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1.
J Nucl Med ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39362770

ABSTRACT

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis-associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

2.
IET Syst Biol ; 2024 Oct 06.
Article in English | MEDLINE | ID: mdl-39370684

ABSTRACT

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single-cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17-1.15]) and could distinguish between PTC and non-PTC tissues (AUC = 0.74 [0.70-0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

3.
Brief Bioinform ; 25(5)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39256199

ABSTRACT

Deoxyribonucleic acid (DNA) methylation plays a key role in gene regulation and is critical for development and human disease. Techniques such as whole-genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS) allow DNA methylation analysis at the genome scale, with Illumina NovaSeq 6000 and MGI Tech DNBSEQ-T7 being popular due to their efficiency and affordability. However, detailed comparative studies of their performance are not available. In this study, we constructed 60 WGBS and RRBS libraries for two platforms using different types of clinical samples and generated approximately 2.8 terabases of sequencing data. We systematically compared quality control metrics, genomic coverage, CpG methylation levels, intra- and interplatform correlations, and performance in detecting differentially methylated positions. Our results revealed that the DNBSEQ platform exhibited better raw read quality, although base quality recalibration indicated potential overestimation of base quality. The DNBSEQ platform also showed lower sequencing depth and less coverage uniformity in GC-rich regions than did the NovaSeq platform and tended to enrich methylated regions. Overall, both platforms demonstrated robust intra- and interplatform reproducibility for RRBS and WGBS, with NovaSeq performing better for WGBS, highlighting the importance of considering these factors when selecting a platform for bisulfite sequencing.


Subject(s)
CpG Islands , DNA Methylation , Sequence Analysis, DNA , Humans , Sequence Analysis, DNA/methods , Genome, Human , High-Throughput Nucleotide Sequencing/methods , Sulfites/chemistry , Base Pairing , Whole Genome Sequencing/methods , Reproducibility of Results
4.
BMC Med ; 22(1): 401, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300460

ABSTRACT

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.


Subject(s)
Antitubercular Agents , Clofazimine , Cycloserine , Diarylquinolines , Levofloxacin , Linezolid , Rifampin , Tuberculosis, Multidrug-Resistant , Humans , Male , Female , Adult , Clofazimine/therapeutic use , Clofazimine/administration & dosage , Tuberculosis, Multidrug-Resistant/drug therapy , Linezolid/therapeutic use , Linezolid/administration & dosage , Diarylquinolines/therapeutic use , Diarylquinolines/administration & dosage , Middle Aged , China/epidemiology , Cycloserine/therapeutic use , Cycloserine/administration & dosage , Levofloxacin/therapeutic use , Levofloxacin/administration & dosage , Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Rifampin/therapeutic use , Rifampin/administration & dosage , Prospective Studies , Drug Therapy, Combination , Treatment Outcome , Young Adult , Aged
5.
Adv Sci (Weinh) ; : e2400176, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162029

ABSTRACT

Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.

6.
J Comp Pathol ; 213: 59-72, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39116802

ABSTRACT

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.


Subject(s)
Bibliometrics , Chorioallantoic Membrane , Neoplasms , Animals , Chick Embryo , Biomedical Research , Disease Models, Animal
7.
BMC Med Imaging ; 24(1): 207, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123136

ABSTRACT

BACKGROUND: The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. METHODS: In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. RESULTS: Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. CONCLUSIONS: It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.


Subject(s)
Signal-To-Noise Ratio , Humans , Endoscopy/methods , Image Enhancement/methods , Algorithms , Nonlinear Dynamics , Image Processing, Computer-Assisted/methods
8.
Biomed Environ Sci ; 37(7): 785-789, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39198242

ABSTRACT

Lung cancer is the top cause of cancer deaths globally. Advances in immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but their use in lung cancer has led to more side effects. This study examined if past pulmonary tuberculosis (TB) affects ICIs' effectiveness and safety in lung cancer treatment. We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022. We compared outcomes and side effects between patients with and without prior TB. Of 116 patients (40 with TB history, 76 without), prior TB didn't reduce treatment effectiveness but did increase severe side effects. Notably, older patients (≥ 65 years) faced a higher risk of severe side effects. Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs, stressing the need for careful monitoring and personalized care.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Male , Female , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Middle Aged , Incidence , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology , Aged, 80 and over , Retrospective Studies
9.
J Phys Chem Lett ; 15(34): 8804-8812, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39167049

