Probing impact on magnetic behavior of cobalt layer grown on thick MoS 2 layer.

Understanding the metal-semiconductor heterostructure interface is crucial for the development of spintronic devices. One of the prospective candidates and extensively studied semiconductors is molybdenum disulfide (MoS 2 ). Herein, utilizing Kerr microscopy, we investigated the impact of thick MoS 2 on the magnetic properties of the 10 nm Co layer. A comparative study on Co / MoS 2 and Co/Si shows that coercivity increased by 77% and the Kerr signal decreased by 26% compared to Co grown on Si substrate. In addition, the Co domain structure significantly changed when grown on MoS 2 . The plausible reason for the observed magnetic behavior can be that the Co interacts differently at the interface of MoS 2 as compared to Si. Therefore, our studies investigate the interfacial effect on the magnetic properties of Co grown on thick MoS 2 layer. Furthermore, our results will help in developing next-generation spintronic devices.

Macrophages reprogramming driven by cancer-associated fibroblasts under FOLFIRINOX treatment correlates with shorter survival in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a clinically challenging cancer, mainly due to limited therapeutic options and the presence of a highly prominent tumor microenvironment (TME), facilitating tumor progression. The TME is predominated by heterogeneous populations of cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs), in constant communication with each other and with tumor cells, influencing many tumoral abilities such as therapeutic resistance. However how the crosstalk between CAFs and macrophages evolves following chemotherapeutic treatment remains poorly understood, limiting our capacity to halt therapeutic resistance. METHODS: We combined biological characterization of macrophages indirectly cocultured with human PDAC CAFs, under FOLFIRINOX treatment, with mRNAseq analyses of such macrophages and evaluated the relevance of the specific gene expression signature in a large series of primary PDAC patients to search for correlation with overall survival (OS) after FOLFIRINOX chemotherapy. RESULTS: Firstly, we demonstrated that CAFs polarize naïve and M1 macrophages towards an M2-like phenotype with a specific increase of CD200R and CD209 M2 markers. Then, we demonstrated that CAFs counteract the pro-inflammatory phenotype induced by the FOLFIRINOX on Macrophages. Indeed, we highlighted that, under FOLFIRINOX, CAFs limit the FOLFIRINOX-induced cell death of macrophages and further reinforce their M2 phenotype as well as their immunosuppressive impact through specific chemokines production. Finally, we revealed that under FOLFIRINOX CAFs drive a specific macrophage gene expression signature involving SELENOP and GOS2 that correlates with shortened OS in FOLFIRINOX-treated PDAC patients. CONCLUSION: Our study provides insight into the complex interactions between TME cells under FOLFIRINOX treatment. It suggests potential novel candidates that could be used as therapeutic targets in combination with FOLFIRINOX to prevent and alleviate TME influx on therapeutic resistance as well as biomarkers to predict FOLFIRINOX response in PDAC patients. Video Abstract.

Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a vast stromal reaction that arises mainly from cancer-associated fibroblasts (CAFs) and promotes both immune escape and tumor growth. Here, we used a mouse model with deletion of the activin A receptor ALK4 in the context of the KrasG12D mutation, which strongly drives collagen deposition that leads to tissue stiffness. By ligand-receptor analysis of single-cell RNA-sequencing data, we identified that, in stiff conditions, neoplastic ductal cells instructed CAFs through sustained platelet-derived growth factor (PDGF) signaling. Tumor-associated tissue rigidity resulted in the emergence of stiffness-induced CAFs (siCAFs) in vitro and in vivo. Similar results were confirmed in human data. siCAFs were able to strongly inhibit CD8+ T-cell responses in vitro and in vivo, promoting local immunosuppression. More importantly, targeting PDGF signaling led to diminished siCAF and reduced tumor growth. Our data show for the first time that early paracrine signaling leads to profound changes in tissue mechanics, impacting immune responses and tumor progression. Our study highlights that PDGF ligand neutralization can normalize the tissue architecture independent of the genetic background, indicating that finely tuned stromal therapy may open new therapeutic avenues in pancreatic cancer.

SK2 channels set a signalling hub bolstering CAF-triggered tumourigenic processes in pancreatic cancer.

