Design, synthesis, and evaluation of quinoxaline-based survivin inhibitors for castration-resistant prostate cancer.

Survivin, a member of the Inhibitors of Apoptosis Protein (IAP) family, is a homodimer and plays a vital role in cell survival and cell cycle progression. Due to its unique expression pattern in nearly all cancers but not normal adult tissues, survivin has been regarded as an ideal anticancer drug target. Targeting its hydrophobic dimerization interface has recently resulted in novel survivin degraders that induce its degradation in the proteasome.

Boric Acid-Catalyzed Synthesis: A scalable strategy for High-Yield and Tunable red fluorescent carbon dots.

Red fluorescent carbon dots (RCDs) have garnered significant attention in the fields of lighting and bioimaging due to their exceptional optical properties and favorable biocompatibility. However, existing synthesis strategies often involve complex processes and rely on expensive, toxic polycyclic aromatic hydrocarbons, which fundamentally limit their yield and applicability. In this study, RCDs with a high quantum yield of 45 % were synthesized via a one-step solvothermal method using citric acid and urea as precursors, with boric acid as a catalyst.

5-Aminolevulinic Acid: from pyrrole biosynthetic precursor to multifunctional plant growth regulator.

5-Aminolevulinic acid (ALA) is a non-protein δ-amino acid and an essential precursor of tetrapyrrole compound biosynthesis. Nowadays, it is a well-known natural plant growth regulator with multiple biological regulatory functions. In this review, we summarize the regulatory effects of ALA in promoting plant growth and the development of organs such as roots, stems, leaves, flowers, and fruits under normal conditions as well as stressful conditions.

CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex.

Aims: Genotoxic drug resistance is one of the major obstacles for cancer treatment. Our previous study demonstrates that cold shock domain containing E1 (CSDE1) is associated with drug resistance. In this study, we aim to demonstrate that CSDE1 regulates cellular response to genotoxic drugs and to investigate its mechanism of action in drug resistance.

eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through mA modification.

eIF3a is a -methyladenosine (mA) reader that regulates mRNA translation by recognizing mA modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation mA during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation .

A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC.

DNA damage-based drugs are widely used in cancer therapy, yet resistance remains a major challenge. In this study, we uncovered a non-DNA repair mechanism contributing to resistance in pancreatic ductal adenocarcinoma (PDAC). We show that in gemcitabine-resistant PDAC cells, CIP2A undergoes ubiquitin-mediated degradation, resulting in enhanced PP2A phosphatase activity.

Gap-App: A sex-distinct AI-based predictor for pancreatic ductal adenocarcinoma survival as a web application open to patients and physicians.

In this study, using RNA-Seq gene expression data and advanced machine learning techniques, we identified distinct gene expression profiles between male and female pancreatic ductal adenocarcinoma (PDAC) patients. Building on this insight, we developed sex-specific 3-year survival predictive models alongside a single comprehensive model. Despite smaller sample sizes, the sex-specific models outperformed the general model.

5-Aminolevulinic acid activates the MdWRKY71-MdMADS1 module to enhance anthocyanin biosynthesis in apple.

5-Aminolevulinic acid (ALA), as a natural plant growth regulator, is well known for promoting red fruit coloring by enhancing anthocyanin accumulation. However, the underlying mechanisms remain elusive. In this study, we firstly demonstrated that ALA upregulates gene expression of the transcription factor MdMADS1, which in turn directly binds to and activates transcription of the key anthocyanin biosynthetic genes, MdCHS and MdUFGT.

Formation Water Genesis Mechanism of Deep Tight Sandstone Gas Reservoirs in the Southern Ordos Basin and Its Indication for Development.

By analyzing the chemical characteristics of the formation water in the tight sandstone reservoirs of the P2x8 and P1s1 in the southern Ordos Basin, combined with rock mineral composition, reservoir physical properties, and well gas testing data, the genesis mechanism of formation water and its guiding role in gas reservoir development were discussed. The results show that the formation water is derived from the mixture of syngenetic seawater and meteoric water and has undergone remarkable modification by water-rock interactions, showing characteristics of Ca enrichment and Mg and SO depletion. The albitization of plagioclase in reservoir rock components causes Ca excess and Na deficiency in formation water, while the chloritization of albite leads to the increase of Na.

5-Aminolevulinic acid improves strawberry salt tolerance through a NO-HO signaling circuit regulated by FaWRKY70 and FaWRKY40.

Introduction: 5-Aminolevulinic acid (ALA) is an essential biosynthetic precursor of tetrapyrrole compounds, naturally occurring in all living organisms. It has also been suggested as a new plant growth regulator. Treatment with ALA promotes strawberry Na homeostasis under salt stress.

Comparative analysis of heart rate variability indices from ballistocardiogram and electrocardiogram: a study on measurement agreement.

Ballistocardiogram (BCG) captures minute vibrations generated by heart movements. These vibrations are converted into heart rate variability (HRV) indices, allowing their unobtrusive monitoring over extended periods, while reducing the burden on patients or subjects. In this study, to evaluate the agreement between the HRV indices, we compared the HRV indices estimated from the BCG device with those obtained from the gold standard electrocardiogram (ECG).

