With the breakthroughs and innovative developments in nanotechnology, research on the application of nanomedicine in cancer therapy has so far seen tremendous expansion and success. Intelligent stimulus-responsive nanocarriers are an emerging field of research and have great interest in cancer therapy owing to the fascinating properties such as excellent targeting function, high drug loading capacity, and targeted on-demand release properties. Responsive nanomaterials can be designed and constructed according to the dosing context and therapeutic needs, at the same time, activated by internal bio-stimuli (pH, redox, and enzymes) and/or external stimuli (ultrasound, light, temperature, and magnetic), respectively. What’s more, smart nanocarriers are also utilized for the precise and controllable release of antitumor drugs from cancer tissues and cells to achieve efficient diagnosis and treatment of tumors. Deeply investigated, responsive nanocarriers have attracted considerable attention due to their ability to release precisely at tumor-specific sites. Herein, we review the recent advances of novel stimuli-responsive nanocarriers in the field of cancer therapy. Finally, the challenges and application prospects of smart nanocarriers are further elaborately discussed.

This study was carried out to evaluate the effect of exogenous proline on growth, biochemical responses, and plant recovery of drought-stressed oilseed rape plants after renewed irrigation. The experiment was conducted under controlled laboratory conditions. After 21 days of cultivation, 3-4 leaf stage seedlings were sprayed with proline (1 mM), then subjected to prolonged drought stress for 8 days to achieve a severe water deficit, then irrigation was resumed and recovery was assessed after 4 days. The results show that exogenous application of proline reduced drought-induced growth inhibition of seedlings while maintaining relative water content (RWC) and growth parameters closer to those of irrigated plants. Proline had a positive effect on chlorophyll accumulation and membrane permeability while decreasing ethylene, H2O2, and MDA levels. Moreover, after 4 days of recovery, the H2O2 content of the proline-treated plants was significantly lower (2-fold) and the MDA content was close to that of continuously irrigated plants. Thus, all these biochemical reactions influenced plant survival: after drought + proline treatment, the number of surviving plants was 2 times higher than that of drought-treated plants. The findings show that exogenous proline has antioxidant, osmotic, and growth-promoting properties that improve the drought tolerance of winter oilseed rape plants and is, therefore, beneficial for drought adaptation in oilseed rape.

Continuous and uncontrolled extraction of groundwater often creates tremendous pressure on groundwater levels. As a part of the sustainable planning and effective management of water resources, it is crucial to assess the existing as well as future groundwater level (GWL) condition. In the current study, an attempt was made to model and forecast GWL using artificial neural networks (ANN) and multivariate time series models. Autoregressive integrated moving average (ARIMA) and ARIMA incorporating exogenous variables (ARIMAX) were adopted as the time series models. Kushtia district in Bangladesh was selected as the case study area, and GWL data of five monitoring wells in the study are used to demonstrate the modeling exercise. Rainfall was taken as the exogeneous variable to explore whether its inclusion enhanced the performance of GWL forecasting using the developed models. The performance of each time series and ANN model was assessed based on various model evaluation criteria. It was evident from the results that the multivariate ARIMAX model (SSE of 15.361) performed better than the univariate ARIMA model with an SSE of 17.217 for GWL forecasting. This demonstrates the fact that the multivariate time series models generated enhanced forecasting of GWL compared to the univariate time series models. When comparing the time series and ANN models, it was found that the ANN-based model outperformed the time series models with the enhanced forecasting accuracy (SSE of 9.894). Results also exhibit a significant correlation coefficient value R of 0.995 (ANN 6-8-1) for the existing and predicted data. The current study conclusively proves the superiority of ANN over the time series models for the enhanced forecasting of GWL in the study area. Thus, the ANN approach was not only carried out for model building and simulation but also to provide a valuable tool for managing water resources amidst changing environmental conditions.

In tropical and subtropical climate regions, heat stress is one of the main causes of production losses in laying quails, aggravated by the antinutritional effects of the phytate in diet ingredients, which negatively affect the bioavailability of minerals, especially calcium and phosphorus. This situation results in a reduction in production and quality of eggs from commercial laying hens. Several nutritional strategies are utilized to reduce the adverse effects of high temperatures and antinutritional factors such as phytate. Among these strategies, the use of exogenous enzymes, such as phytase, stands out as a viable alternative. Phytase breaks down phytate molecules, optimizing the absorption of essential minerals and improving productive performance and egg quality under unfavorable conditions. In this context, this bibliographic review sought to produce a document demonstrating the beneficial effects of the phytase enzyme on the hydrolysis of the phytate molecule and the availability of calcium for Japanese quails (Coturnix coturnix japonica), and its implications in thermal stress due to heat.

