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1.
Cancer Invest ; 42(6): 527-537, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965994

ABSTRACT

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Rectal Neoplasms/immunology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Aged , Chemoembolization, Therapeutic/methods , Prognosis , Treatment Outcome , Adult , Chemoradiotherapy/methods
2.
Front Nutr ; 11: 1418305, 2024.
Article in English | MEDLINE | ID: mdl-38993240

ABSTRACT

Background and objective: Allergic rhinitis (AR) is a common chronic inflammatory disease that significantly impacts the quality of life of patients. However, there is limited research on the relationship between the Dietary Inflammatory Index (DII) and the risk of AR. Our study aimed to assess the association between DII and AR in a sample of adults from North China. Methods: In a case-control study, we selected 166 cases of AR and 166 age- and gender-matched controls. Dietary intake was assessed using a validated food frequency questionnaire. The energy-adjusted DII (E-DII) scores were calculated based on the quantity of diet components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between E-DII and AR. Results: Our findings indicate a positive correlation between E-DII and AR risk. After controlling for confounders, individuals in the highest E-DII tertile exhibited a 4.41-fold increased risk of AR compared to those in the lowest tertile (OR 4.41, 95% CI 2.31-8.41). Additionally, stratified analysis showed that E-DII was positively associated with AR subtype (seasonal vs. perennial), duration (≤6 years vs. >6 years), severity (mild vs. moderate-severe), and onset time (intermittent vs. persistent). Furthermore, individuals in the highest E-DII tertile had higher intake of total fat, SFA, PUFAs, and n-6 PUFAs. Conclusion: In conclusion, we realized that there is a positive association between the E-DII score and AR. The consumption of diets abundant in anti-inflammatory nutrients and low in pro-inflammatory nutrient contents is recommended as a preventative strategy against AR.

3.
Front Neurosci ; 18: 1399653, 2024.
Article in English | MEDLINE | ID: mdl-38979126

ABSTRACT

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

4.
CNS Neurosci Ther ; 30(7): e14829, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961264

ABSTRACT

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.


Subject(s)
B7-H1 Antigen , Calcitonin Gene-Related Peptide , Mice, Inbred C57BL , Paclitaxel , Peripheral Nervous System Diseases , Sex Characteristics , TRPV Cation Channels , Animals , Paclitaxel/toxicity , Male , Female , Mice , Calcitonin Gene-Related Peptide/metabolism , TRPV Cation Channels/metabolism , TRPV Cation Channels/antagonists & inhibitors , B7-H1 Antigen/metabolism , Peripheral Nervous System Diseases/chemically induced , Antineoplastic Agents, Phytogenic/toxicity , Spinal Cord/drug effects , Spinal Cord/metabolism , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Hyperalgesia/metabolism
5.
ACS Nano ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976394

ABSTRACT

Ceramic aerogel is an appealing fireproof and heat-insulation material, but synchronously improving its mechanical and thermal properties is a challenge. Moreover, the expensive discontinuous processing techniques inhibit the large-scale fabrication of ceramic aerogels. Here, we propose a water-based electrospinning method, based on the hydrolysis and condensation reactions of ceramic precursor salts themselves, for the continuous and rapid (0.025 m3/min) fabrication of ceramic fiber sponge aerogels with dual micronano fiber networks, which show synchronous enhanced fireproof, thermal insulation, and resilience performance. The elastic ceramic micro/nano fiber sponge aerogels contain robust silica-based microfibers as a firm skeleton and alumina-based nanofibers as elastic thermal insulation filler. The sponges have a high porosity of >99.8%, a low mass density (6.21 mg/cm3), a small thermal conductivity (0.022 W/m·K), and a large compression strength (21.15 kPa at 80% strain). The ceramic fiber sponges can effectively prevent the propagation of thermal runaway when a lithium battery experiences catastrophic thermal shock (>1000 °C) in the power battery packs. The proposed strategy is feasible for low-cost and rapid synthesizing ceramic aerogels toward effective battery thermal management.

