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1.
Light Sci Appl ; 13(1): 110, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724516

ABSTRACT

Entanglement plays a vital role in quantum information processing. Owing to its unique material properties, silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities. To date, however, only entanglement of nuclear spins has been reported in silicon carbide, while an entangled photon source, whether it is based on bulk or chip-scale technologies, has remained elusive. Here, we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time. Specifically, strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform. The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW, corresponding to a pair generation rate of (9 ± 1) × 103 pairs/s. Energy-time entanglement is created and verified for such signal-idler photon pairs, with the two-photon interference fringes exhibiting a visibility larger than 99%. The heralded single-photon properties are also measured, with the heralded g(2)(0) on the order of 10-3, demonstrating the SiC platform as a prospective fully integrated, complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.

2.
Biotechnol Lett ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733437

ABSTRACT

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

3.
Clinics (Sao Paulo) ; 79: 100376, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733690

ABSTRACT

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

4.
Opt Lett ; 49(9): 2405-2408, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691730

ABSTRACT

Two-dimensional (2D) MXenes stand out as promising platforms for surface-enhanced Raman scattering (SERS) sensing owing to their metallic feature, various compositions, high surface area, compatibility with functionalization, and ease of fabrication. In this work, we report a high-performance 2D titanium carbonitride (Ti3CN) MXene SERS substrate. We reveal that the abundant electronic density of states near the Fermi level of Ti3CN MXene boosts the efficiency of photo-induced charge transfer at the interface of Ti3CN/molecule, resulting in significant Raman enhancement. The SERS sensitivity of Ti3CN MXene is further promoted through a 2D morphology regulation and molecular enrichment strategies. Moreover, prohibited drugs are detectable on this substrate, presenting the potential of trace-amount analysis on Ti3CN MXene. This work provides a deep insight of the SERS mechanisms of Ti3CN MXene and broadens the practical application of transition metal carbonitride MXene SERS substrates.

5.
Ecotoxicol Environ Saf ; 278: 116354, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38691882

ABSTRACT

After the resumption of work and production following the COVID-19 pandemic, many cities entered a "transition phase", characterized by the gradual recovery of emission levels from various sources. Although the overall PM2.5 emission trends have recovered, the specific changes in different sources of PM2.5 remain unclear. Here, we investigated the changes in source contributions and the evolution pattern of pollution episodes (PE) in Wuhan during the "transition period" and compared them with the same period during the COVID-19 lockdown. We found that vehicle emissions, industrial processes, and road dust exhibited significant recoveries during the transition period, increasing by 5.4%, 4.8%, and 3.9%, respectively, during the PE. As primary emissions increased, secondary formation slightly declined, but it still played a predominant role (accounting for 39.1∼ 43.0% of secondary nitrate). The reduction in industrial activities was partially offset by residential burning. The evolution characteristics of PE exhibited significant differences between the two periods, with PM2.5 concentration persisting at a high level during the transition period. The differences in the evolution patterns of the two periods were also reflected in their change rates at each stage, which mostly depend on the pre-PE concentration level. The transition period shows a significantly higher value (8.4 µg m-3 h-1) compared with the lockdown period, almost double the amount. In addition to local emissions, regional transport should be a key consideration in pollution mitigation strategies, especially in areas adjacent to Wuhan. Our study quantifies the variations in sources between the two periods, providing valuable insights for optimizing environmental planning to achieve established goals.

6.
World J Hepatol ; 16(4): 625-639, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38689750

ABSTRACT

BACKGROUND: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. AIM: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. METHODS: We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models. RESULTS: Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value. CONCLUSION: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

7.
Front Pharmacol ; 15: 1379338, 2024.
Article in English | MEDLINE | ID: mdl-38738180

ABSTRACT

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

8.
Nutrients ; 16(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38732518

ABSTRACT

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.


Subject(s)
Cholecalciferol , Energy Metabolism , Fasting , Homeostasis , Zebrafish , Animals , Cholecalciferol/metabolism , Cholecalciferol/pharmacology , Liver/metabolism , Gluconeogenesis , Gastrointestinal Microbiome/physiology , Blood Glucose/metabolism , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/blood
9.
Molecules ; 29(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731458

