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1.
iScience ; 27(6): 110064, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38947514

ABSTRACT

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.

2.
Cell Rep ; 43(7): 114423, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38968072

ABSTRACT

Actin assembly and dynamics are crucial for maintaining cell structure and changing physiological states. The broad impact of actin on various cellular processes makes it challenging to dissect the specific role of actin regulatory proteins. Using actin waves that propagate on the cortex of mast cells as a model, we discovered that formins (FMNL1 and mDia3) are recruited before the Arp2/3 complex in actin waves. GTPase Cdc42 interactions drive FMNL1 oscillations, with active Cdc42 and the constitutively active mutant of FMNL1 capable of forming waves on the plasma membrane independently of actin waves. Additionally, the delayed recruitment of Arp2/3 antagonizes FMNL1 and active Cdc42. This antagonism is not due to competition for monomeric actin but rather for their common upstream regulator, active Cdc42, whose levels are negatively regulated by Arp2/3 via SHIP1 recruitment. Collectively, our study highlights the complex feedback loops in the dynamic control of the actin cytoskeletal network.

4.
Chemosphere ; 361: 142544, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38844100

ABSTRACT

Nuclear energy is playing an increasingly important role on the earth, but the nuclear plants leaves a legacy of radioactive waste pollution, especially uranium-containing pollution. Straw biochar with wide sources, large output, low cost, and easy availability, has emerged as a promising material for uranium extraction from radioactive wastewater, but the natural biomass with suboptimal structure and low content of functional groups limits the efficiency. In this work, microbial etch was first came up to regulate the biochar's structure and function. The surface of the biochar becomes rougher and more microporous, and the mineral contents (Ca, P) indirectly increased by microbial etch. The biochar was modified by calcium phosphate and exhibited a remarkable uranium extraction capacity of 590.8 mg g-1 (fitted value). This work provides a cost-effective and sustainable method for preparing functionalized biochar via microbial etch, which has potential for application to uranium extraction from radioactive wastewater.


Subject(s)
Charcoal , Uranium , Wastewater , Charcoal/chemistry , Uranium/chemistry , Wastewater/chemistry , Radioactive Waste/analysis , Water Pollutants, Radioactive , Calcium Phosphates/chemistry
5.
Genes (Basel) ; 15(5)2024 05 14.
Article in English | MEDLINE | ID: mdl-38790252

ABSTRACT

Genetic variation facilitates the evolution, environmental adaptability, and biodiversity of organisms. Danish Large White (LW) pigs have more desirable phenotypes compared with local Chinese pigs, which have difficulty adapting to the modern swine industry. However, the genome-wide mutational differences between these pig breeds are yet to be evaluated. Therefore, this study aimed to evaluate genomic variation and identify breed-specific SNPs in Danish LW pigs. Here, 43 LW, 15 Diqing Tibetan (DQZ), and 15 Diannan small-ear (DN) pigs whose genomes were re-sequenced with 5× depth were selected. This was followed by a conjoined analysis of our previous resequencing data of 24 Anqing six-end white (AQ) and six Asian wild (SS) pigs. In total, 39,158,378 SNPs and 13,143,989 insertion-deletions were obtained in all breeds. The variation number of LW pigs was the lowest, with 287,194 breed-specific and 1289 non-synonymous SNPs compared with Chinese breeds. Functional analysis of the breed-specific non-synonymous SNPs indicated that these mutations were mainly associated with the reproductive performance, feed intake, and feed conversion ratio of LW pigs. These findings provide a theoretical basis for genetic improvements in the Chinese swine industry.