6.
Acta Pharmacol Sin ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992118

ABSTRACT

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 105 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries.

7.
Article in English | MEDLINE | ID: mdl-38958649

ABSTRACT

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Fatty Acids/chemistry , Geologic Sediments/microbiology , China , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Genome, Bacterial , Phospholipids/chemistry
8.
Front Oncol ; 14: 1393684, 2024.
Article in English | MEDLINE | ID: mdl-38966070

ABSTRACT

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

9.
Neuroimage ; 296: 120683, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38880308

ABSTRACT

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.


Subject(s)
Epilepsy, Temporal Lobe , Machine Learning , Magnetic Resonance Imaging , Humans , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/diagnostic imaging , Adult , Male , Female , Middle Aged , Magnetic Resonance Imaging/methods , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Brain/physiopathology , Brain/diagnostic imaging , Young Adult , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/diagnostic imaging , Connectome/methods
10.
Nutrients ; 16(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38892715

ABSTRACT

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.


Subject(s)
Gastrointestinal Microbiome , Gynostemma , Non-alcoholic Fatty Liver Disease , Plant Extracts , Animals , Gastrointestinal Microbiome/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Mice , Gynostemma/chemistry , Plant Extracts/pharmacology , Male , Inflammation/drug therapy , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacology
11.
Reprod Biol ; 24(3): 100914, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38875746

ABSTRACT

DIS3L, a catalytic exoribonuclease associated with the cytoplasmic exosome complex, degrades cytoplasmic RNAs and is implicated in cancers and certain other diseases in humans. Epididymis plays a pivotal role in the transport, maturation, and storage of sperm required for male fertility. However, it remains unclear whether DIS3L-mediated cytoplasmic RNA degradation plays a role in epididymis biology and functioning. Herein, we fabricated a Dis3l conditional knockout (Dis3l cKO) mouse line in which DIS3L was ablated from the principal cells of the initial segment (IS). Morphological analyses showed that spermatogenesis and IS differentiation occurred normally in Dis3l cKO mice. Additionally, the absence of DIS3L had no dramatic influence on the transcriptome of IS. Moreover, the sperm count, morphology, motility, and acrosome reaction frequency in Dis3l cKO mice were comparable to that of the control, indicating that the Dis3l cKO males had normal fertility. Collectively, our genetic model demonstrates that DIS3L inactivation in the IS is nonessential for sperm maturation and male fertility.

13.
Drug Des Devel Ther ; 18: 2347-2356, 2024.
Article in English | MEDLINE | ID: mdl-38915865

ABSTRACT

Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.


Subject(s)
Benzodiazepines , Dose-Response Relationship, Drug , Fentanyl , Gastroscopy , Humans , Aged , Benzodiazepines/administration & dosage , Male , Female , Fentanyl/administration & dosage , Aged, 80 and over
14.
Am J Med Sci ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944203

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.

15.
Nat Microbiol ; 9(7): 1686-1699, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38898217

ABSTRACT

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.


Subject(s)
Antifungal Agents , Mutagenesis , Animals , Mice , Humans , Virulence/genetics , Antifungal Agents/pharmacology , China , Body Temperature , Disease Models, Animal , Ascomycota/genetics , Ascomycota/pathogenicity , Ascomycota/drug effects , Caspofungin/pharmacology , Microbial Sensitivity Tests , Fluconazole/pharmacology , Mycoses/microbiology , Drug Resistance, Multiple, Fungal/genetics , Drug Resistance, Fungal/genetics
17.
Food Chem ; 455: 139862, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38833866

ABSTRACT

Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B1 (AFB1). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p-coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB1 degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p-coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB1 degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3-3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.


Subject(s)
Laccase , Zea mays , Laccase/metabolism , Laccase/chemistry , Zea mays/chemistry , Zea mays/metabolism , Fungal Proteins/chemistry , Fungal Proteins/metabolism , Aflatoxin B1/chemistry , Aflatoxin B1/metabolism , Oxidation-Reduction , Plant Extracts/chemistry , Fermentation , Coumaric Acids/chemistry , Coumaric Acids/metabolism
18.
Small Methods ; : e2400565, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38923872

ABSTRACT

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe2 and Co9Se8 heterojunction rich in selenium vacancies (VSe·) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E1/2) = 0.878 V and limiting current density (JL) = 21.88 mA cm-2). The JL exceeds the 20 wt% Pt/C (19.34 mA cm-2) and the E1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm-2), which even exceeds that of the commercial RuO2 (427 mV@10 mA cm-2). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced VSe· and the CoNiSe2-Co9Se8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm-2, outperforming the 20 wt% Pt/C+RuO2 (73.9 mW cm-2) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm-2 and ultra-robust cycling stability even under bending.

19.
Cancer Rep (Hoboken) ; 7(6): e2079, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923313

ABSTRACT

BACKGROUND: Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is involved in the development of a variety of tumours, but its effect on colorectal cancer progression has been poorly elucidated. METHODS: Based on the GEO database, this study identifies the core gene SERPINC1 associated with liver metastasis in CRC. We used transcriptomic data and immunohistochemical staining to explore the expression of SERPINC1 in normal, cancer, and liver metastases tissue from CRC patients. Clinical data obtained from our hospital were used to explore the impact of SERPINC1 on the prognosis of colon cancer patients. Mechanistically, the biological functions exerted by SERPINC1 in CRC were predicted by bioinformatics, and the results were validated by the results of the experiments in vitro. Cell lines with knockdown of SERPINC1 were performed a series assay such as trans well, CCK-8 and colony formation assay to explore the relationship between SERPINC1 and proliferation and metastasis of CRC cells. Finally, the effect of SERPINC1 on the sensitivity of colon cancer patients to immune checkpoint therapy was evaluated. RESULTS: In CRC liver metastatic tissues, we found significantly high expression of SERPINC1. Briefly, 212 CRC cohorts showed that SERPINC1 was significantly associated with TNM stage and plasma CA19-9 and CEA in CRC patients. Univariate and multivariate Cox demonstrated that SERPINC1 was significantly associated with 5-year survival after radical surgery for colorectal cancer (p < 0.001). Bioinformatics predicted that SERPINC1 affects metastasis of colon cancer through epithelial-mesenchymal transition (EMT). Colony formation assay and CCK-8 assay showed that SERPINC1 promotes malignant proliferation of CRC cells, trans well assay showed that SERPINC1 promotes distant migratory behaviour of CRC cells and protein blotting assay showed that SERPINC1 may promote migration by promoting the TGF-ß1-mediated EMT of CRC cells. In addition, several immunotherapy cohorts also reflected that the expression of SERPINC1 reduced the sensitivity of CRC patients to immune checkpoint therapy. CONCLUSION: Our study identified SERPINC1 as a novel liver metastasis-associated gene in CRC. Targeting SERPINC1 may be a novel therapeutic strategy for patients with liver metastases from CRC.


Subject(s)
Biomarkers, Tumor , Cell Proliferation , Colonic Neoplasms , Disease Progression , Epithelial-Mesenchymal Transition , Liver Neoplasms , Humans , Prognosis , Liver Neoplasms/secondary , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Colonic Neoplasms/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/mortality , Female , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Middle Aged , Cell Line, Tumor , Cell Movement , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality
20.
Food Chem Toxicol ; 190: 114776, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851522

ABSTRACT

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA + MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology.


Subject(s)
Asthma , Lung , Mice, Inbred BALB C , Microplastics , Ovalbumin , Animals , Asthma/chemically induced , Microplastics/toxicity , Mice , Lung/pathology , Lung/drug effects , Female , Microbiota , Cytokines/metabolism
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