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The effects of cauliflower treated with atmospheric cold plasma (ACP), as a natural nitrite source, on the curing of ground ham and nitrosamine formation were investigated. Ground ham was prepared using sodium nitrite and ACP-treated cauliflower powder (PTCP) to achieve initial nitrite concentrations of 60 and 100 mg/kg, respectively. ACP treatment generated nitrite in cauliflower but significantly reduced the antioxidant activity (P < 0.05). As a nitrite source, PTCP had similar effects as sodium nitrite in the development of cured color in ground ham, with a comparable residual nitrite content (P ≥ 0.05). Three nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosopyrrolidine (NPYR), were detected in ground ham. NPYR formation was significantly lower in ground ham treated with PTCP at an initial nitrite concentration of 100 mg/kg (P < 0.05). Therefore, the use of a natural nitrite source manufactured through ACP treatment can prospectively achieve suitable curing efficiency while simultaneously suppressing nitrosamine formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis ( DROSHA , DICER , and AGO2 ) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.

The differences in the proteolytic patterns and shear force of pork and beef during aging were evaluated. Pork and beef semitendinosus muscles were obtained at 24 and 48 h postmortem, respectively, and aged at 4°C for 0 (Day 0), 7 (Day 7), and 14 days (Day 14). Changes in the electrical conductivity were observed in pork on Day 7 and beef on Day 14. The calpain activity increased in pork (p<0.05) after 14 days of aging, whereas that of beef decreased on Day 7 (p<0.05). The cathepsin B activity in pork and beef increased between Day 7 and 14 (p<0.05). The content of α-amino group in the 10% trichloroacetic acid-soluble fraction increased between Day 7 and 14 in pork (p<0.05), but increased steadily in beef throughout aging (p<0.05). The electrophoretogram of the myofibrillar proteins revealed a 30 kDa protein band only in the beef lane on Day 14. The cooked pork had no significant changes in the shear force during aging periods (p>0.05), while the gradual decrease in the shear force with the increasing aging periods was shown in the cooked beef (p<0.05). Circular dichroism analysis of myosin extracts from pork and beef revealed thermal denaturation temperatures of 55°C and 58°C, respectively. This study highlights the different post-mortem proteolytic patterns and thermal denaturation temperatures of myosin in pork and beef semitendinosus muscles, which contribute to distinct changes in the shear force during aging between pork and beef., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Recently, micro/nanorobots (MNRs) with self-propulsion have emerged as a promising smart platform for diagnostic, therapeutic and theranostic applications. Especially, polymer-based MNRs have attracted huge attention due to their inherent biocompatibility and versatility, making them actively explored for various medical applications. As the translation of MNRs from laboratory to clinical settings is imperative, the use of appropriate polymers for MNRs is a key strategy, which can prompt the advancement of MNRs to the next phase. In this review, we describe the multifunctional versatile polymers in MNRs, and their biodegradability, motion control, cargo loading and release, adhesion, and other characteristics. After that, we review the theranostic applications of polymer-based MNRs to bioimaging, biosensing, drug delivery, and tissue engineering. Furthermore, we address the challenges that must be overcome to facilitate the translational development of polymeric MNRs with future perspectives. This review would provide valuable insights into the state-of-the-art technologies associated with polymeric MNRs and contribute to their progression for further clinical development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Optical anisotropy is a fundamental attribute of some crystalline materials and is quantified via birefringence. A birefringent crystal gives rise to not only asymmetrical light propagation but also attenuation along two distinct polarizations, a phenomenon called linear dichroism (LD). Two-dimensional (2D) layered materials with high in-plane and out-of-plane anisotropy have garnered interest in this regard. Mithrene, a 2D metal-organic chalcogenate (MOCHA) compound, exhibits strong excitonic resonances due to its naturally occurring multiquantum well (MQW) structure and in-plane anisotropic response in the blue wavelength (∼400-500 nm) regime. The MQW structure and the large refractive indices of mithrene allow the hybridization of the excitons with photons to form self-hybridized exciton-polaritons in mithrene crystals with appropriate thicknesses. Here, we report the giant birefringence (∼1.01) and the tunable in-plane anisotropic response of mithrene, which stem from its low symmetry crystal structure and strong excitonic properties. We show that the LD in mithrene can be tuned by leveraging the anisotropic exciton-polariton formation via the cavity coupling effect, exhibiting giant in-plane LD (∼77.1%) at room temperature. Our results indicate that mithrene is a polaritonic birefringent material for polarization-sensitive nanophotonic applications in the short wavelength regime.

This study investigated the relationship of carcass characteristics such as hot carcass weight and back fat thickness (BFT) and the pH of s emispinalis capitis (SC) with the cooking loss (CL) of pork shoulder butt and the CL and Warner-Bratzler shear force (WBSF) of belly. BFT was correlated with the CLs of the butt slices ( r s  = -0.30) and the belly slices ( r s  = -0.27 to -0.32). The pH of the SC muscle showed a correlation with the CLs of the butt slices ( r s  = -0.45) and the belly slices of the 6th and 11th thoracic vertebrae ( r s  = -0.28 to -0.33). Additionally, the correlations ( r s  = 0.62 to 0.77) were observed in the CLs among the belly slices. However, the WBSF of the belly slices did not show correlations with others. Therefore, the pH of the SC muscle as well as BFT can be used to obtain information on the CL of shoulder butts and bellies in carcasses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Two-dimensional (2D) semiconductors are promising candidates for optoelectronic application and quantum information processes due to their inherent out-of-plane 2D confinement. In addition, they offer the possibility of achieving low-dimensional in-plane exciton confinement, similar to zero-dimensional quantum dots, with intriguing optical and electronic properties via strain or composition engineering. However, realizing such laterally confined 2D monolayers and systematically controlling size-dependent optical properties remain significant challenges. Here, we report the observation of lateral confinement of excitons in epitaxially grown in-plane MoSe 2 quantum dots (~15-60 nm wide) inside a continuous matrix of WSe 2 monolayer film via a sequential epitaxial growth process. Various optical spectroscopy techniques reveal the size-dependent exciton confinement in the MoSe 2 monolayer quantum dots with exciton blue shift (12-40 meV) at a low temperature as compared to continuous monolayer MoSe 2 . Finally, single-photon emission (g 2 (0) ~ 0.4) was also observed from the smallest dots at 1.6 K. Our study opens the door to compositionally engineered, tunable, in-plane quantum light sources in 2D semiconductors., (© 2024. The Author(s).)

