Therapeutic Context Research Articles

Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.

To realize the potential of engineered cells in therapeutic applications, transgenes must be expressed within the window of therapeutic efficacy. Differences in copy number and other sources of extrinsic noise generate variance in transgene expression and limit the performance of synthetic gene circuits. In a therapeutic context, supraphysiological expression of transgenes can compromise engineered phenotypes and lead to toxicity. To ensure a narrow range of transgene expression, we design and characterize Compact microRNA-Mediated Attenuator of Noise and Dosage (ComMAND), a single-transcript, microRNA-based incoherent feedforward loop. We experimentally tune the ComMAND output profile, and we model the system to explore additional tuning strategies. By comparing ComMAND to two-gene implementations, we highlight the precise control afforded by the single-transcript architecture, particularly at relatively low copy numbers. We show that ComMAND tightly regulates transgene expression from lentiviruses and precisely controls expression in primary human T cells, primary rat neurons, primary mouse embryonic fibroblasts, and human induced pluripotent stem cells. Finally, ComMAND effectively sets levels of the clinically relevant transgenes FMRP1 and FXN within a narrow window. Together, ComMAND is a compact tool well-suited to precisely specify expression of therapeutic cargoes.

A Systematic Review of Light Therapy on Mental Health on and Beyond Earth

Light can influence human emotional well-being, sleep quality, and circadian rhythms. The application of these qualities in a therapeutic context is currently being explored. Research has been conducted into the effects of light therapy on wound healing, sleep enhancement, stress management, and the improvement of depressive symptoms. Despite the extensive amount of studies in this field, a satisfactory framework for categorizing light therapies has yet to be developed. To address this problem, our research team proposes to categorize light therapy by wavelength (color). The benefit of this categorization is that, while therapeutic applications may evolve, the fundamental properties of light colors remain constant. Categorizing by color supports scientific innovation and maintains consistent categories even as new research emerges. On the other hand, light therapy’s potential is undermined. Light therapy is characterized by its affordability, durability, consistency, and minimal side effects. While light therapy is interchangeable with other therapeutic methods in common scenarios, it is specifically suited for environments where all those attributes are essential. Space missions represent one such environment. Space exploration is a major frontier for humanity, yet the mental health and living conditions of astronauts have received limited attention. Space missions present unique environmental challenges to astronauts due to altered light exposure, high-pressure, and isolated living environments. These environmental problems need to be addressed, but the resource-scarce space environment requires a reliable and durable solution. Light therapy’s advantages align well with these constraints. Moreover, its ability to address issues such as disrupted circadian rhythms and psychological stress caused by space environmental problems renders it an optimal intervention for space exploration. This article will examine the therapeutic effects of light therapy, with a particular focus on the ways in which different light colors address various health issues and recent discoveries. The potential of light therapy will be demonstrated through the use of space missions as an illustrative example. Additionally, we will briefly discuss future research directions for light therapy. Our primary objective is to establish an intuitive and stable categorization of light therapy. We will examine the potential of light therapy in unique environments, such as space missions, and discuss how it can address common symptoms experienced during these missions. Our ultimate goal is to fully realize the potential of light therapy in tailored environments and inspire the discovery of other scenarios where light therapy can be equally effective.

The significance of connectedness: avoidant personality disorder patients' subjective experiences of change after attending a specialized treatment program.

This study aimed to inquire into the subjective experiences and meaning-making of change of people diagnosed with avoidant personality disorder (AvPD) after attending a treatment program developed for AvPD. Eighteen AvPD patients were interviewed 1 year after completing their treatment using a semi-structured interview guide. The interviews were analyzed through reflexive thematic analysis. Three main themes were found to capture the various subjective experiences of change. The first main theme "being more alive" included the subthemes "talking and listening together" and "opening up and grounding into myself." The second main theme was "still longing for more," and the third main theme "I cannot even manage therapy" included the subthemes "as if we were together" and "capitulation." Although these findings may not be specific to AvPD, they shed light on the importance of attending to the dynamic interplay of intersubjectivity, social motivations, and agency in a therapeutic context. Discovering a sense of agency within an interpersonal context in which the patient feels connected may lead to them opening up for development in accordance with their social motivational intentions.

