N-Acetylserotonin is an oxidation-responsive activator of Nrf2 ameliorating colitis in rats.

N-Acetylserotonin (NAS) is an intermediate in the melatonin biosynthetic pathway. We investigated the anti-inflammatory activity of NAS by focusing on its chemical feature oxidizable to an electrophile. NAS was readily oxidized by reaction with HOCl, an oxidant produced in the inflammatory state. HOCl-reacted NAS (Oxi-NAS), but not NAS, activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in cells. Chromatographic and mass analyses demonstrated that Oxi-NAS was the iminoquinone form of NAS and could react with N-acetylcysteine possessing a nucleophilic thiol to form a covalent adduct. Oxi-NAS bound to Kelch-like ECH-associated protein 1, resulting in Nrf2 dissociation. Moreover, rectally administered NAS increased the levels of nuclear Nrf2 and HO-1 proteins in the inflamed colon of rats. Simultaneously, NAS was converted to Oxi-NAS in the inflamed colon. Rectal NAS mitigated colonic damage and inflammation. The anticolitic effects were significantly compromised by the coadministration of an HO-1 inhibitor.

Quasi-Fermi level splitting in nanoscale junctions from ab initio.

The splitting of quasi-Fermi levels (QFLs) represents a key concept utilized to describe finite-bias operations of semiconductor devices, but its atomic-scale characterization remains a significant challenge. Herein, the nonequilibrium QFL or electrochemical potential profiles within single-molecule junctions obtained from the first-principles multispace constrained-search density-functional formalism are presented. Benchmarking the standard nonequilibrium Green's function calculation results, it is first established that algorithmically the notion of separate electrode-originated nonlocal QFLs should be maintained within the channel region during self-consistent finite-bias electronic structure calculations. For the insulating hexandithiolate junction, the QFL profiles exhibit discontinuities at the left and right electrode interfaces and across the molecule the accompanying electrostatic potential drops linearly and Landauer residual-resistivity dipoles are uniformly distributed. For the conducting hexatrienedithiolate junction, on the other hand, the electrode QFLs penetrate into the channel region and produce split QFLs. With the highest occupied molecular orbital entering the bias window and becoming a good transport channel, the split QFLs are accompanied by the nonlinear electrostatic potential drop and asymmetric Landauer residual-resistivity dipole formation. Our findings underscore the importance of the first-principles extraction of QFLs in nanoscale junctions and point to a future direction for the computational design of next-generation semiconductor devices.

Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses.

Lactobacillus plantarum (L. plantarum) is a probiotic that has emerged as novel therapeutic agents for managing various diseases, such as cancer, atopic dermatitis, inflammatory bowel disease, and infections. In this study, we investigated the potential mechanisms underlying the anticancer effect of the metabolites of L. plantarum. We cultured L. plantarum cells to obtain their metabolites, created several dilutions, and used these solutions to treat human colonic Caco-2 cells. Our results showed a 10% dilution of L. plantarum metabolites decreased cell viability and reduced the expression of autophagy-related proteins. Moreover, we found co-treatment with L. plantarum metabolites and chloroquine, a known autophagy inhibitor, had a synergistic effect on cytotoxicity and downregulation of autophagy-related protein expression. In conclusion, we showed the metabolites from the probiotic, L. plantarum, work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy.

Exploration of Sugar and Starch Metabolic Pathway Crucial for Pollen Fertility in Rice.

Starch is the primary storage carbohydrate in mature pollen grains in many crop plants, including rice. Impaired starch accumulation causes male sterility because of the shortage of energy and building blocks for pollen germination and pollen tube growth. Thus, starch-defective pollen is applicable for inducing male sterility and hybrid rice production. Despite the importance of pollen starch, the details of the starch biosynthesis and breakdown pathway in pollen are still largely unknown. As pollen is isolated from the maternal tissue, photoassimilate transported from leaves must pass through the apoplastic space from the anther to the filial pollen, where it is stored as starch. Several sugar transporters and enzymes are involved in this process, but many are still unknown. Thus, the current review provides possible scenarios for sucrose transport and metabolic pathways that lead to starch biosynthesis and breakdown in rice pollen.

Aesthetic Reconstruction After Removal of Huge Epidermal Cyst Involving the Calvarium and Dura on the Scalp.

