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1.
Int J Biol Macromol ; : 132566, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38795883

ABSTRACT

Nowadays, the development of sustainable molecularly imprinted polymers (MIPs) with high selectivity is still challenging due to the limitations of bio-based functional monomers. In this study, the highly selective and porous MIPs (LC-TMIPs) were designed and prepared on short amylose (SAM) as bio-based functional monomers, λ-cyhalothrin (LC) as a template molecule, and tetrafluoroterephthalonitrile as a rigid crosslinking agent. Static, dynamic, and selective adsorption experiments were conducted to investigate the adsorption performance. The results indicated that, compared to MIPs prepared using epichlorohydrin as flexible crosslinking agents, LC-TMIPs exhibited higher imprinting factor (3.93), selectivity (5.78), and adsorption capacity (35.79 mg g-1), as well as faster adsorption/desorption kinetics. The LC-TMIPs were used as sorbents for the selective determination of LC in both apple and cucumber samples by high-performance liquid chromatography. Under the optimal extraction conditions, the recoveries of the method reached 92.1-106.1 %, with a linear range of 1.5-30 ng g-1 and a detection limit of 0.5 ng g-1. The proposed preparation method of LC-TMIPs is expected to open a new way to prepare highly selective and sustainable MIPs for hydrophobic compounds.

2.
Front Immunol ; 15: 1380720, 2024.
Article in English | MEDLINE | ID: mdl-38694502

ABSTRACT

Background: Infection with Treponema pallidum instigates complex immune responses. Prior research has suggested that persistent Treponema pallidum infection can manipulate host immune responses and circumvent host defenses. However, the precise role of immune cells in Treponema pallidum infection across different stages remains a contentious issue. Methods: Utilizing summary data from genome-wide association studies, we employed a two-sample Mendelian randomization method to investigate the association between 731 immunophenotypes and syphilis. Syphilis was categorized into early and late stages in this study to establish a more robust correlation and minimize bias in database sources. Results: Our findings revealed that 33, 36, and 27 immunophenotypes of peripheral blood were associated with syphilis (regardless of disease stage), early syphilis and late syphilis, respectively. Subsequent analysis demonstrated significant variations between early and late syphilis in terms of immunophenotypes. Specifically, early syphilis showcased activated, secreting, and resting regulatory T cells, whereas late syphilis was characterized by resting Treg cells. More B cells subtypes emerged in late syphilis. Monocytes in early syphilis exhibited an intermediate and non-classical phenotype, transitioning to classical in late syphilis. Early syphilis featured naive T cells, effector memory T cells, and terminally differentiated T cells, while late syphilis predominantly presented terminally differentiated T cells. Immature myeloid-derived suppressor cells were evident in early syphilis, whereas the dendritic cell immunophenotype was exclusive to late syphilis. Conclusion: Multiple immunophenotypes demonstrated associations with syphilis, showcasing substantial disparities between the early and late stages of the disease. These findings hold promise for informing immunologically oriented treatment strategies, paving the way for more effective and efficient syphilis interventions.


Subject(s)
Immunophenotyping , Mendelian Randomization Analysis , Syphilis , Humans , Syphilis/immunology , Syphilis/genetics , Treponema pallidum/immunology , Treponema pallidum/genetics , Genome-Wide Association Study , Polymorphism, Single Nucleotide , T-Lymphocytes, Regulatory/immunology
3.
Cryobiology ; 115: 104902, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38734365

ABSTRACT

In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10-9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.

4.
Clin Transl Sci ; 17(5): e13819, 2024 May.
Article in English | MEDLINE | ID: mdl-38747478

ABSTRACT

The equivalence of absorption rates and extents between generic drugs and their reference formulations is crucial for ensuring therapeutic comparability. Bioequivalence (BE) studies are widely utilized and play a pivotal role in substantiating the approval and promotional efforts for generic drugs. Virtual BE simulation is a valuable tool for mitigating risks and guiding clinical BE studies, thereby minimizing redundant in vivo BE assessments. Herein, we successfully developed a physiologically based absorption model for virtual BE simulations, which precisely predicts the BE of the apixaban test and reference formulations. The modeling results confirm that the test and reference formulations were bioequivalent under both fasted and fed conditions, consistent with clinical studies. This highlights the efficacy of physiologically based absorption modeling as a powerful tool for formulation screening and can be adopted as a methodological and risk assessment strategy to detect potential clinical BE risks.


