Correlation Between the Expression of DNA Damage Repair Protein OGG1 and Ubiquitination Pathway Protein STUB1 in Pediatric Neuroblastoma.

BACKGROUND: Neuroblastoma, a pediatric malignancy, is significantly influenced by genetic factors. Prior research indicates that the OGG1 rs1052133 G > C polymorphism correlates with a decreased risk of neuroblastoma. METHODS: We analyzed 57 neuroblastoma and 21 adrenal samples, using immunohistochemistry to measure OGG1 and STUB1 expression levels. We conducted a survival analysis to explore relationship between the expressions and neuroblastoma prognosis. RESULTS: Notably higher OGG1 expression and significantly lower STUB1 expression in neuroblastoma. OGG1 levels were significantly correlated with patient age, tumor location, histological grade, Shimada classification, INSS stage, and risk category. A negative association was observed between OGG1 and STUB1 expressions. Higher OGG1 expression was linked to reduced PFS and OS. Lower STUB1 expression was associated with unfavorable PFS. Additionally, OGG1 expression and risk category emerged as independent predictors of prognosis. CONCLUSION: OGG1 potentially functions as an oncogene in NB, with its activity possibly modulated by STUB1 through the ubiquitination pathway.

The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families.

Purpose: This study aims to evaluate the genetic and phenotypic characteristics and elucidate the genotype-phenotype correlations of a large Chinese cohort with PAX6-related disorders. Methods: Variants detected with exome sequencing were filtered through multistep bioinformatic and co-segregation analyses, and validated by Sanger sequencing. The related clinical data were collected, and cluster analysis and statistical analysis of the PAX6-related phenotypes across different variant groups were carried out. Parental mosaicism was investigated using cloning analysis and Droplet digital PCR. Results: A total of 119 pathogenic or likely pathogenic PAX6 variants, including 74 truncation, 31 missense, and 14 others, were identified in 228 patients from 164 unrelated families. The most common phenotypes were foveal hypoplasia (97.8%), nystagmus (92.6%), aniridia (76.7%), cataract (36.8%), and iris hypoplasia (22.4%). Mosaicism ranging from 13.9% to 18.8% was identified in 3 unrelated patients' parents with relatively mild phenotypes. Missense variants in the linker region of the paired domain were associated with high myopia, whereas truncation variants in the homeodomain and proline-serine-threonine-rich domain were associated with hyperopia. Similarly, the degree of iris defects, visual acuity, and associated ocular comorbidity varied among the different types and locations of PAX6 variants. Conclusions: Our data indicate that foveal hypoplasia but not aniridia is the most common sign of PAX6-related disorders, contributing to subtle iris changes that might easily be overlooked in clinical practice. Recognition of mosaicism in atypical cases or parents with very mild phenotypes is important in genetic counseling as their offspring are at increased risk of typical aniridia. Recognition of the genotype-phenotype relationship emphasizes involvement of PAX6 regulation in shaping complex ocular phenotypes.

Development of a Methodology Based on Optical Interferometry for Measuring Fibrinolytic Activity.

Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12-6000 and 10-2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.

Origins of Severe Structural Changes during Alloying-Dealloying Reactions in Black Phosphorus.

Li-alloying reactions facilitate the incorporation of a large number of Li atoms into the crystalline structures of electrodes, such as black phosphorus (BP). However, the reactions inevitably induce multistep phase transitions characterized by drastic atomic rearrangements and lattice collapse. Despite many theoretical and experimental studies on alloying mechanisms, long-term debates persist regarding the structures of the intermediate phases, the accurate pathways of phase transitions, the formation of specific configurations, and alloying/dealloying reversibility. Here, through a combination of operando electron diffraction measurements and ab initio simulations at the atomic and electronic scales, we identify key factors that govern the severe structural changes during alloying-dealloying reactions in BP. P-P bonds of three-bond P atoms are continuously broken during lithiation, generating two-bond P atoms with a high ability to accept inserted electrons and Li ions. Consequently, the pristine layered structure in BP is transformed to P7 cages in Li3P7, which then evolve to chain configurations in LiP and finally to isolated P atoms in Li3P. Specifically, the preferential formation of the P7 cage results from its lowest binding energy with three Li ions compared to other cage isomers. Furthermore, only LiP can be reversibly transformed to the crystalline structure of Li3P7 during charge, but it is thermodynamically favorable for Li3P7 and Li3P intermediates to be delithiated to amorphous structures. Our findings offer unique insights into the alloying mechanisms and deepen the fundamental understanding of alloying anode systems.

