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1.
JCI Insight ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954480

ABSTRACT

Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 RA patients and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFITM3 overexpressing Interferon-activated (IFN-activated) monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate to high disease activity (DAS28-CRP ≥ 3.2), and a decrease in non-classical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of pro-inflammatory genes in the gamma-delta T cells subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and non-classical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of pro-inflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.

2.
J Neurochem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946496

ABSTRACT

Alzheimer's disease (AD) is characterized by the accumulation of abnormally folded amyloid ß-protein (Aß) in the brain parenchyma and phosphorylated tau in neurons. Presenilin (PS, PSEN) 1 and PS2 are essential components of γ-secretase, which is responsible for the cleavage of amyloid precursor protein (APP) to generate Aß. PSEN mutations are associated with tau aggregation in frontotemporal dementia, regardless of the presence or absence of Aß pathology. However, the mechanism by which PS regulates tau aggregation is still unknown. Here, we found that tau phosphorylation and secretion were significantly increased in PS double-knock-out (PS1/2-/-) fibroblasts compared with wild-type fibroblasts. Tau-positive vesicles in the cytoplasm were significantly increased in PS1/2-/- fibroblasts. Active GSK-3ß was increased in PS1/2-/- fibroblasts, and inhibiting GSK3ß activity in PS1/2-/- fibroblasts resulted in decreased tau phosphorylation and secretion. Transfection of WT human PS1 and PS2 reduced the secretion of phosphorylated tau and active GSK-3ß in PS1/2-/- fibroblasts. However, PS1D257A without γ-secretase activity did not decrease the secretion of phosphorylated tau. Furthermore, nicastrin deficiency also increased tau phosphorylation and secretion. These results suggest that deficient PS complex maturation may increase tau phosphorylation and secretion. Thus, our studies discover a new pathway by which PS regulates tau phosphorylation/secretion and pathology independent of Aß and suggest that PS serves as a potential therapeutic target for treating neurodegenerative diseases involving tau aggregation.

3.
Heliyon ; 10(11): e32502, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961967

ABSTRACT

Objective: This study aimed to investigate the incidence, treatment status, and impact position of impacted third molars (ITM) and their effects on patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A retrospective analysis was conducted on the medical records of 454 patients who underwent HSCT, out of which 188 patients had ITM. The presence of ITM and its association with transplant-related infections and complications were recorded and analyzed. Results: Patients with ITM were significantly younger. The number of mandibular ITM was notably higher than maxillary ones, and the risk of pericoronitis in mandibular ITM was significantly higher than in maxillary ones. Out of 311 ITM in 188 patients, 25 were extracted before transplantation. The proportion of extraction and treatment for ITM with pericoronitis or caries was significantly higher than that for ITM without such problems. Moreover, patients with a history of pre-transplant pericoronitis had a significantly higher probability of developing tooth-related complications during transplantation, caused by pericoronitis in ITM compared to patients without a history of pericoronitis. Conclusion: Pre-transplant examination and treatment of ITM are essential, especially in cases with a history of pericoronitis. Oral intervention can significantly reduce the occurrence of tooth-related complications related to ITM during transplantation.

4.
Drug Des Devel Ther ; 18: 2745-2760, 2024.
Article in English | MEDLINE | ID: mdl-38974120

ABSTRACT

Purpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti-liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells. Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR. Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein-protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion-signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK. Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion-signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP.


Subject(s)
Carcinoma, Hepatocellular , Cell Movement , Cell Proliferation , Ferroptosis , Liver Neoplasms , Pollen , Schisandra , Humans , Cell Proliferation/drug effects , Cell Movement/drug effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Hep G2 Cells , Animals , Schisandra/chemistry , Pollen/chemistry , Ferroptosis/drug effects , Bees/chemistry , Focal Adhesions/drug effects , Focal Adhesions/metabolism , Wnt Signaling Pathway/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Signal Transduction/drug effects , Biological Products , Polyphenols
5.
PLoS One ; 19(7): e0306442, 2024.
Article in English | MEDLINE | ID: mdl-38980842

