Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate endothelial cell proliferation and migration, while VEGF-B, VEGF-C, and VEGF-D interact with VEGFR-1 and VEGFR-3 to regulate tumor angiogenesis, lymphangiogenesis, and metastasis. The VEGF/VEGFR signaling pathway activates various downstream effectors, including phospholipase Cγ1, MAPK, and PI3K/Akt, which are essential for maintaining vascular homeostasis and promoting angiogenesis. In NSCLC, elevated serum VEGF levels have been observed, and the VEGF/VEGFR axis is frequently impaired, leading to irregular blood vessel formation and metastatic spread. Despite the development of anti-VEGF therapies, their impact on lung cancer outcomes has been limited. Further research is needed to optimize the effectiveness of these treatments and elucidate the potential of serum VEGF as a predictive biomarker in NSCLC.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcome. In this study we evaluated whether Naples Prognostic Score, a novel index which considers both inflammatory and nutritional values, was associated with long-term survival. The study is a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered four pre-operative parameters: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, serum albumin and total cholesterol. Kaplan-Meier method and Cox regression analysis were performed to evaluate the relation between the score and disease-free survival, overall survival and cancer-related survival. A total of 260 patients were selected for the study, reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between Naples Prognostic Score and overall survival (p=0.018) and cancer-related survival (p=0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both these survivals (p=0.007 and p=0.010 respectively). Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

Arboviruses of medical and veterinary significance have been identified on all 7 continents with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are found wherever there are humans. Viral parkinsonism has been documented for a variety of human pathogens though there are few studies that evaluate the effects of viral infection on degenerative neurological diseases. Significant differences in baseline gene and protein expression have been determined between Human Induced Pluripotent Stem Cell lines derived from a non-Parkinson’s disease individual and from an individual with reported Parkinson’s disease. While the organoids generated from each cell line were physically indistinguishable, significant differences were observed in gene and protein expression for neurotransmission and immunity. It was hypothesized that these inherent differences would impact cerebral organoid responses to viral infection. In this preliminary observational study, cerebral organoids from a non-Parkinson’s and Parkinson’s patient were infected with Chikungunya virus and observed for 2 weeks. Parkinson’s organoids lost mass and exhibited a dysfunctional antiviral response. Neurotransmission data from both non-Parkinson’s and Parkinson’s organoids had dysregulation of IL-1, IL-10, IL-6. These cytokines are associated with mood and could be contributing to persistent depression seen in patients following CHIKV infection. Both organoid types had increased expression of CCR5 and CXCL10 which are linked to demyelination, highlighting a potential mechanism for virus-associated parkinsonism. The dysfunctional antiviral response of Parkinson’s organoids highlights the need for more research in neurotropic infections in a neurologically compromised host.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has changed considerably, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could lead not only to stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumor that finally permits liver transplantation. There are increasing reports of patients that have performed liver transplantation after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs to stimulate the immune response against tumors, they could also cause graft rejection. This review aims to evaluate the readiness and outcomes of liver transplantation in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to liver transplantation. While early evidence supports the feasibility of LT following ICI therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

The normative and safeguarding role of ethics and law in the development of biomedical science and technology, as well as their importance in promoting the progress of the industry, analyzed the key role of ethics and law in the field of biomedical science and technology, by restricting scientific research behavior, protecting the rights and safety of subjects, providing a solid guarantee for scientific research activities, and promoting the healthy development of biomedical science and technology. At the same time, the positive role of ethics and law in promoting international cooperation and exchange of biomedical science and technology is also discussed, which will inject strong impetus into the global development of biomedical science and technology. In addition, through case analysis, the paper demonstrates the key role of ethical review in the field of biomedical science and technology, as well as the importance of law in maintaining market order, protecting subjects' rights and interests, and fairness and justice. The successful practice of ethics and law in the development of biomedical science and technology is emphasized, which proves that following ethical principles and legal framework is the key factor to promote the progress of biomedical science and technology. This paper explores the important role of ethics and law in the development of biomedical science and technology, and provides valuable reference and guidance for practitioners in the industry. By following ethical principles and legal norms, we will jointly promote the prosperity and development of biomedical science and technology, and contribute to the common progress of human health.

In this study, we propose a radiomics-clinical probability weighted model for the prediction of prognosis for NSCLC. The model combines radiomics features extracted from RT planning images with clinical factors such as age, gender, histology, and tumor stage. CT images with radiotherapy structures of 422 NSCLC patients were retrieved from The Cancer Imaging Archive (TCIA). Radiomic features were extracted from gross tumor volume (GTV). Five machine learning algorithms, namely decision trees (DT), random forests (RF), extreme boost (EB), support vector machine (SVM) and generalized linear model (GLM), were optimized by a voted ensemble machine learning (VEML) model. A probabilistic weighted approach is used to incorporate the uncertainty associated with both radiomic and clinical features and to generate a probabilistic risk score for each patient. The performance of the model is evaluated using a receiver operating characteristic (ROC). Radiomic model, clinical factors model and combined radiomic-clinical probability weighted model demonstrated good performance in predicting NSCLC survival with AUC of 0.941, 0.856 and 0.949 respectively. The combined radiomics-clinical probability weighted enhanced model achieved significantly better performance than radiomic model in 1-year survival prediction (chi-square test, p<0.05). The proposed model has the potential to improve NSCLC prognosis and facilitate personalized treatment decisions.

In this study the formation of thin-film barrier coatings based on a highly-conducting Bi1.60Er0.4O3 (EDB) solid electrolyte on supporting Ce0.8Sm0.2O1.9 (SDC) electrolyte substrates is implemented for the first time using electrophoretic deposition (EPD). Electrokinetic properties of EDB-based suspensions in a non-aqueous dispersion medium of isopropanol modified with small additions of polyethyleneimine (PEI, 0.26 g/L) and acetylacetone (0.15 g/L), as well as in a mixed isopropanol/acetylacetone (70/30 vol.%) medium are studied. The dependences of the thickness of EDB coatings on voltage and deposition time are obtained using deposition on a model Ni-foil electrode. Preliminary synthesis of a conductive polypyrrole (PPy) polymer film is used to create surface conductivity of non-conductive SDC substrates. The efficiency of using a modified dispersion medium based on isopropanol to obtain a continuous EDB coating 12 μm thick, sintered at a temperature of 850 °C for 5 h, is shown. The microstructure and morphology of the surface of the EDB coating are studied. Pt/SDC/EDB/Pt cell is used to characterize the coating conductivity. The EPD method is shown to be promising for the formation of barrier coatings based on doped bismuth oxide. The developed method can be used for creating cathode barrier layers in SOFC technology.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

The use of chimeric antigen receptors (CAR-T cells) for the treatment of patients with malignant haematological diseases has become a well-established application, for conditions such as refractory or relapsed B cell acute lymphoblastic leukaemia (B-ALL), B cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR-T cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR-T cells with approval by different regulatory agencies around the globe. In the USA the Food and Drug Administration (FDA) has approved 6 commercial CAR-T cells that are widely distributed worldwide. At the time of this writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR-T cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all the current areas of treatments with CAR-T cells, we offer a brief summary of some of the most relevant aspects of the use of CAR-T cells for some of these conditions.

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but it is unknown the degree to which such cultures retain the characteristics of the source tumors. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

Evidence indicates that the long noncoding RNAs are involved in the metformin-mediated anti-cancer processes. However, the potential effects of the long noncoding RNAs in metformin-mediated anti-tumor processes in esophageal squamous cell carcinomas (ESCC) are still elusive. This study uncovered that metformin decreases the level of long noncoding RNAs CCAT1 and SPRY4-IT1 thereby contributing to the down-regulation of c-Myc and vimentin. Also, the RNA level test of human ESCC tissue confirmed the positive correlation between CCAT1 and c-Myc. These findings demonstrated that metformin facilitated anti-cancer effects by targeting the 2 long noncoding RNAs (CCAT1 and SPRY4-IT1) and their consequential targets c-Myc and vimentin. Therefore, the CCAT1 and SPRY4-IT1 might act as novel molecular targets that mediate the anti-tumor effects in esophageal squamous cell carcinoma. This helps in predicting the treatment response of metformin in patients diagnosed with esophageal squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.

