Preferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.

Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.

Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition.

Breast cancer utilizes diverse immunosuppressive mechanisms to evade immune surveillance, thereby impairing immunotherapeutic effects. In this work, a chimeric peptide functionalized immunostimulant (designated as aGlyR) is fabricated to boost photodynamic immunotherapy through PD-L1 deglycosylation and CD47 inhibition. The photosensitizer protoporphyrin IX (PpIX) is conjugated to a PD-L1 deglycosylation peptide via a hydrophilic PEG linker, yielding the chimeric peptide Fmoc-K(PpIX)-PEG-GFTATPPAPDSPQEP.

Four New or Newly Recorded Species from Freshwater Habitats in Jiangxi Province, China.

Freshwater fungi consist of a highly diverse group of organisms in freshwater habitats worldwide. During a survey of fungal diversity in freshwater habitats across different regions of Jiangxi Province, China, four freshwater fungi were collected. To study their phylogenetic relationships, the internal transcribed spacer (ITS1-5.

Genome Sequencing Providing Molecular Evidence of Tetrapolar Mating System and Heterothallic Life Cycle for Edible and Medicinal Mushroom Fr.

is a species whose sclerotia have been extensively employed in traditional Chinese medicine, which has diuretic, antitumor, anticancer, and immune system enhancement properties. However, prolonged asexual reproduction has resulted in significant homogenization and degeneration of seed sclerotia. In contrast, sexual reproduction has emerged as an effective strategy to address these challenges, with a distinct mating system serving as the foundation for the implementation of sexual breeding.

Discovery of First-in-Class FXR and HSD17B13 Dual Modulator for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated steatohepatitis (MASH) is a complex disease driven by diverse metabolic and inflammatory pathways. Farnesoid X receptor (FXR) is a promising target for MASH due to its role in bile acid and lipid metabolism, while HSD17B13 regulates liver lipid droplet homeostasis. However, the existing HSD17B13 inhibitors have several druglike property challenges due to the common phenolic structure, a key pharmacophore for the HSD17B13 inhibitor.

Iron/phosphorus co-doped carbon nanozyme for colorimetric sensing of organophosphorus pesticides in food.

In this work, a peroxidase-like (POD-like) nanozyme of Fe/P-NC was synthesized by doping phosphorus (P) and nitrogen (N) to manipulate iron (Fe) activity centers, which showed catalytic activity and kinetics comparable to those of natural HRP. Based on the efficient POD-like activity of the Fe/P-NC nanozyme and cascaded catalytic reactions with acetylcholinesterase (AChE), we constructed a colorimetric, affordable and sensitive sensing platform to detect organophosphorus pesticides (OPs). In the presence of AChE, the POD-like activity of the prepared Fe/P-NC was suppressed, which weakened the Fe/P-NC-catalyzed oxidation of TMB.

Antarctic Krill Protein Amyloid Fibrils as a Novel Iron Carrier for the Improvement of Iron Deficiency.

Iron fortification with food supplements remains the primary dietary strategy for improving iron deficiency anemia (IDA). This study used Antarctic krill protein for fibrillar design to form an Antarctic krill protein amyloid fibril (AKAF). The results indicated that peptides generated by proteolysis were a prerequisite for fibril assembly, forming elongated fibril structures and cross-linking upon heating.

Clinical Application of a Big Data Machine Learning Analysis Model for Osteoporotic Fracture Risk Assessment Built on Multicenter Clinical Data in Qingdao City.

Background: Osteoporotic fractures (OPF) pose a public health issue, imposing significant burdens on families and societies worldwide. Currently, there is a lack of comprehensive and validated risk assessment models for OPF. This study aims to develop a model to assess and predict the risk of OPF in Qingdao City, China.

Chitosan-Based Porous Carbon Materials with Built-In Lewis Acid Boron Sites for Enhanced CO Capture and Conversion via an Electron-Inducing Effect.

Electron-induced effects, which are prevalent in adsorption and heterogeneous catalytic reactions, can significantly influence the state and uptake of adsorbates. Here, we demonstrate the in situ doping of electron-deficient boron into the backbone of chitosan-based porous carbon materials. Despite a reduction in specific surface area, the resulting boron-doped porous carbons (NBPCs) exhibit an enhanced CO adsorption performance, with sample NBPC-10 achieving CO adsorption capacities of 7.

Dual Lone Pair Strategy for High Birefringence in Antimony(III)-Based Tellurite Sulfates with Short-Wave UV Transparency.

We present two novel antimony(III)-based tellurite sulfate crystals, Sb(TeO)(SO)-1̅ (I) and Sb(TeO)(SO)-2/ (II), synthesized using a dual lone pair strategy that incorporates Sb and Te ions into a sulfate framework. This approach significantly enhances the birefringence of these compounds, with values of 0.11 and 0.

Metal-Support Interactions in PdCu/NiZnP Nanohybrids Enhance Alcohol Electrooxidation.

Developing high-performance catalysts for the alcohol electrooxidation reaction is of significant importance for the practical application of direct fuel cells. Herein, a supported catalyst consisting of well-dispersive PdCu nanoparticles (NPs) and ultrathin NiZnP nanosheets (NSs) is synthesized. The high-surface-area NiZnP NSs provide a platform for good dispersion of PdCu NPs, resulting in stable catalysts with a large number of exposed surface atoms.

Advances in Structural Types and Pharmacochemistry of CDK12 Inhibitors.

Cyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA Damage Response (DDR) genes in Cyclin-Dependent Kinase (CDK). However, the development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13.

