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1.
Front Cell Infect Microbiol ; 14: 1366908, 2024.
Article En | MEDLINE | ID: mdl-38725449

Background: Metagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses. Methods: This retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests. Results: mNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results. Conclusions: mNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.


Febrile Neutropenia , High-Throughput Nucleotide Sequencing , Metagenomics , Humans , Metagenomics/methods , Male , Retrospective Studies , High-Throughput Nucleotide Sequencing/methods , Female , Middle Aged , Febrile Neutropenia/microbiology , Febrile Neutropenia/blood , Febrile Neutropenia/diagnosis , Adult , Aged , Young Adult , Adolescent , Aged, 80 and over , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/classification , Mycoses/diagnosis , Mycoses/microbiology , Virus Diseases/diagnosis , Virus Diseases/virology
2.
Biochem Pharmacol ; 225: 116275, 2024 May 08.
Article En | MEDLINE | ID: mdl-38729447

Atherosclerosis (AS) is the common pathophysiological basis of various cardiovascular diseases and the leading cause of death from cardiovascular disease worldwide. When the body is in a hypoxic environment, enhanced oxidative stress and significant accumulation of reactive oxygen species (ROS) in tissue cells exacerbate the inflammatory response, resulting in increased release of myeloperoxidase (MPO), catalyzing the formation of large quantities of hypochlorous acid (HOCl), further oxidative modification of low-density lipoprotein (LDL), and exacerbating the formation and progression of atherosclerotic plaques. The MAPK signaling pathway is important in oxidative stress-mediated promotion of atherogenesis. MPO -/- mice were used in this study to establish a hypoxia model simulating 5000 m altitude and a Western high-fat diet-induced atherosclerosis model for 12 weeks. Exploring the role of MPO in the atherosclerotic process in hypoxic mice by observing the MAPK signaling pathway to provide a therapeutic target for the prevention and treatment of hypoxic atherosclerotic disease in the plateau. We found that hypoxia promotes the formation of atherosclerosis in mice, and the mechanism may be that increased MPO in vivo promotes an inflammatory response, which plays a crucial role in the formation of atherosclerosis. In addition, hypoxia further exacerbates plaque instability by activating the MAPK signaling pathway to upregulate vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9), which in turn promotes angiogenesis within the plaque. Therefore, a potential target for preventing and treating hypoxic atherosclerotic disease is the inhibition of MPO.

3.
Mol Biol Rep ; 51(1): 607, 2024 May 05.
Article En | MEDLINE | ID: mdl-38704801

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.


Endoplasmic Reticulum Stress , Neurons , Neuroprotective Agents , Oxidative Stress , Peroxiredoxins , Pyroptosis , Reactive Oxygen Species , Pyroptosis/drug effects , Endoplasmic Reticulum Stress/drug effects , Animals , Oxidative Stress/drug effects , Neurons/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Mice , Reactive Oxygen Species/metabolism , Peroxiredoxins/metabolism , Signal Transduction/drug effects , Cell Line , Mitochondria/metabolism , Mitochondria/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/complications
4.
Psychiatry Investig ; 21(4): 387-395, 2024 Apr.
Article En | MEDLINE | ID: mdl-38695046

OBJECTIVE: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). METHODS: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. RESULTS: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. CONCLUSION: Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

5.
J Alzheimers Dis Rep ; 8(1): 589-600, 2024.
Article En | MEDLINE | ID: mdl-38746638

Background: Sleep disturbances frequently affect Alzheimer's disease (AD), with up to 65% patients reporting sleep-related issues that may manifest up to a decade before AD symptoms. Objective: To construct a nomogram that synthesizes sleep quality and cognitive performance for predicting cognitive impairment (CI) conversion outcomes. Methods: Using scores from three well-established sleep assessment tools, Pittsburg Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and Epworth Sleepiness Scale, we created the Sleep Composite Index (SCI), providing a comprehensive snapshot of an individual's sleep status. Initially, a CI conversion prediction model was formed via COX regression, fine-tuned by bidirectional elimination. Subsequently, an optimized prediction model through COX regression, depicted as a nomogram, offering predictions for CI development in 5, 8, and 12 years among cognitively unimpaired (CU) individuals. Results: After excluding CI patients at baseline, our study included 816 participants with complete baseline and follow-up data. The CU group had a mean age of 66.1±6.7 years, with 36.37% males, while the CI group had an average age of 70.3±9.0 years, with 39.20% males. The final model incorporated glial fibrillary acidic protein, Verbal Fluency Test and SCI, and an AUC of 0.8773 (0.792-0.963). Conclusions: In conclusion, the sleep-cognition nomogram we developed could successfully predict the risk of converting to CI in elderly participants and could potentially guide the design of interventions for rehabilitation and/or cognitive enhancement to improve the living quality for healthy older adults, detect at-risk individuals, and even slow down the progression of AD.

6.
J Cell Mol Med ; 28(9): e18286, 2024 May.
Article En | MEDLINE | ID: mdl-38742843

Osteosarcoma, the primary bone cancer in adolescents and young adults, is notorious for its aggressive growth and metastatic potential. Our study delved into the prognostic impact of inflammasome-related gene signatures in osteosarcoma patients, employing comprehensive genetic profiling to uncover signatures linked with patient outcomes. We identified three patient subgroups through consensus clustering, with one showing worse survival rates correlated with high FGFR3 and RARB expressions. Immune profiling revealed significant immune cell infiltration differences among these subgroups, affecting survival. Utilising advanced machine learning, including StepCox and gradient boosting machine algorithms, we developed a prognostic model with a notable c-index of 0.706, highlighting CD36 and MYD88 as key genes. Higher inflammasome risk scores from our model were associated with poorer survival, corroborated across datasets. In vitro experiments validated CD36 and MYD88's roles in promoting osteosarcoma cell proliferation, invasion and migration, emphasising their therapeutic potential. This research offers new insights into inflammasomes' role in osteosarcoma, introducing novel biomarkers for risk assessment and potential therapeutic targets. Our findings suggest a pathway towards personalised treatment strategies, potentially improving patient outcomes in osteosarcoma.


Biomarkers, Tumor , Bone Neoplasms , Gene Expression Regulation, Neoplastic , Inflammasomes , Osteosarcoma , Humans , Osteosarcoma/genetics , Osteosarcoma/pathology , Osteosarcoma/immunology , Osteosarcoma/mortality , Inflammasomes/metabolism , Inflammasomes/genetics , Biomarkers, Tumor/genetics , Prognosis , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/mortality , Bone Neoplasms/immunology , Bone Neoplasms/diagnosis , Gene Expression Profiling , Female , Male , Transcriptome/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Adolescent , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism
7.
Se Pu ; 42(5): 474-480, 2024 Apr 08.
Article Zh | MEDLINE | ID: mdl-38736391

A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including ß2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and ß-glucuronidase/aryl sulfatase (40 µL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 µL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 µg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 µg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.


Drug Residues , Tandem Mass Spectrometry , Veterinary Drugs , Animals , Tandem Mass Spectrometry/methods , Swine , Chromatography, High Pressure Liquid/methods , Veterinary Drugs/urine , Veterinary Drugs/analysis , Drug Residues/analysis , Chloramphenicol/urine , Chloramphenicol/analysis
8.
Front Pharmacol ; 15: 1378782, 2024.
Article En | MEDLINE | ID: mdl-38716235

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU. Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro. Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = -1.18, 95% CI = -1.58 to -0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = -1.79, 95% CI = -2.67 to -0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very low-certainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = -1.66, 95% CI = -3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001). Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=471154, Identifier CRD42023471154.

9.
Org Lett ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38722200

We have developed an efficient protocol for the synthesis of spiro[indoline-pyridine]dicarboxylates and substituted alkylidene oxindoles through [3 + 3] cycloaddition and Michael addition individually by azomethine ylides and various MBH carbonates of isatins. The selective generation of cyclic products and chain products was achieved by changing the substituents at the 3-position of the oxindoles. The features of this method include convenient catalysts, mild reaction conditions, and broad substrate scopes.

10.
Cancer Commun (Lond) ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38715348

Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called "cold" tumors which are unresponsive to immunotherapy, and the opposite are "hot" tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of "cold" tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming "cold" tumors into "hot" tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in "cold" tumor.

11.
Light Sci Appl ; 13(1): 101, 2024 May 06.
Article En | MEDLINE | ID: mdl-38705921

Temporal solitons have been the focus of much research due to their fascinating physical properties. These solitons can form bound states, which are fundamentally crucial modes in fiber laser and present striking analogies with their matter molecules counterparts, which means they have potential applications in large-capacity transmission and all-optical information storage. Although traditionally, second-order dispersion has been the dominant dispersion for conventional solitons, recent experimental and theoretical research has shown that pure-high-even-order dispersion (PHEOD) solitons with energy-width scaling can arise from the interaction of arbitrary negative-even-order dispersion and Kerr nonlinearity. Despite these advancements, research on the bound states of PHEOD solitons is currently non-existent. In this study, we obtained PHEOD bound solitons in a fiber laser using an intra-cavity spectral pulse shaper for high-order dispersion management. Specifically, we experimentally demonstrate the existence of PHEOD solitons and PHEOD bound solitons with pure-quartic, -sextic, -octic, and -decic dispersion. Numerical simulations corroborate these experimental observations. Furthermore, vibrating phase PHEOD bound soliton pairs, sliding phase PHEOD bound soliton pairs, and hybrid phase PHEOD bound tri-soliton are discovered and characterized. These results broaden the fundamental understanding of solitons and show the universality of multi-soliton patterns.

12.
Research (Wash D C) ; 7: 0354, 2024.
Article En | MEDLINE | ID: mdl-38711474

To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer's disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model's performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor.

13.
Heliyon ; 10(9): e30483, 2024 May 15.
Article En | MEDLINE | ID: mdl-38737277

Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a "public health emergency of international concern." The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.

14.
Chem Commun (Camb) ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38742271

A new macrocyclic arene, dibenzofuran[3]arene, was synthesized, which could be conveniently transformed to an O-doped aromatic belt with a rigid ring-shaped structure and deep cavity. Moreover, the O-doped aromatic belt also showed a high HOMO energy and a narrow HOMO-LUMO gap experimentally and theoretically.

15.
J Photochem Photobiol B ; 255: 112907, 2024 Jun.
Article En | MEDLINE | ID: mdl-38677259

OBJECTIVE: The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. METHODS: HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. RESULTS: OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. CONCLUSIONS: OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.


Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Epithelial Cells , Leukoplakia, Oral , Mesenchymal Stem Cells , Mouth Mucosa , Mouth Neoplasms , Photochemotherapy , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mouth Mucosa/pathology , Mouth Mucosa/cytology , Leukoplakia, Oral/pathology , Leukoplakia, Oral/therapy , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Movement/drug effects , Cell Movement/radiation effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Mouth Neoplasms/therapy , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Photosensitizing Agents/pharmacology , Cell Line, Tumor , Aminolevulinic Acid/pharmacology , Cell Differentiation/drug effects , Transcriptome/drug effects
16.
Organometallics ; 43(8): 879-888, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38665773

The bimetallic species, [{SiNDipp}MgNa]2 [{SiNDipp} = {CH2SiMe2N(Dipp)}2; (Dipp = 2,6-i-Pr2C6H3)], is shown to be a potent reducing agent, able to effect one- or two-electron reduction of either dioxygen, TEMPO, anthracene, benzophenone, or diphenylacetylene. In most cases, the bimetallic reaction products imply that the dissimilar alkaline metal centers react with a level of cooperativity. EPR analysis of the benzophenone-derived reaction and the concurrent isolation of [{SiNDipp}Mg(OCPh2)2], however, illustrate that treatment with such reducible, but O-basic, species can also result in reactivity in which the metals provide independent reaction products. The notable E-stereochemistry of the diphenylacetylene reduction product prompted a computational investigation of the PhC≡CPh addition. This analysis invokes a series of elementary steps that necessitate ring-opening via Mg+ → Na+ amido group migration of the SiNDipp ligand, providing insight into the previously observed lability of the bidentate dianion and its consequent proclivity toward macrocyclization.

17.
Int J Biol Macromol ; 267(Pt 2): 131533, 2024 May.
Article En | MEDLINE | ID: mdl-38608988

As a renewable aromatic compound with enormous production potential, lignin has various potential high-value utilization pathways, but the success achieved in the field of photocatalysis is limited. Herein, this work prepares a new type of photocatalyst by modifying Graphitic Carbon Nitride Nanotubes (CNT) with self-assembled lignin nanospheres for the photocatalytic production of H2O2 and the degradation of azo dyes. Under light conditions, lignin enhances the production of H2O2 through oxygen reduction and collaborates with carbon nitride tubes to generate O2- and 1O2. Furthermore, carbon nitride tubes form electron-rich regions with lignin, promoting the transfer of electrons from adsorbed aromatic pollutants to this region, thereby facilitating their degradation. The experimental results indicate that the addition of 5 % lignin significantly enhances the photocatalytic degradation efficiency of azo dyes, with a degradation rate 1.87 times higher than that of the original carbon nitride tubes. Furthermore, CNL also have excellent degradation ability to pollutants in actual wastewater. This study provides new insights and prospects for the high-value utilization of lignin, enabling it to be used as a photocatalytic co-catalyst to participate in the photocatalytic degradation of environmental pollutants.


Graphite , Hydrogen Peroxide , Lignin , Lignin/chemistry , Graphite/chemistry , Catalysis , Hydrogen Peroxide/chemistry , Nanotubes/chemistry , Nitriles/chemistry , Azo Compounds/chemistry , Boron Compounds/chemistry , Water Pollutants, Chemical/chemistry , Photochemical Processes , Nanotubes, Carbon/chemistry , Nitrogen Compounds
18.
Am J Ophthalmol ; 264: 187-193, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38614194

PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None. SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24 to 2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean ± SD age at first test 12.0 ± 3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (P < .04). Mean ± SD patient-level reliability score was 51.7 ± 38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all P < .02), and number of prior VF tests was not (P = .56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

19.
Cell Commun Signal ; 22(1): 231, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637880

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.


MicroRNAs , Mitochondrial Diseases , Neurodegenerative Diseases , Humans , Peroxiredoxins/genetics , Reactive Oxygen Species/metabolism , Oxidative Stress , Apoptosis , Endoplasmic Reticulum Stress , MicroRNAs/metabolism
20.
Sci Data ; 11(1): 399, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643170

Dynamical downscaling is vital for generating finer-scale climate projections. Recently, a set of simulations under four types of 1.5/2 °C global warming scenarios are available with Nanjing University of Information Science and Technology Earth System Model (NESM). However, NESM3's bias in large-scale driving variables would degrade downscaled simulations. We corrected NESM3 bias in terms of climate mean and inter-annual variance against ERA5 using a novel bias correction method and then produced a set of bias-corrected datasets for dynamical downscaling. The bias-corrected NESM3 spans the historical period for 1979-2014 and four future scenarios (i.e., 1.5 °C overshoot for 2070-2100, stabilized 1.5/2 °C for 2070-2100, and transient 2 °C for 2031-2061) with 1.25° × 1.25° horizontal resolution at six-hourly intervals. Our evaluation suggests that bias-corrected NESM3 outperforms the original NESM3 in the climatological mean of seasonal mean and variability, as well as climate extreme events during the historical period. This bias-corrected dataset is expected to generate more reliable projections for regional climate and environment under 1.5/2 °C global warming.

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