Subject(s)
Genome , Polymorphism, Single Nucleotide , Animals , Swine/genetics , Genome/genetics , Breeding , China , Sus scrofa/genetics , Phenotype
6.
Adv Colloid Interface Sci ; 329: 103197, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38781827

ABSTRACT

The semiconductor industry has long been driven by advances in a nanofabrication technology known as lithography, and the fabrication of nanostructures on chips relies on an important coating, the photoresist layer. Photoresists are typically spin-coated to form a film and have a photolysis solubility transition and etch resistance that allow for rapid fabrication of nanostructures. As a result, photoresists have attracted great interest in both fundamental research and industrial applications. Currently, the semiconductor industry has entered the era of extreme ultraviolet lithography (EUVL) and expects photoresists to be able to fabricate sub-10 nm structures. In order to realize sub-10 nm nanofabrication, the development of photoresists faces several challenges in terms of sensitivity, etch resistance, and molecular size. In this paper, three types of lithographic mechanisms are reviewed to provide strategies for designing photoresists that can enable high-resolution nanofabrication. The discussion of the current state of the art in optical lithography is presented in depth. Practical applications of photoresists and related recent advances are summarized. Finally, the current achievements and remaining issues of photoresists are discussed and future research directions are envisioned.

7.
Int J Oral Sci ; 16(1): 38, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734708

ABSTRACT

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.


Subject(s)
Basic-Leucine Zipper Transcription Factors , Flavonoids , Oxidative Stress , Periodontitis , Ubiquitination , Animals , Humans , Male , Rats , Antioxidants/pharmacology , Basic-Leucine Zipper Transcription Factors/drug effects , Basic-Leucine Zipper Transcription Factors/metabolism , Blotting, Western , Chromatin Immunoprecipitation , Disease Models, Animal , Molecular Docking Simulation , Oxidative Stress/drug effects , Periodontal Ligament/drug effects , Periodontal Ligament/metabolism , Periodontal Ligament/cytology , Periodontitis/drug therapy , Periodontitis/prevention & control , Periodontitis/metabolism , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Ubiquitination/drug effects , Flavonoids/pharmacology
8.
BMC Anesthesiol ; 24(1): 185, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789968

ABSTRACT

BACKGROUND: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. RESULTS: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. CONCLUSIONS: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.


Subject(s)
Gastrectomy , Ketamine , Laparoscopy , Pain, Postoperative , Postoperative Complications , Stomach Neoplasms , Humans , Ketamine/administration & dosage , Ketamine/therapeutic use , Stomach Neoplasms/surgery , Male , Female , Double-Blind Method , Laparoscopy/methods , Middle Aged , Gastrectomy/methods , Postoperative Complications/prevention & control , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Fatigue/prevention & control , Aged
9.
J Transl Med ; 22(1): 490, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790013

ABSTRACT

N6-methyladenosine (m6A) stands as the most prevalent modified form of RNA in eukaryotes, pivotal in various biological processes such as regulating RNA stability, translation, and transcription. All members within the YT521-B homology (YTH) gene family are categorized as m6A reading proteins, capable of identifying and binding m6A modifications on RNA, thereby regulating RNA metabolism and functioning across diverse physiological processes. YTH domain-containing 2 (YTHDC2), identified as the latest member of the YTH family, has only recently started to emerge for its biological function. Numerous studies have underscored the significance of YTHDC2 in human physiology, highlighting its involvement in both tumor progression and non-tumor diseases. Consequently, this review aims to further elucidate the pathological mechanisms of YTHDC2 by summarizing its functions and roles in tumors and other diseases, with a particular focus on its downstream molecular targets and signaling pathways.


Subject(s)
Adenosine , Neoplasms , RNA-Binding Proteins , Humans , Adenosine/analogs & derivatives , Adenosine/metabolism , Neoplasms/metabolism , Neoplasms/genetics , Neoplasms/pathology , RNA-Binding Proteins/metabolism , Animals , Disease , Signal Transduction , RNA Helicases
10.
J Am Chem Soc ; 146(19): 13236-13246, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38701635

