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1.
MycoKeys ; 106: 173-200, 2024.
Article in English | MEDLINE | ID: mdl-38948915

ABSTRACT

Zhujiangyuan Nature Reserve, located in Qujing City, Yunnan Province, China, is reported with high fauna and floral diversity, while the fungal diversity of the region is poorly documented. During the summer season in 2023, decaying wood-inhabiting microfungi were collected from different microhabitats. The novel species were identified based on morphological characteristics and phylogenetic analyses (based on combined datasets of ITS, LSU, SSU, tef1-α, and rpb2 regions). Two species belong to Dothideomycetes (viz., Spegazziniazhujiangyuanensis sp. nov. and Phaeoseptumzhujiangyuanense sp. nov. in Pleosporales) while the other one resides in Sordariomycetes (Synnemasporellafanii sp. nov. in Diaporthales). The results are in conformity with the earlier studies that predicted higher fungal diversity in this region.

2.
Microb Pathog ; : 106768, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960217

ABSTRACT

Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.

3.
ACS Omega ; 9(26): 28485-28493, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38973881

ABSTRACT

Predicting the drug-target binding affinity (DTA) is crucial in drug discovery, and an increasing number of researchers are using artificial intelligence techniques to make such predictions. Many effective deep neural network prediction models have been proposed. However, current methods need improvement in accuracy, complexity, and efficiency. In this study, we propose a method based on a multiscale 2-dimensional convolutional neural network (CNN), namely ImageDTA. Many studies have shown that CNN achieves good learning effects with limited data. Therefore, we take a unique perspective by treating the word vector encoded with a simplified molecular input line entry system (SMILES) string as an "image" and processing it like handling images, fully leveraging the efficient processing capabilities of CNN for image data. Furthermore, we show that ImageDTA has higher training and inference efficiency than pretrained large models and outperforms attention-based graph neural network models in accuracy and interpretability. We also use visualization techniques to select appropriate convolutional kernel sizes, thereby increasing the network's interpretability.

4.
Cell Prolif ; : e13653, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867378

ABSTRACT

Understanding the cellular composition and trajectory of human tooth development is valuable for dentistry and stem cell engineering research. Previous single-cell studies have focused on mature human teeth and developing mouse teeth, but the cell landscape of human embryonic dental development is still unknown. In this study, tooth germ tissues were collected from aborted foetus (17-24 weeks) for single-cell RNA sequence and spatial transcriptome analysis. The cells were classified into seven subclusters of epithelium, and seven clusters of mesenchyme, as well as other cell types such as Schwann cell precursor and pericyte. For epithelium, the stratum intermedium branch and the ameloblast branch diverged from the same set of outer enamel-inner enamel-ALCAM+ epithelial cell lineage, but their spatial distribution of two branches was not clearly distinct. This trajectory received spatially adjacent regulation signals from mesenchyme and pericyte, including JAG1 and APP. The differentiation of pulp cell and pre-odontoblast showed four waves of temporally distinct gene expression, which involved regulation networks of LHX9, DLX5 and SP7, and these genes were regulated by upstream ligands such as the BMP family. This provides a reference landscape for the research on early human tooth development, covering different spatial structures and developmental periods.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 685-692, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926954

ABSTRACT

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.


Subject(s)
Leukemia, Myeloid, Acute , Mucormycosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Mucormycosis/diagnosis , Male , Female , Adult , Middle Aged , Prognosis , Retrospective Studies , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antifungal Agents/therapeutic use , Young Adult , Leukemia/complications , Leukemia/drug therapy
6.
Org Lett ; 26(25): 5274-5279, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38885640

ABSTRACT

Chiral α-aminophosphonates with adjacent carbon and phosphonate stereogenic centers have been employed as ligands in the copper-catalyzed oxidative coupling of 2-naphthols, resulting in the production of chiral BINOLs in favorable yields and moderate to good enantiomeric excess. This represents the first application of chiral P-based ligands to enable such a transformation. The synthesis of these chiral α-aminophosphonate ligands offers a significant advantage over approaches that typically necessitate elaborate synthetic processes for chiral ligand production.