Plastome Evolution, Phylogenomics, and DNA Barcoding Investigation of Gastrochilus (Aeridinae, Orchidaceae), with a Focus on the Systematic Position of Haraella retrocalla.

Gastrochilus is an orchid genus containing about 70 species in tropical and subtropical Asia with high morphological diversity. The phylogenetic relationships among this genus have not been fully resolved, and the plastome evolution has not been investigated either. In this study, five plastomes of Gastrochilus were newly reported, and sixteen plastomes of Gastrochilus were used to conduct comparative and phylogenetic analyses. Our results showed that the Gastrochilus plastomes ranged from 146,183 to 148,666 bp, with a GC content of 36.7-36.9%. There were 120 genes annotated, consisting of 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. No contraction and expansion of IR borders, gene rearrangements, or inversions were detected. Additionally, the repeat sequences and codon usage bias of Gastrochilus plastomes were highly conserved. Twenty hypervariable regions were selected as potential DNA barcodes. The phylogenetic relationships within Gastrochilus were well resolved based on the whole plastome, especially among main clades. Furthermore, both molecular and morphological data strongly supported Haraella retrocalla as a member of Gastrochilus (G. retrocallus).

Flavopereirine exerts anti-cancer activities in various human thyroid cancer cells.

Thyroid cancer (TC) stands out as the most prevalent endocrine malignancy globally, with a steadily increasing incidence. Its clinical manifestations include enlarged thyroid nodules, dysphagia, enophthalmos, and various other symptoms. While standard treatments such as thyroidectomy and radioiodine therapy effectively manage most cases of differentiated thyroid cancers (DTC), some recurrent cases of DTC or those involving poorly differentiated thyroid cancers (PDTC) require specialized interventions. However, existing drugs primarily address symptom management without offering a curative solution. Therefore, the development of a new therapeutic agent for these challenging cases is of utmost importance. Flavopereirine, derived from Geissospermum vellosii, has demonstrated promise as a potential anti-cancer agent across various human cancers. However, its specific anti-cancer effects on human thyroid cancer (TC) have remained unclear. Therefore, this study aims to investigate the anti-cancer activity of flavopereirine in human TC. The research findings revealed that flavopereirine effectively hinders the growth of human TC cells, induces cell cycle arrest, promotes apoptosis, and modulates autophagy. Moreover, the study delved into the underlying mechanisms by which flavopereirine influenced signaling pathways. To validate these anti-cancer effects, an in vivo zebrafish model was utilized, confirming the efficacy of flavopereirine against human TC cells. In summary, this study establishes that flavopereirine exhibits notable anti-human TC activities, positioning it as a promising therapeutic candidate for the treatment of human thyroid cancer.

Phosphatidylethanolamines link ferroptosis and autophagy during appressorium formation of rice blast fungus.

A cell death pathway, ferroptosis, occurs in conidial cells and is critical for formation and function of the infection structure, the appressorium, in the rice blast fungus Magnaporthe oryzae. In this study, we identified an orthologous lysophosphatidic acid acyltransferase (Lpaat) acting at upstream of phosphatidylethanolamines (PEs) biosynthesis and which is required for such fungal ferroptosis and pathogenicity. Two PE species, DOPE and SLPE, that depend on Lpaat function for production were sufficient for induction of lipid peroxidation and the consequent ferroptosis, thus positively regulating fungal pathogenicity. On the other hand, both DOPE and SLPE positively regulated autophagy. Loss of the LPAAT gene led to a decrease in the lipidated form of the autophagy protein Atg8, which is probably responsible for the autophagy defect of the lpaatΔ mutant. GFP-Lpaat was mostly localized on the membrane of lipid droplets (LDs) that were stained by the fluorescent dye monodansylpentane (MDH), suggesting that LDs serve as a source of lipids for membrane PE biosynthesis and probably as a membrane source of autophagosome. Overall, our results reveal novel intracellular membrane-bound organelle dynamics based on Lpaat-mediated lipid metabolism, providing a temporal and spatial link of ferroptosis and autophagy.