ABSTRACT: Epidermal or epidermoid cysts are one of the most frequent benign masses at the subepidermal level. They are typically smooth, movable, and fluctuant masses covered with stratified squamous epithelium. They rarely grow to a huge size, and only a few cases have been reported. A 69-year-old woman visited the authors' clinic for treatment of a well-defined huge mass in the right temporoparietal and occipital regions of the scalp that had regrown and spontaneously increased in size after excision 30 years prior. Computed tomography revealed a large lobulated mass with an air-fluid level and calvarial bone erosion invading the inner table in the right parietal region. Dural exposure was suspected based on magnetic resonance imaging, which depicted diffuse dural thickening with enhancement.The authors aesthetically excised the mass in cooperation with the Department of Neurosurgery using an inverted T-shaped excisional flap design for the reduction of the redundant scalp similar to that used in reduction mammoplasty surgery. Two months later there was no evidence of recurrence or complications, and the patient was satisfied with the results of the surgery.The authors report the case of a huge scalp mass with skull defect and propose an aesthetic treatment option for this unusual mass on the scalp.

Direct replication of a glass micro Fresnel zone plate array by laser irradiation using an infrared transmissive mold.

It is not yet possible to fabricate micrometer-scale, glass optical components with nanometer-scale precision. Glass thermal imprinting enhances production efficiency. However, dimensional changes caused by shrinkage are inevitable because of phase transitions. Replication is very difficult when high-level pitch precision is essential. We used an infrared-transparent silicon mold and a CO2 laser to perform replica-type, thermal surface texturing at the nanoscale level; we analyzed a glass Fresnel zone plate array to this end. The Fresnel zone plate array was 10 × 10 mm2 in area and featured a 20 × 20 array. The individual Fresnel zone plate diameter was 500 µm and had 21 rings of minimum linewidth 2.9 µm and height 737 nm.

Curcumin Nanocrystal/pH-Responsive Polyelectrolyte Multilayer Core-Shell Nanoparticles for Inflammation-Targeted Alleviation of Ulcerative Colitis.

In this study, we developed oral core-shell nanoparticles composed of curcumin nanocrystals in the core and chitosan/alginate multilayers in the shell for inflammation-targeted alleviation of ulcerative colitis (UC). The release rate of curcumin from the core-shell nanoparticles was low at a pH mimicking the stomach and small intestine, whereas it was higher at a pH mimicking the colon. Further, biodistribution studies in the gastrointestinal tract of mice showed that distribution of nanoparticles was significantly higher in the colon than that in the stomach and small intestine. Quantitative analysis of drugs in colonic tissues and confocal imaging of colons revealed preferential accumulation of nanoparticles in inflamed tissues than that in healthy tissues. In vivo anti-inflammatory studies revealed that nanoparticles exhibit enhanced efficacy in alleviating inflammation-related symptoms in a mouse colitis model. The results suggest that the core-shell nanoparticles presented here can be exploited as efficient colon-targeted drug delivery systems for UC therapy.

Time-Sensitive Network (TSN) Experiment in Sensor-Based Integrated Environment for Autonomous Driving.

Recently, large amounts of data traffic from various sensors and image and navigation systems within vehicles are generated for autonomous driving. Broadband communication networks within vehicles have become necessary. New autonomous Ethernet networks are being considered as alternatives. The Ethernet-based in-vehicle network has been standardized in the IEEE 802.1 time-sensitive network (TSN) group since 2006. The Ethernet TSN will be revised and integrated into a subsequent version of IEEE 802.1Q-2018 published in 2018 when various new TSN-related standards are being newly revised and published. A TSN integrated environment simulator is developed in this paper to implement the main functions of the TSN standards that are being developed. This effort would minimize the performance gaps that can occur when the functions of these standards operate in an integrated environment. As part of this purpose, we analyzed the simulator to verify that the traffic for autonomous driving satisfies the TSN transmission requirements in the in-vehicle network (IVN) and the preemption (which is one of the main TSN functions) and reduces the overall End-to-End delay. An optimal guard band size for the preemption was also found for autonomous vehicles in our work. Finally, an IVN model for autonomous vehicles was designed and the performance test was conducted by configuring the traffic to be used for various sensors and electronic control units (ECUs).

pH-triggered surface charge-reversal nanoparticles alleviate experimental murine colitis via selective accumulation in inflamed colon regions.