Is there a multidisciplinary role for 5-methyltetrahydrofolate? The obstetric evidence in perspective.

5-methyltetrahydrofolate (5-MTHF), or its synthetic precursor, folic acid, is traditionally used as a supplement for improving fertility and for the prevention of embryonal neural tube defects. However, in the last decade, starting from the effectiveness of this preventive treatment in the gynecological setting, the use of 5-MTHF was extended to other medical and pathological areas. Thus, there might be a rationale for the use of 5-MTHF for purposes other than the protection of the growing embryo linked to the possible effect of MTHFR variants in different pathological conditions. A narrative review was conducted to provide an overview of the available evidence on the use of 5-MTHF in the obstetric field and to critically discuss the available data regarding the use of 5-MTHF across other different therapeutic areas. Results showed that the use of 5-MTHF in pregnancy presents some advantages if compared with folic acid, such as immediate action, the non-necessity of metabolic activation, and the immediate bioavailability of the mother and fetus. Otherwise, the role of 5-MTHF in the management of cardiovascular risk is still debated due to the multiple confounding factors that characterize this patient setting. A link between folate deficiency in pregnancy and postpartum depression has been proposed, as well as between folate levels and the onset of depression. In conclusion, evidence from the literature supports the additional role of 5-MTHF as a pleiotropic drug with a transversal effect in different therapeutic contexts. With regard to the prevention of cardiovascular disorders, available evidence is not conclusive.

Ubiquitin: Not just a one-way ticket to the proteasome, but a therapeutic dial to fine-tune the molecular landscape of disease.

Recently, there is a rise in studies that recognize the importance of targeting ubiquitin and related molecular machinery in various therapeutic contexts. Here we briefly discuss the history of ubiquitin, its biological roles in protein degradation and beyond, as well as the current state of ubiquitin-targeting therapeutics across diseases. We conclude that targeting ubiquitin machinery is approaching a renaissance, and tapping its full potential will require embracing a wholistic perspective of ubiquitin's multifaceted roles.

WITHDRAWN: LSAC-Net: A lightweight scale-aware CNN with densely connected focal modulation for retinal blood vessel segmentation

The diagnosis of sight-threatening eye conditions typically involves segmenting retinal structures in fundus images. The segmentation process enables clinicians to identify alterations in retinal morphology, facilitating the detection and diagnosis of various eye diseases. Despite recent developments in image processing, current approaches often fail to partition delicate arteries precisely. Although deep learning has great potential for segmenting medical images, the accuracy of the segmentation process may be limited due to its dependence on repetitive convolution and pooling processes, which may impair the representation of edge information. In this study, we present LSAC-Net, a pixel-level convolutional neural network (CNN) designed specifically for retinal vessel segmentation. Moreover, it is lightweight, with only 37.5 K learnable parameters. LSAC-Net integrates a unique scale-aware feature extraction block (SAFEB) and a densely connected focal modulation block (DCFMB) to improve segmentation accuracy. In addition, careful selection of filter numbers to avoid overlap effectively shortens training times and boosts computational performance, both of which improve overall model efficiency. We performed extensive tests on different aspects of retinal images to evaluate the robustness and generalizability of LSAC-Net. In particular, a thorough evaluation of the model's precision in retinal artery segmentation, a crucial task for ophthalmological diagnosis and treatment, was carried out. We evaluated the performance and efficacy of LSAC-Net with a particular focus on RBV. The model obtains 98.65% specificity, 97.54% accuracy, and 98.88% area under the curve surpassing existing approaches. Experimental results confirm that LSAC-Net is robust, generalizable, and maintains a high level of segmentation accuracy. These features highlight LSAC-Net's potential as a useful instrument for accurate and timely retinal image segmentation in a variety of therapeutic contexts.