The role of FGF is the least understood of the morphogens driving mammalian gastrulation. Here we investigated the function of FGF in a stem cell model for human gastrulation known as a 2D gastruloid. We found a ring of FGF-dependent ERK activity that closely follows the emergence of primitive streak (PS)-like cells but expands further inward. We showed that this ERK activity pattern is required for PS-like differentiation and that loss of PS-like cells upon FGF receptor inhibition can be rescued by directly activating ERK. We further demonstrated that the ERK-ring depends on localized activation of basally localized FGF receptors (FGFR) by endogenous FGF gradients. We confirm and extend previous studies in analyzing expression of FGF pathway components, showing the main receptor to be FGFR1 and the key ligands FGF2/4/17, similar to the human and monkey embryo but different from the mouse. In situ hybridization and scRNA-seq revealed that FGF4 and FGF17 expression colocalize with the PS marker TBXT but only FGF17 is maintained in nascent mesoderm and endoderm. FGF4 and FGF17 reduction both reduced ERK activity and differentiation to PS-like cells and their derivatives, indicating overlapping function. Thus, we have identified a previously unknown role for FGF-dependent ERK signaling in 2D gastruloids and possibly the human embryo, driven by a mechanism where FGF4 and FGF17 signal through basally localized FGFR1 to induce PS-like cells., Competing Interests: Competing Interests Statement The authors declare no competing interests.

Achieving robust and electrically controlled valley polarization in monolayer transition metal dichalcogenides (ML-TMDs) is a frontier challenge for realistic valleytronic applications. Theoretical investigations show that the integration of 2D materials with ferroelectrics is a promising strategy; however, an experimental demonstration has remained elusive. Here, we fabricate ferroelectric field-effect transistors using a ML-WSe 2 channel and an Al 0.68 Sc 0.32 N (AlScN) ferroelectric dielectric and experimentally demonstrate efficient tuning as well as non-volatile control of valley polarization. We measure a large array of transistors and obtain a maximum valley polarization of ∼27% at 80 K with stable retention up to 5400 s. The enhancement in the valley polarization is ascribed to the efficient exciton-to-trion (X-T) conversion and its coupling with an out-of-plane electric field, viz., the quantum-confined Stark effect. This changes the valley depolarization pathway from strong exchange interactions to slow spin-flip intervalley scattering. Our research demonstrates a promising approach for achieving non-volatile control over valley polarization for practical valleytronic device applications.

Nukadoko, a fermented rice bran employed in traditional Japanese pickling, uses lactic acid bacteria to ferment vegetables. Here, we report the microbial and chemical data of a mixture of matured 150-year-old nukadoko and commercially available rice bran placed in two open environments over 29 days. Across the two environments, Loigolactobacillus was identified as the dominant microbial genera in the later stages of fermentation in nukadoko. The period of increase in the relative abundance of Loigolactobacillus correlated with a decrease in pH and Oxidation-Reduction Potential (ORP) values. While the two environments showed a difference in the rate of change in microbial diversity, they shared the common process through which Loigolactobacillus outcompeted adventitious bacteria in nukadoko, as indicated by the alpha and beta diversity index. Thus, the similarities in microbial and chemical data across two open environments during fermentation using starters indicate that starters contribute to the stability of fermentation in open environments., (© 2024. The Author(s).)

This paper presents the first scanning electron microscopy (SEM)-based DNA imaging in biological samples. This novel approach incorporates a metal-free electro-stain reagent, formulated by combining DNA-binding proteins and synthetic polymers to enhance the visibility of 2-nm-thick DNA under SEM. Notably, DNA molecules stain with proteins and polymers appear as dark lines under SEM. The resulting DNA images exhibit a thickness of 15.0±4.0 nm. As SEM is the primary platform, it integrates seamlessly with various chemically functionalized large surfaces with the aid of microfluidic devices. The approach allows high-resolution imaging of various DNA structures including linear, circular, single-stranded DNA and RNA, originating from nuclear and mitochondrial genomes. Furthermore, quantum dots are successfully visualized as bright labels that are sequence-specifically incorporated into DNA molecules, which highlights the potential for SEM-based optical DNA mapping. In conclusion, DNA imaging using SEM with the novel electro-stain offers electron microscopic resolution with the ease of optical microscopy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Freeze-drying is a preservation method known for its effectiveness in dehydrating food products while minimizing their deterioration. However, protein denaturation and oxidation during freezing and drying can degrade the quality of meat and aquatic products. Therefore, finding the strategies to ensure the dried products' sensory, functional, and nutritional attributes is crucial. This study aimed to summarize protein denaturation mechanisms and overall quality changes in meat and aquatic products during freezing and drying, while also exploring methods for quality control. Different freeze-drying conditions result in varying levels of oxidation and functionality in meat and aquatic products, leading to changes in quality, such as altered fatty and amino acid compositions, protein digestibility, and sensory attributes. To obtain high-quality dried products by freeze-drying, several parameters should be considered, including sample type, freezing and drying temperatures, moisture content, pulverization effects, and storage conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, urban particulate matter (UPM) exposure has been associated with the development of brain disorders. This study uses bioinformatic analyses to elucidate the molecular unexplored mechanisms underlying the effects of UPM exposure on the brain. Mice are exposed to UPM (from 3 days to 20 weeks), and their behavioral patterns measured. We measure pathology and gene expression in the hippocampus and cortical regions of the brain. An integrated interactome of genes is established, which enriches information on metabolic processes. Using this network, we isolate the core genes that are differentially expressed in the samples. We observe cognitive loss and pathological changes in the brains of mice at 16 or 20 weeks of exposure. Through network analysis of core-differential genes and measurement of pathway activity, we identify differences in the response to UPM exposure between the hippocampus and cortex. However, neurodegenerative disease pathways are implicated in both tissues following short-term exposure to UPM. There were also significant changes in metabolic function in both tissues depending on UPM exposure time. Additionally, the cortex of UPM-exposed mice shows more similarities with psychiatric disorders than with neurodegenerative diseases. The connectivity map database is used to isolate genes contributing to changes in expression due to UPM exposure. New approaches for inhibiting or preventing the brain damage caused by UPM exposure can be developed by targeting the functions and selected genes identified in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Existing reviews address bioactive peptides of meat proteins; however, comprehensive reviews summarizing the released sequences and their corresponding parent meat proteins in the digesta are limited. This review explores the bioactive peptides released during the in vitro gastrointestinal (GI) digestion of meat, connecting with parent proteins. The primary bioactivities of meat-derived peptides include angiotensin-converting enzyme (ACE) and dipeptidyl peptidase (DPP)-IV inhibition and antioxidant effects. Myofibrillar, sarcoplasmic, and stromal proteins play a significant role in peptide release during digestion. The release of bioactive peptides varies according to the parent protein and cryptides had short chains, non-toxicity, and great bioavailability and GI absorption scores. Moreover, the structural stability and bioactivities of peptides can be influenced by the digestive properties and amino acid composition of parent proteins. Investigating the properties and origins of bioactive peptides provides insights for enhancing the nutritional quality of meat and understanding its potential health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The efficacy and safety of galacto-oligosaccharides (GOS) in treating functional constipation were evaluated in a four-week randomized, double-blind clinical trial on 63 patients who met Rome IV criteria (34 GOS, 29 placebo group). The number of bowel movements per day and changes in the shape of bowel movements in the treatment group significantly improved compared to those in the control group after four weeks. The Patient Assessment Constipation Quality of Life questionnaire showed that satisfaction with constipation significantly increased in the treatment group. The levels of Bifidobacterium sp. and Lactobacillus sp. significantly increased after four weeks of GOS treatment compared to those measured at baseline. No significant adverse drug reactions were identified in any indicator except for pulse rate. Thus, the prebiotic GOS can be safely used in foods and pharmaceuticals to alleviate symptoms of functional constipation by improving the intestinal flora.

