Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

The role of microbial electrogenesis in regulating methane and nitrous oxide emissions from constructed wetland-microbial fuel cell

This study assesses a sustainable solution to greenhouse gases (GHGs) mitigation using constructed wetland-microbial fuel cells (CW-MFC). Roots of wetland plant Acorus Calamus L. are placed in biological anode to better enable anode microorganisms to obtain rhizosphere secretion for power improvement. Three selected cathode materials have a large difference in GHG emissions, and among them, carbon fiber felt (CFF) shows the lowest emissions of methane and nitrous oxide, which are 0.77 ± 0.04 mg/(m²·h) and 130.78 ± 13.08 μg/(m²·h), respectively. The CFF CW-MFC achieves the maximum power density of 2.99 W/m³. As the influent pH value is adjusted from acidic to alkaline, the GHGs emissions are reduced. The addition of Ni inhibits GHGs emission but decreases the electricity, the power density is reduced to 1.09 W/m³, and the methane and nitrous oxide emission fluxes decline to 0.20 ± 0.04 mg/(m²·h) and 15.49 ± 1.86 μg/(m²·h), respectively. Low C/N ratio reduces methane emission, while high C/N ratio effectively inhibits nitrous oxide emission. At the influent pH 8 and C/N = 5:1, the methane emission flux is approximately 10.60 ± 0.27 mg/(m²·h), and the nitrous oxide emission flux is only 10.90 ± 1.10 μg/(m²·h). Based on the above experimental results by controlling variable factors, it is proposed that CW-MFC offers an environment-friendly solution to regulate GHG emissions.     

Microstructure and electric properties of Pr-doped Pb(Zr0.52Ti0.48)O3 ceramics

Improving the piezoelectric activity of lead zirconate titanate (PZT) ceramics is of great importance for practical applications. In this study, the influence of Pr³⁺ doping on the ferroelectric phase composition, microstructure, and electric properties on the A-site of (Pb_1-1.5xPr_x)(Zr_0.52Ti_0.48)O₃ is extensively investigated. A dense and fine microstructural sample is obtained with the introduction of Pr³⁺. The results show that the morphotropic phase boundary (MPB) moves to the rhombohedral phase region. The rhombohedral and tetragonal phases exhibit an ideal coexistence in the 4 mol.% Pr³⁺ doped (PPZT4) samples. Lead vacancy and the reduction of the potential energy barrier are considered to be the key mechanisms for donor doping, which is upheld by the Pr³⁺ doping. Combining the I-E hysteresis loops with the P-E hysteresis loops, it becomes apparent that both contribution maximums of the domain switching and residual polarisation are in PPZT4. Moreover, the thermal aging resistance of PZT is improved by doping, and the temperature stability is optimised from 83% in PZT to 96% in PPZT4. Hence, an appropriate amount of Pr³⁺ doping can effectively improve the piezoelectric activity of PZT ceramics in the MPB area and optimise the performance stability of the material under application temperatures.     

Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.     

Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Progress and major BARRIERS of nanocatalyst development in direct methanol fuel cell: A review

Direct methanol fuel cells (DMFC), among the most suited and prospective alternatives for portable electronics, have lately been treated with nanotechnology. DMFCs may be able to remedy the energy security issue by having low operating temperatures, high conversion efficiencies, and minimal emission levels. Though, slow reaction kinetics are a significant restriction of DMFC, lowering efficiency and energy output. Nowadays, research is more focused on fundamental studies that are studying the factors that can improve the capacity and activity of catalysts. In DMFC, among the most widely explored catalysts are platinum and ruthenium which are enhanced in nature by the presence of supporting materials such as nanocarbons and metal oxides. As a result, this research sheds light on nanocatalyst development for DMFCs based on Platinum noble metal. To summarize, this research focuses on the structure of nanocatalysts, as well as support materials for nanocatalysts that can be 3D, 2D, 1D, or 0D. The support material described is made up of CNT, CNF, and CNW, which are the most extensively used because they improve the performance of catalysts in DMFCs. In addition, cost estimations for fuel cell technology are emphasized to show the technology's status and requirements. Finally, challenges to nanocatalyst development have been recognized, as well as future prospects, as recommendations for more innovative future research.     

Identifying catalyst layer compositions of proton exchange membrane fuel cells through machine-learning-based approach

Membrane electrode assembly (MEA) is considered a key component of a proton exchange membrane fuel cell (PEMFC). However, developing a new MEA to meet desired properties, such as operation under low-humidity conditions without a humidifier, is a time- and cost-consuming process. This study employs a machine-learning-based approach using K-nearest neighbor (KNN) and neural networks (NN) in the MEA development process by identifying a suitable catalyst layer (CL) recipe in MEA. Minimum redundancy maximum relevance and principal component analysis were implemented to specify the most important predictor and reduce the data dimension. The number of predictors was found to play an essential role in the accuracy of the KNN and NN models although the predictors have self-correlations. The KNN model with a K of 7 was found to minimize the model loss with a loss of 11.9%. The NN model constructed by three corresponding hidden layers with nine, eight, and nine nodes can achieve the lowest error of 0.1293 for the Pt catalyst and 0.031 for PVA as a good additive blending in the CL of the MEA. However, even if the error is low, the prediction of PVA seems to be inaccurate, regardless of the model structure. Therefore, the KNN model is more appropriate for CL recipe prediction.     

Understanding grain refining and anti Si-poisoning effect in Al-10Si/Al-5Nb-B system

Grain refinement is critical for fabricating high-quality Al-Si casting components in the application of automobile and aerospace industries,while the well-known Si-poisoning effect makes it difficult.Nbbased refiners offer an effective method to refine Al-Si casting alloys,but their anti Si-poisoning capability is far from being understood.In this work,the grain refining mechanism and the anti Si-poisoning effect in the Al-10 Si/Al-5 Nb-B system were systematically investigated by combining transmission electron microscope,first-principles calculations,and thermodynamic calculations.It is revealed that NbB₂provides the main nucleation site in the Al-10 Si ingot inoculated by 0.1 wt.%Nb Al-5 Nb-B refiner.The exposed Nb atoms on the(0001)NbB₂and(1-100)NbB₂surface can be substituted by Al to form(Al,Nb)B₂intermedia layers.In addition,a layer of NbAl₃-like compound(NbAl₃')can cover the surface of NbB₂with the orientation relation of(1-100)[11-20]NbB_2//(110)[110]NbAl₃'.Both of the(Al,Nb)B₂and NbAl₃'intermedia layers contribute to enhancing the nucleation potency of NbB₂particles.These discoveries provide fundamental insight to the grain refining mechanism of the Nb-B based refiners for Al-Si casting alloys and are expected to guide the future development of stronger refiners for Al-Si casting alloys.