Multiparameter Optimization of Broad-Spectrum Antibacterial Activity, ADMET Properties, and MAO-A/B Inhibition of Novel Biaryloxazolidinone-Hydrazone Derivatives: Identification of a Lead with In Vivo Efficacy against Linezolid-Resistant .

In our previous study, oxazolidinone - demonstrated potent antibacterial activity and drug-likeness but was limited by MAO-A inhibition, high plasma protein binding, and inferior in vivo efficacy compared to linezolid. Herein, we report the discovery of a promising compound , which exhibited excellent antibacterial activity against , MSSA, MRSA, LRSA, and LREFa with MIC values of <0.03, 0.

Effects of Pregnancy on Liver and Kidney Cyst Growth Rates in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

: Polycystic liver disease (PLD) is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). PLD is more prevalent in women, and women have larger liver cysts, possibly due to estrogen-related mechanisms. Maternal estrogen levels normally increase during pregnancy.

The Role of Baseline Total Kidney Volume Growth Rate in Predicting Tolvaptan Efficacy for ADPKD Patients: A Feasibility Study.

: Although tolvaptan efficacy in ADPKD has been demonstrated in randomized clinical trials, there is no definitive method for assessing its efficacy in the individual patient in the clinical setting. In this exploratory feasibility study, we report a method to quantify the change in total kidney volume (TKV) growth rate to retrospectively evaluate tolvaptan efficacy for individual patients. Treatment-related changes in estimated glomerular filtration rate (eGFR) are also assessed.

Model-Assisted Spleen Contouring for Assessing Splenomegaly in Myelofibrosis: A Fast and Reproducible Approach to Evaluate Progression and Treatment Response.

: Accurate and reproducible spleen volume measurements are essential for assessing treatment response and disease progression in myelofibrosis. This study evaluates techniques for measuring spleen volume on abdominal MRI. : In 20 patients with bone marrow biopsy-proven myelofibrosis, 5 observers independently measured spleen volume on 3 abdominal MRI pulse sequences, 3D-spoiled gradient echo T1, axial single-shot fast spin echo (SSFSE) T2, and coronal SSFSE T2, using ellipsoidal approximation, manual contouring, and 3D nnU-Net model-assisted contouring comparing coefficients of variation.

A Universal Design of Lithium Anode via Dynamic Stability Strategy for Practical All-Solid-State Batteries.

All-solid-state Li-metal battery (ASSLB) chemistry with thin solid-state electrolyte (SSE) membranes features high energy density and intrinsic safety but suffers from severe dendrite formation and poor interface contact during cycling, which hampers the practical application of rechargeable ASSLB. Here, we propose a universal design of thin Li-metal anode (LMA) via a dynamic stability strategy to address these issues. The ultra-thin LMA (20 μm) is in situ constructed with uniform highly Li-ion conductive solid-electrolyte interphase and composite-polymer interphase (CPI) via electroplating process.

Automatically Detecting Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease on MRI Using Deep Learning.

Background: Pancreatic cysts in autosomal dominant polycystic kidney disease (ADPKD) correlate with PKD2 mutations, which have a different phenotype than PKD1 mutations. However, pancreatic cysts are commonly overlooked by radiologists. Here, we automate the detection of pancreatic cysts on abdominal MRI in ADPKD.

Improved predictions of total kidney volume growth rate in ADPKD using two-parameter least squares fitting.

Mayo Imaging Classification (MIC) for predicting future kidney growth in autosomal dominant polycystic kidney disease (ADPKD) patients is calculated from a single MRI/CT scan assuming exponential kidney volume growth and height-adjusted total kidney volume at birth to be 150 mL/m. However, when multiple scans are available, how this information should be combined to improve prediction accuracy is unclear. Herein, we studied ADPKD subjects ( ) with 8+ years imaging follow-up (mean = 11 years) to establish ground truth kidney growth trajectory.

A Primer for Utilizing Deep Learning and Abdominal MRI Imaging Features to Monitor Autosomal Dominant Polycystic Kidney Disease Progression.

Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of ADPKD are incompletely evaluated or not deemed to be clinically significant, and because of this, treatment options are limited. However, total kidney volume (TKV) measurement has become important for assessing the risk of disease progression (i.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S.

