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.

The presence of electrical harmonics in low voltage networks causes many problems for customers, the most important of which is the decrease in the power quality beyond the permissible limits, which leads to a decrease in voltage for long periods, a decrease in power factor and a large losses in the electrical network due to the deformation of the electric waveform of voltage and current. The aim of this paper is to design an optimal passive filter and its optimal location to suppress the harmonic distortion in the distribution system that results from nonlinear loads. This filter will use single objective functions and multi objective functions that will minimize the proposed filter cost, the real power losses, total harmonic distortion "THD" and individual harmonic distortion "IHD". This will be done under the equality constraint of power balance and some inequality constraints such as filter parameters limits, quality factor limits, voltage limits, harmonic distortion limits. The optimal passive filter parameters and location will be calculated using the modern optimization techniques such jellyfish optimization technique. IEEE 33 bus radial system will be used for demonstrating results obtained by the proposed method.

With the improvement of people's living standards and the increasing emphasis on health, new and higher demands are also placed on the medical industry. The diagnosis and treatment methods combining artificial intelligence and medicine are bound to receive more and more attention and promotion. At present, drug design is stepping into the era of artificial intelligence, and academia and industry are actively applying artificial intelligence technology to all aspects of drug research and development, including drug screening, molecular characterization, drug activity and druggability optimization, chemical reaction design, etc. Relying on the big data information of millions of patients, the artificial intelligence system can quickly and accurately mine and screen out suitable drugs. Through computer simulations, artificial intelligence can make predictions about drug activity, safety, and side effects, and find the best drug that matches the disease. This technology will shorten the drug development cycle, reduce the cost of new drugs and improve the success rate of new drug development.

Cancer treatment faces multiple challenges, including tumor heterogeneity, drug resistance, microenvironment influence, treatment side effects, and treatment cost. The heterogeneity of the tumor makes the effect of the same treatment vary in different patients, so the development of personalized treatment strategies is crucial. In addition, resistance of tumor cells to therapeutic drugs is a major challenge, and new strategies to overcome resistance are needed. As a cutting-edge field of science and technology, nanotechnology has brought great potential and opportunities for tumor treatment. Nanoparticle drug delivery systems improve drug efficacy and reduce side effects through precise targeted delivery and controlled release. Cell-membrane coated nanoparticles show great promise in tumor therapy. Nanoparticles coated with cell membranes have good biocompatibility, can reduce the obstacles of immune rejection and cell uptake, improve the accumulation and retention of drugs in tumor tissues, and have good drug delivery ability, drug stability and control release ability. This review discusses advances in the use of cell-membrane coated nanoparticles to target tumor drugs.

The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.

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.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

Cell-penetrating peptides (CPPs) have emerged as a promising strategy for enhancing the membrane permeability of bioactive molecules, particularly in the treatment of central nervous system diseases. CPPs possess the ability to deliver a diverse array of bioactive molecules into cells using either covalent or non-covalent approaches, with a preference for non-covalent methods to preserve the biological activity of the transported molecules. By effectively traversing various physiological barriers, CPPs have exhibited significant potential in preclinical and clinical drug development. The discovery of CPPs represents a valuable solution to the challenge of limited membrane permeability of bioactive molecules and will continue to exert a crucial influence on the field of biomedical science.

Deposit insurance systems are designed to balance the benefits of preventing bank runs and protecting ordinary savers against the costs of reduced market discipline and potential burdens on taxpayers. Design flaws of deposit insurance make the benefits too low and the costs too high. This paper presents an example in which solvent banks can effectively manage runs, depositors discipline banks to a reasonable extent, and taxpayers have a fair deal. It has three key features: the bank’s authority to activate deposit insurance early, a coinsurance scheme that transfer money from those who run on solvent banks to those who stay put, and a shareholder position for taxpayers. Early activation of deposit insurance prevents fire sales of assets and provides opportunities to verify the bank’s solvency. The coinsurance scheme weakens the incentive to run and strengthens the incentive to hold on to their accounts. As shareholders, taxpayers receive dividends in normal times in exchange for large payouts in catastrophic events.

Pseudomonas aeruginosa is a common pathogen, and its presence in medical environments and water bodies has attracted widespread attention. Traditional detection methods are usually time-consuming and cumbersome, so it is necessary to develop a rapid and sensitive detection technology. DNase can specifically recognize and cut DNA molecules complementary to its substrate sequence. The researchers took advantage of this property to design various DNase-based sensors for detecting the presence of Pseudomonas aeruginosa. These sensors usually use DNase as a recognition element to identify target strains by hybridizing with specific DNA sequences. When the target strain is present, DNase is activated and begins to catalyze the cleavage reaction, producing a detectable signal. This DNase-based sensor has the advantages of rapidity, high sensitivity, and high specificity. In addition, the researchers also explored combining DNase with nanomaterials, fluorescent dyes, etc. to further improve the performance of the sensor. These improvements have improved the detection ability of the sensor in complex samples, laying the foundation for practical applications. With the continuous improvement of technology, these sensors are expected to be widely used in medical, environmental monitoring and other fields, and provide more efficient and convenient solutions for bacterial detection. This study reviewed the research progress of DNase-based sensors for the rapid detection of Pseudomonas aeruginosa.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.