ABSTRACT

The excited-state property determines the occurrence of photofunctions in organic materials. We have developed a fragment frontier molecular orbital model for the donor-acceptor-type (D-A-type) systems and constructed molecular descriptors of the excited-state property with charge transfer (CT) or local excitation (LE) based on the orbital information on constituent D and A fragments. Applying these descriptors, we rapidly screened 1CT or 1LE and 3CT or 3LE molecules from 2500 molecules generated by the binding of 50 donors and 50 acceptors, and the results of 26 molecules were confirmed by available experiments and first-principles calculations. Moreover, the modulation of these descriptors by chemical groups allows the rational design of target excited states. This work is significant for high-throughput screening of excellent organic photofunctional materials from a giant chemical database.

11.
Int J Biol Macromol ; 276(Pt 1): 133777, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38996880

ABSTRACT

In this study, three types of dodecyl chitosan quaternary ammonium salts, each with different spacer groups were synthesized. These chitosan derivatives are N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-amino-acetyl chitosan (DMDAC), N'-dodecyl-N-isonicotinyl chitosan chloride (DINCC) and N',N'-dimethyl-N'-dodecyl-ammonium chloride-N-benzoyl chitosan (DMDBC). The synthesized products were characterized using Fourier transform infrared spectrometers, nuclear magnetic resonance, thermogravimetric analysis, and elemental analysis. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated. The experimental results indicated that the introduction of hydrophobic groups of spacer groups could enhance the antibacterial and antibiofilm activities of the chitosan derivatives. The antibacterial rates of the chitosan derivatives were over 90 % for both E. coli and S. aureus at a concentration of 0.5 mg/mL. The chitosan derivatives removed >50 % of the mature biofilm of E. coli and over 90 % of the mature biofilm of S. aureus at a concentration of 2.5 mg/mL. Further, the synthesized chitosan derivatives were determined to be non-toxic to L929 cells. Among them, DMDBC exhibited the most promising overall performance and show potential for wide-ranging applications in food preservation, disinfectants, medical, and other fields.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chitosan , Escherichia coli , Microbial Sensitivity Tests , Quaternary Ammonium Compounds , Staphylococcus aureus , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Quaternary Ammonium Compounds/chemical synthesis , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Spectroscopy, Fourier Transform Infrared , Mice
12.
EMBO Mol Med ; 16(8): 1755-1790, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39030302

ABSTRACT

Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target.


Subject(s)
HLA-G Antigens , Killer Cells, Natural , Leukocyte Immunoglobulin-like Receptor B1 , Mycobacterium tuberculosis , Tuberculosis , Leukocyte Immunoglobulin-like Receptor B1/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , HLA-G Antigens/metabolism , HLA-G Antigens/genetics , HLA-G Antigens/immunology , Humans , Animals , Tuberculosis/immunology , Tuberculosis/microbiology , Mice , Mycobacterium tuberculosis/immunology , Macrophages/immunology , Macrophages/metabolism , Receptors, Immunologic/metabolism , Receptors, Immunologic/genetics , Antigens, CD
13.
Colloids Surf B Biointerfaces ; 242: 114084, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39018911

ABSTRACT

Chitosan exhibits good biocompatibility and some antibacterial activity, making it a popular choice in biomedicine, personal care products, and food packaging. Despite its advantages, the limited antibacterial effectiveness of chitosan hinders its widespread use. Introducing a six-membered heterocyclic structure through chemical modification can significantly enhance its antimicrobial properties and broaden its potential applications. In order to explore the effect of six-membered heterocyclic structure on the antibacterial and antibiofilm activities of chitosan. In this study, seven chitosan derivatives containing six-membered heterocyclics were prepared. They were characterized using Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Cell viability assay showed that they were non-toxic. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated. Our research findings demonstrate that increasing the hydrophobicity, alkalinity and charge density of the substitute groups improved the antibacterial and antibiofilm activities of chitosan. This study also offers valuable insights into the quantitative structure-activity relationships of chitosan derivatives in terms of antibacterial and antibiofilm activities.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chitosan , Escherichia coli , Microbial Sensitivity Tests , Staphylococcus aureus , Chitosan/chemistry , Chitosan/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Escherichia coli/drug effects , Biofilms/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Cell Survival/drug effects , Humans , Spectroscopy, Fourier Transform Infrared
14.
Nature ; 631(8020): 409-414, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961288

ABSTRACT

Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.


