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Abstract As the role of RNA modification in gene expression regulation and human diseases, the “epitranscriptome” has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m1A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), pseudouridine (Ψ) and N7-methylguanosine (m7G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m6A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.

Abstract Objective The purpose of this study is to assess the impact of physical activity on both therapeutic efficacy and immune-related adverse events (irAEs) during immunotherapy for non-small cell lung cancer (NSCLC). Methods Physical activity was divided into three groups: light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) for laboratory indexes, efficacy, and irAEs. A multivariate logistic regression was employed to analyze the relationship between sedentary behavior with efficacy and irAEs. Results The study included 121 patients. The three levels of physical activity were not significantly associated with efficacy or irAEs. However, noteworthy disparities were observed in base-hemoglobin levels (F = 3.4, P = 0.037) and base-lymphocyte levels (χ2 = 6.13, P = 0.047) among the three groups. After treatment, we identified statistically significant variations in albumin levels (P = 0.012) and lymphocyte counts (P = 0.035). Furthermore, a negative correlation emerged between pre-treatment sedentary behavior duration and immune-efficacy (β: −0.005, P = 0.027). Conclusions In summary, within the cohort of NSCLC patients undergoing single immunotherapy or a combination of immunotherapy and chemotherapy, physical activity is closely related to immune and inflammatory indicators in patients, and prolonged sitting will reduce the therapeutic effect.

Abstract Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients.

Of all malignancies, pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, has the worst prognosis. Glycolysis is overactive in PDAC patients and is associated with poor prognosis. Drugs that inhibit glycolysis as well as induce cell death need to be identified. However, glycolysis inhibitors often fail to induce cell death. We here found that FV-429, a derivative of the natural flavonoid wogonin, can induce mitochondrial apoptosis and inhibit glycolysis in PDAC in vivo and in vitro. In vitro, FV-429 inhibited intracellular ATP content, glucose uptake, and lactate generation, consequently leading to mitochondrial dysfunction and apoptosis in PDAC cells. Furthermore, it decreased the expression of PKM2 (a specific form of pyruvate kinase) through the ERK signaling pathway and enhanced PKM2 nuclear translocation. TEPP-46, the activator of PKM2, reversed FV-429-induced glycolysis inhibition and mitochondrial apoptosis in the PDAC cells. In addition, FV-429 exhibited significant tumor suppressor activity and high safety in BxPC-3 cell xenotransplantation models. These results thus demonstrated that FV-429 decreases PKM2 expression through the ERK signaling pathway and enhances PKM2 nuclear translocation, thereby resulting in glycolysis inhibition and mitochondrial apoptosis in PDAC in vitro and in vivo, which makes FV-429 a promising candidate for pancreatic cancer treatment.

Summary: Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20–30% of PCa cases develop into castration-resistant prostate cancer (CRPC). This article investigates the anti-PCa effect of a drug candidate named GL-V9 and highlights the significant mechanism involving the AKT-hexokinase II (HKII) pathway. In both androgen receptor (AR)-expressing 22RV1 cells and AR-negative PC3 cells, GL-V9 suppressed phosphorylated AKT and mitochondrial location of HKII. This led to glycolytic inhibition and mitochondrial pathway-mediated apoptosis. Additionally, GL-V9 inhibited AR activity in 22RV1 cells and disrupted the feedback activation of AKT signaling in condition of AR inhibition. This disruption greatly increased the anti-PCa efficacy of the AR antagonist bicalutamide. In conclusion, we present a novel anti-PCa candidate and combination drug strategies to combat CRPC by intervening in the AR-AKT-HKII signaling network.

Microbubble’s mass transfer under external acoustic excitation holds immense potential across various technological fields. However, the current state of acoustic technology faces limitations due to inadequate control over bubble size in liquids under external excitation. Here, we conducted numerical investigations of the mass transfer behavior of microbubbles in liquids under multifrequency acoustic excitations with different frequencies (in the MHz range), pressure amplitudes (in the range of several atmospheric pressures), and amplitude ratios. We identified various pressure threshold regions for the growth of gas bubbles (radii range from a few microns to tens of microns) and observed common intersections between single and multifrequency excitations that enable effective control of the growth intervals and final size of bubbles by adjusting the ratio of pressure amplitude and frequency value. Allocating power to the lower frequency component of multifrequency acoustic excitation is recommended to facilitate mass transfer or diffusion, as small-frequency acoustic excitation has a more significant effect than the higher frequency in the growth region. Our study provides a better understanding of the dynamics of bubbles under complex excitations and has practical implications for developing methods to control and promote bubble-related processes.

