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1.
Sci Rep ; 14(1): 23824, 2024 10 11.
Article in English | MEDLINE | ID: mdl-39394394

ABSTRACT

This study aims to assess how the construction patterns within residential communities influence the adolescent myopia using general survey. In a private high school from a megacity in mid-west China, a questionnaire gathered data on the 10th-grade students' level of myopia, home address, and some potential confounding factors. Additionally, satellite digital images were utilized to calculate the proportion of shadow area (PSA) and the proportion of greenness area (PGA) within a 500 m×500 m area centered on each student's home address. Correlations between myopia levels and PSA, along with other variables, were analyzed. The prevalence of mild, moderate, and high myopia were 39.2%, 32.5%, and 8.3%, respectively. A negative correlation was observed between myopia levels and PSA, albeit marginally significant (r=-0.189*, P = 0.05). Upon dividing the sample into higher and lower PSA groups using a cut-off point of 20%, a significant difference in myopia levels was evident (χ2 = 8.361, P = 0.038), while other confounding factors remained comparable. In conclusion, high-rise apartment constructions, which often cast more shadows on digital satellite maps, may not exacerbate myopia progression. Instead, they could potentially serve as a protective factor against adolescent myopia in densely populated megacities, as they allow for more ground space allocation.


Subject(s)
Myopia , Humans , Adolescent , Myopia/prevention & control , Myopia/epidemiology , Male , Female , China/epidemiology , Surveys and Questionnaires , Remote Sensing Technology/methods , Prevalence , Satellite Imagery/methods
2.
Schizophr Bull ; 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39393024

ABSTRACT

BACKGROUND AND HYPOTHESIS: Numerous studies have found that being born or raised in urban environments increases the odds of developing psychosis in Northern and Western Europe. However, available research from Southern Europe, Latin America, and Asia has reported null results. A limitation in most studies to date is the inadequate characterization of urban and rural life components that may contribute to varying psychosis risk across regions. STUDY DESIGN: To deepen our understanding of the different concepts and measures of urbanicity and related factors in psychosis research, we conducted a qualitative systematic literature review extracting information from studies published between 2000 and 2024. STUDY RESULTS: Sixty-one articles met the inclusion and exclusion criteria and were used in the thematic analysis. The analysis revealed that urbanicity lacked a single, coherent definition across studies and regions. Three major categories of themes were developed from the analysis: (1) Urbanicity comprises several interconnected constructs, (2) Urbanicity measurements vary between countries from the Global North and the Global South, and (3) Urbanicity operates through key neighborhood-level mechanisms. CONCLUSIONS: Future research on urbanicity and psychosis should consider the potential limitations of urbanicity's conceptualization and operationalization and aim to address these limitations by focusing on contextual, historical, and community-level factors, utilizing locally validated measures, and employing mixed-method designs.

3.
J Adv Res ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39270978

ABSTRACT

INTRODUCTION: Heart failure (HF) is a systemic metabolic disorder disease, across multiorgan investigations advancing knowledge of progression and treatment of HF. Whole-body MSI provides spatiotemporal information of metabolites in multiorgan and is expected to be a potent tool to dig out the complex mechanism of HF. OBJECTIVES: This study aimed at exploring the systemic metabolic disorder in multiorgan and catecholamines biosynthesis alteration on heart-gut axis after HF. METHODS: Whole-body MSI was used to characterize metabolic disorder of the whole rat body after HF. An integrated method by MSI, LC-MS/MS and ELISA was utilized to analyze key metabolites and enzymes on heart, small intestine, cecum and colon tissues of rat. Gut microbiota dysbiosis was investigated by 16S rDNA sequencing and metagenomic sequencing. Validation experiments and in vitro experiments were performed to verify the effect of catecholamines biosynthesis alteration on heart-gut axis after HF. RESULTS: Whole-body MSI exhibited varieties of metabolites alteration in multiple organs. Remarkably, catecholamine biosynthesis was significantly altered in the serum, heart and intestines of rats. Furthermore, catecholamines and tyrosine hydroxylase were obviously upregulated in heart and colon tissue. Turicibacter_sanguinis was relevant to catecholamines of heart and colon. Validation experiments demonstrated excessive norepinephrine induced cardio-intestinal injury, including significantly elevating the levels of BNP, pro-BNP, LPS, DAO, and increased the abundance of Turicibacter_sanguinis. These alterations could be reversed by metoprolol treatment blocking the effect of norepinephrine. Additionally, in vitro studies demonstrated that norepinephrine promoted the growth of Turicibacter_sanguinis and Turicibacter_sanguinis could import and metabolize norepinephrine. Collectively, excessive norepinephrine exerted bidirectional effects on cardio-intestinal function to participate in the progression of HF. CONCLUSION: Our study provides a new approach to elucidate multiorgan metabolic disorder and proposes new insights into heart-gut axis in HF development.