Subject(s)
Antitubercular Agents , Diarylquinolines , Imidazoles , Mitochondrial Proton-Translocating ATPases , Mycobacterium tuberculosis , Piperidines , Pyridines , Humans , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Binding Sites , Cryoelectron Microscopy , Diarylquinolines/chemistry , Diarylquinolines/pharmacology , Imidazoles/chemistry , Imidazoles/pharmacology , Mitochondrial Proton-Translocating ATPases/antagonists & inhibitors , Mitochondrial Proton-Translocating ATPases/chemistry , Mitochondrial Proton-Translocating ATPases/metabolism , Mitochondrial Proton-Translocating ATPases/ultrastructure , Models, Molecular , Mycobacterium tuberculosis/enzymology , Mycobacterium tuberculosis/drug effects , Piperidines/chemistry , Piperidines/pharmacology , Protein Subunits/metabolism , Protein Subunits/chemistry , Protein Subunits/antagonists & inhibitors , Pyridines/chemistry , Pyridines/pharmacology
15.
New Phytol ; 243(4): 1329-1346, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38898642

ABSTRACT

Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.


Subject(s)
Cycadopsida , Droughts , Plant Leaves , Water , Xylem , Xylem/physiology , Xylem/anatomy & histology , Plant Leaves/anatomy & histology , Plant Leaves/physiology , Cycadopsida/physiology , Cycadopsida/anatomy & histology , Species Specificity
16.
Carbohydr Res ; 542: 109194, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38897018

ABSTRACT

N-(sodium 2-hydroxypropylsulfonate) chitosan (HSCS), N-sulfonate chitosan (SCS) and N-isonicotinic sulfonate chitosan (ISCS) were prepared. The structures of the prepared chitosan derivatives were characterized by nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and elemental analysis (EA). Antibacterial and antibiofilm activities of these chitosan derivatives were evaluated in vitro. The minimum inhibitory concentration (MIC) of HSCS and SCS against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were 0.625 mg/mL and 0.156 mg/mL, respectively. ISCS exhibited MIC values of 0.313 mg/mL and 0.078 mg/mL against E. coli and S. aureus, respectively. ISCS demonstrated superior antibacterial and antibiofilm properties compared to SCS and HSCS. These findings suggest that the incorporation of a pyridine structure into sulfonate chitosan enhances its antibacterial and antibiofilm activities, and the prepared ISCS has a promising application prospect for controlling the reproduction of microorganisms in the field of food packaging.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chitosan , Escherichia coli , Microbial Sensitivity Tests , Staphylococcus aureus , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/chemical synthesis , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Escherichia coli/drug effects , Sulfonic Acids/chemistry , Sulfonic Acids/pharmacology , Sulfonic Acids/antagonists & inhibitors
17.
Sci Rep ; 14(1): 13742, 2024 06 14.
Article in English | MEDLINE | ID: mdl-38877107

ABSTRACT

In the process of human aging, significant age-related changes occur in brain tissue. To assist individuals in assessing the degree of brain aging, screening for disease risks, and further diagnosing age-related diseases, it is crucial to develop an accurate method for predicting brain age. This paper proposes a multi-scale feature fusion method called Tri-UNet based on the U-Net network structure, as well as a brain region information fusion method based on multi-channel input networks. These methods address the issue of insufficient image feature learning in brain neuroimaging data. They can effectively utilize features at different scales of MRI and fully leverage feature information from different regions of the brain. In the end, experiments were conducted on the Cam-CAN dataset, resulting in a minimum Mean Absolute Error (MAE) of 7.46. The results demonstrate that this method provides a new approach to feature learning at different scales in brain age prediction tasks, contributing to the advancement of the field and holding significance for practical applications in the context of elderly education.