Observation of interlayer, charge transfer (CT) excitons in van der Waals heterostructures (vdWHs) based on 2D-2D systems has been well investigated. While conceptually interesting, these charge transfer excitons are highly delocalized and spatially localizing them requires twisting layers at very specific angles. This issue of localizing the CT excitons can be overcome via making nanoplate-2D material heterostructures (N2DHs) where one of the components is a spatially quantum confined medium. Here, we demonstrate the formation of CT excitons in a mixed dimensional system comprising MoSe 2 and WSe 2 monolayers and CdSe/CdS-based core/shell nanoplates (NPLs). Spectral signatures of CT excitons in our N2DHs were resolved locally at the 2D/single-NPL heterointerface using tip-enhanced photoluminescence (TEPL) at room temperature. By varying both the 2D material and the shell thickness of the NPLs and applying an out-of-plane electric field, the exciton resonance energy was tuned by up to 100 meV. Our finding is a significant step toward the realization of highly tunable N2DH-based next-generation photonic devices.

This study investigated whether the freezing-then-aging treatment of beef affects protein digestibility and release of potentially bioactive peptides using an in vitro infant digestion model. After 28 days of storage, aged-only (AO) and frozen-then-aged (FA) beef exhibited higher α-amino group contents in the 10% trichloroacetic acid-soluble fraction compared to day 0 (P < 0.05). Following in vitro digestion in the infant model, FA showed higher contents of α-amino groups and smaller proteins (<3 and 1 kDa) than day 0 and AO (P < 0.05). Relative contributions of myofibrillar, sarcoplasmic, and stromal proteins to the bioactive peptides released from AO and FA differed from those of day 0. In addition, FA exhibited a higher proportion of potential bioactive peptide sequences. Overall, freezing-then-aging treatment can enhance the potential health benefits of beef to be used as a protein source for complementary foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/aims: The prevalence and incidence of ulcerative colitis (UC) in Korea is increasing. Each patient has a different disease course and treatment response. Recently, with the development of biologic agents, histological remission has become a treatment goal. In this study, we aimed to identify the predictors of histological remission after first-line biologic agent treatment in patients with biologic agent-naïve UC., Methods: We retrospectively analyzed the medical records of 92 patients who had been diagnosed with UC and treated with first-line biologic agent treatment at our center, between 2015 and 2022. The clinical characteristics, laboratory test results, and endoscopic and biopsy findings were analyzed. Histological remission was defined as the absence of cryptitis, crypt abscesses, and inflammatory cells on histology. Univariate and multivariate logistic regression analyses were performed to identify the predictors of histological remission after first-line treatment., Results: Of the total 92 patients, 25 (27.2%) achieved histological remission. Each cohort had a varied body mass index (BMI) distribution, with a statistically significant overweight ratio, as defined by the Asian-Pacific BMI category of 23-25 kg/m2, of 48.0% in the histological remission cohort (P= 0.026). A causal correlation between the overweight category and histological remission was confirmed (odds ratio, 3.883; 95% confidence interval, 1.141-13.212; P= 0.030)., Conclusions: We confirmed that the overweight category was a predictor of histological remission after first-line treatment with a biological agent. However, as BMI does not account for skeletal muscle mass, future studies are required to confirm the correlation between skeletal muscle mass and histological remission.

Active pharmaceutical ingredients (APIs) have gained direct pharmaceutical interest, along with their in vitro properties, and thus utilized as auxiliary solid dosage forms upon FDA guidance and approval on pharmaceutical cocrystals when reacting with coformers, as a potential and attractive route for drug substance development. However, screening and selecting suitable and appropriate coformers that may potentially react with APIs to successfully form cocrystals is a time-consuming, inefficient, costly, and labour intensive task. In this study, we implemented graph neural networks to predict the formation of cocrystals using our first created API coformers interactions graph dataset. We further compared our work with previous studies that implemented descriptor-based models (e.g., random forest, support vector machine, extreme gradient boosting, and artificial neural networks). All built graph-based models show compelling performance accuracies (i.e., 91.36, 94.60 and 95. 95% for GCN, GraphSAGE, and R-GCN respectively). Furthermore, R-GCN prevailed among the built graph-based models because of its capability to learn the topological structure of the graph from the additionally provided information (i.e., non-ionic and non-covalent interactions or link information) between APIs and coformers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To directly compare the radiation and imaging isocenters of a proton treatment machine, we developed and evaluated a real-time radiation isocenter verification system., Methods: The system consists of a plastic scintillator (PI-200, Mitsubishi Chemical Corporation, Tokyo, Japan), an acrylic phantom, a steel ball on the detachable plate, Raspberry Pi 4 (Raspberry Pi Foundation, London, UK) with camera module, and analysis software implemented through a Python-based graphical user interface (GUI). After kV imaging alignment of the steel ball, the imaging isocenter defined as the position of the steel ball was extracted from the optical image. The proton star-shot was obtained by optical camera because the scintillator converted proton beam into visible light. Then the software computed both the minimum circle radius and the radiation isocenter position from the star-shot. And the deviation between the imaging isocenter and radiation isocenter was calculated. We compared our results with measurements obtained by Gafchromic EBT3 film (Ashland, NJ, USA)., Results: The minimum circle radii were averaged 0.29 and 0.41 mm while the position deviations from the radiation isocenter to the laser marker were averaged 0.99 and 1.07 mm, for our system and EBT3 film, respectively. Furthermore, the average position difference between the radiation isocenter and imaging isocenter was 0.27 mm for our system. Our system reduced analysis time by 10 min., Conclusions: Our system provided automated star-shot analysis with sufficient accuracy, and it is cost-effective alternative to conventional film-based method for radiation isocenter verification., (© 2024 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Management of newborns and healthcare workers (HCWs) exposed to congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) has been reported rarely., Aim: To outline a contact investigation process for individuals exposed to congenital TB in the NICU and investigate nosocomial transmission. Additionally, to assess the efficacy and safety of window prophylaxis in exposed newborns., Methods: A baby, born at a gestational age of 28 + 1 weeks, was diagnosed with isoniazid-resistant congenital TB on the 39th day of admission to the level IV NICU. Newborns and HCWs exposed cumulatively for ≥8 h underwent contact investigation and follow-up for a year., Findings: Eighty-two newborns underwent contact investigation. All newborns displayed normal chest X-rays, and 42 hospitalized newborns tested negative for acid-fast bacilli stain and Xpert® MTB/RIF assay in their endotracheal sputum or gastric juices. Eighty received window prophylaxis: six of 75 on rifampin experienced mild adverse events, and none of the five on levofloxacin. After 12 weeks, five (6.1%) had a positive tuberculin skin test, all of whom had already received the Bacillus Calmette-Guérin vaccine and tested negative on TB interferon-gamma releasing assay. Of 119 exposed HCWs, three (2.5%) were diagnosed with latent TB infection and completed a four-month rifampin therapy. There was no active TB disease among exposed newborns and HCWs during a one-year follow-up., Conclusion: Timely diagnosis of congenital TB is crucial for minimizing transmission among exposed neonates and HCWs in the NICU setting. In cases of isoniazid-resistant index patients, even premature newborns may consider the use of rifampin or levofloxacin for window prophylaxis., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H 2 O 2 )-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca 2+ ) influx induced by H 2 O 2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca 2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H 2 O 2 -induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

A robust hybrid visual servoing (HVS) method for a single camera-mounted omnidirectional mobile manipulator (OMM) with kinematic uncertainties caused by slipping is proposed herein. Most existing studies pertaining to the visual servoing of mobile manipulators do not consider the kinematic uncertainties and the singularity of the manipulator that can occur during actual operations; furthermore, they required external sensors other than a single camera. In this study, the kinematics of an OMM are modeled considering kinematic uncertainties. Accordingly, an integral sliding-mode observer (ISMO) is designed to estimate the kinematic uncertainties. Subsequently, an integral sliding-mode control (ISMC) law is proposed to achieve robust visual servoing using the estimates of the ISMO. Additionally, an ISMO-ISMC-based HVS method is proposed to address the singularity issue of the manipulator; this method guarantees both robustness and finite-time stability in the presence of kinematic uncertainties. Overall, the entire visual servoing task is performed using only a single camera attached to the end effector without any other external sensors, unlike in previous studies. The stability and performance of the proposed method are verified numerically and experimentally in a slippery environment that generates kinematic uncertainties.

Context: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption., Objective: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data., Design/setting/participants: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study., Results: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study., Conclusion: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions., Objective: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD., Methods: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7,719 ultrasonography images from 351 patients with GD and 2,980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0&#95;2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image pre-processing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform., Results: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0&#95;2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99., Conclusion: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Localized emission in atomically thin semiconductors has sparked significant interest as single-photon sources. Despite comprehensive studies into the correlation between localized strain and exciton emission, the impacts of charge transfer on nanobubble emission remains elusive. Here, we report the observation of core/shell-like localized emission from monolayer WSe 2 nanobubbles at room temperature through near-field studies. By altering the electronic junction between monolayer WSe 2 and the Au substrate, one can effectively adjust the semiconductor to metal junction from a Schottky to an Ohmic junction. Through concurrent analysis of topography, potential, tip-enhanced photoluminescence, and a piezo response force microscope, we attribute the core/shell-like emissions to strong piezoelectric potential aided by induced polarity at the WSe 2 -Au Schottky interface which results in spatial confinement of the excitons. Our findings present a new approach for manipulating charge confinement and engineering localized emission within atomically thin semiconductor nanobubbles. These insights hold implications for advancing the nano and quantum photonics with low-dimensional semiconductors.

This study investigated the effects of heating temperature of egg white gels (EWGs) on the digestive characteristics by heating egg white (EW) to reach 75 °C (EWG-75) and 95 °C (EWG-95). The gel protein structure showed a decrease in the maximum tryptophan fluorescence intensity and a significant increase in the surface hydrophobicity of EWGs compared to EW (P < 0.05). The total and reactive free sulfhydryl groups were higher in the EWGs than in the EW (P < 0.05). While the proportions of α-helical and β-sheet structures remained similar in EW and EWG-75 (P > 0.05), EWG-95 exhibited a notable decrease in α-helix content (P < 0.05) and an increase in β-sheet content (P < 0.05). Furthermore, EWG-95 displayed higher hardness and cohesiveness than EWG-75 (P < 0.05). In the adult and elderly in vitro digestion models, EWG-95 exhibited the highest protein digestibility (50.44 % and 54.65 % in the models of elderly and adult subjects, respectively) after GI digestion (P < 0.05), followed by EWG-75 and EW. The electrophoretogram of the digesta revealed more intense protein bands in the elderly digestion model, particularly in the gastric digesta of EW, indicating slower digestion compared to the adult model. Therefore, EW should be appropriately heated before consumption, especially for elderly individuals, to facilitate efficient protein digestion and absorption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Genome wide association studies (GWAS) have identified a number of genomic loci that are associated with Parkinson's disease (PD) risk. However, the majority of these variants lie in non-coding regions, and thus the mechanisms by which they influence disease development, and/or potential subtypes, remain largely elusive. To address this, we used a massively parallel reporter assay (MPRA) to screen the regulatory function of 5254 variants that have a known or putative connection to PD. We identified 138 loci with enhancer activity, of which 27 exhibited allele-specific regulatory activity in HEK293 cells. The identified regulatory variant(s) typically did not match the original tag variant within the PD associated locus, supporting the need for deeper exploration of these loci. The existence of allele specific transcriptional impacts within HEK293 cells, confirms that at least a subset of the PD associated regions mark functional gene regulatory elements. Future functional studies that confirm the putative targets of the empirically verified regulatory variants will be crucial for gaining a greater understanding of how gene regulatory network(s) modulate PD risk., (© 2024. The Author(s).)

How paracrine signals are interpreted to yield multiple cell fate decisions in a dynamic context during human development in vivo and in vitro remains poorly understood. Here we report an automated tracking method to follow signaling histories linked to cell fate in large numbers of human pluripotent stem cells (hPSCs). Using an unbiased statistical approach, we discover that measured BMP signaling history correlates strongly with fate in individual cells. We find that BMP response in hPSCs varies more strongly in the duration of signaling than the level. However, both the level and duration of signaling activity control cell fate choices only by changing the time integral. Therefore, signaling duration and level are interchangeable in this context. In a stem cell model for patterning of the human embryo, we show that signaling histories predict the fate pattern and that the integral model correctly predicts changes in cell fate domains when signaling is perturbed. Our data suggest that mechanistically, BMP signaling is integrated by SOX2., (© 2024. The Author(s).)

Diblock copolymer (dBCP) particles capable of dynamic shape and color changes have gained significant attention due to their versatility in programmable shapes and intricate nanostructures. However, their application in photonic systems remains limited due to challenges in achieving a sufficient number of defect-free photonic layers over a tens-of-micrometer scale. In this study, we present a pioneering demonstration of photonic dBCP particles featuring over 300 axially stacked photonic layers with responsive color- and shape-transforming capabilities. Our approach leverages the complex interplay between the macrophase separation of multiple incompatible components and the microphase separation of dBCP from solvent-evaporative microemulsions. Specifically, continuous phase separation of silicone oil from polystyrene- block -poly(2-vinylpyridine) (PS- b -P2VP), triggered by solvent evaporation, promotes the anisotropic growth of PS- b -P2VP layers. This results in the formation of Janus colloids, where an oil droplet merges with a nanostructured polymer cone and lamellar structures align along the long axis of the cone. We highlight the capability to precisely adjust the particle morphology and the corresponding orientation, dispersion, and structural color window by modulating both the molecular weight of PS- b -P2VP and the volume ratio between PS- b -P2VP and silicone oil. Furthermore, reversible swelling/deswelling of photonic colloids is visualized and correlated with their structural colors. Finally, we demonstrate the potential of this study by presenting a multicolor-patterned array of photonic colloids, highlighting the possibilities for applications in smart photonic ink and devices.

This study investigated the effect of temperature control during freeze-drying of beef on the in vitro protein digestibility. Frozen (at - 50 °C for 2 days)-then-aged (at 4 °C for 26 days) beef was freeze-dried at 25 °C (FD1) and 2 °C (FD2) to obtain freeze-dried beef powder. Tryptophan fluorescence intensity and total free sulfhydryl groups of beef myofibrillar proteins decreased (P < 0.05) and increased (P < 0.05) after freeze-drying, respectively. In the myosin fraction of FD2, α-helix increased and β-sheet decreased (P < 0.05) compared to raw beef. In contrast, the actin fraction of FD1 showed a decrease in α-helix and increase in β-sheet (P < 0.05) compared to raw beef. The contents of α-amino group and proteins digested to<3 kDa in the in vitro digesta of beef were retained in FD2 while the α-amino group of FD1 decreased (P < 0.05). Therefore, freeze-drying at 2 °C can efficiently retain in vitro protein digestibility of beef., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

BACKGROUND: Following the WHO???s announcement in 2018, the use of new drugs was recommended for all patients with multidrug-resistant TB (MDR-TB) in Korea. This study aimed to evaluate adherence to new anti-TB drug regimens and implementation of molecular drug susceptibility testing (mDST) in Korea. METHODS: Nationwide, 560 patients were reported as having MDR-TB in 2021. The implementation of mDST and new anti-TB drug use were analysed. The discrepancy between mDST and phenotypic DST (pDST) results and their implications on the use of new anti-TB drugs were also analysed. The use of novel anti-TB drugs has been approved by the National TB Expert Committee. RESULTS: The non-adherence rate in MDR-TB patients was 14.3%. The mDST implementation rate was 96.1%. Of the 459 patients who underwent both mDST and pDST, the discordance rate for rifampicin (RIF) resistance was 22.6% (n = 104), of which 72.1% (n = 75) were resistant on mDST but susceptible on pDST. The discrepancy in mDST and pDST results related to RIF resistance was found to be the main cause of non-adherence to new drug regimen. CONCLUSION: Comprehensive training on how to interpret conflicting results between mDST and pDST could enhance the utilisation of new drugs in the treatment of MDR/RIF-resistant TB.

In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis., (© 2024. The Author(s).)

Background: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake., Methods: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation., Results: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success., Conclusion: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation., (© 2024. The Author(s).)

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group ( p = 0.04), but did not differ by age, sex, or RAI dose ( p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Freezing is commonly used to extend the shelf life of meat and meat products but may impact the overall quality of those products by inducing structural changes in myofibrillar proteins (MPs) through denaturation, chemical modification, and encouraging protein aggregation. This review covers the effect of freezing on the denaturation of MPs in terms of the effects of ice crystallization on solute concentrations, cold denaturation, and protein oxidation. Freezing-induced denaturation of MPs begins with ice crystallization in extracellular spaces and changes in solute concentrations in the unfrozen water fraction. At typical temperatures for freezing meat (lower than -18 °C), cold denaturation of proteins occurs, accompanied by an alteration in their secondary and tertiary structure. Moreover, the disruption of muscle cells triggers the release of cellular enzymes, accelerating protein degradation and oxidation. To minimize severe deterioration during the freezing and frozen storage of meat, there is a vital need to use an appropriate freezing temperature below the glass transition temperature and to avoid temperature fluctuations during storage to prevent recrystallization. Such an understanding of MP denaturation can be applied to determine the optimum freezing conditions for meat products with highly retained sensory, nutritional, and functional qualities.

Biological macromolecules such as proteins and DNA are known to self-assemble into various structural moieties with distinct functions. While nucleic acids are the structural building blocks, peptides exemplify diversity as tailorable biochemical units. Thus, combining the scaffold properties of the biomacromolecule DNA and the functionality of peptides could evolve into a powerful method to obtain tailorable nano assemblies. In this review, we discuss the assembly of non-DNA-coated colloidal NPs on DNA/peptide templates using functional anchors. We begin with strategies for directly attaching metallic NPs to DNA templates to ascertain the functional role of DNA as a scaffold. Followed by methods to assemble peptides onto DNA templates to emphasize the functional versatility of biologically abundant DNA-binding peptides. Next, we focus on studies corroborating peptide self-assembling into macromolecular templates onto which NPs can attach to emphasize the properties of NP-binding peptides. Finally, we discuss the assembly of NPs on a DNA template with a focus on the bifunctional DNA-binding peptides with NP-binding affinity (peptide anchors). This review aims to highlight the immense potential of combining the functional power of DNA scaffolds and tailorable functionalities of peptides for NP assembly and the need to utilize them effectively to obtain tailorable hierarchical NP assemblies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The oxygen vacancy formation behavior and electrochemical and thermal properties of Ba 0.5 Sr 0.5 Fe 1-x Mn x O 3-δ (BSFMnx, x = 0-0.15) cathode materials were investigated. For thermogravimetric analysis, the weight decreased from 1.98% (x = 0) to 1.81% (x = 0.15) in the 400-950 °C range, which was due to oxygen loss from the lattice. The average oxidation state of the B-site increased, the O ads /O lat ratio decreased, and the binding energy of the O lat peak increased with Mn doping. These results indicate that Mn doping increases the strength of the metal-oxygen bond and decreases the amount of oxygen vacancies in the lattice. The electrical conductivity of BSFMnx increased with the temperature due to the thermally activated small-polaron hopping mechanism showing a maximum value of 10.4 S cm -1 (x = 0.15) at 450 °C. The area-specific resistance of BSFMn0.15 was 0.14 Ω cm 2 at 700 °C and the thermal expansion coefficient (TEC) gradually decreased to 12.7 × 10 -6 K -1 , which is similar to that of Ce 0.8 Sm 0.2 O 2 (SDC) (12.2 × 10 -6 K -1 ). Mn doping increased the metal-oxygen bonding energy, which reduced the oxygen reduction reaction activity but improved the electrical conductivity and thermal stability with SDC.

Excess growth hormone (GH) has been implicated in multiple cancer types and there is increasing interest in the development of therapeutic inhibitors targeting GH-GH receptor (GHR) signalling. Here we describe a panel of anti-GH monoclonal antibodies (mAbs) generated using a hybridoma approach and identify two novel inhibitory mAbs (1-8-2 and 1-46-3) that neutralised GH signalling. mAbs 1-8-2 and 1-46-3 exhibited strong inhibitory activity against GH-dependent cell growth in a Ba/F3-GHR cell viability assay, with EC50 values of 1.00 ± 0.27 and 0.5 ± 0.1 µg/mL, respectively. Cross-reactivity with the human placental hormones, placental lactogen (PL) and placental GH, was observed by ELISA, but neither antibody cross-reacted with mouse GH or human prolactin (PRL). mAb 1-8-2 had a binding affinity for GH of KD 0.62 ± 0.5 nM, while mAb 1-46-3 had a KD of 2.68 ± 0.53 nM, as determined by bio-layer interferometry. mAb 1-46-3 inhibited GH-dependent signal transduction in T-47D and LNCaP cancer cell lines and reduced GH-dependent cell growth and migration in the breast cancer cell line T-47D. mAb 1-46-3 inhibited T-47D cell viability more effectively than the GHR antagonist B2036. In conclusion, we describe two novel inhibitory anti-GH mAbs and provide in vitro evidence supporting development of these entities as anti-cancer therapeutics.

BACKGROUND: Linezolid (LZD) is a key treatment option for patients with multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We investigated the long-term treatment outcomes and safety of MDR/RR-TB treatment using low-dose LZD. METHODS: Medical records of patients with MDR/RR-TB treated with LZD ≥4 weeks between 2004 and 2018 at the Asan Medical Center, Seoul, Republic of Korea, were reviewed. Standard-dose and low-dose LZD groups were defined as patients initially administered LZD ≥600 mg/day or 300 mg/day, respectively. RESULTS: Among 94 patients, 65 were included in the low-dose LZD group; mean age was 43.1 ± 15.6 years, 53 (56.4%) were men and 77 (83.7%) were resistant to fluoroquinolone. The low-dose LZD group showed features of less severe disease, such as limited MDR-TB history and less severe radiological findings. There was no difference in treatment outcomes, relapse and safety between groups. In the low-dose LZD group, 54 (83.1%) succeeded treatment, of whom 48 (88.9%) were followed-up for a median of 38 months; there was no recurrence. Adverse drug reactions were reported in 41 (63.1%); peripheral neuropathy was most frequently reported ( n = 31, 47.7%), while myelosuppression was reported in 12 (18.5%). CONCLUSION: Low-dose LZD in selected patients with less severe disease is both effective in the long-term and safe for the treatment of MDR/RR-TB.

MnO 2 and CeO 2 were doped to improve the corrosion resistance of CSZ (calcia-stabilized zirconia), and we studied the phase formation, mechanical properties, and corrosion resistance by molten mold flux. The volume fraction of the monoclinic phase gradually decreased as the amount of MnO 2 doping increased. The splitting phenomenon of the t(101) peak was observed in 2Mn&#95;CSZ, and in 4Mn&#95;CSZ, it was completely split, forming a cubic phase. The relative density increased and the monoclinic phase decreased as the doping amount increased, leading to an increase in Vickers hardness and flexural strength. However, in 3Mn&#95;CSZ and 4Mn&#95;CSZ, where cubic phase formation occurred, the tetragonal phase decreased, leading to a reduction in these properties. MnO 2 -doped CSZ exhibited a larger fraction of the monoclinic phase compared to the original CSZ after the corrosion test, indicating worsened corrosion resistance. These results are attributed to the predominant presence of Mn 3+ and Mn 2+ forms, rather than the Mn 4+ form, which has a smaller basicity difference with SiO 2 , and due to the low melting point. The monoclinic phase fraction decreased as the doping amount of CeO 2 increased in CeO 2 -doped CSZ, but the rate of decrease was lower compared to MnO 2 -doped CSZ. The monoclinic phase decreased as the doping amount increased, but the Vickers hardness and flexural strength showed a decreasing trend due to the low relative density. The destabilization behavior of Ca in SEM-EDS images before and after corrosion was difficult to identify due to the presence of Ca in the slag, and the destabilization behavior of Ce due to slag after corrosion was not observed. In the XRD data of the specimen surface after the corrosion test, the fraction of the monoclinic phase increased compared to before the test but showed a lower monoclinic phase fraction compared to CSZ. It is believed that CeO 2 has superior corrosion resistance compared to CaO because Ce predominantly exists in the form of Ce 4+ , which has a smaller difference in basicity within the zirconia lattice.

This study retrospectively analyzed the treatment outcomes of 110 patients with non-cavitary nodular bronchiectatic-type Mycobacterium avium complex pulmonary disease who received intermittent or daily treatment with a three-drug oral antibiotic regimen (i.e., a macrolide, ethambutol, and rifampin) at a tertiary referral center in South Korea. Among these patients, 36 had sputum smear positivity. Of these 36 patients, intermittent treatment led to a lower culture conversion rate than daily treatment [50.0% (8/16) vs 85.0% (17/20), P = 0.034]., Competing Interests: The authors declare no conflict of interest.

Background: Quality assurance (QA) is a prerequisite for safe and accurate pencil-beam proton therapy. Conventional measurement-based patient-specific QA (pQA) can only verify limited aspects of patient treatment and is labor-intensive. Thus, a better method is needed to ensure the integrity of the treatment plan., Purpose: Line scanning, which involves continuous and rapid delivery of pencil beams, is a state-of-the-art proton therapy technique. Machine performance in delivering scanning protons is dependent on the complexity of the beam modulations. Moreover, it contributes to patient treatment accuracy. A Monte Carlo (MC) simulation-based QA method that reflects the uncertainty related to the machine during scanning beam delivery was developed and verified for clinical applications to pQA., Methods: Herein, a tool for particle simulation (TOPAS) for nozzle modeling was used, and the code was commissioned against the measurements. To acquire the beam delivery uncertainty for each plan, patient plans were delivered. Furthermore, log files recorded every 60 μs by the monitors downstream of the nozzle were exported from the treatment control system. The spot positions and monitor unit (MU) counts in the log files were converted to dipole magnet strengths and number of particles, respectively, and entered into the TOPAS. For the 68 clinical cases, MC simulations were performed in a solid water phantom, and two-dimensional (2D) absolute dose distributions at 20-mm depth were measured using an ionization chamber array (Octavius 1500, PTW, Freiburg, Germany). Consequently, the MC-simulated 2D dose distributions were compared with the measured data, and the dose distributions in the pre-treatment QA plan created with RayStation (RaySearch Laboratories, Stockholm, Sweden). Absolute dose comparisons were made using gamma analysis with 3%/3 mm and 2%/2 mm criteria for 47 clinical cases without considering daily machine output variation in the MC simulation and 21 cases with daily output variation, respectively. All cases were analyzed with 90% or 95% of passing rate thresholds., Results: For 47 clinical cases not considering daily output variations, the absolute gamma passing rates compared with the pre-treatment QA plan were 99.71% and 96.97%, and the standard deviations (SD) were 0.70% and 3.78% with the 3%/3 mm or 2%/2 mm criteria, respectively. Compared with the measurements, the passing rate of 2%/2 mm gamma criterion was 96.76% with 3.99% of SD. For the 21 clinical cases compared with pre-treatment QA plan data and measurements considering daily output variations, the 2%/2 mm absolute gamma analysis result was 98.52% with 1.43% of SD and 97.67% with 2.72% of SD, respectively. With a 95% passing rate threshold of 2%/2 mm criterion, the false-positive and false-negative were 21.8% and 8.3% for without and with considering output variation, respectively. With a 90% threshold, the false-positive and false-negative reduced to 11.4% and 0% for without and with considering output variation, respectively., Conclusions: A log-file-based MC simulation method for patient QA of line-scanning proton therapy was successfully developed. The proposed method exhibited clinically acceptable accuracy, thereby exhibiting a potential to replace the measurement-based dosimetry QA method with a 90% gamma passing rate threshold when applying the 2%/2 mm criterion., (© 2023 American Association of Physicists in Medicine.)

Beef is an ideal protein source for use as a complementary food in infants. Considering the limited protein-digesting capacity of infants, it is required to enhance protein digestibility while minimizing the deterioration of beef quality. Thus, this study aimed to determine the effects of high-pressure processing (HPP) on the physicochemical properties and in vitro digestibility of beef proteins in an infant digestion model. HPP at 200 and 300 MPa decreased the tryptophan fluorescence intensity of the myosin and actin fractions relative to that at 0.1 MPa (P < 0.05). Compared to treatment at 0.1 and 100 MPa, HPP at 300 MPa decreased α-helix and β-turn contents in the myosin and actin fractions (P < 0.05), whilst increasing the β-sheet content (P < 0.05). Beef actomyosin content decreased (P < 0.05) during HPP at 200 and 300 MPa (c.f., 0.1 and 100 MPa). After in vitro digestion of beef, HPP at 200 and 300 MPa increased the α-amino group content and the abundance of proteins below 3 kDa in the digesta (P < 0.05). However, due to the considerable lipid oxidation at 300 MPa, HPP at 200 MPa is ideal for improving the protein digestibility of beef when incorporated into complementary foods for infants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Although lettuce is traditionally known to have hypnotic and sedative effects, to date, only a few studies have documented its sleep-promoting effects and elucidated the related mechanisms., Aim of the Study: We aimed to investigate the sleep-promoting activity of Heukharang lettuce leaf extract (HLE) with increased lactucin content, known as a sleep-promoting substance in lettuce, in animal models., Materials and Methods: To evaluate the effect of HLE on sleep behavior, analysis of electroencephalogram (EEG), gene expression of brain receptors, and activation mechanisms using antagonists were investigated in rodent models., Results: High-performance liquid chromatography analysis showed that HLE contained lactucin (0.78 mg/g of extract) and quercetin-3-glucuronide (1.3 mg/g of extract). In the pentobarbital-induced sleep model, the group administered 150 mg/kg of HLE showed a 47.3% increase in sleep duration time as compared to the normal group (NOR). The EEG analysis showed that the HLE significantly increased non-rapid eye movement (NREM), where delta waves were improved by 59.5% when compared to the NOR, resulting in increased sleep time. In the caffeine-induced arousal model, HLE significantly decreased the awake time increased by caffeine administration (35.5%) and showed a similar level to NOR. In addition, HLE increased the gene and protein expression of gamma-aminobutyric acid receptor type A (GABA A ), GABA type B, and 5-hydroxytryptamine (serotonin) receptor 1A. In particular, in comparison to the NOR, the group administered 150 mg/kg HLE showed an increase in expression levels of GABA A and protein by 2.3 and 2.5 times, respectively. When the expression levels were checked using GABA A receptor antagonists, HLE showed similar levels to NOR, as the sleep duration was reduced by flumazenil (45.1%), a benzodiazepine antagonist., Conclusions: HLE increased NREM sleep and significantly improved sleep behavior due to its action on the GABA A receptors. The collective findings suggest that HLE can be used as a novel sleep-enhancing agent in the pharmaceutical and food industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, concentration levels of beet powder (BP) and caramel color (CC) were optimized to simulate beef color in meat analogs before and after cooking. The central composite design of response surface methodology (RSM) was used to set the levels of BP and CC, and the CIE L*, CIE a*, and CIE b* were selected as the responses for RSM. After optimization, myoglobin-free beef patties were prepared with three optimized levels of BP and CC. When raw, all the patties had the same color as natural beef; however, CIE L*, CIE a*, and CIE b* were statistically different from those of beef after cooking (p<0.05). Moreover, the use of BP and CC induced "browning" after the cooking process, with no excessive yellow color. Therefore, based on the overall desirability in the color optimization using RSM, the combination of BP (1.32%) and CC (1.08%) with the highest overall desirability can be used to simulate the color change of beef in meat analogs., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Blood shortages for transfusion are global issues of grave concern. As in vitro manufactured platelets are promising substitutes for blood donation, recent research has shown progresses including different cell sources, different bioreactors, and three-dimensional materials. The first-in-human clinical trial of cultured platelets using induced pluripotent stem cell-derived platelets began in Japan and demonstrated its quality, safety, and efficacy. A novel bioreactor with fluid motion for platelet production has been reported. Herein, we discuss various cell sources for blood cell production, recent advances in manufacturing processes, and clinical applications of cultured blood., (© 2023 American Institute of Chemical Engineers.)

Growth hormone (GH) actions are mediated through binding to its cell-surface receptor, the GH receptor (GHR), with consequent activation of downstream signalling. However, nuclear GHR localisation has also been observed and is associated with increased cancer cell proliferation. Here we investigated the functional implications of nuclear translocation of the GHR in the human endometrial cancer cell-line, RL95-2, and human mammary epithelial cell-line, MCF-10A. We found that following GH treatment, the GHR rapidly translocates to the nucleus, with maximal localisation at 5-10 min. Combined immunoprecipitation-mass spectrometry analysis of RL95-2 whole cell lysates identified 40 novel GHR binding partners, including the transcriptional regulator, HMGN1. Moreover, microarray analysis demonstrated that the gene targets of HMGN1 were differentially expressed following GH treatment, and co-immunoprecipitation showed that HMGN1 associates with the GHR in the nucleus. Therefore, our results suggest that GHR nuclear translocation might mediate GH actions via interaction with chromatin factors that then drive changes in specific downstream transcriptional programs., (© 2023. The Author(s).)