A novel index evaluating left atrioventricular coupling function in chronic kidney disease with diabetes patients.

The left atrioventricular coupling index (LACI) evaluates the coupling function between the left atrial (LA) and left ventricular (LV) chambers. However, little is known about LACI in chronic kidney disease (CKD) patients. This study aimed to assess the impact of concurrent CKD and type 2 diabetes mellitus (T2DM) on left atrioventricular coupling function compared to CKD patients without T2DM.

Construction of CS-SDAEM long-chain polysaccharide derivative on TA@CNTs coated PVDF membrane with effective oil-water emulsion purification and low contamination rate.

Currently, the most effective way to improve the anti-fouling performance of water treatment separation membrane is to enhance the hydrophilicity of the membrane surface, but it can still cause contamination, leading to the occurrence of flux reduction. The construction of a strong hydration layer to resist wastewater contamination is still a challenging task. In this study, a defect-free hydration layer barrier was achieved by grafting chitosan polysaccharide derivatives (CS-SDAEM) on the membrane, which achieved in effective fouling prevention and low flux decline rate.

Nephrotoxicity of targeted therapy used to treat lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide, especially non-small cell lung cancer. Early diagnosis and better treatment choices have already provided a more promising prognosis for cancer patients. In targeted therapy, antagonists target specific genes supporting cancer growth, proliferation and metastasis.

Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's Disease.

The accumulation of hyperphosphorylated tau protein aggregates is a key pathogenic event in Alzheimer's disease (AD) and induces mitochondrial dysfunction and reactive oxygen species overproduction. However, the treatment of AD remains challenging owning to the hindrance caused by the blood-brain barrier (BBB) and the complex pathology of AD. Nasal delivery represents an effective means of circumventing the BBB and delivering drugs to the brain.

Extracellular vesicles: a rising star for therapeutics and drug delivery.

Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers.

Not All Photoactive Yellow Proteins Are Built Alike: Surprises and Insights into Chromophore Photoisomerization, Protonation, and Thermal Reisomerization of the Photoactive Yellow Protein Isolated from .

We demonstrate that the (Hhal) photoactive yellow protein (PYP) is not representative of the greater PYP family. The photodynamics of the PYP isolated from (Srub) is characterized with a comprehensive range of spectroscopic techniques including ultrafast transient absorption, photostationary light titrations, Fourier transform infrared, and cryokinetics spectroscopies. We demonstrate that the dark-adapted pG state consists of two subpopulations differing in the protonation state of the chromophore and that both are photoactive, with the protonated species undergoing excited-state proton transfer.

Formononetin ameliorates IL‑13‑induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1/Nrf2 signaling pathway.

Formononetin has proven to be anti‑inflammatory and able to alleviate symptoms of certain allergic diseases. The present study aimed to determine and elucidate the potential effects of formononetin in allergic rhinitis. JME/CF15 cells were pretreated with formononetin at different doses, followed by stimulation with IL‑13.

Photoreceptors Take Charge: Emerging Principles for Light Sensing.

The first stage in biological signaling is based on changes in the functional state of a receptor protein triggered by interaction of the receptor with its ligand(s). The light-triggered nature of photoreceptors allows studies on the mechanism of such changes in receptor proteins using a wide range of biophysical methods and with superb time resolution. Here, we critically evaluate current understanding of proton and electron transfer in photosensory proteins and their involvement both in primary photochemistry and subsequent processes that lead to the formation of the signaling state.

Structure and stability of an azoreductase with an FAD cofactor from the strict anaerobe Clostridium perfringens.

Azoreductase enzymes present in many microorganisms exhibit the ability to reduce azo dyes, an abundant industrial pollutant, to produce carcinogenic metabolites that threaten human health. All biochemically-characterized azoreductases, around 30 to date, have been isolated from aerobic bacteria, except for AzoC, the azoreductase of Clostridium perfringens, which is from a strictly anaerobic bacterium. AzoC is a recently biochemically-characterized azoreductase.

Strong ionic hydrogen bonding causes a spectral isotope effect in photoactive yellow protein.

Standard hydrogen bonds are of great importance for protein structure and function. Ionic hydrogen bonds often are significantly stronger than standard hydrogen bonds and exhibit unique properties, but their role in proteins is not well understood. We report that hydrogen/deuterium exchange causes a redshift in the visible absorbance spectrum of photoactive yellow protein (PYP).

Side-chain specific isotopic labeling of proteins for infrared structural biology: the case of ring-D4-tyrosine isotope labeling of photoactive yellow protein.

An important bottleneck in the use of infrared spectroscopy as a powerful tool for obtaining detailed information on protein structure is the assignment of vibrational modes to specific amino acid residues. Side-chain specific isotopic labeling is a general approach towards obtaining such assignments. We report a method for high yield isotope editing of the bacterial blue light sensor photoactive yellow protein (PYP) containing ring-D(4)-Tyr.

