Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). ...In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p<0.001). The expression level of caspase-8 in tumors was elevated in patients with lymph node invasion. Moreover, positive expression of cleaved caspase-3 was associated with shorter disease-free survival (DFS) in OTSCC patients with moderate differentiation and lymph node invasion. Combination of either positive cleaved caspase-3 or higher caspase-3 expression or both was associated with poor DFS. Interestingly, stratification analysis showed that co-expression levels of positive cleaved caspase-3 or/and higher caspase-3 were associated with better disease-specific survival in patients with advanced stages of the disease, such as large tumor size and lymph node invasion, whereas it was associated with poor DFS in OTSCC patients with moderate cell differentiation and small tumor size. Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status.
Triple-negative breast cancer (TNBC), which lacks estrogen receptor α (ERα), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression, is closely related to basal-like ...breast cancer. Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). Here, we show that transgenic expression of phospho-mimicking EZH2 mutant EZH2
in mammary glands leads to tumors with TNBC phenotype. Coexpression of EZH2
in mammary epithelia of HER2/Neu transgenic mice reprograms HER2-driven luminal tumors into basal-like tumors. Pharmacological inhibition of CDK2 or EZH2 allows re-expression of ERα and converts TNBC to luminal ERα-positive, rendering TNBC cells targetable by tamoxifen. Furthermore, the combination of either CDK2 or EZH2 inhibitor with tamoxifen effectively suppresses tumor growth and markedly improves the survival of the mice bearing TNBC tumors, suggesting that the mechanism-based combination therapy may be an alternative approach to treat TNBC.
Ultraviolet (UV) radiation from sunlight has various adverse effects; thus, UV blockage is recommended for preventing sunburn. Common sunscreen ingredients, such as nanosized titanium dioxide and ...zinc oxide, offer effective protection and enhance cosmetic appearance; however, health concerns have been raised regarding their photocatalytic activity, which generates reactive oxygen species under UV illumination. Silver nanoparticles (AgNPs) are known as safe materials for use in a wide spectrum of biomedical applications. In vitro studies have revealed that AgNPs may have a protective effect against UV irradiation, but the effects in animal studies remain unclear. The present study demonstrated that AgNPs effectively protect against UVB-induced skin damage both in cell cultures and mouse models. These results suggested that AgNPs are feasible and safe as sunscreen ingredients for protection against UVB-induced skin damage.
We report a strategy for stereoselective O‐aryl‐glycoside synthesis by copper‐catalyzed cross‐coupling of a variety of anomeric sugars and (hetero)aromatic iodides. Stereocontrol of the α/β ...selectivity can be successfully realized by slight structural modifications of the oxalic diamide ligands. Mechanistic studies indicated a dynamic kinetic resolution (DKR) reaction mechanism controlled by the ligand structures. This reaction could be performed on gram scale, and has also been applied to the synthesis of some natural products.
This study aims to scale up a membrane capacitive deionization (MCDI) stack for the reuse of domestic wastewater for industry applications. The desalination performance of the pilot-scale MCDI was ...investigated for the removal of ions from the effluent of a domestic wastewater treatment plant in terms of water quality, ion selectivity, water productivity and fouling/scaling phenomena. The MCDI stack was composed of 40 pairs of 20 cm × 20 cm activated carbon electrodes and operated in a single-pass mode. The MCDI stack achieved good removal efficiency of ions from the wastewater effluent (up to 94% Ca2+ and 84% NO3−). For electrode regeneration, the pump-off operation enabled a much higher water recovery of 75%. In particular, the average conductivity after the MCDI treatment was 103 μS/cm, which meets the standard for industrial reuse. For the electrosorption selectivity of cations, Ca2+ and Mg2+ were favored due to their high charge. Among the anions, NO3− had the highest electrosorption selectivity owing to its hydration ratio. Notably, the water quality of MCDI-treated effluents remained stable during consecutive charging-discharging cycles over 5 months of operation. These results provide essential data to scale up the MCDI stack with application to water reclamation.
Display omitted
•A scaled-up MCDI stack was developed to desalinate wastewater.•MCDI in pilot scale can reclaim wastewater with long-term stability.•MCDI reclaimed water achieved the water quality standard for industrial use.•Preferential electrosorption of Ca2+, Mg2+ and NO3− was observed.•MCDI scaling and fouling conditions were assessed after long-term operation.
There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a ...tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory.
BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test.
The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation.
Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.
