Macrophage-specific in vivo RNA editing promotes phagocytosis and antitumor immunity in mice.

Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.

Health Benefits of Monk Fruit under Traditional Dietary Patterns: Perspective on Immunity and Gut Microbiota Modulatory Functions.

Monk fruit is the mature fruit of Siraitia grosvenorii (Swingle) C. Jeffrey (SG), which contains mogrosides and various nutrients with diverse benefits as a traditional edible herb. The immunomodulatory effects of the ingredients of monk fruit in daily diets are poorly understood.

Unveiling the Antibacterial Mechanism of Gold Nanoparticles by Analyzing Bacterial Metabolism at the Molecular Level.

The threat of drug-resistant bacteria is challenging, and it is urgent to explore new antibiotics. Gold nanoparticles (AuNPs) are known to be a group of promising antibacterial agents for replacing conventional antibiotics. Nevertheless, their antibacterial mechanism remains to be elucidated.

Methoxyflavone glucosides and caffeoyl phenylethanoid glycoside from Lysionotus pauciflorus: their structures and anti-ferroptosis activity.

Phytochemical investigation on the aerial parts of Lysionotus pauciflorus Maxim. (Gesneriaceae), a medicinal plant used in Guangxi Zhuang Autonomous Region, China, resulted in the isolation of 13 secondary metabolites including two methoxyflavones, six flavonoid glycosides, and five caffeoyl phenylethanoid glycosides. Among these, the chemical structures of previously undescribed metabolites (1-3) were elucidated to be nevadensin 7-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranoside (1), nevadensin 7-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), and 2-(3,4-dihydroxyphenyl)ethyl-1-O-β-D-apiofuranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-β-D-(6'-O-E-caffeoyl)glucopyranoside (3) by detailed spectroscopic and HPLC analyses.

The DLEU2/miR-15a/miR-16-1 cluster shapes the immune microenvironment of chronic lymphocytic leukemia.

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2γ MEC1-based xenotransplantation model.

Network pharmacology and experimental verification to explore the anti-inflammatory activities of triterpenoids from .

(Swingle) C. Jeffrey (SG), a Chinese medicinal plant, exhibits promising anti-inflammatory properties. Based on previous reports, aglycone and mogrosides bearing lesser glucosyl groups may contribute to the bioactivity of SG .

Effects of individualized positive end-expiratory pressure on intraoperative oxygenation and postoperative pulmonary complications in patients requiring pneumoperitoneum with Trendelenburg position: A systematic review and meta-analysis.

Background: Whether individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and reduces postoperative pulmonary complications (PPCs) remains unclear. This systematic review and meta-analysis examined whether individualized PEEP is associated with improved intraoperative oxygenation and reduce PPCs for patients needing pneumoperitoneum with the Trendelenburg position during surgery.

Methods: Medline, Embase, the Cochrane Library, and www.

Molecular insights into degron recognition by CRL5 ubiquitin ligase.

The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1-18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron.

Gold nanoclusters cure implant infections by targeting biofilm.

The biofilm-mediated implant infections pose a huge threat to human health. It is urgent to explore strategies to reverse this situation. Herein, we design 3-amino-1,2,4-triazole-5-thiol (ATT)-modified gold nanoclusters (AGNCs) to realize biofilm-targeting and near-infrared (NIR)-II light-responsive antibiofilm therapy.

Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer.

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment.

Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects.

Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy.

The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided.

Supramolecular Genome Editing: Targeted Delivery and Endogenous Activation of CRISPR/Cas9 by Dynamic Host-Guest Recognition.

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs.

A review of mitigation technologies and management strategies for greenhouse gas and air pollutant emissions in livestock production.

One of the key issues in manure management of livestock production is to reduce greenhouse gas (GHG) and air pollutant emissions, which lead to significant environmental footprint and human/animal health threats. This study provides a review of potentially efficacious technologies and management strategies that reduce GHG and air pollutant emissions during the three key stages of manure management in livestock production, i.e.

Metabolism of Two Mogroside Isomers, Mogroside III and Mogroside IIIE, in Normal and Drug-Metabolizing Enzyme-Induced Rats.

