AutoDock and molecular dynamics-based therapeutic potential prediction of flavonoids for primary Sjögren's syndrome.

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that leads to reduced saliva production, primarily affecting women due to estrogen deficiency. The estrogen receptor α (ERα) plays a crucial role in mediating the expression of the aquaporin 5 (AQP5) gene through the estrogen response element-dependent signaling pathway, making ERα a key drug target for pSS. Several flavonoids have been reported to have the potential to treat pSS. This study aimed to screen and compare flavonoids binding to ERα using AutoDock, providing a basis for treating pSS with flavonoids. The estrogenic potential of six representative flavonoids was examined in this study. Molecular docking revealed that the binding energy of all six flavonoids to ERα was less than -5.6 kcal/mol. Apigenin, naringenin, and daidzein were the top three flavonoids with even lower binding energies of -7.8, -8.09, and -8.59 kcal/mol, respectively. Similar to the positive control estradiol, apigenin, naringenin, and daidzein showed hydrogen bond interactions with GLU353, GLY521, and HIS524 at the active site. The results of luciferase reporter assays demonstrated that apigenin, naringenin, and daidzein significantly enhanced the transcription of estrogen receptor element (ERE) in the PGL3/AQP5 promoter. Furthermore, molecular dynamics simulations using GROMACS for a time scale of 100 ns revealed relatively stable binding of apigenin-ERα, naringenin-ERα, and daidzein-ERα. Mechanistically, homology modeling indicated that GLU353, GLY521, and HIS524 were the key residues of ERα exerting an estrogenic effect. The therapeutic effect of apigenin on dry mouth in pSS models was further validated. In conclusion, these results indicate the estrogenic and pSS therapeutic potential of apigenin, naringenin, and daidzein.

Rh(III)-catalyzed selective mono- and dual-functionalization/cyclization of 1-aryl-5-aminopyrazoles with iodonium ylides.

An efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as a single coupling partner was demonstrated, in which fused benzodiazepine skeletons were obtained in excellent yields. This method greatly improved an effective approach to dual C-H unsymmetrical functionalization.

Synthesis of Tetrahydro-indolones through Rh(III)-Catalyzed [3 + 2] Annulation of Enaminones with Iodonium Ylides.

An unprecedented protocol for a Rh(III)-catalyzed [3 + 2] annulation from simple and readily available enaminones and iodonium ylides has been developed. The novel strategy allows for access to a new class of structurally diverse tetrahydro-indolones with high efficiency and a broad substrate scope. In addition, this transformation represents the first example of the selective Rh(III)-catalyzed alkenyl C-H bond functionalization and annulation of enaminones. Finally, the potential applications of this protocol are demonstrated through gram-scale reaction and late-stage modification.

Rh(III)-Catalyzed [3 + 2] Annulation/Pinacol Rearrangement Reaction of Enaminones with Iodonium Ylides: Direct Synthesis of 2-Spirocyclo-pyrrol-3-ones.

A novel Rh(III)-catalyzed cascade alkenyl C-H activation/[3 + 2] annulation/pinacol rearrangement reaction of enaminones with iodonium ylides has been developed. This methodology provides a new and straightforward synthetic strategy to afford highly functionalized 2-spirocyclo-pyrrol-3-ones in satisfactory yield from readily available starting materials under mild conditions. Moreover, gram-scale reactions and further derivatization experiments are implemented to demonstrate the potential utility of this developed approach.

Oxygen Vacancies Defective La2Ti2O7 Nanosheets Enhanced Photocatalytic Activity of Hydrogen Evolution under Visible Light Irradiation.

A novel and efficient technique has been designed for the creation of oxygen vacancies on La2Ti2O7 (LTO) nanosheets. This is achieved via a controlled solid-state reaction between NaBH4 and LTO nanosheets. Transmission electron microscopy (TEM) analyses expose that these processed LTO specimens possess a unique crystalline core/amorphous shell structure, represented as La2Ti2O7@La2Ti2O7-x. According to X-ray photoelectron spectroscopy (XPS) observations, there is a notable correlation between the reaction time, temperature, and the concentration of oxygen vacancies. The concentration of these vacancies tends to increase along with the reaction time and temperature. Concurrently, UV-Visible spectra and photocatalytic tests reveal a significant impact of oxygen vacancies on the LTO surface on both light absorption and photocatalytic functionality. Most notably, the LTO nanosheets with engineered oxygen vacancies have demonstrated an exceptional photocatalytic capacity for hydrogen production under visible light. The maximal activity recorded was an impressive 149 µmol g-1 h-1, which is noticeably superior to the performance of the pristine La2Ti2O7.

Synthesis of 4-Alkylated 1,4-Dihydropyridines: Fe(II)-Mediated Oxidative Cascade Cyclization Reaction of Cyclic Ethers with Enaminones.

Syntheses of highly functionalized 4-alkylated 1,4-dihydropyridines (1,4-DHPs) from cyclic ethers and enaminones via iron(II)-mediated oxidative free radical cascade C(sp3)-H bond functionalization/C(sp3)-O bond cleavage/cyclization reaction have been first developed. This novel synthetic strategy offers an alternative method for the construction of 1,4-DHPs by using esters as the C4 sources, as well as expands the application of ethers in heterocycle synthesis.

