Fusing a Novel Anti-CTLA-4 Nanobody to the IgG1 Fc Region Strengthens Its Ability to Induce CD8 T Cell-Mediated Immune Responses Against Solid Tumors.

Background: Our previously described a nanobody precisely targeting CTLA-4 and demonstrated that it can promote the antitumor response of adoptive T cells. Here we examined whether fusing it to the IgG1 Fc region would induce stronger, longer-lasting T-cell immune responses after exposure to the dendritic-tumor cell fusions.

Methods: The fusion of nanobody to Fc region was overexpressed in .

Brevetoxin Aptamer Selection and Biolayer Interferometry Biosensor Application.

Brevetoxins (PbTxs) are very potent marine neurotoxins that can cause an illness clinically described as neurologic shellfish poisoning (NSP). These toxins are cyclic polyether in chemistry and have increased their geographical distribution in the past 2 decades. However, the ethical problems as well as technical difficulties associated with currently employed analysis methods for marine toxins have spurred the quest for suitable alternatives to be applied in a regulatory monitoring regime.

A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8 T cells in solid tumours.

Background: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions.

Results: The fusion protein enhanced the response of CD8 T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts.

Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future.

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor.

Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH.

Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.

Aims: The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients.

Methods: Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets.

Uncommon Epoxyquinols Pyrrolocytosporin A and Cytosporin E from the Fungus Eutypella sp. D-1.

Two uncommon epoxyquinols, pyrrolocytosporin A (1) and cytosporin E (2), along with the known cytosporin Y (3), were isolated from the solid defined medium of the Arctic-derived fungus Eutypella sp. D-1. Their structures were established through comprehensive analyses of spectroscopic and electronic circular dichroism data.

Eutypellaolides A-J, Sesquiterpene diversity expansion of the polar fungus sp. D-1.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (-), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (-), along with four known 12,8-eudesmanolide compounds -, were isolated from the culture extract of the polar fungus sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis.

Cytosporin Derivatives from Arctic-Derived Fungus sp. D-1 via the OSMAC Approach.

A chemical investigation of the Arctic-derived fungus sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds - and -) from rice medium and eight cytosporins (compounds and -) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (), cytosporin Y (), cytosporin Z (), cytosporin Y (), cytosporin Y (), cytosporin Y (), and cytosporin E (), were elucidated by analyzing their detailed spectroscopic data.

Quality by design driven development and evaluation of thermosensitive hydrogel loaded with IgY and LL37-SLNs to combat experimental periodontitis.

Egg yolk immunoglobulin (IgY) and LL37, potent antibacterial substances, can fight against periodontitis. This work aimed to develop a locally injectable hydrogel for potential co-delivery of special IgY and LL37-loaded solid lipid nanoparticles (LL37-SLNs) to synergistically inhibit the proliferation of oral pathogens, thus relieving periodontal inflammation and redness. The formulation of thermosensitive hydrogel loaded with IgY and LL37-SLNs was developed by adopting the Quality by Design approach.

Prodigiosin derived from chromium-resistant Serratia sp. prevents inflammation and modulates gut microbiota homeostasis in DSS-induced colitis mice.

Prodigiosin (PG) is a secondary metabolite of microorganisms with anticancer, antimalarial, antibacterial and immunomodulatory effects. However, the modulatory effects on gut microbiome and intestinal immune microenvironment have never been explored in the ulcerative colitis (UC) mice model. In this study, 2.

Alterations of oral microbiota in patients with obstructive sleep apnea-hypopnea syndrome treated with continuous positive airway pressure: a pilot study.

Purpose: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for cardiovascular diseases, including hypertension. In our previous study, it was demonstrated that oral microbiota alteration in patients with OSAHS, particularly in the genera Aggregatibacter and Porphyromonas, may influence the development of hypertension. Continuous positive airway pressure (CPAP) is the main therapy for OSAHS and OSAHS-associated hypertension.

Palitantin derivatives from the Antarctic fungus sp. 3-1.

Two new polyketides, palitantins B and C ( and ), along with one known related compound (+)-palitantin () were obtained from the culture of the Antarctic fungus sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data.

Eutypellacytosporins A-D, Meroterpenoids from the Arctic Fungus sp. D-1.

The Arctic fungus sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (-), along with the known biogenetically related compound cytosporin D ().

Eutypellenoids A⁻C, New Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D-1.

Three new pimarane diterpenes, eutypellenoids A⁻C (⁻), together with a known compound, eutypenoid C (), were isolated from the culture extract of sp. D-1 derived from the Arctic region. Compounds ⁻ possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton.

Bone morphogenetic proteins and inner ear development.

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.

Libertellenones O-S and Eutypellenones A and B, Pimarane Diterpene Derivatives from the Arctic Fungus Eutypella sp. D-1.

Seven new pimarane-type diterpene derivatives, libertellenones O-S (1-5) and eutypellenones A and B (6 and 7), together with two known compounds (8 and 9), were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures were elucidated from spectroscopic data, as well as experimental and calculated electronic circular dichroism (ECD) analysis.

Bioactive metabolites from the Arctic fungus sp. B-13.

Two new cyclohexanone derivatives, nectriatones A-B (-), and one new natural product, nectriatone C (), together with three known phenolic sesquiterpene derivatives (-), were isolated from the culture of sp. B-13 obtained from high-latitude soil of the Arctic. The structures of all compounds were unambiguously elucidated by extensive spectroscopic analysis, as well as by comparison with the literature.

Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy.

Background: Inhibition of aging of vascular endothelial cells (VECs) may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 (AUF1) gene (CD31-PILs-AUF1) and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs.

Methods: The mean particle sizes of various PEGylated immunoliposomes (PILs) were measured using a Zetasizer Nano ZS.

Furanone derivative and sesquiterpene from Antarctic marine-derived fungus Penicillium sp. S-1-18.

A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses.

Biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9.

The biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2), and lecaniside C (3). The chemical structures of these metabolites were elucidated based on extensive spectral data, including 2D NMR and HRMS. The hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these metabolites were observed in the present study.

A new sesquiterpene lactone from fungus Eutypella sp. D-1.

We isolated and identified a new sesquiterpene lactone which we named eut-Guaiane sesquiterpene (1), along with four cytochalasins from the fungus Eutypella sp. derived from the soil of high latitude of Arctic. The new structure was determined by spectroscopic studies such as 1D and 2D NMR and MS analyses, while the known compounds were identified by comparison of the NMR data with those in literatures.

Marine Antibody-Drug Conjugates: Design Strategies and Research Progress.

Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs.

Doxorubicin-Conjugated Heparin-Coated Superparamagnetic Iron Oxide Nanoparticles for Combined Anticancer Drug Delivery and Magnetic Resonance Imaging.

In this study, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with an average size of 10±2 nm were coated with doxorubicin (Dox)-conjugated heparin (DH-SPIO) and were used for targeted anticancer drug delivery, and as a magnetic resonance imaging (MRI) contrast agent. The DH-SPIO NPs had a mean particle size of 125±10 nm and a zeta potential of –35±3 mV. Fourier transform-infrared spectroscopy, X-ray diffraction spectroscopy, transmission electron microscopy, vibrating sample magnetometry, and MTT assay were used to investigate the properties of DH-SPIO NPs.