Oral ruthenium-based PAD4 inhibitor modulates immunogenic cell death and neutrophil extracellular traps in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterized by a poor prognosis and resistance to conventional therapies. Peptidylarginine deiminase 4 (PAD4), which catalyzes the conversion of arginine to citrulline, facilitating neutrophil extracellular trap (NET) formation and promoting tumor immune evasion, has been identified as a promising target for TNBC treatment. However, current PAD4 inhibitors have low bioavailability and inadequate stability.

A silk fibroin/chitosan hydrogel with ferulic acid derivatives: Promoting diabetic wound healing through immune modulation and angiogenesis.

The impaired wound healing observed in diabetes is closely associated with immune system imbalance, in which the dysregulation of positive feedback mechanisms disrupts normal tissue repair processes. This study addresses the limited bioavailability of the natural anti-inflammatory compound ferulic acid (FA) by developing a novel derivative, FA-1a, via a phenylboronic acid modification strategy. Leveraging the reversible covalent interaction between chitosan (CS) and phenylboronic acid, the FA-1a-CS complex was successfully synthesized and subsequently incorporated into a silk fibroin (SF) dual-network hydrogel to create a multifunctional FA-1a-CS/SF composite hydrogel.

A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair.

Diabetic bone defects are associated with chronic inflammation, impaired healing, and high susceptibility to infection, posing serious clinical challenges. Recent studies have identified macrophage metabolic dysfunction as a key contributor to this impaired regenerative process. Targeting macrophage metabolism offers a promising strategy to rebalance the inflammatory microenvironment and promote bone repair.

Nanomedicine in ophthalmology: conquering anatomical barriers and enhancing therapeutic efficacy.

Ocular diseases pose a significant threat to vision and even lead to irreversible blindness, severely impacting patients' quality of life. Traditional ocular therapies often fall short of providing effective treatment due to the unique anatomical structure of the eye, particularly in the penetration of eye barriers. Recent advancements in nanotechnology have demonstrated significant potential for addressing these limitations.

Association of gestational weight gain patterns with preterm birth subtypes in a population based cohort study from China.

This study examined the association between gestational weight gain (GWG) patterns and preterm birth (PTB) subtypes using data from a registry system in Wuhan, China. A total of 57,138 women with live singleton births were included. Total GWG in the first and second trimesters was categorized as insufficient, appropriate, or excessive based on Chinese guidelines, and weekly early GWG (< 20 weeks; eGWG) was classified into Class I (< 100 g/week), Class II (100-399 g/week), and Class III (≥ 400 g/week).

Discovery of novel cathepsin K inhibitors for osteoporosis treatment using a deep learning-based strategy.

Background: Cathepsin K (CTSK), a cysteine protease of the papain family, exhibits high expression in activated osteoclasts, making it a key therapeutic target for osteoporosis. However, there are currently no CTSK inhibitors available for clinical use.

Research Design And Methods: The authors employed a combination of deep learning approaches and experimental methods to identify novel CTSK inhibitors.

Micro-needle jet injection technology for tunable drug dispersion at delivery.

Extravascular injection represents the predominant modality for contemporary drug administration. Needle injection (NI), a 180-year-old technology, provides a low-cost and effective method for delivering small-molecule drugs. However, it often results in low bioavailability for biomacromolecular drugs.

Discovery of highly potent naphthalene/quinoline-based PAD inhibitors: Structure-activity relationship, selectivity, and cytotoxicity.

This study focuses on developing highly potent inhibitors targeting peptidyl arginine deiminases (PADs), particularly PAD4 and PAD1, which play critical roles in citrullination-linked diseases such as cancer and autoimmune disorders. A series of benzylamine- and benzimidazole-substituted compounds were synthesized and evaluated for their inhibitory activity. Key findings include the identification of naphthalene and quinoline-based scaffolds with hydroxyl substitutions, which exhibited superior inhibition of PAD1 and PAD4 (IC values as low as 0.

New structural scaffolds to enhance the metabolic stability of arginine-derived PAD4 inhibitors.

