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Although berberine (BBR) is well known as an active constituent in traditional medicines used in the treatment of gastrointestinal diseases, its potential against viral gastroenteritis has not been specifically reported. This study aims to investigate the antiviral activity of BBR against rotavirus and evaluate its cytotoxicity and pharmacological efficacies, including antioxidant and anti-inflammatory activities in vitro. Using ultraviolet-visible absorption spectroscopy, the saturation concentration of BBR was determined as 2261 μg/mL, indicating that BBR is a poor water-soluble compound. The inhibition rate of nitric oxide (NO) production of BBR solution at a concentration of 283 μg/mL was similar to that of Cardamonin 0.3 μM with a cell viability of 92.46±0.35 %, revealing the anti-inflammatory activity of BBR. The cytotoxicity of the BBR solution depended on its concentration, whereby the 50 % cytotoxicity concentration (CC 50 ) of BBR after 96 h exposure was 664 μg/mL. Investigation of cytopathic effects (CPEs) of MA104 cells treated with BBR and BBR-incubated rotavirus indicates that BBR could effectively inhibit the replication of rotavirus. CPEs were not observed in the cells inoculated with rotavirus (100TCID 50 ) which was pre-incubated with BBR for 96 hours at a BBR concentration of 283 μg/mL. Therefore, the study provides reliable results to demonstrate the ability of BBR to inhibit the replication of rotavirus., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In this study, a multifunctional composite membrane based on polycaprolactone nanofibers having controlled drug release, shape memory effect, and antibacterial ability was successfully prepared by the electrospinning technique. The addition of graphene oxide (GO), zinc oxide nanoparticles (ZnO NPs), polyethylene glycol (PEG), and berberine (BBR) strongly affected the morphology, crystalline degree, melting temperature, and shape memory performance of the composite membrane, thanks to the physical crosslinking network formed by the hydrogen bonding or van der Waals interactions between the components. As a result, the recovery ratio of the composite membrane reached a higher value (76.3% ± 0.7%) than that of the PCL fiber membrane (22.8% ± 0.7%). The additional components significantly improved the wettability of the composite membrane, leading to a high amount of BBR released (42.7 wt%) during 40 hours, as well as effective antibacterial ability. Besides, the BBR release can be feasibly controlled by modulating the deformation ratio of the composite membrane, whereby the higher deformation ratio resulted in a higher BBR release. Therefore, it is suggested that the prepared composite nanofiber membrane is a potential smart material used in biomedical applications, such as wound dressing and drug release systems., Competing Interests: The authors have no competing interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

The use of decellularized extracellular matrix products in tissue regeneration is quite alluring yet practically challenging due to the limitations of its availability, harsh processing techniques, and host rejection. Scaffolds obtained by either incorporating extracellular matrix (ECM) material or coating the surface can resolve these challenges to some extent. However, these scaffolds lack the complex 3D network formed by proteins and growth factors observed in natural ECM. This study introduces an approach utilizing 3D nanofiber scaffolds decorated with dECM to enhance cellular responses and promote tissue regeneration. Notably, the dECM can be customized according to specific cellular requirements, offering a tailored environment for enhanced therapeutic outcomes. Two types of 3D expanded scaffolds, namely radially aligned scaffolds (RAS) and laterally expanded scaffolds (LES) fabricated by the gas-foaming expansion were utilized. To demonstrate the proof-of-concept, human dermal fibroblasts (HDFs) seeded on these scaffolds for up to 8 weeks, resulted in uniform and highly aligned cells which deposited ECM on the scaffolds. These cellular components were then removed from the scaffolds through decellularization (e.g., SDS treatment and freeze-thaw cycles). The dECM-decorated 3D expanded nanofiber scaffolds can direct and support cell alignment and proliferation along the underlying fibers upon recellularization. An in vitro inflammation assay indicates that dECM-decorated LES induces a lower immune response than dECM-decorated RAS. Further, subcutaneous implantation of dECM-decorated RAS and LES shows higher cell infiltration and angiogenesis within 7 and 14 days than RAS and LES without dECM decoration. Taken together, dECM-decorated 3D expanded nanofiber scaffolds hold great potential in tissue regeneration and tissue modeling. STATEMENT OF SIGNIFICANCE: Decellularized ECM scaffolds have attained widespread attention in biomedical applications due to their intricate 3D framework of proteins and growth factors. Mimicking such a complicated architecture is a clinical challenge. In this study, we developed natural ECM-decorated 3D electrospun nanofiber scaffolds with controlled alignments to mimic human tissue. Fibroblasts were cultured on these scaffolds for 8 weeks to deposit natural ECM and decellularized by either freeze-thawing or detergent to obtain decellularized ECM scaffolds. These scaffolds were tested in both in-vitro and in-vivo conditions. They displayed higher cellular attributes with lower immune response making them a good grafting tool in tissue regeneration., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this paper, we propose a novel system integrating reconfigurable intelligent surfaces (RISs) with cognitive radio (CR) technology, presenting a forward-looking solution aligned with the evolving standards of 6G and beyond networks. The proposed RIS-assisted CR networks operate with a base station (BS) transmitting signals to two users, the primary user (PU) and secondary user (SU), through direct and reflected signal paths, respectively. Our mathematical analysis focuses on deriving expressions for SU in the RIS-assisted CR system, validated through Monte Carlo simulations. The investigation covers diverse aspects, including the impact of the signal-to-noise ratio (SNR), power allocations, the number of reflected surfaces, and blocklength variations. The results provide nuanced insights into RIS-assisted CR system performance, highlighting its sensitivity to factors like the number of reflectors, fading severity, and correlation coefficient. Careful parameter selection, such as optimizing the configuration of reflectors, is shown to prevent a complete outage, showcasing the system's robustness. Additionally, the work suggests that the optimization of reflectors configuration can significantly enhance overall system performance, and RIS-assisted CR systems outperform reference schemes. This work contributes a thorough analysis of the proposed system, offering valuable insights for efficient performance evaluation and parameter optimization in RIS-assisted CR networks.

Background: Busulfan plus cyclophosphamide (Bu/Cy) is considered one of the classical myeloablative conditioning regimens. However, its toxicity can significantly increase mortality rates. To reduce both acute and long-term complications after hematopoietic stem cell transplantation (HSCT), newer conditioning regimens are being investigated. The purposes of this study were to assess the efficacy and safety of busulfan plus cyclophosphamide (Bu/Cy) and busulfan plus fludarabine (Bu/Flu) conditioning regimen for allogeneic HSCT (allo-HSCT) in acute myelogenous leukemia (AML). Materials and Methods: We conducted a single-center, retrospective analysis of AML, both adults and children, who underwent either Bu/Cy or Bu/Flu conditioning regimen for allo-HSCT and received peripheral blood stem cell transplants from HLA-matched donors. Results: From 2005 - 2019, 49 AML patients receiving Bu/Cy and 21 receiving Bu/Flu were identified, meeting inclusion criteria. The two groups showed no significant differences in age, gender, disease status pre-transplant, the median time to neutrophil and platelet engraftment. Bu/Flu patients had a shorter duration of neutropenia (median 7 days vs 10 days, p = 0.001) and shorter duration of thrombocytopenia (median 10 days vs 15 days, p = 0.016) than Bu/Cy.  No difference was observed in disease-free survival (DFS) and overall survival (OS) between the two groups. Both univariate and multivariate analyses showed that age, disease status pre-transplant, and chronic graft-versus-host disease (GvHD) are related to worse DFS and OS. Conclusion : With similar efficacy to Bu/Cy but faster neutrophil and platelet recovery time, Bu/Flu is suitable as a pre-HSCT conditioning regimen for patients with AML., (Copyright © 2024 Tehran University of Medical Sciences.)

