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Nypa fruticans Wurmb is known to contain large amounts of polyphenols and flavonoids with antioxidative and anti-inflammatory effects. However, the biological and physiological functions of N. fruticans have not been scientifically investigated. Thus, we investigated the immunomodulatory effect of N. fruticans hot water extract (YSK-N) in mice using an immune compromised model established by forced swimming (FS). Intensive exercise decreased body weight, organ index, and various immunological parameters in FS mice. However, oral administration of YSK-N significantly restored the FS-induced decreases in body, thymus, and spleen weights, as well as the reduction in the numbers of white blood cells and lymphocytes in the whole blood of mice. Additionally, YSK-N increased splenic cell proliferation in the absence and presence of concanavalin A or lipopolysaccharide stimulation in a concentration-dependent manner. Notably, YSK-N enhanced the cytotoxic activity of natural killer cells against YAC-1 tumor cells under immunosuppressive conditions. Furthermore, YSK-N supplementation reverted the FS-induced downregulation in immunoglobulin production and Il2 , Il6 , Il12 , Ifnγ , Gzmb , and Prf1 mRNA expression. Therefore, our observations suggested that YSK-N promotes immune function and has potential as an immunomodulatory agent.

Lithium-sulfur batteries (LSBs) have emerged as a promising next-generation energy storage application owing to their high specific capacity and energy density. However, inherent insulating property of sulfur, along with its significant volume expansion during cycling, and shuttling behavior of lithium-polysulfides (LiPSs), hinder their practical application. To overcome these issues, a crosslinked cationic waterborne polyurethane (CCWPU) is rationally designed as a binder for LSBs. The mechanical robustness of CCWPU enables it to withstand the high stress derived from volume expansion of sulfur, facilitating charge-transferring through conserved charge-transfer pathway and promoting interconversion of LiPSs. Additionally, polar urethane groups offer favorable interaction sites with LiPSs, mitigating shuttling behavior of LiPSs via polar-polar interaction. Density functional theory investigations further elucidate that the incorporation of cationic moieties enhances LiPSs immobilization by confining S n x- (x = 1 or 2) in LiPSs, thereby improving sulfur utilization. Benefiting from these, the cell with CCWPU demonstrates reduced polarization, superior LiPSs conversion rates, and stable cycling performance. Moreover, water-processable nature of CCWPU aligns with environmental consciousness. These diverse functionalities of CCWPU provide valuable insights for the development of advanced binder for LSBs, ultimately improving the electrochemical performances of LSBs., (© 2024 Wiley‐VCH GmbH.)

Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10 -15 ) with PD risk. Moreover, 80.5% of SMPD1 carriers harbored the Asian-specific p.Pro332Arg variant (OR = 2.16; P = 4.47 × 10 -8 ). Our findings highlight the utility of performing exome sequencing in diverse ancestry groups to identify rare protein-altering variants in genes previously unassociated with disease., Competing Interests: Competing interests: Z.G.-O. received consultancy fees from Lysosomal Therapeutics, Idorsia, Prevail Therapeutics, Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, Bial Biotech, Bial, UCB, Capsida, Vanqua Bio, Congruence Therapeutics, Takeda, Jazz Pharmaceuticals, Guidepoint, Lighthouse and Deerfield. R.N.A. received consultation fees from Biogen, Biohaven, Capsida, Gain Therapeutics, Genzyme/Sanofi, Janssen, Servier, SK Biopharmaceuticals, Takeda and Vanqua Bio. Y.X. holds a stock option in NeoCytogen Therapeutics where she is scientific co-founder and Chief Scientific Officer. M.A.N.’s participation in this project was part of a competitive contract awarded to DataTecnica, LLC by the National Institutes of Health to support open science research. M.A.N. also owns stock in Character Bio, Inc. and Neuron23, Inc. The other authors declare no competing interests., (© 2024. The Author(s).)

