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Fermi bubbles are giant gamma-ray structures extended north and south of the Galactic center with characteristic sizes of the order of 10 kpc discovered by the Fermi Large Area Telescope. Good correlation between radio and gamma-ray emission in the region covered by Fermi bubbles implies the presence of high-energy electrons in this area. Due to high energy losses it is rather problematic to transfer relativistic electrons from the Galactic disk toward the Fermi bubbles. Therefore it is natural to assume that these electrons are accelerated in-situ. Additionally this acceleration mechanism should also affect protons. In particular it may re-accelerate Galactic cosmic rays produced by supernova remnants. Unlike electrons, protons have huge life-times and therefore re-acceleration should not be a local effect but affect the whole Galaxy. The effect may even be observed near the Earth. In our model we propose that hadronic cosmic rays (CR) below the “knee” of the observed CR spectrum are produced by Galactic supernova remnants distributed in the Galactic disk. Re-acceleration of these particles in Fermi Bubbles produces CRs above the knee. This model provides a natural explanation of the observed CR flux, spectral indices, and matching of spectra at the knee.

In order to assess the potential of fractionated Schizochytrium sp. protein as functional proteins, the proteins were fractionally extracted. The structure, thermal characteristic and cross-linking interaction of proteins, along with the gel properties of heat-induced gels were analyzed and compared to those of albumin from chicken egg white (ACEW). Water fraction of Schizochytrium sp. protein (WFSP) was identified as the dominant fractionated protein. Classified as globular proteins, WFSP exhibited a molecular weight range of 30-250 kDa. Compared to ACEW, WFSP displayed a significantly lower denaturation temperature, indicating reduced energy consumption during food processing. Moreover, at a concentration of 50 g/L, WFSP gels displayed superior strength and stability by higher G' (114.7 kPa) and fracture strain (2.38 %) compared to ACEW gels (92.2 kPa and 1.33 %). Besides, WFSP gels had lower hardness, chewiness and water holding capacity, but higher springiness and cohesiveness than ACEW gels. WFSP formed porous particulate stranded three-dimensional gel network structures with uniform pore size, flat surface and complete sheet. The temperature sweeps and protein-protein interactions results suggested that hydrogen bonds played a dominant role in the formation of WFSP gel network. Overall, WFSP exhibits excellent gelation properties and holds promise as a functional protein for food production., 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 B.V.)

Background: Smokeless Tobacco (SLT) use prevalence among youth in the United States (US) is comparable to youth prevalence of cigarette smoking. However, it is in general understudied compared to cigarettes and draws less attention nowadays compared to e-cigarettes (ECs)., Aim: We estimate the own- and cross-tax elasticities of SLT use among US youth and explicitly test how SLT use changes in response to taxes on SLT, cigarettes, ECs, and beer., Methods: We standardized SLT taxes for chewing tobacco, moist snuff, dry snuff, and snus, and computed average SLT taxes. We implemented a logit regression model within the state- and year-fixed effects framework., Results: A 10 % increase in SLT excise taxes reduced youth SLT use by 4 % (p < 0.01). This result is primarily driven by males, Whites, multiple non-Hispanic races, other races, and individuals living in non-Appalachian states. In addition, a 10 % increase in cigarette taxes increases youth SLT use by 8 % (p < 0.05), suggesting substitutional effects. A 10 % increase in EC and beer taxes reduce SLT use by 0.5 % and 2.4 % (p < 0.01), respectively, suggesting complementary effects., Conclusion: Raising excise taxes on SLT products can effectively curtail their usage among the youth population. Furthermore, increasing EC and beer taxes reduces youth SLT use. However, an increase in cigarette taxes leads to an unintended consequence of promoting SLT use among youth. In addition, increasing SLT taxes does not appear to significantly impact the disparities in youth SLT use by whether living in Appalachian states. Future research is needed to assess whether SLT taxes reduce disparities in use by rural/urban divisions., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The invasion of luminal antigens and an aberrant immune response resulting from a disrupted physical epithelial barrier are the key characteristics of ulcerative colitis (UC). The restoration of damaged epithelial function is crucial for maintaining mucosal homeostasis and disease quiescence. Current therapies for UC primarily focus on suppressing inflammation. However, most patients fail to respond to therapy or develop secondary resistance over time, emphasizing the need to develop novel therapeutic targets for UC. Our study aimed to identify the potential targets of a novel modified herbal formula from the Zhen Wu Decoction, namely CDD-2103, which has demonstrated promising efficacy in treating chronic colitis., Methods: The effect of CDD-2103 on epithelial barrier function was examined using in vitro and ex vivo models of tissue injury, as well as a chronic colitis C57BL/6 mouse model. Transcriptomic analysis was employed to profile gene expression changes in colonic tissues following treatment with CDD-2103., Results: Our in vivo experiments demonstrated that CDD-2103 dose-dependently reduced disease severity in mice with chronic colitis. The efficacy of CDD-2103 was mediated by a reduction in goblet cell loss and the enhancement of tight junction protein integrity. Mechanistically, CDD-2103 suppressed epithelial cell apoptosis and tight junction protein breakdown by activating the soluble guanynyl cyclase (sGC)-mediated cyclic guanosine monophosphate (cGMP)/PKG signaling cascade. Molecular docking analysis revealed strong sGC ligand recognition by the CDD-2103-derived molecules, warranting further investigation., Conclusion: Our study revealed a novel formulation CDD-2103 that restores intestinal barrier function through the activation of sGC-regulated cGMP/PKG signaling. Furthermore, our findings suggest that targeting sGC can be an effective approach for promoting mucosal healing in the management of UC., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Current occupational recommendations limit fetal radiation dose to 1 mSv. With increased gender diversity in urology, understanding radiation exposure during pregnancy is crucial. The purpose of this study was to determine surgeon uterine radiation dose during percutaneous nephrolithotomy (PCNL) and compare effectiveness of several radiation reduction strategies in a cadaver model., Materials and Methods: Two cadavers were used to simulate the surgeon and the patient in a PCNL model. An ion chamber was placed behind the surgeon's anterior uterine wall to measure the radiation dose. Three radiation reduction methods were compared: pulsed fluoroscopy (1, 4, 8, 15, 30 pps), low-dose (LD) fluoroscopy, and surgeon shielding (none, 0.35-, 0.50-, 0.70-mm lead equivalents). The average radiation dose per second was recorded for 20 trials per combination. Assuming 5 minutes of fluoroscopy per PCNL, the number of cases required to exceed the fetal occupational limit was determined., Results: Decreasing pulse frequency from 30 to 1 pps reduced the dose by 96% ( P < .001). The LD setting decreased the dose by 56% ( P < .001). A 0.35-mm lead apron resulted in a 94% dose reduction ( P < .001), and the 0.50- and 0.70-mm lead aprons further reduced the dose by 12% and 47%, respectively. In conventional fluoroscopy settings of automatic exposure control and at 30 pps, a surgeon could perform 12 PCNLs using no lead or 189 PCNLs using a 0.35-mm lead apron before reaching the 1 mSv limit. In addition to shielding, using 1 pps with LD fluoroscopy further decreased radiation exposure, allowing over 6000 cases to be performed with < 1 mSv uterine radiation exposure., Conclusions: Within the limitations of this cadaver study, these data support that high-volume pregnant surgeons using active radiation reduction techniques such as pulsed fluoroscopy, LD fluoroscopy, and appropriate shielding can maintain surgical volume with relatively low risk. Fetal dosimeter use with monthly monitoring is still encouraged to confirm safety throughout pregnancy.