Developing a diffusion barrier layer on material interfaces has potential applications in various fields such as in packaging materials, pharmaceuticals, chemical filtration, microelectronics, and medical devices. Although numerous physical and chemical methods have been proposed to generate the diffusion barrier layer, the complexity of fabrication techniques and the high manufacturing costs limit their practical utility. Here, we propose an innovative approach to fabricate the diffusion barrier layer by irradiating poly(dimethylsiloxane) (PDMS) with a mid-infrared (λ = 10.6 μm) CO 2 laser. This process directly creates a diffusion barrier layer on the PDMS surface by forming a heavily cross-linked network in the polymer matrix. The optimal irradiation conditions were investigated by modulating the defocusing distance, laser power, and number of scanning passes. The barrier thickness can reach up to 70 μm as observed by the scanning electron microscope (SEM). The attenuated total reflectance (ATR), electron dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS) analyses collectively confirmed the formation of the SiO x structure on the modified surface based on the decreased methyl group signal and the increased oxygen/silicon ratio. The diffusion test with the model drugs (rhodamine B and donepezil) demonstrated that the modified surface exhibits effective diffusion barrier properties and the rate of drug diffusion through the modified barrier layer can be controlled by the optimization of the irradiation parameters. This novel approach provides the possibility to develop a controllable diffusion barrier layer in a biocompatible polymer with prospective applications in the fields of pharmaceuticals, packing materials, and medical devices.

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three dimensional (3D) multiphasic scaffolds using a 'solids-of-revolution' inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates the number of cells migrated and proliferated onto the scaffolds are mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration., Competing Interests: CONFLICT OF INTEREST STATEMMENT The authors declare no conflict of interest.

Hydrophobic berberine powder (BBR) and hydrophilic BBR nanoparticles (BBR NPs) were loaded into an electrospun polylactic acid (PLA) nanofiber scaffold for modulating the release behavior of BBR in an aqueous medium. The BBR release from the BBR/PLA and BBR NPs/PLA nanofiber scaffolds was investigated in relation to their chemical characteristics, BBR dispersion into nanofibers, and wettability. The BBR release profiles strongly influenced the antibacterial efficiency of the scaffolds over time. When the BBR was loaded, the BBR/PLA nanofiber scaffold exhibited an extremely hydrophobic feature, causing a triphasic release profile in which only 9.8 wt % of the loaded BBR was released in the first 24 h. This resulted in a negligible inhibitory effect against methicillin-resistant Staphylococcus aureus bacteria. Meanwhile, the BBR NPs/PLA nanofiber scaffold had more wettability and higher concentration of BBR NPs dispersed on the surface of PLA nanofibers. This led to a sustained release of 75 wt % of the loaded BBR during the first 24 h, and consequently boosted the antibacterial effectiveness. Moreover, the cytotoxicity test revealed that the BBR NPs/PLA nanofiber scaffold did not induce any changes in morphology and proliferation of MA-104 cell monolayers. It suggests that the BBR/PLA and BBR NPs/PLA nanofiber scaffolds can be used in different biomedical applications, such as wound dressing, drug delivery systems, and tissue engineering, according to the requirement of BBR concentration for the desired therapeutic effects., (Copyright © 2024, Le et al.)

Vaccines are strongly recommended globally as an effective measure to prevent serious illness from and spread of COVID-19. Concerns about safety following vaccination continue to be the most common reason that people do not accept the vaccine. This retrospective study was carried out on 4341 people who received the first dose of ChAdOx1 nCoV-19, BBIBP-CorV, or mRNA-1273 vaccine at Jio Health Clinic in Ho Chi Minh City, Vietnam. Post-injection side effects were either reported by participants or actively collected by health care staff by means of telemedicine. Local side effects were reported by 35.5% of all individuals, with pain being the most common symptom (33.3%). Systemic side effects were reported by 44.2% of individuals, with fever (25.3%) and fatigue (21.4%) being the most common. Age ≤60 years, female gender, and ChAdOx1 nCoV-19 were significant independent risk factors for both local and systemic side effects, while a history of allergy was significant as a risk factor for local side effects. A total of 43 individuals (1.0%) reported concerning symptoms of rare severe complications, which were addressed and treated by physicians via Jio Health app.

Background: The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care., Methods: This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment.  RESULTS: The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group., Conclusions: Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants., Trial Registration: This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115-DHYD)., (© 2023. The Author(s).)

Phytochemical research of Perilla frutescens aerial parts led to isolation of 12 secondary metabolites, including one new 3-benzoxepin glucoside, perillafrutoside A ( 1 ), one new megastigmane glycoside, perillafrutoside B ( 2 ), and 10 known compounds. Their chemical structures were identified based on 1D/2D NMR, HRESIMS, and ECD spectroscopic analyses. The structure of 2 was elucidated based on revision of the previously reported stereoisomer, (6 R ,9 R )-blumenyl α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside. Evaluation of their antimicrobial effect revealed that compounds 1 and 5-11 inhibit Enterococcus faecalis growth, compounds 6 , 7 and 9 suppress Staphylococcus aureus growth, whereas compounds 6 and 11 attenuate Candida albicans growth. This is the first report of the isolation of 3-5 , 8-10 and 12 from the genus Perilla and the antimicrobial effect of compounds 3 , 8 and 10 .

Significance: Nowadays, the wound dressing is no longer limited to its primary wound protection ability. Hydrogel, sponge-like material, three dimensional-printed mesh, and nanofiber-based dressings with incorporation of functional components, such as nanomaterials, growth factors, enzymes, antimicrobial agents, and electronics, are able to not only prevent/treat infection but also accelerate the wound healing and monitor the wound-healing status. Recent Advances: The advances in nanotechnologies and materials science have paved the way to incorporate various functional components into the dressings, which can facilitate wound healing and monitor different biological parameters in the wound area. In this review, we mainly focus on the discussion of recently developed functional wound dressings. Critical Issues: Understanding the structure and composition of wound dressings is important to correlate their functions with the outcome of wound management. Future Directions: "All-in-one" dressings that integrate multiple functions ( e.g. , monitoring, antimicrobial, pain relief, immune modulation, and regeneration) could be effective for wound repair and regeneration.

Background/aim: Radiation cystitis is a frequent complication that can occur after therapeutic irradiation of pelvic cancers. The current treatment for this condition is complex and often ineffective., Case Report: We present a clinical case of a 54-year-old patient diagnosed with small cell cervical cancer FIGO stage IIIC who developed grade 2-3 radiation cystitis following post-operational chemoradiation therapy. The patient exhibited increased urinary urgency and frequency, dysuria, and low abdominal pain, which failed to respond to acupuncture and corticosteroid treatments. A course of Ich Nieu Khang phytotherapy tablets, resulted in significant improvement of symptoms within 24 hours of initiation. The symptoms resolved completely within 10 days, and ultrasonography documented a marked decrease in bladder wall thickening and improved bladder evacuation function. The phytotherapy was well-tolerated, and no side-effects were observed during the 60-day treatment period., Conclusion: These findings suggest that phytotherapy may be viable for managing radiation cystitis. However, further controlled clinical trials are needed to confirm the efficacy of Ich Nieu Khang and promote its broader clinical applications., Competing Interests: The Authors report no conflicts of interest., (Copyright 2023, International Institute of Anticancer Research.)