[Expressions of zinc homeostasis proteins, GPR39 and ANO1 mRNA in the sperm of asthenozoospermia patients and their clinical significance].

OBJECTIVE: To explore the expressions of zinc homeostasis-related proteins, G protein-coupled receptor 39 (GPR39) and ANO1 mRNA in the sperm of patients with asthenozoospermia (AS), and analyze their correlation with sperm motility. METHODS: We collected semen samples from 82 male subjects with PR+NP < 40%, PR < 32% and sperm concentration > 15×106/ml (the AS group, n = 40) or PR+NP ≥ 40%, PR ≥ 32% and sperm concentration > 15×106/ml (the normal control group, n = 42). We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system, detected the expressions of zinc transporters (ZIP13, ZIP8 and ZNT10), metallothioneins (MT1G, MT1 and MTF), GPR39, and calcium-dependent chloride channel protein (ANO1) in the sperm by real-time quantitative PCR (RT qPCR), examined free zinc distribution in the sperm by laser confocal microscopy, and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining, followed by Spearman rank correlation analysis of their correlation with semen parameters. RESULTS: There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups (P>0.05). Compared with the controls, the AS patients showed a significantly reduced free zinc level (P<0.05), relative expressions of MT1G, MTF, ZIP13, GPR39 and ANO1 mRNA (P<0.05), and that of the GPR39 protein in the AS group (P<0.05). No statistically significant differences were observed in the relative expression levels of ZIP8, ZNT10 and MT1 mRNA between the two groups (P>0.05). The relative expression levels of GPR39, ANO1, MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm (P<0.05). CONCLUSION: The expressions of zinc homeostasis proteins (MT1G, MTF and ZIP13), GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia patients, and positively correlated with sperm motility.

Use of a mobile application to monitor drain sites and surgical wounds after discharge from acute care - A feasibility study in Singapore.

PURPOSE: This study aimed to demonstrate the compliance, feasibility, and acceptability of telehealth monitoring among surgical patients discharged with wounds or drains. METHODOLOGY: This is a cross-sectional feasibility study. Post-surgical breast, plastic, and hepatobiliary patients with wounds and/or surgical drains were recruited using convenience sampling. The control group received conventional care which consisted of daily telephone follow-up. The intervention group used a mobile wound application to take wound and drain images, report drainage amount and symptoms. Compliance was assessed by measuring the percentage of actual to expected patient entries, feasibility was assessed by comparing detection of abnormalities and unexpected hospital visits, and acceptability was assessed by subjective feedback from nurses and patients from the intervention group. RESULTS: 59 patients were recruited, with 30 patients in the control group and 29 patients in the intervention group. 9 specialty nurses were involved in the patients' post-discharge care. The mean compliance rate for the hepatobiliary, breast and plastic patients were 89.9 %, 89.5 % and 75.9 % respectively. 4 patients from the intervention group (13.8 %) and 6 patients from the control group (20.1 %) were flagged as having potential abnormalities. As for unexpected hospital visits, there were 2 (6.9 %) in the intervention group and 1 (3.4 %) in the control group. 25 patients and 9 specialty nurses responded to the feedback survey. 22 patients (88 %) did not face any application issues. 18 patients (72 %) preferred to self-report symptoms via the application rather than to call the nurses and reported feeling safe knowing that they are remotely monitored. Most nurses found the app convenient and timesaving (n = 7, 78 %), with monitoring through pictures as more accurate than phone conversation (n = 8, 89 %). CONCLUSION: The results suggest that use of a mobile application by surgical patients discharged with wounds or drains is feasible and serves as a viable monitoring tool.

Effect of Implementing an Informatization Case Management Model on the Management of Chronic Respiratory Diseases in a General Hospital: Retrospective Controlled Study.

