Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

Tripartite motif-containing (TRIM) proteins consist of over 80 proteins, the majority of which exhibit E3 ubiquitin ligase activity. E3 ligases have a critical role in various cellular processes by specifically recognizing and ubiquitinating substrate proteins to promote their proteasomal degradation or alter their activities. Numerous studies have indicated that TRIMs are involved in carcinogenesis through various mechanisms. However, the regulatory mechanisms delimitating TRIMs’ function as E3 ligases has not yet been specifically addressed in a previous review article. In this review, we focus on recent advancements in understanding how certain TRIMs function solely as E3 ligases during cancer cell proliferation, apoptosis, and metastasis. We comprehensively summarize the target proteins of TRIMs involved in disordered signaling pathways such as Wnt/β-catenin, PI3K/AKT, NF-κB, p53, ERK, and STAT3, as well as those regulating the cell cycle and glycolysis. Following ubiquitination modification by TRIM E3 ligases, these target proteins either undergo proteasome-mediating degradation, maintain steady levels, or get activated/inactivated. This review provides a foundation for the development of E3 ligase-based cancer treatments.

 In the past, researchers investigated the immune response acting against mycobacterial antigens in tuberculosis (TB). Several ELISA tests have been conducted for the diagnosis of tuberculosis. Other researchers manipulated 16 kDa antigen from Mycobacterium Tuberculosis to develop a tuberculosis diagnostic test while some others studied the subspecies of M. tuberculosis. In the present study, we explored the possibilities of detecting 16 kDa protein derived from M. tuberculosis, on an interdigitated electrode (IDE). Measurements with Electrochemical impedance spectroscopy and current-volt systems were demonstrated using antibody as the probe.  Further, the involvement of gold nanoparticle for the signal-enhancement and high-performance are evidenced. The specificity in the serum containing samples is used to show the clinical relevancy. 16 kDa antigen used in this experiment is highly reliable for TB diagnosis as it largely expresses and can be implemented in other sensing system.

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.

Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

Given the rapid development of live streaming commerce in China, this study focuses on the interactivity and sociability of live streaming shopping activities and explores online consumers’ real-time interaction intentions and trust-building behaviours with online merchants. To discover the real-time interaction between online consumers and online merchants, this study builds a research model based on the Theory of Planned Behaviour (TPB). Through the data analysis based on the partial least squares path modelling and variance-based structural equation modelling (PLS-SEM), the key findings state that, three factors, including attitude, subject norm, and perceived control, positively affect online consumers’ real-time interaction intentions and lead them to build trust with online merchants. Meanwhile, control variables, including gender, age, and educational background, demonstrate insignificant effects across the model. Unlike existing literature, the current study pays much attention to the interactive characteristics of live streaming shopping activities and can provide some valuable suggestions both for online consumers and online merchants, which can promote the co-development of the commercial and social aspects of live streaming platforms.

Objective: The DSS was utilized to construct colitis model of mouse. The colitis mice were colonized with gut microbiota. The effects of gut microbial metabolites on colitis were studied. The mechanisms of gut microbial metabolites to improve intestinal immunity were also further explored. Methods: The male BALB/c mice were selected to construct colitis mouse model with DSS and colonized with gut microbiota. The content of short-chain fatty acids in intestinal metabolites of mice during modeling were detected with GC-MS. After the mice were sacrificed, the colon tissue was stained to observe the colitis in different groups of mice. The contents of IL-22 and IL-17 in colon tissue was determined with ELISA method. To study the mechanism of relieving colitis, qRT-PCR and western blotting were used to study the horizontal of Ffar2 gene and pSTAT3 and pAKT in colon tissue, respectively. The congenital lymphocytes were isolated and purified, and the migration ability of the congenital lymphocytes was examined by cell scratch plane migration test. Results: The colonization of the gut microbiota had significant effects on the contents of short-chain fatty acids in the intestinal metabolites of colitis mice, of which the effect on the content of acetic acid and butyric acid was more significant. The colonization of gut microbiota could effectively relieve colitis in mice and effectively promote the secretion of IL-22 in colon tissue. Studying the remission mechanism indicated that colonization of gut microbiota with colitis could effectively promote the expression of Ffar2 gene in colon tissue and increase the expression of pSTAT3 and pAKT protein. The migration ability of the lymphocyte was significantly upregulated in the model group compared with the other groups, demonstrating that DSS can effectively activate the lymphocyte; The migration of congenital lymphocyte in the experimental group was significantly alleviated than that in the model group, but it was up-regulated than that in the positive control group, and the colonic tissue of the positive control group was similar to that of the normal group. Conclusion: The short-chain fatty acids in the intestinal flora metabolites can promote the gene expression of the metabolite-sensitive receptor Ffar2. The effective combination of short-chain fatty acids and Ffar2 receptors can promote the phosphorylation of STAT3 and AKT proteins, effectively promote the secretion of IL-22 in intestinal ILC3 cells, alleviate colitis in mice, and thereby improve their intestinal immune function.

