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1.
Nano Lett ; 24(19): 5714-5721, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38695488

ABSTRACT

The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).

2.
J Transl Med ; 22(1): 460, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750462

ABSTRACT

BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.


Subject(s)
Adenocarcinoma of Lung , Cell Proliferation , Chaperonin Containing TCP-1 , Disease Progression , Glycolysis , Hexokinase , Lung Neoplasms , STAT1 Transcription Factor , Humans , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/genetics , Hexokinase/metabolism , STAT1 Transcription Factor/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Chaperonin Containing TCP-1/metabolism , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, Neoplastic , Apoptosis , Signal Transduction , Neoplasm Invasiveness
3.
Article in English | MEDLINE | ID: mdl-38808715

ABSTRACT

BACKGROUND: Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions. AIMS: This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection. METHODS: Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval. CONCLUSION: We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.

4.
Cell Mol Biol Lett ; 29(1): 79, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783169

ABSTRACT

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.


Subject(s)
Brain-Derived Neurotrophic Factor , CA1 Region, Hippocampal , Down-Regulation , Neuronal Plasticity , Neurons , Postoperative Cognitive Complications , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Mice , Neurons/metabolism , Postoperative Cognitive Complications/metabolism , Postoperative Cognitive Complications/etiology , CA1 Region, Hippocampal/metabolism , Male , Mice, Inbred C57BL , Long-Term Potentiation , Glutamic Acid/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology
5.
Nature ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811729

ABSTRACT

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.

6.
IEEE Trans Med Imaging ; PP2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652607

ABSTRACT

Proximal femoral fracture segmentation in computed tomography (CT) is essential in the preoperative planning of orthopedic surgeons. Recently, numerous deep learning-based approaches have been proposed for segmenting various structures within CT scans. Nevertheless, distinguishing various attributes between fracture fragments and soft tissue regions in CT scans frequently poses challenges, which have received comparatively limited research attention. Besides, the cornerstone of contemporary deep learning methodologies is the availability of annotated data, while detailed CT annotations remain scarce. To address the challenge, we propose a novel weakly-supervised framework, namely Rough Turbo Net (RT-Net), for the segmentation of proximal femoral fractures. We emphasize the utilization of human resources to produce rough annotations on a substantial scale, as opposed to relying on limited fine-grained annotations that demand a substantial time to create. In RT-Net, rough annotations pose fractured-region constraints, which have demonstrated significant efficacy in enhancing the accuracy of the network. Conversely, the fine annotations can provide more details for recognizing edges and soft tissues. Besides, we design a spatial adaptive attention module (SAAM) that adapts to the spatial distribution of the fracture regions and align feature in each decoder. Moreover, we propose a fine-edge loss which is applied through an edge discrimination network to penalize the absence or imprecision edge features. Extensive quantitative and qualitative experiments demonstrate the superiority of RT-Net to state-of-the-art approaches. Furthermore, additional experiments show that RT-Net has the capability to produce pseudo labels for raw CT images that can further improve fracture segmentation performance and has the potential to improve segmentation performance on public datasets. The code is available at: https://github.com/zyairelu/RT-Net.

7.
Anim Biotechnol ; 35(1): 2334725, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38623994

ABSTRACT

The lactation character of dairy goats is the most important characteristic, and milk protein is an important index to evaluate milk quality. Casein accounts for more than 80% of the total milk protein in goat milk and is the main component of milk protein. Using GMECs (goat mammary epithelial cells) as the research object, the CHECK2 vector of the CSN1S1 gene and the overexpression vector of pcDNA 3.1 were constructed, and the mimics of miR-2284b and the interfering RNA of CSN1S1 were synthesized. Using PCR, RT-qPCR, a dual luciferase activity detection system, EdU, CCK8, cell apoptosis detection and ELISA detection, we explored the regulatory mechanism and molecular mechanism of miR-2284b regulation of αs1-casein synthesis in GMECs. miR-2284b negatively regulates proliferation and apoptosis of GMECs and αs1-casein synthesis. Two new gene sequences of CSN1S1 were discovered. CSN1S1-1/-2 promoted the proliferation of GMECs and inhibited cell apoptosis. However, it had no effect on αs1-casein synthesis. MiR-2284b negatively regulates αs1-casein synthesis in GMECs by inhibiting the CSN1S1 gene. These results all indicated that miR-2284b could regulate αs1-casein synthesis, thus playing a theoretical guiding role in the future breeding process of dairy goats and accelerating the development of dairy goat breeding.