7.
Sci Rep ; 14(1): 12922, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839921

ABSTRACT

The incidence of non-alcoholic fatty liver disease (NAFLD) tends to be younger. And the role of theobromine in fatty liver disease remains unclear. The purpose of this study was to investigate the relationship between dietary theobromine intake and degree of hepatic steatosis in individuals aged 45 and below, using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and liver ultrasonography transient elastography. A total of 1796 participants aged below 45 years were included from NHANES 2017-2020 data after applying exclusion criteria. Multivariate regression and subgroup analyses were conducted to examine the associations between theobromine intake and controlled attenuation parameter (CAP), adjusting for potential confounders. Generalized additive models and two-piecewise linear regression were used to analyze nonlinear relationships. In the unadjusted Model 1 and preliminarily adjusted Model 2, there was no significant correlation between theobromine intake and CAP values. However, in Models 3 and 4, which accounted for confounding factors, a higher intake of theobromine was significantly associated with lower CAP values. Subgroup analyses in the fully adjusted Model 4 revealed a significant negative correlation among individuals aged 18-45, women, and white populations. Nonlinear analysis revealed a U-shaped relationship in black Americans, with the lowest CAP values at 44.5 mg/day theobromine. This study provides evidence that higher theobromine intake is correlated with lower degree of hepatic steatosis in young people, especially those aged 18-45 years, women, and whites. For black Americans, maintaining theobromine intake around 44.5 mg/day may help minimize liver steatosis. These findings may help personalize clinical nutritional guidance, prevent the degree of hepatic steatosis, and provide pharmacological approaches to reverse fatty liver disease in young people.


Subject(s)
Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Theobromine , Humans , Theobromine/administration & dosage , Female , Male , Adult , Non-alcoholic Fatty Liver Disease/epidemiology , Adolescent , Young Adult , Middle Aged , Liver/diagnostic imaging , Liver/pathology , Elasticity Imaging Techniques , Fatty Liver/epidemiology , Fatty Liver/diagnostic imaging
8.
Phytomedicine ; 130: 155537, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38823344

ABSTRACT

BACKGROUND: Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects. OBJECTIVE: Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms. STUDY DESIGN: For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice. METHODS: In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation. RESULTS: In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability. CONCLUSION: In summary, our research reveals that PT increases STUB1 m6A modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.


Subject(s)
Autophagy , Methyltransferases , Mice, Inbred BALB C , Mice, Nude , Triple Negative Breast Neoplasms , Ubiquitin-Protein Ligases , Animals , Triple Negative Breast Neoplasms/drug therapy , Humans , Autophagy/drug effects , Female , Cell Line, Tumor , Methyltransferases/metabolism , Ubiquitin-Protein Ligases/metabolism , Mice, SCID , Mice, Inbred NOD , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Xenograft Model Antitumor Assays , Panax/chemistry , Adenosine/analogs & derivatives , Adenosine/pharmacology
9.
Front Endocrinol (Lausanne) ; 15: 1401648, 2024.
Article in English | MEDLINE | ID: mdl-38899007

ABSTRACT

Background: Metabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency. Method: The Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations. Result: The IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including "Basal metabolic rate" (OR= 1.24, P= 6.86×10-4); "Body fat percentage" (OR= 1.22, P= 8.20×10-3); "Hip circumference" (OR= 1.20, P= 5.92×10-4); "Trunk fat mass" (OR= 1.15, P= 1.03×10-2); "Trunk fat percentage" (OR= 1.25, P= 8.55×10-4); "Waist circumference" (OR= 1.23, P= 3.28×10-3); "Weight" (OR= 1.21, P= 9.82×10-4); "Whole body fat mass" (OR= 1.21, P= 4.90×10-4); "Whole body fat-free mass" (OR= 1.19, P= 4.11×10-3) and "Whole body water mass" (OR= 1.21, P= 1.85×10-3). Conclusion: Several metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/epidemiology , Risk Factors , Polymorphism, Single Nucleotide
10.
Adv Sci (Weinh) ; : e2401716, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840455

ABSTRACT

The demand for miniaturized and integrated multifunctional devices drives the progression of high-performance infrared photodetectors for diverse applications, including remote sensing, air defense, and communications, among others. Nonetheless, infrared photodetectors that rely solely on single low-dimensional materials often face challenges due to the limited absorption cross-section and suboptimal carrier mobility, which can impair sensitivity and prolong response times. Here, through experimental validation is demonstrated, precise control over energy band alignment in a type-II van der Waals heterojunction, comprising vertically stacked 2D Ta2NiSe5 and the topological insulator Bi2Se3, where the configuration enables polarization-sensitive, wide-spectral-range photodetection. Experimental evaluations at room temperature reveal that the device exhibits a self-powered responsivity of 0.48 A·W-1, a specific directivity of 3.8 × 1011 cm·Hz1/2·W-1, a response time of 151 µs, and a polarization ratio of 2.83. The stable and rapid photoresponse of the device underpins the utility in infrared-coded communication and dual-channel imaging, showing the substantial potential of the detector. These findings articulate a systematic approach to developing miniaturized, multifunctional room-temperature infrared detectors with superior performance metrics and enhanced capabilities for multi-information acquisition.