This study reports on the synthesis and characterization of ZnO-Ag@AgBr/SBA-15 composites using natural halloysite clay from Yenbai Province, Vietnam, as a silica aluminum source. The synthesized materials demonstrated visible light absorption with a band gap energy range of 2.63-2.98 eV. The dual Z-scheme ZnO-Ag@AgBr/SBA-15 heterojunction exhibited superior catalytic performance compared to ZnO/SBA-15 and Ag@AgBr/SBA-15, owing to its improved electron transfer and reduced electron and hole recombination rate. In particular, the photocatalytic efficiency of ZnO-Ag@AgBr/SBA-15 was evaluated for the removal of harmful phenol red from wastewater under visible light irradiation. The photocatalytic process was optimized by varying the phenol red concentration, pH, and catalyst dosage, and showed that 98.8% of phenol red in 100 mL wastewater (pH = 5.5) can be removed using 40 mg of 20%ZnO-Ag@AgBr/SBA-15 within 120 min. Furthermore, the degradation pathway of phenol red was predicted using liquid chromatographic-mass spectrometry (LC-MS). Finally, the photocatalytic process was successfully tested using water samples collected from the four main domestic waste sources in Hanoi, including the To Lich River, the Hong River, the Hoan Kiem Lake, and the West Lake, demonstrating the high potential of the ZnO-Ag@AgBr/SBA-15 photocatalyst for phenol red degradation in real-world wastewater treatment applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This work reports the use of mesoporous silica rods as templates for the step-wise preparation of multifunctional Fe 3 O 4 NPs filled polydopamine hollow rods (Fe 3 O 4 @PDA HR). The capacity of as-synthesized Fe 3 O 4 @PDA HR as a new drug carrier platform was assessed by its loading and the triggered release of fosfomycin under various stimulations. It was found that the release of fosfomycin was pH dependent with ~89% of fosfomycin being released in pH 5 after 24 h, which was 2-fold higher than that in pH 7. The magnetic properties of Fe 3 O 4 NPs and the photothermal properties of PDA enabled the triggered release of fosfomycin upon the exposure to rotational magnetic field, or NIR laser irradiation. Additionally, the capability of using multifunctional Fe 3 O 4 @PDA HR to eliminate preformed bacterial biofilm was demonstrated. Upon exposure to the rotational magnetic field, the biomass of a preformed biofilm was significantly reduced by 65.3% after a 20 min treatment with Fe 3 O 4 @PDA HR. Again, due to the excellent photothermal properties of PDA, a dramatic biomass decline (72.5%) was achieved after 10 min of laser exposure. This study offers an alternative approach of using drug carrier platform as a physical mean to kill pathogenic bacteria along with its traditional use for drug delivery.

This study provides new data on ecology of testate amoebae in the waterbodies of the Central Highlands and South-Central Coast regions of Vietnam. A total of 108 species and subspecies including six new records for Vietnam were identified. One new species Difflugia quangtrani sp. nov. was described. Difflugia, Arcella, and Centropyxis were the most species-rich genera, and Centropyxis aculeata was the most common species. The results of NMDS and ANOSIM analyses for the first time showed significant differences in composition of tropical freshwater testate amoeba communities within both various types of waterbodies (reservoir, river, and wetland) and biotopes (plankton and benthos). Average species richness per sample in different types of waterbodies was similar, while that of plankton was statistically higher than in benthos. The distance decay of similarity in tropical freshwater testate amoeba community of both plankton and benthos was observed for the first time indicating the importance of geographical distance in testacean species composition changes between samples. Redundancy analyses followed by the forward selection have determined elevation, pH, and dissolved oxygen as significant factors that affect tropical freshwater testacean community. More large-scale climatic and small-scale hydrological and hydrochemical variables should be included into further studies to find out most important factors determining structure of freshwater testacean assemblages., 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 © 2022 Elsevier GmbH. All rights reserved.)

Oral vaccination of wildlife has shown to be a very effective management tool in rabies control. Evaluation of the genetic stability of vaccine viruses before distributing vaccine baits in the environment is essential because all available oral rabies vaccines, including the genetically engineered rabies virus vaccine strain SPBN GASGAS (Rabitec), are based on replication-competent viruses. To evaluate the genetic stability of this vaccine strain, five serial passages of the Master Seed Virus (MSV) in the production cell line BHK21 Cl13 were performed. Furthermore, to test possible reversion to virulence, a back-passage study in suckling mouse brain (SMB) was performed. Subsequently, the pooled 5th SMB passage was inoculated intracerebrally (i.c.) in adult and suckling mice. The full genome sequences of the isolated 5th passage, in vivo and in vitro, were compared at both the consensus and the quasispecies level with the MSV. Additionally, the full genome sequence of the 6th SMB passage from the individual animals was determined and compared. Full-length integration of the double glycoprotein and modified base substitutions at amino acid position 194 and 333 of the glycoprotein could be verified in all 5th and 6th passage samples. Overall, 11 single nucleotide polymorphisms (SNPs) were detected in the 5th pooled SMB passage, 4 with frequency between 10 and 20%, and 7 with between 2.5 and 10%. SNPs that resulted in amino acid exchange were found in genes: N (one SNP), G (four SNPs), and L (three SNPs). However, none of these SNPs were associated with reversion to virulence since all adult mice inoculated i.c. with this material survived. In the individual samples of the 6th SMB passage 24 additional SNPs (>2.5%) were found, of which only 1 SNP (L-gene, position 6969) had a prevalence of >50% in 3 of 17 samples. The obtained results confirmed the stable expression of genetic modifications and the genetic stability of the consensus strain after serial in vivo and in vitro passaging.

