Balancing enthalpy and entropy in inhibitor binding to the prostate-specific membrane antigen (PSMA).

Understanding the molecular mechanism of inhibitor binding to prostate-specific membrane antigen (PSMA) is of fundamental importance for designing targeted drugs for prostate cancer. Here we designed a series of PSMA-targeting inhibitors with distinct molecular structures, which were synthesized and characterized using both experimental and computational approaches. Microsecond molecular dynamics simulations revealed the structural and thermodynamic details of PSMA-inhibitor interactions.

Probiotic LP28 and improve the bioactive content and quality of fruit-based rice beverage.

The increasing demand for plant-based beverages with improved functional and sensory qualities has guided this study, which examines the bioactive content, functional, and sensory properties of a rice, apple pomace, and sea buckthorn beverage (RASB) fermented with probiotic and . We found out that total polyphenol content (TPC), total flavonoid content (TFC), and β-carotene were significantly higher in samples with , particularly in coculture samples. These samples also exhibited elevated alcohol by volume (ABV).

Pharmacokinetics of polymyxin B in different populations: a systematic review.

Background And Objectives: Despite being clinically utilized for the treatment of infections, the limited therapeutic range of polymyxin B (PMB), along with considerable interpatient variability in its pharmacokinetics and frequent occurrence of acute kidney injury, has significantly hindered its widespread utilization. Recent research on the population pharmacokinetics of PMB has provided valuable insights. This study aims to review relevant literature to establish a theoretical foundation for individualized clinical management.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer.

Background And Purpose: Ultra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose.

Role of ATF3 triggering M2 macrophage polarization to protect against the inflammatory injury of sepsis through ILF3/NEAT1 axis.

Background: Sepsis is a systemic inflammatory response which is frequently associated with acute lung injury (ALI). Activating transcription factor 3 (ATF3) promotes M2 polarization, however, the biological effects of ATF3 on macrophage polarization in sepsis remain undefined.

Methods: LPS-stimulated macrophages and a mouse model of cecal ligation and puncture (CLP)-induced sepsis were generated as in vitro and in vivo models, respectively.

Intakes of folate, vitamin B6, and vitamin B12 and cardiovascular disease risk: a national population-based cross-sectional study.

Background: Only a few studies that investigated dietary intakes of folate, vitamin B6, and vitamin B12 in relation to cariovascular disease (CVD). This study aimed to assess the association of dietary folate, vitamin B6, and vitamin B12 with CVD in the United States population.

Methods: A cross-sectional analysis of 65,322 adults aged ≥ 20 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2018.

Erythrophagocytosis is not a reproducible finding in liver biopsies, and is not associated with clinical diagnosis of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this finding is thought to suggest or support the diagnosis of HLH.

Ursolic acid attenuates cholestasis through NRF2-mediated regulation of UGT2B7 and BSEP/MRP2.

Ursolic acid (UA), a pentacyclic triterpenoid, exhibits various pharmacological actions, such as anti-inflammation, anti-tumor, anti-diabetes, heart protection, and liver protection. However, the role of nuclear factor E2-related factor 2 (NRF2)-mediated regulation of uridine diphosphate glucuronosyltransferase (UGT2B7) and bile salt export pump (BSEP)/multidrug resistance-associated protein 2 (MRP2) in UA against cholestatic liver injury has not been cleared. The purpose of this study is to explore the effect of UA on cholestatic liver injury and its potential mechanism.

CircEXOC5 Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis Through the IGF2BP2/ATF3 Axis.

Background: Patients with sepsis resulting in acute lung injury (ALI) usually have increased mortality. Ferroptosis is a vital regulator in sepsis-induced ALI. Exploring the association of ferroptosis and sepsis-induced ALI is crucial for the management of sepsis-induced ALI.

Hetero-Anionic Structure Activated CoS Bonds Promote Oxygen Electrocatalytic Activity for High-Efficiency Zinc-Air Batteries.

The electronic structure of transition metal complexes can be modulated by replacing partial ion of complexes to obtain tuned intrinsic oxygen reduction reaction (ORR) or oxygen evolution reaction (OER) electrocatalytic activity. However, the anion-modulated transition metal complexes ORR activity of is still unsatisfactory, and the construction of hetero-anionic structure remains challenging. Herein, an atomic doping strategy is presented to prepare the CuCo O S /NC-2 (CCSO/NC-2) as electrocatalysts, the structrual characterization results favorably demonstrate the partial substitution of S atoms for O in CCSO/NC-2, which shows excellent catalytic performance and durability for OER and ORR in 0.

Design and Characterization of Squaramic Acid-Based Prostate-Specific Membrane Antigen Inhibitors for Prostate Cancer.

Prostate-specific membrane antigen (PSMA) overexpressed on prostate cancer (PCa) cells is a satisfactory theranostic target in PCa. To seek novel non-glutamate-urea-based PSMA inhibitors by the strategy of bioisosterism, 10 ligands were designed, synthesized, and characterized. Among them, ligands , , and bearing the squaramic acid moiety proved to be potent PSMA inhibitors, with values ranging from 0.