4.
J Agric Food Chem ; 72(38): 20763-20774, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39271247

ABSTRACT

Trichoderma longibrachiatum is a filamentous fungus used as a biological control agent against different plant diseases. The multifunctional secondary metabolites synthesized by Trichoderma, called peptaibols, have emerged as key elicitors in plant innate immunity. This study obtained a high-quality genome sequence for the T. longibrachiatum strain 40418 and identified two peptaibol biosynthetic gene clusters using knockout techniques. The two gene cluster products were confirmed as trilongin AIV a (11-residue) and trilongin BI (20-residue) using liquid chromatography coupled with tandem mass spectrometry. Further investigations revealed that these peptaibols induce plant resistance to Pseudomonas syringae pv tomato (Pst) DC3000 infection while triggering plant immunity and cell death. Notably, the two peptaibols exhibit synergistic effects in plant-microbe signaling interactions, with trilongin BI having a predominant role. Moreover, the induction of tomato resistance against Meloidogyne incognita showed similarly promising results.


Subject(s)
Disease Resistance , Peptaibols , Plant Diseases , Pseudomonas syringae , Solanum lycopersicum , Trichoderma , Plant Diseases/microbiology , Plant Diseases/parasitology , Plant Diseases/prevention & control , Solanum lycopersicum/microbiology , Solanum lycopersicum/immunology , Trichoderma/chemistry , Trichoderma/metabolism , Trichoderma/genetics , Peptaibols/pharmacology , Peptaibols/chemistry , Fungal Proteins/genetics , Fungal Proteins/metabolism , Tylenchoidea/drug effects , Plant Immunity , Animals
5.
Genes (Basel) ; 15(9)2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39336797

ABSTRACT

Background/Objectives: Induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells into cells with most of the ESC (embryonic stem cell) characteristics show promise toward solving ethical problems currently facing stem cell research and eventually yield clinical grade pluripotent stem cells for therapies and regenerative medicine. In recent years, an increasing body of research suggests that the chemical induction of pluripotency (CIP) method can yield iPSCs in vitro, yet its application in avian species remains unreported. Methods: Herein, we successfully obtained stably growing chicken embryonic fibroblasts (CEFs) using the tissue block adherence method and employed 12 small-molecule compounds to induce chicken iPSC formation. Results: The final optimized iPSC induction system was bFGF (10 ng/mL), CHIR99021 (3 µM), RepSox (5 µM), DZNep (0.05 µM), BrdU (10 µM), BMP4 (10 ng/mL), vitamin C (50 µg/mL), EPZ-5676 (5 µM), and VPA (0.1 mM). Optimization of the induction system revealed that the highest number of clones was induced with 8 × 104 cells per well and at 1.5 times the original concentration. Upon characterization, these clones exhibited iPSC characteristics, leading to the development of a stable compound combination for iPSC generation in chickens. Concurrently, employing a deletion strategy to investigate the functionality of small-molecule compounds during induction, we identified CHIR99021 and BrdU as critical factors for inducing chicken iPSC formation. Conclusions: In conclusion, this study provides a reference method for utilizing small-molecule combinations in avian species to reprogram cells and establish a network of cell fate determination mechanisms.