The use of insect meal in aquafeed formulations has recently gained attention. Detailed knowledge about the inclusion levels for pikeperch ( Sander lucioperca ), a promising candidate for intensive aquaculture in Europe remains, however, fragmented. In the present study, 4 isoproteic (45% dry matter) and isoenergetic (21 MJ/kg) diets were formulated, including a control diet (H0) containing 30% fishmeal (FM) on an as-fed basis and the other 3 diets in which FM protein was replaced by defatted black soldier fly ( Hemetia illucens ) meal (HIM) at 25%, 50%, and 100% (diet abbreviation H9, H18 and H36, corresponding to an inclusion level of 9%, 18% and 36%, respectively). The feeding trial was performed in triplicate groups of 50 juvenile pikeperch (mean weight, 68.7 g) fed with experimental diets for 84 d during which the growth performance, nutrient digestibility, fillet quality and economic and environmental sustainability of rearing pikeperch were evaluated. Our findings indicated that pikeperch in H0, H9, and H18 groups displayed better results regarding growth performance indices, except for survival rate where no significant difference among groups was recorded ( P  = 0.642). A significantly lower organ-somatic index, including hepatosomatic, viscerosomatic and perivisceral fat index, was found in fish in H18 groups than other groups ( P  < 0.05). Inclusion of HIM affected the digestibility of the nutrients and resulted in an almost linear reduction in the apparent digestibility coefficient of dry matter and protein. Concerning the fillet quality, dietary HIM negatively affected the protein and ash contents of the fish fillets, while the crude fat remained unchanged. Dietary HIM did not significantly modify total saturated, monounsaturated and polyunsaturated fatty acids in the fillets of fed pikeperch ( P  > 0.05) but did reduce total n-3 fatty acids ( P  = 0.001) and increased total n-6 ( P  < 0.001). Increasing inclusion levels of HIM reduced the environmental impacts associated with fish in-to-fish out ratio but entailed heavy burdens on energy use and eutrophication. Low and moderate inclusion levels of HIM did not negatively affect land use and water use compared to an HIM-free diet ( P  > 0.05). The addition of HIM at a level as low as 9% elicited a similar carbon footprint to that of the control diet. The economic conversion ratio and economic profit index were negatively affected at increased insect meal inclusion levels. This study has shown that the incorporation of HIM in feed formulations for pikeperch is feasible at inclusion levels of 18% without adverse effects on growth performance parameters. The feasibility also highlighted the environmental benefits associated with land use and marine resources required to produce farmed fish., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Compelling animal studies report increased intestinal permeability, inflammation, and colorectal carcinogenesis with exposure to certain emulsifiers commonly added to processed foods, but human data are lacking. Highly processed food consumption is also associated with obesity and higher risk of chronic diseases. We cross-sectionally examined the association of emulsifier and highly processed food consumption estimated from six 24-h dietary recalls among 588 U.S. men and women over one year, with biomarkers of intestinal permeability and inflammation measured from two fasting blood samples collected six months apart. In multivariable-adjusted generalized linear models, greater emulsifier intake (g/d) was not associated with antibodies to flagellin ( P -trend = 0.88), lipopolysaccharide (LPS) ( P -trend = 0.56), or the combined total thereof ( P -trend = 0.65) but was positively associated with an inflammatory biomarker, glycoprotein acetyls (GlycA) ( P -trend = 0.02). Highly processed food intake (% kcal/d) was associated with higher anti-LPS antibodies ( P -trend = 0.001) and total anti-flagellin and anti-LPS antibodies ( P -trend = 0.005) but not with other biomarkers, whereas processed food intake expressed as % g/d was associated with higher GlycA ( P -trend = 0.02). Our findings suggest that, broadly, highly processed food consumption may be associated with intestinal permeability biomarkers, and both emulsifier and highly processed food intakes may be associated with inflammation. Additional studies are warranted to further evaluate these relationships.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1957947.

The study was executed to find out the potential effects spent coffee ground (SCG) on Nile tilapia's skin mucosal and serum immunities, disease prevention, and growth rate reared in a biofloc system. Nile tilapia fingerlings (average weight 15.25 ± 0.07 g) were disseminated into 15 aquaria (150 L tank -1 ) at a density of 20 fish per aquarium and treated five diets: SCG1 (control), SCG2 (10 g kg -1 ), SCG3 (20 g kg -1 ), SCG4 (40 g kg -1 ), and SCG5 (80 g kg -1 ) for eight weeks. A Completely Randomized Design (CRD) with three replications was applied. Growth rate, skin mucus, and serum immunities were quantified every 4 weeks; whereas the challenge study was conducted at the termination of the feeding trial. The outputs indicated that dietary incorporation of SCG give rise to the enhancement of SGR and FCR in comparison with the control, with best levels noted in fish fed SCG2 diet. Similarly, significant enhancements in skin mucosal and serum immunities were revealed in fish treated SCG2 over the control and other SCG diets. Likewise, higher survival rates against Streptococcus agalactiae were displayed in fish fed SCG, with the maximum level displayed in the fish treated SCG2. In conclusion, dietary supplementation of SCG2 (10 g kg -1 ) can be potential used as immunostimulants in tilapia aquaculture., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

High-throughput sequencing (HTS) allows detection of known and unknown viruses in samples of broad origin. This makes HTS a perfect technology to determine whether or not the biological products, such as vaccines are free from the adventitious agents, which could support or replace extensive testing using various in vitro and in vivo assays. Due to bioinformatics complexities, there is a need for standardized and reliable methods to manage HTS generated data in this field. Thus, we developed LABRADOR-an analysis pipeline for adventitious virus detection. The pipeline consists of several third-party programs and is divided into two major parts: (i) direct reads classification based on the comparison of characteristic profiles between reads and sequences deposited in the database supported with alignment of to the best matching reference sequence and (ii) de novo assembly of contigs and their classification on nucleotide and amino acid levels. To meet the requirements published in guidelines for biologicals' safety we generated a custom nucleotide database with viral sequences. We tested our pipeline on publicly available HTS datasets and showed that LABRADOR can reliably detect viruses in mixtures of model viruses, vaccines and clinical samples.

Restocking programmes of different fish species have been implemented worldwide. However, the survival of hatchery-reared fish after release to riverine ecosystems is at a very low level. One of the reasons for the high mortality rate of post-released fish is their modified swimming behaviour due to the hatchery rearing practice. To investigate one of the possible causes for modified swimming behaviour, Acipenser baerii larvae were exposed to surface- and bottom-feeding applications with day and night light regimes in a factorial design. We also analysed the effect of 5 and 10 days of starvation after different feeding applications on sturgeon swimming behaviour. The surface-feeding application was previously expected to promote the frequent Siberian sturgeon swim up to the mid- and top-water layers in our rearing facilities. However, our results indicated that the modified behaviour of the Siberian sturgeon in our study was caused by fish starvation and a possible predator-free environment rather than by the method of feed application or the day/night light regimes. These results may be used to improve the implementation of restocking programmes either through modified hatchery rearing practice or the training of foraging skills with predator stimuli.

The supplementation of fish diets with phytogenics can increase growth performance and can modulate immune system response. European perch Perca fluviatilis (initial weight 25.0 ± 0.4 g) were fed a diet including 0 (Control), 10 (G10), 20 (G20), and 30 (G30) g kg -1 garlic powder. No significant difference in the growth parameters and somatic indices were observed. Significantly higher fat digestibility was observed in G10 and G30 diets compared to in the control and G20 diets( p < 0.05). Significantly greater red blood cell and white blood cell counts were observed with the G10 diet ( p < 0.05). Garlic significantly decreased serum cholesterol in all of the experimental groups. Serum albumin was significantly higher in the G10 and G20 diets ( p < 0.05). Immediately after the overcrowding stress challenge, the garlic groups showed significantly higher cortisol levels than the control group, while no significant difference was observed in the glucose concentration among groups. At 1 h post-stress, all of the groups that had been fed a garlic-supplemented diet showed lower cortisol levels than the control group, and this trend was maintained at 6 and 24 h post stress ( p < 0.05), and glucose level in all garlic groups was significantly lower than control ( p < 0.05). Garlic at 10 g kg -1 in feed can improve apparent fat digestibility and selected blood parameters and can enhance resistance against high-density and net handling stress in Eurasian perch.

In the present study, a possible nature immunostimulant and growth promoter-humic substances (HS) originating from Siberian leonardite mineraloid-were tested on juvenile Clarias gariepinus performance. Feed additive was applied onto commercial pelleted feed at four HS levels-0, 1, 3, and 6% w/w (HS0, HS1, HS3, HS6, respectively). Diets were tested in five repetitions (in total, n = 1800 individuals, mean body weight 28.1 ± 6.2 g) for 56 days. Growth and production parameters, fish condition and somatic indices, and overall mortality were evaluated after 14, 28, 42, and 56 days of exposure. Whereas, plasma samples were collected only after 0, 28, and 56 days, when fish health status was assessed with biochemical parameters (total proteins, TP; alanine aminotransferase, ALT; aspartate aminotransferase, AST; lactate dehydrogenase, LDH; cholesterol, CHOL; triglycerides, TAG) and fish antioxidant status with glutathione (reduced glutathione, GSH; oxidized glutathione, GSSG; glutathione ratio GSH/GSSG). Although a significantly positive effect of HS feed additive on growth performance was not found in the present study, moderately positive effects were found regarding biochemical parameters (ALT, AST, LDH, CHOL, and TAG) and antioxidants (GSH/GSSG ratio) that were improved especially in the HS3 group.

Objectives: Immediate ischemic stroke treatment improves outcomes and early alteplase administration is recommended for patients within window. We implemented stroke guidelines through a neuro-resuscitation initiative (NRI) and hypothesized that the intervention would decrease times to assessment and treatment., Methods: We analyzed quality assurance data for EMS and triage patients arriving to our academic emergency department with suspected ischemic stroke to compare outcomes 12 months before to 6 months after initiative implementation at an academic certified primary stroke center in the U.S. Southwest. We examined four time-based outcomes: neurology at bedside, CT head without contrast, CT head angiogram, and alteplase administration. We summarized times with median and IQR values and compared pre and post times to event (in minutes) with Wilcoxon rank sum tests and Kaplan-Meier survival curves., Results: We identified 203 EMS (83 pre, 120 post) and 66 (11 pre, 55 post) triage Stroke Alert patients. We observed decreased times for all outcomes in both the EMS and triage samples; however, only those in the EMS sample were significant. In the EMS sample, neurology at bedside median times decreased from 20 min to 2 min (p < 0.001); median minutes to CT head without contrast decreased from 16 min to 9 min (p < 0.001); median minutes to CT head angiogram decreased from 71 min to 21 min (p = 0.007); and, median minutes to alteplase decreased from 72 min to 49.5 min (p = 0.04)., Conclusions: An academic ED led stroke care initiative streamlined evaluation and care with significantly shortened times to all four events., Competing Interests: Declaration of competing interest None of the authors report any conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Gut barrier dysfunction promotes chronic inflammation, contributing to several gastrointestinal diseases, including colorectal cancer. Preliminary evidence suggests that vitamin D and calcium could prevent colorectal carcinogenesis, in part, by influencing gut barrier function. However, relevant human data are scarce. We tested the effects of supplemental calcium (1,200 mg/day) and/or vitamin D 3 (1,000 IU/day) on circulating concentrations of biomarkers of gut permeability (anti-flagellin and anti-lipopolysaccharide IgA and IgG, measured via ELISA) from baseline to 1 and 3 or 5 years postbaseline among 175 patients with colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. We also assessed factors associated with baseline concentrations of these biomarkers. We found no appreciable effects of supplemental vitamin D 3 and/or calcium on individual or aggregate biomarkers of gut permeability. At baseline, a combined permeability score (the summed concentrations of all four biomarkers) was 14% lower among women ( P = 0.01) and 10% higher among those who consumed >1 serving per day of red or processed meats relative to those who consumed none ( P trend = 0.03). The permeability score was estimated to be 49% higher among participants with a body mass index (BMI) > 35 kg/m 2 relative to those with a BMI < 22.5 kg/m 2 ( P trend = 0.17). Our results suggest that daily supplemental vitamin D 3 and/or calcium may not modify circulating concentrations of gut permeability biomarkers within 1 or 3-5 years, but support continued investigation of modifiable factors, such as diet and excess adiposity, that could affect gut permeability. PREVENTION RELEVANCE: Calcium and vitamin D may be involved in regulating and maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which results in exposure of the host to luminal bacteria, endotoxins, and antigens leading to potentially cancer-promoting endotoxemia and chronic colon inflammation. While our results suggest that daily supplementation with these chemopreventive agents does not modify circulating concentrations of gut permeability biomarkers, they support continued investigation of other potential modifiable factors, such as diet and excess adiposity, that could alter gut barrier function, to inform the development of treatable biomarkers of risk for colorectal neoplasms and effective colon cancer preventive strategies., (©2020 American Association for Cancer Research.)

In 2009, Vietnam officially decriminalised drug use through amendments to the criminal law. The amendments outlined explicitly that illicit drug use would be seen as an administrative violation, but not a criminal offence. This legal transition has not been without implementation challenges, and police particularly have struggled to find a balance between drug law enforcement and decriminalisation. Despite being a health-orientated drug policy amendment, in practice it allows police to send suspected drug users to compulsory treatment centres without judicial oversight and people who use drugs continue to face challenges in their interface with law enforcement which can negatively impact access to harm reduction and community-based treatment programs. Using policy desk research combined with indepth interviews with 14 key informants from people representing a range of relevant Vietnamese government (n = 10) and non-government agencies (n = 4), this paper explores some insights and considerations into how decriminalisation of drug use in the amended law was implemented. We explore key informant perspectives into how the decriminalisation amendment could be implemented more effectively in order to improve health outcomes for people who use drugs in Vietnam through re-envisioned police protocols and practices. Findings show that while decriminalising drug use in Vietnam was designed as a progressive and health-orientated drug policy, the ongoing disconnect between the health intent of the policy and the police-led oversight of its implementation in the community persists. Part of this disconnect is explained by the lack of training and clear protocols that would enhance the police in their ability to contribute to the health intent of the policy rather than continue to view drug use through a drug law enforcement only lens. The paper calls for further collaboration across policing and the health and community-based organisations delivering services for people who use drugs. We suggest that through developing a deeper understanding of the interplay between policing and the implementation of harm reduction policy and programs, decriminalisation can co-exist within a broader and deeply entrenched drug control strategy in Vietnam., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Acute management of blood pressure in ischemic stroke treated with reperfusion therapy remains uncertain. We evaluated blood pressures during the first 24-hours after reperfusion therapy in relation to in-hospital outcomes., Methods: We conducted a single-center retrospective study of blood pressure in the first 24 hours among ischemic stroke patients who underwent reperfusion therapy with intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) at a tertiary referral center. Blood pressure variability was expressed as the range between the highest and the lowest pressures. Outcomes of interest were discharge disposition and in-hospital mortality. Favorable outcome was defined as a discharge destination to home or inpatient rehabilitation facility (IRF). Multivariable logistic regression analysis was performed with adjustment for age, National Institutes of Health Stroke Scale score, and patients receiving reperfusion therapy., Results: Among the 140 ischemic stroke patients (117 IVT, 84 MT and 61 both), 95 (67.8%) had favorable discharge disposition and 24 (17.1%) died. Higher 24-hour peak systolic blood pressures (SBPs) and peak mean arterial pressures (MAPs) were independently associated with a lower likelihood of favorable discharge disposition, with an adjusted odds ratio (aOR) 0.868, 95 % CI 0.760 - 0.990 per 10 mm Hg for SBP and aOR 0.710, 95% CI 0.515 - 0.980 for MAP, and with increased odds of death aOR 1.244, 95% CI 1.056-1.467 and aOR 1.760, 95% CI 1.119 - 2.769 respectively. Greater variability of SBP and MAP was also associated with odds of death aOR 1.327, 95% CI 1.104 - 1.595 and aOR 1.577, 95% CI 1.060- 2.345 respectively, without a significant effect on discharge disposition., Conclusion: In the first 24 hours after reperfusion therapy, higher peak and variable blood pressures are associated with unfavorable discharge outcomes and increased in-hospital mortality. Further studies in stroke patients undergoing reperfusion therapy might target blood pressure reduction and variability to improve patient outcomes., Competing Interests: Declaration of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Insect meal is gaining increased attention in aquafeed formulations due to high protein content and an essential amino acid profile similar to that of fishmeal. To investigate insect meal in feed for European perch Perca fluviatilis , a promising candidate for European intensive culture, we replaced standard fishmeal with partially defatted black soldier fly Hermetia illucens larva meal at rates of 0%, 20%, 40% and 60% (groups CON, H20, H40 and H60, respectively) and compared growth performance, somatic indices, hematological parameters, whole-body proximate composition and occurrence of spleen lipidosis. In addition, we assessed the economic and environmental sustainability of the tested feeds by calculating economic conversion ratio (ECR) and economic profit index (EPI). The tested groups did not differ in survival rate. Significant differences were documented in final body weight and specific growth rate, with the highest values in CON, H20 and H40. The proximate composition of fish whole-body at the end of the experiment did not differ in dry matter, crude protein or ether extract, while organic matter, ash and gross energy composition showed significant differences. The fatty acid content and n-3/n-6 ratio showed a decreasing trend with increasing H. illucens larva meal inclusion. No differences were found in hematological parameters among tested groups. The H. illucens larva meal inclusion significantly affected ECR and EPI, even at 20% inclusion level the cost of diets did not differ from the control fish meal based diet. Results suggested that 40% inclusion of H. illucens larva meal can be used successfully in standard diets for perch.