The development of the four stomachs of yak is closely related to its health and performance, however the underlying molecular mechanisms are largely unknown. Here, we systematically analyzed mRNAs of four stomachs in five growth time points [0 day, 20 days, 60 days, 15 months and 3 years (adult)] of yaks. Overall, the expression patterns of DEmRNAs were unique at 0 d, similar at 20 d and 60 d, and similar at 15 m and adult in four stomachs. The expression pattern in abomasum was markedly different from that in rumen, reticulum and omasum. Short Time-series Expression Miner (STEM) analysis demonstrated that multi-model spectra are drastically enriched over time in four stomachs. All the identified mRNAs in rumen, reticulum, omasum and abomasum were classified into 6, 4, 7, and 5 cluster profiles, respectively. Modules 9, 38, and 41 were the most significant three colored modules. By weighted gene co-expression network analysis (WGCNA), a total of 5,486 genes were categorized into 10 modules. CCKBR, KCNQ1, FER1L6, and A4GNT were the hub genes of the turquoise module, and PAK6, TRIM29, ADGRF4, TGM1, and TMEM79 were the hub genes of the blue module. Furthermore, functional KEGG enrichment analysis suggested that the turquoise module was involved in gastric acid secretion, sphingolipid metabolism, ether lipid metabolism, etc., and the blue module was enriched in pancreatic secretion, pantothenate and CoA biosynthesis, and starch and sucrose metabolism, etc. Our study aims to lay a molecular basis for the study of the physiological functions of rumen, reticulum, omasum and abomasum in yaks. It can further elucidate the important roles of these mRNAs in regulation of growth, development and metabolism in yaks, and to provide a theoretical basis for age-appropriate weaning and supplementary feeding in yaks.

With the emergence of generative AI technologies like ChatGPT, the conversation has shifted increasingly toward the possibility that machines will take over human jobs. The rise of artificial intelligence (AI) poses a double challenge to job security and the labor market organization while also bringing about remarkable efficiencies and introducing fresh job sectors. The complex landscape requires intentional government intervention based on fundamental economic principles. Information asymmetry is emphasized in discussing AI’s incorporation into the labor market, utilizing Joseph Stiglitz’s information theory. Discrepancies in access to information about emerging technologies and the required skills for the AI-driven economy could exacerbate market inefficiencies and result in job loss. Stiglitz’s remarks underscore the crucial need for governments to actively address these information gaps to enhance market efficiency and promote worker well-being. Potential actions could involve promoting partnerships between educational institutions and businesses to align curriculum with evolving labor market demands and mandating that companies reveal the incorporation of AI into their practices to enhance the accuracy of workforce development plans. This paper analyses the role of government in harmonizing AI’s impact on the labor market, AI’s influence on labor market dynamics, and navigating job displacement in the AI era. In addition, the relevant recommendations are proposed.

The aim of this study is to investigate clinical features of atypical pulmonary tuberculosis (aPTB) mimicking bacterial pneumonia, determine imaging features with the highest degree of correlation, and identify predictors for acid-fast bacilli (AFB) positivity.

Soil pollution with heavy metals has become a global issue because of anthropogenic activities causing gradual loss of soil nutrients and fertility, thus, reducing agricultural production. Biochar is recommended as an organic and environment-friendly option to address the issue of nutrient deficiency and heavy metal pollution. The present study was performed with biochar derived from Cannabis sativa to surplus soil nutrient pool and heavy metal immobilization. The characterization through scanning electron microscopy (SEM) revealed that biochar was brittle, porous, alkaline, and labile in nature. The elemental composition of biochar was carbon (75.3%), oxygen (19.2%), calcium (3.9%), potassium (1.5%), and chlorine (0.08%) determined by energy dispersive X-ray spectroscopy. Fourier transform infrared (FTIR) spectroscopy revealed the occurrence of carbonyl group, phenols, and alcohols in biochar derived from Cannabis sativa. The soil was spiked with lead and cadmium salt solution (25 ppm and 250) and incubated for 30 days. It was found that biochar amendments (1% = BC1 and 5% = BC5) significantly (p < 0.05) increased the soil physicochemical properties such as pH, electrical conductivity (EC), oxidizable organic carbon (OC), total organic carbon (TOC), and organic matter (OM). In the case of BC5, OC increased by 189.86%, TOC increased by 189.13%, and OM increased by 188.68%, as compared to the control. Similarly, soil available nitrogen (AN) and soil available phosphorous improved by 233.3% and 101.79%, respectively, compared to control. On the other hand, BC1 showed a significant reduction (p < 0.05) in lead and cadmium concentrations by 45.74% and 56.58%, respectively, in comparison to BC5 and control. In conclusion, we suggest that Cannabis sativa biochar may serve as an effective treatment for enhancing soil fertility and remediation of soil polluted with heavy metals.

Developing an effective task offloading strategy has been a focus of research to improve the task processing speed of IoT devices in recent years. Some of the reinforcement learning-based policies can improve the dependence of heuristic algorithms on models through continuous interactive exploration of the edge environment; however, when the environment changes, such reinforcement learning algorithms cannot adapt to the environment and need to spend time on retraining. This paper proposes an adaptive task offloading strategy based on meta reinforcement learning with task latency and device energy consumption as optimization targets to overcome this challenge. An edge system model with a wireless charging module is developed to improve the ability of IoT devices to provide service constantly. A Seq2Seq-based neural network is built as a task strategy network to solve the problem of difficult network training due to different dimensions of task sequences. A first-order approximation method is proposed to accelerate the calculation of the Seq2Seq network meta-strategy training, which involves quadratic gradients. The experimental results show that, compared with existing methods, the algorithm in this paper has better performance in different tasks and network environments, can effectively reduce the task processing delay and device energy consumption, and can quickly adapt to new environments.