Background: The use of chronic disease information systems in hospitals and communities plays a significant role in disease prevention, control, and monitoring. However, there are several limitations to these systems, including that the platforms are generally isolated, the patient health information and medical resources are not effectively integrated, and the "Internet Plus Healthcare" technology model is not implemented throughout the patient consultation process. Objective: The aim of this study was to evaluate the efficiency of the application of a hospital case management information system in a general hospital in the context of chronic respiratory diseases as a model case. Methods: A chronic disease management information system was developed for use in general hospitals based on internet technology, a chronic disease case management model, and an overall quality management model. Using this system, the case managers provided sophisticated inpatient, outpatient, and home medical services for patients with chronic respiratory diseases. Chronic respiratory disease case management quality indicators (number of managed cases, number of patients accepting routine follow-up services, follow-up visit rate, pulmonary function test rate, admission rate for acute exacerbations, chronic respiratory diseases knowledge awareness rate, and patient satisfaction) were evaluated before (2019-2020) and after (2021-2022) implementation of the chronic disease management information system. Results: Before implementation of the chronic disease management information system, 1808 cases were managed in the general hospital, and an average of 603 (SD 137) people were provided with routine follow-up services. After use of the information system, 5868 cases were managed and 2056 (SD 211) patients were routinely followed-up, representing a significant increase of 3.2 and 3.4 times the respective values before use (U=342.779; P<.001). With respect to the quality of case management, compared to the indicators measured before use, the achievement rate of follow-up examination increased by 50.2%, the achievement rate of the pulmonary function test increased by 26.2%, the awareness rate of chronic respiratory disease knowledge increased by 20.1%, the retention rate increased by 16.3%, and the patient satisfaction rate increased by 9.6% (all P<.001), while the admission rate of acute exacerbation decreased by 42.4% (P<.001) after use of the chronic disease management information system. Conclusions: Use of a chronic disease management information system improves the quality of chronic respiratory disease case management and reduces the admission rate of patients owing to acute exacerbations of their diseases.

Effects of virtual distant viewing technology on preventing nearwork-induced ocular parameter changes.

Purpose: This study investigates whether virtual distant viewing technology can prevent nearwork-induced ocular parameter changes. Methods: Twenty-six volunteers read a textbook on one day and the same content on a virtual distant viewing display on another day based on a randomization sequence, with both reading sessions at 33 cm for 4 hours. Visual acuity, diopter, ocular biology, visual fatigue, and accommodative function before and after the nearwork, as well as the number of pages read, were recorded. Results: After 4 hours of nearwork in the textbook group, the spherical equivalent refraction decreased from -3.13 ± 2.65 D to -3.32 ± 2.70 D (P < 0.001), corneal thickness decreased from 531.6 ± 33.5 µm to 528.9 ± 33.0 µm (P = 0.015), anterior chamber depth decreased from 3.65 ± 0.35 mm to 3.60 ± 0.30 mm (P = 0.002), accommodative facility increased from 15.1 ± 3.5 to 16.4 ± 3.9 (P = 0.018), and subjective visual fatigue increased from 14.0 ± 9.2 to 19.3 ± 7.6 (P = 0.002); no significant changes were seen in the other parameters. In the virtual distant viewing group, the spherical equivalent refraction (from -3.17 ± 2.60 D to -3.11 ± 2.73 D, P = 0.427), corneal thickness (from 531.9 ± 32.8 µm to 529.7 ± 33.2 µm, P = 0.054), and anterior chamber depth (from 3.67 ± 0.35 mm to 3.69 ± 0.32 mm, P = 0.331) did not show significant changes, whereas accommodative facility increased from 14.7 ± 5.8 to 15.9 ± 5.5 (P = 0.042) and subjective visual fatigue increased from 13.5 ± 8.4 to 18.9 ± 8.6 (P = 0.002). In addition, choroidal thickness (from 217.7 ± 76.0 µm to 243.0 ± 85.0 µm, P = 0.043), positive relative accommodation (from -2.32 ± 1.07 D to -2.85 ± 0.89 D, P = 0.007), and amplitude of accommodation (from 7.26 ± 1.41 D to 7.89 ± 1.69 D, P = 0.022) also significantly increased in the virtual distant viewing group. The textbook group and the virtual distant viewing group read 176.0 ± 133.1 pages and 188.0 ± 102.0 pages, respectively, and there was no significant difference between the two groups (P = 0.708). Conclusion: Virtual distant viewing technology can prevent the increase in myopia degree due to nearwork and improve accommodation function without increasing visual fatigue.

The Microbiome Protocols eBook initiative: Building a bridge to microbiome research.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

Construction and regulation of high active sites in montmorillonite composite catalyst for the removal of ofloxacin via persulfate activation.

