The Herbal Blend of Sphaeranthus indicus and Garcinia mangostana Reduces Adiposity in High-Fat Diet Obese Mice.

Obesity is swiftly becoming a global epidemic, leading to numerous metabolic disorders and substantial socio-economic burdens. Investigating natural bioactive compounds is crucial to support the use of traditional anti-obesity medications while mitigating the adverse effects. This study posited that a combination of Sphaeranthus indicus and Garcinia mangostana (Meratrim) could prevent fat accumulation in obese mice. We used 4-week-old C57BL/6NTac mice, dividing them into six groups: (1) normal diet (ND); (2) high-fat diet (HFD, 45% kcal from fat); (3-5) Meratrim150, Meratrim300, and Meratrim450 (HFD with 150, 300, and 450 mg/kg bw of Meratrim); and (6) Metformin (HFD with 150 mg/kg bw of metformin). Meratrim was administered orally each day for 20 weeks. The group receiving 450 mg/kg of Meratrim showed a significant reduction in body weight and fat mass without changes in food consumption. The Meratrim450 group had markedly lower triglyceride levels in both serum and liver. Importantly, Meratrim-supplemented mice improved lipid homeostasis by inhibiting hepatic de novo lipogenesis and activating energy catabolic pathways such as non-shivering thermogenesis in brown adipose tissue. Our results suggest that the herbal mixture of Sphaeranthus indicus and Garcinia mangostana (Meratrim) is a promising natural anti-obesity agent, owing to its efficacy in reducing body fat and enhancing lipid homeostasis.

Graphene-enabled laser lift-off for ultrathin displays.

Laser lift-off (LLO) of ultrathin polyimide (PI) films is important in the manufacturing of ultrathin displays. However, conventional LLO technologies face challenges in separating the ultrathin PI films without causing mechanical and electrical damage to integrated devices. Here, we propose a graphene-enabled laser lift-off (GLLO) method to address the challenges. The GLLO method is developed by integrating chemical vapor deposition (CVD)-grown graphene at the interface between a transparent carrier and an ultrathin PI film, exhibiting improved processability and lift-off quality. In particular, the GLLO method significantly mitigates plastic deformation of the PI film and minimizes carbonaceous residues remaining on the carrier. The role of graphene is attributed to three factors: enhancement of interfacial UV absorption, lateral heat diffusion, and adhesion reduction, and experimentations and numerical simulations verify the mechanism. Finally, it is demonstrated that the GLLO method separates ultrathin organic light-emitting diode (OLED) devices without compromising performance. We believe that this work will pave the way for utilizing CVD graphene in various laser-based manufacturing applications.

Exploring the multifaceted role of ginkgolides and bilobalide from Ginkgo biloba in mitigating metabolic disorders.

The ancient Ginkgo biloba tree grows across various regions, with distinctive leaves emitting a unique fragrance. Its extract contains flavonoids, organic acids, and terpenoids. Ginkgolide and bilobalide, which are G. biloba leaf extracts, offer diverse pharmaceutical benefits, including antioxidant, anti-inflammatory, and neuroprotective properties. The antioxidant and anti-inflammatory properties of these compounds are crucial for mitigating neurodegeneration, particularly in diseases such as Alzheimer's disease. Additionally, their effectiveness in countering oxidative stress and inflammation highlights their potential to prevent cardiovascular ailments. This study also suggests that these compounds have a promising impact on lipid metabolism, suggesting their significance in addressing obesity-related metabolic disorders. In conclusion, ginkgolides and bilobalide exhibit promising effects in sustaining the integrity of the nervous and endocrine systems, along with the modulation of lipid metabolism. The diverse health benefits suggest that these compounds could serve as promising therapeutic interventions for various conditions, including neurological, cardiovascular, and metabolic diseases.

Black beans (Glycine max (L.) Merrill) included in a multi-grain rice reduce total cholesterol and enhance antioxidant capacity in high-fat diet-induced obese mice.

