the underlying mechanisms that link aberrant PP2Cδ levels with cancer development remain elusive. Here, we found that aberrant PP2Cδ activity decreases p53 acetylation and its transcriptional activity and suppresses doxorubicin-induced cell apoptosis. Mechanistically, we show that BRCA1 facilitates p300-mediated p53 acetylation by complexing with these two proteins and that S1423/1524 phosphorylation is indispensable for this regulatory process.