Environmental pollution continues to increase with industrial development and has become a threat to human health. Atmospheric particulate matter (PM) was designated as a Group 1 carcinogen by the International Agency for Research on Cancer in 2013 and is an emerging global environmental risk factor that is a major cause of death related to cardiovascular and respiratory diseases. PM is a complex composed of highly reactive organic matter, chemicals, and metal components, which mainly cause excessive production of reactive oxygen species (ROS) that can lead to DNA and cell damage, endoplasmic reticulum stress, inflammatory responses, atherosclerosis, and airway remodeling, contributing to an increased susceptibility to and the exacerbation of various diseases and infections. PM has various effects on human health depending on the particle size, physical and chemical characteristics, source, and exposure period. PM smaller than 5 μm can penetrate and accumulate in the alveoli and circulatory system, causing harmful effects on the respiratory system, cardiovascular system, skin, and brain. In this review, we describe the relationship and mechanism of ROS-mediated cell damage, oxidative stress, and inflammatory responses caused by PM and the health effects on major organs, as well as comprehensively discuss the harmfulness of PM.

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: : Functional dyspepsia (FD) has long been regarded as a syndrome because its pathophysiology is multifactorial. However, recent reports have provided evidence that changes in the duodenal ecosystem may be the key. This study aimed to identify several gastrointestinal factors and biomarkers associated with FD, specifically changes in the duodenal ecosystem that may be key to understanding its pathophysiology., Methods: : In this case-control study, 28 participants (12 with FD and 16 healthy control individuals) were assessed for dietary nutrients, gastrointestinal symptom severity, immunological status of the duodenal mucosa, and microbiome composition from oral, duodenal, and fecal samples. Integrated data were analyzed using immunohistochemistry, real-time polymerase chain reaction, 16S rRNA sequencing, and network analysis., Results: : Duodenal mucosal inflammation and impaired expression of tight junction proteins were confirmed in patients with FD. The relative abundance of duodenal Streptococcus (p=0.014) and reductions in stool Butyricicoccus (p=0.047) were confirmed. These changes in the gut microbiota were both correlated with symptom severity. Changes in dietary micronutrients, such as higher intake of valine, were associated with improved intestinal barrier function and microbiota., Conclusions: : This study emphasizes the relationships among dietary nutrition, oral and gut microbiota, symptoms of FD, impaired function of the duodenal barrier, and inflammation. Assessing low-grade inflammation or increased permeability in the duodenal mucosa, along with changes in the abundance of stool Butyricicoccus , is anticipated to serve as effective biomarkers for enhancing the objectivity of FD diagnosis and monitoring.

Chronic obstructive pulmonary disease (COPD), the major leading cause of mortality worldwide, is a progressive and irreversible respiratory condition characterized by peripheral airway and lung parenchymal inflammation, accompanied by fibrosis, emphysema, and airflow limitation, and has multiple etiologies, including genetic variance, air pollution, and repetitive exposure to harmful substances. However, the precise mechanisms underlying the pathogenesis of COPD have not been identified. Recent multiomics-based evidence suggests that the plasticity of alveolar macrophages contributes to the onset and progression of COPD through the coordinated modulation of numerous transcription factors. Therefore, this review focuses on understanding the mechanisms and functions of macrophage polarization that regulate lung homeostasis in COPD. These findings may provide a better insight into the distinct role of macrophages in COPD pathogenesis and perspective for developing novel therapeutic strategies targeting macrophage polarization.

After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8 + T cell-mediated and dependent on antigen presentation by CD14 + cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.

Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema, dysfunction of endothelial and epithelial barriers, and the activation of inflammatory cascades. Despite the increasing number of deaths attributed to ARDS, a comprehensive therapeutic approach for managing patients with ARDS remains elusive. To elucidate the pathological mechanisms underlying ARDS, numerous studies have employed various preclinical models, often utilizing lipopolysaccharide as the ARDS inducer. Accumulating evidence emphasizes the pivotal role of reactive oxygen species (ROS) in the pathophysiology of ARDS. Both preclinical and clinical investigations have asserted the potential of antioxidants in ameliorating ARDS. This review focuses on various sources of ROS, including NADPH oxidase, uncoupled endothelial nitric oxide synthase, cytochrome P450, and xanthine oxidase, and provides a comprehensive overview of their roles in ARDS. Additionally, we discuss the potential of using antioxidants as a strategy for treating ARDS.