The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans, and fungi (AMF) and its systemic germline, which serves as a blueprint for all germlines capable of asymmetric cell division (ACD) and stem cell differentiation. Consequently, the oxygen sensitivity of the ancient non-gametogenic germline (Urgermline) was inherited by all germ and stem cell lines including the cancer germline. They all respond to Ugermline’s hyperoxia with loss of stemness and ACD ability and a dysregulated phenotype with irreparable DNA defects and defective symmetric cell divisions (DSCD). In protists, defective DSCD cells undergo an ancient MGRS repair program involving cell and nuclear fusion and hyperploid giant nuclei that restores the damaged genome to its former pre-DSCD state, with ACD potential and stemness. Human and metazoan DSCD use the same MGRS repair program inherited from the AMF ancestor. Ectopic DSCDs and DSCD-like phenotypes can survive in humans for many years in suitable niches. Under favorable environmental conditions, they also have access to the ancient MGRS repair mechanism including the ancient gene regulatory network (aGRN) and all other AMF genes. The aGRN takes control of cancer’s hybrid genome and represses human genes. It installs a G+S cancer life cycle of AMF imprinting that shapes the differentiation of naïve cancer stem cells (CSCs). CSCs are deeply homologous to the aGSCs of the AMF ancestor. Reprogramming of the DSCD genome by MGRS paves the way for oncogenesis. In this light, cancer is not a mutational or genetic disease, but a non-mutational genome-altering disease.

Malignant lymphomas, encompassing Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), represent a significant category of hematological malignancies with diverse presentations and prognoses. This review synthesizes current understanding of malignant lymphomas, focusing on their classification, incidence, epidemiology, staging, histopathology, and evolving treatment strategies. Malignant lymphomas are broadly classified into HL and NHL, with NHL further subdivided into B-cell, T-cell, and NK-cell neoplasms. The emergence of grey zone lymphomas, which exhibit overlapping features and heightened aggressiveness, underscores the complexity of diagnosis and treatment. Epidemiologically, HL predominantly affects younger individuals, while NHL incidence increases with age, reflecting a global rise in both incidence and mortality rates. Advances in diagnostic techniques and treatments have led to improved outcomes, yet challenges persist, particularly in distinguishing between overlapping lymphoma types and managing increasing incidence rates. The management of HL and NHL involves a variety of treatment options tailored to the disease stage and individual patient characteristics. After diagnosis and staging, treatment regimens may include radiotherapy, chemotherapy (either alone or in combination), and immunotherapy. Monitoring patient response is crucial, with adjustments made in cases of therapeutic failure. Achieving remission—either partial or complete—depends on the normalization of biomarkers and imaging results, reduction of lymphoid organ size, and resolution of symptoms. Despite therapeutic advances, treatment complications, including short-term effects like myelosuppression and long-term issues such as cardiomyopathy and secondary cancers, remain significant. The future of HL and NHL treatment lies in refining these approaches, minimizing adverse effects, and enhancing efficacy through innovative therapies and personalized medicine strategies.

Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Mehtods: In Trypanosoma cruzi, the causal agent of the Chagas disease, an NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that are clearly detached from the other Trypanosomatidae such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that an NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS&gt;50%; n=10) or low (TPS&lt;1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

Effective biomarkers are essential to the early diagnosis of non-small cell lung cancer (NSCLC). Herein, a retrospective study of 49 newly diagnosed and recurrent NSCLC patients, 31 patients with benign pulmonary disease and 24 healthy volunteers was conducted, to evaluate the diagnostic value of circulating rare cells for NSCLC. The expression of circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in peripheral blood were measured by subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH). The level of CTCs (P＜0.001) and CTECs (P＜0.001) was significantly higher in NSCLC group than that in benign pulmonary disease group. The proportion of small CTCs (P＜0.001) and CTECs (P＜0.0001) significantly increased from benign lung disease individuals to NSCLC patients. The AUC of ROC curves of total CTCs and CTECs were 0.815 (95%CI: 0.722~0.907), 0.739 (95%CI: 0.618~0.860), respectively. The cut-off values for discriminating NSCLC with benign lung disease patients were total CTCs 11.5 units/6ml and total CTECs 10.5 units/6ml, with sensitivity and specificity being 67.3% and 83.9%, 77.6% and 77.4%, respectively. When CTCs and CTECs were combined, predictive value significantly increased to 82.6% as measured by the area under the curve. Small CTCs and triploid CTCs had high positive predictive value (PPV) and positive likelihood ratio (LR+) of the diagnosis of NSCLC in early stage. CTCs and CTECs can not only be used as new biomarkers for the diagnosis of NSCLC, but can also improve diagnostic performance of the early stage NSCLC. Moreover, the combined examination of CTCs and CTECs is be superior to the single.

Diabetes mellitus is a chronic metabolic disease that affects over 10.5 percent of the global adult population. Biochemical and hematological parameters such as albumin (ALB) and red cell dis-tribution width (RDW) have been shown to be altered in diabetic patients. This study aims to cor-relate hematological and biochemical parameters with glycated hemoglobin (HbA1c). 777 adult individuals (372 women and 405 men, aged 19-85 years) were divided into three groups: 218 par-ticipants with HbA1c < 5.7% (group A: non diabetic), 226 with HbA1c ≥ 5.7% and < 6.5% (group B: prediabetic) and 333 with HbA1c ≥ 6.4% (group C: diabetic). Biochemical and hematological parameters were compared among the 3 groups. Analysis of variance was performed to deter-mine the correlations of the parameters among groups. ALB and sodium (Na) levels were signifi-cantly decreased in group C compared to groups A (ALB: 3.8 g/dL vs. 4.1 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.3 mmol/L, p < 0.001), and B (ALB: 3.8 g/dL vs. 4.0 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.6 mmol/L, p < 0.0001), while RDW-standard deviation (RDW-SD) and urea were increased in group C compared to group A ( RDW: 45.8 vs. 43.9 fL, p < 0.0001, Urea: 55.6 mg/dL vs. 38.5 mg/dL, p < 0.0001) . Mean platelet volume (MPV) was increased in group C com-pared to group A (9.3 fL vs. 9.1 fL, p < 0.05, respectively). Τhe increase of RDW-SD from group A towards B and C demonstrates the impact of hyperglycemia on red blood cells. RDW may be re-garded as a potential innovative biomarker for improving risk assessment of developing diabetes. These results highlight the potential role of these parameters as an indication for prediabetes that would alert for measurement of HbA1c.

Autoantibodies against specific lung cancer-associated antigens have been suggested for lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of anti-gen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, NGAL, and NSE in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9G DNA chip method. The ratios of AICs to their antigens and combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than their free antigens in all participants. The levels of each free antigen distinguished patients with NSCLC from HCs. The ratios of AIC to its antigen and seven combinations consisting of two to four ratios were significantly higher in patients with NSCLC than those in HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at cutoff 3.51. Higher sensitivity was observed in the very early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. The combination of all ratios of AICs and their antigens for all four markers is useful in the diagnosis of NSCLC.

Perovskite solar cells have shown significant progress, but their commercialization remains hindered by lead-based toxicity. Many nontoxic perovskite-based solar cells have demonstrated potential such as Cs2AgBi0.75Sb0.25Br6, but their power-conversion efficiency is inadequate. To address this issue, some researchers are focusing on emerging acceptor-donor-acceptor'-donor-acceptor (A-DA'D-A) type non-fullerene acceptors (NFAs) for Cs2AgBi0.75Sb0.25Br6 to find effective electron transport layers for high-performance photovoltaic responses with low voltage drops. In this comparative study, four novel A-DA'D-A types NFAs such as BT-LIC, BT-BIC, BT-L4F, and were used as an electron transport layer (ETL) for the proposed devices, FTO/PEDOT: PSS/ Cs2AgBi0.75Sb0.25Br6/ETL/Au. Comprehensive simulations were conducted to optimize the devices. The simulations showed that all optimized devices exhibit photovoltaic responses, with the BT-BIC device having the highest power conversion efficiency (13.2%) and the BT-LIC device having the lowest (6.8%). The BT-BIC as ETL provides fewer interfacial traps and better band alignment, enabling greater open-circuit voltage for efficient photovoltaic responses.