Fe-mediated oxidative cascade [1 + 2 + 3]-cyclization/esterification reaction: synthesis of 4-alkylated 1,4-dihydropyridines.

An Fe-mediated four-component reaction of enaminones, anhydrides and tetrahydrofuran through a cascade [1 + 2 + 3]-cyclization/esterification process is presented. This protocol provides a new and effective method to construct 4-alkylated 1,4-dihydropyridines with an ester fragment. Cyclic ether is employed as the C4 source of 1,4-dihydropyridines for the first time.

Access to thiionized-, selenolized-, and alkylated 5-alkylidene 3-pyrrolin-2-one derivatives via a regioselective oxidative annulation reaction.

A metal-free regioselective oxidative annulation reaction of readily available 2,4-pentanediones with primary amines has been described. This protocol provides a divergent strategy for the incorporation of various radical donors into 5-alkylidene 3-pyrrolin-2-one skeletons, producing a variety of thiionized-, selenolized-, and alkylated 5-alkylidene 3-pyrrolin-2-one derivatives. Moreover, the diverse synthetic transformations of the 5-alkylidene 3-pyrrolin-2-one products were also investigated.

Copper-Catalyzed Oxidative [1+2+1+2] Cascade Cyclization of N,N-Dimethyl Enaminones with Benzylamines: A Facile Access to Functionalized 1,4-Dihydropyridines.

Using benzylamines as the C4 source of 1,4-dihydropyridines (1,4-DHPs), a Cu-catalyzed oxidative [1+2+1+2] cascade cyclization for the synthesis of 1,4-DHPs was firstly developed. A broad range of easily available N,N-dimethyl enaminones and benzylamines are employed smoothly to provide a diverse range of 1,4-DHPs with high efficiency. This method is performed by a one-pot cascade C(sp3 )-H bond functionalization/C(sp3 )-N cleavage/cyclization strategy to form simultaneously two C(sp3 )-C(sp2 ) bonds, two C(sp2 )-N bonds, and a 1,4-DHP ring.

High Accuracy in Classifying Endoscopic Severity in Ulcerative Colitis Using Convolutional Neural Network.

INTRODUCTION: The evaluation of endoscopic disease severity is a crucial component in managing patients with ulcerative colitis (UC). However, endoscopic assessment suffers from substantial intraobserver and interobserver variations, limiting the reliability of individual assessments. Therefore, we aimed to develop a deep learning model capable of distinguishing active from healed mucosa and differentiating between different endoscopic disease severity degrees. METHODS: One thousand four hundred eighty-four unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independently of one another according to the Mayo endoscopic subscore (MES). In cases of disagreement, a third expert classified the images. Different convolutional neural networks were considered for automatically classifying UC severity. Five-fold cross-validation was used to develop and select the final model. Afterward, unseen test data sets were used for model evaluation. RESULTS: In the most challenging task-distinguishing between all categories of MES-our final model achieved a test accuracy of 0.84. When evaluating this model on the binary tasks of distinguishing MES 0 vs 1-3 and 0-1 vs 2-3, it achieved accuracies of 0.94 and 0.93 and areas under the receiver operating characteristic curves of 0.997 and 0.998, respectively. DISCUSSION: We have developed a highly accurate, new, automated way of evaluating endoscopic images from patients with UC. We have demonstrated how our deep learning model is capable of distinguishing between all 4 MES levels of activity. This new automated approach may optimize and standardize the evaluation of disease severity measured by the MES across centers no matter the level of medical expertise.

Development of LAMP Assays Using a Novel Target Gene for Specific Detection of Pythium terrestris, Pythium spinosum, and 'Candidatus Pythium huanghuaiense'.

Pythium terrestris, Pythium spinosum, and 'Candidatus Pythium huanghuaiense' are closely related species and important pathogens of soybean that cause root rot. However, the sequences of commonly used molecular markers, such as rDNA internal transcribed spacer 2 and cytochrome oxidase 1 gene, are similar among these species, making it difficult to design species-specific primers for loop-mediated isothermal amplification (LAMP) assays. The genome sequences of these species are also currently unavailable. Based on a comparative genomic analysis and de novo RNA-sequencing transcript assemblies, we identified and cloned the sequences of the M90 gene, a conserved but highly polymorphic single-copy gene encoding a Puf family RNA-binding protein among oomycetes. After primer design and screening, three LAMP assays were developed that specifically amplified the targeted DNA sequences in P. terrestris and P. spinosum at 62°C for 70 min and in 'Ca. Pythium huanghuaiense' at 62°C for 60 min. After adding SYBR Green I, a positive yellow-green color (under natural light) or intense green fluorescence (under ultraviolet light) was observed by the naked eye only in the presence of the target species. The minimum concentration of target DNA detected in all three LAMP assays was 100 pg·µl-1. The assays also successfully detected the target Pythium spp. with high accuracy and sensitivity from inoculated soybean seedlings and soils collected from soybean fields. This study provides a method for identification and cloning of candidate detection targets without a reference genome sequence and identified M90 as a novel specific target for molecular detection of three Pythium species causing soybean root rot.