Subject(s)
Models, Biological , Pyrazoles , Pyridones , Therapeutic Equivalency , Pyridones/pharmacokinetics , Pyridones/administration & dosage , Pyrazoles/pharmacokinetics , Pyrazoles/administration & dosage , Humans , Factor Xa Inhibitors/pharmacokinetics , Factor Xa Inhibitors/administration & dosage , Drugs, Generic/pharmacokinetics , Drugs, Generic/administration & dosage , Computer Simulation , Administration, Oral , Male
5.
Heliyon ; 10(7): e29027, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596103

ABSTRACT

Objective: To examine the correlation of neutrophil CD64 (nCD64) index with neurosyphilis (NS) across different stages of syphilis. Methods: A total of 1243 syphilis patients at different stages (344 of primary, 385 of secondary, and 514 of tertiary) included in this study were divided into NS and non-NS (NNS). Correlations of nCD64 index with currently used syphilis biomarkers were explored using Spearman correlation test. Relationships between nCD64 index and NS at different stages were investigated by stratified analysis and restricted cubic spline model. The diagnostic performance of nCD64 index for NS was assessed by receiver operating characteristic (ROC) curve. Results: Significant statistical correlations of nCD64 index with cerebrospinal fluid (CSF) NS indicators were found in secondary and tertiary syphilis. Increased nCD64 index was associated with increased risk of NS in secondary and tertiary syphilis. ROC analysis values further confirmed the diagnostic potential of nCD64 index for NS. Marked decrease of nCD64 index was observed in NS patients after effective antisyphilitic treatments. Conclusions: The nCD64 index may help to the diagnosis of NS in secondary and tertiary syphilis.

6.
Article in English | MEDLINE | ID: mdl-38641235

ABSTRACT

BACKGROUND: It is widely acknowledged that mild traumatic brain injury (MTBI) leads to either functionally or anatomically abnormal brain regions. Structural covariance networks (SCNs) that depict coordinated regional maturation patterns are commonly employed for investigating brain structural abnormalities. However, the dynamic nature of SCNs in individuals with MTBI who suffer from posttraumatic headache (PTH) and their potential as biomarkers have hitherto not been investigated. METHODS: This study included 36 MTBI patients with PTH and 34 well-matched healthy controls (HCs). All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Structural covariance matrices of cortical thickness were generated for each group, and global as well as nodal network measures of SCNs were computed. RESULTS: MTBI patients with PTH demonstrated reduced headache impact and improved cognitive function from the acute to subacute phase. In terms of global network metrics, MTBI patients exhibited an abnormal normalized clustering coefficient compared to HCs during the acute phase, although no significant difference in the normalized clustering coefficient was observed between the groups during the subacute phase. Regarding nodal network metrics, MTBI patients displayed alterations in various brain regions from the acute to subacute phase, primarily concentrated in the prefrontal cortex (PFC). CONCLUSIONS: These findings indicate that the cortical thickness topography in the PFC determines the typical structural-covariance topology of the brain and may serve as an important biomarker for MTBI patients with PTH.

7.
Bioresour Bioprocess ; 11(1): 22, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38647993

ABSTRACT

Amyloid fibrils derived from different proteins have been proved as a promising material for adsorption of various pollutants from wastewater, which showed advantages of low cost and eco-friendliness. However, most of the amyloid fibrils derived from animal-based proteins with high environmental footprint, while more sustainable amyloid fibrils derived from plant materials are desirable. In this study, a plant-derived amyloid fibril was extracted from the commonly used wheat flour with a simple and scalable protein purification and fibrillization process. Interestingly, the amyloid fibrils showed good adsorption capacity towards typical organic dyes (Eosin Y (EY) and Congo red (CR)) from contaminated water. Adsorption kinetic analysis indicated the adsorption process to EY or CR by wheat flour amyloid well fitted with a pseudo-second-order model. The adsorption also followed a Langmuir isothermal model with adsorption capacities of 333 mg/g and 138 mg/g towards CR and EY, respectively. This work demonstrated the feasibility to utilize the plant-based amyloid fibril for organic dyes removal from contaminated water, which provided an affordable, sustainable and scalable tool for organic dyes removal from wastewater.

8.
Open Life Sci ; 19(1): 20220821, 2024.
Article in English | MEDLINE | ID: mdl-38585636

ABSTRACT

Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

9.
Clin Transl Sci ; 17(4): e13787, 2024 04.
Article in English | MEDLINE | ID: mdl-38558535

ABSTRACT

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.


Subject(s)
Anticoagulants , Blood Coagulation , Adult , Humans , Partial Thromboplastin Time , Healthy Volunteers , China , Double-Blind Method , Dose-Response Relationship, Drug
10.
Adv Mater ; : e2313219, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597361

ABSTRACT

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

11.
Opt Express ; 32(7): 12172-12180, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571048

ABSTRACT

A narrow-linewidth and low relative intensity noise (RIN) Tm/Ho co-doped fiber laser based on a saturable absorber and self-injection locking was demonstrated for the first time. Utilizing self-injection locking technology, the frequency noise power spectral density is remarkably reduced by more than 17.1 dB from 1.21 × 106 Hz2/Hz to 7.30 × 103 Hz2/Hz when the frequency is approximately 1 kHz. Furthermore, a laser with a linewidth compressed to a quarter of the original linewidth from 44.386 kHz to 2.850 kHz, a RIN of less than -127.74 dB/Hz, and an optical signal-to-noise ratio of more than 71.6 dB can be obtained. Using a delay fiber, the relaxation oscillation peak frequencies move to lower frequencies, from 27.9 kHz to 15.8 kHz. The proposed laser is highly competitive in advanced coherent light detection fields, including coherent Doppler wind lidar, high-speed coherent optical communication, and precise absolute distance coherent measurement.