Subject(s)
Caseins , MicroRNAs , Female , Animals , Caseins/genetics , Caseins/metabolism , Milk Proteins , Goats/physiology , Epithelial Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Mammary Glands, Animal/metabolism
8.
Org Lett ; 26(12): 2478-2482, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38501865

ABSTRACT

A novel method for the glycosylation of selenoglycosides activated by iodosylbenzene was developed. The glycosylation reaction conditions were mild, fast, and efficient, with a high tolerance to diverse protecting groups and a wide substrate scope, which is advantageous for synthesizing complex glycosides. In addition, selenoglycosides were shown to be orthogonal to thioglycosides under the promotion of iodosylbenzene. Notably, a high yield of the poorly reactive glucuronidation reaction product was obtained by acetyl-protected selenoglycoside. Finally, the orthogonal one-pot synthesis of ß-(1→6) oligoglucans demonstrated the usefulness of this method in oligosaccharide synthesis.


Subject(s)
Iodobenzenes , Thioglycosides , Glycosylation , Glycosides , Oligosaccharides
9.
Cancer Res ; 84(10): 1680-1698, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38501978

ABSTRACT

Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune-stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2″ PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when cross-linked with PD-L1-positive cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/regulatory T cells in the tumor microenvironment (TME), rendering an immunologically "cold" tumor "hot." Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well tolerated and did not induce hepatotoxicity in non-human primates. According to computational semimechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1-rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 cross-linking-dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors. SIGNIFICANCE: The tetravalent PD-L1×4-1BB bispecific antibody ATG-101 activates 4-1BB+ T cells in a PD-L1 cross-linking-dependent manner, minimizing the hepatotoxicity of existing 4-1BB agonists and suppressing growth of ICI-resistant tumors. See related commentary by Ha et al., p. 1546.


Subject(s)
Antibodies, Bispecific , B7-H1 Antigen , Animals , Antibodies, Bispecific/pharmacology , Antibodies, Bispecific/immunology , Humans , Mice , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9/antagonists & inhibitors , Female , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Xenograft Model Antitumor Assays , Cell Line, Tumor , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/pathology , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects
10.
Front Genet ; 15: 1326828, 2024.
Article in English | MEDLINE | ID: mdl-38544805

ABSTRACT

Xiangdong black goats, indigenous to Hunan Province, China, exhibit remarkable adaptation to challenging environments and possess distinct black coat coloration alongside exceptional meat quality attributes. Despite their significance, comprehensive genomic investigations of this breed have been notably lacking. This study involved a comprehensive examination of population structure, genomic diversity, and regions of selection in Xiangdong black goats utilizing whole-genome sequencing data from 20 samples of this breed and 139 published samples from six other Chinese goat breeds. Our genomic analysis revealed a total of 19,133,125 biallelic single nucleotide polymorphisms (SNPs) within the Xiangdong black goat genome, primarily located in intergenic and intronic regions. Population structure analysis indicated that, compared with Jintang, Guizhou and Chengdu goats, Xiangdong black goats exhibit a reduced level of genetic differentiation but exhibit relatively greater divergence from Jining goats. An examination of genetic diversity within Xiangdong black goats revealed a moderate level of diversity, minimal inbreeding, and a substantial effective population size, which are more reflective of random mating patterns than other Chinese goat breeds. Additionally, we applied four distinct selective sweep methods, namely, the composite likelihood ratio (CLR), fixation index (F ST), θ π ratio and cross-population extended haplotype homozygosity (XP-EHH), to identify genomic regions under positive selection and genes associated with fundamental biological processes. The most prominent candidate genes identified in this study are involved in crucial aspects of goat life, including reproduction (CCSER1, PDGFRB, IFT88, LRP1B, STAG1, and SDCCAG8), immunity (DOCK8, IL1R1, and IL7), lactation and milk production (SPP1, TLL1, and ERBB4), hair growth (CHRM2, SDC1, ITCH, and FGF12), and thermoregulation (PDE10A). In summary, our research contributes valuable insights into the genomic characteristics of the Xiangdong black goat, underscoring its importance and utility in future breeding programs and conservation initiatives within the field of animal breeding and genetics.