Embracing Deliberate Practice and Cultural Humility to Deepen Our Understanding of the Multicultural Feminist Approach: The Cases of “Bashiir” and “Jaquann”

In this article, we respond with gratitude to commentaries from Dr. Renata Fire (2024) and Dr. Melissa Phillips (2024) on our cases of “Bashiir” and “Jaquann” (Singer, Deboard-Lucas, & Fuentes, 2024). Dr. Fire’s commentary encouraged additional reflection on the inclusion of siblings within the therapeutic context. Dr. Phillips explored themes related to the ecological model. In the following response, guided by multicultural feminist tenets, we reflect on the commentaries provided by our colleagues and offer additional feedback on strategies for increasing engagement of family-centered cases and expanding interventions through deliberate practice to include other systems, including siblings, broader structures, and current developments in the field.

Chronic Procrastination Among Iranians: Prevalence Estimation, Latent Profile and Network Analyses.

Procrastination is the deliberate, unjustified postponing of an intended course of action despite its costs or unfavorable effects. The present study used a self-report online survey and collected data from a large convenience sample of the general adult population (N = 2,076; females = 55.73%; Mage = 35.1years [SD ± 12.7]) with diverse demographics. Following the ring-curve distribution, the results indicated a 15.4% prevalence rate of procrastination among the Iranian community, which was significantly higher among women and divorced individuals and lower among nomadic individuals and those with higher academic degrees. A latent profile analysis demonstrated two distinct profiles, one for procrastinators (high scores on chronic procrastination, psychological distress, neuroticism, and extraversion; and low scores on general self-efficacy, self-esteem, satisfaction with life, openness, agreeableness, and conscientiousness) and one for non-procrastinators (demonstrating a reverse pattern compared to procrastinators). Moreover, additional network analysis suggested that the examined networks were invariant across procrastination status and gender. The results indicate that procrastination differs by demographic characteristics and is associated with a unique psychological profile. However, none of the aforementioned key study variables were considered a potential vulnerability for procrastinators due to the finding that all variables were peripheral and none were central in the examined networks.Therefore, relying on the differences in mean scores on psychometric scales does not appear to be an optimal way of determining the most important variables in a therapeutic context when treating procrastination.

Roll for Insight: Understanding How the Experience of Playing Dungeons & Dragons Impacts the Mental Health of an Average Player

Dungeons & Dragons (D&D) is a fantasy tabletop role-playing game published by Wizards of the Coast. Evidence shows that D&D is being used as therapeutic practice by clinical psychologists, and the reported success of these interventions indicate that it may have positive outcomes for its players. However, there is little research that establishes, from a psychosocial perspective, how playing D&D provides opportunities for supporting frequent player’s mental health. Using semi-structured interviews and a reflexive thematic analysis, we aimed to understand better how playing D&D interacted with players’ well-being psychologically and socially, as well as exploring factors that may prove challenging or problematic in the therapeutic context. 6 men, 2 women, and 2 nonbinary people participated in the study. Analysis illustrated several processes that are supportive for players’ mental health. These features were identified as five key themes: escapism, exploration of self, creative expression, social support, and routine. These findings highlight the transformative potential of D&D in a therapeutic setting, offering insights into its positive impact.

Interventions through Art Therapy and Music Therapy in Autism Spectrum Disorder, ADHD, Language Disorders, and Learning Disabilities in Pediatric-Aged Children: A Systematic Review.