This study investigated the effects of black bean (BB) supplementation on the growth performance, lipid metabolism, and antioxidant capacity of high-fat diet-induced obese mice. The results demonstrated that although the inclusion of BBs led to increased body weight, total energy intake, and feed efficiency ratio, it did not significantly alter the overall body composition, including adiposity. Notably, BB consumption reduced total cholesterol levels, suggesting its potential to manage dyslipidemia and reduce the risk of atherosclerotic cardiovascular diseases. Furthermore, BBs significantly enhanced in the total antioxidant capacity, as indicated by the notable increase in both the total antioxidant capacity and superoxide dismutase activity. These findings provide significant insights into the promising health benefits of BBs in the context of metabolic syndrome and related health complications.

Correction to: A combined extract containing Schisandra chinensis (SCE) reduced hepatic triglyceride accumulation in rats fed a high­sucrose diet.

[This corrects the article DOI: 10.1007/s10068-023-01464-1.].

Social Type-Aware Navigation Framework for Mobile Robots in Human-Shared Environments.

As robots become increasingly common in human-populated environments, they must be perceived as social beings and behave socially. People try to preserve their own space during social interactions with others, and this space depends on a variety of factors, such as individual characteristics or their age. In real-world social spaces, there are many different types of people, and robots need to be more sensitive, especially when interacting with vulnerable subjects such as children. However, the current navigation methods do not consider these differences and apply the same avoidance strategies to everyone. Thus, we propose a new navigation framework that considers different social types and defines appropriate personal spaces for each, allowing robots to respect them. To this end, the robot needs to classify people in a real environment into social types and define the personal space for each type as a Gaussian asymmetric function to respect them. The proposed framework is validated through simulations and real-world experiments, demonstrating that the robot can improve the quality of interactions with people by providing each individual with an adaptive personal space. The proposed costmap layer is available on GitHub.

Transformable Gaussian Reward Function for Socially Aware Navigation Using Deep Reinforcement Learning.

Robot navigation has transitioned from avoiding static obstacles to adopting socially aware navigation strategies for coexisting with humans. Consequently, socially aware navigation in dynamic, human-centric environments has gained prominence in the field of robotics. One of the methods for socially aware navigation, the reinforcement learning technique, has fostered its advancement. However, defining appropriate reward functions, particularly in congested environments, holds a significant challenge. These reward functions, crucial for guiding robot actions, necessitate intricate human-crafted design due to their complex nature and inability to be set automatically. The multitude of manually designed reward functions contains issues such as hyperparameter redundancy, imbalance, and inadequate representation of unique object characteristics. To address these challenges, we introduce a transformable Gaussian reward function (TGRF). The TGRF possesses two main features. First, it reduces the burden of tuning by utilizing a small number of hyperparameters that function independently. Second, it enables the application of various reward functions through its transformability. Consequently, it exhibits high performance and accelerated learning rates within the deep reinforcement learning (DRL) framework. We also validated the performance of TGRF through simulations and experiments.

Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel.

Mechanically activating (MA) channels transduce numerous physiological functions. Tentonin 3/TMEM150C (TTN3) confers MA currents with slow inactivation kinetics in somato- and barosensory neurons. However, questions were raised about its role as a Piezo1 regulator and its potential as a channel pore. Here, we demonstrate that purified TTN3 proteins incorporated into the lipid bilayer displayed spontaneous and pressure-sensitive channel currents. These MA currents were conserved across vertebrates and differ from Piezo1 in activation threshold and pharmacological response. Deep neural network structure prediction programs coupled with mutagenetic analysis predicted a rectangular-shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit center. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These findings suggest that TTN3 is a pore-forming subunit of a distinct slow inactivation MA channel, potentially possessing a tetrameric structure.

A combined extract containing Schisandra chinensis (SCE) reduced hepatic triglyceride accumulation in rats fed a high-sucrose diet.

Excessive hepatic lipid accumulation is closely linked to inflammation, insulin resistance, and metabolic syndromes. We hypothesized that a combined extract containing Schisandra chinensis (SCE) could alleviate hepatic lipid accumulation. Male Sprague-Dawley rats fed a high-sucrose diet (HSD) were randomly assigned to three groups (n = 6): normal diet (ND), HSD (60% kcal from sucrose), and HSD + SCE (HSD with 2.44% SCE). Liquid chromatography-tandem mass spectrometry revealed that SCE contains chlorogenic acid (5.514 ± 0.009 mg/g) and schisandrin (0.179 ± 0.002 mg/g) as bioactive components. SCE did not alter the body weight, fat mass, lean mass, or glucose levels. Strikingly, SCE effectively reduced the plasma triglyceride (TG) and hepatic TG levels compared to the HSD group. Adiposity reduction is due to decreased activity of hepatic de novo lipogenic enzymes. These results indicated that SCE has nutraceutical potential for the prevention and treatment of hepatic steatosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01464-1.

Junctionless Negative-Differential-Resistance Device Using 2D Van-Der-Waals Layered Materials for Ternary Parallel Computing.

Negative-differential-resistance (NDR) devices offer a promising pathway for developing future computing technologies characterized by exceptionally low energy consumption, especially multivalued logic computing. Nevertheless, conventional approaches aimed at attaining the NDR phenomenon involve intricate junction configurations and/or external doping processes in the channel region, impeding the progress of NDR devices to the circuit and system levels. Here, an NDR device is presented that incorporates a channel without junctions. The NDR phenomenon is achieved by introducing a metal-insulator-semiconductor capacitor to a portion of the channel area. This approach establishes partial potential barrier and well that effectively restrict the movement of hole and electron carriers within specific voltage ranges. Consequently, this facilitates the implementation of both a ternary inverter and a ternary static-random-access-memory, which are essential components in the development of multivalued logic computing technology.

Area-selective atomic layer deposition on 2D monolayer lateral superlattices.

The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.

Ambivalence towards pork belly: exploring its significance and contradictions from the perspectives of the food industry and nutritional science.

Pork is the most consumed meat in South Korea, and pork belly is the preferred cut. However, pork production cannot meet the demand, leading to a heavy reliance on imports, particularly for pork bellies. In contrast, low-fat cuts face oversupply problems owing to low demand and export challenges. Pork belly fat content varies with breed, sex, growth rate, and fatty acid composition. Western countries favor higher fat saturation for processed products, whereas South Koreans prefer grilled or roasted bellies. Excessive consumption of high-fat pork cuts like pork belly, which is rich in saturated fatty acids, can increase the risk of severe diseases, highlighting the importance of reducing saturated fat intake and increasing the consumption of monounsaturated fatty acids and polyunsaturated fatty acids to mitigate these risks. The pork industry and public health sector should diversify production, promote leaner pork, and raise awareness about the implications of excessive pork consumption.

Effect of MIND diet on cognitive function in elderly: a narrative review with emphasis on bioactive food ingredients.

As the world becomes a super-aged society, cognitive decline is public health problems that are increasing rapidly. A healthy diet has great potential for maintaining cognitive health. A diet that could delay the onset of neurodegenerative diseases has been developed: the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, a hybrid form of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. In this review, the effects of the MIND diet on improving cognitive function, including memory, are summarized. In most studies, the higher the adherence to the MIND diet, the higher the cognitive function evaluation score, and the lower the incidence of dementia. This is because of the anti-inflammatory and antioxidant effects of the major nutritional components of the MIND diet: folate, carotenoids, polyphenols, and polyunsaturated fatty acids. Adherence to the MIND diet, containing various bioactive food ingredients, is related to cognitive improvement in the elderly population.

Simple Protein Analysis by Droplet Paper Spray Ionization Mass Spectrometry with Polyolefin Silica-Based Paper.

Paper spray ionization mass spectrometry (PSI MS) has emerged as a notable method for the rapid analysis of biological samples. However, the typical cellulose-based paper tip is incompatible with protein detection due to the strong interaction between cellulose hydroxyl groups and proteins. In this study, we utilized a commercially available polyolefin-based synthetic paper, Teslin®, as an alternative PSI substrate for simple protein analysis. We have named this method "droplet PSI" MS, as the aqueous protein solution droplet retains its shape on the Teslin® paper tip. For droplet PSI, no further chemical pretreatment was necessary for the Teslin® substrate; the only required preparation was shaping the Teslin® paper into a triangular tip. In droplet PSI MS, protein ion signals were instantly detected from a protein solution droplet upon applying a spray solvent in situ along with high voltage (HV). When compared with conventional PSI MS, our method demonstrated superior sensitivity. The droplet PSI MS utilizing Teslin® also showcased flexibility in real-time observation of protein alterations induced by an acid additive. Additionally, the effects of spray solvent composition and the application method were discussed.

Recent Advances in Nutraceuticals for the Treatment of Sarcopenic Obesity.

Sarcopenic obesity, low muscle mass, and high body fat are growing health concerns in the aging population. This review highlights the need for standardized criteria and explores nutraceuticals as potential therapeutic agents. Sarcopenic obesity is associated with insulin resistance, inflammation, hormonal changes, and reduced physical activity. These factors lead to impaired muscle activity, intramuscular fat accumulation, and reduced protein synthesis, resulting in muscle catabolism and increased fat mass. Myostatin and irisin are myokines that regulate muscle synthesis and energy expenditure, respectively. Nutritional supplementation with vitamin D and calcium is recommended for increasing muscle mass and reducing body fat content. Testosterone therapy decreases fat mass and improves muscle strength. Vitamin K, specifically menaquinone-4 (MK-4), improves mitochondrial function and reduces muscle damage. Irisin is a hormone secreted during exercise that enhances oxidative metabolism, prevents insulin resistance and obesity, and improves bone quality. Low-glycemic-index diets and green cardamom are potential methods for managing sarcopenic obesity. In conclusion, along with exercise and dietary support, nutraceuticals, such as vitamin D, calcium, vitamin K, and natural agonists of irisin or testosterone, can serve as promising future therapeutic alternatives.

Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes.

Rottlerin is isolated from Mallotus japonicus, a plant rich in polyphenols. Rottlerin is a selective PKCδ-inhibitor and is also known as an uncoupler of oxidative phosphorylation and anti-neoplastic agent. However, its anti-obesity effect is yet to be established. Therefore, this study tested whether rottlerin inhibits adipogenesis and de novo lipogenesis via the LRP6/mTOR/SREBP1C pathway in 3T3-L1 adipocytes. Rottlerin dramatically decreased lipid accumulation assessed by Oil Red O as evidence to support the cellular phenotype (p < 0.001). Pivotal messenger RNA and protein expressions associated with de novo lipogenesis (SREBP1C, ACC1, FAS, and SCD1) and adipogenesis (PPARγ and C/EBPα) were subsequentially verified by rottlerin in a dose-dependent manner (p < 0.05). Further investigation revealed that rottlerin reduced the AKT/mTOR pathway via diminished total protein of LRP6 (p < 0.05). Collectively, these findings establish a causal link between rottlerin, LRP6, and the altered nutrient-sensing mTOR pathway, in which rottlerin regulates de novo lipogenesis and adipogenesis in white adipocytes.

Succinyl-CoA ligase ADP-forming subunit beta promotes stress granule assembly to regulate redox and drive cancer metastasis.

Although recent studies demonstrate active mitochondrial metabolism in cancers, the precise mechanisms through which mitochondrial factors contribute to cancer metastasis remain elusive. Through a customized mitochondrion RNAi screen, we identified succinyl-CoA ligase ADP-forming subunit beta (SUCLA2) as a critical anoikis resistance and metastasis driver in human cancers. Mechanistically, SUCLA2, but not the alpha subunit of its enzyme complex, relocates from mitochondria to the cytosol upon cell detachment where SUCLA2 then binds to and promotes the formation of stress granules. SUCLA2-mediated stress granules facilitate the protein translation of antioxidant enzymes including catalase, which mitigates oxidative stress and renders cancer cells resistant to anoikis. We provide clinical evidence that SUCLA2 expression correlates with catalase levels as well as metastatic potential in lung and breast cancer patients. These findings not only implicate SUCLA2 as an anticancer target, but also provide insight into a unique, noncanonical function of SUCLA2 that cancer cells co-opt to metastasize.

Abiotic and biotic factors controlling sexual reproduction in populations of Pseudo-nitzschia pungens (Bacillariophyceae).

Pseudo-nitzschia pungens is a widely distributed marine pennate diatom. Hybrid zones, regions in which two different genotypes may interbreed, are important areas for speciation and ecology, and have been reported across the globe for this species. However, sexual reproduction between differing clades in the natural environment is yet to be observed and is difficult to predict. Here we carried out experiments using two mono-clonal cultures of P. pungens from different genotypes to measure the frequency and timing of sexual reproduction across varying biotic (growth phases and cell activity potential) and abiotic conditions (nutrients, light, turbulence). We found the mating rates and number of zygotes gradually decreased from exponential to late stationary growth phases. The maximum zygote abundance observed was 1,390 cells mL-1 and the maximum mating rate was 7.1%, both which occurred during the exponential growth phase. Conversely, only 9 cells mL-1 and a maximum mating rate of 0.1% was observed during the late stationary phase. We also found the higher the relative potential cell activity (rPCA) in parent cells, as determined by the concentration of chlorophyll a per cell and the ratio of colony formation during parent cultivations, revealed higher mating rates. Furthermore, sexual events were reduced under nutrient enrichment conditions, and mating pairs and zygotes were not formed under aphotic (dark) or shaking culture conditions (150 rpm). In order to understand the sexual reproduction of Pseudo-nitzschia in the natural environment, our results highlight that it is most likely the combination of both biotic (growth phase, Chl. a content) and abiotic factors (nutrients, light, turbulence) that will determine the successful union of intraspecific populations of P. pungens in any given region.

A robust antibody discovery platform for difficult-to-express G protein-coupled receptors.

G protein-coupled receptors (GPCRs) are in the spotlight as drug targets due to the fact that multiple research results have verified the correlation between the activation of GPCRs and disease indications. This is because the GPCRs are present across the cell membranes, which interact with either extracellular ligands or other types of compartments and simultaneously mediate intracellular signaling. Despite the importance of the GPCRs as drug targets, they are too difficult to express in soluble forms. Currently, the difficulty of preparing functional GPCRs and the lack of efficient antibody screening methods are the most challenging steps in the discovery of antibodies targeting GPCRs. In this study, we developed a powerful platform that facilitates isolating GPCR-specific antibodies by obviating difficulties in GPCR preparation. The strategies include (i) conjugation of the P9 peptide, an envelope protein of Pseudomonas phi6, to the N-terminus of GPCRs to improve the expression level of the GPCRs in Escherichia coli, (ii) stabilization of the GPCRs in their active forms with amphiphilic poly-γ-glutamate (APG) to shield the seven hydrophobic transmembrane domains, and (iii) further limiting the size of the APG complex to improve the chance to isolate antibodies targeting the proteins-of-interest. Capitalizing on the above strategies, we could prepare GPCR proteins in their active forms as facile as other general-soluble antigen proteins. Furthermore, this protocol was validated to be successful in discovering three individual GPCR-specific antibodies targeting glucagon-like peptide-1 receptor, C-X-C chemokine receptor type 4, and prostaglandin E2 receptor 4 in this study.

EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer.

The cancer metastasis process involves dysregulated oncogenic kinase signaling, but how this orchestrates metabolic networks and signal cascades to promote metastasis is largely unclear. Here we report that inhibition of glutamate dehydrogenase 1 (GDH1) and ribosomal S6 kinase 2 (RSK2) synergistically attenuates cell invasion, anoikis resistance, and immune escape in lung cancer and more evidently in tumors harboring epidermal growth factor receptor (EGFR)-activating or EGFR inhibitor-resistant mutations. Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. Co-targeting RSK2 and GDH1 leads to enhanced intratumoral CD8 T cell infiltration. Moreover, GDH1, RSK2, and CREB phosphorylation positively correlate with EGFR mutation and activation in lung cancer patient tumors. Our findings reveal a crosstalk between kinase, metabolic, and transcription machinery in metastasis and offer an alternative combinatorial therapeutic strategy to target metastatic cancers with activated EGFRs that are often EGFR therapy resistant.