In this study, we developed pH-triggered surface charge-reversal lipid nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the drug to inflamed colon segments for the treatment of ulcerative colitis. Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and Eudragit® S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge-reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic conditions mimicking the stomach and early small intestine environments and showed a sustained release in the colon. The surface charge of ES-PEI-LNPs switched from negative to positive under colonic conditions owing to pH-triggered removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs could be a promising drug carrier for ulcerative colitis therapy and other colon-targeted treatments.

Stretching-Induced Conductance Variations as Fingerprints of Contact Configurations in Single-Molecule Junctions.

Molecule-electrode contact atomic structures are a critical factor that characterizes molecular devices, but their precise understanding and control still remain elusive. Based on combined first-principles calculations and single-molecule break junction experiments, we herein establish that the conductance of alkanedithiolate junctions can both increase and decrease with mechanical stretching, and the specific trend is determined by the S-Au linkage coordination number (CN) or the molecule-electrode contact atomic structure. Specifically, we find that the mechanical pulling results in the conductance increase for the junctions based on S-Au CN two and CN three contacts, while the conductance is minimally affected by stretching for junctions with the CN one contact and decreases upon the formation of Au monatomic chains. Detailed analysis unravels the mechanisms involving the competition between the stretching-induced upshift of the highest occupied molecular orbital-related states toward the Fermi level of electrodes and the deterioration of molecule-electrode electronic couplings in different contact CN cases. Moreover, we experimentally find a higher chance to observe the conductance enhancement mode under a faster elongation speed, which is explained by ab initio molecular dynamics simulations that reveal an important role of thermal fluctuations in aiding deformations of contacts into low-coordination configurations that include monatomic Au chains. Pointing out the insufficiency in previous notions of associating peak values in conductance histograms with specific contact atomic structures, this work resolves the controversy on the origins of ubiquitous multiple conductance peaks in S-Au-based single-molecule junctions.

Molecular Insights into the Adsorption Mechanism of Human ß-Defensin-3 on Bacterial Membranes.

Human ß-defensin-3 (hBD3) is an endogenous antimicrobial peptide that exhibits broad-spectrum antibacterial activity without eukaryotic cytotoxicity. In this work, we carried out molecular dynamics (MD) simulations to explore its adsorption mechanism on, and the structural and thermodynamic contributions of individual residues to its antibacterial activity with both Gram-negative (GN) and Gram-positive (GP) bacterial membrane. Due to the strong electrostatic interaction of hBD3 with POPG lipids, which are more prevalent on the GP membrane, its adhesion to the GP membrane is stronger than to the GN membrane and stabilized more rapidly. On the surface of both bacterial membranes, the orientation of hBD3 is dominated by an electric dipole. We next analyzed the binding free energy decompositions of the hBD3-membrane complex using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The results of both the GN and the GP membrane simulations show that Arg17, Arg36, and Arg38 form both polar and nonpolar interactions and are potentially the key residues for hBD3 antibacterial activity. On the other hand, there was a significant difference in the energy contribution of Arg12 between the GP and GN membrane simulations, suggesting that Arg12 is a key factor in the toxicity of hBD3 to specifically GP bacteria. Our findings shed light on the antibacterial activity of hBD3 on bacterial membranes and yield insights useful for the design of potent antimicrobial peptides targeting multidrug resistant bacteria.

Large litters have a detrimental impact on litter performance and postpartum maternal behaviour in primiparous sows.

BACKGROUND: Our previous study confirmed that large litter size adversely affects prepartum maternal hormones and behaviour, concurrently with heightened oxidative stress in primiparous sows. The purpose of this study was to examine the effect of large litter size on litter performance, postpartum maternal behaviour, salivary cortisol levels, and colostral immunoglobulin levels in sows, as well as investigate their correlations with the levels of oxidative stress parameters. RESULTS: A total of 24 primiparous sows (Landrace[Formula: see text]Large white) and their offspring were categorised into two groups based on litter size: NORMAL (n = 8) with litter size ranging from 7 to 14 (mean 11.5[Formula: see text]2.7), and LARGE (n=16) with litter size ranging from 15 to 20 (mean 15.9[Formula: see text]1.4). All sows were housed in a group housing system during gestation and transitioned to an adaptable loose housing system (2.4[Formula: see text]2.3 m) during the farrowing and lactation periods. The nursing and carefulness behaviour of the sows was monitored over a 24-h period between 72 and 96 h after parturition. Saliva samples were collected for cortisol assay on 35, 21, and 7 days before parturition (D-35, D-21, and D-7, respectively), as well as on days 1, 7, and 28 after parturition (D1, D7, and D28, respectively). On D1, higher piglet mortality rates were observed among the LARGE group compared to the NORMAL group (p<0.01). The total and successful nursing behaviours of the sows were less frequent in the LARGE group than in the NORMAL group (p<0.05, for both), and the carefulness score of the LARGE group was also lower than that of the NORMAL group (p< 0.01). On D1, cortisol levels in LARGE sows were higher than those in NORMAL sows (p< 0.05), and for other time points (D-21, D-7, D7, and D28), cortisol levels in LARGE sows tended to be higher than those in NORMAL sows (p < 0.10, for all). Successful nursing behaviour displayed negative correlations with levels of salivary cortisol and certain oxidative stress parameters measured on D1. CONCLUSIONS: These findings suggest that the strategy for alleviating physiological and oxidative stress during the peripartum periods could benefit potential postpartum maternal behaviour and litter performance in the sows with large litters.

Effects of Nesting Material Provision and High-Dose Vitamin C Supplementation during the Peripartum Period on Prepartum Nest-Building Behavior, Farrowing Process, Oxidative Stress Status, Cortisol Levels, and Preovulatory Follicle Development in Hyperprolific Sows.

Hyperprolific sows often experience increased oxidative stress during late gestation and lactation periods, which can adversely affect the farrowing process and overall lactation performance. This study examines the influence of providing a coconut coir mat (CCM; 1 × 1 m) as nesting material, supplementing high-dose vit-C (HVC; 20% vit-C, 10 g/kg feed) as an antioxidant, or both on maternal behavior, the farrowing process, oxidative status, cortisol levels, and preovulatory follicle developments in sows with large litters. In total, 35 sows (Landrace × Yorkshire; litter size 15.43 ± 0.27) were allocated to the following four treatment groups: control (n = 9, basal diet), vit-C (n = 8, basal diet + HVC), mat (n = 10, basal diet + CCM), and mat + vit-C (n = 8, basal diet + HVC + CCM). A post-hoc analysis showed that compared with sows that were not provided CCM, mat and mat + vit-C groups demonstrated increased durations of nest-building behavior during the period from 24 h to 12 h before parturition (p < 0.05 for both), reduced farrowing durations, and decreased intervals from birth to first udder contact (p < 0.01 for both). The mat group exhibited lower advanced oxidation protein product (AOPP) levels during late gestation and lactation periods than the control group (p < 0.05). Sows with HVC supplementation showed longer farrowing durations than those without HVC supplementation (p < 0.0001). The vit-C group had higher salivary cortisol levels on day 1 after farrowing than the other treatment groups (p < 0.05). Furthermore, the follicle diameters on day 3 after weaning in the vit-C group tended to be smaller than those in the control group (p = 0.077). HVC supplementation prolonged farrowing and increased the physiological stress on postpartum, and no advantageous effects on maternal behavior and developmental progression of preovulatory follicles were observed. Hence, alternative solutions beyond nutritional approaches are required to address increased oxidative stress in hyperprolific sows and secure their welfare and reproductive performance. The present results substantiated the positive impact of providing CCM as nesting material for sows with large litters on nest-building behavior and the farrowing process, which could mitigate the deleterious consequences induced by peripartum physiological and oxidative stress.

Structural and dynamic features of cold-shock proteins of Listeria monocytogenes, a psychrophilic bacterium.

Cold-shock proteins (Csps), proteins expressed when the ambient temperature drops below the growth-supporting temperature, bind to single-stranded nucleic acids and act as RNA chaperones to regulate translation. Listeria monocytogenes is a psychrophilic food-borne pathogen that is problematic for the food industry. Structures of Csps from psychrophilic bacteria have not yet been studied. Despite dramatic differences in the thermostability of Csps of various thermophilic microorganisms, these proteins share a high degree of primary sequence homology and a high degree of three-dimensional structural similarity. Here, we investigated the structural and dynamic features as well as the thermostability of L. monocytogenes CspA (Lm-CspA). Lm-CspA has a five-stranded ß-barrel structure with hydrophobic core packing and two salt bridges. When heptathymidine (dT(7)) binds, values for the heteronuclear nuclear Overhauser effect and order parameters of residues in surface loop regions near nucleic acid binding sites increase dramatically. Moreover, Carr-Purcell-Meiboom-Gill experiments showed that slow motions observed for the nucleic acid binding residues K7, W8, F15, F27, and R56 disappeared in Lm-CspA-dT(7). Lm-CspA is less thermostable than mesophilic and thermophilic Csps, with a lower melting temperature (40 °C). The structural flexibility that accompanies longer surface loops and less hydrophobic core packing and a number of salt bridges and unfavorable electrostatic repulsion are likely key factors in the low thermostability of Lm-CspA. This implies that the large conformational flexibility of psychrophilic Lm-CspA, which more easily accommodates nucleic acids at low temperature, is required for RNA chaperone function under cold-shock conditions and for the cold adaptation of L. monocytogenes.

Effects of genomic changes in hepatitis B virus on postoperative recurrence and survival in patients with hepatocellular carcinoma.

PURPOSE: To determine whether the genomic changes in hepatitis B virus (HBV) affect the clinical outcomes of hepatocellular carcinoma (HCC) in patients with HBV-associated HCC treated with curative surgical resection. METHODS: A total of 247 patients with HBV-associated HCC were treated with curative surgical resection. They were followed regularly for a median of 30 months. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced. RESULTS: The genomic changes such as the G1896A at precore, the A1762T/G1764A at BCP, the C1653T and the T1753V at X gene, and pre-S2 deletion were not significantly associated with postoperative recurrence of HCC or survival of patients after curative resection. However, in univariate analysis, younger age, elevated serum α-fetoprotein level, elevated serum alanine aminotransferase level, larger tumor size, microvascular invasion, and advanced Cancer of the Liver Italian Program stage were closely associated with shorter survival after surgical resection. In multivariate analysis, only microvascular invasion revealed to be an independent risk factor of postoperative recurrence (relative risk [RR] 5.406; P < 0.001); the independent risk factors of shorter survival appeared to be infiltrative type (RR 5.110; P = 0.032), larger tumor size (RR 1.976; P = 0.047), and microvascular invasion (RR 6.118; P < 0.001). CONCLUSIONS: The postoperative recurrence or survival period may not be affected by the genomic changes at the precore, BCP, X, and pre-S2 regions in HBV of genotype C2 in patients with HBV-associated HCC treated with curative surgical resection. Rather, it may be closely associated with tumor characteristics, such as the size and type of HCC or presence of microvascular invasion.

Large litter size increases oxidative stress and adversely affects nest-building behavior and litter characteristics in primiparous sows.

The study examined 24 primiparous sows (Landrace × Large white) and their offspring, which were grouped based on litter size: NORMAL (n = 8, average litter size 11.5 ± 1.2), with litter size between 7 and 14, and LARGE (n = 16, average litter size 15.9 ± 1.0), with litter size between 15 and 20. Sows were group-housed during gestation, and housed in an adjustable loose housing system (2.4 × 2.3 m) during farrowing and lactation. All the sows were confined in the farrowing crates (0.6 × 2.3 m) for 7 days after the onset of parturition. Saliva samples of sows were collected on days 35, 21, and 7 before farrowing (D-35, D-21 and D7, respectively), and on days 1, 7, and 28 after farrowing (D1, D7, and D28, respectively) to measure the levels of Trolox equivalent antioxidant capacity (TEAC), hydrogen peroxide (H2O2), advanced oxidation protein products (AOPP), and tumor necrosis factor-alpha (TNF-α). Colostrum samples were collected for oxytocin and prolactin assays. Nest-building behavior (NB) for 24 h before parturition and farrowing was observed through video analysis. The results showed that LARGE sows had higher levels of H2O2 on D1 and D7 and AOPP during late gestation (p < 0.05, for all) and lower TEAC levels during late gestation and on D7 and D28 after farrowing (p < 0.05, for all) than NORMAL sows. Additionally, LARGE sows tended to have higher levels of TNF-α on D1 and D7 (p < 0.10, for both). LARGE sows showed shorter duration and lower frequency of NB during 24-12 h before parturition (p < 0.05, for both), and tended to have lower prolactin levels (p = 0.10). Furthermore, large sows tended to show longer farrowing duration and higher stillbirth rate (p = 0.06, p = 0.07, respectively). In conclusion, this study confirmed that large litter size may increase oxidative stress in sows during late gestation and lactation. The data also suggested that this could adversely impact prolactin release, leading to reduced NB.

Plant-made pharmaceuticals: exploring studies for the production of recombinant protein in plants and assessing challenges ahead.

The production of pharmaceutical compounds in plants is attracting increasing attention, as plant-based systems can be less expensive, safer, and more scalable than mammalian, yeast, bacterial, and insect cell expression systems. Here, we review the history and current status of plant-made pharmaceuticals. Producing pharmaceuticals in plants requires pairing the appropriate plant species with suitable transformation technology. Pharmaceuticals have been produced in tobacco, cereals, legumes, fruits, and vegetables via nuclear transformation, chloroplast transformation, transient expression, and transformation of suspension cell cultures. Despite this wide range of species and methods used, most such efforts have involved the nuclear transformation of tobacco. Tobacco readily generates large amounts of biomass, easily accepts foreign genes, and is amenable to stable gene expression via nuclear transformation. Although vaccines, antibodies, and therapeutic proteins have been produced in plants, such pharmaceuticals are not readily utilized by humans due to differences in glycosylation, and few such compounds have been approved due to a lack of clinical data. In addition, achieving an adequate immune response using plant-made pharmaceuticals can be difficult due to low rates of production compared to other expression systems. Various technologies have recently been developed to help overcome these limitations; however, plant systems are expected to increasingly become widely used expression systems for recombinant protein production.

Modern concepts and biomarkers of blood stasis in cardio- and cerebrovascular diseases from the perspectives of Eastern and Western medicine: a scoping review protocol.

OBJECTIVE: The objective of this review is to provide a modern definition and identify potential biomarkers of blood stasis in cardio- and cerebrovascular diseases by mapping, comparing, and combining Eastern and Western concepts. INTRODUCTION: Blood stasis is a pathological concept found in both Eastern and Western medical literature. In traditional East Asian medicine, blood stasis is a differential syndrome characterized by stagnant blood flow in various parts of the body. Similarly, in Western medicine, various diseases, especially cardio- and cerebrovascular diseases, are known to be accompanied by blood stasis. Numerous scientific studies on blood stasis have been conducted over the last decade, and there is a need to synthesize those results. INCLUSION CRITERIA: We will use the keywords "blood stasis," "blood stagnation," "blood stagnant," and "blood congestion" in 3 electronic databases: PubMed, Cochrane CENTRAL, and Google Scholar. In addition, we will use the keywords "어혈" and "혈어" in 4 Korean electronic databases (ie, NDSL, OASIS, KISS, and DBpia). Peer-reviewed articles published from 2010 to the present that focus on blood stasis in cardio- and cerebrovascular diseases in human subjects according to the International Classification of Diseases 11 th revision categories BA00-BE2Z, 8B00-8B2Z, 8E64, and 8E65 will be included. Reviews, opinion articles, in vivo, in vitro, and in silico preclinical studies will be excluded. METHODS: We will follow the frameworks by Arksey and O'Malley and Levac et al. as well as JBI guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Two reviewers will independently search and screen titles and abstracts followed by full-text screening of eligible studies. If there are discrepancies between the 2 reviewers, a third reviewer will be consulted to make the final decision. We will use descriptive narrative, tabular, and graphical displays, and content analysis to present the results. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/gv4ym.

pH-sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosusGG.

The gut microbiome is closely linked to gastrointestinal health and disease status. Oral administration of known probiotic strains is now considered a promising therapeutic strategy, especially for refractory diseases such as inflammatory bowel disease. In this study, we developed a nanostructured hydroxyapatite/alginate (HAp/Alg) composite hydrogel that protects its encapsulated probiotic Lactobacillus rhamnosus GG (LGG) by neutralizing hydrogen ions that penetrate the hydrogel in a stomach without inhibiting LGG release in an intestine. Surface and transection analyses of the hydrogel revealed characteristic patterns of crystallization and composite-layer formation. TEM revealed the dispersal of the nanosized HAp crystals and encapsulated LGG in the Alg hydrogel networks. The HAp/Alg composite hydrogel maintained its internal microenvironmental pH, thereby enabling the LGG to survive for substantially longer. At intestinal pH, the encapsulated LGG was completely released upon disintegration of the composite hydrogel. In a dextran sulfate sodium-induced colitis mouse model, we then assessed the therapeutic effect of the LGG-encapsulating hydrogel. This achieved intestinal delivery of LGG with minimal loss of enzymatic function and viability, ameliorating colitis by reducing epithelial damage, submucosal edema, inflammatory cell infiltration, and the number of goblet cells. These findings reveal the HAp/Alg composite hydrogel as a promising intestinal-delivery platform for live microorganisms including probiotics and live biotherapeutic products.

Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes.

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS: Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION: Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.