ABSTRACT

We aimed to determine the molecular characteristics of carbapenem-resistant Pseudomonas aeruginosa strains 18081308 and 18083286, which were isolated from the urine and the sputum of two Chinese patients, respectively. Additionally, we conducted a comparative analysis between Tn6411 carrying blaIMP-1 in strain 18083286 and transposons from the same family available in GenBank. Bacterial genome sequencing was carried out on strains 18081308 and 18083286 to obtain their whole genome sequence. Average nucleotide identity (ANI) was used for their precise species identification. Serotyping and multilocus sequence typing were performed. Furthermore, the acquired drug resistance genes of these strains were identified. The carbapenem-resistant P. aeruginosa strains isolated in the present study were of sequence type ST865 and serotype O6. They all carried the same resistance genes (aacC2, tmrB, and blaIMP-1). Tn6411, a Tn7-like transposon carrying blaIMP-1, was found in strain 18083286 by single molecule real time (SMRT) sequencing. We also identified the presence of this transposon sequence in other chromosomes of P. aeruginosa and plasmids carried by Acinetobacter spp. in GenBank, indicating the necessity for heightening attention to the potential transferability of this transposon.


Subject(s)
DNA Transposable Elements , Genomics , Pseudomonas aeruginosa , beta-Lactamases , Pseudomonas aeruginosa/genetics , DNA Transposable Elements/genetics , beta-Lactamases/genetics , Humans , Genomics/methods , Genome, Bacterial , Pseudomonas Infections/microbiology , Carbapenems/pharmacology , Multilocus Sequence Typing , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics
6.
Discov Oncol ; 15(1): 289, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023820

ABSTRACT

Chimeric antigen receptor (CAR)-T-cell therapy is one of the most effective immunotherapies. CAR-T-cell therapy has achieved great success in the treatment of hematological malignancies. However, due to the characteristics of solid malignant tumors, such as on-target effects, off-tumor toxicity, an immunosuppressive tumor microenvironment (TME), and insufficient trafficking, CAR-T-cell therapy for solid tumors is still in the exploration stage. Mesothelin (MSLN) is a molecule expressed on the surface of various solid malignant tumor cells that is suitable as a target of tumor cells with high MSLN expression for CAR-T-cell therapy. This paper briefly described the development of CAR-T cell therapy and the structural features of MSLN, and especially summarized the strategies of structure optimization of MSLN-targeting CAR-T-cells and the enhancement methods of MSLN-targeting CAR-T cell anti-tumor efficacy by summarizing some preclinical experiment and clinical trials. When considering MSLN-targeting CAR-T-cell therapy as an example, this paper summarizes the efforts made by researchers in CAR-T-cell therapy for solid tumors and summarizes feasible treatment plans by integrating the existing research results.

7.
FASEB J ; 38(14): e23832, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39046354

ABSTRACT

This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.


Subject(s)
Apoptosis , Cataract , Forkhead Box Protein M1 , NF-E2-Related Factor 2 , Oxidative Stress , Ultraviolet Rays , YAP-Signaling Proteins , Apoptosis/radiation effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Ultraviolet Rays/adverse effects , Humans , Animals , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Mice , Cataract/etiology , Cataract/metabolism , Cataract/pathology , YAP-Signaling Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Lens, Crystalline/metabolism , Lens, Crystalline/radiation effects , Transcription Factors/metabolism , Transcription Factors/genetics , Reactive Oxygen Species/metabolism , Male , Signal Transduction , Mice, Inbred C57BL
8.
Article in English | MEDLINE | ID: mdl-39046891

ABSTRACT

An orange-pigmented, Gram-stain-negative, strictly aerobic, non-flagellated and rod-shaped bacterium, designated strain DF17T, was isolated from coastal sediment collected from Jingzi Wharf, Weihai, PR China. The optimal growth conditions were determined to be at 30 °C, pH 7.5, and in 3 % (w/v) NaCl. According to phylogenetic analysis of the 16S rRNA gene sequence, strain DF17T showed the highest sequence similarity of 96.9 % to Winogradskyella aquimaris KCTC 23502T. The DNA G+C content was 35.8 mol%, and the major fatty acids were iso-C15 : 1 G, iso-C15 : 0, and iso-C17 : 0 3-OH. The major polar lipids were two aminoglycolipids, one phosphatidylethanolamine and four unidentified lipids. The predominant respiratory quinone was menaquinone-6 (MK-6). The average nucleotide identity, digital DNA-DNA hybridization, and amino acid identity values between strain DF17T and other Winogradskyella species were below the species delineation thresholds of 69.35-72.95 %, 16.9-19.6 % and 71.25-78.93 %, respectively. On the basis of its phenotypic, genetic and physiological characteristics, strain DF17T is suggested to represent a novel species of the genus Winogradskyella, for which the name Winogradskyella pelagia sp. nov. is proposed. The type strain is DF17T (MCCC 1H00456T=KCTC 82421T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Geologic Sediments/microbiology , Fatty Acids/chemistry , DNA, Bacterial/genetics , Vitamin K 2/analogs & derivatives , Vitamin K 2/analysis , China , Seawater/microbiology , Molecular Sequence Data , Phosphatidylethanolamines
9.
Environ Res ; 260: 119664, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39048069

ABSTRACT

The preparation of nitrogen-doped TiO2 (i.e., N-TiO2) catalysts is a highly effective option to improve the photocatalytic activity of TiO2. Nonetheless, relatively little is known about the effects of dopant precursors selected for their preparation with regard to the photocatalytic efficacy. In this study, three types of dopants are selected and used as N sources (urea (U), melamine (M), and aqueous ammonia (A)) for N-TiO2 samples with the name codes of NTU, NTM, and NTA, respectively. The photocatalytic efficacy of these N-TiO2 samples is examined against toluene in a packed bed flow reactor. Under optimal conditions (e.g., relative humidity (RH) = 20% and gas hourly space velocity (GHSV) = 1698 h-1), the superiority of NTA is evident over others with a quantum efficiency (QE) of 7.03 × 10-4 molecules photon-1, a space time yield (STY) of 1.38 × 10-4 molecules photon-1 mg-1, and a specific clean air delivery rate (SCADR) of 1148.8 L g-1 h-1. The analysis based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry confirms the formation of several intermediates such as benzyl alcohol, benzaldehyde, benzoic acid, and alkane species through ring opening reactions. In addition, the prepared NTA photocatalyst exhibits the highest toluene photocatalytic degradation efficiency among all TiO2-based catalysts surveyed to date. Overall, this study offers as a valuable guideline for the development of advanced TiO2 catalytic systems (such as N-TiO2) for the treatment of aromatic hydrocarbons in indoor air.

10.
Nat Commun ; 15(1): 5919, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004626

ABSTRACT

Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of ß-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.


Subject(s)
Diet, High-Fat , Galactosyltransferases , Insulin Resistance , Intestinal Mucosa , Mice, Inbred C57BL , Mice, Knockout , Obesity , Pregnane X Receptor , Animals , Obesity/metabolism , Obesity/genetics , Pregnane X Receptor/metabolism , Pregnane X Receptor/genetics , Galactosyltransferases/metabolism , Galactosyltransferases/genetics , Mice , Diet, High-Fat/adverse effects , Intestinal Mucosa/metabolism , Male , Intestines , Humans
11.
J Clin Invest ; 134(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949024

ABSTRACT

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.


Subject(s)
Cilia , Kidney Diseases, Cystic , Leigh Disease , Mitochondria , Zebrafish , Humans , Zebrafish/metabolism , Zebrafish/genetics , Leigh Disease/genetics , Leigh Disease/metabolism , Leigh Disease/pathology , Cilia/metabolism , Cilia/pathology , Cilia/genetics , Animals , Mitochondria/metabolism , Mitochondria/pathology , Mitochondria/genetics , Kidney Diseases, Cystic/genetics , Kidney Diseases, Cystic/metabolism , Kidney Diseases, Cystic/pathology , Electron Transport Complex I/metabolism , Electron Transport Complex I/genetics , Armadillo Domain Proteins/metabolism , Armadillo Domain Proteins/genetics , Retina/metabolism , Retina/pathology , Retina/abnormalities , Eye Abnormalities/genetics , Eye Abnormalities/pathology , Eye Abnormalities/metabolism , Mice , Abnormalities, Multiple/genetics , Abnormalities, Multiple/metabolism , Abnormalities, Multiple/pathology , Cerebellum/metabolism , Cerebellum/pathology , Cerebellum/abnormalities , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Male
12.
J Orthop Surg Res ; 19(1): 417, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030552

ABSTRACT

STUDY DESIGN: A systematic review and Bayesian network meta-analysis (NMA). OBJECTIVE: To compare the effectiveness and safety of different posterior decompression techniques for LSS. Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS. METHODS: An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. RESULTS: In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates. CONCLUSION: Overall, SPO was found to be a good surgical choice for patients with LSS.


Subject(s)
Bayes Theorem , Decompression, Surgical , Lumbar Vertebrae , Network Meta-Analysis , Spinal Stenosis , Spinal Stenosis/surgery , Humans , Decompression, Surgical/methods , Lumbar Vertebrae/surgery , Treatment Outcome , Laminectomy/methods
13.
Pestic Biochem Physiol ; 203: 106025, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39084764

ABSTRACT

Peanut web blotch (PWB) caused by Phoma arachidicola, is one of the most serious foliar diseases of peanut. Although prochloraz is an active fungicide with broad anti-fungal spectrum, it has not been registered for the control of PWB in China. The activity of prochloraz against P. arachidicola and the risk of resistance to prochloraz in P. arachidicola are still unclear. In current study, the inhibitory activity of prochloraz against 96 P. arachidicola strains was determined with the average EC50 value of 1.2700 ± 0.7786 µg/mL. Prochloraz exhibited excellent protective and curative effect on detached peanut leaves, and the effect was obviously better than that of carbendazim and difenoconazole at the same concentration. After prochloraz treatment, the mycelium of P. arachidicola contorted, shrunk and ruptured, with shrinking of cell wall and membrane, enhanced cell membrane permeability, and reduced ergosterol content. Totally 80 prochloraz-resistant mutants were obtained by fungicide adaptation with the frequency of 6.7 × 10-3. All the selected 12 prochloraz-resistant mutants lost their resistance to prochloraz after 10 transfers on PDA plates. And these mutants exhibited decreased biological fitness in mycelial growth and pathogenicity. Moreover, there was positive cross-resistance between prochloraz and other demethylation inhibitor (DMI) fungicides, such as tebuconazole, triflumizole and difenoconazole, but no cross-resistance was found between prochloraz and other classes of fungicides, such as carbendazim, pydiflumetofen or fludioxonil. Overexpression of PaCYP51 and PaAtrB genes were detected in the resistant mutants. All the above results demonstrated that prochloraz has a great potential in management of PWB. The risk of P. arachidicola developing resistance to prochloraz is relatively low-to-medium. Overexpressing of PaCYP51 and PaAtrB might be linked to prochloraz resistance in P. arachidicola.


Subject(s)
Arachis , Ascomycota , Drug Resistance, Fungal , Fungicides, Industrial , Imidazoles , Plant Diseases , Ascomycota/drug effects , Ascomycota/genetics , Fungicides, Industrial/pharmacology , Imidazoles/pharmacology , Drug Resistance, Fungal/genetics , Plant Diseases/microbiology , Arachis/microbiology , Risk Assessment , Carbamates/pharmacology , Mutation , Benzimidazoles
14.
Pestic Biochem Physiol ; 203: 105990, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39084767

ABSTRACT

Rice blast, caused by Magnaporthe oryzae, is a devastating fungal disease worldwide. Pydiflumetofen (Pyd) is a new succinate dehydrogenase inhibitor (SDHI) that exhibited anti-fungal activity against M. oryzae. However, control of rice blast by Pyd and risk of resistance to Pyd are not well studied in this pathogen. The baseline sensitivity of 109 M. oryzae strains to Pyd was determined using mycelial growth rate assay, with EC50 values ranging from 0.291 to 2.1313 µg/mL, and an average EC50 value of 1.1005 ± 0.3727 µg/mL. Totally 28 Pyd-resistant (PydR) mutants with 15 genotypes of point mutations in succinate dehydrogenase (SDH) complex were obtained, and the resistance level could be divided into three categories of very high resistance (VHR), high resistance (HR) and moderate resistance (MR) with the resistance factors (RFs) of >1000, 105.74-986.13 and 81.92-99.48, respectively. Molecular docking revealed that all 15 mutations decreased the binding-force score for the affinity between Pyd and target subunits, which further confirmed that these 15 genotypes of point mutations were responsible for the resistance to Pyd in M. oryzae. There was positive cross resistance between Pyd and other SDHIs, such as fluxapyroxad, penflufen or carboxin, while there was no cross-resistance between Pyd and carbendazim, prochloraz or azoxystrobin in M. oryzae, however, PydR mutants with SdhBP198Q, SdhCL66F or SdhCL66R genotype were still sensitive to the other 3 SDHIs, indicating lack of cross resistance. The results of fitness study revealed that the point mutations in MoSdhB/C/D genes might reduce the hyphae growth and sporulation, but could improve the pathogenicity in M. oryzae. Taken together, the risk of resistance to Pyd might be moderate to high, and it should be used as tank-mixtures with other classes of fungicides to delay resistance development when it is used for the control of rice blast in the field.


Subject(s)
Amino Acid Substitution , Drug Resistance, Fungal , Fungicides, Industrial , Succinate Dehydrogenase , Succinate Dehydrogenase/genetics , Succinate Dehydrogenase/antagonists & inhibitors , Succinate Dehydrogenase/metabolism , Drug Resistance, Fungal/genetics , Fungicides, Industrial/pharmacology , Plant Diseases/microbiology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Molecular Docking Simulation , Magnaporthe/drug effects , Magnaporthe/genetics , Point Mutation , Oryza/microbiology , Ascomycota
15.
BMC Gastroenterol ; 24(1): 238, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075408

ABSTRACT

PURPOSE: To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. METHODS: Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. RESULTS: Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P < 0.05). In terms of research on distension medium, it was found that the first constant sensation volume measured in the squatting position (when the distension medium was water) was significantly lower than that of gas (P < 0.05). CONCLUSION: For patients with functional constipation, there are differences in the results of rectal sensory tests between body positions and distension mediums. When conducting multicenter studies, it is necessary to unify the standard operating procedure (SOP) for operational details to ensure consistency and reliability of the test results.


Subject(s)
Constipation , Patient Positioning , Rectum , Humans , Constipation/physiopathology , Constipation/diagnosis , Female , Rectum/physiopathology , Male , Adult , Middle Aged , Patient Positioning/methods , Defecation/physiology , Sensation/physiology , Aged , Young Adult
16.
Int Breastfeed J ; 19(1): 41, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840129

ABSTRACT

BACKGROUND: Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women's ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. METHODS: We retrospectively analysed data from patients aged 20-40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. RESULTS: With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of 'exclusive breastfeeding' was 5.1 months, and the mean duration of 'any breastfeeding' was 8.8 months. The rate of 'ever breastfeeding' is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. CONCLUSIONS: There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.


Subject(s)
Breast Diseases , Breast Feeding , Humans , Breast Feeding/psychology , Breast Feeding/statistics & numerical data , Female , Adult , Retrospective Studies , Breast Diseases/surgery , Breast Diseases/psychology , China/epidemiology , Young Adult , Surveys and Questionnaires
17.
Sci Rep ; 14(1): 13192, 2024 06 08.
Article in English | MEDLINE | ID: mdl-38851826

ABSTRACT

Water eutrophication has emerged as a pressing concern for massive algal blooms, and these harmful blooms can potentially generate harmful toxins, which can detrimentally impact the aquatic environment and human health. Consequently, it is imperative to identify a safe and efficient approach to combat algal blooms to safeguard the ecological safety of water. This study aimed to investigate the procedure for extracting total flavonoids from Z. bungeanum residue and assess its antioxidant properties. The most favorable parameters for extracting total flavonoids from Z. bungeanum residue were a liquid-solid ratio (LSR) of 20 mL/g, a solvent concentration of 60%, an extraction period of 55 min, and an ultrasonic temperature of 80 °C. Meanwhile, the photosynthetic inhibitory mechanism of Z. bungeanum residue extracts against M. aeruginosa was assessed with a particular focus on the concentration-dependent toxicity effect. Z. bungeanum residue extracts damaged the oxygen-evolving complex structure, influenced energy capture and distribution, and inhibited the electron transport of PSII in M. aeruginosa. Furthermore, the enhanced capacity for ROS detoxification enables treated cells to sustain their photosynthetic activity. The findings of this study hold considerable relevance for the ecological management community and offer potential avenues for the practical utilization of resources in controlling algal blooms.


Subject(s)
Flavonoids , Microcystis , Photosynthesis , Zanthoxylum , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Zanthoxylum/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Allelopathy , Harmful Algal Bloom , Reactive Oxygen Species/metabolism , Photosystem II Protein Complex/metabolism
18.
Opt Express ; 32(10): 17953-17965, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38858963

ABSTRACT

This article presents a dual-wavelength signal wave output system capable of generating a broad range of adjustable wavelength intervals. The setup involved the creation of a dual-wavelength cascaded Raman laser featuring composite cavities operating at 1176 nm and 1313 nm. Experimental investigations were carried out on an external cavity MgO:PPLN-OPO driven by the cascaded Raman laser. By setting the crystal polarization period to 27.6-34.4 µm and the temperature to 50-130°C, adjustable tunable output of dual-wavelength signal wave at 1176 nm-MgO:PPLN-OPO (1550-2294 nm) and 1313 nm-MgO:PPLN-OPO (1768-2189 nm) was achieved with a wavelength interval of 0-218 nm. Under the conditions of a period of 34.4 µm, temperature of 90°C, and an incident Raman power of 2.6 W, the highest conversion efficiency of Raman to dual-wavelength signal wave (2212, 2182 nm) was 34.2%. Furthermore, the maximum output power of dual-wavelength signal wave was recorded at 1.02 W with an incident Raman power of 3.33 W.

19.
J Glaucoma ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884623

ABSTRACT

PRECIS: Wang et al compare an FDA-registered head-mounted smartphone device (PalmScan VF2000) with standard automated perimetry (SAP) in glaucoma patients and find that the head-mounted device may not fully recapitulate SAP testing. PURPOSE: This study prospectively compared visual field testing using the PalmScan VF2000 Visual Field Analyzer, a head-mounted smartphone device, with standard automated perimetry (SAP). METHODS: Patients with glaucoma undergoing Humphrey Field Analyzer SAP testing were asked to complete in-office PalmScan testing using a Samsung S5 smartphone in a virtual reality-style headset. Glaucoma severity was defined as SAP mean deviation (MD) >-6 dB for mild, between -6 and -12 dB for moderate, and <-12 dB for severe. Global parameters MD and pattern standard deviation (PSD) from PalmScan and SAP were compared using t-tests and Bland-Altman analyses. Bland-Altmann analyses of PalmScan and SAP MD were conducted for the superonasal, superotemporal, inferonasal, and inferotemporal visual field quadrants. The repeatability of PalmScan was assessed using Spearman's correlations and intraclass correlation coefficients (ICCs). RESULTS: Fifty-one patients (51 eyes) completed both SAP and PalmScan testing and met criteria for analysis. Compared to SAP, global MD and PSD measurements from PalmScan differed by an average of +0.62±0.26 dB (range: -3.25 to +4.60 dB) and -1.00±0.24 dB (range: -6.03 to +2.77 dB), respectively, while MD scores from individual visual field quadrants differed by as much as -6.58 to +11.43 dB. Agreement of PalmScan and SAP in classifying glaucoma severity was 86.3% across all eyes. PalmScan and SAP identified the same quadrant as having the worst visual field defect in 66.7% of eyes. CONCLUSIONS: Despite advantages in cost and accessibility, the PalmScan head-mounted perimetry device may not be able to fully recapitulate SAP testing.

20.
Nat Commun ; 15(1): 5041, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871694

ABSTRACT

Microspherical structures find broad application in chemistry and materials science, including in separations and purifications, energy storage and conversion, organic and biocatalysis, and as artificial and bioactive scaffolds. Despite this utility, the systematic diversification of their morphology and function remains hindered by the limited range of their molecular building blocks. Drawing upon the design principles of reticular synthesis, where diverse organic molecules generate varied porous frameworks, we show herein how analogous microspherical structures can be generated under mild conditions. The assembly of simple organic molecules into microspherical structures with advanced morphologies represents a grand challenge. Beginning with a partially condensed Schiff base which self-assembles into a hierarchical organic microsphere, we systematically synthesized sixteen microspheres from diverse molecular building blocks. We subsequently explicate the mechanism of hierarchical assembly through which these hierarchical organic microspheres are produced, isolating the initial monomer, intermediate substructures, and eventual microspheres. Furthermore, the open cavities present on the surfaces of these constructs provided distinctive adsorptive properties, which we harnessed for the immobilization of enzymes and bacteriophages. Holistically, these hierarchical organic microspheres provide an approach for designing multi-functional superstructures with advanced morphologies derived from simple organic molecules, revealing an extended length scale for reticular synthesis.

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