Cancer chemotherapy is generally associated with many severe adverse effects. Many cancer studies are currently focused on repurposing conventional non-toxic anti-parasite drugs for cancer treatment. Since cancer cells and parasites have many features in common, some anti-parasite drugs such as benzimidazoles have been recently found to possess the anti-cancer activity. Benzimidazoles act against cancer by inhibiting tubulin polymerization, inducing cancer cell apoptosis, arresting cell cycle and over-generating reactive oxygen specimen. In this review, we summarize the anticancer features of these drugs in recent investigations, lead to reconsideration of benzimidazoles as a family of anti-cancer chemotherapeutics with non-toxicity or low toxicity to the normal cells and tissues. We particularly highlight the recent progresses using nanoformulations for enhanced cancer therapy and provide our prospects in the future research.

Giving full play to the interaction of multi-dimensional environmental regulation is an important method to accelerate the green transformation of manufacturing enterprises which is a significant way to achieve carbon peaking and carbon neutrality goals. Based on the theory of evolution game, a green transformation strategy evolution game model participated by the government, consumers, and manufacturing enterprises has been constructed. Stability research is conducted based on the behavioral mode of the three parties participating subjects and the paper uses MATLAB for numerical simulation to analyze the impact of environmental regulations of different dimensions on the green transformation of enterprises. The research shows that: (1) When the government adopts a single environmental regulation of carbon emission right transaction or green consumption subsidy, it will not affect the choice of green transformation strategies of the enterprise. (2) When the government adopts a single environmental regulation of environmental protection tax, it only promotes enterprises to choose green transformation strategies under limited conditions. (3) Under the multi-dimensional environmental regulations of the government, by affecting the cost and income of enterprise green technology innovation, consumers’ green consumption behavior, and the manufacturing enterprises choose green transformation as a stable strategy. Therefore, the government should give full play to the role of multi-dimensional environmental regulations in promoting consumers' green consumption and enterprises’ green technology innovation to accelerate the green transformation of manufacturing enterprises.

Using an international dataset, this letter finds that high stock returns are associated with increased death rates from drug use disorders. Although the out-of-pocket expenditure on healthcare also rises following a stock market surge, the net effect on life expectancy is significantly negative.

Nanomaterials have shown great potential in anti-tumor applications and are currently the focus of research. This review article aims to provide a comprehensive overview of the challenges encountered in oncology treatment and how nanomaterials are being utilized to overcome these obstacles. The authors discuss the limitations of conventional treatments, including limited efficacy, side effects, and toxicity issues. They highlight the importance of early tumour diagnosis and personalized treatment plans, as well as the need for innovative therapeutic approaches such as targeted therapy, immunotherapy, and gene therapy. The article primarily focuses on how nanomaterials can be engineered to achieve specific recognition and aggregation within tumour tissues through surface modifications involving targeting molecules such as antibodies, peptides, and receptor ligands. This surface modification technique facilitates improved targeting in the targeting of photodynamic therapy, while minimizing harm to normal tissues. The authors also discuss the potential and future prospects of nanomaterials in tumour therapy, including breakthroughs in their application, biosafety concerns, biocompatibility issues, preparation processes, clinical translation challenges, interdisciplinary cooperation, international exchange, relevant regulations and ethical guidelines. Overall, this review highlights the substantial potential of nanomaterials in oncology treatment, emphasizing the need for careful consideration of safety concerns to ensure their safe and effective application. The authors conclude that strengthening interdisciplinary cooperation and international exchange will contribute to the healthy development of nanomaterials in oncology treatment.

This study considers the effects of disclosure conditions on firms' investment decisions when facing an identical competitor in multiple markets. Assuming that there are congestion costs between multiple investments to reduce marginal cost for each market, this study focuses on the cases where the disclosure conditions may differ by market. Like previous studies on single Cournot competition, these results show that firms invest more in the observable investment markets than in the unobservable markets under symmetric disclosure conditions. However, firms invest more in the unobservable market if there are asymmetric disclosure conditions.

Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.

The current study examines the performance of 76 Japanese equity Exchange Traded Funds (ETFs) over the period 1/1/2018-12/31/2022. Performance is estimated in several ways, that is, raw returns, alphas from single- and multi-factor regression models, and risk-adjusted returns. The market timing skills of ETF managers are examined too. The results reveal that, on average, the examined ETFs do not produce any material alpha. The results also indicate that the risk factors suggested by Fama and French (1993 & 2015) are more or less capable of explaining the performance of the Japanese ETFs. Finally, the findings show that 21% of ETF managers possess some sort of market timing skills. However, the managers fail to time the volatility of the stock market.

Considering that housing is the single biggest asset for most households, owning a home may create barriers to entrepreneurship for young people who generally accumulate relatively little wealth due to a short-term career and low income. Using longitudinal data from the China Family Panel Studies (CFPS) survey, our empirical work suggests that homeowners are associated with significantly less propensity for entrepreneurial engagement and the negative homeownership effect on entrepreneurship is much larger for younger homeowners. These findings are robust to omitted variable bias, reverse causality and model misspecification. We explore the mechanism through which capital constraints related to housing purchase may more affect younger homeowners from starting entrepreneurial activities. We find strong supportive evidence for this mechanism.

Major economic and financial contractions usually go hand-in-hand with muted inflation. This has been true for the Great Depression, the Global Financial Crisis, as well as the Covid-19 crisis. In this paper, we theoretically highlight and discuss the evolution of instruments and approaches monetary-policy decision makers at the Federal Reserve have in lifting inflation to desired levels in times of the zero-lower bound, paying particular focus on more rigorous developments like asymmetric average inflation and temporary price-level targeting.