Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Despite the status of the United States as one of the world’s economic superpowers, the country is plagued by child poverty. The issue of child poverty is most prominent in rural, majority-minority communities, where years of limited opportunity, often created by systematic oppression, have created a vicious cycle of economic despair. There are a number of policies that have been explored which could limit the effects of child poverty, most notably the Expanded Child Tax Credit (ECTC), which was introduced as part of the American Rescue Plan Act (ARPA) of 2021. This paper uses a combination of qualitative and quantitative methods to thoroughly examine this policy (ECTC) and its potential to both cut child poverty in the short term and increase educational attainment and economic mobility in the long term for recipients. The ECTC program ended in 2022 and only lasted in a short period. By examining the impacts of a similar and long-standing but less accessible and generous program, the Earned Income Tax Credit (EITC), on educational attainment in specific communities we can theorize and determine the significance the Expanded CTC would have. We use EITC program as a proxy of ECTC and reach inference of the long-term impact of ECTC program on children’s education attainment. The result of this research indicates a number of benefits of the Expanded Child Tax Credit, including its potential to cut child poverty and increase educational attainment, its impact on future economic prosperity in rural, majority-minority communities, and the policy’s ability to decrease economic disparities between non-metro and metropolitan areas.

Environmental concerns are increasing and business firms are inclined towards adoption of eco-friendly products and services. They are hiring employees via set of green HRM practices and struggling to become an environmentally sustainable firm. Pakistani food industry is booming day by day. However, less is known about the green HRM practices executed in the fast food industry of Pakistan. Therefore, this research is interested in examining the impact of Green recruitment and selection, green training and development and green performance and compensation management on the P-O fit, affective commitment and green recovery performance in Pakistan’s fast food industry. The moderating effects of transformational leadership will be examined between Green HRM practices and green recovery performance. A sample of 408 employees who are working at different designations were selected to accomplish the purpose of the research. These managers will be selected through convenient sampling technique. There were 21 fast food restaurants (Burger Joints) selected from all over Karachi, few of them includes; KFC, Burger Lab, Burger O Clock, Vintage, Plan B and more. The collected primary data will be tested through the application of structural equation modeling technique. Smart PLS software is used to assess the objectives. The results of the study revealed significant association between Green R&S, Green T&D and P-O fit. A non-significant association is found between Green P& C and P-O Fit. The study affirmed that Affective commitment posit a direct influence on GRP. The Green R&S and Green P&C revealed insignificant impacts on the green recovery performance within the fast food industry. The indirect association was analyzed between P&C, P-O fit, AF and GRP and revealed an insignificant result. Likewise, an indirect association is found between R/S, P-O Fit, AF and GRP. The future researchers are recommended to analysis the remaining elements of GHRM and investigate their impacts on the fast food industry of Pakistan. There is a need to create awareness regarding green HRM practices and their influence on the Green recovery performance in Pakistan. Policy makers are recommended to develop such policies that promotes GHRM in Pakistan.

Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.