ABSTRACT

Utilizing hydrogen as a viable substitute for fossil fuels requires the exploration of hydrogen storage materials with high capacity, high quality, and effective reversibility at room temperature. In this study, the stability and capacity for hydrogen storage in the Sc-modified C3N4 nanotube are thoroughly examined through the application of density functional theory (DFT). Our finding indicates that a strong coupling between the Sc-3d orbitals and N-2p orbitals stabilizes the Sc-modified C3N4 nanotube at a high temperature (500 K), and the high migration barrier (5.10 eV) between adjacent Sc atoms prevents the creation of metal clusters. Particularly, it has been found that each Sc-modified C3N4 nanotube is capable of adsorbing up to nine H2 molecules, and the gravimetric hydrogen storage density is calculated to be 7.29 wt%. It reveals an average adsorption energy of -0.20 eV, with an estimated average desorption temperature of 258 K. This shows that a Sc-modified C3N4 nanotube can store hydrogen at low temperatures and harness it at room temperature, which will reduce energy consumption and protect the system from high desorption temperatures. Moreover, charge donation and reverse transfer from the Sc-3d orbital to the H-1s orbital suggest the presence of the Kubas effect between the Sc-modified C3N4 nanotube and H2 molecules. We draw the conclusion that a Sc-modified C3N4 nanotube exhibits exceptional potential as a stable and efficient hydrogen storage substrate.

10.
World J Gastrointest Oncol ; 16(4): 1344-1360, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660669

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer, characterized by frequent mucin overexpression. MUC1 has been identified as a critical oncogene in the progression of CCA. However, the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete. AIM: To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients. METHODS: Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins, complemented by bioinformatic analyses. Subsequent validations were conducted through spatial transcriptomics and immunohistochemistry. The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm, which was further confirmed by independent cohorts and diverse data types. RESULTS: CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness. MUC5AC-high cells were found to promote CCA progression through WNT signaling. MUC5B-high cells exhibited robust cellular oxidation activities, leading to resistance against antitumoral treatments. MUC13-high cells were observed to secret chemokines, recruiting and transforming macrophages into the M2-polarized state, thereby suppressing antitumor immunity. MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils. Utilizing the expression levels of these mucins, a risk factor evaluation formula for CCA was developed and validated across multiple cohorts. CCA samples with higher risk factors exhibited stronger metastatic potential, chemotherapy resistance, and poorer prognosis. CONCLUSION: Our study elucidates the functional mechanisms through which mucins contribute to CCA development, and provides tools for risk stratification in CCA.

11.
J Cardiothorac Surg ; 19(1): 227, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627839

ABSTRACT

OBJECTIVE: To investigate the clinical significance of the creatine kinase (CK)-MB/total CK ratio, neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width in acute myocardial infarction (AMI). METHODS: A retrospective analysis was conducted of 196 AMI cases from our hospital's cardiology department; healthy people were selected over the same period as the control. The two groups' test indexes were compared through multivariate logistic regression analysis to screen for AMI risk factors; the receiver operating characteristic (ROC) curve was used to evaluate their AMI predictive values. RESULTS: The serum CK, CK-MB, CK index, neutrophils and NLR values in the AMI group were significantly higher compared with those in the control group (p < 0.05); however, the levels of serum lymphocytes were significantly lower compared with those in the control group (p < 0.05). Multivariate logistic regression analysis showed that elevated CK-MB and NLR levels were risk factors for AMI (p < 0.05). The ROC curve showed that the area under the curve of the NLR and CK levels were 0.917 and 0.594, respectively. CONCLUSION: The CK index and NLR have a clinical predicting value for AMI and could be used as a clinical auxiliary diagnostic index for the assessment of patients with AMI.


Subject(s)
Myocardial Infarction , Neutrophils , Humans , Creatine Kinase , Retrospective Studies , Sensitivity and Specificity , Biomarkers , Creatine Kinase, MB Form , Myocardial Infarction/diagnosis , ROC Curve , Lymphocytes
12.
Chemphyschem ; : e202400052, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629246

ABSTRACT

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X = dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] could be considered as metallic glass-forming liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 ℃) without melting, considerably low viscosities (33.876~58.117 mPa·s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

13.
Huan Jing Ke Xue ; 45(5): 2581-2595, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629523

ABSTRACT

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

14.
Front Cell Infect Microbiol ; 14: 1378379, 2024.
Article in English | MEDLINE | ID: mdl-38606295

ABSTRACT

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Pneumonia , Respiratory Distress Syndrome , Humans , Prospective Studies , Cohort Studies , Influenza, Human/complications , Quality of Life , Respiratory Distress Syndrome/diagnostic imaging , Survivors
15.
Front Biosci (Landmark Ed) ; 29(4): 141, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38682199

ABSTRACT

Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed in individuals with the severe lung disease of pulmonary fibrosis (PF). The presence of pericytes leads to inflammation and fibrosis in the lung interstitium and alveolar space due to the release of various cytokines and chemokines. Pericytes also stimulate the proliferation and activation of fibroblasts, thereby promoting the progression of PF. Previous studies examining the mechanism of action of pericytes have primarily focused on cell signal transduction pathways, cell growth and death processes, and the synthesis and breakdown of extracellular matrix (ECM). Notably, the transforming growth factor-ß (TGF-ß) and Wnt signaling pathways have been associated with the action of pericytes in driving the progression of PF. It is therefore clear that pericytes play an essential role in the development of PF, while also offering possible avenues for targeted therapeutic intervention against this condition. The current article provides a comprehensive review on how pericytes contribute to inflammatory responses, as well as their importance for understanding the mechanism of PF. In addition, this review discusses the potential use of pericyte-targeted approaches for the treatment of patients affected by this debilitating lung disease.


Subject(s)
Pericytes , Pulmonary Fibrosis , Pericytes/pathology , Pericytes/metabolism , Humans , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Animals , Transforming Growth Factor beta/metabolism , Signal Transduction , Extracellular Matrix/metabolism , Wnt Signaling Pathway
16.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167161, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38599260

ABSTRACT

The tongue epithelium is maintained by a proliferative basal layer. This layer contains long-lived stem cells (SCs), which produce progeny cells that move up to the surface as they differentiate. B-lymphoma Mo-MLV insertion region 1 (BMI1), a protein in mammalian Polycomb Repressive Complex 1 (PRC1) and a biomarker of oral squamous cell carcinoma, is expressed in almost all basal epithelial SCs of the tongue, and single, Bmi1-labelled SCs give rise to cells in all epithelial layers. We previously developed a transgenic mouse model (KrTB) containing a doxycycline- (dox) controlled, Tet-responsive element system to selectively overexpress Bmi1 in the tongue basal epithelial SCs. Here, we used this model to assess BMI1 actions in tongue epithelia. Genome-wide transcriptomics revealed increased levels of transcripts involved in the cellular response to hypoxia in Bmi1-overexpressing (KrTB+DOX) oral epithelia even though these mice were not subjected to hypoxia conditions. Ectopic Bmi1 expression in tongue epithelia increased the levels of hypoxia inducible factor-1 alpha (HIF1α) and HIF1α targets linked to metabolic reprogramming during hypoxia. We used chromatin immunoprecipitation (ChIP) to demonstrate that Bmi1 associates with the promoters of HIF1A and HIF1A-activator RELA (p65) in tongue epithelia. We also detected increased SC proliferation and oxidative stress in Bmi1-overexpressing tongue epithelia. Finally, using a human oral keratinocyte line (OKF6-TERT1R), we showed that ectopic BMI1 overexpression decreases the oxygen consumption rate while increasing the extracellular acidification rate, indicative of elevated glycolysis. Thus, our data demonstrate that high BMI1 expression drives hypoxic signaling, including metabolic reprogramming, in normal oral cavity epithelia.

17.
Cereb Cortex ; 34(3)2024 03 01.
Article in English | MEDLINE | ID: mdl-38436464

ABSTRACT

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Connectome , Humans , Female , Breast Neoplasms/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Brain/diagnostic imaging , Fear
18.
Chin J Integr Med ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38532154

ABSTRACT

As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed.

19.
Int J Oral Sci ; 16(1): 26, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548747

ABSTRACT

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-ß1 promotes abnormal glycosylation of SEMA7A via induction of epithelial-mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.


Subject(s)
Head and Neck Neoplasms , Semaphorins , Humans , Glycosylation , Squamous Cell Carcinoma of Head and Neck , CD8-Positive T-Lymphocytes/metabolism , Fucosyltransferases/metabolism , Tumor Microenvironment , RNA-Binding Proteins/metabolism , Antigens, CD/metabolism , Semaphorins/metabolism , GPI-Linked Proteins/metabolism
20.
Food Chem ; 448: 139100, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38552457

ABSTRACT

Phytosterol esters (PEs) and diacylglycerols (DAGs) have various health benefits in humans. In this study, PEs and DAGs were synthesized by lipase-catalyzed transesterification between a natural oil and phytosterols. First, commercial lipases were screened for transesterification and were further verified using multiple-ligand molecular docking. AYS "Amano" (a lipase from Candida rugosa) was found to be the optimum lipase. Subsequently, the enzymatic transesterification conditions were optimized. The optimized conditions were determined to be a 1:2 M ratio of phytosterols to oil, 100 mmol/L phytosterols, and 9 % AYS "Amano", and 50 °C for 24 h in 20 mL n-hexane. Under these conditions, over 70 % of phytosterols were converted to PEs. In this study, an efficient enzymatic process was developed to produce value-added functional oils rich in PEs and DAGs, with PEs content ≥ 31.6 %, DAGs content ≥ 11.2 %, acid value ≤ 0.91 mg KOH/g, and peroxide value ≤ 2.38 mmol/kg.

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