Oridonin Suppresses the Malignant Progression of Lung Cancer by Targeting S100A11.

Background: Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties.

Synergistic Enhancement of Ferroptosis via Mitochondrial Accumulation and Photodynamic-Controlled Release of an Organogold(I) Cluster Prodrug.

Effective delivery and controlled release of metallo-prodrugs with sustained activation and rapid response feed the needs of precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding and extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy of newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) with their photosensitization character to augment the mitochondrial release of Au(I) in tumors.

The synergetic effect of edaravone and scutellarin in the MPP(+)-induced cell model of Parkinson's disease.

Parkinson's disease (PD) is a limb movement disorder caused by the degeneration of brain neurons and seriously affects the quality of life of the elderly. However, the current drugs are symptomatic treatments that cannot prevent or delay the development of the disease. Targeted therapy for pathogenesis may be the direction of development in the future.

Complex hierarchical structures analysis in single-cell data with Poincaré deep manifold transformation.

Single-cell RNA sequencing (scRNA-seq) offers remarkable insights into cellular development and differentiation by capturing the gene expression profiles of individual cells. The role of dimensionality reduction and visualization in the interpretation of scRNA-seq data has gained widely acceptance. However, current methods face several challenges, including incomplete structure-preserving strategies and high distortion in embeddings, which fail to effectively model complex cell trajectories with multiple branches.

Flexible deformation and special interface structure in nanoparticle-stabilized Pickering bubbles strengthen the immunological response as adjuvant.

Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization.

Multi-Label Zero-Shot Learning Via Contrastive Label-Based Attention.

Multi-label zero-shot learning (ML-ZSL) strives to recognize all objects in an image, regardless of whether they are present in the training data. Recent methods incorporate an attention mechanism to locate labels in the image and generate class-specific semantic information. However, the attention mechanism built on visual features treats label embeddings equally in the prediction score, leading to severe semantic ambiguity.

The role of lnc‑MAPKAPK5‑AS1 in immune cell infiltration in hepatocellular carcinoma: Bioinformatics analysis and validation.

The oncogenic and tumor suppressor roles of lnc-MAPKAPK5-AS1 in multiple cancers suggest its complexity in modulating cancer progression. The expression and promoter methylation level of lnc-MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) was investigated through data mining from The Cancer Genome Atlas and Gene Expression Omnibus and its significance in prognosis and immunity was explored. lnc-MAPKAPK5-AS1 was co-expressed with its protein-coding gene MAPKAPK5 in HCC and exhibited upregulation in HCC tissues as a result of hypomethylation of its promoter region.

Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.

Chemoresistance is a major obstacle in the treatment of gastric cancer (GC). Notably, aberrant expression of microRNAs (miRs) is closely related to tumor development and progression. In the present study, the role of miR-424-5p in the chemoresistance of GC was investigated.

The prognostic importance of the negative regulators of ferroptosis, GPX4 and HSPB1, in patients with colorectal cancer.

The prognostic value of negative regulators of ferroptosis in patients with colorectal cancer (CRC) has not yet been fully elucidated. The present study performed a systematic identification and selection of candidate negative regulators of ferroptosis using The Cancer Genome Atlas data cohort (n=367), followed by clinical validation through immunohistochemistry of samples from patients with CRC (n=166) and further evaluation. analysis identified specific light-chain subunit of the cystine/glutamate antiporter, AIFM2, NFE2L2, FTH1, GLS2, glutathione peroxidase 4 (GPX4) and heat shock protein β-1 (HSPB1) genes as possible candidates.

Gut microbiota and plasma metabolites in pregnant mothers and infant atopic dermatitis: A multi-omics study.

Background: Many studies reported the influence of infants' gut microbiota on atopic dermatitis (AD) postnatally, yet the role of maternal gut microbiota and plasma metabolites in infants' AD remains largely unexplored.

Methods: Sixty-three pregnant mother-infants were enrolled and followed after childbirth in Guangzhou, China. Demographic information, maternal stool and plasma samples, and records for infants' AD were collected.

Exploring the toxicology, socio-ecological impacts and biodegradation of microplastics in Africa: Potentials for resource conservation.

Achieving upcycling and circularity in the microplastic economy predominantly depends on collecting and sorting plastic waste from the source to the end-user for resource conservation. Microplastics, whether from packaging or non-packaging materials, pose a significant environmental challenge as they are often not prioritized for collection or recycling initiatives. The presence of additives impedes the quality of plastic recyclates and the persistence of microplastics as shredded resultants remain a threat to the aquatic and terrestrial ecosystem and its biodiversity.

3D modeling to predict vascular involvement in resectable pancreatic adenocarcinoma.

Background: Current management of patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC) depends on the degree of involvement of the major arterial and venous structures. The aim of this study was to evaluate 3D segmentation and printing to predict tumor size and vascular involvement of BR-PDAC to improve pre-operative planning of vascular resection and better select patients for neoadjuvant therapy.

Methods: We retrospectively evaluated 16 patients with BR-PDAC near vascular structures who underwent pancreatoduodenectomy (PD) with or without vascular resection between 2015 and 2021.

Development and validation of a prediction model for coronary heart disease risk in depressed patients aged 20 years and older using machine learning algorithms.

Background: Depression is being increasingly acknowledged as an important risk factor contributing to coronary heart disease (CHD). Currently, there is no predictive model specifically designed to evaluate the risk of coronary heart disease among individuals with depression. We aim to develop a machine learning (ML) model that will analyze risk factors and forecast the probability of coronary heart disease in individuals suffering from depression.