Traditional pharmacological treatments, although effective, often carry potential side effects, which positions art therapy and music therapy as promising non-pharmacological alternatives to alleviate symptoms and improve social, cognitive, and emotional skills without the associated risks. Through a review in the SCOPUS and WOS databases following the PRISMA protocol, a total of 80 articles were analyzed through a series of determined categories and subcategories of analysis. The aim of this study is to evaluate and synthesize the existing evidence on the efficacy and applicability of art therapy and music therapy in the treatment of children with autism spectrum disorder (ASD), hyperactivity disorder (HSDD), developmental language disorders, and language learning difficulties, identifying best practices and key areas for future research. Among the main findings is that art therapy and music therapy have a significant impact on symptomatology, behavior, and communication as well as social, cognitive, and emotional skills in the pediatric populations studied. These therapies are highly valued by the participants with a large majority recognizing their adaptability to different educational and clinical contexts. It is concluded that these therapies have a high potential as viable alternatives or complements to traditional pharmacological treatments, justifying their application and further study in broader therapeutic contexts.

Enhancing Working Memory and Reducing Anxiety in University Students: A Neurofeedback Approach.

(1) Background: Neurofeedback training (NFT) has emerged as a promising approach for enhancing cognitive functions and reducing anxiety, yet its specific impact on university student populations requires further investigation. This study aims to examine the effects of NFT on working memory improvement and anxiety reduction within this demographic. (2) Methods: A total of forty healthy university student volunteers were randomized into two groups: an experimental group that received NFT and a control group. The NFT protocol was administered using a 14-channel Emotiv Epoc X headset (EMOTIV, Inc., San Francisco, CA 94102, USA) and BrainViz software version Brain Visualizer 1.1 (EMOTIV, Inc., San Francisco, CA 94102, USA), focusing on the alpha frequency band to target improvements in working memory and reductions in anxiety. Assessment tools, including the Corsi Block and Memory Span tests for working memory and the State-Trait Anxiety Inventory-2 (STAI-2) for anxiety, were applied pre- and post-intervention. (3) Results: The findings indicated an increase in alpha wave amplitude in the experimental group from the second day of NFT, with statistically significant differences observed on days 2 (p < 0.05) and 8 (p < 0.01). Contrary to expectations based on the previous literature, the study did not observe a concurrent positive impact on working memory. Nonetheless, a significant reduction in state anxiety levels was recorded in the experimental group (p < 0.001), corroborating NFT's potential for anxiety management. (4) Conclusions: While these results suggest some potential of the technique in enhancing neural efficiency, the variability across different days highlights the need for further investigation to fully ascertain its effectiveness. The study confirms the beneficial impact of NFT on reducing state anxiety among university students, underscoring its value in psychological and cognitive performance enhancement. Despite the lack of observed improvements in working memory, these results highlight the need for continued exploration of NFT applications across different populations and settings, emphasizing its potential utility in educational and therapeutic contexts.

Revealing the Curative Possibilities: A Comprehensive Exploration of Caffeic Acid.

Caffeic acid, a phenolic compound of the hydroxycinnamic acid family, is abundant in various plant-based foods, such as fruits, vegetables, and coffee, alongside other biologically active compounds. Recognizing its potential to address various health issues and its widespread presence in commonly consumed foods underscores the importance of comprehending and harnessing the benefits of caffeic acid for human nutrition and well-being. This versatile substance, characterized by acrylic and phenolic functional groups, plays a pivotal role in the food and pharmaceutical industries. Furthermore, a detailed exploration of its pharmacokinetic properties, absorption, distribution, metabolism, and excretion enhances our understanding of how the human body processes it. Functioning as a precursor for essential compounds, caffeic acid contributes to formulations with notable anti-inflammatory, antiviral, anti-cancer, anti-diabetic, antibacterial, neuroprotective, and hepatoprotective qualities. Its current applications in treating Parkinson's and Alzheimer's disease underscore its therapeutic significance. This comprehensive analysis sheds light on caffeic acid's importance, showcasing its diverse applications across various domains and paving the way for further research and development to fully unlock its therapeutic potential. In conclusion, caffeic acid emerges as a bioactive substance with a broad spectrum of pharmacological properties, suggesting its potential utility in diverse therapeutic contexts. The comprehensive information provided in this article serves as a foundation for further research and learning regarding the various ways that caffeic acid supports human health.