Silicon has garnered significant attention as a promising anode material for high-energy density Li-ion batteries. However, Si can be easily pulverized during cycling, which results in the loss of electrical contact and ultimately shortens battery lifetime. Therefore, the Si anode binder is developed to dissipate the enormous mechanical stress of the Si anode with enhanced mechanical properties. However, the interfacial stability between the Si anode binder and Cu current collector should also be improved. Here, a multifunctional thiourea polymer network (TUPN) is proposed as the Si anode binder. The TUPN binder provides the structural integrity of the Si anode with excellent tensile strength and resilience due to the epoxy-amine and silanol-epoxy covalent cross-linking, while exhibiting high extensibility from the random coil chains with the hydrogen bonds of thiourea, oligoether, and isocyanurate moieties. Furthermore, the robust TUPN binder enhances the interfacial stability between the Si anode and current collector by forming a physical interaction. Finally, the facilitated Li-ion transport and improved electrolyte wettability are realized due to the polar oligoether, thiourea, and isocyanurate moieties, respectively. The concept of this work is to highlight providing directions for the design of polymer binders for next-generation batteries., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.

Background and Purpose: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data., Methods: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty., Results: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p =0.002) and amyloid-PET-positive (OR=3.80, p =0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p =0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p =0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests., Conclusions: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Superbase-based ionic liquids (ILs) have demonstrated excellent dissolution capability for cellulose, and employing the dry-jet wet spinning process, high-tenacity regenerated textile fibers have been made. Among a range of superbase-based ILs, [mTBDH][OAc] exhibited not only good spinnability but also exceptional recyclability, making it highly suitable for a closed-loop production of regenerated cellulose fibers. To further optimize the spinning process, we investigated the influence of the cellulosic raw materials and the IL with residual water on spinnability and fiber properties. In addition, single-filament spinning and multifilament spinning using spinnerets with different hole densities were investigated to reveal the upscaling challenges of the dry-jet wet spinning process. The air gap conditions, for example, temperature and moisture concentration were simulated using COMSOL multiphysics. The results indicate that the presence of a small amount of water (3 wt%) in the IL has a positive effect on spinnability, while the mechanical properties of the fibers remain unchanged., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Particulate matter (PM) induces and augments oxidative stress and inflammation, leading to respiratory diseases. Although Artemisia gmelinii Weber ex Stechm has antioxidant and anti-inflammatory effects, there are no reports on whether Artemisia gmelinii extract (AGE) regulates lung inflammation in a PM-induced model. Thus, we investigated the protective effects of AGE using a PM-induced mouse lung inflammation model. AGE significantly decreased the expression of inflammatory chemokines, neutrophil extracellular trap formation, and the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Furthermore, AGE attenuated lung inflammation through the suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, while promoting the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway in lung tissues. Concordant with these observations, AGE suppressed inflammatory cytokines, chemokines, reactive oxygen species, NETosis, myeloperoxidase, and neutrophil elastase by decreasing the mRNA expression of High mobility group box 1, Runt-related transcription factor 1, and Kruppel-like factor 6 in differentiated HL-60 cells. In summary, our data demonstrated that AGE suppresses PM-induced neutrophil infiltration, lung damage, and pulmonary inflammation by suppressing NF-κB/MAPK signaling pathways and enhancing the NRF2/HO-1 signaling pathway. These findings suggest that AGE administration is an effective approach for preventing and treating PM-induced respiratory inflammation.

Behavioral state plays an important role in determining astroglia Ca 2+ signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca 2+ elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca 2+ elevations depend on their α 1A -adrenergic receptors. With increasing availability and implementation of locomotion as behavioral parameter it becomes important to understand the constraints of noradrenergic signaling to astroglia. Here we evaluated the effect of speed, duration and interval of locomotion on Ca 2+ signals in Bergmann glia as well as cerebellar noradrenergic axon terminals. We found almost no dependence on locomotion speed, but following the initial Ca 2+ transient prolonged locomotion events revealed a steady-state Ca 2+ elevation. Comparison of time course and recovery of transient Bergmann glia and noradrenergic terminal Ca 2+ dynamics suggested that noradrenergic terminal Ca 2+ activity determines Bergmann glia Ca 2+ activation and does not require noradrenergic receptor desensitization to account for attenuation during prolonged locomotion. Further, analyzing the correlation among Ca 2+ dynamics within regions within the field of observation we found that coordinated activity among noradrenergic terminals accounts for fluctuations of steady-state Bergmann glia Ca 2+ activity. Together, our findings will help to better understand astroglia Ca 2+ dynamics during less controlled awake behavior and may guide the identification of behavioral contexts preferably dependent on astroglia Ca 2+ signaling., (© 2023 Wiley Periodicals LLC.)

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.