Summary
DICER‐LIKE (DCL) enzymes process double‐stranded RNA into small RNAs that act as regulators of gene expression. Arabidopsis DCL4 and DCL2 each allow the post‐transcriptional gene silencing ...(PTGS) of viruses and transgenes, but primary PTGS‐prone DCL4 outcompetes transitive PTGS‐prone DCL2 in wild‐type plants. This hierarchy likely prevents DCL2 having any detrimental effects on endogenous genes. Indeed, dcl4 mutants exhibit developmental defects and increased sensitivity to genotoxic stress. In this study, the mechanism underlying dcl4 defects was investigated using genetic, biochemical and high‐throughput sequencing approaches. We show that the purple phenotype of dcl4 leaves correlates with carbohydrate over‐accumulation and defective phloem transport, and depends on the activity of SUPPRESSOR OF GENE SILENCING 3, RNA‐DEPENDENT RNA POLYMERASE 6 (RDR6) and DCL2. This phenotype correlates with the downregulation of two genes expressed in the apex and the vasculature, SMAX1‐LIKE 4 (SMXL4) and SMXL5, and the accumulation of DCL2‐ and RDR6‐dependent small interfering RNAs derived from these two genes. Supporting a causal effect, smxl4 smxl5 double mutants exhibit leaf pigmentation, enhanced starch accumulation and defective phloem transport, similar to dcl4 plants. Overall, this study elucidates the detrimental action of DCL2 when DCL4 is absent, and indicates that DCL4 outcompeting DCL2 in wild‐type plants is crucial to prevent the degradation of endogenous transcripts by DCL2‐ and RDR6‐dependent transitive PTGS.
Significance Statement
The Arabidopsis Dicer‐Like enzymes DCL2 and DCL4 have overlapping functions in post‐transcriptional silencing of viruses and transgenes, but it was not clear why they have antagonistic functions in development. Here by dissecting the impact of DCL2 activity on the small RNA profile of dcl4 plants, we uncovered the unusual accumulation of 22‐nt siRNAs from two protein‐coding genes that are specifically expressed in the apex and the vasculature, and found that the concurrent disruption of these two genes causes leaf pigmentation, starch over‐accumulation and phloem transport defects similar to those observed in some of dcl4 plants.
In this study, we employed carbon nanotubes (CNTs) to improve the performance of flow-electrode capacitive deionization (FCDI) for wastewater desalination in isolated closed-cycle (ICC) mode. The ...effects of CNTs loading and initial salt concentration on FCDI desalination were evaluated with energetic performance analysis. FCDI was carried out for the desalination with real wastewater for technology demonstration. The addition of CNTs significantly improved the average salt removal rate (ASRR), associated with a decrease in the flow-electrode flowability. FCDI with 0.25 wt% CNTs had an ASRR of 1.59 μmol/cm2–min, which was 1.7-fold higher than that without CNTs. This was attributed to the bridging effect of CNTs for more rapid charge transfer. Increasing the initial salt concentration from 0.05 to 0.30 M led to a higher ASRR, resulting from a reduction in the electrical resistance in the cell. After further increasing the salt concentration to 0.50 M, the charge efficiency was relatively decreased due to co-ion leakage. Notably, FCDI for the desalination of real saline wastewater achieved a high decrease in conductivity (94%), a high charge efficiency (>99%), and low energy consumption (0.034 kWh/mol). Our results demonstrated that adding CNTs is a feasible approach to achieve high-performance FCDI for sustainable wastewater desalination.
Display omitted
•CNTs were employed to enhance the desalination performance of the FCDI process.•CNTs improved the salt removal rate and energy performance of ICC-mode FCDI.•FCDI can desalinate saline water with a wider concentration range.•FCDI exhibits great potential for real wastewater desalination.
Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules ...to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-γ (IFN-γ) levels were twofold lower than those without fibrosis (
> 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-γ levels with an estimate of 0.43 (
= 0.02). Per the 1-SD increase of basal IFN-γ level in circulation, the fibrosis volume decreased by 0.070% (
= 0.04) at the discharge of participants. The basal circulating IFN-γ levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-γ is a risk factor of lung fibrosis in COVID-19.
The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS.
This ...multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed.
A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 CI: 0.89-1.99) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 CI: 0.68-2.72), 0-5 years (HR: 1.34 CI: 0.75-2.39), and 6-18 years (HR: 1.15 CI: 0.67-1.96) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 CI: 0.87-2.56) or males (HR: 0.82 CI: 0.48-1.41) with DS compared to their respective non-DS comparators.
Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.
PDF