Photoinduced EnT-mediated sulfonamidylimination of alkenes and (hetero)arenes with iminophenylacetic acid oxime esters.

A photoinduced EnT-mediated generation of sulfonamidyl radicals has been accomplished using rationally designed iminophenylacetic acid oxime ester reagents under metal-free conditions. This approach offers a mild, regio- and diastereoselective synthesis of -sulfonyl diamines diamination of alkenes and (hetero)arenes.

Gap-App: A sex-distinct AI-based predictor for pancreatic ductal adenocarcinoma survival as a web application open to patients and physicians.

In this study, using RNA-Seq gene expression data and advanced machine learning techniques, we identified distinct gene expression profiles between male and female pancreatic ductal adenocarcinoma (PDAC) patients. Building upon this insight, we developed sex-specific 3-year survival predictive models along with a single comprehensive model. These sex-specific models outperformed the single general model despite the smaller sample sizes.

Comparison of dual-plane micro-drop injection of botulinum toxin type A with two traditional methods for treating hypertrophic scars in the tension zone: A long-term clinical application study.

Background: Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension.

Aims: To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension.

Methods: Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO via fractional CO laser.

[First-line Treatment with Furmonertinib Mesylate in Lung Adenocarcinoma Patient with EGFR Exon 20 Insertion Mutantion].

With the continuous innovation of genomics, proteomics and molecular biological detection technology, the treatment of non-small cell lung cancer (NSCLC) has changed from traditional chemotherapy to immunotherapy and targeted therapy. Among them, molecular tumor markers targeting tyrosine kinase pathways play more important roles in clinical practice. For advanced NSCLC patients with positive epidermal growth factor receptor (EGFR) mutations, there are many first-line drugs on the market and they could bring significant efficacy, thus completely subverting the treatment pattern of advanced NSCLC.

FASN negatively regulates p65 expression by reducing its stability via Thr phosphorylation and isomerization by Pin1.

FASN, the sole cytosolic enzyme responsible for de novo palmitate synthesis in mammalian cells, has been associated with poor prognosis in cancer and shown to cause drug and radiation resistance by upregulating DNA damage repair via suppression of p65 expression. Targeting FASN by repurposing proton pump inhibitors has generated impressive outcomes in triple-negative breast cancer patients. While p65 regulation of DNA damage repair was thought to be due to its suppression of poly(ADP-ribose) polymerase 1 gene transcription, the mechanism of FASN regulation of p65 expression was unknown.

Smart exosomes enhance PDAC targeted therapy.

Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen.

Changepoint Detection in Heart Rate Variability Indices in Older Patients Without Cancer at End of Life Using Ballistocardiography Signals: Preliminary Retrospective Study.

Background: In an aging society such as Japan, where the number of older people continues to increase, providing in-hospital end-of-life care for all deaths, and end-of-life care outside of hospitals, such as at home or in nursing homes, will be difficult. In end-of-life care, monitoring patients is important to understand their condition and predict survival time; this information gives family members and caregivers time to prepare for the end of life. However, with no clear indicators, health care providers must subjectively decide if an older patient is in the end-of-life stage, considering factors such as condition changes and decreased food intake.

NIR-switchable local hydrogen generation by tandem bimetallic MOFs nanocomposites for enhanced chemodynamic therapy.

The inadequate quantity of hydrogen peroxide (HO) in cancer cells promptly results in the constrained success of chemodynamic therapy (CDT). Significant efforts made throughout the years; nevertheless, researchers are still facing the great challenge of designing a CDT agent and securing HO supply within the tumor cell. In this study, taking advantage of HO level maintenance mechanism in cancer cells, a nanozyme-based bimetallic metal-organic frameworks (MOFs) tandem reactor is fabricated to elevate intracellular HO levels, thereby enhancing CDT.

N-Coordinated Iridium-Molybdenum Dual-Atom Catalysts Enabling Efficient Bifunctional Hydrogen Electrocatalysis.

Achieving effective hydrogen evolution/oxidation reaction (HER/HOR) across a wide pH span is of critical importance in unlocking the full potential of hydrogen energy but remains intrinsically challenging. Here, we engineer the N-coordinated Ir-Mo dual atoms on a carbon matrix by ultrafast high-temperature sintering, creating an efficient bifunctional electrocatalyst for both HER and HOR in both acidic and alkaline electrolytes. The optimized catalyst, Ir-Mo DAC/NC, demonstrates exceptional performance, with a significantly reduced HER overpotential of 11.

Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.

Survivin, a homodimeric protein and a member of the IAP family, plays a vital function in cell survival and cycle progression by interacting with various proteins and complexes. Its expression is upregulated in cancers but not detectable in normal tissues. Thus, it has been regarded and validated as an ideal cancer target.

Identification of Genetic Risk Factors Based on Disease Progression Derived From Longitudinal Brain Imaging Phenotypes.

Neurodegenerative disorders usually happen stage-by-stage rather than overnight. Thus, cross-sectional brain imaging genetic methods could be insufficient to identify genetic risk factors. Repeatedly collecting imaging data over time appears to solve the problem.