Background: The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients., Methods: In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data., Findings: 156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30-44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm 3 (IQR 349-828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2-9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period., Interpretation: Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In May 2022, the World Health Organisation declared a multi-country monkeypox outbreak in non-endemic countries following cases reported from 12 member states that were not endemic for monkeypox virus., Sources of Data: Pubmed search., Areas of Agreement: The virology, epidemiology, transmission, incubation and aspects of infection control are described. Clinical features of previous and current outbreaks are described, with growing observations that the current outbreak presents with clinical features distinct from previous outbreaks., Areas of Controversy: There are variations in clinical presentations seen in the current outbreak that have not been seen in prior outbreaks. More research is needed to investigate the reasons for these differences., Growing Points: The higher numbers of HIV-positive patients in the current outbreak has allowed better description of the disease in patients co-infected with HIV and monkeypox. The absence of more severe symptoms in HIV-positive patients in the current outbreak could possibly be due to the fact that most of these patients had well-controlled HIV, although further characterization of this cohort of patients would be useful., Areas for Developing Research: Current treatment and vaccination options have been extrapolated from studies of other Orthopox viruses. There remains a need for more data on the safety and efficacy of these options in the context of monkeypox infections., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Human cytomegalovirus (HCMV) infection and periodic reactivation is, generally, well controlled by adaptative immune responses in the healthy. In older people, overt HCMV disease is rarely seen despite the association of HCMV with increased risk of mortality; evidence from studies of unwell aged populations suggest that HCMV seropositivity is an important co-morbidity factor. HCMV genomes have been detected in urine from older donors, suggesting that the immune response prevents systemic disease but possibly immunomodulation due to lifelong viral carriage may alter its efficacy at peripheral tissue sites. Previously we have demonstrated that there were no age-related expansions of T cell responses to HCMV or increase in latent viral carriage with age and these T cells produced anti-viral cytokines and viremia was very rarely detected. To investigate the efficacy of anti-HCMV responses with increasing age, we used an in vitro Viral Dissemination Assay (VDA) using autologous dermal fibroblasts to determine the anti-viral effector capacity of total PBMC, as well as important subsets (T cells, NK cells). In parallel we assessed components of the humoral response (antibody neutralization) and combined this with qPCR detection of HCMV in blood, saliva and urine in a cohort of young and old donors. Consistent with previous studies, we again show HCMV specific cIL-10, IFNγ and TNFα T cell responses to peptides did not show an age-related defect. However, assessment of direct anti-viral cellular and antibody-mediated adaptive immune responses using the VDA shows that older donors are significantly less able to control viral dissemination in an in vitro assay compared to young donors. Corroborating this observation, we detected viral genomes in saliva samples only from older donors, these donors had a defect in cellular control of viral spread in our in vitro assay. Phenotyping of fibroblasts used in this study shows expression of a number of checkpoint inhibitor ligands which may contribute to the defects observed. The potential to therapeutically intervene in checkpoint inhibitor pathways to prevent HCMV reactivation in the unwell aged is an exciting avenue to explore., 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 © 2022 Davies, Noor, Lim, Houldcroft, Okecha, Atkinson, Reeves, Jackson and Wills.)

Both biochar supplementation as well as bioaugmentation have been shown in literature to improve the methane yield of anaerobic digestion. In this study, the combination of both are evaluated by growing Methanosarcina thermophila on biochar support particles prior to augmentation of thermophilic food waste anaerobic digestion. Biochar stand alone, bioaugmentation solely, a combination of both added separately or grown together, and utilizing polypropylene (PP) microplastics as growth support instead were all tested when starting up a thermophilic process from mesophilic inoculum. Methanosarcina thermophila and biochar supplementation displayed synergy, with 5% M. thermophila on 1 g/L biochar presenting a 32% increase in specific methane yield over the control. Double the bioaugmentation dosage/concentration was also trialled with a thermophilic inoculum, and 10% M. thermophila grown on 2 g/L biochar displayed the best results with a 20% increase specific methane yield from its control standard., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study presents the effect of bioaugmentation of thermophilic anaerobic digestion of food waste with Methanosarcina thermophila grown on a wood-derived biochar. Two different supplementation regimes were tested, namely a single bioaugmentation (SBABC) in which 10% v/v of the microbes grown on biochar (1 g/L) is added at setup of the reactors, versus a routine bioaugmentation (RBABC) wherein the same amount of supplements were added over 10 feeding cycles. The optimally performing 'R' and 'S' reactors had increased methane yields by 37% and 32% over their respective controls while reactors SBABC 2 and 3 produced 21.89% and 56.09% higher average methane yield than RBABC 2 and 3, respectively. It appears that a single dose bioaugmentation is advantageous for improving AD as analysed in terms of average methane yield and VFA production. This study provides the basis for understanding how biochar and bioaugmentation can be used for engineering sustainable pilot-scale AD processes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative., Methods: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients., Findings: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses., Interpretation: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID., Funding: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1)., Competing Interests: Declaration of interests The authors declare no competing interests, (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