This study aimed to develop complex coacervates utilizing lactoferrin (LF) and chia seed mucilage (CSM) for promoting intestinal delivery of quercetin (Q) and fortification of set yogurt. Three cross-linkers, including calcium chloride (CC), transglutaminase (TG), and polyphenolic complex (HP), were used to further reinforce the coacervate network. Cross-linked coacervates had higher values of coacervate yield, encapsulation efficiency, and loading capacity. They efficiently preserved Q under gastric condition (⁓87%-99%), with CSM-TG-Q-LF being most effective for intestinal delivery of Q. Moreover, digested pellets of the cross-linked coacervates displayed better antioxidant activity than the uncross-linked coacervates with CSM-TG-Q-LF pellets showing maximum bioactivity. The Q-loaded coacervates demonstrated superior assembly in the yogurt matrix compared to the unencapsulated Q. Moreover, the coacervate systems, especially CSM-TG-Q-LF significantly improved the textural properties of yogurt and the stability of Q in it. Therefore, CSM-TG-LF is a promising carrier to promote intestinal delivery and food application of hydrophobic molecules., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Children with vesicoureteral reflux (VUR), particularly high-grade VUR, are known to be at increased risk for urinary tract infection (UTI). Current guidelines highlight certain clinical factors in the management of children with VUR; however, the clinical utility of upper tract dilation in the setting of VUR remains unclear., Objective: The purpose of this study is to evaluate risk factors for febrile UTI (fUTI) in children with primary VUR in a modern cohort with emphasis on upper tract dilation parameters, including hydronephrosis and hydroureter., Methods: A prospectively maintained database of children with VUR at a single academic institution from July 2013 to February 2023 was reviewed. Demographic and clinical data were included. Ultrasounds closest to initial VCUG were reviewed for upper tract dilation, including the presence of hydronephrosis, Society of Fetal Urology (SFU) hydronephrosis grade, presence of hydroureter, and anterior-posterior renal pelvic diameter (APRPD). The primary outcome of interest was the development of a fUTI after VUR diagnosis. Patients were censored after their first fUTI or after VUR surgery., Results: A total of 235 children with primary VUR were evaluated, including 125 (53.2 %) females and 110 (46.8 %) males. The median age of VUR diagnosis was 10.8 months (IQR: 2.3-63.6 months). A total of 41 (17.4 %) children developed a fUTI after VUR diagnosis with a median follow up of 2.3 years (IQR: 0.9-4.6 years). On univariate analysis, variables found to be associated with fUTI included age <1 year at VUR diagnosis (p = 0.021), female sex (p = 0.013), high-grade VUR (p = 0.024), APRPD ≥7 mm (p = 0.007), high-grade hydronephrosis (p = 0.004), presence of hydronephrosis (p = 0.029), and hydroureter (p = 0.008). In children with VUR and high-grade hydronephrosis, a larger APRPD was associated with higher fUTI rates (p = 0.008). On multivariate analysis controlling for age, sex, and VUR grade, APRPD ≥7 mm (OR 2.8, p = 0.009), high-grade hydronephrosis (OR 2.5, p = 0.025), and presence of hydronephrosis (OR 2.3, p = 0.049) were independent risk factors for fUTI. On multivariate models controlling for other upper tract dilation parameters, APRPD ≥7 mm was the most significant parameter associated with increased fUTI risk in primary VUR., Conclusion: Upper tract dilation is a novel, independent risk factor for fUTI in children with primary VUR, with APRPD being the strongest predictor. Clinicians may consider upper tract dilation parameters in addition to age, sex, and VUR grade when individualizing care in children with primary VUR., Competing Interests: Conflict of interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The thulium fiber laser (TFL) generates a focused beam, which can be transmitted to laser fibers with small core diameters and may facilitate in situ lower-pole lithotripsy. This study compares lithotripsy performance of the 150 and 200 µm TFL in a lower pole benchtop kidney model. Materials and Methods: Using a 3D model printed from an actual kidney, in situ laser lithotripsy was performed on 1 cm lower-pole BegoStones (calcium oxalate monohydrate consistency) using four different settings (all 20W) and two fiber sizes (150 and 200 µm). Procedure time, laser time, total pulse energy, and fiber stripping were compared between the two fibers using an ANOVA or independent t-test . Results: The 150 µm fiber at 0.2 J × 100 Hz had the shortest lasing and procedure time (17.3 and 18.5 minutes) and lowest total pulse energy (20.75 kJ) compared with other study arms ( p < 0.001). Overall procedure time, lasing time, and total pulse energy were significantly different between the 8 settings ( p < 0.001 for all). At higher frequency (100 and 200 Hz), lasing time was significantly faster compared with 20 and 50 Hz (19.9 vs 27.3 minutes; p < 0.001). Furthermore, the average total procedure time was shorter with 150 µm compared with 200 µm regardless of settings (23.2 vs 29.8 minutes; p < 0.001). Conclusion: The 150 µm fiber results in shorter procedure and lasing time at lower total energy levels during lower-pole in situ lithotripsy. Overall, the fastest setting was 0.2 J and 100 Hz with the 150 µm fiber. Smaller laser fibers can potentially allow more efficient in situ laser lithotripsy with better irrigation and visibility at higher deflection angles.

