Responsive Degradable Bottlebrush Polymers Enable Drugs With Superior Efficacy and Minimal Systemic Toxicity.

Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains.

Inhibition of TTX-S Na currents by a novel blocker QLS-278 for antinociception.

Genetic loss-of-function mutations of Nav1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain (CIP) in humans, indicating that selective inhibition of the channel may lead to potential therapy of pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.

Discovery of an Ortho-Substituted -Cyclopropylmethyl-7α-phenyl-6,14-ethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of -substituted -cyclopropylmethyl-7α-phenyl-6,14-ethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, = 3.

Synthesis of easily-modified and useful dibenzo-[]azepines by palladium(II)-catalyzed cyclization/addition with a green solvent.

A novel strategy in which palladium(II)-catalyzed tandem cyclization is used to obtain N-heterocyclic architectures containing a seven-membered ring has been developed and used to synthesize a series of derivatives. The reaction uses an eco-friendly mixed solvent (water : EtOH = 2 : 1) instead of DMSO and maintains a high yield (91%). Its potential application value and reaction mechanism have also been explored.

Machine Learning-derived Multi-omics Prognostic Signature of Pyroptosis-related lncRNA with Regard to ZKSCAN2-DT and Tumor Immune Infiltration in Colorectal Cancer.

Background: Colorectal cancer (CRC) has become the most prevalent gastrointestinal malignant tumor, ranking third (10.2%) in incidence and second (9.2%) in death among all malignancies globally.

Reversal of subtype-selectivity and function by the introduction of a para-benzamidyl substituent to N-cyclopropylmethyl nornepenthone.

The discovery and development of novel μ-opioid receptor (MOR) antagonists is a significant area to combat Opioid Use Disorder (OUD). In this work, a series of para-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized and pharmacologically assayed. Compound 6a was identified as a selective MOR antagonist both in vitro and in vivo.

Design, synthesis, and biological evaluation of acyl sulfonamide derivatives with spiro cycles as Na1.7 inhibitors for antinociception.

Chronic pain, as an unmet medical need, severely impacts the quality of life. The voltage-gated sodium channel Na1.7 preferentially expressed in sensory neurons of dorsal root ganglia (DRG) serves a promising target for pain therapy.

Environmental and economic assessment of the construction, operation, and demolition of a decentralized composting facility.

Decentralized waste treatment facilities are recently highlighted for the treatment of solid waste in rural areas for being cheap, flexible, and reliable. Among them, decentralized composting is most commonly used. Many forms of decentralized composting facilities also develop and apply in developing countries, but the environmental and economical performances remain unknown.

A critical review on odor measurement and prediction.

Odor pollution has become a global environmental issue of increasing concern in recent years. Odor measurements are the basis of assessing and solving odor problems. Olfactory and chemical analysis can be used for odor and odorant measurements.

Rapid progress in neuroimaging technologies fuels central nervous system translational medicine.

Central nervous system (CNS) drug discovery suffers from high attrition rates; translational neuroscience approaches aiming to reduce these high rates include the use of brain imaging technologies. However, there is a need to better understand what methods are being used and for what diseases and purposes. Our analysis of the literature found that magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) were the neuroimaging techniques used most often in clinical trials for the most prevalent CNS diseases: Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia.

ALKBH1-mediated m A demethylation of METTL3 mRNA promotes the metastasis of colorectal cancer by downregulating SMAD7 expression.

Colorectal cancer (CRC) is one of the most common malignancies, and the main cause of death from CRC is tumor metastasis. m A RNA modification plays critical role in many biological processes. However, the role of m A modification in CRC remains unclear.

Primary balloon angioplasty for chronic occlusion of intracranial internal carotid artery: A case report.

Chronic occlusion of large intracranial arteries is the main cause of ischemic stroke in China. Patients with symptomatic intracranial artery occlusion and hemodynamic impairment are at high risk of recurrent stroke. Chronic occlusion of the intracranial segment of the internal carotid artery is a common type of intracranial artery occlusion.