11.
Environ Res ; 251(Pt 2): 118725, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38518915

ABSTRACT

To achieve rapid enrichment of the targeted hydrogen-producing bacterial population and reconstruction of the microbial community in the biological hydrogen-producing reactor, the activated sludge underwent multiple pretreatments using micro-aeration, alkaline treatment, and heat treatment. The activated sludge obtained from the multiple pretreatments was inoculated into the continuous stirred tank reactor (CSTR) for continuous operations. The community structure alteration and hydrogen-producing capability of the activated sludge were analyzed throughout the operation of the reactor. We found that the primary phyla in the activated sludge population shifted to Proteobacteria, Firmicutes, and Bacteroidetes, which collectively accounted for 96.69% after undergoing several pretreatments. This suggests that the multiple pretreatments facilitated in achieving the selective enrichment of the fermentation hydrogen-producing microorganisms in the activated sludge. The CSTR start-up and continuous operation of the biological hydrogen production reactor resulted in the reactor entering a highly efficient hydrogen production stage at influent COD concentrations of 4000 mg/L and 5000 mg/L, with the highest hydrogen production rate reaching 8.19 L/d and 9.33 L/d, respectively. The main genus present during the efficient hydrogen production stage in the reactor was Ethanoligenens, accounting for up to 33% of the total population. Ethanoligenens exhibited autoaggregation capabilities and a superior capacity for hydrogen production, leading to its prevalence in the reactor and contribution to efficient hydrogen production. During high-efficiency hydrogen production, flora associated with hydrogen production exhibited up to 46.95% total relative abundance. In addition, redundancy analysis (RDA) indicated that effluent pH and COD influenced the distribution of the primary hydrogen-producing bacteria, including Ethanoligenens, Raoultella, and Pectinatus, as well as other low abundant hydrogen-producing bacteria in the activated sludge. The data indicates that the multiple pretreatments and reactor's operation has successfully enriched the hydrogen-producing genera and changed the community structure of microbial hydrogen production.


Subject(s)
Bioreactors , Hydrogen , Sewage , Hydrogen/metabolism , Bioreactors/microbiology , Sewage/microbiology , Bacteria/metabolism , Bacteria/genetics , Waste Disposal, Fluid/methods , Fermentation , Microbiota
12.
Science ; 383(6682): eadh4859, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38301022

ABSTRACT

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.


Subject(s)
DNA Cleavage , Endonucleases , RNA, Catalytic , Animals , Cryoelectron Microscopy , Endonucleases/chemistry , Endonucleases/genetics , Hydrolysis , Introns , Nucleic Acid Conformation , RNA Splicing , RNA, Catalytic/chemistry , RNA, Catalytic/genetics
13.
Chemistry ; 30(24): e202304287, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38380560

ABSTRACT

Aqueous zinc ion batteries have been extensively researched due to their distinctive advantages such as low cost and high safety. Vanadium oxides are important cathode materials, however, poor cycle life caused by vanadium dissolution limits their application. Recent studies show that the lattice NH4 + in vanadium oxides can act as a pillar to enhance structural stability and play a crucial role in improving its cycling stability. Nevertheless, there is still a lack of research on the effect of the lattice NH4 + content on structural evolution and electrochemical performance. Herein, we synthesize vanadium oxides with different contents of lattice NH4 + by a one-step hydrothermal reaction. The vanadium oxides with lattice NH4 + exhibit high initial capacity, as well as good cycling stability and rate performance compared to bare vanadium oxide. Combined with electrochemical analyses, ex-situ structural characterizations, and in-situ X-ray diffraction tests, we reveal that the lattice NH4 + content plays a positive role in vanadium oxides' structural stability and cation diffusion kinetics. This work presents a direction for designing high-performance vanadium cathodes for aqueous zinc ion batteries.

14.
Clin Lung Cancer ; 25(2): 100-108, 2024 03.
Article in English | MEDLINE | ID: mdl-38172024

ABSTRACT

The discovery of epidermal growth factor receptor (EGFR) mutations has greatly changed the clinical outlook for patients with advanced non-small-cell lung cancer (NSCLC). Unlike the most common EGFR mutations, such as exon 19 deletion (del19) and exon 21 L858R point mutation, EGFR exon 20 insertion mutation (EGFR ex20ins) is a rare mutation of EGFR. Due to its structural specificity, it exhibits primary resistance to traditional epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), leading to poor overall survival prognosis for patients. In recent years, there has been continuous progress in the development of new drugs targeting EGFR ex20ins, bringing new hope for the treatment of this patient population. In this regard, we conducted a systematic review of the molecular characteristics, diagnostic advances, and treatment status of EGFR ex20ins. We summarized the latest data on relevant drug development and clinical research, aiming to provide reference for clinical diagnosis, treatment, and drug development.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutagenesis, Insertional , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , ErbB Receptors , Mutation/genetics , Exons/genetics
15.
Adv Healthc Mater ; 13(5): e2303042, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37786308

ABSTRACT

The healing of chronic diabetic wounds is a common and significant challenge in the medical field. Despite extensive efforts, the development of hydrogel dressings with satisfactory functionality remains an ongoing concern. In this study, a multifunctional hydrogel wound dressing (PAN/Ag-PLG) with adhesion, antibacterial, hemostatic, and other properties, which can effectively repair diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA), is presented. The hydrogel dressing is composed of gallic acid (GA)-functionalized polylysine (PL)-reduced silver nanoparticles (Ag-PLG), oxidized hyaluronic acid (OHA), and cross-linked polyacrylic acid grafted with N-hydrosuccinimide ester. Notably, compared to most conventional wound dressing that lack adhesion or are difficult to remove, the prepared hydrogels exhibit excellent adhesion and mild stimulation-triggered detachment. In vitro and in vivo experiments reveal that the PAN/Ag-PLG hydrogel exhibits outstanding biocompatibility and antibacterial properties and promotes diabetic wound repair by reducing oxidative damage and promoting cell migration and angiogenesis. The smart PAN/Ag-PLG hydrogel reported in this study provides an approach for the potential clinical development of painless antibacterial dressings.


Subject(s)
Anti-Infective Agents , Diabetes Mellitus , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Hydrogels/pharmacology , Silver/pharmacology , Silver/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
16.
Angew Chem Int Ed Engl ; 63(2): e202313985, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38014418

ABSTRACT

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an eight-carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method for the stereoselective synthesis of α-Kdo glycosides with a C3-p-tolylthio-substituted Kdo phosphite donor. The presence of the p-tolylthio group enhanced the reactivity, suppressed the formation of elimination by-products (2,3-enes), and provided complete α-stereocontrol. A variety of Kdo α-glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p-tolylthio group can be efficiently removed by free-radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one-pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5-branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8-branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.


Subject(s)
Glycosides , Phosphites , Oligosaccharides , Sugar Acids , Lipopolysaccharides , Trisaccharides
17.
Molecules ; 28(21)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37959866

ABSTRACT

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.