In the last decades, many publicly available large fundus image datasets have been collected for diabetic retinopathy, glaucoma, and age-related macular degeneration, and a few other frequent pathologies. These publicly available datasets were used to develop a computer-aided disease diagnosis system by training deep learning models to detect these frequent pathologies. One challenge limiting the adoption of a such system by the ophthalmologist is, computer-aided disease diagnosis system ignores sight-threatening rare pathologies such as central retinal artery occlusion or anterior ischemic optic neuropathy and others that ophthalmologists currently detect. Aiming to advance the state-of-the-art in automatic ocular disease classification of frequent diseases along with the rare pathologies, a grand challenge on "Retinal Image Analysis for multi-Disease Detection" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2021). This paper, reports the challenge organization, dataset, top-performing participants solutions, evaluation measures, and results based on a new "Retinal Fundus Multi-disease Image Dataset" (RFMiD). There were two principal sub-challenges: disease screening (i.e. presence versus absence of pathology - a binary classification problem) and disease/pathology classification (a 28-class multi-label classification problem). It received a positive response from the scientific community with 74 submissions by individuals/teams that effectively entered in this challenge. The top-performing methodologies utilized a blend of data-preprocessing, data augmentation, pre-trained model, and model ensembling. This multi-disease (frequent and rare pathologies) detection will enable the development of generalizable models for screening the retina, unlike the previous efforts that focused on the detection of specific diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effectiveness of magic-themed interventions in improving daily bimanual task performance in children with unilateral spastic cerebral palsy (CP) and to elucidate the variability in outcomes., Method: This systematic literature review searched databases including Embase, MEDLINE, Scopus, Cochrane Central, and CINAHL. Outcome measures selected for the meta-analysis included the Children's Hand-use Experience Questionnaire, its three subscales, and the Besta subscale C. The overall efficacy of magic-themed interventions was analysed using Hedges' g as the summary measure for these outcomes. Subgroup analysis compared the efficacy of different modes of training, and a meta-regression investigated the impact of training duration., Results: Analyses of four studies involving 78 children showed magic-themed training significantly improved bimanual task performance (Hedges' g = 0.327, 95% confidence interval [CI] = 0.107-0.547, p = 0.004), especially in group settings (Hedges' g = 0.435, 95% CI = 0.176-0.693, p = 0.001), compared with non-significant gains from video interventions (Hedges' g = 0.041, 95% CI = -0.380 to 0.462, p = 0.850). Additionally, training duration positively correlated with performance gains (coefficient = 0.0076 per hour, p = 0.001)., Interpretation: Magic-themed training, especially through group sessions and extended durations, enhances bimanual skills in children with unilateral spastic CP., (© 2024 Mac Keith Press.)

Tumor cell-induced platelet aggregation (TCIPA) is a mechanism for the protection of tumor cells in the bloodstream and the promotion of tumor progression and metastases. The platelet C-type lectin-like receptor 2 (CLEC-2) can bind podoplanin (PDPN) on a cancer cell surface to facilitate TCIPA. Selective blockage of PDPN-mediated platelet-tumor cell interaction is a plausible strategy for inhibiting metastases. In this study, we aimed to screen for aptamers, which are the single-stranded DNA oligonucleotides that form a specific three-dimensional structure, bind to specific molecular targets with high affinity and specificity, bind to PDPN, and interfere with PDPN/CLEC-2 interactions. The systematic evolution of ligands by exponential enrichment (SELEX) was employed to enrich aptamers that recognize PDPN. The initial characterization of ssDNA pools enriched by SELEX revealed a PDPN aptamer designated as A1 displaying parallel-type G-quadruplexes and long stem-and-loop structures and binding PDPN with a material with a dissociation constant (K d ) of 1.3 ± 1.2 nM. The A1 aptamer recognized both the native and denatured form of PDPN. Notably, the A1 aptamer was able to quantitatively detect PDPN proteins in Western blot analysis. The A1 aptamer could interfere with the interaction between PDPN and CLEC-2 and inhibit PDPN-induced platelet aggregation in a concentration-dependent manner. These findings indicated that the A1 aptamer is a candidate for the development of biosensors in detecting the levels of PDPN expression. The action by A1 aptamer could result in the prevention of tumor cell metastases, and if so, could become an effective pharmacological agent in treating cancer patients.

To investigate the impact of extrusion parameters on the formation of N ε -(carboxymethyl)lysine (CML), N ε -(carboxyethyl)lysine (CEL) and acrylamide in plant-based meat analogues (PBMAs), the content changes and the correlations of compounds related to their formation were studied. The extrusion promoted CML, CEL and acrylamide formation, with more CEL being formed than CML. Variations in the moisture level and barrel temperature exerted a greater influence on the CML, CEL, acrylamide and α-dicarbonyl compounds than the screw speed and the feed rate. An increase in the moisture content led to a decrease in the CEL content, whereas it enhanced CML formation. The impact of moisture on acrylamide formation varied depending on whether low- or high-moisture extrusion was applied. Elevated temperatures promoted the accumulation of CEL, methylglyoxal and 2,3-butanedione while diminishing the accumulation of CML, acrylamide, glyoxal and 3-deoxyglucosone. CML and CEL were positively correlated with glyoxal and methylglyoxal, respectively. CEL and methylglyoxal were negatively correlated with protein and water content, whereas CML, glyoxal and 3-deoxyglucosone displayed positive correlations. In summary, higher moisture levels and feed rates and lower screw speeds and barrel temperatures are advantageous for producing PBMAs with lower CEL and total advanced glycation end-products contents, while lower or higher moisture contents, a lower feed rate and a higher barrel temperature are beneficial to reducing the acrylamide content.

Baked oyster is a popular seafood dish around the world. The present study investigated the effect of various concentrations of a green-tea extract (GTE) marinade on the safety and sensory profiles of oysters baked for different durations. The results showed 10 g/L of GTE and 10-min baking time was the optimal combination, as supported by significantly attenuated lipid oxidation (35.29 %) and N ε -(carboxyethyl)lysine (CEL) content (48.51 %) without appreciable negative impact on the sensory or nutritional quality of the oysters. However, high concentrations of the marinade or prolonged baking promoted protein oxidation and N ε -(carboxymethyl)lysine (CML) formation likely through the pro-oxidative action of the GTE phytochemicals. Correlation analysis further revealed the main factors that affected CML, CEL, and fluorescent AGEs generation, respectively. These findings provide theoretical support for the protective effect and mechanism of GTE against quality deterioration of baked oysters and would help broaden the application of GTE in the food industry., 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.)

Backgrounds: The efficacy of medium-chain triglycerides (MCTs) for weight management and mitigating metabolic disorders among individuals with overweight and obesity remains a topic of ongoing discussion. Notably, there is a gap in the distinction between pure MCTs and medium-long-chain triglycerides (MLCTs)., Methods: This meta-analysis investigates the efficacy of MCTs on weight loss and glucolipid metabolism in these populations, explicitly evaluating the differential effects of pure MCTs and MLCTs. We performed a random-effects meta-analysis on relevant studies examining weight loss and glucolipid parameters, incorporating a subgroup analysis conducted based on intervention types, pure MCTs versus MLCTs., Results: Our findings revealed diets enriched with MCTs are more effective in achieving weight reduction (WMD: -1.53%; 95% CI: -2.44, -0.63; p < 0.01), particularly those containing pure MCTs (WMD: -1.62%; 95% CI: -2.78, -0.46; p < 0.01), compared to long-chain fatty acids (LCTs) enriched diets. However, our subgroup analysis indicates that an MLCTs-enriched diet did not significantly reduce weight loss. Additionally, MCTs-enriched diets were associated with significant reductions in blood triglyceride levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores, compared to LCTs-enriched diets., Conclusions: Hence, the authors recommend incorporating pure MCTs in dietary interventions for individuals with overweight and obesity, particularly those with comorbidities such as dyslipidemia and impaired glucose metabolism., Competing Interests: Conflict of interest The authors reported no potential conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: CDD-2103 is an herbal prescription used to treat ulcerative colitis (UC). This study aimed to uncover its mechanism by integrating metabolomics and serum-feces pharmacochemistry-based network pharmacology., Methods: A DSS-induced chronic colitis mice model was used to evaluate the anti-colitis effect of CDD-2103. Serum and feces metabolomics were conducted to identify differential metabolites and pathways. In the serum-feces pharmacochemistry study, biological samples were collected from rats treated with CDD-2103. Then, network pharmacology was utilized to predict the targets of the identified compounds. Critical genes were extracted through the above-integrated analysis. The interactions between targets, CDD-2103, and its compounds were validated through molecular docking, immunoblotting, and enzyme activity assays., Results: CDD-2103 alleviated ulcerous symptoms and colonic injuries in colitis mice. Metabolomics study identified differential metabolites associated with tryptophan, glycerophospholipid, and linoleic acid metabolisms. The serum-feces pharmacochemistry study revealed twenty-three compounds, which were subjected to network pharmacology analysis. Integration of these results identified three key targets (AHR, PLA2, and PTGS2). Molecular docking showed strong affinities between the compounds and targets. PTGS2 was identified as a hub gene targeted by most CDD-2103 compounds. Immunoblotting and enzyme activity assays provided further evidence that CDD-2103 alleviates UC, potentially through its inhibitory effect on cyclooxygenase-2 (COX-2, encoded by PTGS2), with alkaloids and curcuminoids speculated as crucial anti-inflammatory compounds., Conclusion: This integrated strategy reveals the mechanism of CDD-2103 and provides insights for developing herbal medicine-based therapies for UC., Competing Interests: Declaration of competing interest All authors have claimed no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: While retail sales and retailer inspection studies generally indicate high compliance with state sales restrictions on Nicotine Vaping Products (NVPs) within the restricted area, studies using survey data generally indicate that most users could readily continue gaining access to restricted NVPs. Our study bridges a gap in the current literature and investigates the potential role of cross-state border purchases to evade state emergency NVP sales restrictions in 2019., Aims and Methods: The study sample was restricted to NVP sales from the states neighboring Massachusetts, Rhode Island, and Washington, three states that implemented all NVP or flavored NVP sales restrictions in 2019. Among these neighboring states, the 2019 weekly county-level NVP sales by flavors (tobacco, mint/menthol, and other flavors) were compiled using Nielsen Scanner data. A quasi-experimental, comparison group pre-post study design was used to study the impacts of NVP sales restrictions on cross-state border NVP purchases., Results: Weekly NVP sales for border counties significantly increased in response to the MA, RI, and WA bans for tobacco flavored (56%, 45%, 14%, respectively), menthol/mint flavored (51%, 2%, 41%, respectively), and other flavored (79%, 3%, 4%, respectively) products, compared to sales for non-border counties (all p-values < .01)., Conclusions: Our study identified significant cross-state border NVP purchases in all studied states to circumvent NVP emergency sales restrictions in response to the EVALI outbreak. Policymakers should factor in these purchasing behaviors to evade sales restrictions when evaluating any future potential policies at the state or local levels., Implications: While retail sales data and retailer inspections indicate high compliance with Nicotine Vaping Product (NVP) flavor sales restrictions from major retail outlets, survey data obtain mixed findings on the effects of sales restrictions on vaping behaviors. Our study identified a significant increase in cross-state border NVP purchases to circumvent NVP sales restrictions in 2019, consistent across all three settings of Massachusetts, Rhode Island, and Washington. Policymakers should factor in these cross-state border NVP purchases in response to sales restrictions when evaluating any future potential NVP sales restrictions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. 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.)

The modification of starch digestibility can be achieved through the formation of complexes with polyphenols. We studied the combined impacts of ultrasound and high-pressure homogenization (UT-HPH) on the structure and in vitro digestibility of rice starch-chlorogenic acid complexes. The development of V-type complexes was supported by our findings, which also showed that synergistic UT-HPH therapy exhibited the highest absorbance value for the complexing index (0.882). Significant alterations in digestibility were also observed in the complexes, with the content of RDS decreasing from 49.27% to 27.06%, the content of slowly SDS increasing from 25.69% to 35.35%, and the percentage of RS increasing from 25.05% to 37.59%. Furthermore, a high positive correlation was found by applying the Pearson correlation coefficient in our research between RS, weight, PSD, and CI. This study presents a sustainable processing approach for utilizing chlorogenic acid in starch-rich food systems., 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.)

Background: Ulcerative colitis (UC) is associated with intestinal macrophage infiltration due to disruption of the mucosal barrier and bacterial invasion. Therefore, it is crucial to identify therapeutic agents capable of attenuating the macrophage-induced inflammatory response to preserve mucosal homeostasis and immune tolerance. The modified Zhenwu decoction (CDD-2103) is a novel herbal formulation developed based on the principles of Traditional Chinese medicine. To date, there are no clinically approved herbal formulations for UC with a well-known mechanism of action on macrophages., Purpose: The objective of this study was to systematically investigate the inhibitory effect of the active fraction of CDD-2103 in a mouse model of chronic colitis and delineate the mechanisms underlying its inhibitory action., Methods: CDD-2103 was extracted into four fractions using organic solvents with increasing polarity. A chronic 49-day dextran sulfate sodium (DSS)-induced colitis mice model, closely resembling human clinical conditions, was used to examine the effect of CDD-2103 on chronic colitis. To confirm the effect of CDD-2103 on macrophages in this chronic colitis model, adoptive macrophage transfer and CCL2 supplementation were conducted. The mechanisms of action of CDD-2103 were further elucidated utilizing bone marrow-derived macrophages (BMDMs). Transcriptome analysis was conducted to gain insights into the underlying mechanism of action of CDD-2103 in BMDMs., Results: Our in vitro and in vivo findings demonstrated that the ethanol-enriched fraction of CDD-2103 exhibited significant anti-inflammatory effects, leading to the suppression of colitis severity. This effect was associated with diminished accumulation of colonic macrophages in the lamina propria of CDD-2103-intervened colitis mice. Specifically, CDD-2103 inhibited CCR2/L2-mediated proinflammatory macrophage infiltration into the colon without affecting macrophage proliferation. Mechanistically, CDD-2103 inhibited Fyn expression-mediated p38 MAPK activation and subsequently suppressed CCR2 expression in BMDMs., Conclusions: Collectively, our study supports the potential use of CDD-2103 to limit macrophage infiltration, thereby reducing inflammation during UC treatment. CDD-2103 and the components in the ethanolic fraction are promising candidates for the development of novel drugs for UC management. Additionally, our study underscores Fyn-mediated CCR2 expression as a potential therapeutic target for the management of UC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Seed mucilages are potential sources of natural polysaccharides. They are biodegradable, biocompatible, sustainable, renewable, and safe for human consumption. Due to the desirable physicochemical and functional properties (e.g. gelling, thickening, stabilizing, and emulsifying), seed mucilages have attracted extensive attention from researchers for utilization as a promising material for the development of advanced carrier systems. Seed mucilages have been utilized as natural polymers to improve the properties of various carrier systems (e.g. complex coacervates, beads, nanofibers, and gels) and for the delivery of diverse hydrophilic and lipophilic compounds (e.g. vitamins, essential oils, antioxidants, probiotics, and antimicrobial agents) to achieve enhanced stability, bioavailability, bioactivity of the encapsulated molecules, and improved quality attributes of food products. This review highlights the recent progress in seed mucilage-based carrier systems for food and nutraceutical applications. The main contents include (1) sources, extraction methods, and physicochemical and functional characteristics of seed mucilages, (2) application of seed mucilages for the development of advanced carrier systems, (3) major issues associated with carrier fabrication, and (4) mechanisms of carrier development, latest improvements in carrier formulation, carrier efficiency in the delivery of bioactive agents, and application in food and nutraceuticals. Furthermore, major challenges and future perspectives of seed mucilage-based carriers for a commercial application are discussed.