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) derived from dental pulp tissue, which have high self-renewal ability and multi-lineage differentiation potential. With the discovery of the immunoregulatory ability of stem cells, DPSCs have attracted much attention because they have similar or even better immunomodulatory effects than MSCs from other sources. DPSCs and their exosomes can exert an immunomodulatory ability by acting on target immune cells to regulate cytokines. DPSCs can also migrate to the lesion site to differentiate into target cells to repair the injured tissue, and play an important role in tissue regeneration. The aim of this review is to summarize the molecular mechanism and target cells of the immunomodulatory effects of DPSCs, and the latest advances in preclinical research in the treatment of various immune-mediated diseases, providing new reflections for their clinical application. DPSCs may be a promising source of stem cells for the treatment of immune-mediated diseases.

Efficient nutritional assimilation and energy metabolism in the stomachs of yaks contribute to their adaption to harsh environments. Accurate gene expression profile analysis will help further reveal the molecular mechanism of nutrient and energy metabolism in the yak stomach. RT-qPCR is regarded as an accurate and dependable method for analyzing gene expression. The selection of reference genes is essential to obtain meaningful RT-qPCR results, especially in longitudinal gene expression studies of tissues and organs. Our objective was to select and validate optimal reference genes from across the transcriptome as internal controls for longitudinal gene expression studies in the yak stomach. In this study, 15 candidate reference genes (CRGs) were determined according to transcriptome sequencing (RNA-seq) results and the previous literature. The expression levels of these 15 CRGs were quantified using RT-qPCR in the yak stomach, including the rumen, reticulum, omasum and abomasum at five stages: 0 days, 20 days, 60 days, 15 months and three years old (adult). Subsequently, the expression stabilities of these 15 CRGs were evaluated via four algorithms: geNorm, NormFinder, BestKeeper and the comparative CT method. Furthermore, RefFinder was employed to obtain a comprehensive ranking of the stability of CRGs. The analysis results indicate that RPS15, MRPL39 and RPS23 are the most stable genes in the yak stomach throughout the growth cycle. In addition, to verify the reliability of the selected CRGs, the relative expression levels of HMGCS2 were quantified via RT-qPCR using the three most stable or the three least stable CRGs. Overall, we recommend combining RPS15, MRPL39 and RPS23 as reference genes for the normalization of RT-qPCR data in the yak stomach throughout the growth cycle.

Adriamycin (ADR) is an important chemotherapy agent in many advanced cancers, but the emergence of drug resistance during treatment is a major limitation to its successful use. Recent studies have suggested that drug-resistant cells become less fit and their growth could be inhibited by parental cells without cytotoxic treatment. In this study, we examined the fitness differences between HeLa and HeLa/ADR cells. Compared with the parental cell line, HeLa/ADR cells showed significantly lower growth rates, both in vitro and in vivo. There was no difference in the apoptosis rate between them, but G1 arrest and reduced DNA synthesis were found in HeLa/ADR cells. Further study indicated that HeLa/ADR cells failed to compete for space and nutrition against parental cells in vivo. Taken together, we demonstrate that HeLa/ADR cells are less fit and their growth can be inhibited by parental cells in the absence of ADR; therefore, the maintenance of a certain amount of ADR-sensitive cells during treatment may facilitate the control of the development of ADR resistance.

Through the theoretical simulation and analysis of the whole process of laser ablating target and producing plasma with high spatio-temporal resolution, it is helpful for people to gain a more complete understanding of the ablation process of target and the evolution process of plasma parameters, which has an important guiding role for the improvement and optimization of laser ablation technology. Alloys are commonly used in daily life, but there are few researches on laser-induced alloy targets at present. Therefore, based on the thermal model of laser ablation and the two-dimensional axisymmetric multi-species hydrodynamic model, the process of laser ablating Al-Mg alloy under atmospheric pressure argon is theoretically simulated, and the ablation process of alloy target and the spatio-temporal evolution results of plasma parameters under different laser irradiances are compared. At high laser irradiance, the melt and evaporation depth, laser energy absorption and plasma characterization parameters are much greater than those at low laser irradiance, and the species energy distribution at different laser irradiance also presents different trends. In addition, the velocity of different species is calculated according to the position-time diagram of the maximum emission intensity, and they expand at a constant speed during the studied time. These results can provide some theoretical guidance for the early application of laser-induced breakdown spectroscopy in metallurgy.

Although television, computer games and the Internet play an important role in the lives of children they still also play with physical toys, such as dolls, cars and LEGO bricks. The LEGO company has become the world's largest toy manufacturer. Our study investigates if the LEGO company's products have become more violent over time. First, we analyzed the frequency of weapon bricks in LEGO sets. Their use has significantly increased. Second, we empirically investigated the perceived violence in the LEGO product catalogs from the years 1978-2014. Our results show that the violence of the depicted products has increased significantly over time. The LEGO Company's products are not as innocent as they used to be.