Drought and water scarcity are significant factors limiting the development of China's maize industry. Deep sowing, as a method to mitigate drought and preserve soil moisture and seedlings, can effectively mitigate the adverse effects of drought stress on their growth. However, deep sowing can influence the emergence of maize seedlings and has a certain impact on their growth and development. To investigate the physiological and transcriptomic changes in maize inbred lines under deep sowing stress, and the alleviation effects of exogenous hormones, this study investigated the response of mesocotyl in deep-seeding tolerant maize inbred line Qi319 and deep-seeding sensitive maize inbred line Zi330 to deep-seeding stress under exogenous MeJA treatment. The physiological and transcriptomic mechanisms underlying the alleviation of deep-seeding stress by exogenous MeJA were elucidated. Results showed that compared to normal sowing depth, mesocotyl length (MES), mesocotyl and coleoptile length (MESCOL) significantly increased under deep-seeding stress for both inbred lines, while seedling length (SDL) was significantly inhibited. However, after adding 1.5 μmol·L^-1 MeJA, MES, MESCOL, and SDL significantly increased compared to deep-seeding stress alone. Exogenous MeJA promoted cell elongation, enhanced mesocotyl length, and improved seedling emergence ability. RNA-Seq sequencing revealed differentially expressed genes (DEGs). Under deep-seeding stress compared to normal sowing depth conditions, 1248 DEGs were identified in Qi319 and 1288 DEGs were identified in Zi330. After adding exogenous MeJA under deep-seeding stress compared to normal sowing depth with exogenous MeJA treatment conditions, 538 DEGs were identified in Qi319 and 2284 DEGs were identified in Zi 330. GO enrichment analysis showed that differentially expressed genes were mainly concentrated in biological processes, cell components and molecular functions. KEGG enrichment analysis showed that differentially expressed genes were mainly concentrated in transport and catabolism, signal transduction, amino acid metabolism and lipid metabolism processes. Compared with the deep-seeded treatment, 12 differentially expressed genes were co-expressed in the two inbred lines under exogenous MeJA treatment, and 10 key genes, including ornithine decarboxylase, terpene synthase 7 and ethylene reaction transcription factor 11, were screened out. Our findings elucidate the molecular mechanism underlying maize's tolerance response to deep seeding and offer valuable insights into candidate gene resources for improving deep seeding tolerance in maize.

The adapted Posner spatial cue-target paradigm was used to explore the relationship between exogenous temporal attention caused by rhythm and endogenous and exogenous spatial attention. The study was divided into two experiments. In Experiment 1, 33 participants used arrow cues to orient endogenous spatial attention and rhythm to orient exogenous temporal attention. In Experiment 2, with 29 participants, exogenous spatial attention was directed by highlighting the cue box. Exogenous temporal attention was directed by rhythm. Experiment 1 indicated that RTs were faster for attended targets than the unattended. The main effect of temporal attention was significant, with RTs being faster for synchrony and late compared to early. RTs were faster for late compared to synchrony. The main effect of stimulus repetition was significant, with faster RTs for targets when the rhythmic cue consisted of five compared to four. The interaction between spatial attention and temporal attention was not significant. Experiment 2 demonstrated that exogenous spatial attention only exhibited IOR under early four stimulus repetitions. The main effect of temporal attention was significant, with RTs being faster for synchrony and late compared to early. The main effect of stimulus repetition was significant, with faster RTs for targets when the rhythmic cue consisted of five compared to four. The interaction between spatial attention and temporal attention was significant. The results indicated that rhythmic temporal attention supported foreperiod effects. Exogenous temporal attention and endogenous spatial attention independently affect behavior, while exogenous temporal attention and exogenous spatial attention mutually influenced behavior.

The neural system has limited resources to interact with the environment, and this is where attention comes into play. Attention is a complex process that provides numerous benefits, but there has been a longstanding debate about the mechanisms involved in attentional orientation. Two widely proposed mechanisms are top-down and bottom-up, which relate to the organism's current behavioral goal and the salience of environmental stimuli, respectively. However, distinguishing between these mechanisms can be challenging in both behavioral and neural studies. This review introduces a new conceptualization in which both top-down and bottom-up mechanisms are viewed as aspects of the same process. This unified approach aims to prepare the organism to face stimuli and events based on its prior experiences, immediate (the current task that he/she is aware of), and innate (to be alive) demands.

The inclusion of exogenous phytase in broiler P and Ca deficient diets in response to heightened concerns over excessive P excretion into the environment over the years has remarkably been documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to: 1) quantitatively summarize the size of phytase effect on growth performance, bone strength, and mineralization in broilers fed P and Ca deficient basal diets and 2) estimate and explore the heterogeneity of the effect sizes of outcomes using sub-group and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration’s SYRCLE Risk of Bias checklists for animal studies. Additionally, applying the random-effects models, Hedges’ g effect size of supplementation with phytase was calculated using the R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (P_SMD ≤ 0.05, I² > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and reduces FCR at each time point of growth (< 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (< 0.0001) of broilers fed P and Ca deficient diets. Results of the subgroup and meta-regression analyses showed that age and strain of broiler, dietary P source, and duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary available phosphorus and calcium and improve ADFI, BWG, and reduced FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and duration of phytase exposure rather than the dosage.

Indole-3-acetic acid (IAA) is a key vegetative hormone that plays crucial roles in plant growth and development. In this study, the effect of the exogenous application of IAA as a biostimulant in the cultivation of onions (Allium cepa) was investigated. Different IAA concentrations were evaluated to determine their effects on onion growth and chemical parameters. Various physical and chemical parameters such as total fresh weight, plant height, chlorophyll content, nitrates, total phenols, and antioxidant capacity (DPPH) were analyzed. The results revealed that exogenous application of IAA had a significant impact on onion growth and quality. Specifically, it was found that certain concentrations of IAA fostered a greater fresh weight of the bulb, an increase in the levels of phenolic compounds and a greater DPPH. However, the onion response to IAA was dependent on the concentration. In conclusion, the present study provides evidence that the exogenous application of IAA as a biostimulant can improve onion growth and quality. These results are relevant for the development of sustainable agricultural practices and could be oriented towards crop improvement.

As an option to deal with the insulin-dependent disease, a recent commuted PD control strategy is designed and carefully analyzed for different clinic diabetic patients. This controller approach is mainly conceived to stabilize the glucose blood concentration in a diabetic patient around its basal value, hence avoiding extreme situations such as hypoglycemia and hyperglycemia. This control strategy receives two inputs carefully tuned to actuate when the measured variable is out of a prescribed healthy zone. Therefore, one of these variables is invoked to decrease the glucose concentration to insulin injection, and the other is employed to increase the glucose absorption, both by using a proper PD controller. According to our numerical experiments, our controller approach performs well, even when there is an external disturbance in the controlled system.

Any effort to combat corruption can benefit from an examination of past and projected worldwide trends. In this paper, we forecast the level of corruption in countries by integrating an artificial neural network modeling and time series analysis. The data were obtained from 113 countries from 2007 to 2017. The study is carried out at two levels: (a) global level where all countries are considered as a monolithic group; and (b) cluster level, where countries are placed into groups based on their development-related attributes. For each cluster, we use the findings from our previous study on the cluster analysis of global corruption using machine learning methods that identified the four most influential corruption factors, and we use those as independent variables. Then, using the identified influential factors, we forecast the level of corruption in each cluster using a nonlinear autoregressive recurrent neural network with exogenous inputs (NARX), an artificial neural network technique. The NARX models were developed for each cluster, with the objective function in terms of the Corruption Perceptions Index (CPI). For each model, the optimal neural network is determined by finetuning the hyperparameters. The analysis was repeated for all countries as a single group. The accuracy of the models is assessed by comparing the mean square errors (MSE) of the time series models. The results suggest that the NARX artificial neural network technique yields reliable future values of CPI globally or for each cluster of countries. This can assist policymakers and organizations in assessing the expected efficacies of their current or future corruption control policies from a global perspective as well as for groups of countries.

