Characteristic roadmap of linker governs the rational design of PROTACs.

Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease. PROTAC is characterized by its unique heterobifunctional structure, which comprises two functional domains connected by a linker. The linker plays a pivotal role in determining PROTAC's biodegradative efficacy.

The identification of essential cellular genes is critical for validating drug targets.

Accurately identifying biological targets is crucial for advancing treatment options. Essential genes, vital for cell or organism survival, hold promise as potential drug targets in disease treatment. Although many studies have sought to identify essential genes as therapeutic targets in medicine and bioinformatics, systematic reviews on their relationship with drug targets are relatively rare.

Molecular Detection of and Mutation Sites and Analysis of the Binding Modes of Pyrethroid Insecticides with Voltage-Gated Sodium Channels in the Plant Bug (Hemiptera: Miridae).

This study identified genetic mutations linked to resistance to pyrethroid insecticides in the plant pest . The voltage-gated sodium channel (VGSC) gene was cloned, revealing two mutations (Met918Thr and Leu1014Phe) in laboratory strains and field populations from Inner Mongolia, resulting in variable pyrethroid resistance. A 3D model of LpVGSC was created using homology modeling, and pyrethroid binding patterns were analyzed via molecular docking.

Perioperative and palliative systemic treatments for biliary tract cancer.

Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established.

Targeting Fks1 proteins for novel antifungal drug discovery.

Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development.

Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer: Long-Term Follow-Up of the ASSO-LM1 Trial.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively.

Transfer learning empowers accurate pharmacokinetics prediction of small samples.

Accurate assessment of pharmacokinetic (PK) properties is crucial for selecting optimal candidates and avoiding downstream failures. Transfer learning is an innovative machine learning approach enabling high-throughput prediction with limited data. Recently, transfer learning methods showed promise in predicting ADME/PK parameters.

PlantPAD: a platform for large-scale image phenomics analysis of disease in plant science.

Plant disease, a huge burden, can cause yield loss of up to 100% and thus reduce food security. Actually, smart diagnosing diseases with plant phenomics is crucial for recovering the most yield loss, which usually requires sufficient image information. Hence, phenomics is being pursued as an independent discipline to enable the development of high-throughput phenotyping for plant disease.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

Objective And Background: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE).

Methods: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C.

Exploration for cobalt/nitrogen-doped catalyst to creatinine degradation via peroxymonosulfate activation: toxicity evaluation, statistical modeling, and mechanisms study.

Developing multifunctional catalysts applied in diversiform modes via advanced oxidation processes (AOPs) is a promising and attractive approach for organic pollution degradation. Herein, a novel hollow bamboo-like structural cobalt/nitrogen-doped carbonized material (CoC/N) was employed as a catalyst for AOPs, in which CoC/N was prepared in situ through calcining a Co-based coordination polymer. When CoC/N was utilized as a peroxymonosulfate (PMS) activator, the catalyst stood out prominent activities for effective CA oxidation.

Design, synthesis and biological evaluation of 4-arylamino-pyrimidine derivatives as focal adhesion kinase inhibitors.

A novel series of 4-arylamino-pyrimidine derivatives were designed and synthesized as focal adhesion kinase (FAK) inhibitors under the strategy of structure-based drug design. Most compounds performed excellent anti-proliferative activity against U87-MG cells. Especially, compounds 8d and 9b revealed the highest activity with IC values of 0.

In silico resources help combat cancer drug resistance mediated by target mutations.

Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance (CDR). Global research has generated considerable CDR-related data and well-established knowledge bases and predictive tools.

Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis.

Background: Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker.

Effects of vegetation succession on soil microbial stoichiometry in Phyllstachys edulis stands following abandonment.

Moso bamboo (Phyllostachys edulis) is China's most important economic bamboo species. With a continuous decline in the value of its shoots and timber and an increase in affiliated labor and production costs, many of these stands have been abandoned, resulting in the occurrence of vegetation succession. Currently, our understanding on changes in soil microbial stoichiometric and entropic effects and associated imbalances following stand abandonment is limited.

The Effect of Induction Chemotherapy with VEGF Inhibition on Tumor Response in Synchronously Metastasized Potentially Resectable Colorectal Cancer.

(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies.

Discovery of Novel Isoxazoline Compounds that Incorporate a -Diamide Moiety as Potential Insecticidal Agents against Fall Armyworm ().

is a major migratory agricultural pest, which seriously impedes agricultural production around the world. To discover potent compounds against , a number of novel isoxazoline derivatives were designed and synthesized and created on account of the identified lead compound (4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl--(3-propionamidophenyl)benzamide). Based on the three-dimensional quantitative structure-activity relationship of those compounds, the compound (-(4-acetamidophenyl)-4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide) was developed.

Design, Synthesis, and Insecticidal Activity of Novel Isoxazoline Compounds That Contain -diamides against Fall Armyworm ().

Fall armyworm () is a major migratory pest around the entire world that causes severe damage to agriculture. We designed and synthesized a series of novel isoxazoline derivatives based on the previously discovered active compound to find new and effective candidates against . Most of them showed excellent insecticidal activity.

Influence of biochar incorporation on the collector surface properties and the transport of silver nanoparticles in porous media.

Biochar is widely used as a soil amendment due to its environmental friendliness and convenient availability. It is believed that the presence of biochar in porous media can influence the transport of colloidal and solute contaminants. In this study, different mass ratios of biochar were added to packed sand with a rough or smooth surface to determine the significance of biochar on the retention and release of silver nanoparticles (AgNPs).

Unraveling dissolved organic matter in drinking water through integrated ozonation/ceramic membrane and biological activated carbon process using FT-ICR MS.

The performance of an integrated process comprising coagulation, ozonation, and catalytic ceramic membrane filtration (CMF) followed by treatment with biological active carbon (BAC) was evaluated in a pilot-scale (96 m/d) experiment to understand the biostability and quality of the finished water. The fate of dissolved organic matter (DOM) at the molecular level was explored using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Biostable finished water with an assimilable organic carbon (AOC) concentration of 30.

[Spatial variation and optimization of ecological carrying capacity in Jiangsu coastal area, China].

The research on spatial pattern and optimization of regional ecological carrying capacity is especially necessary to promote the overall development of economic transformation, upgrading and ecological protection and restoration. This study chose the natural, social and economic complex ecosystem of Jiangsu coastal area as subject. The concept model of pressure-state-potential (PSP) of ecological carrying capacity was established.