Hepatic macrophages play critical roles in the establishment and growth of hydatid cysts in the liver during Echinococcus granulosus sensu stricto infection.

Cystic echinococcosis (CE) is a worldwide neglected zoonotic disease caused by infection with the larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.

4'-Ethynyl-2'-deoxy-2'-β-fluoro-2-fluoroadenosine: A Highly Potent and Orally Available Clinical Candidate for the Treatment of HIV-1 Infection.

2'-Deoxy-2'-β-fluoroadenosines bearing 4'-azido or 4'-ethynyl groups designed for the treatment of HIV-1 infection have been synthesized. All these compounds possess nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog () being the most potent compound with low cytotoxicity (EC = 0.9 nM, CC > 100 μM).

Activation of the phenylpropanoid pathway in Citrus sinensis collapsed vesicles during segment drying revealed by physicochemical and targeted metabolomics analysis.

Segment drying is a common internal physiological disorder in citrus fruit, and vesicles get granulated or collapsed. This study aimed to probe whether and how the phenylpropanoid metabolism changes in vesicles during collapse of blood orange (Citrus sinensis cv. Tarocco).

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45 lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology.

Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity.

Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) activity for immune signaling. TIR-NLR signaling requires the helper NLRs N requirement gene 1 (NRG1), Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1), which forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene 101 (SAG101). Here, we show that TIR-containing proteins catalyze the production of 2'-(5''-phosphoribosyl)-5'-adenosine monophosphate (pRib-AMP) and diphosphate (pRib-ADP) in vitro and in planta.

TIR-catalyzed ADP-ribosylation reactions produce signaling molecules for plant immunity.

Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners, Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded nicotinamide adenine dinucleotide hydrolase (NADase) produces signaling molecules to promote exclusive EDS1-PAD4 and EDS1-SAG101 interactions with helper NLR subclasses. In this work, we show that TIR-containing proteins catalyze adenosine diphosphate (ADP)-ribosylation of adenosine triphosphate (ATP) and ADP ribose (ADPR) through ADPR polymerase-like and NADase activity, forming ADP-ribosylated ATP (ADPr-ATP) and ADPr-ADPR (di-ADPR), respectively.

Analysis of the Dynamic Relationship between Green Economy Efficiency and Urban Land Development Intensity in China.

The improvement of green economic efficiency (GEE) should be realized under reasonable urban land development intensity (ULDI). Improving GEE can also help alleviate the negative externalities of excessive or unreasonable ULDI. Clarifying the interactive response mechanism between GEE and ULDI is a key link in regional sustainable development.

An -Benzyl Phosphonamidate Prodrug of Tenofovir for the Treatment of Hepatitis B Virus Infection.

A series of new -(substituted benzyl) phosphoramidate prodrugs of tenofovir for the treatment of hepatitis B virus (HBV) infections have been designed and synthesized. An investigation of structure-activity relationships revealed that the compound bearing an -methylbenzyl group () has the most potent anti-HBV activity. This prodrug () was well-tolerated in KM mice via intragastric administration at a dosage of up to 1.

Dual Role of Hepatic Macrophages in the Establishment of the Metacestode in Mice.

larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an "immunosuppressive" microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of , we investigated the phenotype and function of hepatic macrophages during the parasite infection.

Mechanistic Insight into Antiretroviral Potency of 2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) with a Long-Lasting Effect on HIV-1 Prevention.

In preclinical and phase I and II clinical studies, 2'-deoxy-2'-β-fluoro-4'-azidocytidine (FNC) displays a potent and long-lasting inhibition of HIV-1 infection. To investigate its mechanism of action, we compared it with the well-documented lamivudine (3TC). Pharmacokinetic studies revealed that the intracellular retention of FNC triphosphate in peripheral blood mononuclear cells was markedly longer than that of the 3TC triphosphate.

Synthesis of phenanthridines by I-mediated sp C-H amination.

An I2-mediated synthesis of phenanthridines via intramolecular sp3 C-H amination of readily accessible aniline precursors is reported. The present synthetic process is straightforward and applicable to a broad variety of unprotected aniline substrates, and provides facile and efficient access to phenanthridine derivatives. This C-H amination protocol does not use transition metals, is operationally simple, and can be achieved on a gram scale.

Annulation Reactions of In-Situ-Generated N-(Het)aroyldiazenes with Isothiocyanates Leading to 2-Imino-1,3,4-oxadiazolines.

A novel annulation reaction of N-(het)aroyldiazenes and isothiocyanates has been established. This transformation involves a sequential cyclization and desulfurization/intramolecular rearrangement to produce 2-imino-1,3,4-oxadiazolines. The less-stable N-(het)aroyldiazenes can be conveniently generated in situ by I-mediated oxidation of hydrazides, which allows a one-pot synthesis of the products directly from readily accessible hydrazide and isothiocyanate substrates.

Synthesis of 2 H-Azirines via Iodine-Mediated Oxidative Cyclization of Enamines.

A facile and practical oxidative cyclization reaction of enamines to 2 H-azirines has been developed, employing molecular iodine. The features of the present synthetic approach include no use of transition metals, mild reaction conditions, and simplicity of operation. Under the optimal reaction conditions, a variety of 2 H-azirine derivatives were synthesized from simple and readily accessible enamine precursors in an efficient and scalable fashion.

Synthesis of imidazo[1,5-a]pyridines via I-mediated sp C-H amination.

A transition-metal-free sp3 C-H amination reaction has been established for imidazo[1,5-a]pyridine synthesis employing molecular iodine from 2-pyridyl ketones and alkylamines. In the presence of sodium acetate (NaOAc), the I2-mediated oxidative annulations of readily available substrates produced a variety of imidazo[1,5-a]pyridine derivatives efficiently in a one-pot manner. The present synthetic approach is operationally simple and can be conveniently carried out on a gram scale.