Mogrosides III () and IIIE () are two important bioactive cucurbitane-type triterpenoid triglycosides in the edible fruits of (Swingle), which are isomers and have only a minor difference in their structures. To clarify the effects of structural difference and drug-metabolizing-enzyme induction on their metabolism in vivo, their metabolites in normal rats and drug-metabolizing-enzyme-induced rats were tentatively identified and semiquantified by using the HPLC-DAD-ESI-IT-TOF-MS technique. Totally, 76, 78, 96, and 121 metabolites of mogrosides were identified in the NIII (normal rats orally administered with mogroside III), NIIIE (normal rats orally administered with mogroside IIIE), EIII (drug-metabolizing-enzyme-induced rats orally administered with mogroside III), and EIIIE (drug-metabolizing-enzyme-induced rats orally administered with mogroside IIIE) groups, respectively.

Recent advances in nanoantibiotics against multidrug-resistant bacteria.

Multidrug-resistant (MDR) bacteria-caused infections have been a major threat to human health. The abuse of conventional antibiotics accelerates the generation of MDR bacteria and makes the situation worse. The emergence of nanomaterials holds great promise for solving this tricky problem due to their multiple antibacterial mechanisms, tunable antibacterial spectra, and low probabilities of inducing drug resistance.

Boosting the output performance of triboelectric nanogenerators surface engineering and structure designing.

Triboelectric nanogenerators (TENGs) have been utilized in a wide range of applications, including smart wearable devices, self-powered sensors, energy harvesting, and high-voltage power sources. The surface morphology and structure of TENGs play a critical role in their output performance. In this review, we analyze the working mechanism of TENGs with the aim to improve their output performance and systematically summarize the morphological engineering and structural design strategies for TENGs.

The Triterpenoids from and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (-), were extracted from the whole plants of using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (-) were established using carbon-proton spin-coupling constants () and inter-proton spin-coupling constants ().

Identification and Isolation of α-Glucosidase Inhibitors from Roots Using Bio-Affinity Ultrafiltration and Comprehensive Chromatography.

The discovery of bioactive compounds from medicinal plants has played a crucial role in drug discovery. In this study, a simple and efficient method utilizing affinity-based ultrafiltration (UF) coupled with high-performance liquid chromatography (HPLC) was developed for the rapid screening and targeted separation of α-glucosidase inhibitors from roots. First, an active fraction of roots (SGR2) was prepared, and 17 potential α-glucosidase inhibitors were identified based on UF-HPLC analysis.

Iridoid-glycoside isolation and purification from Premna fulva leaves.

Premna fulva Craib, rich in iridoid glycosides, is widely used to treat periarthritis, osteoproliferation, pain, and other diseases. However, no studies have reported effective purification methods for obtaining iridoid glycosides as active materials. This paper describes an efficient strategy for separating iridoid glycosides from Premna fulva leaves using high-speed counter-current chromatography and preparative high-performance liquid chromatography.

Acylated iridoid glucoside and xanthones from Canscora lucidissima: Their structures and ferroptosis inhibitory activity.

Phytochemical study on the whole plants of a Gentianaceous medicinal plant, Canscora lucidissima, gave one new acylated iridoid glucoside, canscorin A (1), and two new xanthone glycosides (2 and 3) together with 17 known compounds including five xanthones, eight xanthone glycosides, two benzophenone glucosides, caffeic acid, and loganic acid. Canscorin A (1) was assigned as a loganic acid derivative having a hydroxyterephthalic acid moiety by spectroscopic analysis together with chemical evidence, while 2 and 3 were elucidated to be a rutinosylxanthone and a glucosylxanthone, respectively. The absolute configurations of the sugar moieties of 2 and 3 were determined by HPLC analysis.

Highly Deformable High-Strength SiO Aerogel Designed with an Alternating Structure of Hard Cores and Flexible Chains for Thermal Insulation.

Thermally insulating aerogels can now be prepared from ceramics, polymers, carbon, and metals and composites between them. However, it is still a great challenge to make aerogels with high strength and excellent deformability. We propose a design concept of hard cores and flexible chains that alternately construct the aerogel skeleton structure.

Recognition of an Ala-rich C-degron by the E3 ligase Pirh2.

The ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron.

CLL stereotyped B-cell receptor immunoglobulin sequences are recurrent in the B-cell repertoire of healthy individuals: Apparent lack of central and early peripheral tolerance censoring.

Introduction: The leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, "stereotyped BCRs". The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance.

Results: Using bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors.

Acceptance and attitude towards the traditional chinese medicine among asymptomatic COVID-19 patients in Shanghai Fangcang hospital.

Objective: The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment.