Tumors are complex tissues of malignant cells surrounded by a diverse cellular micro-environment with which they interact. The molecular and cellular underpinnings of cancer cells have been increasingly understood during the last few decades. Nonetheless, a great deal remains unknown regarding the ways in which tumour cells modify their surroundings and impact the organisation and makeup of cells. This review aims to concentrate on recent advancements in molecular characterization of tumor cells and its immunology, provides recent and general insight into cancer immunity and immunotherapy, and discusses the immunobiology of human adaptive and innate immunity to malignant growth of cancer cells, the mechanisms that support human immune response from beneath, an up-to-date scientific development to cancer immunotherapy, and how tumor and host responses can Encircle as a military tactic effective anti-cancer immunity.

The influence of the secondary process of evaporation of the reaction product on the kinetics of interaction of gases (O₂, Cl₂, NH₃, H₂O and N₂H₄ vapors) with the surface of some metals (Cr, Pb, Si, Ge) and compounds (BN, SiO₂, SiC) is discussed. Also is considered the case when the growth of the scale is preceded by the process of gas etching of the metal surface. A general equation is given that describes the scale growth-evaporation kinetic (sample mass change - time) curves during the interaction of gases with the surface of metals and compounds. Special cases of parabolic, cubic and fourth degree processes are discussed.

The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Gastric cancer has become the cancer with the highest incidence rate in the world.Immunotherapy, especially immune point inhibitors targeting programmed cell death 1（PD-1） or its ligand programmed cell death ligand 1 (PD-L1), has become an indispensable part of the clinical treatment of GC. But, only a few of sufferers experience persistent clinical responses during immunotherapy. In this article, we discuss the current mainstream immunotherapy methods for gastric cancer, introduce the mechanisms that lead to immunotherapy resistance, potential biomarkers that can forecast the occurrence of immunotherapy resistance, and measures to improve the efficacy of immunotherapy.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

The prevalence of allergic diseases, including food allergy, is increasing, especially in developed countries. Implementation of an elimination diet is not a sufficient therapeutic strategy in patients with food allergy, whose quality of life is significantly impaired. In recent years, new effective therapeutic strategies have been developed, such as the application of oral, sublingual, and epicutenous immunotherapy. Oral immunotherapy is the most often applied strategy because of its effectiveness and ease of application, with an acceptable safety profile. The effectiveness of oral immunotherapy in patients with egg, cow's milk and peanut allergy has been proven both in terms of raising of the threshold and the development of tolerance, and in some patients, the development of sustainable unresponsiveness. Although oral immunotherapy is an effective treatment for food allergy, several limitations, including long duration and a significant rate of reported adverse events, reduces its success. Therefore, new therapeutic options, such as treatment with biologicals, either as combinations with food allergen immunotherapy or as monotherapy with the aim of improving the efficacy and safety of treatment are being investigated..

Immunotherapy with programmed Cell Death Protein/Programmed Cell Death Ligand 1 (PD-1/PD-L1) targeting antibodies has transformed clinical outcomes for patients with non-small cell lung cancer (NSCLC) and has become an integral part of standard treatment regimens. However, the response to PD-1/PD-L1 inhibitors varies, and many tumors present with either primary or acquired resistance to immunotherapy. There are emerging data on potential mechanisms underlying resistance to immunotherapy which is derived mainly from either preclinical studies or secondary correlative analyses from clinical trials. Resistance to immunotherapy is complex and can present immediately after treatment initiation (primary resistance) or after initial clinical benefit (secondary or acquired resistance). The tumor microenvironment, particularly the presence, and activity of T cells, also significantly influences resistance with both tumor-extrinsic as well as tumor-intrinsic mechanisms such as lack of T-cell infiltration, insufficient neoantigens, or absence of an interferon signature identified as being associated with ICI resistance. Improved understanding of the molecular and immunologic mechanisms underlying immunotherapy resistance is essential for the future development of effective therapies targeting immunotherapy resistance. In this review, we discuss the emerging data identifying the molecular mechanisms of primary resistance to immunotherapy and explore potential therapeutic strategies to target these.

Resistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy that otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq defined fraction. Finally, we generated a 15-genes prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes.

Bio-absorbable stents are a novel tool which relieve stenosis and then resorb as the patient grows, avoiding obligatory re-intervention. This case describes the novel use of an iron bio-absorbable stent in a child with surgically repaired Tetralogy of Fallot who post-operatively developed a severely stenotic right ventricular outflow tract.

The interplay between the human gut microbiota and the peripheral immune system significantly affects the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. Despite this profound connection, the practical implications of microbiota dysbiosis in cancer immunotherapy ICIs & and CAR-T remain intricate and poorly understood in practical terms. This paper offers a comprehensive review of current literature on the role of gut microbiota dysbiosis in tumor development, and emerging microbiota modulation interventions, with a focus on fecal microbiota transplantation (FMT). FMT is a cost-effective therapeutic avenue, particularly in addressing diseases rooted in antibiotic-resistant bacteria, such as Clostridium difficile. Here we provided insights into the applications of FMT and other gut microbiota therapies in the landscape of cancer treatment, emphasizing their influence on the tumor microenvironment and the efficacy of ICIs with suggestions for future research directions and their implications for clinical practice.

Tumor immunotherapy represented by immune target blocking and chimeric antigen receptor cell therapy has developed rapidly. Among them, Natural Killer Cell (NK) is gradually becoming another preferred immunotherapy method after T cell immunotherapy because of its unique killing effect in innate immunity and adaptive immunity. Although NK cell therapy has achieved promising results in clinical trials, there are still some problems, such as low efficacy in solid tumors, insufficient penetration of NK cells and high cost of treatment. Nanomaterials are expected to be an excellent tool to improve the anti-tumor immune response of NK cells due to their advantages such as chemical specificity, biocompatibility and simple synthesis. Nanomaterials can enhance the cytotoxicity of NK cells, participate in the modification and noninvasive cell-tracking patterns of NK cells，and mediate their homing and infiltration, and thus significantly improve the efficiency of NK cell immunotherapy. In this review, we will briefly introduce the methods and mechanisms of tumor immunotherapy, emphasize the research progress of NK cell-based immunotherapy and imaging, and finally summarize the direction and research progress of nanomaterials in NK cell-based immunotherapy.

The ocean of the planet Earth, which is as thin as a cicada's wings, play a role of catalyst to the evolving of the ancient plates. The ocean and the ancient plates of the planet Earth formed a magic Whirlpool of the Cross “十” shape with double whirl arms. The central core of the Cross “十” shape Ocean-Plate Whirlpool is the Hint Black Hole (HBH) located at the Northwestern Pacific Ocean floor which is decorated with invisible geological age distribution of clam shell. The double whirl arms of ancient plates are distinguished to be left and right at Bering Strait and just formed the ring of fire of the Pacific Ocean.The Cross “十” shape Ocean-Plate Whirlpool of the planet Earth was born at the equatorial area about 66 Ma ago and is rotating anticlockwise and drifting northward by a mini footprint of spiral at s speed of as slow as a snail moves. Obviously, it would come to an end at the North Pole about 100 Ma in the future. So, the lifespan of the Cross “十” shape Ocean-Plate Whirlpool would be about 166 Ma, from birth to death on the planet Earth.What is hidden behind of the evolving of the oceans and the ancient plates is the golden law of geometrical progression of ladder pagoda of attributes evolving of them, which is “1➨2➨4➨2➨1”, including upgrading and downgrading process. It seems to hint that what is happening on the planet Earth, including the top-level species of human race, is actually unique in the Milky Way galaxy in essence.The property roles of expanding and shrinking are existing in the Cross “十” shape Ocean-Plate Whirlpool by face to face and the exchange of property roles took place tens of millions of years ago. And that situation would happen again tens of millions of years in the future. It seems a giant circle of evolving of the exchange of property roles would be drawn by the Cross “十” shape Ocean-Plate Whirlpool in her lifetime.

The rare abscopal effect during radiotherapy is thought to be caused by the release of immune-stimulated damage-associated molecular patterns, such as high mobility group box-1 protein (HMGB1), from cancer cells. Although external irradiation of cancer cells increases HMGB1 release, it is not clear if HMGB1 is released from cells after administering 131I-labeled m-iodobenzylguanidine (131I-MIBG) as an internal targeted radiotherapeutic agent. This study aimed to determine if HMGB1 is released from human-derived cancer and normal cells after administering 131I-MIBG. Methods: Extracellular lactate dehydrogenase (LDH) and HMGB1 released from H441 (human-derived lung adenocarcinoma cell line) and HaCaT (human keratinocyte cell line) 1 day after 2- and 10-Gy X-ray irradiation were measured. Accumulations of 131I-MIBG in SH-SY5Y (human-derived neuroblastoma cell line) and HaCaT were measured 60 min after administering 131I-MIBG (0.37, 1.85, 3.7 MBq/well). Extracellular LDH and HMGB1 released from SH-SY5Y and HaCaT 1 day after administering 131I-MIBG were also measured. Results: The extracellular LDH and HMGB1 released from H441 after 10-Gy X-ray irradiation were significantly increased. However, the extracellular LDH and HMGB1 released from HaCaT after 2-Gy and 10-Gy X-ray irradiation were not increased. After administering 1.85 MBq and 3.7 MBq 131I-MIBG, the extracellular LDH and HMGB1 released from SH-SY5Y were both significantly increased, but only the extracellular LDH released from HaCaT was significantly increased. Conclusions: HMGB1 was released from neuroblastomas but not from normal cells after 131I-MIBG administration, suggesting that a combination of 131I-MIBG and immunotherapy may be feasible.

A cross-sectional survey was distributed to 1322 members of a 1-on1 personalized strength training studio. 366 respondents (n=134 male and n=232 female), all aged over 20 years reported considerable training experience; 55% of males and 42% of females reporting 5+ years. Data were analyzed and reported descriptively with differences >5% identified based on use of the 5-point likert scale, sample size and nature of the observations. Disparity between males and females were identified; males reported higher perceptions of managing effort, technique, and programming without supervision compared to females. Safety was noted as being more important to females compared to males. Qualitatively, additional themes were raised including analogy of the personal relationship between trainer and trainee being similar to that of medical professionals. This was validated where participants discussed their adaptations from supervised strength training including quality of life in aging, and recovery from medical conditions and injury. Data is discussed in context of a previous body of literature suggesting males falsely report higher confidence in tasks compared to females, particularly in relation to effort, role models, and verbal encouragement. This research proves beneficial for strength training practitioners in enhancing their understanding and expectations of clients, as well as hopefully proving insightful in engaging more people in strength training.

The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and non-tumoral cells. The success of TME-targeted therapies highlights their potential in achieving better cancer control or even a cure.

Background and introduction: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases; Case report: A 65-year-old ex-smoker man presented to our facility with nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis; Discussion and Conclusion: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.

Introduction: pembrolizumab showed to increase survival in patients with metastatic melanoma, Con-sidering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. (2) Methods: A search was conducted on Pubmed using "pembrolizumab," and "metastatic melanoma" as keywords, considering studies from 2022 onward. (3) results: we reviewed pembroli-zumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, re-al-life data, biomarkers, obesity, and vaccines (4) Conclusions: pembrolizumab is a fundamental op-tion in the therapy of metastatic melanoma. However, a certain group of patients do not respond and therefore new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm preliminary results.

This study aims to assess the impact of deforestation and carbon sequestration within the Gandoca-Manzanillo Wildlife Refuge, Costa Rica, using high-resolution satellite imagery from Planet NICFI and Sentinel-2. The research evaluates the impact of forest degradation on forest health and carbon absorption during two periods in 2024 (January and August). Advanced vegetation indices (NDVI, GNDVI, EVI, and SAVI) were applied to assess changes in forest cover and health. Planet NICFI data revealed a 0.41% loss in forest cover, identifying subtle degradation less detectable with Sentinel-2. In terms of carbon sequestration, Sentinel-2 showed a modest increase in CO₂ absorption from 180,231.88 tons to 186,211.33 tons, while Planet NICFI indicated a decrease from 3,984,470.82 tons to 3,820,917.83 tons, suggesting forest degradation. These findings highlight the importance of high-resolution satellite imagery in detecting fine-scale disturbances that lower-resolution data might miss. However, the study’s short timeframe, covering only two periods in 2024, limits long-term trend analysis. The research underscores the need for improved remote sensing technologies and stronger legal frameworks to protect areas like Gandoca-Manzanillo from illegal logging. Despite programs like Payment for Ecosystem Services (PES) in Costa Rica, significant challenges remain in protecting biodiversity-rich regions.

Burnout, characterized by emotional and physical exhaustion, poses a significant challenge to adolescent athletes, particularly in high-intensity sports like basketball. Emotional Intelligence (EI) is the ability to manage emotions, which is negatively associated with burnout. Emotional labor, including strategies of surface acting (SA), deep acting (DA), and genuine expression (GE), is a potential key role in emotion management between EI and burnout for athletes. This study aims to investigate the relationship between EI and burnout, as well as the mediating role of emotional labor strategies among adolescent basketball players. Our cross-sectional study, conducted in youth sports schools in four different places of China, involved 260 basketball players. Our study found EI to be negatively associated with burnout. SA and GE were identified as significant mediators in this relationship, with SA positively associated with burnout and GE negatively associated. These findings suggest that enhancing EI and optimizing emotional labor strategies could be key in mitigating burnout among young athletes, thereby improving their well-being and performance.

The boosted interest in the use of rare earth elements (REEs) in modern technologies had also increase the necessity of their recovery from various sources, including raw materials and wastes. Though Hydrometallurgy plays a key role in these recovery processes, some drawbacks (apparent or not) of these processes, had led to the development of a more environmental friendship subclass named Solvometallurgy, in which non-aqueous solvents substituted to the aqueous media of the hydrometallurgical processing. The non-aqueous solvents chosen for these usages are, besides ionic liquids (ILs), the so-named Deep Eutectic Solvents (DEEs). The utilization of DEEs included the leaching of REEs from the different sources containing them, and also in the separation-purification steps necessary for the yielding of these elements, normally as oxides or salts, in the most purified form. This work reviewed the most recent literature (2023 year) about the utilization of deep eutectic solvents in the recovery of REEs from various sources, and in the coupling of these two (DESs and REEs) to derived compounds to be used in other fields.

The freshwater bodies of Nepal host a great deal of fish diversity; however, the molecular study of Nepalese fish is still in its early stages. Conservation management tactics require knowledge of the real species composition, often impeded by descriptions of intermittent species based on traditional taxonomy. Catfish, one of the most overfished taxa on the planet are abundant and heavily exploited in the eastern region of Nepal. Hence, actual catfish diversity in this region needs to be examined using a combined morphological and molecular DNA barcoding approach. In this study, we sequenced the cytochrome oxidase subunit I (COI) gene in Nepalese fish species for the first time and used it for molecular identification. Altogether, 99 specimens representing 29 species belonging to 21 genera and 8 families were successfully barcoded. They were found to be 98.5–100% identical to the known sequences deposited in the GenBank and BOLD databases. Of these, two species, Amblyceps arunachalense and Erethistoides sicula were recorded for the first time in Nepal. Out of 29 species, one species was found to be Endangered, one species as Vulnerable, two species were classified as Near Threatened, one species as Data Deficient, and 24 species were categorized as Least Concern. The intraspecific genetic distances within species ranged from 0 to 5%. The highest intraspecific genetic distances (Kimura 2 parameter) were found among the individuals of two species, namely E. sicula (4%) and Glyptothorax telchitta (5%), indicating the presence of putative (sub) species. The interspecific genetic distances among the catfishes in eastern Nepal ranged between 8.47% (between Glyptothorax trilineatus and G. cavia) and 26.38% (between Amblyceps arunachalense and Chaca chaca). The GC content at the 1st, 2nd, and 3rd positions of the codons was found to be 42.4%, 49.3% and 43.8%, respectively. These findings will support future initiatives for fish resource inventory, monitoring and management. It is also an important input to the DNA barcode library of catfish in the eastern region of Nepal.

The Ali-Cesaro Stolz theorem, introduced in this paper, extends the classical Cesaro-Stolz theorem by addressing cases where the latter does not yield results or provides a "Does Not Existe (DNE) form. This novel theorem leverages the properties of limits and Z-transforms, offering a robust framework for analyzing sequences and series. The theorem is particularly effective in scenarios where traditional approaches fail, providing new insights and tools for mathematical analysis. This paper presents a detailed formulation of the Ali-Cesaro Stolz theorem, including proofs, applications, and a discussion on its implications and advantages over existing methods.

Bands of interdendritic porosity and positive macrosegregation are commonly observed in pressure die castings, with previous studies demonstrating their close relation to dilatant shear bands in granular materials. Despite recent technological developments, the micromechanism governing dilatancy in the high pressure die casting (HPDC) process for alloys between liquidus and solidus temperature region is still not fully understood. To investigate the influence of fluid flow and the size of externally solidified crystals (ESCs) on the evolution of dilatant shear bands in HPDC, various filling velocities were trialled to produce HPDC samples of Al8SiMnMg alloy. This study demonstrates that crystal fragmentation is accompanied by a decrease in dilatational concentration, thus producing an indistinct shear band. Once crystal fragmentation stagnates, the enhanced deformation rate associated with a further increase in filling velocity (from 2.2 ms^-1 to 4.6 ms^-1) localises dilatancy into a highly concentrated shear band. The optimal piston velocity is 3.6 ms-1, under which the average ESC size reaches the minimum and the average yield stress and overall product of strength and elongation reaches the maximum value of 144.6 MPa and 3.664 GPa%, respectively. By adopting the concept of force chain buckling in granular media, the evolution of dilatant shear bands in equiaxed solidifying alloys can be adequately explained based on further verification with DEM-type modelling in OpenFOAM. Three mechanisms for ESC enhanced dilation are presented, elucidating previous reports relating the presence of ESCs to the subsequent shear band characteristics. By applying the physics of granular materials to equiaxed solidifying alloys, unique opportunities are presented for process optimization and microstructural modelling in HPDC.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

The Indorama Eleme Petrochemical Limited (IEPL) is found in the southern part of Nigeria more specifically on the Rivers State southern religion Nigeria. It consists of five distinct units, each of which generates its own unique trash at a rate of around 3115.98 tonnes per year. This study had the goal of concentrating on the management of the processing wastes in order to minimize the negative effects that they have on the environment. It is necessary to have an understanding of the number, nature, and make-up of IEPL's industrial wastes in order to effectively manage and regulate the development of waste there. As a result, we decided to collect data through the use of questionnaires. The classification of industrial wastes was accomplished by doing a comparative study and synthesis of research that were relevant to the management of petrochemical waste. Because an individual coding system is required for the integrated management of industrial waste, we gave each type of trash a code that consists of thirteen digits. The primary components of trash were catalysts (9.58 percent), metallic materials (7.62 percent), plastic barrels (35.77 percent), coke (12.66 percent), wood (4.47%), oil (4.15%), glass (0.028 percent), cooling tower packaging (6.7 percent), and other material (18.83 percent). According to the findings of the investigation into the physical qualities of the wastes, only 11.81% of these residues were liquid, while 88.19% were solid. The current handling of these wastes has been experiencing significant difficulties as of late. garbage management at IEPL was particularly challenging due to the wide variety of wastes produced there and the dangerous nature of the wastes themselves (88.19% of garbage was hazardous waste). Recycling and reuse of garbage may have been the greatest decision in some situations; yet, incineration and disposal of waste are also necessary options.

This article examines air sampling as an environmental surveillance strategy for early pathogen detection and offers a preliminary comparison of air and wastewater surveillance. Air sampling involves collecting bioaerosols to analyze the microbial composition of the air, utilizing techniques like PCR and metagenomic sequencing. Air sampling appears especially promising for detecting respiratory pathogens and highly transmissible pandemic agents, as these spread primarily via aerosols and droplets. The article details various air sampling techniques, their efficiency, and practical considerations, categorizing them into filtration, impaction, impingement, electrostatic precipitation, and condensation methods. It also explores the composition of airborne microbes, emphasizing the low concentration of viral nucleic acids and the challenges this poses for metagenomic sequencing. The selection of sampling locations, including indoor environments and airplanes, is discussed as critical for effective pathogen detection. Finally, the article contrasts air and wastewater sampling, concluding that while both methods should ideally be explored as layered defenses, air sampling does not collectively appear more promising than wastewater sampling.

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing anti-tumor immune response. However, recombinant IL-12 had significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors and cellular vectors. Previous studies have found that IL-12 fusion with extracellular matrix proteins, collagen and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses and poxviruses have been used to deliver IL-12, and testing has been conducted in various cancer models. Local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective anti-tumor immunity and acting synergistically with other therapies without compromising safety. Also, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the antitumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.

Nanotechnology has provided an opportunity for unparalleled development of the treatment of various severe diseases. The unique properties of nanoparticles offer a promising strategy in enhancing antitumor immunity by enhancing immunogenicity and presentation of tumor autoantigens for cancer immunotherapy. Polymeric, liposomal, carbon or silica-based nanoparticles are among those with major immunomodulatory roles in various cancer treatments. Cancer vaccines, in particular digestive cancer vaccines have been researched and developed on nanotechnological platforms. Due to their safety, controlled release, targeting of dendritic cells(DCs) and improved antigen uptake, as well as enhanced immunogenicity, nanoparticles have been used as carriers, as adjuvants for increased effect at the tumor level, for their immunomodulating effect, or for targeting tumor microenvironment, increasing tumor immunogenicity and reducing tumor inflamatory response. This review looks at digestive cancer vaccines developed on nanoparticle platforms and the impact nanoparticles have on the effects of these vaccines.

The emergence of bispecific antibodies has transformed cancer immunotherapy, highlighting increased clinical efficacy, especially in hematological malignancies. These innovative molecules uniquely target two distinct tumor antigens or separate epitopes simultaneously, demonstrating potent antitumor activity across various cancers. Despite their promise, challenges like rapid drug clearance, off-target effects, and cytokine release syndrome hinder their widespread therapeutic application. Recent engineering advancements in bispecific antibody systems aim to overcome these challenges, broadening therapeutic coverage. This review offers insights into the latest clinical and preclinical progress in bispecific immunotherapy, outlining key challenges faced by the technique, and exploring emerging strategies to address these obstacles.

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based in platinum and antifolate is the standard treatment and the addition of bevacizumab adds two months of gain in median survival. Recently in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM, however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy in different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20-40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review state of art of MPM treatment in the year 2023 focusing in the efficacy results of first-line or subsequent immunotherapy studies in patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.

Probiotics are now being looked at as a possible addition to cancer treatments in both study and clinical settings. This study tries to give an overview of probiotic research as it relates to cancer, with a focus on how it might help avoid cancer, treat it, and improve the health of cancer patients. We look at developmental studies that use cell culture and animal models to look at how well probiotics work in cancer. We focus on how probiotics change the immune system, inflammation, and gut bacteria. The results of clinical studies that looked at probiotics as an add-on therapy for cancer patients are looked at to see how they affected the treatment success, side effects, and quality of life of the patients. We look at the possible benefits of probiotics for certain types of cancer, such as colorectal cancer, breast cancer, and stomach tumors. We also find the best probiotic strains for each type of cancer. We also look at the synergistic benefits of combining probiotics with standard cancer treatments like chemotherapy, radiation therapy, and immunotherapy to improve the effectiveness of treatment and lower side effects. Lastly, we talk about the present problems and future directions of probiotic research for cancer. We focus on personalized methods, ideal doses and treatment plans, finding signs of treatment success, and making probiotic-based therapies. By learning more about how probiotics could be used to treat cancer, we can create personalized, successful, and well-tolerated probiotic treatments to improve cancer outcomes.

Background Successful treatment for patients with metastatic colorectal cancer who failed to response to first-line treatment has been a challenge due to their low response rate for later-line treatment and poor progression free survival and overall survival. The application of dendritic cell-cytokine-induced killer cells (DC-CIK) immunotherapy combined with conventional treat-ment, either surgical resection or chemotherapy, showed improvement in survivals in first-line treatment for metastatic colorectal cancer. In this retrospective study, we aimed to evaluate the benefit of dendritic cell-cytokine-induced killer cells (DC-CIK) immunotherapy for patient with refractory metastatic colorectal cancer. Methods A total of 20 patients with refractory metastatic colorectal cancer receiving cell-cytokine-induced killer cells (DC-CIK) immunotherapy were enrolled to this study. Among these patients, 11 patients responded to the treatment and the remaining 9 patients did not. All patients were followed for at least one years and the determination of treatment response was mainly based on image study at 6 months after the completion of treatment. Data were analyzed with Kaplan-Meier method and log-rank test. Results The treatment response rate of the study group is 55% (11/20). The median progression free sur-vival (PFS) and median overall survival (OS) of responsive patients was 7 months and 12 months, respectively. The median overall survival of irresponsive patients was 9.5 months. Four responsive patients received subsequent metastectomy or cytoreduction plus hyperthermic in-traperitoneal chemotherapy surgery (CRS + HIPEC). Conclusion DC-CIK cell-based immunotherapy may provide benefits for patients with refractory mCRC with improved response rate and progression free survival.

The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of ‘checkpoint blockade’ and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient’s own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function. The production of extracellular adenosine is mediated by the cell surface ectoenzymes CD73, CD39 and CD38 and therapeutic agents have been developed to target these as well as the downstream adenosine receptors (A₁R, A_2AR, A_2BR, A₃R) to enhance anti-tumor immune responses. This review will discuss the role of adenosine and adenosine receptor signaling in tumor and immune cells with a focus on their cell-specific function and their potential as targets in cancer immunotherapy.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

In general, during emergencies, healthcare is provided by tents and temporary structures that do not consider the environmental and social impact of the structure as a first term, in favor of swift response. The resultant construction intended as a temporary solution often persists long-term. This paper aims to analyze an alternative and innovative modular structure designed as a transitory solution in emergency and everyday life. In the first part of the paper, the conceptual framework, and the preliminary design for the new approach to basic non-conventional sanitary spaces are described, by investigating the benefits of a safe space as a generator space for care services and community. In the second part, the technological requirements of the system, its energy efficiency, and environmental impact are analyzed.

Ensuring the security of vertical applications in fifth-generation (5G) mobile communication systems and previous generations is crucial. These systems must prioritize maintaining the confidentiality, integrity, and availability of services and data. Examples of vertical applications include smart cities, smart transportation, public services, Industry 4.0, smart grids, smart health, and smart agriculture. Each vertical application has specific security requirements and faces unique threats within the mobile network environment. Thus, it is essential to implement comprehensive and robust security measures. This approach helps minimize the attack surface and effectively manage risks. This survey thoroughly examines mobile networks and their security challenges in vertical applications, shedding light on associated threats and potential solutions. Our study considers the interplay between security considerations in 5G, legacy networks, and vertical applications. We emphasize the challenges, opportunities, and promising directions for future research in this field and the importance of securing vertical applications in the evolving landscape of mobile technology.

This document serves as supplemental information to Shapero et al. (2023), which is itself a comment on Nowell et al. (2022). Environmental Health Perspective’s publishing standards for article comments have strict word counts and do not allow the addition of new primary data analyses; therefore, this document provides an additional level of detail and supporting analyses that serve as an important backup to and expansion of Shapero et al. (2023) and that also respond to some comments within the author’s reply to our comments (Holmes and Nowell, 2023). Nowell et al. (2022) evaluated potential PM_2.5 community impacts from sugarcane harvesting. However, their analysis is flawed by erroneous assumptions and misapplied technical approaches, as discussed in Shapero et al. (2023) and as detailed in this supplemental information document. Additionally, the authors ended their analysis with 2018 data, but later data shows no marginal increase in PM_2.5 during sugarcane harvest following 2019 even using the authors’ approach (Holmes and Nowell, 2023). Therefore, the authors’ evaluations have no relevance to current conditions. Nonetheless, even their evaluation and conclusions regarding PM_2.5 concentrations purportedly attributable to sugarcane harvesting prior to 2019 are unsupported and technically unsound as detailed below.

Bearing fault diagnosis is crucial for ensuring the stable operation of mechanical equipment. With the continuous development of deep learning technology, Convolutional Neural Networks (CNNs) have demonstrated significant advantages in the field of fault diagnosis. This paper proposes a new method that combines various CNN architectures to improve the accuracy of bearing fault diagnosis. We designed five different convolutional network structures, including SerConv, ResConv, One-Shot Aggregation Convolution (OSAConv), Cross-Stage Aggregation Convolution (CSAConv), and MD-DAConv. Experimental results on the Case Western Reserve University (CWRU) bearing dataset show that the proposed method exhibits high accuracy and robustness in fault diagnosis. The results indicate that strategies such as multi-directional, multi-scale, and residual connections play a crucial role in enhancing the depth and breadth of feature extraction, while simple and effective feature fusion and information transmission mechanisms are key to ensuring the robustness and generalization ability of the model.

Background: Immune evasion in cancer is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Recent developments have immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy effectively impede this process but benefit a limited patient cohort. This investigation introduces a systemic immunotherapeutic strategy by inhibition of master-regulators of immune evasion (MR-IE). Methods: We utilized the TCGA PanCancer Atlas transcriptomic data to subset and stratify cancer samples based on IC expression levels and CIBERSORT to estimate immune cell infiltration. Differential gene expression analysis was conducted to unravel pathways associated with the immune evasion. Transcription Factor Enrichment Analysis and Survival Analysis was conducted to identify and rank candidate MR-IE per cancer type. The top-ranking candidate MR-IE of cholangiocarcinoma (CCA) was validated for its regulation of ICs using quantitative PCR and western blots. Orbitrap Proteomics was employed to assess changes in the immune-related proteome of CCA cells after MR-IE is inhibited or knocked-down. Lastly, CCA cell viability and immune-mediated cell death was assessed after MR-IE inhibition in combination with fourth-generation anti-folate receptor alpha (FRɑ) CAR-T cell therapy. Results: This workflow ranked and identified candidate MR-IE for 33 tumor types. MYC was identified as the high-ranking candidate MR-IE for CCA. MYC modulated PD-L1 expression adn key markers of inflammation and IC expression in CCA cells. Moreover, MYC inhibition was able to potentiate CAR-T mediated cell death in CCA cells. Conclusions: Cumulatively, these results offer a candidate list of MR-IE immunotherapeutic targets per cancer type that can be further explored and validated. This study also highlights the promise of MR-IE inhibition as a novel potent immunotherapeutic strategy for the treatment of CCA.

Melanoma, a deadly form of skin cancer, has seen improved survival rates due to advances in diagnosis and treatment, yet the need for further improvement remains critical. Tumor-associated antigens, such as PRAME (Preferentially Expressed Antigen in Melanoma), offer promising avenues for enhanced diagnostic precision, prognostic assessment, and targeted immunotherapy. PRAME, a cancer-testis antigen, is selectively expressed in various cancers, including melanoma, and plays a key role in promoting tumorigenesis through inhibition of retinoic acid signaling, epithelial-to-mesenchymal transition, and immune evasion. This review explores the diagnostic utility of PRAME in distinguishing melanoma from benign nevi, its prognostic value in aggressive melanoma subtypes, and its potential as a therapeutic target in cancer vaccines and adoptive T-cell therapies. While PRAME-targeted therapies face challenges such as tumor heterogeneity and immune suppression, ongoing research aims to overcome these barriers, offering hope for more effective melanoma treatments.

Multiple Myeloma (MM), is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. Our analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2024, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, overall response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.

This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy in pancreatic cancer. We discuss novel strategies targeting the desmoplastic barrier and immunosuppressive cells to enhance immune cell infiltration and activation. Recent clinical trials, particularly those involving novel immunotherapeutic agents and tumor vaccines, are examined to understand their efficacy and limitations. This review aims to highlight the ongoing efforts to refine immunotherapy approaches for better patient outcomes.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1>49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p<0.05). In addition, patients diagnosed with adenocarcinoma, PDL1<49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p<0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Pediatric brain tumors are the most common solid tumors in children, causing the highest number of cancer-related deaths at young ages. Although existing therapies have improved the 5-year overall survival rate of PBT patients, some high-risk brain tumors continue to resist current treatments. Additionally, the survivors endure devastating long-term side effects, including cognitive defects and sensory and endocrinal dysfunctions. In the past two decades, immunotherapies have evolved significantly, with great success in many cancers. Immunotherapies developed specifically for PBTs also show promising results. Currently, scores of clinical trials are underway to evaluate the safety and feasibility of a wide-range of immunotherapeutics for PBTs, and this review overviews the most recent advances, including the exciting progress made toward treating medulloblastoma, pediatric glioma, and ependymoma. We summarized the cutting-edge immunotherapies under development, including immune checkpoint blockade, chimeric antigen receptor (CAR)-T cell therapy, natural killer (NK)-cell therapy, cancer vaccines, and oncolytic virus therapy. We find that the results from the recently concluded or ongoing clinical trials on safety and feasibility are very encouraging; however, non-responsiveness and tumor recurrence still haunt them. While this review judges the scope of the current immunotherapies, it also lays out strategies to find alternate solutions for persisting issues.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Synergy of radiation and immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong antitumor immune responses. It remains unclear, however, what are the best radiation fractionation protocols to maximize the therapeutic benefits of this synergy. Here, we present a novel mathematical model that can be used to predict and dissect the complexity of the immune-mediated response at multiple tumor sites after applying focal irradiation and systemic immunotherapy. We successfully calibrate the proposed framework with published experimental data, in which two tumors were grown in mice at two spatially separated sites from which only one was irradiated using various radiation fractionation protocols with and without concurrent systemic immunotherapy. The proposed model is calibrated to fit the temporal dynamics of tumor volume at both sites and can predict changes in immune infiltration in the non-irradiated tumors. The model was then used to investigate additional radiation fractionation protocols. Model simulations suggest that the optimal radiation doses per fraction to maximize antitumor immunity are between 10-13 Gy, at least for the experimental setting used for model calibration. This work provides the framework for evaluating radiation fractionation protocols for radiation-induced immune-mediated systemic antitumor responses.

Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n=228) or ICI-CHT combination treatment (n=80) for advanced NSCLC. Kaplan-Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10-3.29, p=0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00-1.11, p=0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32-3.15, p=0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03-1.14, p=0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41-11.2, p=0.009) significant for PFS; ECOG≥2 (HR 5.58, 95%CI: 1.88-16.5, p=0.002) and CRP (HR 1.19, 95%CI: 1.06-1.32, p=0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, ECOG≥2 had a significant interaction with OS (HR 1.90, 95%CI 1.04-3.46, p=0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02-1.16, p=0.007) and OS (HR 1.11, 95%CI: 1.03-1.19, p=0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.

Nepal is witnessing a significant rise in obesity as traditional agrarian lifestyles give way to urbanization and sedentary behaviors. The dissolution of agriculture as a cultural practice has led to a reduction in daily physical activity, contributing to an alarming increase in non-communicable diseases such as cardiovascular diseases, type 2 diabetes, and hypertension. This article explores how Nepal can adopt new health-oriented cultural practices to combat obesity, drawing inspiration from the gym culture in the United States and the cycling culture in Europe. It advocates for the promotion of physical activity through community-based fitness programs, active transportation, and integrating exercise into educational curriculums. Additionally, it emphasizes the importance of reviving traditional dietary practices and supporting mental well-being. The article underscores the need for government support in implementing policies and infrastructure that foster a culture of health, ensuring a healthier future for Nepal's population.

first_pagesettingsOrder Article ReprintsOpen AccessArticleThe Carbon Footprint of Spanish University Websitesby Sonia Sanchez-Cuadrado ¹ andJorge Morato ^2,*1Department of Library and Information Science, Complutense University of Madrid, 28010 Madrid, Spain²Department of Computer Science, Carlos III University of Madrid, Leganes, 28911 Madrid, Spain^*Author to whom correspondence should be addressed.Sustainability 2024, 16(13), 5670; https://doi.org/10.3390/su16135670 (registering DOI)Submission received: 31 May 2024 / Revised: 22 June 2024 / Accepted: 23 June 2024 / Published: 3 July 2024(This article belongs to the Special Issue Sustainable Education in the Digital Society: Applying Communication Technologies and Digital Tools to Education) Downloadkeyboard_arrow_down Browse Figures Versions NotesAbstractThe consumption of digital content is essential for economic and scientific development, leading to a high dependence on information and communication technologies, which significantly impacts the environment. Quantifying this ecological impact is challenging due to its intangible nature and the diversity of factors. This research focuses on assessing the energy consumption and CO₂ production of Spanish university websites to evaluate their levels of digital pollution and environmental impact. The calculation of the carbon footprint considers factors related to energy consumption and the use of green or renewable energies. The findings indicate that only 17% of university websites can be considered environmentally friendly. There are significant differences in CO₂ consumption and emissions depending on whether the websites implement environmentally sound practices. This study highlights the lack of initiatives aimed at reducing energy consumption and greenhouse gas emissions associated with web information management. The study shows that Spanish universities have the potential to contribute to the reduction in CO₂ emissions by implementing sustainable development practices on their websites. Furthermore, it fosters awareness about technology usage and its environmental impact, promoting the adoption of green and sustainable approaches.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

