ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.

As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1.

Nucleoside antiviral agents with atypical structures and new targets.

Nucleoside analogs (NAs), as antiviral drugs, play a significant role in clinical medicine, constituting approximately 50 % of all antiviral therapies in current use. Nucleoside inhibitors function by mimicking the structure of natural nucleosides, integrating themselves into viral genetic material during replication, and subsequently inhibiting the virus's ability to reproduce. They are used to treat a variety of viral infections, including herpes simplex, hepatitis B, and acquired immunodeficiency syndrome (AIDS).

IdenHerb: A strategy for identifying constitutive herbs of herbal products by screening exclusive ions of each herb from large-scale multi-group LC-MS data.

Identification of constitutive herbs in an herbal product is critical for ensuring its quality and efficacy. However, current identification methods often lack universality, entail long durations, and involve complex procedures. Therefore, there is an urgent need to develop innovative methods for identifying constitutive herbs.

Optimization of SARS-CoV-2 M Inhibitors by a Structure-Based Multilevel Virtual Screening Method.

With the aim of developing novel anti-SARS-CoV-2 drugs to address the ongoing evolution and emergence of drug-resistant strains, the reported SARS-CoV-2 M inhibitor was selected as a lead to find novel, highly potent, and broad-spectrum inhibitors. Using a fragment-based multilevel virtual screening strategy, 15 hit compounds were identified and subsequently synthesized. Among them, (IC = 1.

Integrated Genetic Diversity and Multi-Omics Analysis of Colour Formation in Safflower.

Safflower ( L.) is a medicinal and edible cash crop that is widely cultivated worldwide. However, the genetic diversity of safflower germplasm resources and the reasons for the variations in safflower flower colour remain unclear.

Radiomicsmetabolic signature profiles for advanced non-small cell lung cancer with chemoimmunotherapy by reflecting biological function and survival.

Background: Resistance to chemoimmunotherapy in patients with advanced non-small cell lung cancer (NSCLC) necessitates effective prognostic biomarkers. Although F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has shown potential for efficacy assessment, it has been mainly evaluated in immuno-monotherapy setting, lacking elaborations in the scenarios of immunotherapy combined with chemotherapy. To tackle this dilemma, we aimed to build a non-invasive PET/CT-based model for stratifying tumor heterogeneity and predicting survival in advanced NSCLC patients undergoing chemoimmunotherapy.

Discovery of Brain-Penetrative Negative Allosteric Modulators of NMDA Receptors Using FEP-Guided Structure Optimization and Membrane Permeability Prediction.

-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role in brain disorders. Specifically, GluN2A-containing NMDA receptors have emerged as a potential therapeutic target for the treatment of depressive disorders and epilepsy. However, the development of GluN2A-containing NMDA receptor-selective antagonists, represented by -(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) and its derivatives, faces a significant challenge due to their limited ability to penetrate the blood-brain barrier (BBB), hampering their characterization and further advancement.

Clinical features, risk factors, outcomes, and prediction model for intrahepatic and perihepatic abscess following hepatectomy for hepatocellular carcinoma.

Background: Intrahepatic and perihepatic abscess (IPHA) is a severe yet understudied complication that can occur after hepatectomy. This multicenter study aimed to elucidate the clinical features, risk factors, and outcomes of IPHA after hepatectomy for hepatocellular carcinoma (HCC), and to develop a novel prediction model for personalized risk assessment.

Methods: This was a multicenter cohort study of HCC patients who underwent curative-intent hepatectomy.

Comparison of antifungal drugs in the treatment of invasive pulmonary aspergillosis: a systematic review and network meta-analysis.

Background: Voriconazole, isavuconazole, and amphotericin (AmB) formulations are currently recommended to treat invasive pulmonary aspergillosis (IPA). We aimed to estimate the efficacy of different antifungal drugs in the initial treatment of IPA.

Methods: We included all available randomized controlled trials (RCTs) evaluating first-line treatments for IPA by searching PubMed, Medline, EMBASE, the Cochrane Library, and the ClinicalTrials.

Trace-elements driven up-regulation of secreted proteases expression in the human-pathogenic fungus Trichophyton rubrum.

Background: Trichophyton rubrum is a widespread human pathogenic fungus, colonizing keratinized tissue of outer body-parts. Thereby, the pathogen is relying on nutrients available from the host. The invasive mechanism of the pathogen is relaying on secreted proteases, which hydrolyze skin-proteins for subsequent up-take.