Effect of cancer immunotherapy with CD39/PD-L1 bispecific antibody OriA631-b.

e14508 Background: Despite significant advancements in cancer immunotherapy through the use of immune checkpoint inhibitors, there remains a need for more robust strategies to enhance anti-tumor immune responses. This study introduces and characterizes OriA631-B, an innovative CD39/PD-L1 bispecific antibody. By simultaneously targeting the metabolic checkpoint CD39 and the immune checkpoint PD-L1, this novel antibody has the potential to significantly augment anti-tumor efficacy, particularly in cold tumors characterized by a scarcity of infiltrating immune cells. The development of OriA631-B marks a breakthrough in concurrently addressing two crucial immunosuppressive pathways. Methods: The creation of OriA631-B involved cutting-edge antibody engineering methodologies to guarantee optimal binding affinity and specificity for its target antigens, CD39 and PD-L1. With meticulous design and refinement, OriA631-B was developed to exhibit robust binding capabilities to both CD39 and PD-L1, enabling simultaneous and precise recognition. Leveraging advanced antibody engineering techniques was instrumental in crafting OriA631-B as a potent tool with heightened binding properties, broadening its potential applications across diverse therapeutic contexts. Results: In vitro investigations revealed the efficacy of OriA631-B, derived from the foundation of a clinically validated in-house generated PD-L1 antibody (YN035). This innovative antibody effectively thwarted CD39-mediated adenosine production, resulting in heightened effector T cell function and proliferation. In vivo efficacy assessments conducted on syngeneic hot tumor models MC38 and Hepa1-6 underscored the remarkable effectiveness of OriA631, the CD39 monoclonal antibody (mAb), in controlling tumor growth. Notably, OriA631-B, the CD39/PD-L1 bispecific antibody, exhibited even more profound impacts, significantly restraining tumor growth beyond the effects observed with single-target treatments in the hot tumor model or combination therapies in both the hot tumor model MC38 and the cold tumor model CT26. These findings underscore the potent therapeutic potential of OriA631-B and its capacity to exert robust anti-tumor activity by concurrently targeting CD39 and PD-L1. Additionally, safety profiling revealed an acceptable toxicity profile for OriA631-B, with no significant adverse events observed during the study. Conclusions: In summary, OriA631-B demonstrates potential as an innovative immunotherapeutic strategy for cancer treatment by concurrently targeting CD39-mediated immune suppression and PD-L1-mediated T cell exhaustion. Further exploration, including clinical trials, is imperative to fully uncover the therapeutic capabilities of this groundbreaking bispecific antibody in cancer immunotherapy.

The recent update and advancements of natural products in targeting the Wnt/β-Catenin pathway for cancer prevention and therapeutics.

The Wnt/β-Catenin pathway (Wnt/β-CatP) is implicated in accelerating carcinogenesis and cancer progression, contributing to increased morbidity and treatment resistance. Even though it holds promise as a focus for cancer treatment, its intricate nature and diverse physiological effects pose significant challenges. Recent years have witnessed significant advancements in this domain, with numerous natural products demonstrating promising preclinical anti-tumor effects and identified as inhibitors of the Wnt/β-CatP through various upstream and downstream mechanisms. This study provides a comprehensive overview of the current landscape of Wnt/β-Cat-targeted cancer therapy, examining the impact of natural products on Wnt/β-Cat signaling in both cancer prevention and therapeutic contexts. A comprehensive search was conducted on scientific databases like SciFinder, PubMed, and Google Scholar to retrieve relevant literature on Wnt-signaling, natural products, β-Catenin (β-Cat), and cancer from 2020 to January 2024. As per the analysis of the relevant reference within the specified period, it has been noted that a total of 58 phytoconstituents, predominantly phenolics, followed by triterpenoids and several other classes, along with a limited number of plant extracts, have exhibited activity targeting the Wnt/β-CatP. Most β-Cat regulating modulators restrict cancer cell development by suppressing β-Cat expression, facilitating proteasomal degradation, and inhibiting nuclear translocation. Multiple approaches have been devised to block the activity of β-Cat in cancer therapy, a key factor in cancer progression, leading to the discovery of various Wnt/β-CatP regulators. However, their exploration remains limited, necessitating further research using clinical models for potential clinical use in cancer prevention and therapeutics.