The aim of this study was to quantify methane (CH4) emissions from dairy cows during milking by maximum amplitude of eructation peaks and compare estimates with other metrics for CH4 emissions. Spot measurements of CH4 and carbon dioxide (CO2) emissions were recorded for at least 7 days of continuous sampling using an infrared gas analyser in a robotic milking station whilst cows were milked. Concentrations of CH4 and CO2 were measured at 1 second intervals. A total of 105,701 CH4 spot measurements were obtained from 2,206 dairy cows on 18 farms. Methane emissions per individual cow were quantified by maximum amplitude of eructation peaks, average area under eructation peaks (integral of eructation), average concentration during milking and ratio of CH4 to CO2 concentration. There was a high correlation (r = 0.71) between CH4 emissions quantified by maximum amplitude and integral of eructation peaks. The correlation between maximum amplitude and average CH4 concentration was low, and there was no correlation between maximum amplitude and ratio of CH4 to CO2. As both approaches identify and extract eructation peaks to quantify enteric CH4 emissions, the substantial association between maximum amplitude and eructation integral was expected.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

Attention Deficit Hyperactivity Disorder (ADHD) diagnosis poses significant challenges due to its heterogeneous nature and reliance on subjective assessments. This study leverages deep learning to develop a robust diagnostic model by integrating a comprehensive set of EEG biomarkers. We incorporate parameters such as theta/beta ratio, coherency measures, delta power, event-related potentials (ERPs), power spectral density (PSD), microstates, entropy measures, fractal dimension, and source localization. Our convolutional neural network (CNN) model, designed to process these diverse features, demonstrates high accuracy and stability in distinguishing ADHD patients from controls, from all ages. The model's architecture includes convolutional layers for spatial feature extraction, followed by dense layers that integrate additional EEG parameters. The results indicate that deep learning, coupled with a rich feature set, can significantly enhance the predictive accuracy of ADHD diagnosis, offering a promising tool for clinical application.

Phytopathogenic fungi are living organisms that cause plant diseases and great damage to agri-cultural products. Despite the wide range of commercial fungicide products in use, there is a clear need for new and environmentally friendly fungicides. Here we propose a new ecological fun-gicide, copper alginate microspheres prepared by ionic gelation. The microspheres were charac-terized (morphology and topography, encapsulation efficiency, load capacity, swelling behavior, rheology, kinetics and mechanism of copper ions release) and their in vitro antifungal potential against selected genera of phytopathogenic fungi was evaluated. Novel copper alginate micro-spheres inhibited spore germination of Botrytis cinerea and mycelial growth of Cercospora beticola and Phytophthora ramorum. They offer effective disease control while minimizing environmental impact and promoting sustainable agriculture practices.

Raru’s plants bark has long been used as traditional medicine in Batak’s tribe. Raru’s bark is derived from several trees that are usually used in a mixture in Batak traditional beverages. This bark is generally used as antidiabetic remedies. This study aims to combine the rarus’s bark extract and mocaf activated-carbon (MAC) in order to study antidiabetics in rats. The combination of raru’s bark extract and MAC were tested on male rats as of Sprague Dawley strain for testing antidiabetic bioactivity. The result showed that antidiabetic activity of raru’s extract and MAC exposed the antidiabetic level declines in rat’s blood. The various treatments of different concentration ratios of raru’s extract and MAC useful in the experiments showed that the levels of blood level reduction were slightly different (14-21%). The raru’s extract pure was observed more effective in decreasing the blood glucose level in rat’s blood, in comparison the positive control. The mixture of raru’s extract and MAC with 75:25 ratio is better than 50:50 ratio. The involvement of MAC in the alleged antidiabetic agent did little in improving the blood glucose level decrease in rat’s blood. Raru’s extract and MAC indicate its potential utilization as an antidiabetic agent.

Objectives: Few studies have evaluated and compared artificial intelligence (AI) models for breast cancer detection on the same database. The purpose is to compare the performances of 3 artificial intelligence algorithms on the same dataset at a free operative threshold and to evaluate how the performance is impacted by the chosen threshold. Materials: In this retrospective single-center study, a dataset of 314 2D screening mammograms performed between 2012 and 2020 was established with a prevalence of 19.6% of histologically proven cancer. Three AI constructors using CE (European conformity) marking algorithms have agreed to take part in the study by submitting the cancer-enriched cohort to their algorithm. They chose a free operative threshold to distinguish benign and malignant mammograms. The most suspicious lesion was marked and correctly located by the AI algorithm. Statistical parameters were analyzed and compared between the algorithms. Results: Regarding both sensitivity and specificity, at the chosen threshold, AI 1 had the best compromise between sensitivity (74%) and specificity (79%). AI 2 had a statistically lower sensitivity (52%; p<0.05) with a higher specificity (98.4%) than the other AI algorithms. AI 3 had a nonsignificant sensitivity difference (69.9%) but a significantly lower specificity (45.3%; p<0.001) than the other two. The performances varied depending on the chosen threshold; when the AI 2 threshold was lowered, the sensitivity increased (69.9%), while a higher specificity (86.1%) was maintained. Conclusion: Two AI algorithms stood out in terms of performance when the threshold was optimized, resulting in an acceptable sensitivity and specificity.

The diagnosis of a chronic disease, such as multiple sclerosis, has both psychological and physical effects. Living with the disease and its uncertain consequences requires a great deal of psychological resilience in order to employ more comprehensive coping strategies in stressful situations. This study investigated the effect of a four-week online self-directed resilience training on the perception of psychological resilience among multiple sclerosis patients. A total of 64 MS patients were recruited for a randomized controlled trial. The experimental group underwent a 28-day online self-directed training program consisting of daily exercises aimed at strengthening a resilient mindset. Psychological resilience was measured through self-assessment immediately before, immediately after, and three months after the training. A repeated measures ANOVA revealed a statistically significant improvement in the perception of four factors related to stress: perceived worries, tension, joy and demands. Two resilience coping strategies were measured, of which one, a resilient orientation, improved significantly in the short and long term. The study suggests that online self-directed resilience training might provide an easily accessible, low-cost option for patients with MS to improve their psychological resilience. The transferability to other patient groups should be examined.

The removable partial denture, despite new technologies and new materials, continues to play a significant role in clinical dental practice. The purpose of the following study was to evaluate the design of new retention devices in Kennedy's second grade classrooms. For the study of "lamellar" retentive devices, 4 prosthetists were chosen and selected, according to inclusion and exclusion criteria, 16 patients, 8 women and 8 men, whose upper arch had to be rehabilitated with a removable partial prosthesis. The results showed that the parameters taken into consideration such as satisfaction, stability, aesthetics and retention had an average score higher than 3.30 (range 1-4), with an average standard deviation of 0.6225 in the 4 indicative parameters that the data they are relatively homogeneous and coherent. In conclusion we can state that the skeletonized prosthesis with lamellar retentions, designed in Kennedy's second grade classes, has shown good acceptance in selected patients

Actually, the study aimed to manage and to analyse the results of the laboratory methods, using liver samples, preparing and analizing in pathology service. This mentioned, are known as routinally practice for hepatitis C diagnosis, which conduct to hepatic cirrhosis. In this study direction, chronic liver diseases stimulate a degree of hepatocyte injury. So previously mentioned modifications, alters thet affect the liver architecture and finally ends in cirrhosis are well analyse on microscopic preparates. Folowing morphological steps, it is possible to analyse normal and alterate liver structure, on colored preparates.

Inhalation allergies caused by cats and dogs can lead to a range of discomforting symptoms, such as rhinitis and asthma, in humans. Given the increasing popularity and care provided to these companion animals, the allergens they produce pose a growing threat to the health of susceptible patients. Allergens from cats and dogs have emerged as significant risk factors for triggering asthma and allergic rhinitis worldwide; however, there remains a lack of systematic measures aimed at assisting individuals in recognizing and preventing allergies caused by these animals. This review provides comprhensive insights into the classification of cat and dog allerges, alongwith their pathogenic mechanisms. The study also discusses implementation strategies for prevention and control measures, including physical methods, gene editing technology, immunological approaches, as well as potential strategies for enhancing allergen immunotherapy combined with immunoinformatics. Finally, it presents future prospects for the prevention and treatment of human allergies caused by cats and dogs. This review will improve knowledge regarding allergies to cats and dogs, while identifying potential targets for the development of next-generation treatments.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

The evaluation of nanostructured biomaterials and medicines is associated with 2D cultures that provide insight into the biological mechanisms at the molecular level, while critical aspects of the tumor microenvironment (TME) are provided by the study of animal xenograft models. More realistic models that can histologically reproduce human tumors are provided by tissue engineering methodologies of co-culturing cells of varied phenotypes, to provide 3D tumor spheroids that recapitulate the dynamic TME in 3D matrices. The novel approaches of 3D tumor models are combined with tumor tissue engineering (TTE) scaffolds including hydrogels, bioprinted materials, decellularized tissues, fibrous and nanostructured matrices. This review focuses on the use of nanostructured materials in cancer therapy and regeneration, and the development of realistic models for studying TME molecular and immune characteristics. Tissue regeneration is an important aspect of TTE scaffolds for restoring the normal function of the tissues, while providing cancer treatment. Thus, this article reports recent advancements on the development of 3D TTE models for antitumor drug screening, studying of tumor metastasis, and tissue regeneration. Also, this review identifies the great opportunities of 3D TTE scaffolds in the evaluation of the immunological mechanisms and processes involved in the application of immunotherapies.

