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The stability of a controlled network temperature control system (heat exchanger system) is examined in this study paper. A heat exchanger system keeps the end temperature of a liquid within defined parameters. The study proposes a linearized model of a temperature control system based on a delay-dependent state equation to accomplish this job. For a temperature management system in a network having time-varying delays, the LK functional (Lyapunov–Krasovskii) method is coupled with the reciprocal convex lemma. To get less conservative stability requirements, a new LK functional was assumed in the stability analysis, and the time-dependent of the (LK) functional was taken via the reciprocal convex combination approach. Finally, under the LMI (linear matrix inequalities) paradigm, the suggested stability analysis leads to a stability criterion. The suggested results establish a new stability criterion for a more accurate operating form for a present temperature control system based on a theoretically obtained temperature management system.

The CoWIN Twitter Dataset offers a wide-ranging collection of public opinions on India's COVID-19 vaccination platform CoWIN. The raw dataset has 635,000 tweets that mention "cowin," collected over the period of January to December 2021. The dataset was extracted by employing the Twitter Academic API. It addition to the raw data, it also included a cleaned and processed set of 419,409 English tweets, and a labeled subset with sentiment analysis. The raw data file has tweet details like ID, text, timestamp, user ID, and language. The processed dataset is devoid of URLs and hashtags and other noise, and also adds month and category groupings. Finally,the labelled dataset gives sentiment classifications of positive or negative the relevant tweets. This dataset enables researchers to analyse themes and sentiments related to India's vaccination administration. It can help policymakers gain insights around issues related to large-scale health initiatives and digital health systems. The mix of languages in the data also makes it useful for language processing research., (© 2024 Published by Elsevier Inc.)

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival in Ishikawa and Hec1A endometrial cancer cells and significantly reduced tumor burden in mouse models of endometrial carcinoma. Upon RNA sequencing, the combination was associated with downregulation of cell survival pathways, including senescence, cyclins, and cell cycle regulators. The Axl-PI3K-Akt-mTOR pathway was also decreased by combination therapy. Together, our results highlight EphA2 and histone deacetylase as promising therapeutic targets for endometrial cancer.

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility., (© 2023. The Author(s).)

EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial cancer cell lines. In vivo Hec1A and Ishikawa-Luc orthotopic mouse models of endometrial cancer showed greater anti-tumor responses to combination treatment than to either monotherapy. RNASeq analysis highlighted reduced cell proliferation and defective DNA damage response pathways as potential mediators of the combination's effects. In conclusion, our preclinical findings indicate that Wee1 inhibition can enhance the response to EphA2-targeted therapeutics in endometrial cancer; this strategy thus warrants further development.

CRM1 inhibitors have demonstrated antitumor effects in ovarian and other cancers; however, rational combinations are largely unexplored. We performed a high-throughput drug library screen to identify drugs that might combine well with selinexor in ovarian cancer. Next, we tested the combination of selinexor with the top hit from the drug screen in vitro and in vivo Finally, we assessed for mechanisms underlying the identified synergy using reverse phase protein arrays (RPPA). The drug library screen assessing 688 drugs identified olaparib (a PARP inhibitor) as the most synergistic combination with selinexor. Synergy was further demonstrated by MTT assays. In the A2780luc ip1 mouse model, the combination of selinexor and olaparib yielded significantly lower tumor weight and fewer tumor nodules compared with the control group ( P < 0.04 and P < 0.03). In the OVCAR5 mouse model, the combination yielded significantly fewer nodules ( P = 0.006) and markedly lower tumor weight compared with the control group ( P = 0.059). RPPA analysis indicated decreased expression of DNA damage repair proteins and increased expression of tumor suppressor proteins in the combination treatment group. Collectively, our preclinical findings indicate that combination with selinexor to expand the utility and efficacy of PARP inhibitors in ovarian cancer warrants further exploration., (©2021 American Association for Cancer Research.)

Clinical and experimental studies support the notion that adrenergic stimulation and chronic stress affect inflammation, metabolism, and tumor growth. Eicosanoids are also known to heavily influence inflammation while regulating certain stress responses. However, additional work is needed to understand the full extent of interactions between the stress-related pathways and eicosanoids. Here, we review the potential influences that stress, inflammation, and metabolic pathways have on each other, in the context of eicosanoids. Understanding the intricacies of such interactions could provide insights on how systemic metabolic effects mediated by the stress pathways can be translated into therapies for cancer and other diseases.

Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.TRPA1 has been reported to contribute lung cancer adenocarcinoma (LUAD), but the mechanisms are unclear. Here the authors propose that TRPA1/FGFR2 interaction is functional in LUAD and show that astrocytes oppose brain metastasis by mediating the downregulation of TRPA1 through exosome-delivered miRNA-142-3p.