Subject(s)
Aging , Brain , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Aging/physiology , Aged , Middle Aged , Adult , Male , Female , Neuroimaging/methods , Aged, 80 and over , Image Processing, Computer-Assisted/methods , Young Adult , Algorithms
18.
Front Pharmacol ; 15: 1362544, 2024.
Article in English | MEDLINE | ID: mdl-38873419

ABSTRACT

The most frequent adverse event associated with bedaquiline (BDQ) is the QTc interval prolongation; however, there was no biomarkers that could be used to predict the occurrence of QTc prolongation in BDQ-treated patients. In this study, we employed the ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to generate metabolic profiling for the discovery of potential predictive urine biomarkers of QTc prolongation in these patients. Untargeted metabolomic technique was used to concentrate the differential metabolic pathway, and targeted metabolomic technique was subsequently performed to identify predictive biomarkers for QTc prolongation. A total of 45 rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) patients were enrolled in our study, including 15 RR/MDR-TB patients with QTc interval prolongation (QIP) and 30 RR/MDR-TB patients with QTc interval un-prolongations (QIU). Untargeted technique revealed that the lipid metabolism was the most differential metabolic pathway between two groups. Further targeted technique identified four differential metabolites, including betaine, LPE (18:2), LPE (20:3), and LPE (20:4). The combined analysis of metabolisms revealed that the combined use of LPE (20:3) and LPE (20:4) had the best performance for predicting the occurrence of QTc prolongation in TB patients, yielding a sensitivity of 87.4% and a specificity of 78.5%. In addition, with the progression of BDQ treatment, the LPEs exhibited persistent difference in the BDQ-treated TB patients experiencing QTc interval prolongation. In conclusion, our data demonstrate that the combined use of LPE (20:3) and LPE (20:4) yields promising performance for predicting the occurrence of QTc interval prolongation in BDQ-treated patients.

19.
Antimicrob Resist Infect Control ; 13(1): 59, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853242

ABSTRACT

BACKGROUND: A long-term follow-up of close contacts to monitor their infection status is essential to formulate a promising screening strategy. The study aimed to assess the dynamics of tuberculosis (TB) infection using Interferon-γ release assay (IGRA) and determine risk factors associated with TB infection. METHODS: Definite TB patients were interviewed and their household contacts were screened for TB infection by IGRA during 12-month longitudinal investigation. RESULTS: We included in our analyses 184 household contacts of 92 index TB patients. 87 individuals (47.3%) in contact group progressed to TB infection, of whom 86 developed into IGRA positive within 24 weeks. Close contacts with a higher age and comorbidities are easier to exhibit TB infection. Analysis showed that risk factors for becoming IGRA-positive individuals included residence, older age, comorbidities, BCG scar and high bacterial load. Contacts with BCG scar had a lower IGRA-positive rate. CONCLUSION: IGRA conversion generally occurs within 24 weeks after exposure. The TB transmission happens since subclinical TB stage and the presence of BCG scar is an independent protective factor reducing risk of TB infection among close contacts. Repeated IGRA tests are sensible to conducted among close contacts at 24 weeks after exposure to identify the IGRA-positive individuals.


Subject(s)
Contact Tracing , Interferon-gamma Release Tests , Tuberculosis , Humans , Male , Female , Adult , Prospective Studies , Middle Aged , Risk Factors , Tuberculosis/epidemiology , Tuberculosis/transmission , Young Adult , Aged , Adolescent , Mycobacterium tuberculosis , Longitudinal Studies , Family Characteristics
20.
Food Chem ; 455: 139908, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38850971

ABSTRACT

Chitosan quaternary phosphine salts (NPCS) were synthesized with enhanced antimicrobial properties using a two-step method. Composite films (CNSP) were prepared by incorporating NPCS and polyvinyl alcohol (PVA) as the base material, citric acid as the crosslinker and functional additive, exhibiting antibacterial and UV-blocking properties. The composite film showed a maximum tensile strength of 20.4 MPa, an elongation at break of 677%, and a UV light barrier transmittance of 70%. Application of these composite membranes in preserving strawberries demonstrated effectiveness in maintaining freshness by preventing water loss, inhibiting microbial growth, and extending shelf life. In addition, the composite film demonstrated biosafety. These results indicate that CNSP composite films holds significant promise for safe and sustainable food packaging applications.


Subject(s)
Chitosan , Citric Acid , Food Packaging , Food Preservation , Fragaria , Polyvinyl Alcohol , Polyvinyl Alcohol/chemistry , Fragaria/chemistry , Chitosan/chemistry , Chitosan/pharmacology , Citric Acid/chemistry , Citric Acid/pharmacology , Food Packaging/instrumentation , Food Preservation/methods , Food Preservation/instrumentation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cross-Linking Reagents/chemistry , Tensile Strength
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