The effects of different recovery strategies on inhibited anaerobic digestion (AD) of food waste (FW) was examined in this study, with the finding that dosing pine woodchip biochar could reverse the effect of volatile fatty acids (VFA) inhibition (mainly propionic acid) and yielded 105.55% more methane than the control. The addition of nano-zerovalent iron (nZVI) promoted the generation of VFA while causing a slight inhibition of the methanogens initially. In due time, the nZVI digester was able to recover and eventually produced 192.22% more methane compared to the control. Finally, nZVI-modified biochar was proved to be able to avoid the inhibitory effects brought about by the nanoparticles. The results indicated reduced dosage requirements as compared to using pristine pine woodchip biochar and accumulated 204.84% more methane than the control. The introduction of nZVI-biochar also promoted the growth of Methanosarcina species methanogens, which can perform direct-interspecies electron transfer. While all the recovery strategies using the additives were feasible, the results suggested that the use of modified biochar holds great potential as a significantly lower amount of amendment is required for the recovery of the inhibited AD system., 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 B.V. All rights reserved.)

Black garlic (BG) is a newly explored food stuff obtained via fermentation of raw, healthy garlic, especially in Asian countries. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal (GI) motility. The purpose of this study was to investigate the effects of BG extract on the pacemaker potentials of the ICC in the small intestines of mice and the possibility of controlling GI motility. The antioxidant activity of BG extract was also investigated. The whole-cell electrophysiological method was used to measure pacemaker potentials of the ICC in vitro , whereas GI motility was measured using the intestinal transit rate (ITR) in vivo . BG extract depolarized the pacemaker potentials of the ICC. Y25130 and RS39604 5-HT receptor antagonists could not inhibit the effect of BG extract on the pacemaker potentials of the ICC, whereas the 5-HT receptor antagonist SB269970 could. Pre-treatment with external Na + (5 mM) or Ca 2+ -free solution inhibited the BG extract-induced depolarization of the ICC. With SB203580, PD98059, or c-jun NH 2 -terminal kinase II inhibitor pre-treatment, BG extract did not induce pacemaker potential depolarization. Moreover, the ITR values were increased by BG extract. Elevation of the ITR due to BG extract was related with increased protein expression of the 5-HT 7 receptors. In addition, BG extract showed antioxidant activity. Collectively, these results highlight the ability of BG extract to regulate GI motility and the possibility of using it to develop GI motility modulators in the future. Moreover, BG showed immense potential as an antioxidant., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (-)-epicatechin, and rutin could be novel candidates for neuropathic pain management.