Subject(s)
Cellular Reprogramming , Chickens , Fibroblasts , Induced Pluripotent Stem Cells , Pyridines , Pyrimidines , Animals , Pyridines/pharmacology , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Pyrimidines/pharmacology , Cellular Reprogramming/drug effects , Fibroblasts/drug effects , Fibroblasts/cytology , Fibroblasts/metabolism , Chick Embryo , Cell Differentiation/drug effects , Cells, Cultured , Small Molecule Libraries/pharmacology
6.
Hortic Res ; 11(9): uhae188, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39247885

ABSTRACT

Nuclear-mitochondrial communication is crucial for plant growth, particularly in the context of cytoplasmic male sterility (CMS) repair mechanisms linked to mitochondrial genome mutations. The restorer of fertility-like (RFL) genes, known for their role in CMS restoration, remain largely unexplored in plant development. In this study, we focused on the evolutionary relationship of RFL family genes in poplar specifically within the dioecious Salicaceae plants. PtoRFL30 was identified to be preferentially expressed in stem vasculature, suggesting a distinct correlation with vascular cambium development. Transgenic poplar plants overexpressing PtoRFL30 exhibited a profound inhibition of vascular cambial activity and xylem development. Conversely, RNA interference-mediated knockdown of PtoRFL30 led to increased wood formation. Importantly, we revealed that PtoRFL30 plays a crucial role in maintaining mitochondrial functional homeostasis. Treatment with mitochondrial activity inhibitors delayed wood development in PtoRFL30-RNAi transgenic plants. Further investigations unveiled significant variations in auxin accumulation levels within vascular tissues of PtoRFL30-transgenic plants. Wood development anomalies resulting from PtoRFL30 overexpression and knockdown were rectified by NAA and NPA treatments, respectively. Our findings underscore the essential role of the PtoRFL30-mediated mitochondrion-auxin signaling module in wood formation, shedding light on the intricate nucleus-organelle communication during secondary vascular development.

7.
Front Cell Infect Microbiol ; 14: 1391215, 2024.
Article in English | MEDLINE | ID: mdl-39247056

ABSTRACT

Background: There is increasing focus on HIV-1 CRF55_01B in China. However, there is limited information regarding the dissemination of CRF55_01B across different regions and populations in Guangxi. This study was performed to elucidate the evolutionary history of the introduction and dissemination of CRF55_01B in Guangxi. Methods: Molecular network and phylogenetic analyses were used to investigate the transmission characteristics of CRF55_01B in China. The analyses particularly focused on the cross-provincial spatial and temporal transmission patterns between Guangdong Province and Guangxi, as well as the transmission dynamics among different regions and populations within Guangxi. Results: In total, 2226 partial pol sequences of CRF55_01B strains sampled from 2007 to 2022 were collected, including 1895 (85.09%) sequences from Guangdong, 199 (8.94%) sequences from Guangxi, and 172 (7.59%) sequences from other provinces of China. Most people living with HIV in Guangxi were infected with HIV-1 through heterosexuals (52.76%). Among these, 19.10% had a history of commercial heterosexual contact (CHC) and 15.58% had a history of non-marital non-commercial heterosexual contact (NMNCHC). Overall, 1418 sequences were identified in the molecular network. Notably, the sequences from Guangdong Province were most closely linked to those from Guangxi. Phylogenetic analysis showed that CRF55_01B was first introduced from Shenzhen City to Nanning City around 2007. Subsequently, CRF55_01B established local transmission within Guangxi, with Nanning City serving as the transmission center from 2008 to 2017. After 2017, the CRF55_01B strain spread to other regions of Guangxi. Men who have sex with men (MSM) and men with a history of CHC have played a significant role in the transmission of CRF55_01B among different populations in Guangxi. Conclusions: This study provides evidence on the transmission trajectory of CRF55_01B among different regions and populations in Guangxi. Given the bridging role of men with a history of CHC in the dissemination of CRF55_01B from MSM to the general population, it is imperative to enhance surveillance among key populations to mitigate the secondary transmission of HIV-1.