Folate, vitamin B, and vitamin B intakes are negatively associated with the prevalence of hypertension: A national population-based study.

We hypothesized that the prevalence of hypertension is related to B-vitamin intake in the general population, but it has not been sufficiently studied. This study aimed to investigate the intakes of dietary folate, vitamin B, and vitamin B concerning hypertension in US adults. A total of 55 569 adults from National Health and Nutrition Examination Survey III and 1999-2014 were included in this study.

Evaluation of real-time tumor contour prediction using LSTM networks for MR-guided radiotherapy.

Background And Purpose: Magnetic resonance imaging guided radiotherapy (MRgRT) with deformable multileaf collimator (MLC) tracking would allow to tackle both rigid displacement and tumor deformation without prolonging treatment. However, the system latency must be accounted for by predicting future tumor contours in real-time. We compared the performance of three artificial intelligence (AI) algorithms based on long short-term memory (LSTM) modules for the prediction of 2D-contours 500ms into the future.

Assessment of intrafractional prostate motion and its dosimetric impact in MRI-guided online adaptive radiotherapy with gating.

Purpose: This study aimed to evaluate the intrafractional prostate motion captured during gated magnetic resonance imaging (MRI)-guided online adaptive radiotherapy for prostate cancer and analyze its impact on the delivered dose as well as the effect of gating.

Methods: Sagittal 2D cine-MRI scans were acquired at 4 Hz during treatment at a ViewRay MRIdian (ViewRay Inc., Oakwood Village, OH, USA) MR linac.

CircEXOC5 facilitates cell pyroptosis via epigenetic suppression of Nrf2 in septic acute lung injury.

Acute lung injury (ALI) caused by sepsis is characterized by a destructive high inflammatory response in lungs, which is the ultimate cause of high mortality to patients diagnosed with sepsis. The objective of the present study is to explore the effect and related mechanisms of circEXOC5 on pyroptosis in septic ALI. Sepsis ALI mouse model was induced and established by CLP induction and sepsis MPVEC cell model by LPS.

CircEXOC5 promotes ferroptosis by enhancing ACSL4 mRNA stability via binding to PTBP1 in sepsis-induced acute lung injury.

Background: Sepsis causes severe acute lung injury (ALI). Circular RNA is involved in the regulation of sepsis-related ALI progression. The regulation mechanism of circEXOC5 in sepsis-induced ALI is still unclear.

Offline and online LSTM networks for respiratory motion prediction in MR-guided radiotherapy.

Gated beam delivery is the current clinical practice for respiratory motion compensation in MR-guided radiotherapy, and further research is ongoing to implement tracking. To manage intra-fractional motion using multileaf collimator tracking the total system latency needs to be accounted for in real-time. In this study, long short-term memory (LSTM) networks were optimized for the prediction of superior-inferior tumor centroid positions extracted from clinically acquired 2D cine MRIs.

Conformations and binding pockets of HRas and its guanine nucleotide exchange factors complexes in the guanosine triphosphate exchange process.

The human Son of Sevenless (SOS) activates the signal-transduction protein Ras by forming the complex SOS·Ras and accelerating the guanosine triphosphate (GTP) exchange in Ras. Inhibition of SOS·Ras could regulate the function of Ras in cells and has emerged as an effective strategy for battling Ras related cancers. A key factor to the success of this approach is to understand the conformational change of Ras during the GTP exchange process.

MR-guided radiotherapy in node-positive non-small cell lung cancer and severely limited pulmonary reserve: a report proposing a new clinical pathway for the management of high-risk patients.

Introduction: Online MR-guided radiotherapy (MRgRT) is a relatively novel advancement in the field of radiation oncology, ensuring superior soft-tissue visualisation, allowing for online plan adaptation to anatomical and functional interfractional changes and improved motion management. Platinum-based chemoradiation followed by durvalumab is the recommended treatment for stage IIB(N1)/III NSCLC. However, this is only the case for patients with favourable risk factors and sufficient pulmonary function and reserve.

Upregulation of UGT1A1 expression by ursolic acid and oleanolic acid via the inhibition of the PKC/NF-κB signaling pathway.

Background: Isomeric ursolic acid (UA) and oleanolic acid (OA) compounds have recently garnered great attention due to their biological effects. Previously, it had been shown that UA and OA can exert important pharmacological action via the protein kinase C (PKC) and nuclear factor-κB (NF-κB) signaling, and that they can induce the expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) in HepG2 cells. This study aims to investigate the role of PKC/NF-κB signaling in regulating the expression of UGT1A1 and examine how UA and OA induce UGT1A1 based on this signaling pathway.

Dual Functional Pd-Catalyzed Multicomponent Reaction by Umpolung Chemistry of the Oxygen Atom in Electrophiles.

A Pd-catalyzed multicomponent reaction was developed by trapping oxomium ylide with nitrosobenzene via Pd-promoted umpolung chemistry. The Pd catalyst plays two important roles: diazo compound decomposed catalyst and Lewis acid for the activation of nitrosobenzene. This strategy provides some insight into a new way for discovery of multicomponent methodology to construct complex molecules.