ABSTRACT

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

12.
Front Genet ; 15: 1381917, 2024.
Article in English | MEDLINE | ID: mdl-38746057

ABSTRACT

MicroRNAs (miRNAs) are promising biomarkers for the early detection of disease, and many miRNA-based diagnostic models have been constructed to distinguish patients and healthy individuals. To thoroughly utilize the miRNA-profiling data across different sequencing platforms or multiple centers, the models accounting the batch effects were demanded for the generalization of medical application. We conducted transcription factor (TF)-mediated miRNA-miRNA interaction network analysis and adopted the within-sample expression ratios of miRNA pairs as predictive markers. The ratio of the expression values between each miRNA pair turned out to be stable across multiple data sources. A genetic algorithm-based classifier was constructed to quantify risk scores of the probability of disease and discriminate disease states from normal states in discovery, with a validation dataset for COVID-19, renal cell carcinoma, and lung adenocarcinoma. The predictive models based on the expression ratio of interacting miRNA pairs demonstrated good performances in the discovery and validation datasets, and the classifier may be used accurately for the early detection of disease.

13.
World J Surg ; 48(1): 86-96, 2024 01.
Article in English | MEDLINE | ID: mdl-38686746

ABSTRACT

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.


Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Hyperthermic Intraperitoneal Chemotherapy , Humans , Retrospective Studies , Male , Female , Appendiceal Neoplasms/therapy , Appendiceal Neoplasms/mortality , Appendiceal Neoplasms/pathology , Middle Aged , Adult , Adenocarcinoma, Mucinous/therapy , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Aged , Combined Modality Therapy , Treatment Outcome , Survival Rate , Neoplasm Grading , Intestinal Perforation/etiology , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/mortality
14.
Yi Chuan ; 46(4): 279-289, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38632091

ABSTRACT

H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.


Subject(s)
Histones , Nucleosomes , Histones/metabolism , Chromatin , Gene Expression Regulation , Genome
15.
Nat Commun ; 15(1): 3561, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38670996

ABSTRACT

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.


Subject(s)
Histones , Host Cell Factor C1 , Lysine , Transcription, Genetic , Histones/metabolism , Humans , Lysine/metabolism , HEK293 Cells , Animals , Cell Line, Tumor , Transcription Initiation Site , Gene Expression Regulation , Mice , Protein Processing, Post-Translational
16.
Cell Rep ; 43(4): 114032, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38568805

ABSTRACT

N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.


Subject(s)
AlkB Homolog 5, RNA Demethylase , Carcinogenesis , Feedback, Physiological , Tumor Suppressor Proteins , Tumor Suppressor Proteins/metabolism , AlkB Homolog 5, RNA Demethylase/genetics , AlkB Homolog 5, RNA Demethylase/metabolism , Feedback, Physiological/physiology , Protein Stability , Phosphorylation/genetics , Glioblastoma/enzymology , Glioblastoma/physiopathology , Humans , Animals , Mice , Cell Line, Tumor , Adenosine/analogs & derivatives , Adenosine/metabolism , Cell Count , Proteolysis , Carcinogenesis/genetics , Carcinogenesis/pathology
17.
Adv Mater ; 36(25): e2401597, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38511907

ABSTRACT

Dielectric loss is a crucial factor in determining the long-term endurance for security and energy loss of dielectric composites. Here, chain-like semiconductive fibers of titanium oxide, indium, and niobium-doped titanium oxide are used for enhancing the complex dielectric properties of a polymer through composite construction, which involves significant interface enhancements. The chain-like fibers significantly enhance the dielectric constant owing to the special morphology of the fillers and their interfacial polarization, especially at higher temperatures. The dielectric loss and electrical conductivity of the composites are substantially reduced across the entire investigated temperature range, achieved by passivating the fiber surface with an alumina shell using atomic layer deposition. The as-deposited alumina shell transformed from an amorphous to a crystalline phase through thermal annealing results in a porous shell and more effective suppression of the loss tangent and electrical conductivity. A plausible mechanism for loss suppression is associated with carrier movement along the surface of the fibers and bulk, leading to a higher loss tangent. The alumina shell blocks the carrier transport path, particularly at the interfaces, resulting in a reduced interfacial polarization contribution and energy storage loss. This study provides a method for inhibiting dielectric loss by fabricating fillers with special surfaces.