This study fabricated piezoelectric fibers of polyvinylidene fluoride (PVDF) with graphene using near-field electrospinning (NFES) technology. A uniform experimental design table U*7 (7^4 ) was applied, considering weight percentage (1-13 wt%), distance between needle and disk collector (2.1-3.9 mm), and applied voltage (14.5-17.5 kV). We optimized the parameters using electrical property measurements and the Kriging response surface method. Adding 13 wt% graphene significantly improved electrical conductivity, increasing from 17.7 μS/cm for pure PVDF to 187.5 μS/cm. The fiber diameter decreased from 21.4 μm in PVDF/1% graphene to 9.1 μm in PVDF/13% graphene. Adding 5 wt% graphene increased the β-phase content by 6.9%, reaching 65.4% compared to pure PVDF fibers. Material characteristics were investigated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), contact angle measurements, and tensile testing. Optimal parameters included 3.47 wt% graphene, yielding 15.82 mV voltage at 5 Hz and 5 N force (2.04 times pure PVDF). Force testing showed a sensitivity (S) of 7.67493 log(mV/N). Fibers were attached to electrodes for piezoelectric sensor applications. Results affirmed enhanced electrical conductivity, piezoelectric performance, and mechanical strength. The optimized piezoelectric sensor could be applied to measure physiological signals, such as attaching it to the throat under different conditions to measure the output voltage. The force-to-voltage conversion facilitated subsequent analysis.

Regeneration is a fundamental process much attributed to functions of adult stem cells. In last decades delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading mean of cell therapy. However, adult stem cells can not complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding of mechanisms underlying mammalian regeneration lead us to an assumption that improved outcomes of cell therapy requires a specific microenvironment generated in damaged area prior to stem cell delivery. To certain extent it may be achieved by delivery of mesenchymal stromal cells (MSC), not in dispersed form, but rather self-organized in cell sheets (CS) – tissue-like structures comprising of viable cells and microenvironment components: extracellular matrix and soluble factors deposited in the matrix. In this communication we highlight a potential role of mesenchymal stromal cells (MSC) as regeneration organizers and speculate that this function emerges in CS. This concept shifts our understanding of therapeutic mechanism underlying a widely known CS-based delivery method for regenerative medicine.

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.

There exists a variety of studies about tumor-infiltrating lymphocytes (TILs) in cervical cancer, but their prognostic value in correlation to the histopathological subtype was never investigated. Therefore, the aim of this study was to quantify TILs in a panel of 250 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIL levels were significantly increased in the subgroup of squamous cell carcinomas in comparison to adenocarcinomas. In squamous cell carcinomas, TIL infiltration shows a negative correlation to age, FIGO stage and to the histone protein modification H3K4me3. Moreover, in adenocarcinomas, it was positively correlated to p16 and to the glucocorticoid receptor and inversely correlated to the MDM2 protein and to H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease free survival (DFS) in patients with squamous cell carcinomas, those bearing tumors with the strongest TIL infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIL levels and prognosis in patients with cervix squamous cell carcinomas vs patients with cervix adenocarcinomas.

Regeneration is a fundamental perpetual tissue process much attributed to functions of adult stem cell. In last decades delivery of adult stem cells to restore tissue structure is widely adopted in regenerative medicine. However, delivery of stem cells can not complete the task of human body regeneration effectively as far as cells need a basis to form a tissue. Certain improvement can be achieved when cells are organized to cells sheets (CS) – primitive tissue-engineered structures comprising of viable cells and ECM proteins. This led us to an assumption that after damage an intermediate feeder is structure formed as a ground for future tissue resulting in gradients of stimuli required to attract other cells (vascular, neural, epithelial, parenchyma etc.) in an organized manner. This feeder acquires increasing heterogeneity and becomes a guiding feeder that provides basic level of organization to increase complexity of structure up to normal tissue. We also highlight potential role of adult mesenchymal stromal cells (MSC) as the main source of guiding feeder and support it by our recent knowledge of their biological function. Finally, we assume that CS known to be a feasible delivery tool in therapeutics resemble guiding feeder and show our own data indicating properties of MSC-based CS. Furthermore, this concept shifts our understanding of therapeutic mechanism underlying a widely known delivery method for regenerative medicine.

The population of Bifidobacterium spp in faecal samples from breast-fed and formula-fed infants were investigated and developed antibiogram. The common bacterial growth media such as Man Rogos Sharpe (MRS), Brain Heart Infusion (BHI), Luria Bertani (LB) broth and Bifidobacteria agar were evaluated by the enumeration of Bifidobacterium spp. in faecal material. The results demonstrated that the population of Bifidobacterium spp. in the faecal samples of breast-fed infants is numerically high and, low in formula-fed infants. Phylogenetic analysis of the 16S rRNA, (Xylose/Fructose-6-phosphate phosphoketolase) xfp, and RFLP map of Bifidobacteria isolates suggested a presence of possible new and different Bifidobacterium spp. The intensity of the reddish brown colour formed during the f6ppk (Fructose-6-phosphate phosphoketolase) assay confirms the presence of variable Bifidobacteria. The highest recovery and diversity of Bifidobacteria were obtained from Bifidobacteria agar media. Growth in various media resulted in the formation of small (SCV) and big colony variants (BCV). We understand that the various antibiotic minimum inhibitory concentration (MIC) values obtained by applying different media, growth conditions, after bile salt treatment, and at low pH can vary. This study concludes that the variation of microbiological conditions differentiating resistant and susceptible strains is influenced by the test conditions as well.

We propose a theoretical Photocurrent - Voltage characteristic (PC-V) model to assess the interfacial phenom-ena for a photo-electrochemical cell (PEC). The origin of voltage deficits and the distribution of the photocur-rent across the semiconductor-electrolyte interface (SEI) are reported for the cell. The model predicts the hole exchange current parameter to extract the cell polarization data at the SEI. The potential drop across the SEI across the cell is mapped for the n-type cells. The simulation results of the Pc-V model are used to differentiate the effect of the bulk and space charge region (SCR) recombination in the semiconductor cells. A deep neural network model is developed to assess the electron-hole transfer mechanism using the Pc-V characteristic curve. The applicability of the model is tested and validated with the real time data. The results show good agreement with the experimental data.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Cadmium telluride (CdTe), a metallic dichalcogenide material, has been utilized as an absorber layer for thin film-based solar cells with appropriate configurations, and the SCAPS-1D structures program has been used to evaluate the results. In both known and developing thin film photovoltaic systems, a CdS thin film buffer layer has been frequently employed as a traditional n-type heterojunction partner. In this study, numerical simulation was used to find a suitable non-toxic material for the buffer layer instead of CdS, among various types of buffer layers (ZnSe, ZnO, ZnS, and In2S3), and carrier concentrations for the absorber layer (NA) and buffer layer (ND) were varied to determine the optimal simulation parameters. carrier concentrations (NA from 2 x 1012 cm-3 to 2 x 1017 cm-3 and ND from 1 x 1016 cm-3 to 1 x 1022 ??−3) have been differed. The results showed that the CdS as buffer layer based CdTe absorber layer solar cell has the highest efficiency (?%) of 17.43%. Furthermore, high conversion efficiencies of 17.42% and 16.27% have been found for ZnSe and ZnO based buffer layers, respectively. As a result, ZnO and ZnSe are potential candidates for replacing the CdS buffer layer in thin-film solar cells. Here, the absorber (CdTe) and buffer (ZnSe) layers were chosen to improve the efficiency by finding the optimal density of the carrier concentration (acceptor and donor). The simulation findings above provide helpful recommendations for fabricating high-efficiency metal oxide-based solar cells in the lab.

Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of available drugs make necessary the search for new anti-inflammatory conditions. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60 or 90 mg/Kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in the animals. At the same doses, solidagenone promoted a significative reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significative reduction in nitric oxide, TNF-α, and IL-1β relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of NF-κB pathway by solidagenone. Finally, in silico pharmacokinetics prediction indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of NF-κB signaling pathway.

