Discovery of Bisindoles that Activate Tumor-Associated Macrophages and Enhance Antitumor Immunity.

The clinical successes in immunotherapy have been staggering but remain partially unsatisfactory. Small molecules may play an important role individually or in combination with antibiotics in this field. Therefore, the aim of this work is to identify small molecules that potentiate antitumor immunity.

Multifaceted approaches to promoting the growth potential in small-for-gestational-age infants and their clinical relevance.

Objective: To investigate the multifaceted approaches to promoting growth potential in small-for-gestational-age (SGA) infants and their clinical relevance.

Methods: This was a retrospective study. A total of 196 SGA infants who were born in the Department of Obstetrics at Baoding Maternal & Child Health Hospital from February 2020 to February 2024 were selected as the study subjects and were divided into the control group (n=98) and the catch-up group (n=98) according to different nursing approaches.

Ionones With Promoting Neurite Growth From Cephalotaxus oliveri Mast.

Two undescribed ionones, namely cepolionones A (1) and B (2), together with 13 known compounds (3-15), were isolated from the twigs and leaves of Cephalotaxus oliveri Mast. Their structures were elucidated by spectroscopic data (including mass spectrometry, ultraviolet detection, and one-/two-dimensional nuclear magnetic resonance) analysis, and the absolute configurations of two new compounds were determined by a comparison between their experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 showed significant neurite growth-promoting activity at the concentration of 10 µM.

Deciphering enhancers of hearing loss genes for efficient and targeted gene therapy of hereditary deafness.

Hereditary hearing loss accounts for about 60% of congenital deafness. Although adeno-associated virus (AAV)-mediated gene therapy shows substantial potential for treating genetic hearing impairments, there remain significant concerns regarding the specificity and safety of AAV vectors. The sophisticated nature of the cochlea further complicates the challenge of precisely targeting gene delivery.

Effect of Cu/Au for propylene epoxidation over the AgO(111) surface: a DFT study.

Catalysts belonging to the IB group for propylene epoxidation have garnered significant attention and have been extensively developed in the chemical industry. In this study, spin-polarized density functional theory (DFT) calculations combined with a U correction were performed to study propylene epoxidation on the AgO(111) surface with and without Cu or Au doping. Our calculations revealed a dual propylene epoxidation mechanism: the allylic hydrogen stripping (AHS) route and the intermediary propylene oxametallacycle (OMMP) route.

Relationship between programmed cell death and targeted therapy for thyroid cancer in patients with a poor prognosis: an update.

In recent years, the incidence of thyroid cancer has steadily increased. However, the detailed mechanisms of pathogenesis are still unclear. Therefore, a comprehensive understanding of the underlying carcinogenesis mechanisms of thyroid cancer is required.

PD-1 deficiency impairs eosinophil recruitment to tissue during Trichinella spiralis infection.

Blockade of programmed cell death 1 (PD-1) is considered a promising strategy for controlling pathogen infection by enhancing host immune cell function. Eosinophils, which play a crucial role in type 2 immune responses, are essential components of the host defense against helminth infection. Here, we investigate the role of PD-1 in eosinophilia during Trichinella spiralis infection in mice.

Highly bifunctional RhP on N,P-codoped carbon for hydrazine oxidation assisted energy-saving hydrogen production.

Highly pure RhP nanoparticles on N,P-codoped carbon were synthesized by a simple "mix-and-pyrolyze" method using one kind of low-cost nucleotide as the carbon, nitrogen and phosphorus source, which exhibits excellent bifunctional activity for the hydrogen reduction and hydrazine oxidation reactions, achieving energy-efficient hydrogen production.

Pathogenesis and signaling pathways related to iodine-refractory differentiated thyroid cancer.

Thyroid cancer is the most common malignant neoplasm within the endocrine system and the field of head and neck surgery. Although the majority of thyroid cancers, more than 90%, are well-differentiated thyroid carcinomas with a favourable prognosis, the escalating incidence of this disease has contributed to an increasing number of patients with a propensity for recurrent disease, rapid disease progression, and poor or no response to conventional treatments. These clinical challenges are commonly attributed to alterations in key thyroid oncogenes or signaling pathways, thereby initiating tumour cell dedifferentiation events, accompanied by reduced or virtually absent expression of the sodium/iodine symporter (NIS).

Ancillary ligand effects on α-olefin polymerization catalyzed by zirconium metallocene: a computational study.

The polymerization of α-olefins catalyzed by zirconium metallocene catalyst was systematically studied through experiments and density functional theory (DFT) calculations. Having achieved an agreement between theory and experiment, it was found that the effect of the catalyst ligand on the C[double bond, length as m-dash]C insertion reaction was significantly greater than that on the β-H elimination reaction. Therefore, the molecular weight of polymers can be increased by improving the activity of the C[double bond, length as m-dash]C insertion.

Structure-Based Design of Dual-Acting Compounds Targeting Adenosine A Receptor and Histone Deacetylase as Novel Tumor Immunotherapeutic Agents.

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A adenosine receptor (AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule AR antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of AR antagonists, dual-acting compounds incorporating AR antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of AR.

Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances.

Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools.

Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which are chemically in an overwhelming majority.

Cage-Monoterpenoid Quinoline Alkaloids with Neurite Growth Promoting Effects from the Fruits of .

Meloyunnanines A-C, three alkaloids with an unprecedented skeleton, were isolated from fruits of . The structures featuring a caged-6/6/5/6/5/5 ring system were elucidated by the analysis of comprehensive spectroscopic and X-ray data. Biosynthetically, meloyunnanines A-C were assigned to monoterpenoid quinoline alkaloids (MQAs), derived from monoterpenoid indole alkaloids through oxidation and rearrangement.

A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts.

Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT receptor.

Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury.

Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed.

Enhanced antiproliferative effect of resveratrol in head and neck squamous cell carcinoma using GE11 peptide conjugated liposome.

The present study describes the preparation of a dodecapeptide YHWYGYTPQNVI (GE11)‑conjugated liposome bound with polyethylene glycol to enhance the therapeutic effect of resveratrol (RSV) in head and neck cancer cells. The results indicated that (RSV)‑loaded GE11‑conjugated liposomes (RSV‑GL) exhibited a high entrapment efficiency of >95%, with an active drug loading level of 19.5% w/w.

[Chemical constituents from roots and rhizomes of Rubia oncotricha and their cytotoxic activities].

Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time.