OBJECTIVE: Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC. DESIGN: We evaluated the effects of conditioned media from patient-derived cancer-associated fibroblasts (CAFs) on electrical features of pancreatic cancer cells (PCC). The molecular mechanisms were deciphered using a combination of electrophysiology, bioinformatics, molecular and biochemistry techniques in cell lines and human samples. An orthotropic mouse model where CAF and PCC were co-injected was used to evaluate tumour growth and metastasis dissemination. Pharmacological studies were carried out in the Pdx1-Cre, Ink4afl/fl LSL-KrasG12D (KICpdx1) mouse model. RESULTS: We report that the K+ channel SK2 expressed in PCC is stimulated by CAF-secreted cues (8.84 vs 2.49 pA/pF) promoting the phosphorylation of the channel through an integrin-epidermal growth factor receptor (EGFR)-AKT (Protein kinase B) axis. SK2 stimulation sets a positive feedback on the signalling pathway, increasing invasiveness in vitro (threefold) and metastasis formation in vivo. The CAF-dependent formation of the signalling hub associating SK2 and AKT requires the sigma-1 receptor chaperone. The pharmacological targeting of Sig-1R abolished CAF-induced activation of SK2, reduced tumour progression and extended the overall survival in mice (11.7 weeks vs 9.5 weeks). CONCLUSION: We establish a new paradigm in which an ion channel shifts the activation level of a signalling pathway in response to stromal cues, opening a new therapeutic window targeting the formation of ion channel-dependent signalling hubs.

Donatio organorum- reluctance to organ donation medical students; a cross-sectional descriptive study.

Introduction: Organ donation is the act of removing an organ or tissue from a donor and transplanting the said organ/tissue to a recipient. Despite being the only definitive treatment for end-organ failure, there is a lot of hesitation surrounding the practice of organ donation. Even among medical students, who are more aware of the benefits of organ donation than the general public, this reluctance is widespread.Therefore, we conducted this research to determine the basis of this skepticism, so that the root causes can be identified and eradicated. Our research sought to ascertain the overall attitudes of Rawalpindi Medical University, Pakistan's students towards organ donation, the associated factors that influenced this attitude (religious devotion, gender, age, year of study) and the reasons for the hesitance. Methods: A cross-sectional study targeting the students of first to final year MBBS was conducted at Rawalpindi Medical University, Pakistan in the year 2022. The sample size was calculated using OpenEpi software, and came out to be 292. The students enrolled at Rawalpindi Medical University during the year 2021-2022 were made a part of the study. A self-structured questionnaire that was developed after substantial research was used to collect the data using a non-random convenience sample technique. Chi Square test was used to determine significance after data analysis using SPSS-22. Results: A total of 290 students participated in the study, 58 from each year. All of the participants were Muslim. A very strong correlation was found between high devoutness and willingness towards organ donation (p = 7.4252E-13). Only 9/290 (3%) of people in Pakistan have joined The Transplantation Society of Pakistan; the main cause of this low ratio is that very few people were aware that such a group even existed (according to 62% of the responders). The mistrust of doctors and the belief that appropriate efforts would not be done to resuscitate patients who have signed up for organ donation is a significant factor in the anxiety surrounding organ donation. Conclusions: There are several reasons why people are reluctant to donate their organs, including a lack of understanding of religious perspectives on the subject, mistrust of medical professionals and medical administration, and general public ignorance. We can make a significant progress toward closing the gap between the demand for and supply of organ donations if these problems are remedied. The most effective strategy to stop organ trafficking is through organ donation. Through seminars, conversations, and workshops, we need to raise awareness about organ donation.

Awareness of mothers coming to obstetric wards of allied hospitals regarding neonatal care and the working of community health workers in their districts.

Introduction: Neonatal mortality remains a significant challenge not only to the world,but especially to a developing country like Pakistan. It can be majorly attributed to the sub-par healthcare, insufficient and under-recognised community health workers, and the lack of knowledge of proper newborn care on the part of the parents. This study targets the level of knowledge of the mothers and the services provided by community health care workers as the main factors determining neonatal care. Methods: A cross-sectional study was conducted in the OBS (obstetrics) wards of Hospitals affiliated with Rawalpindi Medical University from January 2022 to June 2022. The sample size was 138. Data was collected by one-on-one interviews, using a standardized USAID Community Health Worker Assessment and Improvement Matrix questionnaire. Data analysis was done using SPSS v28. Chi-square test was applied to check for significance. Results: Out of the total 138 participants, 47.8% (n = 66/138) were between the ages of 21-25. Results showed that women between the ages of 21-25 (P = 0.000058) and women who had their first child between the ages of 23-27 had good knowledge about neonatal care. 45% (n = 62/138) of the participants had poor knowledge of neonatal care, whereas 55% (n = 76/138) had good knowledge (P = 0.000002). As for the role of community health workers, only 20-30% of the participants were being provided with their services; hence their performance was not found to be adequate. Conclusions: The world of medicine is moving rapidly toward a new framework of the health systems in which the real foundation will be based on what actually takes place in the community, therefore, community health workers can play an important role in improving maternal and neonatal care. Family-centered care, appropriate age of first conception and motherhood, and proper guidance to first-time parents can ensure significant improvement in neonatal care in the future.