A conserved helical capping hydrogen bond in PAS domains controls signaling kinetics in the superfamily prototype photoactive yellow protein.

PAS domains form a divergent protein superfamily with more than 20 000 members that perform a wide array of sensing and regulatory functions in all three domains of life. Only nine residues are well-conserved in PAS domains, with an Asn residue at the start of α-helix 3 showing the strongest conservation. The molecular functions of these nine conserved residues are unknown.

Three-dimensional quantitative structure-farnesyltransferase inhibition analysis for some diaminobenzophenones.

A 3D-QSAR investigation of 95 diaminobenzophenone yeast farnesyltransferase (FT) inhibitors selected from the work of Schlitzer et al. showed that steric, electrostatic, and hydrophobic properties play key roles in the bioactivity of the series. A CoMFA/CoMSIA combined model using the steric and electrostatic fields of CoMFA together with the hydrophobic field of CoMSIA showed significant improvement in prediction compared with the CoMFA steric and electrostatic fields model.

Locked chromophore analogs reveal that photoactive yellow protein regulates biofilm formation in the deep sea bacterium Idiomarina loihiensis.

Idiomarina loihiensis is a heterotrophic deep sea bacterium with no known photobiology. We show that light suppresses biofilm formation in this organism. The genome of I.

Tilting after Dutch windmills: probably no long-lived Davydov solitons in proteins.

We present a summary of picosecond pump-probe and photon echo experiments in the mid-IR at 6 mum on the protein myoglobin. The intriguing temperature dependence of the amide I band in Mb is rather similar to the temperature dependence of the amide I band of acetanilide, the molecule that launched Al Scott down the road of looking for Davydov solitons in biology. Alas, after much effort, we believe the data show that there is no long-lived Davydov soliton, at least in myoglobin.

Imidazole-containing farnesyltransferase inhibitors: 3D quantitative structure-activity relationships and molecular docking.

One of the most promising anticancer and recent antimalarial targets is the heterodimeric zinc-containing protein farnesyltransferase (FT). In this work, we studied a highly diverse series of 192 Abbott-initiated imidazole-containing compounds and their FT inhibitory activities using 3D-QSAR and docking, in order to gain understanding of the interaction of these inhibitors with FT to aid development of a rational strategy for further lead optimization. We report several highly significant and predictive CoMFA and CoMSIA models.

Glycogen synthase kinase-3 inhibition by 3-anilino-4-phenylmaleimides: insights from 3D-QSAR and docking.

Glycogen synthase kinase-3, a serine/threonine kinase, has been implicated in a wide variety of pathological conditions such as diabetes, Alzheimer's disease, stroke, bipolar disorder, malaria and cancer. Herein we report 3D-QSAR analyses using CoMFA and CoMSIA and molecular docking studies on 3-anilino-4-phenylmaleimides as GSK-3alpha inhibitors, in order to better understand the mechanism of action and structure-activity relationship of these compounds. Comparison of the active site residues of GSK-3alpha and GSK-3beta isoforms shows that all the key amino acids involved in polar interactions with the maleimides for the beta isoform are the same in the alpha isoform, except that Asp133 in the beta isoform is replaced by Glu196 in the alpha isoform.

Identification of six new photoactive yellow proteins--diversity and structure-function relationships in a bacterial blue light photoreceptor.

Photoactive yellow proteins (PYP) are bacterial photoreceptors with a Per-Arnt-Sim (PAS) domain fold. We report the identification of six new PYPs, thus nearly doubling the size of this protein family. This extends the taxonomic diversity of PYP-containing bacteria from photosynthetic to nonphotosynthetic bacteria, from aquatic to soil-dwelling organisms, and from Proteobacteria to Salinibacter ruber from the phylum Bacteriodetes.

Probing the physicochemical and structural requirements for glycogen synthase kinase-3alpha inhibition: 2D-QSAR for 3-anilino-4-phenylmaleimides.

Glycogen synthase kinase-3alpha (GSK-3alpha) was recently found to be an attractive target for the treatment of Alzheimer's disease due to its dual action in the formation of both amyloid plaques and neurofibrillary tangles. It is also a viable target for many other diseases, such as type 2 diabetes. Reported herein is a 2D-QSAR exploration of the physicochemical (hydrophobic, electronic, and steric) and structural requirements among 3-anilino-4-phenylmaleimides toward GSK-3alpha binding.

3D-QSAR analysis of antimalarial farnesyltransferase inhibitors based on a 2,5-diaminobenzophenone scaffold.

With annual death tolls in the millions and emerging resistance to existing drugs, novel therapies are needed against malaria. Wiesner et al. recently developed a novel class of antimalarials derived from farnesyltransferase inhibitors based on a 2,5-diaminobenzophenone scaffold.

Picosecond thermometer in the amide I band of myoglobin.

The amide I and II bands in myoglobin show a heterogeneous temperature dependence, with bands at 6.17 and 6.43 microm which are more intense at low temperatures.