Subject(s)
HIV Infections , HIV-1 , Heterosexuality , Homosexuality, Male , Phylogeny , Humans , China/epidemiology , Male , HIV-1/genetics , HIV-1/classification , HIV Infections/transmission , HIV Infections/epidemiology , HIV Infections/virology , Adult , Genotype , Molecular Epidemiology , Female , Young Adult , Middle Aged , pol Gene Products, Human Immunodeficiency Virus/genetics
8.
Cancer Sci ; 115(10): 3320-3332, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39105355

ABSTRACT

High expression of truncated O-glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N-acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6-mediated O-glycosylation aggravates malignant behaviors. Gain- and loss-of-function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC-derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site-directed mutagenesis assays, we found that O-glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6-induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium-derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6-mediated abnormal O-glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.


Subject(s)
Carcinoma, Renal Cell , Cell Movement , Cell Proliferation , Disease Progression , Kidney Neoplasms , N-Acetylgalactosaminyltransferases , N-Acetylgalactosaminyltransferases/metabolism , N-Acetylgalactosaminyltransferases/genetics , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/genetics , Animals , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Cell Line, Tumor , Mice , Glycosylation , Female , Male , Antigens, Tumor-Associated, Carbohydrate/metabolism , Mice, Nude , Gene Expression Regulation, Neoplastic
9.
Biology (Basel) ; 13(8)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39194515

ABSTRACT

Breast cancer is a complex and multifaceted disease with diverse risk factors, types, and treatment options. Triple-negative breast cancer (TNBC), which lacks the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is the most aggressive subtype. Hypoxia is a common feature of tumors and is associated with poor prognosis. Hypoxia can promote tumor growth, invasion, and metastasis by stimulating the production of growth factors, inducing angiogenesis, and suppressing antitumor immune responses. In this study, we used mRNA-seq technology to systematically investigate the gene expression profile of MDA-MB-231 cells under hypoxia. We found that the hypoxia-inducible factor (HIF) signaling pathway is the primary pathway involved in the cellular response to hypoxia. The genes in which expression levels were upregulated in response to hypoxia were regulated mainly by HIF1α. In addition, hypoxia upregulated various genes, including Nim1k, Rimkla, Cpne6, Tpbgl, Kiaa11755, Pla2g4d, and Ism2, suggesting that it regulates cellular processes beyond angiogenesis, metabolism, and known processes. We also found that HIF1α was hyperactivated in MDA-MB-231 cells under normoxia. A HIF1α inhibitor effectively inhibited the invasion, migration, proliferation, and metabolism of MDA-MB-231 cells. Our findings suggest that hypoxia and the HIF signaling pathway play more complex and multifaceted roles in TNBC than previously thought. These findings have important implications for the development of new therapeutic strategies for TNBC.

10.
Biology (Basel) ; 13(8)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39194536

ABSTRACT

Animal embryonic development occurs under hypoxia, which can promote various developmental processes. Embryonic fibroblasts, which can differentiate into bone and cartilage and secrete various members of the collagen protein family, play essential roles in the formation of embryonic connective tissues and basement membranes. However, the adaptations of embryonic fibroblasts under hypoxia remain poorly understood. In this study, we investigated the effects of hypoxia on mouse embryonic fibroblasts (MEFs). We found that hypoxia can induce migration, promote metabolic reprogramming, induce the production of ROS and apoptosis, and trigger the activation of multiple signaling pathways of MEFs. Additionally, we identified several hypoxia-inducible genes, including Proser2, Bean1, Dpf1, Rnf128, and Fam71f1, which are regulated by HIF1α. Furthermore, we demonstrated that CoCl2 partially mimics the effects of low oxygen on MEFs. However, we found that the mechanisms underlying the production of ROS and apoptosis differ between hypoxia and CoCl2 treatment. These findings provide insights into the complex interplay between hypoxia, fibroblasts, and embryonic developmental processes.