Review on Recent Advances of Sustained Release Matrix Tablet

A pharmaceutical dosage called a sustain-release matrix tablet is made to distribute drugs over a longer length of time. The design of these tablets ensures a steady and regulated release of active substances, decreasing side effects and lowering dosage frequency while maintaining therapeutic efficacy. The main features and disadvantages of sustain-release matrix tablets will be covered in detail in this review article. We have talked about a number of evaluations, including the in tablet dimensions, hardness, friability, homogeneous drug content, weight fluctuation, and swelling index. Sustained release matrix tablets are useful in a wide range of therapeutic contexts when a steady and extended release of the drug is necessary to preserve therapeutic efficacy, enhance patient compliance, and reduce adverse effects. The particular medication, the demands of the patient, and the intended therapeutic result all influence the decision to take such tablets.

A Viral Pedagogy: Undoing Things with Long COVID’s Autoimmunities

This article focuses on the scientific and political transformations that the COVID-19 pandemic continues to engender through its impact on the epistemological and ontological foundations of autoimmunity. By discussing an online seminar taught during the COVID pandemic winter of 2020–21, the article considers how the viral autoimmunities involved in severe and long-haul COVID pathogenic mechanisms have fostered transformative pedagogical and therapeutic experiences, spaces, and events. As a highly contagious viral disease, COVID highlights disparities in access to healthcare, whereby certain (racialized, disabled, ageing) bodies are unequally burdened with the labor of staying alive. Predicated on a foundational separation between inside and outside, or between the internal, vulnerable, visceral space of the individual(ized) “human” body and an external(ized), hazardous, contaminated, foreign environment, COVID measures for avoiding viral exposure became paramount, reciting a genealogy of distancing, protection, containment, and isolation. By examining how concepts and practices of autoimmunity animate cutting-edge biomedical research, this article asks, How does autoimmunity undo normative models of health predicated on a militarized model of immunity? How might the viral shift our understanding of autoimmunity and what might autoimmune conditions teach us about virality? In short, what can autoimmunity and the viral show us about uncertainty, care, and transformation in therapeutic and pedagogical contexts?

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems.

The growing interest in oleanolic acid (OA) as a triterpenoid with remarkable health benefits prompts an emphasis on its efficient use in pharmaceutical research. OA exhibits a range of pharmacological effects, including antidiabetic, anti-inflammatory, immune-enhancing, gastroprotective, hepatoprotective, antitumor, and antiviral properties. While OA demonstrates diverse pharmacological effects, optimizing its therapeutic potential requires overcoming significant challenges. In the field of pharmaceutical research, the exploration of efficient drug delivery systems is essential to maximizing the therapeutic potential of bioactive compounds. Efficiently delivering OA faces challenges, such as poor aqueous solubility and restricted bioavailability, and to unlock its full therapeutic efficacy, novel formulation strategies are imperative. This discussion thoroughly investigates different approaches and advancements in OA drug delivery systems with the aim of enhancing the biopharmaceutical features and overall efficacy in diverse therapeutic contexts.

Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform.

Protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D), is a serine/threonine phosphatase that is recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses the activation of p53. Consistent with its oncogenic properties, genetic loss or pharmacologic inhibition of PPM1D impairs tumor growth and sensitizes cancer cells to cytotoxic therapies in a wide range of preclinical models. Given the therapeutic potential of targeting PPM1D specifically and the DDR and p53 pathway more generally, we sought to deepen our biological understanding of PPM1D as a drug target and determine how PPM1D inhibition differs from other therapeutic approaches to activate the DDR. We performed a high throughput screen to identify new allosteric inhibitors of PPM1D, then generated and optimized a suite of enzymatic, cell-based, and in vivo pharmacokinetic and pharmacodynamic assays to drive medicinal chemistry efforts and to further interrogate the biology of PPM1D. Importantly, this drug discovery platform can be readily adapted to broadly study the DDR and p53. We identified compounds distinct from previously reported allosteric inhibitors and showed in vivo on-target activity. Our data suggest that the biological effects of inhibiting PPM1D are distinct from inhibitors of the MDM2-p53 interaction and standard cytotoxic chemotherapies. These differences also highlight the potential therapeutic contexts in which targeting PPM1D would be most valuable. Therefore, our studies have identified a series of new PPM1D inhibitors, generated a suite of in vitro and in vivo assays that can be broadly used to interrogate the DDR, and provided important new insights into PPM1D as a drug target.

Quantifying CO-release from a photo-CORM using 19F NMR: An investigation into light-induced CO delivery

Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover, pharmacologically, CO has been substantiated for its therapeutic advantages in animal models of diverse pathological conditions. Given that an excessive level of CO can be toxic, it is imperative to quantify the necessary amount for therapeutic use accurately. However, estimating gaseous CO is notably challenging. Therefore, novel techniques are essential to quantify CO in therapeutic applications and overcome this obstacle precisely. The classical Myoglobin (Mb) assay technique has been extensively used to determine the amount of CO-release from CO-releasing molecules (CORMs) within therapeutic contexts. Nevertheless, specific challenges arise when applying the Mb assay to evaluate CORMs featuring innovative molecular architectures. Here, we report a fluorinated photo-CORM (CORM-FBS) for the photo-induced CO-release. We employed the 19F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new 19F NMR approach opens immense opportunities for researchers to develop reliable techniques for identifying molecular structures, quantitative studies of drug metabolism, and monitoring the reaction process.

Tumor infiltrating B lymphocytes (TIBs) associate with poor clinical outcomes, unfavorable therapeutic benefit and immunosuppressive context in metastatic clear cell renal cell carcinoma (mccRCC) patients treated with anti-PD-1 antibody plus Axitinib

PurposeImmune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) has become first-line therapy for metastatic renal cell carcinoma patients. This study aims to investigate the effect of tumor infiltrating B lymphocytes (TIBs) on the combination therapy.MethodsThe retrospective analysis was conducted on the clinical records of 115 metastatic clear cell renal cell carcinoma (mccRCC) patients treated with anti-PD-1 antibody plus Axitinib between March 2020 and June 2023. Observation target: objective response rate (ORR), and overall survival (OS), progression-free survival (PFS) and immune profile.ResultsPatients with high TIBs portended lower ORR of the combination therapy (p = 0.033). TIBs was an independent predictor for poorer OS (p = 0.013) and PFS (p = 0.021) in mccRCC patients with combination treatment. TIBs infiltration was associated with more CD4+T (p < 0.001), CD8+T (p < 0.001), M2 macrophages (p = 0.020) and regulatory T cells (Tregs) (p = 0.004). In TIBs high patients, the percentages of PD-1, CTLA-4 and TIM-3 positive rate were significantly increased in CD4+T (p = 0.038, 0.029 and 0.002 respectively) and CD8+T cells (p = 0.006, 0.026 and < 0.001 respectively).ConclusionsOur study revealed TIBs infiltration predicted adverse outcomes in mccRCC patients treated with anti-PD-1 antibody plus Axitinib. As a corollary, TIBs positively associated with M2 macrophages and Tregs, leading to subsequent multiple immune checkpoints related exhaustion of T cells. Thus, only PD-1 blockade are inadequate to reverse T cells exhaustion effectively in high TIBs mccRCC patients.