In this study, ionic liquids (ILs) were used as organic modifiers by introducing montmorillonite nanolayers containing potential C and N active sites between the montmorillonite nanolayers. Organically modified montmorillonite (ILs-Mt-p) was further prepared by high-temperature pyrolysis under N2 and used for the removal of ofloxacin (OFL) by activated peroxymonosulfate (PMS). Combined with XPS and other characterization analyses, it was found that the catalyst materials prepared from different organic modifiers had similar surface functional groups and graphitized structures, but contained differences in the types and numbers of C and N active sites. The catalyst (3CPC-Mt-p) obtained after pyrolysis of montmorillonite modified with cetylpyridinium chloride (CPC) had optimal catalytic performance, in which graphitic C, graphitic N, and carbonyl group (C[bond, double bond]O) could synergistically promote the activation of PMS by electron transfer, and 77.3 % of OFL could be removed within 60 min. The effects of OFL concentration, initial pH, and anions on the effects of OFL removal by the 3CPC-Mt-p/PMS system were further investigated. Satisfactory degradation results were obtained over a wide pH range. Cl- promoted the system to degrade OFL, while the presence of SO42-, H2PO4- and HA showed some inhibition, but overall the 3CPC-Mt-p catalysts had a strong anti-interference ability, showing good application prospects. The quenching experiments and EPR tests showed that O2-- and 1O2 in the 3CPC-Mt-p/PMS system were the main reactive oxygen species for the degradation of OFL, and •OH was also involved in the reaction. This study provides ideas for the construction and modulation of active sites in mineral materials such as montmorillonite and broadens the application of montmorillonite composite catalysts in advanced oxidation processes for the treatment of antibiotic wastewater.

Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function.

Individuals with clonal hematopoiesis of indeterminate potential (CHIP) are at increased risk of aging related health conditions and all-cause mortality, but whether CHIP affects risk of infection is much less clear. Using UK Biobank data, we revealed a positive association between CHIP and incident pneumonia in 438,421 individuals. We show that inflammation enhanced pneumonia risk, as CHIP carriers with a hypomorphic IL6 receptor polymorphism were protected. To better characterize the pathways of susceptibility, we challenged hematopoietic Tet Methylcytosine Dioxygenase 2-knockout (Tet2-/-) and floxed control mice (Tet2fl/fl) with Streptococcus pneumoniae. As with human CHIP carriers, Tet2-/- mice had hematopoietic abnormalities resulting in the expansion of inflammatory monocytes and neutrophils in peripheral blood. Yet, these cells were insufficient in defending against S. pneumoniae and resulted in increased pathology, impaired bacterial clearance, and higher mortality in Tet2-/- mice. We delineated the transcriptional landscape of Tet2-/- neutrophils and found that, while inflammation-related pathways were upregulated in Tet2-/- neutrophils, migration and motility pathways were compromised. Using live-imaging techniques, we demonstrated impairments in motility, pathogen uptake, and neutrophil extracellular trap (NET) formation by Tet2-/- neutrophils. Collectively, we show that CHIP is a risk factor for bacterial pneumonia related to innate immune impairments.

Optimizing antigen selection for the development of tuberculosis vaccines.

Tuberculosis (TB) remains a prevalent global infectious disease caused by genetically closely related tubercle bacilli in Mycobacterium tuberculosis complex (MTBC). For a century, the Bacillus Calmette-Guérin (BCG) vaccine has been the primary preventive measure against TB. While it effectively protects against extrapulmonary forms of pediatric TB, it lacks consistent efficacy in providing protection against pulmonary TB in adults. Consequently, the exploration and development of novel TB vaccines, capable of providing broad protection to populations, have consistently constituted a prominent area of interest in medical research. This article presents a concise overview of the novel TB vaccines currently undergoing clinical trials, discussing their classification, protective efficacy, immunogenicity, advantages, and limitations. In vaccine development, the careful selection of antigens that can induce strong and diverse specific immune responses is essential. Therefore, we have summarized the molecular characteristics, biological function, immunogenicity, and relevant studies associated with the chosen antigens for TB vaccines. These insights gained from vaccines and immunogenic proteins will inform the development of novel mycobacterial vaccines, particularly mRNA vaccines, for effective TB control.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.