11.
Appl Opt ; 63(11): 2837-2842, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38856379

ABSTRACT

An X-ray monocapillary with an inner multilayer can be a promising optical device to obtain focused monochromatic X-rays. A focused beam is acquired via controlling the shape of the monocapillary meanwhile monochromatic X-rays are screened out by the inside multilayer. For hard X-rays such as C u-k α line 8.04 keV and M o-k α line 17.44 keV, A l 2 O 3/H f O 2 is an effective material pair for the X-ray multilayer that can reflect the X-rays at an acceptable efficiency. In this work, four tapered-monocapillaries with inner A l 2 O 3/H f O 2 multilayers are designed to focus and monochromatize X-rays (8.04 keV and17.44 keV, respectively) from the point source and collimated beam. The theoretical transmission performance, including the beam size, reflectivity, and monochromaticity of the device, is also calculated. The results show that the ideal optics can focus desired X-rays with efficiency of about 60%. It provides a reference for fabricating this optics in the future, especially via the atomic layer deposition (ALD) technique, which represents great potential to coat uniform film on a curved surface.

12.
J Colloid Interface Sci ; 674: 527-536, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38943913

ABSTRACT

Constructing unique heterostructures is a highly effective approach for enhancing the K+ storage capability of transition metal selenides. Such structures generate internal electric fields that significantly reduce the charge transfer activation energy. However, achieving a flawless interfacial region that maintains the optimal energy level gradient and degree of lattice matching remains a considerable challenge. In this study, we synthesised Setaria-like NiTe2/MoS2@C heterogeneous interfaces at which three-dimensional MoS2 nanosheets are evenly embedded in NiTe2 nanorods to form stabilised heterojunctions. The NiTe2/MoS2 heterojunctions display distinctive electronic configurations and several active sites owing to their low lattice misfits (δ = 13 %), strong electric fields, and uniform carbon shells. A NiTe2/MoS2@C anode in a potassium-ion battery (KIB) exhibited an impressive reversible capacity of 125.8 mAh/g after 1000 cycles at a rate of 500 mA g-1 and a stable reversible capacity of 111.7 mAh/g even after 3000 cycles at 1000 mA g-1. Even the NiTe2/MoS2@C//perylene tetracarboxylic dianhydride full battery configuration maintained a significant reversible capacity of 92.4 mAh/g after 100 cycles at 200 mA g-1, highlighting its considerable potential for application in KIBs. Calculations further revealed that the well-designed NiTe2/MoS2 heterojunction significantly promotes K+ ion diffusion.

13.
J Med Chem ; 67(11): 9536-9551, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38822802

ABSTRACT

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.


Subject(s)
Aminophenols , Ferroptosis , Lipid Peroxidation , Animals , Aminophenols/pharmacology , Aminophenols/chemistry , Ferroptosis/drug effects , Mice , Lipid Peroxidation/drug effects , Humans , Structure-Activity Relationship , Acetaminophen/pharmacology , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Male , Drug Discovery , Mice, Inbred C57BL
14.
Int Immunopharmacol ; 135: 112321, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38795599

ABSTRACT

Sepsis is a life-threatening multi-organ dysfunction syndrome caused by an abnormal host response to infection. Regulated cell death is essential for maintaining tissue homeostasis and eliminating damaged, infected, or aging cells in multicellular organisms. Gasdermin D, as a member of the gasdermin family, plays a crucial role in the formation of cytoplasmic membrane pores. Research has found that GSDMD plays important roles in various forms of regulated cell death such as pyroptosis, NETosis, and necroptosis. Therefore, through mediating regulated cell death, GSDMD regulates different stages of disease pathophysiology. This article mainly summarizes the concept of GSDMD, its role in regulated cell death, its involvement in organ damage associated with sepsis-related injuries mediated by regulated cell death via GSDMD activation and introduces potential drugs targeting GSDMD that may provide more effective treatment options for sepsis patients through drug modification.


Subject(s)
Intracellular Signaling Peptides and Proteins , Phosphate-Binding Proteins , Sepsis , Humans , Sepsis/drug therapy , Sepsis/immunology , Phosphate-Binding Proteins/metabolism , Animals , Intracellular Signaling Peptides and Proteins/metabolism , Regulated Cell Death/drug effects , Pyroptosis/drug effects , Gasdermins
15.
Int J Antimicrob Agents ; 64(2): 107220, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38810939

ABSTRACT

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

16.
J Pharm Biomed Anal ; 246: 116219, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38759325

ABSTRACT

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.