Feasibility of Water Therapy for Slowing Autosomal Dominant Polycystic Kidney Disease Progression.

Key Points: Water therapy in autosomal dominant polycystic kidney disease (ADPKD) reduces urine osmolality and serum copeptin level, a marker of vasopressin activity. Water therapy reduces the ADPKD kidney growth rate indicating it is slowing disease progression. Patients with ADPKD are less likely to report pain on water therapy.

Discovery and optimization of dihydropteridone derivatives as novel PLK1 and BRD4 dual inhibitor for the treatment of cancer.

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC values of 0.

Interface design for all-solid-state lithium batteries.

The operation of high-energy all-solid-state lithium-metal batteries at low stack pressure is challenging owing to the Li dendrite growth at the Li anodes and the high interfacial resistance at the cathodes. Here we design a MgBi interlayer at the Li/LiPSCl interface to suppress the Li dendrite growth, and a F-rich interlayer on LiNiMnCoO (NMC811) cathodes to reduce the interfacial resistance. During Li plating-stripping cycles, Mg migrates from the MgBi interlayer to the Li anode converting MgBi into a multifunctional LiMgS-LiBi-LiMg structure with the layers functioning as a solid electrolyte interphase, a porous LiBi sublayer and a solid binder (welding porous LiBi onto the Li anode), respectively.

Test Retest Reproducibility of Organ Volume Measurements in ADPKD Using 3D Multimodality Deep Learning.

Rationale And Objectives: Following autosomal dominant polycystic kidney disease (ADPKD) progression by measuring organ volumes requires low measurement variability. The objective of this study is to reduce organ volume measurement variability on MRI of ADPKD patients by utilizing all pulse sequences to obtain multiple measurements which allows outlier analysis to find errors and averaging to reduce variability.

Materials And Methods: In order to make measurements on multiple pulse sequences practical, a 3D multi-modality multi-class segmentation model based on nnU-net was trained/validated using T1, T2, SSFP, DWI and CT from 413 subjects.

Design and Synthesis of 1,3,5-Triazines or Pyrimidines Containing Dithiocarbamate Moiety as PI3Kα Selective Inhibitors.

Recent studies have shown that phosphoinositide 3-kinase (PI3K) plays a vital role in cell division, and it has become a therapeutic target for many cancers. In this paper, some new 1,3,5-triazine or pyrimidine skeleton derivatives containing dithiocarbamate were designed and synthesized based on the reasonable drug design strategy from the previously effective compound 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1-benzimidazole (, in order to get effective selective PI3Kα inhibitors that have not been reported in the literature. In addition, the inhibitory activities of these compounds on PI3Kα and two tumor cell lines (HCT-116, U87-MG) were evaluated.

Medicinal chemistry strategies targeting NLRP3 inflammasome pathway: A recent update from 2019 to mid-2023.

Nod-like receptor protein 3 (NLRP3), a therapeutic target that has a close relationship with inflammatory diseases, has drawn significant attention from researchers in the field. An increasing number of NLRP3 inhibitors have been reported since NLRP3 was identified as a biomarker and inflammatory therapeutic target. Inhibiting NLRP3 has been widely studied as therapeutics for the treatment of cryopyrin associated periodic syndrome (CAPS), inflammatory bowel disease (IBD), nonalcoholic steatohepatitis (NASH), arthrolithiasis, Alzheimer's disease (AD) and Parkinson's disease (PD).

Clinical Quality Control of MRI Total Kidney Volume Measurements in Autosomal Dominant Polycystic Kidney Disease.

Total kidney volume measured on MRI is an important biomarker for assessing the progression of autosomal dominant polycystic kidney disease and response to treatment. However, we have noticed that there can be substantial differences in the kidney volume measurements obtained from the various pulse sequences commonly included in an MRI exam. Here we examine kidney volume measurement variability among five commonly acquired MRI pulse sequences in abdominal MRI exams in 105 patients with ADPKD.

Design, synthesis, and biological evaluation of novel dihydropteridone derivatives possessing oxadiazoles moiety as potent inhibitors of PLK1.