Background and Purpose: The purpose of this study was to show dynamic changes in carotid and vertebral artery using carotid Doppler ultrasonography (DUS) through a long-term follow- up exam, and determine their associations with stroke recurrence., Methods: We consecutively enrolled stroke or transient ischemic attack (TIA) patients who had undergone DUS more than twice with intervals of three months or more. Stroke recurrence during follow-up was also investigated by reviewing medical records. Progress or regress of plaque was defined as more than 0.1 mm change from the initial scan with a semi-quantitative measurement. The development of new plaque was also regarded as plaque progress. Increased intima-media thickness and plaque presence were interpreted at the initial and follow-up scans. Factors related to progression or regression were analyzed. The relationship between plaque change and stroke recurrence was investigated., Results: A total of 201 patients were enrolled (186 ischemic stroke patients and 15 TIA patients). There were 61 (30.3%) females. Their mean age was 64.2 ± 9.9 years. During a follow-up of 35.0 ± 22.6 (mean ± SD) months, plaque progress was observed in 92 (45.8%) and plaque regress in 13 (6.5%). Stroke recurred in 18 patients. Plaque progression showed no significant association with age, risk factors, statin use, or subtype. After adjustment of age, sex, diabetes, and stroke subtype, multiple logistic regression showed a significant association of plaque progression with stroke recurrence (odds ratio: 3.8, 95% confidence interval: 1.1 to 13.1, p = 0.034). Patients with plaque regress were significantly younger than those without plaque regress (57.8 years vs. 64.6 years, p = 0.041)., Conclusion: Plaque progression occurred in 46% of stroke or TIA patients. Plaque progression was significantly associated with clinical stroke recurrence. Plaque regressed in 6.5% of patients. Patients with regression were younger than those without., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Anaerobic digestion produces large quantities of digestate as a by-product, which can potentially be applied as an organic fertilizer, but untreated anaerobic digestate (AD) may contain phytotoxins and the large volume of AD makes transportation and storage difficult. This study explored two relatively inexpensive processing methods to improve the agronomic performance of AD as a fertilizer via vegetable cultivation experiments. We first investigated the effect of dilution on AD's performance using four leafy vegetables (Chinese spinach, water spinach, Chinese cabbage and lettuce). The optimal concentrations of the AD were 20-40% (v/v in 250 mL applications per single-plant pot) for all four vegetables based on shoot fresh weight and comparable to the control treatment using commercial fertilizer. AD application also introduced Synergistetes bacteria into the growing medium, but the overall bacterial diversity and composition were similar to those of the control treatment. Considering the nutrient separation in the liquid and solid fractions of AD and the need to reduce the volume, we then experimented with the recovery of nutrients from both the liquid and solid fractions by filtering AD using two types of wood-based biochar (100 g biochar: 1 L AD) before applying the AD-biochar residues as side dressing at 1% (w/w). Both types of biochar achieved yields comparable to the treatment using a commercial fertilizer for the three vegetables tested (kale, lettuce and rocket salad). Our results show that dilution and biochar filtration can improve the agronomic performance of AD, making it a sustainable substitute for commercial fertilizer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes / Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.

In this study, the anaerobic digestion (AD) applications of early & late biochar dosage were compared for municipal leachate treatment, with the objective of studying the flexible use of biochar as a mitigation measure for biomethane recovery. In two experimental phases, biochar was favourable for the immediate promotion of AD performances, as revealed by Gompertz's model of reduced lag phases, higher biomethane generation rates, and increased biomethane yields. Irrespective of late biochar dosage, it could still retrieve 89% of the ultimate biomethane potential. Comparing the residual VFAs (volatile fatty acids) compositions, it was found that the fraction of long-chain VFAs accounted for 81% of total VFAs in reactor set of early biochar dosage, while it was only 38% in the reactor of late one. Parallel evidence suggested that the schedule of biochar dosage not only could affect methanogenic responses but also the VFAs conversion pathways., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The high operating cost is currently a limitation to industrialize microbial lipids production by the yeast Lipomyces starkeyi . To explore economic fermentation technology, the two-stage fermentation of Lipomyces starkeyi using yeast extract peptone dextrose (YPD) medium, orange peel (OP) hydrolysate medium, and their mixed medium were investigated for seven days by monitoring OD 600 values, pH values, cell growth status, C/N ratios, total carbon concentration, total nitrogen concentration, residual sugar concentration, lipid content, lipid titer, and fatty acids profiles of lipids. The results showed that two-stage fermentation with YPD and 50% YPD + 50% OP medium contributed to lipid accumulation, leading to larger internal lipid droplets in the yeast cells. However, the cells in pure OP hydrolysate grew abnormally, showing skinny and angular shapes. Compared to the one-stage fermentation, the two-stage fermentation enhanced lipid contents by 18.5%, 27.1%, and 21.4% in the flasks with YPD medium, OP medium, and 50%YPD + 50%OP medium, and enhanced the lipid titer by 77.8%, 13.6%, and 63.0%, respectively. The microbial lipids obtained from both one-stage and two-stage fermentation showed no significant difference in fatty acid compositions, which were mainly dominated by palmitic acid (33.36-38.43%) and oleic acid (46.6-48.12%). Hence, a mixture of commercial medium and lignocellulosic biomass hydrolysate could be a promising option to balance the operating cost and lipid production.