Subject(s)
Camellia sinensis , Tea , Tea/metabolism , Caffeine/analysis , Taste , Taste Perception , Metabolomics/methods , Camellia sinensis/metabolism
18.
Molecules ; 28(22)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38005200

ABSTRACT

Nanofluid-enhanced oil recovery (EOR) technology is an innovative approach to enhancing oil production in oilfields. It entails the dispersion of nanoparticles within a fluid, strategically utilizing the distinctive properties of these nanoparticles (NPs) to engage with reservoir rocks or crude oil, resulting in a significant enhancement of the oil recovery rate. Despite the notable advantages of nanofluid EOR technology over conventional oil recovery methods such as binary and ternary flooding, practical implementations continue to grapple with a range of pressing challenges. These challenges encompass concerns regarding the economic viability, stability, and adaptability of nanomaterials, which pose significant barriers to the widespread adoption of nanofluid EOR technology in the oil field. To tackle these challenges, addressing the current issues may involve selecting simpler and more readily available materials coupled with straightforward material modification techniques. This approach aims to more effectively meet the requirements of large-scale on-site applications. Within this framework, this review systematically explores commonly employed nanofluids in recent years, including inorganic nanofluids, organic nanofluids, and composite nanofluids. It categorizes the research advancements in optimizing modification techniques and provides a comprehensive overview of the mechanisms that underpin nanofluid EOR technology and its practical applications in oilfields. This comprehensive review aims to offer valuable references and serve as a solid foundation for subsequent research endeavors.

19.
Animals (Basel) ; 13(19)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37835710

ABSTRACT

Cadmium (Cd) is an environmental pollutant, widely existing in soil, and can be absorbed and accumulated by plants. Hunan Province exhibits the worst cadmium contamination of farmland in China. Ruminants possess an abundant microbial population in the rumen, which enables them to tolerate various poisonous plants. To investigate whether the rumen microbiota could respond to Cd and mitigate the toxicity of Cd-accumulated maize to ruminants, 6-month-old cattle were fed with 85.82% (fresh basis) normal whole-plant maize silage diet (CON, n = 10) or Cd-accumulated whole-plant maize silage diet (CAM, n = 10) for 107 days. When compared to the CON cattle, CAM cattle showed significantly higher gain-to-feed ratio and an increased total bacterial population in the rumen, but a decreased total bacterial population in the colon. CAM cattle had higher relative abundance of Prevotella and Lachnospiraceae ND3007 group in the rumen, and Lachnospiraceae NK4A136 group and Clostridia vadinBB60 group in the colon. Notably, microbial correlations were enhanced in all segments of CAM cattle, especially Peptostreptococcaceae in the jejunum. Transcriptome analysis revealed down-regulation of several immune-related genes in the rumen of CAM cattle, and differentially expressed genes in the rumen were mostly involved in immune regulation. These findings indicated that feeding Cd-accumulated maize diet with a Cd concentration of 6.74 mg/kg dry matter (DM) could stimulate SCFA-related bacteria in the rumen, induce hormesis to promote weight gain, and improve energy utilization of cattle.

20.
Anim Nutr ; 15: 1-9, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37701042

ABSTRACT

Eco-friendly and efficient strategies for eliminating cadmium (Cd) phytoremediation plant residues are needed. The present study investigated the feasibility of feeding Cd accumulator maize to beef cattle. In total, 20 cattle at 6 months of age were selected and randomly allocated into two groups fed with 85.82% (fresh basis) Cd accumulator maize (CAM) or normal maize (control [Con]) silage diets for 107 d. Feeding CAM did not affect the body weight (P = 0.24), while it decreased feed intake and increased feed efficiency of beef cattle (P < 0.01). Feeding CAM increased serum concentrations of immunoglobulin A and G, complement 3 and 4, blood urea nitrogen, and low-density lipoprotein cholesterol, decreased serum concentrations of interleukin-6 and lipopolysaccharide (P < 0.05), and caused wider lumens in the renal tubules. The Cd residue in meat was 7 µg/kg beyond the restriction for human food. In the muscle, the unsaturated fatty acids (t11C18:1 and C20:4), Lys, Arg, Pro, and Cys were decreased, while the saturated fatty acids (C10:0, C12:0, and C17:0) and Leu were increased (P < 0.05). Therefore, at the current feeding level, phytoremediation maize increased the feed efficiency of beef cattle, but did present risks to cattle health and production safety, and decreased the meat nutrition and flavor. Further research must be performed to determine whether a lower proper dose of phytoremediation maize and an appropriate feeding period may be possible to ensure no risk to cattle health and the supply of safe meat for humans.

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