Abstract Epithelial ovarian carcinoma (EOC) is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. EOC is poorly responsive to immune check-point inhibitors due to immunologic features including limited tumor mutational burden (TMB), poor infiltration by immune cells and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of preexisting immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC) which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of DCVAC were more pronounced in patients with EOC with lower than-median TMB and scant CD8+ T cells infiltration. Thus, DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically „cold“ EOC. Our findings underscore the need for personalized immunotherapy and clinical relevance of potential tumor-related biomarkers within immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of TMB and immune infiltrate at baseline as biomarkers to guide the clinical management of EOC.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. Recognizing BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift towards CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 Chimeric Antigen Receptors (CAR) T-cells, and Bispecific Antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combining treatments with other anti-leukemic drugs. Exploring combinations, such as CD123-targeted immunotherapies with azacitidine and venetoclax, is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy

(1) Background: Triple negative breast cancer (TNBC) is a distinct subgroup of breast cancer presenting high level of recurrence and neo-adjuvant chemotherapy is beneficial in its therapy management. Anti-PD-L1 immunotherapy improves effect of neo-adjuvant therapy in TNBC. (2) Methods: Immune-modulation and ferroptosis related R-packages were developed for integrative transcriptome to analyze transcriptome datasets: TNBC cells stimulated with ferroptosis inducers (GSE173905, GSE154425), breast tumors with clinical data (TCGA and METABRIC cohorts). Protein level validation was investigated through protein atlas proteome experiments. (3) Results: Erastin/RSL3 ferroptosis inducers up-regulate CD274 in TNBC cells (MDA-MB-231 and HCC38). In breast cancer, CD274 expression is associated to overall survival. Breast tumors presenting high expression of CD274 up-regulated some ferroptosis drivers associated to prognosis: IDO1, IFNG and TNFAIP3. CD274-ferroptosis-driver score computed on breast tumor transcriptome stratified patients on their prognosis: low score was observed in basal subgroup with higher level of recurrent risk scores: oncotypeDx, ggi and gene70 scores. In METABRIC cohort, CD274, IDO1, IFNG and TNFAIP3 were found overexpressed in TNBC subgroup. CD274-ferroptosis-driver score was found associated to overall survival independently of TNM classification and age diagnosis. Tumor expression of CD274, TNFAIP3, IFNG and IDO1 in biopsy of breast ductal carcinoma was confirmed at protein level (4) Conclusion: Ferroptosis inducers up-regulate PD-L1 in TNBC cells, known as effective target of immunotherapy in high risk early TNBC which received neo-adjuvant therapy. Basal and TNBC tumors highly expressed CD274 and ferroptosis drivers: IFNG, TNFAIP3 and IDO1. CD274-ferroptosis driver score is associated to prognosis and to the risk of recurrence in breast cancer. A potential synergy of ferroptosis inducers with anti-PD-L1 immunotherapy is suggested in recurrent TNBC.

The noncoding RNAs (ncRNAs) are small transcript sequences that do not encode proteins but participate in the regulation of gene expression at the post-transcriptional level playing important biological roles such as proliferation and differentiation. In the tumor microenvironment, the dysregulated immunological response can participate in the progression and negative phenotype of cancer, the variability of switch cell differentiation and activation of the different immune cell lineages showed differential regulation by the type of cancer. Recent evidence showed that the upregulation of lncRNA can be used as a biomarker and predictive indicator for cancer progression. The use of lncRNA to turn off the tumor immune response and activate the anti-tumoral immune response is day by day a promising reality for the control of cancer. However, is imperatively elucidated the role of each ncRNA identified as well as its respective molecular pathways regulated, including the immune checkpoints, before its application at the clinical level. The correct delivery of lncRNA or mimics to inhibit its expression using the most efficient carriers to the cell or cellular organelle is a science that should continue to be developed.

Over the last decade, the therapeutic scenario for advanced non-small-cell lung cancer (NSCLC) has undergone a major paradigm shift. Immune checkpoint inhibitors (ICIs) have shown a meaningful clinical and survival improvement in different settings of the disease. However, the real benefit of this therapeutic approach remains controversial in selected NSCLC subsets, such as those of the elderly with active brain metastases or oncogene-addicted mutations. This is mainly due to the exclusion or underrepresentation of these patient subpopulations in most of the pivotal phase III studies; this precludes the generalization of the ICI efficacy in this context. Moreover, no predictive biomarkers of ICI response exist that can help with patient selection for this therapeutic approach. Here, we critically summarize the current state of ICI efficacy in the most common “special” NSCLC subpopulations.

The approval of monoclonal antibodies against programmed death-ligand 1 (PD-L1) and programmed cell death protein (PD1), has changed the landscape of cancer treatment. To date, many Immune Checkpoint Inhibitors (ICIs) have been approved by the FDA for the treatment of metastatic cancer as well as locally recurrent advanced cancer. However, immune-related adverse events (irAEs) of ICIs highlight the need for biomarker analysis with strong predictive value. Liquid biopsy is an important tool for clinical oncologists to monitor cancer patients and administer or change appropriate therapy. CTCs frequently express PD-L1 and this constitutes a clinically useful and non-invasive method to assess PD-L1 status in real time. This review summarizes all the latest findings about the clinical significance of CTC for the management of cancer patients during administration of immunotherapy and mainly focuses on the assessment of PD-L1 expression in CTCs.

Background: Diffuse glioma is a malignant human brain cancer that is hard to overcome. This represents a high risk of mortality. The current challenge is limited to the control of tumor progression and survival improvement. Immunotherapy consists of stimulating the immune system in order to eliminate the non-self-elements that damage the human body, including cancer cells. However, in human glioma, the current immunotherapeutic targets did not show significant benefit. In this study, we aimed at evaluating the expression and potential role of a new immunosuppressive molecule, TIGIT in glioma patients. Methods: A cohort of 667 patients from the TCGA database along with a cohort of 53 Moroccan patients, were analyzed in order to assess the role of TIGIT in human glioma progression and to estimate whether blocking this immune checkpoint molecule would be of a potential therapeutic benefit. Real time RT-PCR from fresh human biopsies and RNAseq data analysis were performed in this study. Results: Our results showed that high expression of TIGIT had prognostic value with some known clinical glioma risk factors such as sex, age and IDH mutation status. High expression of TIGIT was positively associated with advanced grades of glioma. Interestingly, elevated rates of TIGIT were significantly associated to elevated levels of other inhibitory immune checkpoint molecules (PD-1, VISTA and Tim-3) in human glioma patients, also TIGIT showed strong association with Treg cell-secreted cytokines (TGF-beta and IL-10), indicating the high potential involvement of TIGIT in immunosuppression in human glioma. Moreover, we reported that high TIGIT expressing CD8 T-cells displayed more surface inhibitory molecules and, elevated levels of Treg cells and FoxP3 were linked to higher rates of TIGIT, supporting the likely involvement of TIGIT in the suppression of the intra-tumoral immune cells. Finally, high expression of TIGIT was significantly linked to advanced histological subtypes of glioma and was associated with poor overall survival in human glioma. Conclusion: TIGIT blockade might be of valuable therapeutic benefit in patients with advanced glioma.

Gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between response to the anti-PD-1 therapy and the baseline gut microbiome in the Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy and 10 healthy subjects were recruited. Response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis, and metataxonomics of the microbiota. The Bacteroidota to Firmicutes ratio was higher, and the richness was decreased in the responders. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas non-responder gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis, and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption, but also gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota alongside diet were found associated with response to the therapy in the Polish population of melanoma patients.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli and upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. P53 is the most frequently mutated gene in tumors with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) which promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for 1) boosting p53 activity in cancer, 2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, 3) targeting p53 in immunotherapy, and 4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.

Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage. Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy. Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in-depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.

Chimeric antigen receptors (CARs) is one of the curative immunotherapeutic approaches that exploit the antigen specificity and cytotoxicity function of potent immune cells against cancers. Neuroblastoma, the most common extracranial pediatric solid tumors with diverse comportment, could be a promising candidate for using CARs therapies. Several methods harness CARs modified cells in neuroblastoma to increase therapeutic efficiency, albeit the assessment has still been less successful. Regarding the improvement of CARs, various trials have been launched to overcome insufficient capacity. However, the reason behind the inadequate response against neuroblastoma of CARs modified cells are still not well understood. It is essential to update the present reveal of comprehension of CARs to improve the efficiency of CARs therapies. This review summarizes the crucial features of CARs and its design for neuroblastoma, discusses challenges that impact the outcomes of the immunotherapeutic competence, and focuses on devising strategies currently investigated to improve the efficacy of CARs for neuroblastoma immunotherapy.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

Since the outbreak of SARS CoV-2 infection (Covid-19), healthcare professionals worldwide have been trying to find disease management and control alternatives to encourage immunotherapies. Immunotherapy is an efficient therapeutic option used against comparable viral contaminations such as MERS-CoV and SARS-CoV. The aim of the current study is to assess the existing knowledge associated with SARS-CoV-2 immunotherapy. Information available in published articles and their quality highlights the importance of following strict scientific rules for clinical outcomes. Thus, these studies have shown enough data to confirm that immunomodulation is the main topic investigated in research about Covid-19 therapy. Therefore, it is possible saying that immunotherapy is certainly the appropriate option against this virus.