Although arginine-derived PAD inhibitors represented by Cl-amidine () showed strong inhibition of PAD4 enzymes and exhibited efficacies in a variety of cellular assays and animal studies, their metabolic instability is a significant challenge for pre-clinical and clinical research. On the basis of the structure of a well-known PAD4 inhibitor BB-Cl-amidine (), we designed two metabolically stable scaffolds, providing two arginine-derived PAD4 inhibitors ( and ). We evaluated their PAD4 enzyme inhibitory activity and assessed their metabolic stability using liver microsomal assays.

Photoswitchable Antimicrobial Metallohelices.

Chiral subcomponent self-assembly is used to access optically pure, metallo-helical species based on Zn and Fe(II) and incorporating three transazobenzene units. UV-vis, circular dichroism, and NMR spectroscopies, alongside X-ray crystallographic and DFT computational studies are used to unambiguously characterize a highly reversible stepwise photochemical transformation to an all-cis state in which structural integrity and optical purity have been retained. Although the all-trans state of the water-soluble enantiomers exhibited low or moderate activity against Gram-positive strains, irradiation at 365 nm led to up to eight-fold reduction in MIC.

Canonical Wnt Pathway Enhanced Dental Pulp Mesenchymal Stem Cells-Mediated Cementum Regeneration.

Background: Cementum is a mineralised tissue that is essential for maintaining periodontal tissue homeostasis. Our previous research has shown that dental pulp mesenchymal stem cells (DPSCs) can regenerate periodontal tissues. However, the regeneration efficiency and the specific molecular mechanism remain unclear.

Fiber angular displacement sensor utilizing orbital angular momentum beam interference.

In this Letter, a highly sensitive and wide-range sensing system for fiber angular displacement measurement based on orbital angular momentum (OAM) beam interference is proposed and experimentally demonstrated. The system utilizes a micro polarization-maintaining fiber (PMF) as the angular displacement sensing element, effectively converting the angular displacement of fiber bending into an interference phase difference through the interaction of OAM modes and spherical wave interference. A dedicated algorithm is developed to demodulate the rotational characteristics of the interference image, enabling precise angular displacement measurement.

3D-printed fiber-based perfect vortex beam generator.

An all-fiber focused perfect vortex beam (PVB) generator is reported and fabricated by using 3D printing technology. The generator is constructed by integrating a designed spiral axicon zone plate (SAZP) on the fiber-end facet. The ring diameters of the generated beams are independent of the topological charges and positively correlated with the wave vectors in the transverse direction.

A smart photosensitive fluorescent probe for sensing Co in extremely alkaline aqueous solution.

A novel pH-, viscosity-, and photo-sensitive polymorphic fluorescence probe NHP for sensing Co has been developed. The hydrazone-based NHP can be synthesized by only one step of reflux reaction and purified by washing with poor solvents. Three single crystals of NHP-1, NHP-2, and NHP-3 with different conformations were resolved.

Epitope-Imprinted Field-Effect Transistors Overcome Debye Length Limitations for Label-Free Protein Detection.

Graphene-based field-effect transistor (GFET) biosensors face limitations in detecting charged analytes due to ionic screening (Debye screening effect). This limitation restricts their ability to detect charged target analytes in physiological solutions. To overcome this challenge, we present a non-destructive van der Waals (vdW) integration of an epitope molecular-imprinted membrane (EMIM) with a GFET biosensor.

Design, Synthesis, Evaluation, and SAR of 5-Phenylisoindoline Derivatives, a Potent Class of Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 (PD-1/PD-L1) Interaction.

A novel series of 5-phenylisoindoline derivatives were designed, synthesized, and evaluated for their activity to inhibit the interaction of PD-1/PD-L1 through the homogeneous time-resolved fluorescence assay. Meanwhile, structure-activity relationships were discussed according to both experiments and calculations. Several compounds exhibited potent activity with an IC value less than 10 nM, especially (4.