Molecular behavior and interactions with microbes during anaerobic degradation of bio-derived DOM in waste leachate.

It is the key to control bio-derived dissolved organic matters (DOM) in order to reduce the effluent concentration of wastewater treatment, especially for waste leachate with high organic contaminants. In the present study, the anaerobic degradation of aerobically stabilized DOM was investigated with DOM substrate isolated through electrodialysis. The degradation of bio-derived DOM was confirmed by reduction of 15% of total organic carbon in 100 days.

Design, development and evaluation of a prodrug-type TrkA-selective inhibitor with antinociceptive effects in vivo.

Tropomyosin receptor kinase A (TrkA) is considered a therapeutic target in pain treatment, and several TrkA inhibitors have been designed and developed as potential analgesics. The subselectivity toward TrkA is closely associated with safety and efficacy and was achieved by developing an allosteric inhibitor to occupy the less conserved non-ATP binding site. Druggable modifications of potent TrkA inhibitors could be challenging due to the unique requirement of functional groups that supply potency but are accompanied by poor druggability.

Occurrence of macroplastics and microplastics in biogenic waste digestate: Effects of depackaging at source and dewatering process.

Plastic debris, including macroplastics (>5 mm) and microplastics (0.1-5 mm), has proven to be an emerging contaminant. Anaerobic digestion, coupled with energy recovery, can be an effective valorization technology for biogenic waste.

Odor emission rate of a municipal solid waste sanitary landfill during different operation stages before final closure.

This study investigated the odor emission rate from different areas of a municipal solid waste landfill. The surface odor emission rate (SOER) of eight odorous compound groups were determined by flux chamber method. The SOER of working face, seams of daily cover, membrane surface of daily cover, seams of temporary cover, membrane surface of temporary cover, seams of intermediate cover, membrane surface of intermediate cover were 138.

In-situ removal of odorous NH and HS by loess modified with biologically stabilized leachate.

The loess regions distribute widely in Northwestern China, North America and Eastern Europe. For these regions, landfill is a suitable technology for solid waste treatment. However, as a landfill cover material, loess is not very effective in controlling the emission of malodorous gases.

[Temporal and Spatial Variation in Odor Pollution and Membrane Barrier Effect in Municipal Solid Waste Landfill].

In order to explore the source characteristics as well as the temporal and spatial variations in odor pollution in municipal waste landfills, gas samples were collected from a landfill in an eastern coastal area of China throughout winter and summer. The total concentration of malodorous substances reached 60000 μg·m. There were more types of odor pollutants detected in summer than in winter, the average concentration was 30-300 times higher than that in winter, and the concentration of sulfur compounds increased by 4.

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, predominantly expressed in a subset of peripheral sensory neurons for pain signaling. Topical application of agonist capsaicin for desensitizing TRPV1 currents has been approved for relief of chronic pain. However, the potent TRPV1 capsaicin is not ingestible and even topical capsaicin causes common side effects such as skin irritation, swelling, erythema and pruritus, suggesting that a mild TRPV1 agonist might be helpful for reducing side effects while reliving pain.

Discovery of Potent and Selective Transient Receptor Potential Vanilloid 1 (TRPV1) Agonists with Analgesic Effects Based on the Functional Conversion Induced by Altering the Orientation of the Indazole Core.

Transient receptor potential vanilloid 1 (TRPV1) is a promising target for developing antinociceptive agents. Here, we report the synthesis of -indazole-4-aryl piperazine carboxamide analogues as TRPV1 modulators. The structure-activity relationship (SAR) reveals that substituting indazole at the 5-/6-position leads to TRPV1 agonism, whereas the 4- and 7-positions of indazole obtain mild antagonism and loss of activity, respectively.

Vermicomposting leads to more abundant microplastics in the municipal excess sludge.

Municipal excess activated sludge is not only an important reservoir of microplastics particles, but is also a vehicle of entry of microplastics into the environments as soil amendments or organic fertilizer. Vermicomposting is a cost-effective technology for sludge valorization. However, it is not clear whether vermicomposting affects the occurrence of microplastics in residual sludge.