Dewetting transition - a concept borrowed from fluid mechanics - is a physiological process which takes place inside the hydrophobic pores of ion channels. This transient phenomenon causes a metastable state which forbids water molecules to cross the microscopic receptors’ cavities. This leads to a decrease of conductance, a closure of the hole and, subsequently, severe impairment of cellular performance. We suggest that artificially-provoked dewetting transition in ion channels’ hydrophobic pores could stand for a molecular candidate to erase detrimental organisms, such as viruses, bacteria and cancer cells. We describe a novel type of high-affinity monoclonal antibody, which: a) targets specific trans-membrane receptor structures of harmful or redundant cells; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flows inside ion channels. Therefore, we achieve an artificial dewetting transition inside receptors’ cavities which causes transmembrane ionic flows discontinuity, channel blockage and subsequent damage of morbid cells. As an example, we describe dewetting monoclonal antibodies targeting the M2 channel of the Influenza A virus: they might prevent water to enter the pores, thus leading to virion impairment.

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment are considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments are inadequate due to improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co- polyethylenimine (PEI)(PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, non-toxic and enhanced intracellular uptake in immature dendritic cells. In murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and also enhance the antitumor immune response against melanoma tumor in the future clinical trials.

Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Theoretical physics addresses the fundamental principles of nature and the mysteries of the universe. In the last century, the theory of relativity challenged people's understanding of time and space, while quantum mechanics revealed various forms of energy. However, the concept of gravity remains elusive. All matter in the universe is composed of energy that can be converted into other forms, yet it is always conserved. However, achieving a state of equilibrium, represented by the equal sign, can be challenging to achieve on both macro and quantum scales. A phenomenon that can transition from one state to infinity is called collision and is essential for understanding natural phenomena and physical processes throughout the universe. In the study of general relativity cannot be three-dimensional problems to gain mathematical inspiration, understand the application of new dimensions. Here, we elucidate the nature of gravity, which inspires the solution of the Riemann hypothesis. Our results show that the conduction mode of dimensional energy is defined by Euler's formula. And a special mode of collision is derived which translates into vibration.

Background: Glutathione and its related enzymes constitute one of the most important antioxidant defense mechanisms against oxidative stress and cancer formation in the body. Bladder cancer is the second most common urological malignancy after prostate cancer. Oxidative stress plays a significant role in the development and prognosis of bladder cancer. The aim of this study was to examine the effect of glutathione on the prognosis of non-muscle-invasive bladder cancer. Methods: The 98 patients with bladder tumors were those with T1G3 pathology who had undergone intravesical Bacillus Calmette-Guérin therapy, while the 30 controls were healthy individuals with no history of transitional cell carcinoma of the bladder. The 128 participants were divided into four groups: Group 1 comprised 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, Group 3 consisted of 29 patients who progressed to muscle-invasive stages, and Group 4 was composed of 30 healthy volunteers. Blood samples were collected from all participants. Glutathione levels were measured, and statistical analysis were performed. Results: There was a statistically significant difference in reduced glutathione levels among the groups (p < 0.001), attributed to Group 4 exhibiting higher reduced glutathione levels compared to Groups 1, 2, and 3 (p < 0.001). No significant differences were observed in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.999). Total glutathione levels varied significantly among the groups (p < 0.001), with Group 4 having higher levels than Groups 1, 2, and 3 (p < 0.001). However, there were no significant differences between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in terms of total glutathione levels (p = 0.473, p = 0.747, and p > 0.999, respectively). Regarding oxidized glutathione levels, a significant difference was observed (p < 0.001), with Group 4 showing lower levels than the remaining three groups (p < 0.001). No significant differences were found between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in relation to oxidized glutathione levels (p > 0.999, p = 0.171, and p > 0.999, respectively). Conclusions: The current study revealed that glutathione is a factor influencing the development of new bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the effect of glutathione on the prognosis of bladder cancer.

Melanoma, one of the most aggressive forms of skin cancer, is also one of the most diagnosed cancer types. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options are necessary, given the increasing diagnosis rate. In the present study, a norcantharidin-containing nanoemulsion was developed and evaluated in vivo using a syngeneic graft murine model. Our model contemplates an amputation surgery simulating the standard treatment and the role of the nanoemulsion as a potential adjuvant therapy. We observed a significant decrease in the growth rate of the melanoma lesion in the treated groups compared to the control group, both at the 20th and 30th days of treatment. Moreover, we evaluated the drug bioavailability in serum samples, and the results showed that norcantharidin was detectable in a range of 0.1 to 0.18 mg per mL in the treated groups. Furthermore, histopathological analysis was performed on the amputated tumors, where significant differences were found regarding size, mitosis rate, lymphocytic infiltration, and multispectral quantitative image analysis compared to the control group. The norcantharidin-containing nanoemulsion could be a potential alternative or adjuvant therapy if more clinical studies are conducted. Topical nanosystems can become or complement standard therapies, which is needed as melanoma affects not only in terms of mortality but also the patient's morbidity and life quality.

Glycerol conversion to valuable biomolecules has been a research avenue that has attracted a significant interest in recent years due to its increasing over production, with possibilities for chemical transformation for eco-friendly processes and distinct compounds with biological activities. Also, in the current climate change in which a major emphasis is being placed on the design of green processes, solvents are key factors from both an economic and environmental point of view. In this context, due to its abundance and low-price, glycerol represents an innovative solvent coming from biomass and produce in high amount. On the other hand, Epichlorydrin, Glycidol and Solketal have become useful intermediates in chemical transformations when using glycerol as a raw material. This review focuses on glycerol as a green solvent in the synthesis of complex molecules, Epichlorydrin, Glycidol, Solketal and Tosyl solketal as an efficient recycling process for glycerol, as well as building blocks in the synthesis of glycerol derivatives, which are undeniable new source of potentials drugs.

Background: Gender differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, gender-specific analysis remains underexplored. This retrospective study aimed to evaluate the gender-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods: Data were collected from 47 patients (31 women, 16 men), with age > 18 years, BMI ≥ 30 kg/m^2, absence of T2D, and with exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results: Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, % WL, WL >5% and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant gender differences were observed in glucose metabolism or renal function. Conclusion: This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Per- and polyfluoroalkyl substances (PFAS) are arguably the most common water contaminants in the world today. While several research experiments have been done to understand and remove PFAS from the environment, there is still a lot of unknown. Little has been known about the use of Machine learning (ML) to understand PFAS. This work hence reviews some leading ML approaches and applications in PFAS studies in the distribution, transport, removal, and occurrence predictions of PFAS. Several evaluation matrices were examined and used to perform this function. There are still a lot of areas whereby ML can be used to improve our PFAS knowledge base, some of these were briefly stated in this review.

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterised by thrombosis and the presence of antiphospholipid antibodies (aPL): lupus anticoagulant and/or IgG/IgM anti-β2-glycoprotein I and anticardiolipin antibodies. APS carries significant morbidity for a relatively young patient population from recurrent thrombosis in any vascular bed (arterial, venous or microvascular), often despite current standard of care, which is anticoagulation with vitamin K antagonists (VKA). Platelets have established roles in thrombosis at any site, and platelet hyperreactivity is clearly demonstrated in the pathophysiology of APS. Together with excess thrombin generation, platelet activation and aggregation are the common end result of all the pathophysiological pathways leading to thrombosis in APS. However, antiplatelet therapies play little role in APS, reserved as a possible option of low dose aspirin in addition to VKA in arterial or refractory thrombosis. This review outlines the current evidence and mechanisms for excessive platelet activation in APS, how it plays a central role in APS-related thrombosis, what evidence for antiplatelets is available in clinical outcomes studies and potential future avenues to define how to target platelet hyperreactivity better with minimal impact on haemostasis.

Presenting a case report about a 14-year-old female patient presenting with a history of weakness in all four limbs since the age of 5. The patient has a history of difficulty in walking, wearing footwear, climbing stairs, and performing fine motor tasks. During the neurological examination showed mild spasticity, muscle weakness, areflexia, ill-sustained clonus, and sensory deficits. Radiological examination, including a contrast-enhanced MRI of the brain was done which showed findings that are consistent with Megalencephalic leukoencephalopathy with subcortical cysts, also known as Van der Knaap disease.

A high-resolution catalog for the 2014 Ms6.5 Ludian aftershocks was constructed based on the deep learning phase-picking model (CERP) and the seismic-phase association technology (PALM). A specific training strategy, which combines the advantages of the conventional short-long window average energy ratio algorithm (STA/LTA) and AI algorithm, is employed to retrain the CERP model. The P & S phases were accurately detected and picked on continuous seismic waveforms by the retained AI model. Hypoinverse and HypoDD were utilized for precise location of 3286 events. Compared to the previous results, our new catalog exhibits superior performances in terms of location accuracy and the number of aftershock events, thereby enabling a more de-tailed depiction of the deep-seated tectonic features. According to the distribution of aftershocks, it can be inferred that, (1) the seismogenic fault of Ludian earthquake is the NW-trending Baogunao-Xiaohe Fault. (2) the Ludian aftershocks interconnected the discontinuous NW-trending Baogunao-Xiaohe Fault, and intersected with the Zhaotong-Ludian Fault. (3) It suggests that the NE-trending Zhaotong-Ludian Fault may have been intersected by the NW-trending Baogunao -Xiaohe Fault, indicating that the Baogunao-Xiaohe Fault is likely a rela-tively young Neogene fault.