A wood waste-derived biochar was applied to food-waste anaerobic digestion to evaluate the feasibility of its utilisation to create a circular economy. This biochar was first purposed for the upgrading of the biogas from the said anaerobic digestion, before treating and recovering the nutrients in the solid fraction of the digestate, which was finally employed as a biofertilizer for the organic cultivation of three green leafy vegetables: kale, lettuce and rocket salad. Whilst the amount of CO 2 the biochar could absorb from the biogas was low (11.17 mg g -1 ), it could potentially be increased by modifying through physical and chemical methods. Virgin as well as CO 2 -laden biochar were able to remove around 31% of chemical oxygen demand, 8% of the ammonia and almost 90% of the total suspended solids from the digestate wastewater, which was better than a dewatering process via centrifugation but worse than the industry standard of a polytetrafluoroethylene membrane bioreactor. Nutrients were recovered in the solid fraction of the digestate residue filtered by the biochar, and utilised as a biofertilizer that performed similarly to a commercial complete fertilizer in terms of aerial fresh weight growth for all three vegetables cultivated. Contingent on the optimal upgrading of biogas, the concept of a circular economy based on biochar and anaerobic digestion appears to be feasible., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age 1 . Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine 2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating., (© 2021. The Author(s).)

Latent human cytomegalovirus (HCMV) infection is characterized by limited gene expression, making latent HCMV infections refractory to current treatments targeting viral replication. However, reactivation of latent HCMV in immunosuppressed solid organ and stem cell transplant patients often results in morbidity. Here, we report the killing of latently infected cells via a virus-specific nanobody (VUN100bv) that partially inhibits signaling of the viral receptor US28. VUN100bv reactivates immediate early gene expression in latently infected cells without inducing virus production. This allows recognition and killing of latently infected monocytes by autologous cytotoxic T lymphocytes from HCMV-seropositive individuals, which could serve as a therapy to reduce the HCMV latent reservoir of transplant patients., (© 2021. The Author(s).)

Astroglia display a wide range of spontaneous and behavioral state-dependent Ca 2+ dynamics. During heightened vigilance, noradrenergic signaling leads to quasi-synchronous Ca 2+ elevations encompassing soma and processes across the brain-wide astroglia network. Distinct from this vigilance-associated global Ca 2+ rise are apparently spontaneous fluctuations within spatially restricted microdomains. Over the years, several strategies have been pursued to shed light on the physiological impact of these signals including deletion of endogenous ion channels or receptors and reduction of intracellular Ca 2+ through buffering, extrusion or inhibition of release. Some experiments that revealed the most compelling behavioral alterations employed chemogenetic and optogenetic manipulations to modify astroglia Ca 2+ signaling. However, there is considerable contrast between these findings and the comparatively modest effects of inhibiting endogenous sources of Ca 2+ . In this review, we describe the underlying mechanisms of various forms of astroglia Ca 2+ signaling as well as the functional consequences of their inhibition. We then discuss how the effects of exogenous astroglia Ca 2+ modification combined with our knowledge of physiological mechanisms of astroglia Ca 2+ activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca 2+ -dependent function of astroglia., 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 © 2021 Lim, Ye and Paukert.)

Objective: This study aimed to evaluate the reliability and validity of the Korean version of the Pornography Craving Questionnaire (K-PCQ) using classical test theory and item response theory., Methods: The goodness of fit test and differential item functioning (DIF) analysis based on the Rasch model, confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and correlation analysis were used to test its reliability and validity., Results: Response data from 226 students were analyzed. According to the goodness of fit test, the outfit mean square value of only one item, Item 11, was greater than 2. The CFA results revealed that all items of the K-PCQ measured a single construct. The EFA results revealed that the K-PCQ had excellent internal reliability. The DIF analysis results showed that the measurement of pornography craving using the K-PCQ did not differ based on gender. The result of Poly-DIMTEST supported the unidimensionality of the K-PCQ. The cut-off value of pornography craving was suggested as a measure of -0.0908 which corresponds to 46 (54.8%) out of a maximum score of 84., Conclusion: The items of the K-PCQ are unidimensional and have good reliability and validity. The K-PCQ will be useful in clinical practice and research as a screening tool for pornography craving.