Polo like kinase 1 (PLK1) is a serine/threonine kinase that is widely distributed in eukaryotic cells and plays an important role in multiple phases of the cell cycle. Its importance in tumorigenesis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of novel dihydropteridone derivatives (13a-13v and 21g-21l) possessing oxadiazoles moiety as potent inhibitors of PLK1.

Controlling Intermolecular Interaction and Interphase Chemistry Enabled Sustainable Water-tolerance LiMn O ||Li Ti O Batteries.

Solid electrolyte interphase (SEI) formation and H O activity reduction in Water-in-Salt electrolytes (WiSE) with an enlarged stability window of 3.0 V have provided the feasibility of the high-energy-density aqueous Li-ion batteries. Here, we extend the cathodic potential of WiSE by rationally controlling intermolecular interaction and interphase chemistry with the introduction of trimethyl phosphate (TMP) into WiSE.

Enhancing Li Transport in NMC811||Graphite Lithium-Ion Batteries at Low Temperatures by Using Low-Polarity-Solvent Electrolytes.

LiNi Co Mn O (x+y+z=1)||graphite lithium-ion battery (LIB) chemistry promises practical applications. However, its low-temperature (≤ -20 °C) performance is poor because the increased resistance encountered by Li transport in and across the bulk electrolytes and the electrolyte/electrode interphases induces capacity loss and battery failures. Though tremendous efforts have been made, there is still no effective way to reduce the charge transfer resistance (R ) which dominates low-temperature LIBs performance.

PTNet3D: A 3D High-Resolution Longitudinal Infant Brain MRI Synthesizer Based on Transformers.

An increased interest in longitudinal neurodevelopment during the first few years after birth has emerged in recent years. Noninvasive magnetic resonance imaging (MRI) can provide crucial information about the development of brain structures in the early months of life. Despite the success of MRI collections and analysis for adults, it remains a challenge for researchers to collect high-quality multimodal MRIs from developing infant brains because of their irregular sleep pattern, limited attention, inability to follow instructions to stay still during scanning.

Formation of LiF-rich Cathode-Electrolyte Interphase by Electrolyte Reduction.

The capacity of transition metal oxide cathode for Li-ion batteries can be further enhanced by increasing the charging potential. However, these high voltage cathodes suffer from fast capacity decay because the large volume change of cathode breaks the active materials and cathode-electrolyte interphase (CEI), resulting in electrolyte penetration into broken active materials and continuous side reactions between cathode and electrolytes. Herein, a robust LiF-rich CEI was formed by potentiostatic reduction of fluorinated electrolyte at a low potential of 1.

Fully transformer network for skin lesion analysis.

Automatic skin lesion analysis in terms of skin lesion segmentation and disease classification is of great importance. However, these two tasks are challenging as skin lesion images of multi-ethnic population are collected using various scanners in multiple international medical institutes. To address them, most recent works adopt convolutional neural networks (CNNs) for skin lesion analysis.

Solid-State Electrolyte Design for Lithium Dendrite Suppression.

All-solid-state Li metal batteries have attracted extensive attention due to their high safety and high energy density. However, Li dendrite growth in solid-state electrolytes (SSEs) still hinders their application. Current efforts mainly aim to reduce the interfacial resistance, neglecting the intrinsic dendrite-suppression capability of SSEs.

Dense Deconvolutional Network for Skin Lesion Segmentation.

Automatic delineation of skin lesion contours from dermoscopy images is a basic step in the process of diagnosis and treatment of skin lesions. However, it is a challenging task due to the high variation of appearances and sizes of skin lesions. In order to deal with such challenges, we propose a new dense deconvolutional network (DDN) for skin lesion segmentation based on residual learning.

Solid-State Electrolyte Anchored with a Carboxylated Azo Compound for All-Solid-State Lithium Batteries.

Organic electrode materials are promising for green and sustainable lithium-ion batteries. However, the high solubility of organic materials in the liquid electrolyte results in the shuttle reaction and fast capacity decay. Herein, azo compounds are firstly applied in all-solid-state lithium batteries (ASSLB) to suppress the dissolution challenge.