Caudal duplication syndrome is a rare congenital anomaly with various duplications of structures derived from the embryonic cloaca and notochord. A male neonate was born with diphallia, bifid scrotum, and duplicated anorectal malformation. Diagnostic and operative evaluation identified a partially duplicated right kidney with left-to-right crossed fused ectopia, bilateral hydronephrosis, 2 separate hemi-bladders, left ectopic ureter with vesicoureteral reflux, and a left rectourethral fistula. To our knowledge, this is the first reported caudal duplication anomaly with complete genitourinary duplication, with diphallia, duplicated bladder, bifid scrotum, extra-numerary kidneys, and a duplicated rectum., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan-Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035-1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083-2.014), and sepsis (HR: 1.854, 95% CI: 1.091-3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354-2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine.

Ethnopharmacological Relevance: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties., Aim of the Study: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy., Methods and Materials: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-β1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations., Results: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1., Conclusion: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts., 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.)

Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects. Usually, immunoassays are utilized in the preliminary screening method. However, NPSs have poor detectability in commercially available immunoassay kits. Meanwhile, various chromatography combined with the mass spectrometry platform have been developed to quantify NPSs. Still, a significant amount of time and resources are required during these procedures. Therefore, we established a rapid analytical platform for NPSs employing paper-loaded direct analysis in real time triple quadrupole mass spectrometry (pDART-QqQ-MS). We implemented this platform for the semiquantitative analysis of forensic drug tests in urine. This platform significantly shrinks the analytical time of a single sample within 30 s and requires a low volume of the specimen. The platform can detect 21 NPSs in urine mixtures at a lower limit of qualification of concentration ranging from 20 to 75 nanograms per milliliter (ng mL -1 ) and is lower than the cutoff value of currently available immune-based devices for detecting multiple drugs (1000 ng mL -1 ). Urine samples from drug addicts have been collected to verify the platform's effectiveness. By combining efficiency and accuracy, our platform offers a promising solution for addressing the challenges posed by NPSs in drug abuse detection.

Protein glycation in human body is closely linked to the onset/progression of diabetes associated complications. These glycated proteins are commonly known as advanced glycation end products (AGEs). Recent literature has also highlighted the involvement of AGEs in other non-communicable diseases (NCDs) such as cardiovascular, cancer, and Alzheimer's diseases and explored the impact of plant metabolites on AGEs formation. However, the significance of endophytic metabolites against AGEs has recently garnered attention but has not been thoroughly summarized thus far. Therefore, the objective of this review is to provide a comprehensive overview of the importance of endophytic metabolites in combating AGEs under NCDs conditions. Additionally, this review aims to elucidate the processes of AGEs formation, absorption, metabolism, and their harmful effects. Collectively, endophytic metabolites play a crucial role in modulating signaling pathways and enhancing the digestibility properties of gut microbiota (GM) by targeting on AGEs/RAGE (receptor for AGEs) axis. Furthermore, these metabolites exhibit anti-AGEs activities similar to those derived from host plants, but at a lower cost and higher production rate. The use of endophytes as a source of such metabolites offers a risk-free and sustainable approach that holds substantial potential for the treatment and management of NCDs., 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.)

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression., Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis., Methods: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1 -/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component., Results: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1 -/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation., Conclusion: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance., 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. Production and hosting by Elsevier B.V.)

Alzheimer's disease (AD) currently lacks effective treatments, making its prevention a critical focus. While accumulating evidence supports that plant-based fermented foods may contribute to AD prevention, the neuroprotective effect of plant-based fermented foods on AD has not been comprehensively reviewed. In this study, we conducted a systematic review of preclinical studies on the efficacy of plant-based fermented foods in AD. The literature search was based on databases including PubMed, Embase, Web of Science, and Scopus. The PICO approach was employed for report inclusion, and each report was assessed for risk of bias using the SYRCLE's RoB tool. From the analysis of 25 retrieved reports, we extracted essential details, including bibliographic information, animal models and characteristics, sources of plant-based fermented foods, dosages, administration routes, durations, and outcome measures. Our findings indicate that plant-based fermented foods may positively impact acute and long-term cognitive function, as well as beta-amyloid-mediated neurodegeneration. This review sheds light on the potential neuroprotective benefits of plant-based fermented foods for various AD-related aspects, including oxidative stress, synaptotoxicity, neuroinflammation, tau hyperphosphorylation, dysfunctional amyloidogenic pathways, and cognitive deficits, as observed in rodent models of AD. However, the small number of studies obtained from our literature search and the finding that many of them were of moderate methodological quality suggest the need for further investigation to substantiate the beneficial potential of this class of functional food for the management of AD.

The purpose of this study was to measure and compare renal pelvic pressure (RPP) between prone and supine percutaneous nephrolithotomy (PCNL) in a benchtop model. Six identical silicone kidney models were placed into anatomically correct prone or supine torsos constructed from patient CT scans in the corresponding positions. A 30-Fr renal access sheath was placed in either the upper, middle, or lower pole calyx for both prone and supine positions. Two 9-mm BegoStones were placed in the respective calyx and RPPs were measured at baseline, irrigating with a rigid nephroscope, and irrigating with a flexible nephroscope. Five trials were conducted for each access in both prone and supine positions. The average baseline RPP in the prone position was significantly higher than the supine position (9.1 vs 2.7 mmHg; p < 0.001). Similarly, the average RPP in prone was significantly higher than supine when using both the rigid and flexible nephroscopes. When comparing RPPs for upper, middle, and lower pole access sites, there was no significant difference in pressures in either prone or supine positions (p > 0.05 for all). Overall, when combining all pressures at baseline and with irrigation, with all access sites and types of scopes, the mean RPP was significantly higher in the prone position compared to the supine position (14.0 vs 3.2 mmHg; p < 0.001). RPPs were significantly higher in the prone position compared to the supine position in all conditions tested. These differences in RPPs between prone and supine PCNL could in part explain the different clinical outcomes, including postoperative fever and stone-free rates., (© 2024. The Author(s).)

The human PLAA gene encodes Phospholipase-A2-Activating-Protein (PLAA) involved in trafficking of membrane proteins. Through its PUL domain (PLAP, Ufd3p, and Lub1p), PLAA interacts with p97/VCP modulating synaptic vesicles recycling. Although few families carrying biallelic PLAA variants were reported with progressive neurodegeneration, consequences of monoallelic PLAA variants have not been elucidated. Using exome or genome sequencing we identified PLAA de-novo missense variants, affecting conserved residues within the PUL domain, in children affected with neurodevelopmental disorders (NDDs), including psychomotor regression, intellectual disability (ID) and autism spectrum disorders (ASDs). Computational and in-vitro studies of the identified variants revealed abnormal chain arrangements at C-terminal and reduced PLAA-p97/VCP interaction, respectively. These findings expand both allelic and phenotypic heterogeneity associated to PLAA -related neurological disorders, highlighting perturbed vesicle recycling as a potential disease mechanism in NDDs due to genetic defects of PLAA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Iacomino, Houerbi, Fortuna, Howe, Li, Scorrano, Riva, Cheng, Steiman, Peltekova, Yusuf, Baldassari, Tamburro, Scudieri, Musante, Di Ludovico, Guerrisi, Balagura, Corsello, Efthymiou, Murphy, Uva, Verrotti, Fiorillo, Delvecchio, Accogli, Elsabbagh, Houlden, Scherer, Striano, Zara, Chou and Salpietro.)

The present study aimed to investigate the potential of marination with extracts prepared from five legume seeds on heterocyclic amine (HA) formation in chemical models and air-fried fish fillets. In terms of total HAs, clove seed marinade (CSM) was found with the maximum inhibitory effect (43.98 %), followed by tamarind seed marinade (TSM) (40.26 %), fenugreek seed marinade (FSM) (39.07 %), acacia seed marinade (ASM) (37.99 %), and black bean seed marinade (BSM) (29.95 %). In particular, at higher levels (3 mg/mL, 4 mg/mL), CSM and FSM achieved the greatest mitigating effect against 4,8-DiMeIQx, 7,8-DiMeIQx, and MeIQx. Furthermore, all marinades were effective in lowering thiobarbituric acid-reactive substances (TBARS) and carbonyl and retaining thiol content relative to the control. PCA analysis revealed that higher levels of ASM, BSM, and FSM had better mitigating effect against IQ and MeIQx formation, whereas Pearson correlation shows that TBARS and carbonyl were positively correlated to HAs., 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.)

Obesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise. Artesunate promotes weight loss and reduces food intake in obese mice and cynomolgus macaques by increasing circulating levels of Growth Differentiation Factor 15 (GDF15), an appetite-regulating hormone with a brainstem-restricted receptor, the GDNF family receptor α-like (GFRAL). Mechanistically, artesunate induces the expression of GDF15 in multiple organs, especially the liver, in mice through a C/EBP homologous protein (CHOP)-directed integrated stress response. Inhibition of GDF15/GFRAL signalling by genetic ablation of GFRAL or tissue-specific knockdown of GDF15 abrogates the anti-obesity effect of artesunate in mice with diet-induced obesity, suggesting that artesunate controls bodyweight and appetite in a GDF15/GFRAL signalling-dependent manner. These data highlight the therapeutic benefits of artesunate in the treatment of obesity and related comorbidities., (© 2024. The Author(s).)

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people's health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 "CTSA hubs" exist across the nation. Since 2006, the Houston-based Center for Clinical Translational Sciences (CCTS) has assembled a well-integrated, high-impact hub in Texas that includes six partner institutions within the state, encompassing ∼23,000 sq. miles and over 16 million residents. To achieve the NCATS goal of "more treatments for all people more quickly," the CCTS promotes diversity and inclusion by integrating underrepresented populations into clinical studies, workforce training, and career development. In May 2023, we submitted the UM1 application and six "companion" proposals: K12, R25, T32-Predoctoral, T32-Postdoctoral, and RC2 (two applications). In October 2023, we received priority scores for the UM1 (22), K12 (25), T32-Predoctoral (20), and T32-Postdoctoral (23), which historically fall within the NCATS funding range. This report describes the grant preparation and submission approach, coupled with data from an internal survey designed to assimilate feedback from principal investigators, writers, reviewers, and administrative specialists. Herein, we share the challenges faced, the approaches developed, and the lessons learned., Competing Interests: None., (© The Author(s) 2024.)

Tumor metastasis and cancer recurrence are often a result of cell heterogeneity, where specific subpopulations of tumor cells may be resistant to radio- or chemotherapy. To investigate this physiological and phenotypic diversity, single-cell metabolomics provides a powerful approach at the chemical level, where distinct lipid profiles can be found in different tumor cells. Here, we established a highly sensitive platform using nanoflow liquid chromatography (nLC) combined with multinozzle emitter electrospray ionization mass spectrometry for more in-depth metabolomics profiling. Our platform identified 15 and 17 lipids from individual osteosarcoma (U2OS) and glioblastoma (GBM) cells when analyzing single-cell samples. Additionally, we used the functional single-cell selection (fSCS) pipeline to analyze the subpopulations of cells with a DNA damage response (DDR) in U2OS cells and fast migration in GBM cells. Specifically, we observed a down-regulation of polyunsaturated fatty acids (PUFAs) in U2OS cells undergoing DDR, such as fatty acids FA 20:3; O2 and FA 17:4; O3. Furthermore, ceramides (Cer 38:0; O3) and triglycerides (TG 36:0) were found to be down-regulated in fast-migrating GBM cells compared to the slow-migrating subpopulation. These findings suggest the potential roles of these metabolites and/or lipids in the cellular behavior of the subpopulations.

Ethnopharmacological Relevance: Particulate matter 2.5 (PM2.5) is a dangerous airborne pollutant that has become a global issue due to its detrimental effect on macrophages. Chenopodium formosanum Koidz (Djulis), a native plant from Taiwan well known for its high antioxidant content and is frequently used in ethnomedicine, shows promise as a novel phytomedicine to combat against oxidative stress caused by PM2.5. However, the protective mechanism of Djulis against PM2.5 still remains unclear., Aim of the Study: This study aimed to characterize the deleterious effect of emerging PM2.5 contaminants on the alveolar macrophage cell of the respiratory system and explore the underlying mechanisms in the suppression of PM2.5-induced inflammation using the extract of fermented Djulis., Methods and Materials: RNA sequencing, immunoblot, and ChIP assay approaches were used to gain insight into the deleterious effect of PM2.5 on the macrophage cell at the transcriptional and translational level; and to elucidate the contribution of fermented Djulis extract (FCS) as the remedy of PM-induced MH-S cell inflammation. UHPLC-ESI-MS/MS and LC-QQQ/MS were used to identify the bioactive compounds potentially contributing to phytomedicinal properties in the water fraction of FCS. Multiple ligands docking analysis was conducted to predict the in-silico interaction of Djulis metabolites and NF-κB., Results: Here, we showed that PM2.5 exposure at 200 ppm accelerated the production of intracellular ROS and phosphorylated NF-κB (p-NFκB), and negatively affecting the alveolar macrophage cell viability. Treating the cells with water-extracted FCS can restore their viability to 76% while simultaneously suppressing the generation of ROS and p-NFκB up to 38%. These ameliorative effects can be attributed to the occurrence of bioactive compounds such as gluconic acid, uridine, pantothenic acid, L-pyroglutamic acid, L-(-)-malic acid, and acetyl-L-carnitine in the water-extracted FCS which potentially dock to the RELA subunit site and consequently inhibit NF-κB activity along with its downstream inflammation signaling cascade., Conclusion: This work demonstrated the hazardous effect of PM2.5 on alveolar macrophage and unveiled the potential of FCS as a therapeutic phytomedicine to alleviate PM-induced inflammation., 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 Maillard reaction (MR) has been established to be a paramount contributor to the characteristic sensory property of thermally processed food products. Meanwhile, MR also gives rise to myriads of harmful byproducts (HMPs) (e.g., advanced glycation end products (AGEs) and acrylamide). Nutritional additives have attracted increasing attention in recent years owing to their potential to simultaneously improve nutritional quality and attenuate HMP formation. In this manuscript, a brief overview of various nutritional additives (vitamins, minerals, fatty acids, amino acids, dietary fibers, and miscellaneous micronutrients) in heat-processed food is provided, followed by a summary of the formation mechanisms of AGEs and acrylamide highlighting the potential crosstalk between them. The main body of the manuscript is on the capability of nutritional additives to modulate AGE and acrylamide formation besides their traditional roles as nutritional enhancers. Finally, limitations/concerns associated with their use to attenuate dietary exposure to HMPs and future perspectives are discussed. Literature data support that through careful control of the addition levels, certain nutritional additives possess promising potential for simultaneous improvement of nutritional value and reduction of AGE and acrylamide content via multiple action mechanisms. Nonetheless, there are some major concerns that may limit their wide applications for achieving such dual functions, including influence on sensory properties of food products, potential overestimation of nutrition enhancement, and introduction of hazardous alternative reaction products or derivatives. These could be overcome through comprehensive assay of dose-response relationships and systematic evaluation of the diverse combinations from the same and/or different categories of nutritional additives to establish synergistic mixtures., (© 2023 Institute of Food Technologists®.)

Objective: Telemedicine can facilitate social distancing during an infectious disease pandemic and reduce the burden on health-care resources. Moreover, telemedicine can be utilized for medical care in remote island regions, in home health care, and during isolated major disasters such as regional earthquakes. However, the effectiveness of telemedicine for emergency consultation remains unclear. This study introduced and analyzed the national emergency medical teleconsultation (NEMTC) established in Taiwan in 2022 during the COVID-19 pandemic., Methods: In response to the COVID-19 pandemic, Taiwan's Centers for Disease Control established a temporary 24-h NEMTC contingency system. Patient information was collected from consultations through the NEMTC from April 28 to June 28, 2022. After successful consultation, physicians made recommendations for home observation, emergency department (ED) visit, or outpatient follow-up. ED visits were divided into two categories, namely self-transport and transport, by the emergency medical service system (EMSS)., Results: During the aforementioned period, 20,902 consultation requests were made through the NEMTC, and 11,804 consultations (56.5% of 20,902) were successful. Consultation success rates were significantly higher for those who had a consultation between 08:00 and 16:00, had a waiting time of less than 10 min, and were not aged between 18 and 45 years. Moreover, 8.2% of the analyzed patients were advised to visit the ED, and only 0.4% required ambulance transportation. Children and older individuals and patients with cardiovascular symptoms, shortness of breath, or neurological or abdominal symptoms had a significantly higher chance of being referred to the ED than did other individuals., Conclusions: The NEMTC response system can enhance the efficiency of the EMSS and can reduce the burden of patients with mild conditions overloading the EMSS and EDs. The NEMTC could serve as an effective rapid response system during future pandemics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Retroperitoneal lymph node dissection (RPLND) for testicular seminoma with enlarged retroperitoneal lymph nodes has received increased consideration and exposed a new clinical entity: pN0 disease. Enlarged, nonmetastatic retroperitoneal lymph nodes provide insight into the natural history of seminoma while offering a benchmark for improving the accuracy of staging. The purpose of this systematic review was to report the pN0 rates, describe risk factors associated with it, and discuss emerging research that may reduce its incidence. We performed a systemic review of published literature on PubMed, Embase, Web of Science, as well as oncology meeting abstracts evaluating histology of lymph nodes in patients with testicular seminoma treated primarily with retroperitoneal lymph node dissection. Studies were excluded if histology was not reported. A total of 15 publications and abstracts were included. Although study designs were heterogeneous, there was a minimal risk of bias. Overall, the reported pN0 rates were 0% to 22%. In prospective clinical trials it was 9% to 16%. The presence of pN0 was associated with preoperative smaller lymph nodes, a solitary enlarged lymph node, or negative serum miRNA-371. The incidence of pN0 seminoma is concerning as it points to a potential historical overtreatment; however, it also represents an important inflection for testicular cancer research as quantifiable improvements in clinical staging will translate to clear benefits to patients., 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 Inc. All rights reserved.)

Euglena gracilis is one of the few permitted edible microalgae. Considering consumer acceptance, E. gracilis grown heterotrophically with yellow appearances have wider food industrial applications such as producing meat analogs than green cells. However, there is much room to improve the protein content of heterotrophic culture cells. In this study, the effects of nitrogen sources, temperature, initial pH, and C/N ratios on the protein production of E. gracilis were evaluated under heterotrophic cultivation. These results indicated that ammonium sulfate was the optimal nitrogen source for protein production. The protein content of E. gracilis cultured by ammonium sulfate increased by 113% and 44.7% compared with that cultured by yeast extract and monosodium glutamate, respectively. The manipulation of the low C/N ratio further improved E. gracilis protein content to 66.10% ( w / w ), which was 1.6-fold of that in the C/N = 25 group. Additionally, amino acid analysis revealed that the nitrogen-to-protein conversion factor (NTP) could be affected by nitrogen sources. A superior essential amino acid index (EAAI) of 1.62 and a balanced amino acid profile further confirmed the high nutritional value of E. gracilis protein fed by ammonium sulfate. This study highlighted the vast potency of heterotrophic cultured E. gracilis as an alternative dietary protein source.

V-type starch-polyphenol complexes, known for their improved physicochemical properties compared to native starch, are challenging to form efficiently. In this study, the effects of tannic acid (TA) interaction with native rice starch (NS) on digestion and physicochemical properties were investigated using non-thermal ultrasound treatment (UT). Results showed the highest complexing index for NSTA-UT3 (∼ 0.882) compared to NSTA-PM (∼0.618). NSTA-UT complexes reflected the V6I-type complex having six anhydrous glucose per unit per turn with peaks at 2θ = 7°, 13°, and 20°. The maxima of the absorption for iodine binding were suppressed by the formation of V-type complexes depending on the concentration of TA in the complex. Furthermore, rheology and particle size distributions were also affected by TA introduction under ultrasound, as revealed by SEM. XRD, FT-IR, and TGA analyses confirmed V-type complex formation for NSTA-UT samples, with improved thermal stability and increased short-range ordered structure. Ultrasound-induced addition of TA also decreased the hydrolysis rate and increased resistant starch (RS) concentration. Overall, ultrasound processing promoted the formation of V-type NSTA complexes, suggesting that tannic acid could be utilized for the production of anti-digestion starchy foods in the future., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The study utilized fresh fourth-day Chenopodium formosanum sprouts as the substrate for Rhizopus oligosporus fermentation. The resultant products showed higher antioxidant capacity than those from C. formosanum grains. Compared to traditional plate fermentation (PF), fermentation in a bioreactor (BF) (35 °C, 0.4 vvm aeration at 5 rpm) led to higher free peptide content (99.56 ± 7.77 mg casein tryptone/g) and enzyme activity (amylase, glucosidase, and proteinase are 2.21 ± 0.01, 54.57 ± 10.88, and 40.81 ± 6.52 U/g, respectively) than traditional plate fermentation (PF). Using mass spectrometry analysis, two peptides TDEYGGSIENRFMN and DNSMLTFEGAPVQGAAAITEK were predicted to possess high bioactive properties as DPP IV and ACE inhibitors. Additionally, over twenty new metabolites (aromatics, amines, fatty acids, and carboxylic acids) were discovered in the BF system compared to its PF counterpart. Results suggest that using a BF system to ferment C. formosanum sprouts is an appropriate method to scale-up fermentation and enhance nutritional values as well as bioactivities., 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.)

The sterilisation of surgical instruments is a major factor in infection control in the operating room (OR). All items used in the OR must be sterile for patient safety. Therefore, the present study evaluated the effect of far-infrared radiation (FIR) on the inhibition of colonies on packaging surface during the long-term storage of sterilised surgical instruments. From September 2021 to July 2022, 68.2% of 85 packages without FIR treatment showed microbial growth after incubation at 35 °C for 30 days and at room temperature for 5 days. A total of 34 bacterial species were identified, with the number of colonies increasing over time. In total, 130 colony-forming units were observed. The main microorganisms detected were Staphylococcus spp. (35%) and Bacillus spp. (21%) , Kocuria marina and Lactobacillus spp. (14%), and mould (5%). No colonies were found in 72 packages treated with FIR in the OR. Even after sterilisation, microbial growth can occur due to movement of the packages by staff, sweeping of floors, lack of high-efficiency particulate air filtration, high humidity, and inadequate hand hygiene. Thus, safe and simple far-infrared devices that allow continuous disinfection for storage spaces, as well as temperature and humidity control, help to reduce microorganisms in the OR., (© 2023. The Author(s).)

High temperatures applied in the production of plant-based meat analogs (PBMA) lead to the occurrence of Maillard reactions, in which harmful compounds N ε -(carboxymethyl)lysine (CML), N ε -(carboxyethyl)lysine (CEL) and acrylamide are formed. However, little research has focused on these compounds in PBMA. In this study, the contents of CML, CEL and acrylamide in 15 commercial-sold PBMA were determined by an ultra-high performance liquid chromatograph coupled with a triple quadrupole tandem mass spectrometer (UHPLC-QqQ-MS/MS). Nutrients (protein, amino acids, fatty acids and sugars) which are related to the formation of these compounds were also studied. The results showed that CML, CEL and acrylamide contents were in the range of 16.46-47.61 mg/kg, 25.21-86.23 mg/kg and 31.81-186.70 μg/kg, respectively. Proteins account for 24.03-53.18% of PBMA. Except for Met + Cys, which is the limiting amino acid of most PBMA, all other indispensable amino acids met the requirements for adults. Besides, PBMA had more n-6 fatty acids than n-3 fatty acids. A correlation analysis showed that proteins and the profiles of amino acid and fatty acid had little influence on CML but significant influence on CEL and acrylamide. The results of the present study can be used as a reference to produce PBMA with higher amounts of nutrients and lower amounts of CML, CEL and acrylamide.

Red wine polyphenolic complexes have attracted increasing attention as potential modulators of human metabolic disease risk. Our previous study discovered that red wine high-molecular-weight polymeric polyphenolic complexes (HPPCs) could inhibit key metabolic syndrome-associated enzymes and favorably modulate human gut microbiota (GM) in simulated colonic fermentation assay in vitro. In this work, the efficacy of HPPC supplementation (150 and 300 mg/kg/day, respectively) against high-fat diet (HFD)-induced metabolic disturbance in mice was investigated. HPPCs effectively attenuated HFD-induced obesity, insulin resistance, and lipid and glucose metabolic dysregulation and ameliorated inflammatory response and hepatic and colonic damage. It also improved the relative abundance of Bacteroidetes and Firmicutes , consistent with an anti-obesity phenotype. The favorable modulation of GM was further supported by improvement in the profile of fecal short-chain fatty acids. The higher dosage generally had a better performance in these effects than the low dosage. Moreover, serum metabolite profiling and pathway enrichment analysis revealed that HPPCs significantly modulated vitamin B metabolism-associated pathways and identified N -acetylneuraminic acid and 2-methylbutyroylcarnitine as potential biomarkers of the favorable effect on HFD-induced metabolic dysregulation. These findings highlight that dietary supplementation with red wine HPPCs is a promising strategy for the management of weight gain and metabolic dysregulation associated with HFD.