11.
Proc Natl Acad Sci U S A ; 121(35): e2322418121, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39159377

ABSTRACT

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed "shielding-augmenting RBC-in-nanoscale amorphous silica (SARNAS)" has been developed. The key to RBC surface engineering and structure augmentation is the precise control of the hydrolysis form of silicic acid to realize stabilization of RBC within conformal nanoscale silica-based exoskeletons. The formed silicified RBCs (Si-RBCs) maintain membrane/structural integrity, normal cellular functions (e.g., metabolism, oxygen-carrying capability), and enhance resistance to external stressors as well as tunable mechanical properties, resulting in nearly 100% RBC cryoprotection. In vivo experiments confirm their excellent biocompatibility. By shielding RBC surface antigens, the Si-RBCs provide universal blood compatibility, the ability for allogeneic mechanical perfusion, and more importantly, the possibility for cross-species transfusion. Being simple, reliable, and easily scalable, the SARNAS strategy holds great promise to revolutionize the use of engineered blood for future clinical applications.


Subject(s)
Biocompatible Materials , Erythrocytes , Silicon Dioxide , Erythrocytes/metabolism , Silicon Dioxide/chemistry , Biocompatible Materials/chemistry , Animals , Humans , Perfusion/methods , Blood Preservation/methods , Blood Transfusion/methods , Mice
12.
Materials (Basel) ; 17(16)2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39203177

ABSTRACT

The microstructure and mechanical properties of as-cast Al-10Ce-3Mg-xZn (x = 0, 1, 3, 5 wt.%) alloys were systematically investigated, with a focus on the effect of Zn on the Al11Ce3 reinforcing phase in the alloy. The results showed that the Al-10Ce-3Mg alloy consists of α-Al, a Chinese-script Al11Ce3 eutectic phase, and a massive Al11Ce3 primary phase. With the addition of Zn content, most of the Zn atoms are enriched in the Al11Ce3 phase to form the acicular-like Al2CeZn2 phase within the Al11Ce3 phase. Increasing the Zn content can increase the volume fraction of the Al11Ce3 phase. Compared to the alloy without Zn addition, the microhardness and elastic modulus of the Al2CeZn2-reinforced Al11Ce3 phase in the alloy with 5 wt.% Zn increased by 18.9% and 9.0%, respectively. Moreover, the room-temperature mechanical properties of Al-10Ce-3Mg alloys were significantly improved due to the addition of Zn element. The alloy containing 5 wt.% Zn had the best tensile properties with an ultimate tensile strength of 210 MPa and a yield strength of 171MPa, which were 21% and 77% higher than those of the alloy without Zn, respectively. The alloy containing 5 wt.% Zn demonstrated a superior retention ratio of tensile strength at 200-300 °C, indicating that the alloy has excellent heat resistance. The improvement in the mechanical properties is primarily attributed to second-phase strengthening and solid solution strengthening.