To efficiently use its finite resources, the visual system selects for further processing only a subset of the rich sensory information. Visual masking and spatial attention control the information transfer from visual sensory-memory to visual short-term memory. There is still a debate whether these two processes operate independently or interact, with empirical evidence supporting both arguments. However, recent studies pointed out that earlier studies showing significant interactions between common-onset masking and attention suffered from ceiling and/or floor effects. Our review of previous studies reporting metacontrast-attention interactions revealed similar artifacts. Therefore, we investigated metacontrast-attention interactions by using an experimental paradigm in which ceiling/floor effects were avoided. We also examined whether metacontrast masking is differently influenced by endogenous and exogenous attention. We analyzed mean absolute-magnitude of response-errors and their statistical distribution. Our results support the hypothesis that metacontrast and endogenous/exogenous attention are largely independent with negligible likelihood for interactions. Moreover, statistical modeling of the distribution of response-errors suggests weak interactions modulating the probability of “guessing” behavior for some observers in both types of attention. Nevertheless, our data suggest that any joint effect of attention and metacontrast can be adequately explained by their independent and additive contributions.

nutrition, macro and micronutrients, bone health, exercise, exogenous and endogenous microRNA, epigenetics

Knowledge-intensive business services (KIBS) are professional services that create new added value by creating, accumulating, and disseminating new knowledge. When it comes to conducting business involving new technology, KIBS play the roles of innovator, user, and producer of new technology that has led to technological innovation. This study aimed to determine the role of KIBS as a tool for innovation in a country’s economic system. Specifically, the degree and role of their impact on the Korean economy were analyzed and compared for the entire KIBS sector, T-KIBS (a new technology-based professional service), P-KIBS (a traditional professional service), and every subsector. For this purpose, the demand-inducement model, supply inducement model, and interlinkage effects method were applied using the 2019 input-output table published in 2022. The analysis showed that the indirect production inducement effect of the entire KIBS industry on other industries was 0.800 KRW, the indirect added value inducement effect was 0.330 KRW, and the supply disruption effect was 1.144 KRW. For T-KIBS, the indirect production inducement effect was 0.687 KRW, the indirect added value inducement effect was 0.272 KRW, and the supply disruption effect was 0.730 KRW. For P-KIBS, the indirect production inducement effect was 1.472 KRW, the indirect added value inducement effect was 0.646 KRW, and the supply disruption effect was 2.657 KRW. Finally, regarding the economic ripple effect of the KIBS subsector, legal and management support services and advertisements corresponding to P-KIBS showed higher figures than the T-KIBS subsectors in all sectors, including production inducement, the added value inducement effect, and the supply disruption effect. These results revealed that in the South Korean economic system, KIBS contribute to production and value addition across all industrial sectors. It is apparent that the absence of supply significantly disrupts other industries. Furthermore, production inducement effects are evenly distributed among all the KIBS subsectors in the secondary and tertiary sectors, while the value-added effects have a greater impact on the tertiary sector. In terms of the supply shortage effects, the secondary sector experiences a more significant impact. This underscores the crucial role of KIBS in sustaining and enhancing overall economic activity in South Korea. This study is significant in that it not only investigated KIBS as an industry group using the advantages provided by industry linkage analysis but also examined and compared detailed subsectors, thereby elaborately evaluating the influence relationship between KIBS and other industries. Therefore, the results presented in this study are expected to be useful for fostering the KIBS industrial sector and establishing economic innovation policies using KIBS.

The plant graft healing process is an intricate development influenced by numerous endogenous and environmental factors. This process involves the histological changes, physiological and biochemical reactions, signal transduction, and hormone exchanges in the grafting junction. Studies have shown that applying exogenous plant growth regulators can effectively promote the graft healing process and improve the quality of grafted plantlets. However, the physiological and molecular mechanism of graft healing formation remains unclear. In our present study, transcriptome changes in the melon and cucurbita genomes were analyzed between control and NAA treatment, and we provided the first view of complex networks to regulate graft healing under exogenous NAA application. The results showed that the exogenous NAA application could accelerate the graft healing process of oriental melon scion grafted onto squash rootstock through histological observation, increase the SOD, POD, PAL, and PPO activities during graft union development and enhance the contents of IAA, GA3, and ZR except for the IL stage. The DEGs were identified in the plant hormone signal-transduction, phenylpropanoid biosynthesis, and phenylalanine metabolism through transcriptome analysis of CK vs. NAA at the IL, CA, and VB stage by KEGG pathway enrichment analysis. Moreover, the exogenous NAA application significantly promoted the expression of genes involved in the hormone signal-transduction pathway, ROS scavenging system, and vascular bundle formation.

Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and ability to synthesize other needed chemicals. The latter include the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF)of the planet. How complex life forms have accommodated the GMF is not known in detail considering that Homo sapiens evolved a neuro system and a cardiovascular system that develops electromagnetic fields as part of their functioning. In addition, many proteins and physiologic processes utilize Fe ions, an ion that exhibits magnetic properties. Thus, complex organisms such as current humans generate magnetic fields, contain significant quantities of the Fe ion, and also respond to exogenous-supplied static and electromagnetic fields. Whether humans can store information in self-generated magnetic fields remains to be determined. Given the current body of literature, it remains somewhat unclear how Homo sapiens use exogenous magnetic fields to regulate function, and what can happen if the boundary condition of the GMF of Earth is no longer exerting an effect. Proposed deep space flights to destinations such as Mars will provide some insights as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights in the role of magnetic fields on human functioning. The outcomes may also have implications for those on Earth as magnetic field influences may play a role in developmental conditions such as autism and senescence-associated conditions such as dementia when integration of the biological and biophysical aspects of humans of humans are required for effective functioning. This review will discuss the involvement of magnetic fields on various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer available to impact host systems. Thus, the GMF of the Earth has been present throughout evolution but details of its role in human functions still remain to be elucidated.

Globalization and industrialization have significantly disturbed the environmental ecosystem, leading to critical challenges such as global warming, extreme weather events, and water scarcity. Forecasting temperature trends is crucial for enhancing the resilience and quality of life in smart sustainable cities, enabling informed decision-making and proactive urban planning. This research specifically targets Ahmedabad city in India and employs the Seasonal Auto Regressive Integrated Moving Average with eXogenous factors (SARIMAX) model to forecast temperatures over a ten-year horizon using two decades of real-time temperature data. The stationarity of the dataset was confirmed using the Augmented Dickey-Fuller test, and the Akaike Information Criterion (AIC) method helped identify the optimal seasonal parameters of the model, ensuring a balance between fidelity and predictive accuracy. The model achieved an RMSE of 1.0265, indicating high accuracy within the typical range for urban temperature forecasting. This robust measure of error underscores the model’s precision in predicting temperature deviations, which is particularly relevant for urban planning and environmental management. The findings provide city planners and policymakers with valuable insights and tools for preempting adverse environmental impacts, marking a significant step towards operational efficiency and enhanced governance in future smart urban ecosystems. Future work may extend the model's applicability to broader geographical areas and incorporate additional environmental variables to refine predictive accuracy further.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

In the context of healthcare technology management (HTM) in Saudi Arabia and the Gulf region, this study addresses a significant gap by exploring both external and internal risk factors affecting HTM performance. Previous research has primarily focused on modeling or predicting failures in medical devices, mostly examining internal (endogenous) factors that impact device performance and the development of optimal service strategies. However, a comprehensive investigation of external (exogenous) factors has been notably absent. This research introduces a novel hierarchical risk management framework, designed to accommodate the broad array of healthcare technologies, not limited to medical devices. It significantly advances the field by thoroughly investigating and validating a comprehensive set of 53 risk factors and assessing their influence on HTM. Additionally, this study embraces the perspective of enterprise risk management (ERM) and expands it to identify and incorporate a wider range of risk factors, offering a more holistic and strategic approach to risk assessment in healthcare technology management. The findings reveal that several external and internal factors previously underexplored significantly impact HTM performance. Notably, the Fuzzy AHP survey identified “design risk” under facility and environmental risks as the highest risk for HTM in the region. Furthermore, the study reveals that three out of the top ten risks are related to “facility and internal environmental” factors, six are related to technological endogenous factors, and only one is related to managerial factors. This distribution underscores the critical areas for intervention and the need for robust facility and technology management strategies. In conclusion, this research not only fills a critical void by providing a robust framework for healthcare technology risk assessment but also broadens the scope of risk analysis to include a wider array of technologies, thereby enhancing the efficacy and safety of healthcare interventions in the region. Additionally, the proposed hierarchy provides insights into the underlying risk factors for healthcare technology management, with potential applications extending beyond the regional context to a global scale. Moreover, the equation we propose offers a novel perspective on the key risk factors involved in healthcare technology management, presenting insights with far-reaching implications applicable not only regionally but also on a global level. This framework also supports sustainability goals by encouraging the efficient and responsible utilization and management of healthcare technologies, essential for ensuring the long-term economic and environmental sustainability of medical technology use.