Background: Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to micronutrient deficiencies and poor growth in infants from low-resource settings., Objective: We examined associations among EED, SI, growth, and iron status at 6 mo of age., Methods: We performed a cross-sectional analysis of 6-mo-old infants (n = 548) enrolled in a Ugandan birth-cohort study (NCT04233944). EED was assessed via serum concentrations of anti-flagellin and anti- LPS immunoglobulins (Igs); SI was assessed via serum concentrations of ɑ1-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis., Results: At 6 mo, ∼35% of infants were stunted [length-for-age z score (LAZ) < -2] and ∼53% were anemic [hemoglobin (Hb) <11.0 g/dL]. Nearly half (∼46%) had elevated AGP (>1 g/L) and ∼30% had elevated CRP (>5 mg/L). EED and SI biomarkers were significantly correlated (r = 0.142-0.193, P < 0.001 for all). In adjusted linear regression models, which included adjustments for SI, higher anti-flagellin IgA, anti-LPS IgA, and anti-LPS IgG concentrations were each significantly associated with lower LAZ [β (95% CI): -0.21 (-0.41, 0.00), -0.23 (-0.44, -0.03), and -0.33 (-0.58, -0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA concentrations were significantly associated with lower Hb [β (95% CI): -0.24 (-0.45, -0.02), -0.58 (-1.13, 0.00), and -0.26 (-0.51, 0.00)] and higher anti-flagellin IgG and anti-LPS IgG concentrations were significantly associated with higher sTfR [β (95% CI): 2.31 (0.34, 4.28) and 3.13 (0.75, 5.51)]., Conclusions: EED is associated with both low LAZ and iron status in 6-mo-old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

In the present study, we investigated whether mood stabilizer lithium (Li) protects against d-amphetamine (AMP)-induced mania-like behaviours via modulating the novel proinflammatory potential. Repeated treatment with AMP resulted in significant increases in proinflammatory cyclooxygenase-2 (COX-2) and indolemaine-2,3-dioxygenase-1 (IDO)-1 expression in the prefrontal cortex (PFC) of mice. However, AMP treatment did not significantly change IDO-2 and 5-lipoxygenase (5-LOX) expression, suggesting that proinflammatory parameters such as COX-2 and IDO-1 are specific for AMP-induced behaviours. AMP-induced initial expression of COX-2 (15 minutes post-AMP) was earlier than that of IDO-1 (1 hour post-AMP). Mood stabilizer Li and COX-2 inhibitor meloxicam significantly attenuated COX-2 expression 15 minutes post-AMP, whereas IDO-1 inhibitor 1-methyl-DL-tryptophan (1-MT) did not affect COX-2 expression. However, AMP-induced IDO-1 expression was significantly attenuated by Li, meloxicam or 1-MT, suggesting that COX-2 is an upstream molecule for the induction of IDO-1 caused by AMP. Consistently, co-immunoprecipitation between COX-2 and IDO-1 was observed at 30 minutes, 1, 3, and 6 hours after the final AMP treatment. This interaction was also significantly inhibited by Li, meloxicam or 1-MT. Furthermore, AMP-induced hyperlocomotion was significantly attenuated by Li, meloxicam or 1-MT. We report, for the first time, that mood stabilizer Li attenuates AMP-induced mania-like behaviour via attenuation of interaction between COX-2 and IDO-1, and that the interaction of COX-2 and IDO-1 may be critical for the therapeutic intervention mediated by mood stabilizer., (© 2019 John Wiley & Sons Australia, Ltd.)

Porphyromonas gingivalis, the major human pathogen associated to periodontal diseases, utilizes the Bacteroidetes-specific type IX secretion system (T9SS) to export virulence factors. PorE is a periplasmic multi-domain lipoprotein associated to the outer membrane that was recently identified as essential for T9SS function. Little is known on T9SS at the structural level, and in particular its interaction with peptidoglycan. This prompted us to carry out structural studies on PorE full length as well as on its four isolated domains. Here we report the crystal structure of the C-terminal OmpA&#95;C-like putative peptidoglycan-binding domain at 1.55 Å resolution. An electron density volume was identified in the protein cleft, making it possible to build a naturally-occurring peptidoglycan fragment. This result suggests that PorE interacts with peptidoglycan and that PorE could anchor T9SS to the cell wall.

Purpose: Clinical tissue engineering has revolutionized surgery by improving surgical efficiency and decreasing the risks associated with traditional bone graft procurement techniques. Compared with autogenous bone grafts, composite tissue-engineered grafts fulfill the principles of osteoconduction, osteoinduction, and osteogenesis and provide adequate bone volume for maxillofacial reconstruction with less morbidity. The present study aimed to demonstrate the effectiveness, as defined by our success criteria, of a composite tissue-engineered bone graft in the reconstruction of mandibular defects., Patients and Methods: We implemented a retrospective case series and enrolled a sample of patients with mandibular defects that had been reconstructed using allogeneic bone combined with recombinant human bone morphogenic protein-2 and bone marrow aspirate concentrate at our institution during a 5-year period. The success criteria were as follows: 1) bone union, defined as a homogenous radiopaque pattern continuous with native bone without mandibular mobility; and 2) volume of grafted bone adequate for implant placement, defined as at least 1.0 cm (height) by 0.8 cm (width). Clinical examinations and computed tomography scans were performed at 6 months postoperatively. Descriptive statistics were computed for each variable., Results: From 2014 to 2019, tissue engineering reconstruction was used in 31 patients with and 3 patients without mandibular continuity defects, for a total of 34 patients. The median follow-up was 6 months. The mean length of the continuity defects was 5.5 cm (range, 1.0 to 12.5). Of the 30 patients with mandibular continuity defects, 27 achieved success according to our criteria, with an average gained height of 2.12 ± 0.64 cm and width of 1.53 ± 0.46 cm. Of the 34 patients, 1 was lost to follow-up, and treatment failed in 3 patients., Conclusions: Although the use of autogenous graft remains the reference standard, the evolving science behind clinical tissue engineering has resulted in an effective treatment modality for complex head and neck defects with less morbidity and graft material equal to that of autogenous bone., (Copyright © 2019 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e., lithium and valproate) modulate IDO to protect against AMPH-induced mania-like behaviors. AMPH-induced IDO-1 expression was significantly greater than IDO-2 expression in the prefrontal cortex of wild type mice. IDO-1 expression was more pronounced in the mitochondria than in the cytosol. AMPH treatment activated intra-mitochondrial Ca 2+ accumulation and mitochondrial oxidative burden, while inhibited mitochondrial membrane potential and activity of the mitochondrial complex (I > II), mitochondrial glutathione peroxidase, and superoxide dismutase, indicating that mitochondrial burden might be contributable to mania-like behaviors induced by AMPH. The behaviors were significantly attenuated by lithium, valproate, or IDO-1 knockout, but not in IDO-2 knockout mice. Lithium, valproate administration, or IDO-1 knockout significantly attenuated mitochondrial burden. Neither lithium nor valproate produced additive effects above the protective effects observed in IDO-1 KO in mice. Collectively, our results suggest that mood stabilizers attenuate AMPH-induced mania-like behaviors via attenuation of IDO-1-dependent mitochondrial stress, highlighting IDO-1 as a novel molecular target for the protective potential of mood stabilizers., 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 © 2019 Elsevier Ltd. All rights reserved.)

Background & Aims: Consumption of a low-fiber, high-fat, Western-style diet (WSD) induces adiposity and adipose inflammation characterized by increases in the M1:M2 macrophage ratio and proinflammatory cytokine expression, both of which contribute to WSD-induced metabolic syndrome. WSD-induced adipose inflammation might result from endoplasmic reticulum stress in lipid-overloaded adipocytes and/or dissemination of gut bacterial products, resulting in activation of innate immune signaling. Hence, we aimed to investigate the role of the gut microbiota, and its detection by innate immune signaling pathways, in WSD-induced adipose inflammation., Methods: Mice were fed grain-based chow or a WSD for 8 weeks, assessed metabolically, and intestinal and adipose tissue were analyzed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Microbiota was ablated via antibiotics and use of gnotobiotic mice that completely lacked microbiota (germ-free mice) or had a low-complexity microbiota (altered Schaedler flora). Innate immune signaling was ablated by genetic deletion of Toll-like receptor signaling adaptor myeloid differentiation primary response 88., Results: Ablation of microbiota via antibiotic, germ-free, or altered Schaedler flora approaches did not significantly impact WSD-induced adiposity, yet dramatically reduced WSD-induced adipose inflammation as assessed by macrophage populations and cytokine expression. Microbiota ablation also prevented colonic neutrophil and CD103 - dendritic cell infiltration. Such reduced indices of inflammation correlated with protection against WSD-induced dysglycemia, hypercholesterolemia, and liver dysfunction. Genetic deletion of myeloid differentiation primary response 88 also prevented WSD-induced adipose inflammation., Conclusions: These results indicate that adipose inflammation, and some aspects of metabolic syndrome, are not purely a consequence of diet-induced adiposity per se but, rather, may require disturbance of intestine-microbiota interactions and subsequent activation of innate immunity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin's impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases.

Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders. Several mechanisms of action for metformin have been proposed, including that it acts as an anti-inflammatory agent, possibly as a result of its impact on intestinal microbiota. In accord with this possibility, we observed herein that, in mice with diet-induced metabolic syndrome, metformin impacts the gut microbiota by preventing its encroachment upon the host, a feature of metabolic syndrome in mice and humans. However, the ability of metformin to beneficially impact metabolic syndrome in mice was not markedly altered by reduction or elimination of gut microbiota, achieved by the use of antibiotics or germfree mice. Although reducing or eliminating microbiota by itself suppressed diet-induced dysglycemia, other features of metabolic syndrome including obesity, hepatic steatosis, and low-grade inflammation remained suppressed by metformin in the presence or absence of gut microbiota. These results support a role for anti-inflammatory activity of metformin, irrespective of gut microbiota, in driving some of the beneficial impacts of this drug on metabolic syndrome.

Since the first time mussel-inspired polymer polydopamine (PDA) was discovered, it has gained enormous attention from numerous scientists, especially those working in the field of drug delivery and bacterial and tumor treatment, due to its distinctive properties, such as surface chemistry, biocompatibility, capability to adhere to any surface, and excellent photothermal conversion. Studies using PDA in various types of structures for therapeutic purposes have been carried out extensively in recent years. Considering the rapid development in the area, this review aims to cover and highlight the latest achievements (from 2016 to present) with respect to PDA-based materials for therapeutic purposes. A description of the diverse structures of PDA and its formation strategy, including colloidal particles, hollow structures, and coating films, are discussed. In addition, the main focus of this review is on the therapeutic applications of these PDA nanostructures., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. Although genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice ( n = 50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 ( n = 5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. Although future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity., (© 2019 Tran et al.)

Herein, we present a systematic study on the preparation of polydopamine (PDA) hollow capsules by templating silica particles which were subsequently removed by a PDA mediated water dissolution process without using any harsh chemical treatment. It was found that the time required for silica removal varied depending on the PDA coating and dissolution conditions. Factors that could influence the core removal process including the PDA thickness and coating temperature, silica calcination duration and the availability of water were then examined in detail. Additionally, catalase was used as a model enzyme to be encapsulated into PDA hollow capsules and its bio-functionality was found to remain active. The bioactivity test results also indicated that the as-synthesized PDA capsules possessed a porous structure, which allows the penetration of small molecules such as H 2 O 2 . This study offers a better insight into silica dissolution process that mediated by PDA and contributes to the development of an eco-friendly approach for the fabrication of hollow capsules that have promising applications in drug delivery systems.

Objective: To examine whether daily zinc and/or multivitamin supplementation reduce biomarkers of environmental enteric dysfunction (EED), systemic inflammation, or markers of growth in a sample of infants from Dar es Salaam, Tanzania., Study Design: Subgroup analysis of infants participating in a randomized, double-blind, placebo-controlled trial received daily oral supplementation of zinc, multivitamins, zinc + multivitamins, or placebo for 18 months starting at 6 weeks of age. EED (anti-flagellin and anti-lipopolysaccharide immunoglobulins), systemic inflammation (C-reactive protein and alpha-1-acid glycoprotein), and growth biomarkers (insulin-like growth factor-1 and insulin-like growth factor binding protein-3) were measured via enzyme-linked immunosorbent assay in a subsample of 590 infants at 6 weeks and 6 months of age. EED biomarkers also were measured in 162 infants at 12 months of age., Results: With the exception of anti-lipopolysaccharide IgG concentrations, which were significantly greater in infants who received multivitamins compared with those who did not (1.41 ± 0.61 vs 1.26 ± 0.65, P = .006), and insulin-like growth factor binding protein-3 concentrations, which were significantly lower in children who received zinc compared with those who did not (981.13 ± 297.59 vs 1019.10 ± 333.01, P = .03), at 6 months of age, we did not observe any significant treatment effects of zinc or multivitamins on EED, systemic inflammation, or growth biomarkers., Conclusions: Neither zinc nor multivitamin supplementation ameliorated markers of EED or systemic inflammation during infancy. Other interventions should be prioritized for future trials., Trial Registration: Clinicaltrials.gov: NCT00421668., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Methiopropamine (MPA) is structurally categorized as a thiophene ring-based methamphetamine (MA) derivative. Although abusive potential of MPA was recognized, little is known about the neurotoxic potential of MPA up to now. We investigated whether MPA induces dopaminergic neurotoxicity, and whether MPA activates a specific dopamine receptor. Here, we observed that treatment with MPA resulted in dopaminergic neurotoxicity in a dose-dependent manner. MPA treatment potentiated oxidative parameters (i.e., increases in the level of reactive oxygen species, 4-hydroxynonenal, and protein carbonyl), M1 phenotype-related microglial activity, and pro-apoptotic property (i.e., increases in Bax- and cleaved caspase-3-expressions, while a decrease in Bcl-2-expression). Moreover, treatment with MPA resulted in significant impairments in dopaminergic parameters [i.e., changes in dopamine level, dopamine turnover rate, tyrosine hydroxylase (TH) levels, dopamine transporter (DAT) expression, and vesicular monoamine transporter-2 (VMAT-2) expression], and in behavioral deficits. Both dopamine D1 receptor antagonist SCH23390 and D2 receptor antagonist sulpiride protected from these neurotoxic consequences. Therefore, our results suggest that dopamine D1 and D2 receptors simultaneously mediate MPA-induced dopaminergic neurodegeneration in mice via oxidative burdens, microgliosis, and pro-apoptosis., (Copyright © 2019. Published by Elsevier B.V.)