Biochar, produced as a by-product of pyrolysis/gasification of waste biomass, shows great potential to reduce the environment impact, address the climate change issue, and establish a circular economy model. Despite the promising outlook, the research on the benefits of biochar remains highly debated. This has been attributed to the heterogeneity of biochar itself, with its inherent physical, chemical and biological properties highly influenced by production variables such as feedstock types and treating conditions. Hence, to enable meaningful comparison of results, establishment of an agreed international standard to govern the production of biochar for specific uses is necessary. In this study, we analyzed four key uses of biochar: 1) in agriculture and horticulture, 2) as construction material, 3) as activated carbon, and 4) in anaerobic digestion. Then the guidelines for the properties of biochar, especially for the concentrations of toxic heavy metals, for its environmental friendly application were proposed in the context of Singapore. The international status of the biochar industry code of practice, feedback from Singapore local industry and government agencies, as well as future perspectives for the biochar industry were explained., 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 © 2020 Elsevier B.V. All rights reserved.)

Background and Objectives: We conducted this meta-analysis about the effects of Souvenaid on cognition and functional abilities, with the hypothesis that Souvenaid may have beneficial effects in certain groups and the goal of finding the outcome measures, disease states, and so on, applicable for further clinical trials., Methods and Study Design: We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library. Only double- blind randomized controlled trials were included. Outcome measurements were cognition, clinical global change, functional ability, and adverse events. The duration of treatment was not restricted, but trials performed in patients who did not have Alzheimer's disease (AD) were excluded., Results: This review using meta-analyses of 4 clinical trials showed that Souvenaid had no significant effects on cognition as measured by ADAS-Cog (MD=0.08, 95% CI=-0.71-0.88) and the neuropsychological test battery total scores (MD=0.05, 95% CI=-0,02- 0.12), on global clinical function as measured by CDR-SB (MD=-0.21, 95% CI=-0.47-0.06), or on functional ability as measured by ADCS-ADL (MD=0.36, 95% CI=-0.54-1.25). There were no differences in any adverse events (OR=0.84, 95% CI=0.63-1.12) or in serious adverse events (OR=0.95, 95% CI=0.66-1.36). However, Souvenaid may benefit the domains of cognition that are affected by AD (attention, memory, and executive function), and it may have greater potential for benefits earlier rather than later in the disease., Conclusions: The results of current clinical trials do not suggest that Souvenaid has any beneficial effects on cognition, functional ability, or global clinical change. Further studies with outcome measures suitable in patients with early stages of AD will be needed.

Norepinephrine adjusts sensory processing in cortical networks and gates plasticity enabling adaptive behavior. The actions of norepinephrine are profoundly altered by recreational drugs like ethanol, but the consequences of these changes on distinct targets such as astrocytes, which exhibit norepinephrine-dependent Ca 2+ elevations during vigilance, are not well understood. Using in vivo two-photon imaging, we show that locomotion-induced Ca 2+ elevations in mouse astroglia are profoundly inhibited by ethanol, an effect that can be reversed by enhancing norepinephrine release. Vigilance-dependent astroglial activation is abolished by deletion of α 1A -adrenergic receptor from astroglia, indicating that norepinephrine acts directly on these ubiquitous glial cells. Ethanol reduces vigilance-dependent Ca 2+ transients in noradrenergic terminals, but has little effect on astroglial responsiveness to norepinephrine, suggesting that ethanol suppresses their activation by inhibiting norepinephrine release. Since abolition of astroglia Ca 2+ activation does not affect motor coordination, global suppression of astroglial networks may contribute to the cognitive effects of alcohol intoxication.

Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway. While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels. Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65. Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor- α ( TNF-α ), interleukin-1β ( IL-1β ), and monocyte chemoattractant protein-1 ( MCP-1 ) ., Competing Interests: The authors declare no conflicts of interest.

One of the major obstacles for thermophilic anaerobic digestion is the process instability during start-up. This study proposed the use of a cost-effective additive, biochar, to accelerate and stabilize the start-up of thermophilic semi-continuous food waste anaerobic digestion. The results showed that the reactors with biochar addition resulted in up to 18% higher methane yield as compared to the control reactors (without biochar). The key microbial networks were elucidated through thermochemical and microbial analysis. Particularly, the addition of biochar promoted the growth of electroactive Clostridia and other electroactive bacteria, while the absence of biochar promoted the growth of homoacetogenic Clostridia and syntrophic acetate oxidizing bacteria. It was revealed that biochar promoted direct interspecies electron transfer between the microbes and was responsible for the faster degradation of volatile fatty acids. