Design, Synthesis, and Pharmacodynamic Evaluation of Highly Selective PARP1 Inhibitors with Brain Penetrance.

Selective poly(ADP-ribose) polymerase 1 (PARP1) inhibitors not only exhibit antitumor efficacy but also offer the potential to mitigate the toxicities typically associated with broader PARP inhibition. In this study, we designed and synthesized a series of small molecules targeting highly selective PARP1 inhibitors. Among these, demonstrated excellent selectivity to PARP1 along with the capability to effectively cross the blood-brain barrier (BBB).

Design, Synthesis, and Biological Evaluation of 5-Amino-4-fluoro-1-benzo[]imidazole-6-carboxamide Derivatives as Novel and Potential MEK/RAF Complex Inhibitors Based on the "Clamp" Strategy.

Herein, we described the rational drug design and synthesis of a series of 5-amino-4-fluoro-1-benzo[]imidazole-6-carboxamide derivatives that inhibit MEK and RAF kinases. The detailed screening cascades revealed that was a preferred compound, which might act like a "clamp" to stabilize the MEK/RAF complex, thereby effectively inhibiting MEK1, BRAF, and BRAF with IC values of 28, 3, and 3 nM, respectively. possessed an excellent selectivity over other 312 human-related kinases at 1 μM.

Experiment and Simulation Study of the Laser-Induced Cavitation Bubble Technique for Forming a Microgroove in Aluminum Foil.

The present work introduces a laser-induced cavitation bubble technique for forming an axisymmetric structure (i.e., microgroove) and the dynamics of a cavitation bubble from initial expansion to the collapse stages that were also simulated.

Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.

Aggregation of the RNA-binding protein TAR DNA-binding protein 43 (TDP-43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP-43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid-liquid phase separation (LLPS). In disease, TDP-43 forms cytoplasmic or intranuclear inclusions.

Multi-Ion-Based Modelling and Experimental Investigations on Consistent and High-Throughput Generation of a Micro Cavity Array by Mask Electrolyte Jet Machining.

The controllability and consistency in the fabrication of micro-textures on large-scale remains a challenge for existing production processes. Mask electrolyte jet machining (MEJM) is an alternative to Jet-ECM for controllable and high-throughput surface microfabrication with more consistency of dimensional tolerances. This hybrid configuration combines the high-throughput of masked-ECM and the adjustable flow-field of jet-ECM.

The clinical population pharmacokinetics, metabolomics and therapeutic analysis of alkaloids from Alstonia scholaris leaves in acute bronchitis patients.

Background: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients.

FTLD-TDP assemblies seed neoaggregates with subtype-specific features via a prion-like cascade.

Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 follows a prion-like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD-TDP-A and FTLD-TDP-C aggregates.

Investigation on the Electrochemical Deposition of Nanocrystalline Zinc with Cationic Polyacrylamide (CPAM)-ZnSO Electrolyte.

The electrochemical deposition of nanocrystalline zinc has high potential to deposit zinc coatings, which have improved wear and corrosion properties compared to conventional coating methods. Conventionally, two or more additives are used in the electrolyte for the formation nanocrystalline zinc; these electrolyte components are complex, and their maintenance is inconvenient, making it unstable and not suitable for industrial scale production. This paper proposes an electrochemical deposition technique for nanocrystalline zinc using a ZnSO solution with cationic polyacrylamide (CPAM) as the unique additive.

Ultrasonic Particle Manipulation in Glass Capillaries: A Concise Review.

Ultrasonic particle manipulation (UPM), a non-contact and label-free method that uses ultrasonic waves to manipulate micro- or nano-scale particles, has recently gained significant attention in the microfluidics community. Moreover, glass is optically transparent and has dimensional stability, distinct acoustic impedance to water and a high acoustic quality factor, making it an excellent material for constructing chambers for ultrasonic resonators. Over the past several decades, glass capillaries are increasingly designed for a variety of UPMs, e.

Drug-drug interactions between salvianolate injection and aspirin based on their metabolic enzymes.

Background: It is unclear whether the combination of traditional Chinese medicine and Western medicine leads to interactions in pharmacokinetics (PKs) and pharmacodynamics (PDs). In this study, the influence of salvianolate and aspirin on metabolic enzymes, and the relationship between the blood concentration and pharmacodynamic indexes, were determined.

Method: In this, randomized, parallel-grouped, single-center clinical trial, 18 patients with coronary heart disease were randomly allocated into three groups: aspirin (AP) group, salvianolate (SV) group, and combination (A + S) group.

Fast Fabrication of Complex Surficial Micro-Features Using Sequential Lithography and Jet Electrochemical Machining.

This paper presents fabrication of complex surficial micro-features employing a cross-innovative hybrid process inspired from lithography and Jet-ECM. The process is referred here as mask electrolyte jet machining (MEJM). MEJM is a non-contact machining process which combines high resolution of lithography and greater flexibility of Jet-ECM.

Effect of heat-clearing and detoxifying Chinese medicines combined with conventional therapy on mild hand, foot, and mouth disease with fever: An individual patient data meta-analysis.

Background: In China, heat-clearing and detoxifying Chinese medicines combined with conventional therapy are commonly applied to treat the mild hand, foot, and mouth disease (HFMD). However, there is lack of solid evidence on the efficacy and safety of such therapies.

Methods: We conducted a pooled analysis with individual patient data from 5 strictly randomized controlled clinical trials to assess the efficacy and safety of this combination therapy for mild HFMD.

Jet Electrochemical Micromachining of Micro-Grooves with Conductive-Masked Porous Cathode.

Surface structures with micro-grooves have been reported to be an effective way for improving the performance of metallic components. Through-mask electrochemical micromachining (TMEMM) is a promising process for fabricating micro-grooves. Due to the isotropic nature of metal dissolution, the dissolution of a workpiece occurs both along the width and depth.

Experimental Mouse Model of Bleomycin-Induced Skin Fibrosis.

Systemic sclerosis (SSc) refers to an autoimmune disease, which is manifested by inflammation, vasculopathy, and fibrosis of the skin and internal organs. There are a number of different animal models recapitulating specific aspects of SSc. The experimental mouse model of bleomycin-induced skin fibrosis is commonly used to study the pathogenesis observed in SSc.

Fabrication of a Metal Micro Mold by Using Pulse Micro Electroforming.

Microfluidic devices have been widely used for biomedical and biochemical applications. Due to its unique characteristics, polymethyl methacrylate (PMMA) show great potential in fabricating microfluidic devices. Hot embossing technology has established itself as a popular method of preparing polymer microfluidic devices in both academia and industry.

Improving the Cell Viability and Isolating Precision of Laser-induced Forward Transfer Process by Maintaining a Proper Environment with a Microchip.

Background: Aiming to improve the laser-induced forward transfer (LIFT) cell isolation process, a polydimethylsiloxane (PDMS) layer with micro-hole arrays was employed to improve the cell separation precision, and a microchip with heater was developed to maintain the working area at 100% humidity and 37°C with the purpose to preserve the viability of the isolated cells.

Methods: A series of experiments were conducted to verify the contributions of the optimization to LIFT cell isolation process as well as to study the effect of laser pulse energy, laser spot size and the titanium thickness on cell isolation. With 40µm laser spot size and 40nm thick of titanium, laser energy threshold for 100% single cell isolating succeed ratio is 7µJ.

A Rapid One-Step Process for Fabrication of Biomimetic Superhydrophobic Surfaces by Pulse Electrodeposition.

Inspired by some typical plants such as lotus leaves, superhydrophobic surfaces are commonly prepared by a combination of low surface energy materials and hierarchical micro/nano structures. In this work, superhydrophobic surfaces on copper substrates were prepared by a rapid, facile one-step pulse electrodepositing process, with different duty ratios in an electrolyte containing lanthanum chloride (LaCl₃·6H₂O), myristic acid (CH₃(CH₂)COOH), and ethanol. The equivalent electrolytic time was only 10 min.

Single cell isolation process with laser induced forward transfer.

Background: A viable single cell is crucial for studies of single cell biology. In this paper, laser-induced forward transfer (LIFT) was used to isolate individual cell with a closed chamber designed to avoid contamination and maintain humidity. Hela cells were used to study the impact of laser pulse energy, laser spot size, sacrificed layer thickness and working distance.

WITHDRAWN: Herbal medicines for advanced colorectal cancer.

The review is withdrawn due to its insufficient quality. The editorial group responsible for this previously published document have withdrawn it from publication.

[Expertise-based randomized controlled trials and its application in acupuncture clinical research].

Through introduction of the methodological mechanism and comparison with classic randomized controlled trial, the status and the applicability of the expertise-based randomized controlled trials in clinic are explored, and its characteristics in acupuncture clinical application are analyzed. It is held that expertise-based randomized controlled trial is more suitable for the acupuncture clinical research, especially for acupuncture practice which emphasizes manipulations and different schools.

Herbal medicines for advanced colorectal cancer.

Background: Herbal medicine has been widely used in patients with advanced colorectal cancer in China, but its efficacy has not been confirmed.

Objectives: To evaluate the beneficial effect and safety on Chinese herbal medicine therapy for advanced stage colorectal cancer, and it's influence on the patients' quality of life.

Search Methods: The following electronic databases were searched: BIOSIS Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological Abstracts, until Aug.

Extracorporeal photopheresis in a rat model of pulmonary fibrosis.

Extracorporeal photopheresis has anti-inflammatory properties. The development of pulmonary fibrosis includes inflammatory episodes. This study evaluates effects of extracorporeal photopheresis in experimental pulmonary fibrosis.