13.
Vet Sci ; 11(8)2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39195830

ABSTRACT

(1) Background: Bovine viral diarrhea virus (BVDV) causes calf diarrhea, bovine respiratory syndrome, and cow abortion, resulting in substantial economic losses in the cattle industry. Owing to its persistent infection mechanism, BVDV is a major challenge in the treatment of cattle. (2) Methods: To determine how metformin (Met) inhibits the interaction between BVDV and host cells, we treated BVDV-infected cells with Met. We then performed an RNA sequencing (RNA-seq) analysis of Met-treated cells infected with BVDV to identify differentially expressed genes (DEGs). Consequently, the RNA-seq results were validated through real-time quantitative PCR (qPCR). (3) Results: Our analysis revealed 3169 DEGs in the Met-treated cells (Met group) vs. the negative controls (NC group) and 2510 DEGs in the BVDV-infected cells after pretreatment with Met (MetBVDV group) vs. the BVDV-infected cells (BVDV group). The DEGs were involved in MDBK interactions during BVDV infection, as indicated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The potential interactions of the DEGs were confirmed via a protein-protein interaction (PPI) network. Met treatment induced autophagy signaling activity and the expression of the autophagy-related genes ATG2A, ATG4B, ATG10, and ATG12 in BVDV-infected Met-pretreated cells. (4) Conclusions: We found that the host transcriptomic profile was affected by BVDV infection and Met pretreatment. These findings offer valuable new insights and provide support for future studies on the inhibition of BVDV replication by Met.

14.
J Am Chem Soc ; 146(32): 22220-22235, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39088252

ABSTRACT

High-voltage layered oxide cathodes attract great attention for sodium-ion batteries (SIBs) due to the potential high energy density, but high voltage usually leads to rapid capacity decay. Herein, a stable high-voltage NaLi0.1Ni0.35Mn0.3Ti0.25O2 cathode with a ribbon-ordered superlattice is reported, and the intrinsic coupling mechanism between structure evolution and the anion redox reaction (ARR) is revealed. Li introduction constructs a special Li-O-Na configuration activating reversible nonbonded O 2p (|O2p)-type ARR and regulates the structure evolution way, enabling the reversible Li ions out-of-layer migration instead of the irreversible transition metal ions out-of-layer migration. The reversible structure evolution enhances the reversibility of the bonded O 2p (O2p)-type ARR and inhibits the generation of oxygen dimers, thus suppressing the irreversible molecular oxygen (O2)-type ARR. After the structure regulation, the structure evolution becomes reversible, |O2p-type ARR is activated, O2p-type ARR becomes stable, and O2-type ARR is inhibited, which largely suppresses the capacity degradation and voltage decay. The discharge capacity is increased from 154 to 168 mA h g-1, the capacity retention after 200 cycles significantly increases from 35 to 84%, and the voltage retention increases from 78 to 93%. This study presents some guidance for the design of high-voltage, O3-type oxide cathodes for high-performance SIBs.

15.
Arch Microbiol ; 206(9): 378, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143417

ABSTRACT

Human milk oligosaccharides (HMOs) have been recognized as gold standard for infant development. 3-Fucosyllactose (3-FL), being one of the Generally Recognized as Safe HMOs, represents a core trisaccharide within the realm of HMOs; however, it has received comparatively less attention in contrast to extensively studied 2'-fucosyllactose. The objective of this review is to comprehensively summarize the health effects of 3-FL, including its impact on gut microbiota proliferation, antimicrobial effects, immune regulation, antiviral protection, and brain maturation. Additionally, the discussion also covers the commercial application and regulatory approval status of 3-FL. Lastly, an organized presentation of large-scale production methods for 3-FL aims to provide a comprehensive guide that highlights current strategies and challenges in optimization.


Subject(s)
Gastrointestinal Microbiome , Milk, Human , Trisaccharides , Trisaccharides/metabolism , Humans , Milk, Human/chemistry , Oligosaccharides/metabolism , Animals
16.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38958514

ABSTRACT

An Electron Cyclotron Emission (ECE) modeling code has been developed to model ECE radiation with an arbitrary electron momentum distribution, a small oblique angle, both ordinary (O-mode) and extraordinary polarizations (X-mode), and multiple cyclotron frequency harmonics. The emission and absorption coefficients are calculated using the Poynting theorem from the cold plasma dispersion and the electron-microwave interaction from the full anti-Hermitian tensor. The modeling shows several ECE radiation signatures that can be used to diagnose the population of suprathermal electrons in a tokamak. First, in an n = 2 X-mode (X2) optically thick plasma and oblique ECE view, the modeling shows that only suprathermal electrons, which reside in a finite region of the velocity and space domains, can effectively generate cyclotron emissions to the ECE receiver. The code also finds that the O1 mode is sensitive to suprathermal electrons of both a high v⊥ and v‖, while the X2 mode is dominantly sensitive to suprathermal electrons of a high v⊥. The modeling shows that an oblique ECE system with both X/O polarization and a broad frequency coverage can be used to effectively yield information of the suprathermal electron population in a tokamak.