12.
Opt Express ; 32(6): 10408-10418, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571253

ABSTRACT

In recent years, with the development of information networks, higher requirements for transmission capacity have been recommended. Yet, at the same time, the capacity of single-mode fiber is rapidly approaching the theoretical limit. The multidimensional multiplexing technique is an effective way to solve this problem. Since the high differential mode delay (DMD) of transmission fiber increases the complexity of demultiplexing in equalization algorithms, we use an intelligent design method to optimize the trench-assisted gradient refractive index structure in this paper. The maximum DMD of the optimized optical fiber structure is 19.6 ps/km. A least mean squares-feedforward neural network constant modulus algorithm (LMS-FNNCMA) is also designed by using the theory of the least mean squares (LMS), constant modulus algorithm (CMA), and the multiple input multiple output (MIMO) neural networks. In order to verify the accuracy of the algorithm, a polarization division multiplexing-wavelength division multiplexing-mode division multiplexing (PDM-WDM-MDM) optical transmission system is constructed through simulation. The algorithm successfully realizes the de-crosstalk over a transmission distance of 1200 km at a rate of 1.2 Tbps under simulation conditions.

13.
Front Public Health ; 12: 1282575, 2024.
Article in English | MEDLINE | ID: mdl-38450135

ABSTRACT

Objective: This study aimed to evaluate the spatiotemporal distribution of patients with hepatitis C virus (HCV) and the factors influencing this distribution in Jiangsu Province, China, from 2011 to 2020. Methods: The incidence of reported HCV in Jiangsu Province from 2011 to 2020 was obtained from the Chinese Information System for Disease Control and Prevention (CISDCP). R and GeoDa software were used to visualize the spatiotemporal distribution and the spatial autocorrelation of HCV. A Bayesian spatiotemporal model was constructed to explore the spatiotemporal distribution of HCV in Jiangsu Province and to further analyze the factors related to HCV. Results: A total of 31,778 HCV patients were registered in Jiangsu Province. The registered incidence rate of HCV increased from 2.60/100,000 people in 2011 to 4.96/100,000 people in 2020, an increase of 190.77%. Moran's I ranged from 0.099 to 0.354 (P < 0.05) from 2011 to 2019, indicating a positive spatial correlation overall. The relative risk (RR) of the urbanization rate, the most important factor affecting the spread of HCV in Jiangsu Province, was 1.254 (95% confidence interval: 1.141-1.376), while other factors had no significance. Conclusion: The reported HCV incidence rate integrally increased in the whole Jiangsu Province, whereas the spatial aggregation of HCV incidence was gradually weakening. Our study highlighted the importance of health education for the floating population and reasonable allocation of medical resources in the future health work.


Subject(s)
Hepacivirus , Hepatitis C , Humans , Bayes Theorem , Hepatitis C/epidemiology , China/epidemiology , Spatio-Temporal Analysis
15.
Gynecol Oncol ; 185: 148-155, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38422947

ABSTRACT

OBJECTIVE: To evaluate the effects of DEAR weight management in overweight patients undergoing fertility-sparing treatment for endometrial cancer or atypical hyperplasia. METHODS: Women with endometrial cancer or atypical hyperplasia who received fertility-sparing treatment and had a body mass index of >25 kg/m2 were randomly allocated to the DEAR (DEAR weight management) and control (self weight management) groups. Body morphology and composition, glycolipid metabolism, and tumor outcomes were assessed in both groups before and at 3 and 6 months after intervention. RESULTS: Overall, 72 subjects were included (36 in each group). Following intervention, the DEAR group showed significantly lower median body weight (69.45 vs. 78.05), body mass index (26.19 vs. 29.15), lipid accumulation index (29.21 vs. 57.86), body fat mass (24.00 vs. 29.30), visceral fat area (112.5 vs. 133.3), and glycolipid metabolic indices (except high density lipoprotein) than the control group (P < 0.05) and showed a decreasing trend. The test group achieved significantly higher complete remission (88.46% vs. 57.14%; P < 0.05); the time to complete remission did not differ significantly (P > 0.05). CONCLUSIONS: DEAR weight management can improve the studied parameters and complete remission rates in this population. REGISTRATION: NCT06169449.