To face the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. We describe here an innova-tive antibiofilm nano vector, consisting of a Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantly (DspB-β-CD/CIP-Ad). For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, that are 2,3-O-dimethyl-β-CD, 2,6-O-dimethyl-β-CD, and 2,3,6-O-trimethyl-β-CD were tested. A stoichiometry of 1/1 was obtained for the β -CD/CIP-Ad complex by NMR analysis. ITC experiments were carried out to determine Ka, ΔH, ΔS thermodynamic parameters of the complex between β-CD or its different derivatives in the presence of CIP-Ad. A stoichiometry 1/1 of β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubili-ty with CDs concentration, pointing out complex formation. The evaluation of the antibacterial activity of CIP-Ad and the 2,3-O-dimethyl-β-CD/CIP-Ad or 2,3,6-O-trimethyl-β-CD/CIP-Ad complexes was performed on S.epidermidis strains. MIC studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited similar antimicrobial activity to CIP-Ad alone, while the interaction with 2,3,6-O-trimethyl-β-CD increased MIC values. Antimicrobial assays on S. epidermidis biofilms demonstrated that the synergistic effect observed with the DspB/CIP association was partly maintained with the 2,3-O-dimethyl-β-CDs/CIP-Ad complex. To obtain this "all in one" nano vector, able to destroy the biofilm matrix and release the antibiotic simultaneously, we covalently grafted DspB on three carboxylic permethylated CD derivatives with different length spacer arms. The strategy was validated by demonstrating that a DspB-permethylated-β-CD/ciprofloxacin-Ad nanovector exhibited efficient antibiofilm activity.

The production of bio-chemicals requires the use of microbial strains with efficient substrate conversion and excellent environmental robustness, such as Bacillus coagulans spp. So far the genomes of about 50 strains have been sequenced. Herein, we report a comparative genomic analysis of nine strains on the full repertoire of CAZymes, secretion systems, and resistance mechanisms to environmental challenges. Moreover, B. coagulans Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) immune system along with CRISPR-associated Cas) genes, was also analysed. Overall, this study expands our understanding of the strains genomic diversity of B. coagulans to fully exploit its potential in biotechnological applications.

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Introduction: Laeverin is an extravillous trophoblast marker playing a significant role in the trophoblast migration. The purpose of this study was to evaluate the association between the amniotic and serum laeverin concentrations at 16-22 weeks of gestation and the fetal and placental ultrasound measurements in healthy, unaffected pregnancies. Materials and methods: This was a prospective cross-sectional study. Pregnant women with singleton pregnancies undergoing amniocentesis were recruited consecutively. Fetal structural malformations and/or aneuploidy were exclusion criteria. Fetal biometric parameters and placental growth/perfusion were measured in 44 high-risk pregnancies who had no pregnancy complication and any other chronic disease. Maternal serum and amniotic levels of laeverin were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing slightly with the maternal age in mid-gestation. Serum laeverin level correlated negatively slightly with head size of the fetus with the gestational length at delivery (β=-0.38, 95% confidence interval (CI) -0.03-0.01), while the amniotic laeverin level correlated strongly with the abdominal circumference of the fetus (β=-0.64, 95% CI: -0.03-0.01). Furthermore, laeverin level in the amnion correlated moderately and positively with the placental volume (β=0.46, 95% CI: 0.01-0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denotes the fetoplacental growth in uncomplicated high-risk pregnancies.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

This paper comprehensively explores the integration of cloud computing and advanced recommendation systems, emphasizing their pivotal roles in enhancing user experiences and operational efficiencies across digital platforms. It reviews the evolution of recommendation algorithms, highlighting their application in diverse domains such as e-commerce and media. The study evaluates the performance of advanced models like UniLLMRec against traditional counterparts using datasets from news and e-commerce domains. Additionally, the paper discusses the infrastructure architecture of cloud computing, demonstrating its capability to support scalable and efficient data processing. Through experimental insights and methodology, the research underscores the transformative impact of cloud technologies on optimizing recommendation system performance, thereby advancing digital engagement and competitiveness.

The Peripheral giant cell granuloma (PGCG) is an asymptomatic, non-neoplastic and proliferative lesion of unknown etiology. Some possible pre-disposing factors such as hormonal changes dur-ing pregnancy, have been suggested. However, the association between PGCG and pregnancy is controversial. There are few reported clinical cases of pregnancy-associated PGCG in the litera-ture, and they occurred only in the lower jaw. The present report is on a 35-year-old female pa-tient at 36 weeks of gestation who presented with a PGCG in the central and lateral incisors of the upper jaw. The management consisted of surgical excision, along with curettage of the affected bony walls. The diagnosis was based on clinical results and imaging examinations, and it was histopathologically confirmed. The patient underwent postoperative follow-up evaluations at 3, 6 and 12 months, and there were no signs of recurrence.

Plant stem cell cultures have so far been established in only a few plant species using cambial meristematic cells. The presence of stem cells or stem cell-like cells in other organs and tissues of the plant body, as well as the possibility of de novo generation of meristematic cells from differentiated cells, allows to consider the establishment of stem cell cultures in a broader range of species. Therefore, this study aimed to establish a stem cell culture of the medicinal plant Calendula officinalis L. Callus tissues were induced from explants taken from leaves and roots. Appropriate combinations of plant growth regulators and light parameters for in vitro cultivation were selected. Already at this stage, stem and dedifferentiated cells could be identified, and cell suspension cultures were established from specific parts of the formed callus. Cell suspension cultures with a high proportion of stem cells originating from roots (92–93%) or leaves (72–73%) were developed. The amount of stem cells derived from the roots in the cell suspension reached a plateau at a level of 5.60–5.72105.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

The streptavidin and biotin interaction is one of the strongest non-covalent interactions in nature. As a result, this non-covalent interaction has been of great interest when it comes to biochemical assays, diagnosis of diseases, and cell-targeted drug delivery. Past research has proven that biotin-streptavidin is useful in biosensor development to improve the detection of a system when conjugated to nanoparticles. This study aims to prove that streptavidin-coated nanoparticles can be conjugated with biotinylated antibodies using the primary-secondary method to non-invasively detect adenocarcinoma in-vitro. While the use of nanoparticles is not uncommon to the diagnostics area of scientific research, the technique this research aims to investigate is a non-invasive one, utilizing the primary-secondary method. Specifically, the increased stability of fluorophores when bound to antibodies as opposed to nanoparticles directly can be indicative of the particles conjugated through the primary-secondary method’s ability to specifically bind to overexpressed transferrin receptors in the A549 cell line. In this paper, streptavidin-coated nanoparticles were conjugated with biotinylated anti-transferrin receptor antibodies and AlexaFluor-488 secondary antibodies were used to enable fluorescence-based detection. The efficiency of these particles were observed quantitatively through a plate reader and qualitatively through a fluorescence microscope. I demonstrated that these nanoparticles are able to specifically bind to the target proteins in this study. These findings contribute to the field of nanoparticle diagnostics and can be extended to different diseases caused by overexpression of proteins in the future. While this was conducted in-vitro, conjugates can be prepared to detect cancer in-vivo and can be tested with magnetic relaxometry in the future.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

Reduced-order electrothermal models play a key role in the design and control of lithium- ion cell stacks, calling for accurate model parameter calibration. This paper presents a complete electrical and thermal experimental characterization procedure for coupled modeling of cylindrical lithium-ion cells in order to implement them in a prototype Formula SAE hybrid racing car. The main 4goal of the tests is to determine cell capacity variations with temperatures and discharge currents, to predict the open circuit voltage of the cell and its entropic component. A simple approach for the characterization of the battery equivalent electrical circuit and a two-steps thermal characterization method are also shown. The investigations are carried out on four commercial 18650 NMC lithium cells. The model demonstrated to predict the battery voltage at a RMS error lower than 20mV and the temperature to a RMS error equal to 0.5 ◦C. The authors hope that this manuscript can contribute to the development of standardized characterization techniques for such cells, while offering experimental data and validated models that can be used by researchers and BMS designers in different applications.

We conducted a topological analysis of the novel, non-associative, and unital algebraic structure known as Bermejo Algebras, developed by Alejandro Bermejo, which includes the Algebra B and Treon Algebra. This algebras can define Lie and Malcev algebras when their product operations are derived from the Bermejo Algebras product. Central to this study are treons, complex entities that arise as isomorphisms of Algebra B when the field is real. We define the vector spaces associated with Bermejo Algebras to establish equivalence classes and a quotient topology, resulting in Hausdorff spaces that do not depend on traditional norms, inner products, or metrics. Our findings lay the groundwork for constructing new types of differential manifolds, opening new avenues for advanced mathematical research.

The loss of vitamin D3 upregulated protein 1 (VDUP1) has been implicated in the pathogenesis of various inflammation-related diseases. Notably, reduced expression of VDUP1 has been observed in clinical specimens of ulcerative colitis (UC). However, the role of VDUP1 deficiency in colitis remains unclear. In this study, we investigated the role of VDUP1 in dextran sulfate sodium (DSS)-induced experimental colitis in mice. VDUP1-deficient mice were more susceptible to DSS-induced colitis than their wild-type (WT) littermates after 2% DSS administration. VDUP1-deficient mice exhibited an increased disease activity index (DAI) and histological scores, as well as significant colonic goblet cell loss and an increase in apoptotic cells. These changes were accompanied by a significant decrease in MUC2 mRNA expression and a marked increase in proinflammatory cytokines and chemokines within damaged tissues. Furthermore, phosphorylated NF-B p65 expression was significantly upregulated in damaged tissues in the context of VDUP1 deficiency. VDUP1 deficiency also led to significant infiltration of macrophages into the site of ulceration. An in vitro chemotaxis assay confirmed that VDUP1 deficiency enhanced bone marrow-derived macrophage (BMDM) chemotaxis induced by CCL2. Overall, the loss of VDUP1 plays a critical role in the pathogenesis of UC, and blocking VDUP1 dissociation may represent a promising therapeutic strategy for the treatment of UC.

Ultrasonography is a relevant diagnostic tool extensively used andrology of human and do-mestic animals, including dogs. The present review aimed to describe all the technologies based on ultrasound, starting with the basic B-Mode ultrasonography to the recent contrast-enhanced ultrasonography (CEUS) and the ultrasound elastography, available to assess the testicle of the dog. The principles of the different technologies and the relevant findings in normal and ab-normal testicular conditions were described and discussed. B-mode ultrasonography aims at the examination of the testis detecting focal lesions but lacks objectivization. Other technologies, such as Doppler ultrasonography, B-Flow, and CEUS allow the definition of vascular patterns, that could be measured with specific applications, such as spectral Doppler or quantitative CEUS. Finally, ultrasound elastography allows the estimation of parenchyma stiffness, in both qualitatively and quantitatively manner. Ultrasound-based technologies assist the andrology in the evaluation of the testicular function and integrity, offering valuable information to define pathological conditions that could have an impact on the health and life quality of the male dog.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent outbreak in several countries around the world. A 39-year-old male with HIV-HBV coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox infection, presented to our hospital with disseminated dermatosis (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for Mpox. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. After 65 days of Mpox PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox infection because it could be related to higher mortality.

Brucella abortus is a facultative intracellular Gram-negative bacterium that causes chronic persistent infections in humans and livestock. In this study, conventional bio-typing, multiple-locus variable-number tandem repeat analysis (MLVA), and whole-genome sequencing-single-nucleotide polymorphism (WGS-SNP) were used to investigate the molecular epidemiology characteristics of Brucella abortus strains in China and their relationships to world lineages. A total of 100 strains were collected from 1953 to 2013, suggesting that B. abortus circulated in China in the past five decades. Moreover, most strains were mainly distributed in the northwest area. During this period, seven biovars were found, indicating that B. abortus displayed a high diversity of biovars and that the main epidemic areas are in the northern provinces. Strains have high genetic diversity, and bruce07 is the most helpful locus for genotyping of this population. Moreover, 17 MLVA-11 genotypes were found; 13 of them are of known genotypes and four are unassigned genotypes, indicating that B. abortus in this study had several geographic origins. Still, strains from unassigned genotypes may originate from China. Many shared MLVA-16 genotypes were observed in strains from the same provinces in Northern China, which confirmed a brucellosis outbreak within northern regions. WGS-SNP analysis showed that eight Chinese strains formed a ladder-like phylogram (C. Ⅶ) with strains from nine countries, including Uganda, Iraq, Russia, Georgia, Spain, Italy, Egypt, Mongolia, and China; strains were introduced to these countries from a single source. Notably, Chinese strains were closely related to strains from Russia and Mongolia; frequent animal (cattle) trade and exchanges may promote this process. We will provide new and insightful information for strength surveillance and control of B. abortus brucellosis in China.

Pollution caused by copper is one of the key factors of environment contamination. As one of heavy metals, copper is hard to decompose in nature, the biological enrichment of which may lead to severe damage to health. Cu²⁺ detection, thus, possesses a bright application prospect both in environment protection and in human health. In this paper, a dual-functional fluorescence-magnetic composite nano-platform has been designed to sensitively detect, meanwhile capture and remove Cu²⁺ in the solution of water and ethanol (1:1, v/v). The core-shell structure nanoparticle synthesized by using Fe₃O₄ as core and SiO₂ as shell, is covalently bonded with rhodamine derivatives on the silica layer to construct the nano-platform. The emission is increased upon the addition of Cu²⁺, showing fluorescence turn on effect for the detection, and the limit of detection which was as low as 1.68 nM. Meanwhile, Cu²⁺ ions are captured by the coordination with rhodamine derivatives, and can be removable with the help of magnetic field.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumor characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported at the cell membrane of cancer cell from different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. This review summarizes current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cell.

This comprehensive review delves into the multifaceted aspects of ERK signaling and the intricate mechanisms underlying distinct cellular fates. ERK1 and ERK2 (ERK) govern proliferation, transformation, epithelial-mesenchymal transition, differentiation, senescence, or cell death, con-tingent upon activation strength, duration, and context. The biochemical mechanisms underlying these outcomes are inadequately understood, shaped by signaling feedback and the spatial localization of ERK activation. Generally, ERK activation aligns with the Goldilocks principle in cell fate determination. Excessive or insufficient ERK activity inhibits growth, whereas moderated activation supports proliferation and survival. Unraveling the intricacies of how the degree of ERK activation dictates cell fate requires deciphering mechanisms encompassing protein stability, transcription factors downstream of ERK, and the chromatin landscape.

Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.

This article presents the results of isolating and identifying EPF species and screening thermotolerant and highly virulent EPF strains that are promising for controlling Colorado potato beetle populations. Soil samples were collected from southern Kazakhstan for the isolation of fungi used in the experiments. Using the insect bait method, 41 isolates of EPF were obtained from the soils of southern Kazakhstan. PCR analysis based on ITS and TEF loci (elongation factor Ef1a) showed that all the isolates belong to the species B. bassiana. However, analysis of the ITS locus revealed two cryptic species: B. bassiana and B. pseudobassiana. No other fungal species were detected, likely due to the insufficient informativeness of the ITS and TEF loci in distinguishing species. Further studies with other loci are required. As a result of selecting natural isolates for virulence and thermotolerance, the following strains were identified: B13, B14, B15, B22, B23, B24, B25, B23-23, Bc4, Bc7, and Bc8. These strains showed high virulence (100% on the 11th day after treatment) and tolerance to suboptimal temperatures (+15°C and +30°C). Therefore, they are considered the most promising for use in the context of climate change. The data suggest that, despite the source of the isolates, EPF have great potential for controlling Colorado potato beetle populations, as the majority of isolates lead to fatal outcomes. Their geographical origin primarily influences their temperature preferences, which negatively affect their effectiveness in field conditions.

This article explores the use of vegetation indices (VIs) in remote sensing for estimating standing wood volume and volume increments in forest ecosystems. The study investigates the correlations between various VIs and wood volume across different forest stand age classes, focusing on the effectiveness of commonly used indices such as Squared Ratio Simple Red Edge (SQSR) and Red-Edge Ratio Vegetation Index (RERVI), as well as other typical indicators including Enhanced Vegetation Index (EVI), Red-Edge EVI (RE-EVI), and Green Normalized Difference Vegetation Index (GNDVI). Additionally, the analysis considers a pair of indicators based on blue and near-infrared channels, resembling the Blue-normalized Difference Vegetation Index (BNDVI). The research reveals that quadratic and power-law models of SQSR and RERVI demonstrate higher correlations (>0.40) with wood volume, especially in younger forest stands (>0.80). Furthermore, the study highlights the potential of NDII and NDWI indices for estimating volume increments in certain classes of forest stands (0.70). However, correlations vary across different forest stand classes, suggesting the need for further investigation into the reliability of VIs for monitoring wood volume and volume increments in forest ecosystems. Overall, this research contributes to the understanding of the applicability of VIs in remote sensing for forest management and ecosystem monitoring.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

A sustainable, scalable source of energy‐dense chemical fuel is urgently needed to ensure the security of our energy supply for future generations. Solar energy is the only renewable energy source of sufficient scale to replace fossil fuels and meet rising environmental demand. Hydrogen is expected to play a key role as an energy carrier in future energy systems of the world. As fossil fuel supplies become scarcer and environmental concerns increase, hydrogen is likely to become an increasingly important chemical energy carrier and eventually may become the principal chemical energy carrier. When most of the world’s energy sources become non-fossil based, hydrogen and electricity are expected to be the two dominant energy carriers for the provision of end-use services. Photocatalytic hydrogen evolution from water by solar energy over semiconductors offers a promising way for clean and renewable production of hydrogen. The TiO2-based materials have received considerable attention in recent years due to their extensive application in photocatalysis for hydrogen evolution. Though TiO2 is the most widely investigated photocatalyst for hydrogen evolution, it still provides low photocatalytic activity due to the wide bandgap that results in photocatalytic activity only under ultraviolet (UV) irradiation. Modification of TiO2 photocatalysts with several transition metals has been extensively studied to extend the absorbance capacity of TiO2 into the visible range. The effect of different photocatalytic deposition and reaction parameters also play major roles in enhancing the photostability of photoanode and increasing the hydrogen gas output, respectively.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU⁺/αMHC-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP^high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP^low cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Children on farms face high risks of work and non-work-related fatalities, with tractors being a significant contributor. This study examines children's involvement in fatal tractor-related accidents within agriculture in Iceland in 1950-2024, explores adult reflections on childhood tractor-driving experiences, and analyses Members of Parliament´s arguments against setting a minimum age for off-road tractor driving. Data rests on fatal tractor-related accidents using newspaper archives and supplementary sources, narrative interviews with former summer children who stayed at farms in childhood, and parliamentary debates on tractor-related legislation. Over half of the 81 registered accidents involved children, primarily boys, with 75% occurring between 1958 and 1988 when no minimum age for off-road tractor driving existed. Children's fatality incidence rate was more than four times higher than adults. Arguments against minimum age requirements for off-road driving included the need for child labour, children's superior driving skills, and a denial that children were more often victims than adults. Since 1988, no child has died when driving a tractor. A human-centred approach focusing on working conditions, driver capacity, and adherence to safety procedures and legal frameworks is needed to prevent future accidents.

Background: Cardiac development is a complex developmental process. The early cardiac straight tube is composed of an external myocardial layer and an internal endocardial lining. Soon after rightward looping, the embryonic heart becomes externally covered by a new epithelial lining, the embryonic epicardium. A subset of these embryonic epicardial cells migrate and colonize the embryonic myocardium, contributing to distinct cell types. In recent years, our understanding of the molecular mechanisms that govern proepicardium and embryonic epicardium formation has greatly increased. We have recently witnessed a novel layer of complexity governing gene regulation with the discovery of non-coding RNAs. Our laboratory recently identified three distinct lncRNAs, adjacent to the Wt1, Bmp4 and Fgf8 chicken gene loci, with enhanced expression in the proepicardium that are distinctly regulated by Bmp, Fgf and thymosin 4, providing support of their plausible implication in epicardial formation. Methods: Expression of lncRNAs was analyzed in different chicken and mouse tissues as well as their subcellular distribution in chicken proepicardial, epicardial, ventricle explants and in different murine cardiac cell types. lncRNA transcriptional regulation was analyzed by using siRNAs and expression vectors of different transcription factors in chicken and mouse. Antisense oligonucleotides were used to inhibit Gm14014 expression. Cardiac injury was induced ex vivo in mouse ventricle explants by cryoinjury. Furthermore, RT-qPCR, immunocytochemistry, RNA pulldown, Western blot, viability and cell migration assays were conducted to investigate the biological function of Wt1_76127 and Gm14014. Results: We demonstrated that Wt1_76127 in chicken and its evolutionarily conserved homologue Gm14014 in mice are widely distributed in different embryonic and adult tissues and distinctly regulated by cardiac enriched transcription factors, particularly Mef2c and Nkx2.5. Gm14014 is distinctly regulated in mouse ventricular cryoinjury ex vivo models, displaying a negative correlation with epicardial and epithelial to mesenchymal transition markers. Furthermore, silencing assays demonstrated that mouse Gm14014, but not chicken Wt1_76127, is essential for epicardial, but not endocardial or myocardial cell migration. Such process is governed by partnering with Myl9, promoting cytoskeletal remodeling. Conclusion: Our data evidence that Gm14014 plays a pivotal role in epicardial cell migration essential for heart regeneration.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by abnormal growth of mature B cells in the blood, bone marrow, and lymphoid tissues. Although CLL primarily affects the hematopoietic system and lymph nodes, renal involvement is exceptionally rare and presents diagnostic and treatment challenges. Potential causes of renal failure in CLL patients include sepsis, dehydration, tumor lysis syndrome (TLS), compression of the ureter by enlarged lymph nodes, and side effects of cancer therapy. This report presents a case of CLL with renal infiltration leading to severe renal failure, discussing the clinical presentation, diagnostic workup, and management of this condition.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, and polyacrylamides, to the promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies emerge as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA and multiplex assay. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

Potential permanent magnet (Fe0.7Co0.3)2B has large saturation magnetization and high Curie temperature but a moderate magnetocrystalline anisotropy (MCA) and displays relatively low coercivity. One way to improve coercivity is to combine the contribution from magnetocrystalline- and magnetic shape anisotropy by preparing (Fe0.7Co0.3)2B nanowires. We study the effect of size, morphology, and surface defect on the hard magnetic properties of nanowires using micromagnetic simulation. The hard magnetic properties of (Fe0.7Co0.3)2B nanowire bonded magnet have been estimated, including the role of inter-wire magnetostatic interaction. By considering the existence of local reduction of MCA energy up to 30% on the surface layer of nanowires, the anisotropic bonded magnet with 65% vol. of (Fe0.7Co0.3)2B nanowires displays typical magnetic properties of remanence Br=8.4 kG, coercivity Hci=9.9 kOe, and maximum energy product (BH)m=17.8 MGOe. Developing effective technology for synthesizing nanowires and fabricating corresponding bonded magnets is promising for manufacturing practical magnets based on magnetic phase with relatively low or moderate MCA, such as (Fe0.7Co0.3)2B.

Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Current research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on the receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. The results revealed that L-quebrachitol suppressed RANK-mediated signalling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of receptor activator of nuclear factor κB (RANK)-mediated signalling pathways. However, further exploration of L-quebrachitol's potential as a therapeutic approach for osteoporosis is warranted.

(1) Background: The intermediate-depth seismicity in the Vrancea region (Romania) is characterized by localized and persistent earthquake activity that culminates about two or three times in a century with the occurrence of a large event (M 6.5). Here we have revisited some important seismicity characteristics, using earthquake catalog data spanning two different time periods: 2005 – 2013 and 1960 – 2000. (2) Methods: we have determined the b-value of the frequency-magnitude distribution of earthquakes, using a maximum likelihood procedure, and estimated the parameter to quantify anomalous seismicity rate decreases and increases. (3) Results: by using data from the first period, we have confirmed the existence of a decreased b-value in the deepest part of the seismogenic zone; by using data from the second period, we have statistically confirmed the seismic quiescence that preceded the occurrence of the 1977 M7.4 Vrancea earthquake. (4) Conclusions: the decreased b-value has been interpreted either in terms of an increased lithostatic stress with depth or as an indicator of the depth range where the next major Vrancea earthquake may occur. The time variation of the seismicity parameter may reveal anomalous seismic quiescence and increased earthquake rates that may precede the occurrence of large earthquakes.