17.
Nat Commun ; 15(1): 5777, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982111

ABSTRACT

Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.


Subject(s)
Alcohol Drinking , Exome Sequencing , Humans , Alcohol Drinking/genetics , Male , Female , Genetic Predisposition to Disease , United Kingdom/epidemiology , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Exome/genetics , Middle Aged , Brain/metabolism , Brain/pathology
18.
Redox Rep ; 29(1): 2373657, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39023011

ABSTRACT

OBJECTIVES: Intestinal ischemia-reperfusion (I/R) injury is a multifactorial and complex clinical pathophysiological process. Current research indicates that the pathogenesis of intestinal I/R injury involves various mechanisms, including ferroptosis. Methane saline (MS) has been demonstrated to primarily exert anti-inflammatory and antioxidant effects in I/R injury. In this study, we mainly investigated the effect of MS on ferroptosis in intestinal I/R injury and determined its potential mechanism. METHODS: In vivo and in vitro intestinal I/R injury models were established to validate the relationship between ferroptosis and intestinal I/R injury. MS treatment was applied to assess its impact on intestinal epithelial cell damage, intestinal barrier disruption, and ferroptosis. RESULTS: MS treatment led to a reduction in I/R-induced intestinal epithelial cell damage and intestinal barrier disruption. Moreover, similar to treatment with ferroptosis inhibitors, MS treatment reduced ferroptosis in I/R, as indicated by a decrease in the levels of intracellular pro-ferroptosis factors, an increase in the levels of anti-ferroptosis factors, and alleviation of mitochondrial damage. Additionally, the expression of Nrf2/HO-1 was significantly increased after MS treatment. However, the intestinal protective and ferroptosis inhibitory effects of MS were diminished after the use of M385 to inhibit Nrf2 in mice or si-Nrf2 in Caco-2 cells. DISCUSSION: We proved that intestinal I/R injury was mitigated by MS and that the underlying mechanism involved modulating the Nrf2/HO-1 signaling pathway to decrease ferroptosis. MS could be a promising treatment for intestinal I/R injury.


Subject(s)
Ferroptosis , Heme Oxygenase-1 , Methane , NF-E2-Related Factor 2 , Reperfusion Injury , Signal Transduction , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Ferroptosis/drug effects , NF-E2-Related Factor 2/metabolism , Animals , Signal Transduction/drug effects , Mice , Heme Oxygenase-1/metabolism , Methane/pharmacology , Male , Humans , Saline Solution/pharmacology , Intestines/drug effects , Intestines/injuries , Mice, Inbred C57BL , Membrane Proteins
19.
BMC Musculoskelet Disord ; 25(1): 516, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970034

ABSTRACT

BACKGROUND: Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. OBJECTIVE: To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. METHODS: Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. RESULTS: The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. CONCLUSION: Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.


Subject(s)
Bone Screws , Lumbar Vertebrae , Sacrum , Spinal Fusion , Torque , Humans , Male , Female , Sacrum/surgery , Sacrum/diagnostic imaging , Middle Aged , Aged , Spinal Fusion/instrumentation , Spinal Fusion/methods , Spinal Fusion/adverse effects , Lumbar Vertebrae/surgery , Adult , Feasibility Studies , Treatment Outcome , Follow-Up Studies
20.
Neurospine ; 21(2): 712-720, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38955540

ABSTRACT

OBJECTIVE: To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. METHODS: A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1-4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). RESULTS: A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1-4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552-8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). CONCLUSION: The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.

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