Direct covalent functionalization of large-area single-layer hexagonal boron nitride (hBN) with various polymer brushes under mild conditions is presented. The photopolymerization of vinyl monomers results in the formation of thick and homogeneous (micropatterned, gradient) polymer brushes covalently bound to hBN. The brush layer mechanically and chemically stabilizes the material and allows facile handling as well as long-term use in water splitting hydrogen evolution reactions., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Elevated systemic exposure to gut-derived bacterial products has been associated with hepatic inflammation and chronic liver diseases, potentially increasing the risk of liver cancer. However, only one prior study prospectively examined exposure to bacterial products in the circulation and risk of liver cancer, with a relatively limited coverage of biomarkers., Methods: We conducted a nested case-control study (224 liver cancer cases and 224 matched controls) in a large cohort of Finnish male smokers followed from baseline (1985-1988) to 2014. The associations between a panel of biomarkers for bacterial translocation and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression. The biomarkers included immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and the LPS-binding protein., Results: Anti-flagellin IgA [odds ratios (OR), 2.79; 95% confidence intervals (CI), 1.34-5.78; P trend = 0.01] and anti-LPS IgA (2.44; 95% CI, 1.33-4.48; P trend < 0.01) were significantly associated with risk of liver cancer. When restricting the analysis to histologically classified hepatocellular carcinoma, the ORs were 4.18 (95% CI, 1.60-10.92; P trend < 0.01) and 2.48 (95% CI, 1.16-5.29; P trend < 0.01), respectively. The results were not substantially changed after excluding cases diagnosed within the first 5 years of follow-up and those with hepatitis C virus infection., Conclusions: Antibodies to flagellin and LPS were associated with increased risk of liver cancer., Impact: Gut-derived bacterial translocation into the circulation may play a role in the development of primary liver cancer. Our findings could contribute to the understanding of primary liver cancer etiology and further prevention efforts., (©2019 American Association for Cancer Research.)

The abuse of methamphetamine (MA), an amphetamine (AMPH)-type stimulant, has been demonstrated to be associated with various neuropsychotoxicity, including memory impairment, psychiatric morbidity, and dopaminergic toxicity. Compelling evidence from preclinical studies has indicated that protein kinase C (PKC), a large family of serine/threonine protein kinases, plays an important role in MA-induced neuropsychotoxicity. PKC-mediated N-terminal phosphorylation of dopamine transporter has been identified as one of the prerequisites for MA-induced synaptic dopamine release. Consistently, it has been shown that PKC is involved in MA (or AMPH)-induced memory impairment and mania-like behaviors as well as MA drug dependence. Direct or indirect regulation of factors related to neuronal plasticity seemed to be critical for these actions of PKC. In addition, PKC-mediated mitochondrial dysfunction, oxidative stress or impaired antioxidant defense system has been suggested to play a role in psychiatric and cognitive disturbance induced by MA (or AMPH). In MA-induced dopaminergic toxicity, particularly PKCδ has been shown to trigger oxidative stress, mitochondrial dysfunction, pro-apoptotic changes, and neuroinflammation. Importantly, PKCδ may be a key mediator in the positive feedback loop composed of these detrimental events to potentiate MA-induced dopaminergic toxicity. This review outlines the role of PKC and its individual isozymes in MA-induced neuropsychotoxicity. Better understanding on the molecular mechanism of PKCs might provide a great insight for the development of potential therapeutic or preventive candidates for MA (or AMPH)-associated neuropsychotoxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Serotonin syndrome is an adverse reaction due to increased serotonin (5-hydroxytryptophan: 5-HT) concentrations in the central nervous system (CNS). The full 5-HT 1A receptor (5-HT 1A R) agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) has been recognized to elicit traditional serotonergic behaviors. Treatment with 8-OH-DPAT selectively increased PKCδ expression out of PKC isoforms and 5-HT turnover rate in the hypothalamus of wild-type mice. Treatment with 8-OH-DPAT resulted in oxidative burdens, co-immunoprecipitation of 5-HT 1A R and PKCδ, and phosphorylation and membrane translocation of p47phox. Importantly, p47phox also interacted with 5-HT 1A R or PKCδ in the presence of 8-OH-DPAT. Consistently, the interaction and oxidative burdens were attenuated by 5-HT 1A R antagonism (i.e., WAY100635), PKCδ inhibition (i.e., rottlerin and genetic depletion of PKCδ), or NADPH oxidase/p47phox inhibition (i.e., apocynin and genetic depletion of p47phox). However, WAY100635, apocynin, or rottlerin did not exhibit any additive effects against the protective effect by inhibition of PKCδ or p47phox. Furthermore, apocynin, rottlerin, or WAY100635 also significantly protected from pro-inflammatory/pro-apoptotic changes induced by 8-OH-DPAT. Therefore, we suggest that 8-OH-DPAT-induced serotonergic behaviors requires oxidative stress, pro-inflammatory, and pro-apoptotic changes, that PKCδ or p47phox mediates the serotonergic behaviors induced by 8-OH-DPAT, and that the inhibition of PKCδ-dependent p47phox activation is critical for protecting against serotonergic behaviors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of schizophrenia., Aims: We investigated whether antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate oxidase and mitochondrial burdens induced by phencyclidine in mice., Methods: We examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate oxidase activation, mitochondrial burdens (i.e. oxidative stress and mitochondrial dysfunction), and activities of enzymatic antioxidant in the prefrontal cortex, and subsequent abnormal behaviors induced by repeated treatment with phencyclidine. p47 phox Knockout mice and LY294002, a phosphoinositide 3-kinase inhibitor, were employed to elucidate the pharmacological mechanism of clozapine., Results: Phencyclidine treatment resulted in an early increase nicotinamide adenine dinucleotide phosphate oxidase activity, membrane translocation of p47 phox , interaction between p-Akt and p47 phox , and mitochondrial burdens in wild-type mice. Although these increases returned to near control level four days post-phencyclidine, mitochondrial superoxide dismutase and glutathione peroxidase activities were decreased at that time. Clozapine, LY294002, or p47 phox knockout significantly ameliorated social withdrawal and recognition memory deficits produced by phencyclidine. Importantly, LY294002 did not significantly alter the effects of clozapine against abnormal behaviors and the interaction between p-Akt and p47 phox induced by phencyclidine. Furthermore, neither LY294002 nor clozapine exhibited any additive effects to the protection afforded by p47 phox knockout against phencyclidine insult., Conclusion: Our results suggest that p47 phox gene mediates phencyclidine-induced mitochondrial burdens and abnormal behaviors, and that the interactive modulation between p47 phox and phosphoinositide 3-kinase/Akt is important for the understanding on the pharmacological mechanism of clozapine.