Marine seaweeds are nature’s largesse resource in human well-being. Seaweed’s contribution to the food industry is being widened for its rich source of essential vitamins, minerals, and PUFA. ‘Nori’ is a dried sheet of red seaweed Porphyra sp. used to make ‘sushi’ a renowned cuisine in Japan, and other Southeast Asian countries. In this present study, commercial-grade ‘Nori’ was extracted and fractionated with different solvents, and subjected to evaluate the cytotoxic activity on human ovarian tetracarcinoma cells (PA1). As a result, the ethyl acetate fraction was found effective in inhibiting the proliferation of human ovarian cancer cells with an IC50 value of 41.1 µg/mL. The main component responsible for anticancer activity was determined as a sesquiterpene lactone Tatridin B (3h-cyclodeca[b]furan-2-one, 4,9-dihydroxy-6-methyl-3,10-dimethylene-). Moreover, it was found effective in inhibiting NSD2, an important and recently proposed biomarker for several types of cancer. This is a hitherto report on the presence of this compound in ‘Nori’ showing potent anticancer activity on human ovarian tetracarcinoma (PA1).

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

Enzymatic degradation of organic pollutants is a new and promising remediation approach. Peroxidases are one of the most commonly used classes of enzymes to degrade organic pollutants. However, it is generally assumed that all peroxidases behave similarly and produce similar degradation products. In this study, we conducted detailed studies of the degradation of a model aromatic pollutant, Sulforhodamine B dye (SRB dye), using two peroxidases—soybean peroxidase (SBP) and chloroperoxidase (CPO). Our results show that these two related enzymes had different optimum conditions (pH, temperature, H₂O₂ concentration...etc.) for efficiently degrading SRB dye. High-performance liquid chromatography and LC-mass spectrometry analyses confirmed that both SBP and CPO transformed the SRB dye into low molecular weight intermediates. While most of the intermediates produced by the two enzymes were the same, the CPO treatment produced at least one different intermediate. Furthermore, toxicological evaluation using lettuce (Lactuca sativa) seeds demonstrated that the SBP-based treatment was able to eliminate the phytotoxicity of SRB dye, but the CPO-based treatment did not. Our results show, for the first time, that while both of these related enzymes can be used to efficiently degrade organic pollutants, they have different optimum reaction conditions and may not be equally efficient in detoxification of organic pollutants.

Background. Currently, most of the research in breast cancer has been carried out in conventional two-dimensional (2D) cell culture due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell-cell and cell-extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. in this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differ-entially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2×105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both, miRNAs and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene on-tology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cy-toskeleton organization, as well as in the MAPK and AGE-RAGE signaling KEGG-pathways. In-terestingly, hsa-mir-122-5p (Fold Change (FC)=15.4), hsa-mir-369-3p (FC=11.4), and hsa-mir-10b-5p (FC=20.1) regulated up to the 81 % of the 70 downregulated DE-mRNAs. Conclu-sion, the organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of miRNAs-mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell-cell and cell-ECM as well as the change in the culture architecture impacts gene ex-pression, and therefore, support the pertinence of migrating breast cancer research from conven-tional cultures to 3D models.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

Cell viability refers to the proportion of living, healthy cells within a given population. This information is crucial in any cell-based research, especially in toxicology. Over the past century, numerous methods for assessing cell viability have been developed. These methods can be categorized into five main types: non-invasive cell structure damage, invasive cell structure damage, cell growth, cellular metabolism, and cell membrane potential. Each method operates on different principles and has its own advantages and disadvantages, making it essential for researchers to choose the method that best fits their experimental design. Despite the variety of cell viability methods available, most rely on indirect measurements of cell viability, which may compromise their accuracy. In this sense, there is insufficient information regarding their accuracy, highlighting the need for researchers to investigate the accuracy of both existing and future methods.

Background Glioblastoma (GBM) is a poor prognosis malignant grade 4 glioma. After surgical resection, standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. The DC vaccination increased the amount of intratumoral-activated cytotoxic T lymphocytes and decreased the number of FoxP3-positive regulatory T cells. Based on these da-ta, we have developed a phase II protocol with the DC vaccine concomitant to standard RT-CT in patients undergoing surgery for GBM. Methods This is a single-arm, monocentric, phase II trial evaluating progression-free survival (PFS) and the safety of a DC vaccination integrated with standard therapy in resected GBM patients. The vaccine administration begins at the end of the RT-CT (Induction Phase) and is subsequently al-ternated with TMZ cycles (Maintenance Phase). The primary endpoints are PFS and safety. Among the secondary endpoints, are the in vitro and in vivo Immune response evaluations. Results By December 2022 , nine patients had been enrolled in the first step. Two patients progressed within three months after leukapheresis and none had experienced DC vaccine-related G3-4 tox-icity. Five patients had a positive DTH test against KLH. By June 2023. The median OS from leu-kapheresis was 23.1 months and 24.7 from surgery. Conclusions This combination therapy is well-tolerated, and we have achieved the two endpoints required for the first step. Therefore, the study will proceed to enroll the remaining 19 patients.

Biological parameters extracted from electrical signals from various body parts have been used for many years to analyze the human body and its behavior. In addition, electrical signals from cancer cell lines, normal cells, and viruses, among others, have been widely used for the detection of various diseases. Single-cell parameters such as cell and cytoplasmic conductivity, relaxation frequency, and membrane capacitance are important. There are many techniques available to characterize biomaterials, such as scanning tunneling microscopy (STM), nanotechnology, microstrip cavity resonance measurement, dielectric impedance measurement (DEPIM), etc. This article reviews the single cell isolation and sorting techniques, summarizes the common single cell operations such as impedance flow cytometry, cell electrical impedance, electrical impedance sensing, and summarizes the current single cell analysis techniques and their applications.

A new longitudinal flow heat dissipation theory for cylindrical batteries is proposed in order to increase the energy density and uniform temperature performance of cylindrical lithium-ion battery packs while also shrinking their size by roughly 10%. First, a genetic algorithm is used to identify the single cell's thermal properties. Based on this, modeling and simulation are used to examine the thermal properties of the longitudinal flow-cooled battery pack. It is found that the best coolant flow scheme has one inlet and one outlet from the end face, taking into account the cooling effect of the battery pack and engineering viability. Lastly, Thermal Dummy Cells (TDC) is used to conduct a validation test of the liquid cooling strategy. Additionally, the simulation and test results demonstrated that the liquid cooling solution can keep the battery pack's maximum temperature rise under the static conditions of a continuous, high-current discharge at a rate of 3C to 20 °C and under the dynamic conditions of the New European Driving Cycle (NEDC) to 2 °C. In applications where the space requirements for the battery pack are quite severe, the longitudinal flow cooling method has some advantages.

CD8 T cells and Natural Killer (NK) cells are cytotoxic lymphocytes important in the response to intracellular pathogens and cancer. Their activity depends on the integration of a large set of intracellular and environmental cues, including antigenic signal, cytokine stimulation and nutrients availability. This integration is achieved by signaling hubs such as the mechanistic target of Rapamycin (mTOR). mTOR is a conserved protein kinase, controlling cellular growth and metabolism in eukaryotic cells and therefore is essential for lymphocyte development and maturation. However, our current understanding of mTOR signaling comes mostly from studies performed in transformed cell lines, which constitute a poor model to comprehend metabolic pathway regulation. Therefore, it is only quite recently that the regulation of mTOR in primary cells has been assessed. Here we review the signaling pathways leading to mTOR activation in CD8 T and NK cells, focusing on activation by cytokines. We also discussed how this knowledge can contribute to immunotherapy development for intracellular pathogen and cancer treatment.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate and avoiding immune surveillance. Experimental studies showed the association of THCs with a high frequency of cancer metastasis; however, the underlying mechanisms remain unclear. Many other questions also remain to be answered: the role of genetic alterations in tumor cell fusion, the molecular landscape of cells after fusion, the lifetime and fate of different THCs, and the specific markers of THCs, and their correlation with various cancers and clinicopathological parameters. In this review, we discuss the factors and potential mechanisms involved in the occurrence of THCs, the types of THCs, and their role in cancer drug resistance and metastasis, as well as potential therapeutic approaches for the prevention and targeting of tumor cell fusion. In conclusion, we emphasize the current knowledge gaps in the biology of THCs that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

This comprehensive overview of the historical milestones in cell culture underscores key breakthroughs that have shaped the field over time. It begins with Wilhelm Roux's seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel's influential contributions, notably the immortalization of chicken heart cells, mark a significant advancement in cell culture techniques. Holtfreter, Moscona, and Leighton introduced innovations such as 3D cell culture, laying the groundwork for further exploration. The advent of induced pluripotent stem cells by Takahashi and Yamanaka in 2006 was revolutionary, enabling the reprogramming of differentiated cells into a pluripotent state. Since then, recent innovations include spheroids, organoids, and organ-on-a-chip technologies, aiming to mimic the structure and function of tissues and organs in vitro, pushing the boundaries of biological modeling and disease understanding. In this review, we overview the history of cell culture shedding light on the main discoveries, pitfalls and hurdles that were overcome during the transition from 2D to 3D cell culture techniques. Finally, we discussed the future directions for cell culture research that may accelerate the development of more effective and personalized treatments.