16.
BMC Cancer ; 24(1): 245, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38388357

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a high-risk malignant tumor that has been reported in China. Some studies indicate that gut microbiota disorders can affect the occurrence and development of ESCC, but the underlying mechanism remains unclear. In this study, we aimed to explore the possible underlying mechanisms using microbiomics and metabolomics. Fifty ESCC patients and fifty healthy controls were selected as the study subjects according to sex and age, and fecal samples were collected. 16S rDNA sequencing and LC‒MS were used for microbiomics and nontargeted metabolomics analyses. We found significant differences in the composition of the gut microbiota and metabolites between the ESCC patients and control individuals (P < 0.05). ESCC patients exhibited increased abundances of Fusobacteriaceae and Lactobacillus, increased levels of GibberellinA34 and decreased levels of 12-hydroxydodecanoic acid; these metabolites could be diagnostic and predictive markers of ESCC. An increase in the abundance of Enterobacteriaceae and Lactobacillus significantly reduced the content of L-aspartate and pantothenic acid, which may be involved in the occurrence and development of ESCC by downregulating the expression of proteins in the pantothenate and coenzyme A biosynthesis pathways. An imbalance in the intestinal flora may decrease the number of eosinophils in peripheral blood, resulting in the activation of an inflammatory response and immune dysfunction, leading to ESCC deterioration. We hypothesize that this imbalance in the gut microbiota can cause an imbalance in intestinal metabolites, which can activate carcinogenic metabolic pathways, affect inflammation and immune function, and play a role in the occurrence and development of ESCC.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gastrointestinal Microbiome , Humans , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Metabolomics/methods
17.
J Clin Lab Anal ; 38(4): e25012, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38305509

ABSTRACT

BACKGROUND: RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. METHODS: The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro. RESULTS: We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. CONCLUSIONS: Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.


Subject(s)
Uterine Cervical Neoplasms , Humans , Mice , Female , Animals , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Mice, Nude , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Carcinogenesis , Cell Line, Tumor , Cell Proliferation/genetics , Receptors for Activated C Kinase/genetics , Receptors for Activated C Kinase/pharmacology
18.
Article in English | MEDLINE | ID: mdl-38299399

ABSTRACT

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. OBJECTIVE: To explore the role of palmitoyl protein thioesterase 1 (PPT1) in OSCC. METHODS: Differentially Expressed Genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments, including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate the gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. RESULTS: A total of 555 DEGs were obtained, and topological analysis revealed that the PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibiting the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). CONCLUSION: PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.

19.
Adv Sci (Weinh) ; 11(14): e2305979, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38308189

ABSTRACT

Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.


Subject(s)
Interferon Type I , Neoplasms , Humans , Manganese , Hydrogen Peroxide , Signal Transduction , Neoplasms/drug therapy , Immunity , Tumor Microenvironment
20.
Kidney Blood Press Res ; 49(1): 246-257, 2024.
Article in English | MEDLINE | ID: mdl-38382485

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgA nephropathy. METHODS: The study included 718 adult IgAN patients diagnosed based on kidney biopsy. Patients without corticosteroids or immunosuppressive drugs >1 month were regularly followed up for at least 1 year or until the study endpoint. The optimum serum IgA/C3 ratio was calculated by the AUROC-based cutoff ratio. Proteinuria, creatinine, eGFR, serum IgA, and serum C3 were evaluated at baseline. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The degree of glomerular C3 staining was semiquantitatively determined (grade 0, no or trace; grade 1, mild; grade 2, moderate; grade 3, marked) by immunofluorescence microscopy. The patients were divided into four groups by the serum IgA/C3 ratio and glomerular C3 staining. RESULTS: The baseline data suggested that when the serum IgA/C3 ratio was at the same level, patients with a high glomerular C3 staining score (≥2) always had mesangial proliferation, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis (group 1 vs. group 2; group 3 vs. group 4). When glomerular C3 staining was at the same level, proteinuria was significantly higher in patients with serum IgA/C3<2.806 (group 1 vs. group 3; group 2 vs. group 4), which was contrary to previous studies that have suggested that the serum level of IgA/C3 was associated with disease severity. Hence, this study set out to investigate the combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Renal survival analysis indicated that serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients based on the subgroup analysis. Multivariate Cox analysis demonstrated that hypertension, serum creatinine, CKD stage, T1/2 and C3 staining were independent predictive factors of renal survival. CONCLUSIONS: The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease. However, further study is required for validation in the future.


Subject(s)
Complement C3 , Glomerulonephritis, IGA , Immunoglobulin A , Kidney Glomerulus , Humans , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/diagnosis , Complement C3/analysis , Complement C3/metabolism , Adult , Male , Female , Immunoglobulin A/blood , Middle Aged , Kidney Glomerulus/pathology , Prognosis
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