PAD4 Inhibitor-Loaded Magnetic FeO Nanoparticles for Magnetic Targeted Chemotherapy and Magnetic Resonance Imaging of Lung Cancer.

Introduction: Lung cancer is a major health concern worldwide owing to its high incidence and mortality rates. Therefore, identification of new therapeutic targets and strategies for lung cancer is critical for improving patient outcomes. Peptidyl arginine deiminase 4 (PAD4) promotes tumor growth and metastasis by catalyzing the citrullination of histones, making it a potential therapeutic target.

All-fiber focused optical vortex array generator based on a Dammann-Kinoform spiral zone plate.

An optical vortex array (OVA) provides more degrees of freedom for modulation by controlling the number and spatial distribution of optical vortices (OVs). However, traditional approaches such as spatial light modulation need to utilize numerous complex optical components to generate an OVA and bulky objective lenses to focus it. We reported a highly integrated all-fiber generator of the focused optical vortex array (FOVA) in this work.

High Detection Rate of Posterolateral Tibial Plateau Fractures and Poor Functional Outcomes in Type IIIB Impaction Fractures After Anterior Cruciate Ligament Rupture and Reconstruction.

Objective: The incidence of anterior cruciate ligament (ACL) ruptures has been increasing annually. However, clinical surgeons have overlooked the impaction fractures of the posterolateral tibial plateau and lateral femoral condyle in patients with ACL ruptures. The purpose of the present study was to report the detection rate of the posterolateral tibial plateau impaction fractures in patients with ACL ruptures, and to evaluate the functional outcomes of patients following ACL reconstruction (ACLR) without treatment of the tibial fractures at a 2-year postoperative follow-up.

Associations between environmental glyphosate exposure and glucose homeostasis indices in US general adults: a national population-based cross-sectional study.

As glyphosate's application becomes increasingly widespread across the globe, its potential adverse effects on humans have garnered growing concerns. Little evidence has revealed the associations between glyphosate and glucose homeostasis. A total of 2094 individuals were recruited from the NHANES 2013-2018.

Efficacy of different dietary therapy strategies in active pediatric Crohn's disease: a systematic review and network meta-analysis.

Background: Dietary therapy strategies play an important role in the treatment of pediatric patients with Crohn's disease (CD), but the relative efficacy of different dietary therapy strategies for Crohn's remission is unknown. This study aims to compare the effectiveness and tolerance of these dietary therapy strategies for active pediatric CD.

Methods: We searched the medical literature up to August 30, 2024 to identify randomized controlled trials (RCTs) of dietary therapy strategies for pediatric CD.

A turn-on fluorescent probe for imaging of hydroxyl radicals in drug-induced liver injury.

Hydroxyl radical is the most oxidizing type of reactive oxygen species (ROS), which is closely related to body health. In this work, a novel turn-on fluorescent probe BIJ-H for OH with high sensitivity was reported. BIJ-H was synthesized by a three-step reaction, and the pure product was obtained by only washing with poor solvents.

An RGD-Conjugated Prodrug Nanoparticle with Blood-Brain-Barrier Penetrability for Neuroprotection Against Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia-reperfusion injury significantly contributes to global morbidity and mortality. Loganin is a natural product with various neuroprotective effects; however, it lacks targeted specificity for particular cells or receptors, which may result in reduced therapeutic efficacy and an increased risk of side effects. To address the limitations of loganin, we developed LA-1, a novel compound incorporating an Arg-Gly-Asp (RGD) peptide to target integrin receptor αvβ3, enhancing brain-targeting efficacy.

Longitudinal ultra-sensitive mutation burden sequencing for precise minimal residual disease assessment in AML.

Relapse is one of the major challenges in clinical treatment of acute myeloid leukemia (AML). Though minimal residual disease (MRD) monitoring plays a crucial role in quantitative assessment of the disease, molecular MRD analysis has been mainly limited to patients diagnosed with gene fusions and NPM1 mutations. Here, we report a longitudinal ultra-sensitive mutation burden (UMB) monitoring strategy for accurate MRD analysis in AML patients regardless of genetic abnormality types.