Nanomolar activity of coumarin-3-thiosemicarbazones targeting Trypanosoma cruzi cruzain and the T. brucei cathepsin L-like protease.

Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) urgently demand innovative drug development due to their impact on public health worldwide.

Elaborate Structural Modifications Yielding Novel Boron-Containing N-Substituted Oseltamivir Derivatives as Potent Neuraminidase Inhibitors with Significantly Improved Broad-Spectrum Antiresistance Profiles.

Inspired by our previous finding that targeting the 150-cavity with a multisite-binding strategy emerged as an effective approach to obtain more potent and selective neuraminidase (NA) inhibitors against influenza virus, we present here the design, synthesis, and optimization of novel boron-containing N-substituted oseltamivir (OSC) derivatives. Exploratory structure-activity relationship (SAR) studies led to the identification of compounds and as the most potent NA inhibitors, surpassing OSC in potency against both wild-type group-1 NAs and oseltamivir-resistant NAs. These compounds demonstrated significant antiviral activity against several wild-type strains and H1N1pdm09 strains (EC = 0.

Practice Patterns and Trends in the Surgical Management of Mismatch Repair Deficient Colon Cancer.

Introduction: Defects in the DNA mismatch repair (MMR) pathway can predispose individuals to colorectal cancer (CRC), with germline mutations in this pathway leading to Lynch syndrome. Consequently, universal MMR testing is recommended for all newly diagnosed CRC patients to detect mismatch repair deficient (MMR-D) tumors, enabling informed treatment decisions. Given the increased potential for metachronous disease in patients with Lynch syndrome, the current guidelines for surgical management of Lynch-associated colon cancer recommend extended resection in patients under age 60.

Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis.

Mitochondrial dysfunction is a key event driving the maladaptive repair of tubular epithelial cells during the transition from acute kidney injury to chronic kidney disease (CKD). Therefore, identifying potential targets involved in mitochondrial dysfunction in tubular epithelial cells is clinically important. Myeloid-derived growth factor (MYDGF), a novel secreted protein, plays important roles in multiple cardiovascular diseases, but the function of MYDGF in tubular epithelial cells remains unknown.

Case report: A rare case of breast and multiorgan metastases secondary to papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is generally considered a highly indolent endocrine malignancy, often accompanied by cervical lymph node metastasis and rarely involving distant metastases. We present a rare case of a 37-year-old woman with PTC, who exhibited regional lymph node metastasis, right breast metastasis, and probable right psoas major and multiple bone metastases. Initial symptoms included hoarseness, and subsequent examination revealed a secondary malignant tumor in the right breast, originating from the thyroid gland.

Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity.

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in immune exhaustion. However, little is known about the mechanisms that regulate TIM-3 surface expression and turnover. Here, we report that human TIM-3 is palmitoylated by the palmitoyltransferase DHHC9 at residue cysteine 296 (Cys).

Coupling of photonic topological states and their dynamical control based on liquid crystal.

Optical field manipulation inspired by topology theory has recently drawn great research attention in nanophotonic. For flexible and programmable light management, the capacity to dynamically regulate the photonic topological states in fixed optical artificial microstructures is essential. Here, we propose a dynamic light manipulation of a two-dimensional (2D) photonic lattice aided by liquid crystals, which is composed of all-dielectric photonic crystals with distinct topological phases.

Discovery of novel fused-heterocycle-bearing diarypyrimidine derivatives as HIV-1 potent NNRTIs targeting tolerant region I for enhanced antiviral activity and resistance profile.

As an important part of anti-AIDS therapy, HIV-1 non-nucleoside reverse transcriptase inhibitors are plagued by resistance and toxicity issues. Taking our reported XJ-18b1 as lead compound, we designed a series of novel diarypyrimidine derivatives by employing a scaffold hopping strategy to discover potent NNRTIs with improved anti-resistance properties and drug-like profiles. The most active compound 3k exhibited prominent inhibitory activity against wild-type HIV-1 (EC = 0.

Synthesis and Evaluation of Fluorinated Piperazine-Hydroxyethylamine Analogues as Potential Antiplasmodial Candidates.

In this manuscript, twenty-one novel fluorinated piperazine-hydroxyethylamine analogues were synthesized and tested against Plasmodium falciparum (Pf). Among tested compounds, two 13 g and 14 g exhibited promising inhibitory activity on Pf3D7 with IC values of 0.28 and 0.

Heterogeneity between subgroups of first-line chemoimmunotherapy for extensive-stage small cell lung cancer patients: a meta-analysis and systematic review.

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations.

Materials And Methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy.