Matrine disturbs the eimeria necatrix-induced loop of tuft cell-intestinal stem cell-goblet cell by inactivating IL-13/JAK2/STAT3 signaling.

As sensors in the gut, tuft cells integrate a complex array of luminal signals to regulate the differentiation fate of intestinal stem cells (ISCs), which trigger a loop of tuft cell-ISC-goblet cell after parasitic infection. As a plant-derived alkaloid, Matrine plays a prominent role for standardizing ISC functions in Eimeria necatrix (EN)-exposed chicks. In this study, we investigated the modulation effects of Matrine on the specific intestinal epithelial cell loop in EN-exposed chicks in vivo and intestinal organoids (IOs) ex vivo.

[Research progress and prediction of quality markers of Menispermi Rhizoma].

Menispermi Rhizoma, the dried rhizome of Menispermum dauricum, has anti-tumor, anti-inflammatory, anti-arrhythmic, anti-myocardial ischemia, and anti-cerebral ischemia activities. The primary constituents of this herbal medicine include alkaloids, polysaccharides, and fatty oils. This study predicts and evaluates the quality markers(Q-markers) of Menispermi Rhizoma by considering the phylogenetic relationship of the plant, chemical composition, conventional effects, component measurability, blood constituents, and network pharmacology.

Early Weaning Inhibits Intestinal Stem Cell Expansion to Disrupt the Intestinal Integrity of Duroc Piglets via Regulating the Keap1/Nrf2 Signaling.

There are different stress resistance among different breeds of pigs. Changes in intestinal stem cells (ISCs) are still unclear among various breeds of piglets after early weaning. In the current study, Taoyuan Black and Duroc piglets were slaughtered at 21 days of age (early weaning day) and 24 days of age (3 days after early weaning) for 10 piglets in each group.

Constructing more comprehensive pollination networks: integrating diurnal and nocturnal pollen data with visitation in a subalpine wetland community.

Introduction: Sampling for describing plant-pollinator interaction networks has been performed using techniques that either focus on the plants (with flower-visit data) or the animals (with analyzing pollen on the body surface of flower visitors). The differences in the structure of the networks obtained using these methods likely influences our understanding of the contribution of nocturnal pollinators, yet this key finding has yet to be the focus of study.

Methods: In this study, we conducted an intensive diurnal field survey in the subalpine meadows of the Dajiuhu Wetland and supplemented the data with an analysis of diurnal and nocturnal pollen data to examine the changes in pollination networks.

Bismuth-based mesoporous nanoball carrying sorafenib for synergistic photothermal and molecularly-targeted therapy in an orthotopic hepatocellular carcinoma xenograft mouse model.

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release.

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor.

Mulberry Leaf-Derived Morin Activates β-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice.

Matrine reduced intestinal stem cell damage in eimeria necatrix-infected chicks via blocking hyperactivation of Wnt signaling.

Background: Coccidiosis is a rapidly spreading and acute parasitic disease that seriously threatening the intestinal health of poultry. Matrine from leguminous plants has anthelmintic and anti-inflammatory properties.

Purpose: This assay was conducted to explore the protective effects of Matrine and the AntiC (a Matrine compound) on Eimeria necatrix (EN)-infected chick small intestines and to provide a nutritional intervention strategy for EN injury.

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared.

Degree of style coiling is associated with corolla-tube length in the nectarless flowers of .

The plant-pollinator 'arms race' model posits that a major driver of the evolution of elongated corollas in flowers is reciprocal selection for 'morphological fit' between pollinator-tongue length and access distance to nectar (usually corolla-tube length). Evidence for the pollinator-mediated selection on tube length and evolution of multiple, correlated floral traits remains inconclusive. To gain possible insights into the strength of stabilizing selection by assessing standing phenotypic variation, we measured a series of functionally important floral traits, including corolla tube length and 'effective' tube depth and degree of style coiling.

Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.

Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion.

Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases.

ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.

The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target MMR-d cancer cells. Here, we show that inhibition of the ATR kinase preferentially kills MMR-d cancer cells.

The evolution of flower-pollinator trait matching, and why do some alpine gingers appear to be mismatched?

Background And Aims: Morphological matching between flower and pollinator traits has been documented in diverse plant lineages. Indeed, the matching of corolla tube length and pollinator tongue length has been cited repeatedly as a classic case of coevolution. However, there are many possible evolutionary routes to trait matching.

l-Malic Acid Facilitates Stem Cell-Driven Intestinal Epithelial Renewal through the Amplification of β-Catenin Signaling by Targeting Frizzled7 in Chicks.

l-Malic acid (l-MA) contributes to energy metabolism and nutrient digestion, which is an alternative to antibiotics for livestock; however, it is not clear whether l-MA can replace antibiotics to promote intestinal development in chicks. To investigate the effects of l-MA on intestinal stem cells (ISCs) driving epithelial renewal, we employed in vivo chick feeding experiments, chick intestinal organoid (IO) models, and in vitro chick intestinal epithelial cell models. The results showed that the feed conversion rate and diarrhea scores were decreased with improved jejunal morphology and barrier function in the 0.

Pre- and post-pollination barriers between two exotic and five native species: Implications for species conservation.

Anthropogenic introduction of species has resulted in a breakdown of geographical barriers and hybridization in previously allopatric species. Thus, examining hybridization proneness of exotic species contributes to revealing its potential threat. Moreover, reproductive barriers may be strengthened or weakened due to long-term geographical isolation for these newly sympatric species.

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence instead of apoptosis could enable the identification of senolytic agents to restore tissue homeostasis. Here, we identify thrombomodulin (THBD) signaling as a key molecular determinant of the senescent cell fate.

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Background And Aims: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Senescing cells upregulate thrombomodulin-protease-activated receptor-1 (THBD-PAR1) signaling to remain viable.

Maintenance of andromonoecy in an autogamous species: Superior male function in male flowers of the endangered .

Andromonoecy is a rare sexual system in plants. The function of additional male flowers in andromonoecious species has been widely discussed; however, few studies have taken offspring fitness into account. In addition, little is known about the mechanisms that maintain andromonoecy in autogamous species.

Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis.

Background And Aims: Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whether YAP regulates these processes and whether this could be leveraged to treat liver fibrosis are unknown.

Approach And Results: YAP activity was manipulated in MF-HSCs to determine how YAP impacts susceptibility to pro-apoptotic senolytic agents or ferroptosis.

PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1.

Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): New opportunities in establishing faithful pre-clinical cancer models.

One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of pre-clinical models that faithfully recapitulate tumor properties in the patients. Monolayer cultures of cancer cell lines usually lose the heterogeneity of the parental tumors, while patient-derived xenograft (PDX) suffers from its time- and resource-intensive nature. The emergence of organoid culture system and its application in cancer research provides a unique opportunity to develop novel cancer pre-clinical models.