Although docetaxel treatment yields a high survival rate for prostate cancer (PCa), resistance eventually develops in many patients. Understanding the underlying mechanisms of docetaxel resistance is essential for improving treatment strategies. Cytokines, which play a role in cell signaling and immune responses, have been implicated in drug resistance mechanisms. The study revealed that interleukin-8 (IL-8) was consistently overexpressed in both docetaxel-resistant PCa cell lines. Thus, the expression levels of cytokines released from docetaxel-sensitive (PC-3- and DU-145) and resistant (PC-3/R-DU-145/R) PCa cells were compared. IL-8 was found to be commonly expressed in resistant cell lines. This finding led to the hypothesis that IL-8 could play a key role in mediating PCa cell resistance to docetaxel. IL-8 siRNA treatment increased docetaxel sensitivity in both resistant cells. To demonstrate the mechanism of IL-8-related resistance, MDR1 expression was evaluated. After IL-8 siRNA treatment MDR1 expression was reduced in both resistant cells suggesting that IL-8 regulates the docetaxel resistance of PCa cells via modulation of multidrug resistance 1 (MDR1). By expanding the knowledge of the cytokines and their effect mechanisms, novel approaches can be developed for the treatment of docetaxel-resistant prostate cancer. Further investigations into the role of IL-8 in docetaxel resistance could offer valuable insights into the development of effective treatment strategies for PCa patients.

The latent transforming growth factor-beta (TGF-β) binding protein 1 (LTBP1) has been implicated in various cellular processes, but its role in triple-negative breast cancer (TNBC) remains unclear. In this study, we investigated the impact of LTBP1 on TNBC progression and its underlying mechanisms. Analysis of online datasets revealed elevated LTBP1 mRNA expression in breast cancer tissues compared to normal adjacent tissues. Kaplan-Meier Plotter analysis indicated that high LTBP1 expression was negatively correlated with relapse-free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS) of breast cancer patients. Additionally, LTBP1 mRNA levels were associated with chemotherapy resistance. Functional assays in TNBC cells demonstrated that LTBP1 knockdown suppressed cell proliferation, induced apoptosis, and attenuated migration and invasion. In vivo studies confirmed that LTBP1 knockdown inhibited tumor growth in a xenograft mouse model. Mechanistically, LTBP1 positively correlated with genes involved in signaling regulation and organelle organization, with significant associations to GTPase binding and the RhoA/ROCK pathway. LTBP1 knockdown reduced RhoA activity and phosphorylation of Myosin Light Chain 2 (MLC2), suggesting inhibition of the RhoA/ROCK signaling pathway. Moreover, activation of the RhoA/ROCK pathway partially rescued the effects of LTBP1 knockdown on TNBC cell proliferation, apoptosis, migration, and invasion. In conclusion, our findings suggest that LTBP1 promotes TNBC progression through activation of the RhoA/ROCK signaling pathway, highlighting its potential as a therapeutic target for TNBC.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.

The digital transformation of manufacturing industry can promote the development of green transformation and promote the differentiation of workers’ skill structure; On the other hand, it will also hinder the green development due to the huge energy consumption generated by the application of digital technology and facilities. In addition, the green transformation of manufacturing industry will also have differentiated impacts on the employment of labour with different skills due to the innovation of green technology. The existing research has not discussed too much about the interaction among the digital transformation and green transformation in manufacturing industry and labour structure. So, this paper uses the PVAR model to examine the dynamic relationship between digital and green transformation within the industrial sector from the perspective of labour structure, specifically analyzing the impact difference across regions. The results suggest that there is a reciprocal connection between the digitization of manufacturing sector and the labour structure, particularly in the eastern region of China, but the overall interaction between the two remains weak. The interactive between the green transformation of manufacturing industry and the labour structure in the central and western areas has been delayed over periods 1-6. Digital and green manufacturing transformation reinforce each other in central and western regions. However, the digital revolution in the manufacturing industry is hindered by the green transformation in eastern region.

This article discusses the pressing need to integrate artificial intelligence (AI) into education to facilitate customizable, individualized, and on-demand learning pathways. At the same time, while AI has the potential to expand the learner base and improve learning outcomes, the development of NACE Competencies and durable skills – communication, critical thinking, creativity, leadership, adaptability, and emotional intelligence - must be purposefully integrated in curriculum design now more than ever. Recent studies have shown that AI-driven learning pathways can achieve outcomes more quickly, but this comes at the cost of the development of durable skills. Therefore, traditional student-to-student and student-to-teacher interactions must be prioritized. As such, this study proposes a balanced approach to curriculum design to ensure the best outcomes for learners, where durable skill development is prioritized alongside subject-specific skills and rote memorization. Additionally, the article highlights the need for a combination of Just in Time Training (JITT) approaches, facilitated by AI technology, to reach the implementation of durable skills. The article concludes by questioning how to develop human skills in an increasingly AI-driven education system and emphasizes the importance of curriculum design and traditional learning approaches in creating a cohesive learning experience that develops durable skills in students. It is necessary to recognize that AI-driven education cannot replace the development of human skills, and that traditional interactions play a crucial role in developing these skills.

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.

Transition metal sulfides/transition metal phosphides (TMS/TMP) has shown great potential in cancer diagnosis and treatment due to its unique structural, optical, acoustic and magnetic properties. TMS/TMP can be formed from sulfur/phosphorus source and metal into binary compounds, or from the interaction of hydrogen sulfide (or hydrogen sulfuric acid) with metal oxides or hydroxides. It has a series of unique properties, such as high conductivity, metalloid properties, a variety of valence states and adjustable structure and so on. These advantages make it have great potential in biomedical applications, such as diagnostic imaging, disease therapy and drug/gene delivery. This review presents the latest research progress of TMS/TMP on tumor imaging, diagnosis and treatment. Here, we first illustrate the synthesis approaches and surface modification of TMS/TMP. Then, its emerging applications in tumor diagnosis and therapy are highlighted. Moreover, the challenges of TMS/TMP-mediated diagnosis/treat are provided and the prospective for this field are discussed.

This study examines the role of the Corporate Social Responsibility Committee (CSRC) in the adoption of strategic Corporate Social Responsibility (CSR) projects that surpass regulatory requirements and basic stakeholder expectations. Our results demonstrate that the establishment of CSRCs enhances all strategic CSR mechanisms, particularly business reputation, stakeholder interaction, risk mitigation, and innovation. Additionally, strategic CSR practices exhibit a strong correlation with CSRC attributes and organizational characteristics. Specifically, the size of the CSRC is positively associated with all dimensions of strategic CSR. Furthermore, CEO membership is likely to impede risk mitigation and innovation capacity, whereas board chair membership enhances business reputation, stakeholder communication, and innovation potential. In terms of gender diversity, female CSRC members show a greater concern for business reputation and associated risks. Regarding committee functioning, increased meeting frequency has the potential to enhance various aspects of strategic CSR.

The sensitive nature of interest rate has spurred empirical interests on the factors that determine it. This paper examined the joint impact of exchange rate and foreign direct investment inflows on interest rate in Nigeria over the period from 1981-2022. The study made use of the auto regressive distributed lag (ARDL) bounds test and results of findings reveal that in both the short-run and the long-run the impact of the interaction between FDI inflows and exchange rate on real interest rate was negative and significant. Also, while credit to the private sector was found to have significant positive impact on real interest rate in both the time horizons, the impact of consumer price index was negative only in the short. Oil revenue was found to impact positively on real interest rate only in the long-run, but the impact of broad money supply was negative and significant in both the short-run and the long-run. The study suggests that policies to regulate domestic interest rate should focus on joint regulation of both exchange rate and FDI inflows and this requires a synergy between monetary and fiscal policies.

Traditionally, conditions of sustainability of the public debt have long been related quite exclusively to fiscal policy and to budgetary parameters. However, the interaction between fiscal and monetary policies regarding the fixation of the interest rate is fundamental. Indeed, a simple analytical modelling shows that if the nominal interest rate increases exponentially with the public debt, because of a default (credit) risk premium, if the confidence of investors is fundamental, conditions of sustainability of the public debt could be much more difficult to comply with. Indeed, if the interest rate is risk-free, values for which the public debt can be sustainable are less constraining if the long-term GDP growth rate is high, or if the long-term risk-free nominal interest rate is small. They are also less constraining if the country decides to turn to a non-negligible primary budget surplus in case of a high public debt. However, if the interest rate exponentially increases with the public debt level, in case of a significant importance of the default (credit) risk premium, these parameters have very limited consequences on sustainable and equilibrium public debt levels. The sustainable public debt that a government should target is then much smaller than in absence of this risk premium.

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.

Less-Lethal Weapons, including electric Tasers, velocity-reduction bullet-capture projectiles, rubber bullets, beanbag rounds, and other less-lethal projectiles used in police departments, federal and local law enforcement agencies, and military policing operations, as well as for private use, are topics of significant debate in recent years. These weapons can reduce collateral damage, reputational risk, and legal exposure while preventing wrongful and unnecessary deaths caused by conventional bullet wounds. Yet, opponents have highlighted concerns regarding the safety and effectiveness of these weapons, as well as their potential to cause injury or even death. While the primary duty of law enforcement officials is to preserve order and execute the law while protecting individual rights, they ultimately achieve these goals by exercising their coercive authority. Society expects police officers to rely on their professional training and judgment when using physical force to defend citizens and themselves or to apprehend criminal suspects. Because police officers must occasionally participate in physical acts of coercion, it is unavoidable that some of these interactions may result in bodily injuries to individuals, including the officers themselves. These injuries have real costs, such as medical treatment, lost wages, municipal liability, court claims and settlements, riots, and legal or even criminal exposure, as well as less-tangible collateral costs, such as the erosion of police legitimacy and public trust, which are more difficult to quantify but arguably more influential in shaping long-term public perceptions than personal injuries alone. Less lethal technology eliminates some of the concerns raised by lethal weaponry. This study reviews the advantages and disadvantages of these less-lethal weapon technologies versus traditional firearms for use by the police force, federal agencies, and military police while also performing advanced analytics to model the valuation and return on investment for a law enforcement organization implementing such technologies.