18.
Sci Total Environ ; 927: 171875, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38522530

ABSTRACT

Evaporative emission is an important source of vehicle pollutant emission and volatile organic compounds (VOCs), causing serious environmental pollution. Carbon canisters are used to store fuel vapor in evaporative emission control (EVAP) system, but canisters are prone to saturation, leading to the direct release of fuel vapor into the atmosphere. Therefore, accurate estimation of fuel vapor generation is crucial for EVAP system. Gasoline evaporation rate is mainly influenced by vapor-liquid interface area, gasoline saturated vapor pressure, filling level and temperature. The quantitative relation between different parameters and gasoline evaporation rate has rarely been reported, and a gasoline evaporative emission estimation model suitable for China needs to be proposed urgently. In this study, gasoline evaporative emission tests have been carried out in VT-SHED, and the effects of vapor-liquid interface area, filling level and temperature on gasoline evaporative emissions have been analyzed under the premise of consistent gasoline temperature and ambient temperature. Some valuable conclusions are obtained. The results show that different from expectation, gasoline evaporative emissions are not positively correlated with the vapor-liquid interface area. There is an approximately exponential relationship between the headspace volume and gasoline evaporative emissions. The widely used Reddy equation and Hata equation underestimate the gasoline vapor generation in China. Based on China VI test program and gasoline, accurate estimation of mass transfer coefficient has been conducted, and a new semi-empirical estimation model for vapor generation has been proposed. The model can accurately estimate the fuel evaporation of vehicles in China, providing guidance for the matching and optimization of EVAP system.

19.
Genes (Basel) ; 15(2)2024 02 12.
Article in English | MEDLINE | ID: mdl-38397222

ABSTRACT

Baoshan pigs (BS) are a local breed in Yunnan Province that may face inbreeding owing to its limited population size. To accurately evaluate the inbreeding level of the BS pig population, we used whole-genome resequencing to identify runs of homozygosity (ROH) regions in BS pigs, calculated the inbreeding coefficient based on pedigree and ROH, and screened candidate genes with important economic traits from ROH islands. A total of 22,633,391 SNPS were obtained from the whole genome of BS pigs, and 201 ROHs were detected from 532,450 SNPS after quality control. The number of medium-length ROH (1-5 Mb) was the highest (98.43%), the number of long ROH (>5 Mb) was the lowest (1.57%), and the inbreeding of BS pigs mainly occurred in distant generations. The inbreeding coefficient FROH, calculated based on ROH, was 0.018 ± 0.016, and the FPED, calculated based on the pedigree, was 0.027 ± 0.028, which were positively correlated. Forty ROH islands were identified, containing 507 genes and 891 QTLs. Several genes were associated with growth and development (IGFALS, PTN, DLX5, DKK1, WNT2), meat quality traits (MC3R, ACSM3, ECI1, CD36, ROCK1, CACNA2D1), and reproductive traits (NPW, TSHR, BMP7). This study provides a reference for the protection and utilization of BS pigs.


Subject(s)
Inbreeding , Polymorphism, Single Nucleotide , Swine/genetics , Animals , Polymorphism, Single Nucleotide/genetics , China , Homozygote , Quantitative Trait Loci/genetics , Diarrhea
20.
Cell Prolif ; 57(7): e13612, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38348888

ABSTRACT

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Immunomodulation , Mesenchymal Stem Cells , Metformin , Mice, Inbred C57BL , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Animals , Metformin/pharmacology , Mice , Immunomodulation/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Colitis/drug therapy , Colitis/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , Cellular Reprogramming/drug effects , Cell Differentiation/drug effects , Cellular Senescence/drug effects , Cells, Cultured , Cell Movement/drug effects , Bone Marrow Cells/metabolism , Bone Marrow Cells/drug effects , Bone Marrow Cells/cytology , Metabolic Reprogramming
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