Subject(s)
Antipyretics , Drugs, Chinese Herbal , Fever , Metabolomics , Animals , Rabbits , Antipyretics/pharmacology , Drugs, Chinese Herbal/pharmacology , Metabolomics/methods , Fever/drug therapy , Male , Disease Models, Animal , Lipopolysaccharides/pharmacology , Chromatography, High Pressure Liquid/methods
17.
Int J Biol Macromol ; 271(Pt 2): 132708, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38815948

ABSTRACT

κ-Carrageenan (κ-Car) is an important material for preparing food gels and hydrogels. However, κ-Car gel has issues with high hardness and low water-holding capacity. Modification strategy of micronization is proposed for the first time to explore its influence on texture properties and gelling process of κ-Car gel, and to investigate the feasibility of κ-Car as a food matrix with low strength. κ-Car undergoing 60 min of micronization, the d(0.9) decreased by 79.33 %, SBET and Vtotal increased by 89.23 % and 95.27 %. The swelling rate and degree of gelling process increased significantly, and the microstructure changed from loose large pores to dense small pores resembling a "honeycomb". Importantly, the hardness of gel-60, Milk-60 and PNS-60 decreased by 72.52 %, 49.25 % and 81.37 %. In addition, WHC of gel-60, Milk-60 and PNS-60 was improved. IDDSI tests showed that κ-Car gels, milk gels and PNS gels can be categorized as level 6 (soft and bite-sized), except for PNS-60, which belongs to level 5 (crumbly and moist). Furthermore, the texture and bitter masking effect of milk gels and PNS gels were improved. In conclusion, this study demonstrated that micronization can be a novel approach to improve the gel properties of κ-Car, laying the groundwork for developing dysphagia foods.


Subject(s)
Carrageenan , Gels , Carrageenan/chemistry , Gels/chemistry , Deglutition , Milk/chemistry , Animals , Hardness , Administration, Oral , Hydrogels/chemistry
18.
Aging (Albany NY) ; 16(9): 8110-8141, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38728242

ABSTRACT

The management of patients with advanced non-small cell lung cancer (NSCLC) presents significant challenges due to cancer cells' intricate and heterogeneous nature. Programmed cell death (PCD) pathways are crucial in diverse biological processes. Nevertheless, the prognostic significance of cell death in NSCLC remains incompletely understood. Our study aims to investigate the prognostic importance of PCD genes and their ability to precisely stratify and evaluate the survival outcomes of patients with advanced NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression analyses for prognostic gene screening. Ultimately, we identified seven PCD-related genes to establish the PCD-related risk score for the advanced NSCLC model (PRAN), effectively stratifying overall survival (OS) in patients with advanced NSCLC. Multivariate Cox regression analysis revealed that the PRAN was the independent prognostic factor than clinical baseline factors. It was positively related to specific metabolic pathways, including hexosamine biosynthesis pathways, which play crucial roles in reprogramming cancer cell metabolism. Furthermore, drug prediction for different PRAN risk groups identified several sensitive drugs explicitly targeting the cell death pathway. Molecular docking analysis suggested the potential therapeutic efficacy of navitoclax in NSCLC, as it demonstrated strong binding with the amino acid residues of C-C motif chemokine ligand 14 (CCL14), carboxypeptidase A3 (CPA3), and C-X3-C motif chemokine receptor 1 (CX3CR1) proteins. The PRAN provides a robust personalized treatment and survival assessment tool in advanced NSCLC patients. Furthermore, identifying sensitive drugs for distinct PRAN risk groups holds promise for advancing targeted therapies in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/drug therapy , Prognosis , Apoptosis/genetics , Gene Expression Regulation, Neoplastic , Male , Female , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Molecular Docking Simulation , Gene Regulatory Networks , Middle Aged , Gene Expression Profiling
19.
World J Gastrointest Surg ; 16(4): 1149-1154, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38690048

ABSTRACT

BACKGROUND: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. AIM: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. METHODS: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant. RESULTS: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group (P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group (P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 (r = 0.823, P < 0.05). CONCLUSION: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

20.
PLoS One ; 19(5): e0295350, 2024.
Article in English | MEDLINE | ID: mdl-38748674

ABSTRACT

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.


Subject(s)
Talus , Humans , Male , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Female , Adult , Bone Screws , Ankle Fractures/surgery , Ankle Fractures/diagnostic imaging
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