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Abstract Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.

The physiochemical, textural and nutritional properties of novel extrudates generated from various kinds of rice and legume (beans) varieties were comprehensively evaluated and compared in this study. The developed extruded products were composed of 5 %, 10 %, 15 %, or 20 % of different varieties of rice, including brown rice (R1), Asemi (R2), solchanmi (R3), sechanmi (R4), sejongchal (R5), and seosi 1 (R6), and legumes varieties including soybean (B1), chickpea (B2), great northern bean (B3), pea (B4), lentil (B5), and black bean (B6). Visible appearance analysis reveals that legumes (beans) and rice extrudates appeared more compact as the concentration of ingredients increased. Meanwhile, the integrity index decreased as the concentration level of treatment group content decreased (p

ABSTRACTThe objective of this study was to characterize the physicochemical, proximal, textural, and visual properties of plant-based meat (PBM) patties blended with natural pigments such as anthocyanin from black beans, Fe-chlorophyll from spinach, and edible red and purple pigments. A comparison was made between these plant-based pigments and the pigments derived from animal-based sources (control). The values of the color coordinates of the developed patties were broadly distributed (L* [lightness], a* [redness], and b* [yellowness] of raw PBMs: 34–53, 2–25, and 4–27; steamed: 29–42, 4–21, and 5–25; and cooked: 28–43, 5–19, and 9–21, respectively). The proximate chemical analysis revealed no (P > .05) significant difference between the PBMs and the control in terms of moisture (63.28–61.25), crude protein (20.98–19.17) crude fat (3.19–2.92) and ash content (3.80–1.71). Nevertheless, significant differences (P

Abstract Death is the inevitable fate of all living organisms, whether at the individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome of nonfunctioning cells, as inflammation was inevitably triggered in response to damage. However, experimental evidence accumulated over the past few decades has revealed different types of cell death that are genetically programmed to eliminate unnecessary or severely damaged cells that may damage surrounding tissues. Several types of cell death, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, and erebosis, have been discovered and advanced our understanding of cell death and its complexity. In this review, we provide a historical overview of the discovery and characterization of different forms of cell death and highlight their diversity and complexity. We also briefly discuss the regulatory mechanisms underlying each type of cell death and the implications of cell death in various physiological and pathological contexts. This review provides a comprehensive understanding of different mechanisms of cell death that can be leveraged to develop novel therapeutic strategies for various diseases.

The canine pet care industry is steadily growing because of increasing number of households with dogs as principal companions. Canine owners strive to sustain well-being of pets by providing proper care and diet. Like humans, canine health is influenced by diet and gastrointestinal (GI) microbiome. The GI microbiome is a metabolically dynamic organ that is linked to canine health because of its role in nutrient digestion and absorption. Canine foods are normally formulated to contain basic nutrients, but recently, pet diets have been modified to include functional foods that target improvement of gut microbiome health (probiotics, prebiotics, synbiotics, and postbiotics) and/or provision of essential nutrients (polyunsaturated fatty acids, phytonutrients). Although several studies have confirmed the positive impact of supplements on chronic enteropathies, allergies, etc, recent canine health and gut microbiome research has only focused on characterization of symptoms caused by diseases. Less research has been devoted to providing insight into effects of functional foods on canine gut microbiome and overall health. Understanding how functional foods improve canine health through GI microbiome may reveal opportunities for the enhancement of overall canine health and resilience. Thus, in this paper, we focus on the impact of functional foods on the GI microbiome and its ultimate effect on overall health and well-being of the canine host.

A handshake operation can mitigate workload imbalance and interference between twin transporters in a material handling system. Terminal operators in a rail-based automated container terminal can employ the handshake operation to twin overhead shuttle cranes (OSs) under maritime demand uncertainty. Since a handshake location is critical to collaboration performance, terminal operators often rely on simulation experiments with a manual iterative design to determine optimal handshake locations. However, the simulation optimization is still challenging when a simulation execution is computationally expensive. This study proposes a Bayesian optimization-based approach to expedite the decision-making process. The approach infers the conditional outcomes of a simulation and actively searches optimal handshake locations. Our optimization results show that the proposed approach maximizes the collaborations between the twin OSs within fewer simulation runs. This study also provides extensive simulation analysis of the handshake locations. The experiments indicate that a handshake location has a significant influence on the required space for handshake operations and the workloads of the twin OSs.

The K-means algorithm, widely used in cluster analysis, is a centroid-based clustering method known for its high efficiency and scalability. However, in realistic situations, the operating environment is susceptible to contamination issues caused by outliers and distribution departures, which may lead to clustering results from K-means that are distorted or rendered invalid. In this paper, we introduce three other alternative algorithms, including K-weighted-medians, K-weighted-L2-medians, and K-weighted-HLs, to address these issues under the consideration of data with weights. The impact of contamination is investigated by examining the estimation effects on optimal cluster centroids. We explore the robustness of the clustering algorithms from the perspective of the breakdown point, and then conduct experiments on simulated and real datasets to evaluate their performance using two new numerical metrics: relative efficiencies based on generalized variance and average Euclidean distance. The results demonstrate the effectiveness of the proposed K-weighted-HLs algorithm, surpassing other algorithms in scenarios involving both contamination issues.

The purpose of this study was to compare marbling score, meat quality, juiciness, sarcomere length, and skeletal muscle satellite cell (SMSC) growth and related gene expression between Woori black pig (WB) and the Landrace, Yorkshire, and Duroc (LYD) crossbreed at different body weights (b.w.). WB was developed to improve meat quality and growth efficiency by crossbreeding Duroc with Korean native black pig. A total of 24 pigs were sacrificed when their b.w. reached about 50, 75, 100, and 120 kg. SMSC were isolated from the femoris muscles, and muscle and adipose tissues were sampled from the middle and the subcutaneous part of the femoris of hind legs, respectively. Expression levels of genes including Myoblast determination protein 1 (MyoD), Paired box gene 3 (Pax3), Myosin heavy chain (MyHC), and Myogenin, which are responsible for the growth and development of SMSC, were higher in LYD than the WB. Muscle growth inhibitor myostatin (MSTN), however, was expressed more in WB compared to LYD (p < 0.01). Numbers of SMSC extracted from femoris muscle of LYD at 50, 75, 100, and 120 kg b.w. were 8.5 ± 0.223, 8.6 ± 0.245, 7.2 ± 0.249, and 10.9 ± 0.795, and those from WB were 6.2 ± 0.32, 6.2 ± 0.374, 5.3 ± 0.423, and 17.1 ± 0.315, respectively. Expression of adipogenic genes in adipose tissue including CCAAT/enhancer-binding protein (CEBP)-β, peroxisome proliferator activated receptor (PPAR)-γ, and fatty acid synthase (FASN), were greater in WB when compared with LYD (p < 0.01). Results from the current study suggest that different muscle cell numbers between 2 different breeds might be affected by related gene expression and this warrants further investigation on other growth factors regulating animal growth and development.

This study explored the changes in the physiochemical, textural, sensory, and functional characteristics of plant-based meat (PBM) after incorporating novel plant-based ingredients including spirulina (SPI), duck Weed (DW), and yellow Chlorella (YC). In the chromaticity evaluation, the YC group (YCI YC2, and YC3%) displayed significant differences (p < 0.05) in lightness (L*) indices as compared to the control. Whereas, based on concertation gradient of SPI microalgae (SP0.5, SP0.7, and SP1%) incorporated into PBM patties demonstrated that SPI 1 had the lowest values (p < 0.05) in redness (a*) and yellowness (b*) followed by SPI 0.7 and SPI 0.5% concentration, respectively. The concentration gradient of the YC group indicated that YC3 was intended to be the highest crude fat value followed by YC2 and YCI. The ash content in PBM patties increased considerably (p < 0.05) as the concentration level of microalgae advanced in all treated groups. Based on the concentration level of YC incorporated microalgae into PBM patties indicated that YC 3 had the highest (p < 0.05) gumminess and chewiness while YC 1 had the lowest reported values in terms of gumminess and chewiness. Moreover, springiness and cohesiveness showed considerable differences between SPI and YC groups. In the sensory evaluation, SPI 1 showed the lowest value only in color and appearance (p < 0.05), conversely, the other sensory parameters were non-significant among all treatment groups (p > 0.05). The micronutrient in PBM presented an irregular pattern after incorporating various ingredients. However, levels were higher (p < 0.05) in the DW group (DW 0.5 DW 0.7, and DW% 1) than those in the other groups. Moreover, the SPI and YC groups showed detectable levels of diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with, SP 1 showing the highest level of antioxidant activity. Acknowledging the limited research on PBM production, extraction technologies, and selecting various novel suitable ingredients in meat substitutes. Hence, to fill this knowledge gap an attempt has been made to incorporate various concentrations of microalgae including SPI, YC, and DW to enhance the quality and functionality of meat alternatives. To the best of our knowledge, this is the first report that describes the physiochemical, textural, sensory, and nutritional attributes of PBM incorporated with novel microalgae. Collectively these results indicate that the incorporation of SPI, DW, and YC may improve the quality of PBM without showing deleterious outcomes on the quality and functionality of the ultimate PBM products.

This study compared the cellular and genetic characteristics of bovine skeletal muscle satellite cells (SMSCs) from Hanwoo (a Korean native cattle breed), including calves and mature cattle. SMSCs were isolated using magnetic-activated cell sorting (MACS) from tissue samples of six Hanwoo (three calves and three mature cattle) using the CD29 antibody. Calves’ SMSCs exhibited significantly faster growth rates than did those from cattle (P

Abstract To prevent surgical site infection (SSI), which significantly increases the rate morbidity and mortality, eliminating microorganisms is prominent. Antimicrobial resistance is identified as a global health challenge. This work proposes a new strategy to eliminate microorganisms of deep tissue through electrical stimulation with an ultrasound (US)‐driven implantable, biodegradable, and vibrant triboelectric nanogenerator (IBV‐TENG). After a programmed lifetime, the IBV‐TENG can be eliminated by provoking the on‐demand device dissolution by controlling US intensity with no surgical removal of the device from the body. A voltage of ≈4 V and current of ≈22 µA generated from IBV‐TENG under ultrasound in vitro, confirming inactivating ≈100% of Staphylococcus aureus and ≈99% of Escherichia coli. Furthermore, ex vivo results show that IBV‐TENG implanted under porcine tissue successfully inactivates bacteria. This antibacterial technology is expected to be a countermeasure strategy against SSIs, increasing life expectancy and healthcare quality by preventing microorganisms of deep tissue.

Environment, food, and disease have a selective force on the present and future as well as our genome. Adaptation of livestock and the environmental nexus, including forest encroachment for anthropological needs, has been proven to cause emerging infectious diseases. Further, these demand changes in meat production and market systems. Meat is a reliable source of protein, with a majority of the world population consumes meat. To meet the increasing demands of meat production as well as address issues, such as current environmental pollution, animal welfare, and outbreaks, cellular agriculture has emerged as one of the next industrial revolutions. Lab grown meat or cell cultured meat is a promising way to pursue this; however, it still needs to resemble traditional meat and be assured safety for human consumption. Further, to mimic the palatability of traditional meat, the process of cultured meat production starts from skeletal muscle progenitor cells isolated from animals that proliferate and differentiate into skeletal muscle using cell culture techniques. Due to several lacunae in the current approaches, production of muscle replicas is not possible yet. Our review shows that constant research in this field will resolve the existing constraints and enable successful cultured meat production in the near future. Therefore, production of cultured meat is a better solution that looks after environmental issues, spread of outbreaks, antibiotic resistance through the zoonotic spread, food and economic crises.

Self-powered implantable devices have the potential to extend device operation, though current energy harvesters are both insufficient and inconvenient. Here the authors report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator based on body motion and gravity that can be used to charge a lithium-ion battery and integrated into a cardiac pacemaker.

Abstract The magneto-thermal effect, which represents the conversion of magnetostatic energy to heat from magnetic materials, has been spotlighted for potential therapeutic usage in hyperthermia treatments. However, the realization of its potential has been challenged owing to the limited heating from the magnetic nanoparticles. Here, we explored a new-concept of magneto-thermal modality marked by low-power-driven, fast resonant spin-excitation followed by consequent energy dissipation, which concept has yet to be realized for current hyperthermia applications. We investigated the effect of spin resonance-mediated heat dissipation using superparamagnetic Fe3O4 nanoparticles and achieved an extraordinary initial temperature increment rate of more than 150 K/s, which is a significant increase in comparison to that for the conventional magnetic heat induction of nanoparticles. This work would offer highly efficient heat generation and precision wireless controllability for realization of magnetic-hyperthermia-based medical treatment.

Color is a major feature that strongly influences the consumer’s perception, selection, and acceptance of various foods. An improved understanding regarding bio-safety protocols, health welfare, and the nutritional importance of food colorants has shifted the attention of the scientific community toward natural pigments to replace their toxic synthetic counterparts. However, owing to safety and toxicity concerns, incorporating natural colorants directly from viable sources into plant-based meat (PBM) has many limitations. Nonetheless, over time, safe and cheap extraction techniques have been developed to extract the purified form of coloring agents from raw materials to be incorporated into PBM products. Subsequently, extracted anthocyanin has displayed compounds like Delphinidin-3-mono glucoside (D3G) at 3.1 min and Petunidin-3-mono glucoside (P3G) at 5.1 277, 515, and 546 nm at chromatographic lambda. Fe-pheophytin was successfully generated from chlorophyll through the ion exchange method. Likewise, the optical density (OD) of synthesized leghemoglobin (LegH) indicated that pBHA bacteria grow more rigorously containing ampicillin with a dilution factor of 10 after 1 h of inoculation. The potential LegH sequence was identified at 2500 bp through gel electrophoresis. The color coordinates and absorbance level of natural pigments showed significant differences (p < 0.05) with the control. The development of coloring agents originating from natural sources for PBM can be considered advantageous compared to animal myoglobin in terms of health and functionality. Therefore, the purpose of this study was to produce natural coloring agents for PBM by extracting and developing chlorophyll from spinach, extracting anthocyanins from black beans, and inserting recombinant plasmids into microorganisms to produce LegH.

A Steel Plate Rolling Mill (SPM) is a milling machine that uses rollers to press hot slab inputs to produce ferrous or non-ferrous metal plates. To produce high-quality steel plates, it is important to precisely detect and sense values of manufacturing factors including plate thickness and roll force in each rolling pass. For example, the estimation or prediction of the in-process thickness is utilized to select the control values (e.g., roll gap) in the next pass of rolling. However, adverse manufacturing conditions can interfere with accurate detection for such manufacturing factors. Although the state-of-the-art gamma-ray camera can be used for measuring the thickness, the outputs from it are influenced by adverse manufacturing conditions such as the high temperature of plates, followed by the evaporation of lubricant water. Thus, it is inevitable that there is noise in the thickness estimation. Furthermore, installing such thickness measurements for each passing step is costly. The precision of the thickness estimation, therefore, significantly affects the cost and quality of the final product. In this paper, we present machine learning (ML) technologies and models that can be used to predict the in-process thickness in the SPM operation, so that the measurement cost for the in-process thickness can be significantly reduced and high-quality steel plate production can be possible. To do so, we investigate most-known technologies in this application. In particular, Data Clustering based Machine Learning (DC-ML), combining clustering algorithms and supervised learning algorithms, is introduced. To evaluate DC-ML, two experiments are conducted and show that DC-ML is well suited to the prediction problems in the SPM operation. In addition, the source code of DC-ML is provided for the future study of machine learning researchers.

The present study evaluated the properties and ochratoxin A (OTA) degradation capacity of the dietary probiotic Pediococcus pentosaceus BalaMMB-P3, isolated from a milk coagulant. The acidic tolerance of the isolate at pH 2–3 was checked with bile salts. No hemolytic activity was noted, which confirmed the nonpathogenicity of the strain. The isolate was tested in vitro for antibiotic susceptibility, enzymatic activity, bile salts hydrolase activity and antifungal activity against Penicillium verrucosum, Fusarium graminearum and Aspergillus ochraceus. A molecular docking-based OTA toxicity assessment was carried out for multitargeted proteins. The 16S rRNA gene-based phylogenetic assessment identified the strain as P. pentosaceus, and was authenticated in GenBank. The carboxylesterase and glutathione s-transferase enzymes showed active and strong interactions with esters and amide bonds, respectively. The compound exhibited carcinogenic and cytotoxicity effects at an LD50 value of 20 mg/kg. Furthermore, the strain showed a potent ability to reduce OTA and suggested the prospects for utilization in nutritional aspects of food.

Abstract Mobile wireless sensor networks (MWSNs) are a relatively new type of WSN where the sensor nodes are mobile. Compared to static WSNs, MWSNs provide many advantages, but their mobility introduces the problem of frequent reauthentication. Several mobile node reauthentication schemes based on symmetric key cryptography have been proposed to efficiently handle frequent reauthentication. However, due to security weaknesses such as unconditional forwarding or low-compromise resilience, these schemes do not satisfy the security requirements of MWSNs. In this paper, we propose an energy-efficient and secure mobile node reauthentication scheme (ESMR) for MWSNs that satisfies the security requirements of MWSNs by addressing the security weaknesses of previous studies. ESMR prevents unconditional forwarding by allowing a foreign cluster head to authenticate mobile nodes, providing high-compromise resilience because it limits the use of cryptographic keys for different purposes. Security analysis shows that ESMR meets security requirements and can prevent relevant security attacks. Performance evaluation shows that ESMR is suitable for multi-hop communication environment, where the number of hops between the mobile node and cluster head is two or more. Specifically, ESMR requires less than 6% increased total energy consumption and 3% increased reauthentication latency compared with previous studies; hence, it introduces negligible performance overhead. Considering both performance and security aspects, ESMR also can be applied to single-hop communication environment.

In this paper, the dependence of threshold voltage (Vth) changes to amorphous-indium gallium zinc oxide (a-IGZO) thin film transistors (TFTs) under positive bias light illumination (PBIS) on the height of the conduction band offset was studied. Using SiO2, HfO2, and Al2O3 as gate dielectrics, three different types of a-IGZO TFTs were used in the experiment. Electrical parameters and the density of states of each TFT were measured. Of the devices studied, the interface characteristics between the a-IGZO and the gate dielectric were the best using SiO2 and the worst using Al2O3. HfO2 had the smallest conduction band offsets (CBO) of 2.26 eV. We also performed PBS and PBIS evaluation to confirm the stability of TFTs. The Vth shift in the three samples was insignificant under PBS, but the Vth shifts occurred under PBIS in the order of HfO2, Al2O3, and SiO2. The interfacial characteristics of a-IGZO and the dielectric did not change after PBIS in all three devices; the lower the CBO height, the greater the Vth shift after PBIS. The predominant cause of the Vth shift under PBIS is the accumulation of injected photoelectrons that have sufficient energy to tunnel the CBO barrier into the gate dielectric by positive gate bias.

Anesthesia for percutaneous transluminal angioplasty (PTA) involves a high-risk population having a broad spectrum of pain character and intensity. This study delved the anesthetic efficacy of dexmedetomidine versus midazolam, when used with remifentanil. Seventy patients scheduled for femoropopliteal PTA were randomized into two groups receiving either intermittent midazolam boluses (0.03–0.05 mg/kg) (MR group) or dexmedetomidine 0.2–0.7 μg/kg/h after a loading dose of 1.0 μg/kg for 10 min (DR group), both with remifentanil. The primary endpoint was the patients’ satisfaction (1–5, 5; extremely satisfied). Secondary endpoints included postprocedural pain scores (0–10, 10; worst imaginable pain) and adverse events. The satisfaction level of patients was significantly greater in the DR group compared with the MR group (4.0 [3.0, 5.0] versus 4.0 [2.0, 5.0] p = 0.021). The number of patients having a postprocedural pain score of at least 3 was significantly greater in the MR group compared with the DR group (10 [29%] versus 2 [6%], p = 0.013). The number of patients with hypotensive episodes was higher in the DR group (5 [14.7%] versus 0, p = 0.025), which could all be restored with ephedrine. The use of dexmedetomidine in conjunction with remifentanil may be a safe option that provides excellent patient satisfaction while potentially attenuating postprocedural pain.

We propose a quality-aware media access control (MAC) protocol for real-time voice delivery in cognitive radio- (CR-) enabled wireless sensor networks (WSNs). The temporal structure of the system model is addressed by using periodic timeslots in order to make more efficient use of the spectrum. In our proposed temporal structure, a bandwidth broker in such centralized CR networks (CCRNs) is selected as a central counterpart to synchronize with secondary users (SUs) and assign spectral resources to them. We develop an analytical model for SUs for the Call Admission Control (CAC) of voice traffic using the quality of service (QoS) requirements of delay bound and delay bound violation probability. Ours is an approach that provides reliable data transmission and reduces packet delay and packet delay jitter. In addition to the aforementioned packet-level performance metrics, we calculated a call-level performance metric, that is, the number of acceptable SUs, satisfying QoS requirements.