This study seeks to comprehend the complex and diverse dynamics of women's encounters with urban green areas in the specific setting of Jordan. The utilization of the focus group methodology facilitated the organization of unstructured talks involving a cohort of twenty-seven female participants, which yielded intricate and perceptive perspectives on their opinions. This study revealed a widespread pattern of stigmatization and unfavorable assessment of women who utilize public areas, which is strongly ingrained in cultural norms and gender expectations. Women were also concerned about the potential harm to their reputation and the censure of society, which ultimately deterred women from participating in public spheres. The research thus centers on the close proximity and insufficiency of urban green areas in Jordan, which is worsened by high urban density. Insufficient lighting and security measures are responsible for further limiting women's access to areas like these, which also raises concerns about safety. Recent evidence has revealed deficiencies in infrastructure designed to accommodate the needs of women, particularly in public restroom facilities. This study emphasizes the immediate necessity for a fundamental change in urban policy and planning, towards more inclusive approaches. Within this strategic framework for urban policy, there is a strong emphasis on incorporating aesthetics, comfort, and safety elements to enhance the whole urban experience for women. Consequently, addressing this issue necessitates using gender-responsive strategies in urban design and planning. This includes enhancing the quality, cleanliness, and privacy aspects of facilities to cater to the specific needs of women and improve their overall well-being. This study contends that any ongoing discussion on sustainable urban development in Jordan must take into account the interaction between urbanization, accessibility to public spaces, and the well-being of women. Therefore, it is necessary to implement a worldwide effort to advocate for urban policies that include both genders. This program aims to propose innovative approaches to governance, security measures, and municipal infrastructures that are sensitive to gender-related issues.

In this paper, aiming at the safety evaluation of ultimate bearing safety capacity of composite pile bridge foundation, the symmetrical reliability method with forward and inverse analysis con-sidering the randomness of parameters is proposed to evaluate the safety performance of com-posite pile foundation. The proposed method, considering the randomness of parameters, was used to calculate the safety factor of ultimate bearing capacity of composite pile foundation to meet the prescribed target reliability requirements. Through the example calculation of the safety coefficient of pile foundation, the results show that the statistical characteristics of random vari-ables that affect the safety coefficient of pile foundation have a significant impact. The degree of the safety coefficient depends on the probability distribution type and distribution parameters of the random parameters, among which the more important is the variation characteristics of the random variables. The stronger the parameter variability, the lower the safety level of the struc-ture. During design and evaluation, it is necessary to measure the safety reserve of pile founda-tions in accordance with engineering practice to ensure the safe construction and well operation of the pile.

This article presents a comprehensive overview of recent discoveries and advancements in the field of steroid chemistry, highlighting the isolation and characterization of various steroidal compounds from natural sources. The paper discusses a wide range of steroids, including pregnane steroids, steroidal alkaloids, ketosteroids, and novel triterpenoids, derived from marine organisms, fungi, and plants. Significant findings include the isolation of bioactive compounds such as the cytotoxic erectsterates from microorganisms, soft corals, the unusual tetracyclic steroid penicillitone from a fungal culture, and innovative steroidal derivatives with potential anti-inflammatory and anticancer activities. The synthesis of steroids from microorganisms as a tool for pharmaceutical development is also explored, showcasing the role of microbial biotransformation in generating steroidal drugs. Additionally, the paper emphasizes the ecological and medicinal relevance of these compounds, which are often used in traditional medicine and have potential therapeutic applications in treating diseases like cancer and microbial infections. This article serves as a vital resource for researchers interested in the chemical diversity of steroids and their applications in drug discovery and development.

Background: Infective endocarditis (IE) is the result of infections by gram-positive bacteria and, in this condition, the redox homeostasis is lost by overproduction of H2O2 resulting in overstimulation of the immune system and up- regulation of the production of proinflammatory cytokines. Objectives: The aim of this preliminary study of three cases with IE, was to evaluate the levels of oxidative biomarkers and of the enzymatic and non-enzymatic antioxidant system, in subjects with IE. This is a preliminary retrospective analytical study of cases that had undergone aortic valve replacement surgery complicated by IE. Methods: We determined malondialdehyde (MDA), total antioxidant capacity (TAC), carbonyl groups, glutathione (GSH), thiols and the nitrate/nitrite ratio (NO3−/NO2−) in homogenized tissue of cardiac valves. We also measured the activities of GST, GPx, GR and TrxR. The super oxide dismutase (SOD) isoforms and peroxidase activities were determined using native gels. Results: There were increases in the activities of antioxidant enzymes such as GST, SOD isoforms and peroxidases (p=0.01) and decreases in OS markers such as GSH, TAC, (p=0.01); however, MDA was increased (p=0.01). Conclusions: The results suggest that there is loss of the intricate redox homeostasis system in the patients with EI in the aortic valve may be favors the bacterial process and damages the patient probably leading to a fatal outcome.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

Recent advancements in mass spectrometry have significantly enhanced our understanding of complex lipid profiles, opening new avenues for oncological diagnostics. This review highlights the importance of lipidomics in the comprehension of certain metabolic pathways and its potential for the detection and characterization of various cancers, in particular melanoma. Through detailed case studies, we demonstrate how lipidomic analysis has led to significant breakthroughs in the identification and understanding of cancer types and its potential for detecting unique biomarkers that are instrumental in its diagnosis. Additionally, the review addresses the technical challenges and future perspectives of these methodologies, including their potential expansion and refinement for clinical applications. The discussion underscores the critical role of lipidomic profiling in advancing cancer diagnostics, proposing a new paradigm in how we approach this devastating disease, with particular emphasis on its application in comparative oncology.

Background: Angiogenesis is essential for various physiological and pathological processes, such as embryonic development and cancer cell proliferation, migration, and invasion. Long noncoding RNAs (lncRNAs) play pivotal roles in normal homeostasis and disease processes by regulating gene expression through various mechanisms, including as competing endogenous RNAs (ceRNAs) of target microRNAs (miRNAs). The lncRNA MYU is known to promote prostate cancer proliferation via the miR-184/c-Myc regulatory axis, and to be upregulated in vascular endothelial cells under hypoxic conditions, which often occurs in solid tumors. In the present study, we investigated whether MYU might affect cancer growth by regulating angiogenesis in vascular endothelial cells under hypoxia. Methods: The expression of MYU-regulated miR-23a-3p and interleukin-8 (IL-8) in HUVEC cell lines was examined using qRT-PCR. CCK-8 assay, EdU assay, Wound-healing assay and Tube-formation assay were used to assess the effect of MYU on cell proliferation, migration and tube formation of HUVEC cells in vitro. Dual-luciferase reporter assay was performed to examine the effect of miR-23a-3p on MYU and IL-8 expression. Results: We found that overexpression of MYU and knockdown of miR-23a-3p in human umbilical vein endothelial cells (HUVECs) under hypoxia promoted cell proliferation, migration, and tube formation. Mechanistically, MYU was shown to bind competitively to miR-23a-3p, thereby preventing miR-23a-3p binding to the 3′ untranslated region of IL-8 mRNA. In turn, increased production of pro-angiogenic IL-8 promoted HUVEC proliferation, migration, and tube formation under hypoxia. Conclusion: This study identified a new role for lncRNA MYU as a ceRNA for miR-23a-3p, and uncovered a novel MYU–miR-23a-3p–IL-8 regulatory axis for angiogenesis. MYU and/or miR-23a-3p may thus represent new targets for the treatment of hypoxia-related diseases by promoting angiogenesis.

The role of the microbiome in cancer and its crosstalk with the tumor microenvironment (TME) has been extensively studied and characterized. An emerging field in the cancer microbiome research is the concept of the intratumoral microbiome, which refers to the microbiome residing within the tumor. This microbiome primarily originates from the local microbiome of the tu-mor-bearing tissue or from translocating microbiome from distant sites, such as the gut. Despite the increasing number of studies on intratumoral microbiome, it remains unclear whether it is a driver or a bystander of oncogenesis and tumor progression. This review aims to elucidate the intricate role of the intratumoral microbiome in tumor development by exploring its effects on reshaping the multi-leveled ecosystem in which tumors thrive, the TME. To dissect the complexity and the multitude of layers within the TME, we distinguish six specialized tumor microenvironments, namely the immune, metabolic, hypoxic, acidic, mechanical and innervated microenvironments. Accordingly, we attempt to decipher the effects of the intratumoral microbiome on each specialized microenvironment and ultimately decode its tumor-promoting or tumor-suppressive impact. Additionally, we portray the intratumoral microbiome as an orchestrator in the tumor milieu, fine-tuning the responses in distinct, specialized microenvironments and remodeling the TME in a multi-leveled and multi-faceted manner.

This research explores the application of Support Vector Machine (SVM) and Digital Surface Models (DSM) derived from Unmanned Aerial Vehicle (UAV) data for a vertical-horizontal classification of mangrove ecosystems in Tongke-tongke and Samataring Village. The study focuses on integrating high-resolution DSM subtracted from Digital Terrain Models (DTM) to classify mangrove vegetation into sixteen distinct vertical-horizontal classes based on vegetation type and elevation. The analysis revealed that older mangroves, particularly those within the 25-35 meters elevation range, dominate the landscape, accounting for 43.40% of the total classified area. This dominance suggests a mature and ecologically stable mangrove ecosystem, which is crucial for biodiversity conservation and carbon storage. The study demonstrates the effectiveness of SVM and UAV technologies in providing detailed and accurate ecological assessments of mangrove forests. The classification results contribute valuable insights into the structural diversity and health of mangrove ecosystems, facilitating targeted conservation and management strategies. Additionally, the research highlights the utility of advanced remote sensing and machine learning techniques in enhancing the precision of environmental monitoring and the assessment of carbon sequestration capabilities within mangrove ecosystems. The findings underscore the potential of UAV-based remote sensing for ecological studies, offering a replicable method for similar assessments in other regions, thereby supporting global environmental management and climate action initiatives.