Studies performed at single-cell resolution have demonstrated the physiological significance of cell-to-cell variability. Various types of mathematical models and systems analyses of biological networks have further been used to gain a better understanding of the sources and regulatory mechanisms of such variability. In this work, we present a novel sensitivity analysis method, called molecular density function perturbation (MDFP), for the dynamical analysis of cellular heterogeneity. The proposed analysis is based on introducing perturbations to the density or distribution function of the cellular state variables at specific time points, and quantifying how such perturbations affect the state distribution at later time points. We applied the MDFP analysis to a model of signal transduction pathway involved in TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in HeLa cells. The MDFP analysis showed that caspase-8 activation regulates the timing of the switch-like increase of cPARP (cleaved poly(ADP-ribose) polymerase), an indicator of apoptosis. Meanwhile, the cell-to-cell variability in the commitment to apoptosis depended on mitochondrial outer membrane permeabilization (MOMP) and events following MOMP, including the release of Smac (second mitochondria-derived activator of caspases) and cytochrome-C from mitochondria, the inhibition of XIAP (X-linked inhibitor of apoptosis) by Smac and the formation of apoptosome.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Abstract: Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components in NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background of NSCLC is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin. We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the effect of transcription factor (TF) LRF, a known epigenetic silencer, was examined on the epigenome modulation. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060-109,747,960 mouse chromosomal region to micro-RNA upregulated species. Fur-thermore, the novel epigenetic miR-148b-3p/PVT1/ZBTB7A axis was identified, which differentiates lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes. The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease and patient-tailored treatments.

With worsening environmental degradation and increasing international demand for human health, plant cell based technology will be more important. The aim of this review is to give an overview regarding key points of current progress and development trend of nature medical and edible plants from the framework of whole plant cell engineering including cell cultures, cell fusion and cell splitting derived biotechnology. Here we sum up three main application trends of medical plants cell cultures covering industrial output, technology upgrading and potential resource development. We also provide classification and typification insights to summarize the development of somatic hybridization in cereal, vegetables crops and other medicinal and edible plants as well as application of artificial polyploidy induction in major medicinal herbs. Development medicinal and edible homologous plants based on modern plant cell engineering will bring us a promising future.

Viruses can infect a cell via one or both routes viz. cell-to-cell (c-c) or cell-free (c-f) . Pathogenesis studies of various viruses, including HIV, have shown that c-c transmission yields a significantly higher infection magnitude than the c-f route. Expectedly, potent antibodies inhibited c-f infection more efficiently than with c-cell transmission. To achieve a one-step, synchronous infection cycle that provides amplified infection, we have studied a consistent and efficient c-c HIV infection model since 1992. H9 cells persistently infected with HTLV-IIIB (H3B cells) and uninfected target CD4+ lymphocyte line (HuT78) were mixed in a ratio of 1:4 respectively. We have recently used this model to produce HIV designer antigens that have been shown to elicit monoclonal as well as polyclonal specific antibodies against novel epitopes that are formed post virus-cell engagement, but prior to fusion. The model can be extended for HIV neutralizing antibody assays or drug inhibitors against high multiplicity of infection.

We explored an extension of the Cauchy-Riemann equations to the algebra of treons, recently described by Alejandro Bermejo, whose elements are ordered 3-tuples. We leveraged the isomorphism between the algebra of treons and algebra B, and deduced the Cauchy-Riemann equations for the algebra of treons, establishing the necessary conditions for analyticity in this algebraic structure. This work significantly broadened our horizons in complex analysis and introduced new possibilities for applications across various fields of advanced mathematics.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF, then the targets of them were obtained from TCMSP, ETCM, ITCM and Swiss TargetPrediction databases. RA disease related targets were obtained from DisGenet, OMIM and GeneCards databases. 99 overlapped targets were obtained using Venn diagram. The protein-protein interaction network (PPI)、the compound-target network (CT) and the compound-potential target genes-signaling pathways network (CPS) were built and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. And the core therapeutic targets were identified as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, RELA by network pharmacology analysis, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in mice model of xylene-induced ear edema and strong analgesic effect on acetic acid-induced withing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF could alleviate toe swelling and ameliorate joint damage. The elevation of serum content of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may exert regulation on the ERK and NF-κB pathway. The results provided a new perspective for the topical application of CF on RA.

Bacillus subtilis is a model organism used to study molecular processes in Gram-positive bacteria. Sigma factor B, which associates with RNA polymerase, is one of the transcriptional regulators involved in the cell’s response to environmental stress. Experiments have proven that the amounts of free σB (SigB) are controlled by a system of anti- (RsbW) and anti-anti-sigma (RsbV) factors expressed from the same operon as SigB. Moreover, the phosphorylation state of RsbV is controlled by phosphatases RsbP and RsbU, which directly dephosphorylates RsbV. A set of chemical equations describing the network controlling the levels of free SigB was converted to a set of differential equations quantifying the dynamics of the network. The solution of these equations allowed the simulation of the kinetic behavior of the network and its components under real conditions. In this study, the time series of protein expression measured by mass spectrometry were utilized to investigate the role of the phosphatases RsbU/RsbP in transmitting the environmental signal. Additionally, the influence of kinetic constants and the amounts of other network components on the functioning of the network was investigated. A comparison with the same simulation performed using transcriptomic dataset showed that while the time series between the proteomic and transcriptomic datasets) are not correlated, the results are the same. This indicates that when modeling is done within one dataset, it does not matter whether the data come from the mRNA or protein level. In summary, the computational results based on experimental data provide quantitative insight into the functioning of the SigB-dependent circuit and offer a template for the quantitative study of similar systems.

One characteristic of mammalian species is their capacity to produce and secrete milk from their mammary glands to feed and provide vital nutrients for the growth of their offspring. Even though mammary glands provide the same function in different species, their development, shape, and structure can vary according to their reproductive and ecological adaptations. Reproduction studies are important for cetacean conservation because they provide essential information to assess the dynamics of populations and species, particularly in relation to the management of animals under human care. A vast majority of literature on the female cetacean reproductive anatomy and physiology has focused on the ovaries, which can be used to infer life history characteristics, or genital diseases and anomalies. However, literature regarding the morphology, physiology, and developmental pattern of their mammary glands is scarce, with few anatomical and histological descriptions in species such as baleen whales; and more recently it has been assessed with the use of ultrasound in finless porpoises (Neophocaena asiaeorientalis). The aim of this review is to describe the current diagnostic tools applied in human and veterinary medicine to assess the mammary glands and how marine mammal medicine could benefit from these tools to evaluate the mammary glands in free-ranging and captive cetaceans. With the use of imaging techniques such as B-mode ultrasound, non-invasive studies could be performed to assess the mammary tissues, as what has been done to characterize the morphology of other organs in cetaceans, such as the reproductive tract of Indo-Pacific bottlenose dolphins under human care. By understanding and revising the current diagnostic tools to assess the mammary gland of humans and domestic animals, such as ultrasonography, it might be possible to determine which techniques could be applied by marine mammal veterinarians to enhance the evaluation of the cetacean mammary gland morphology and physiology.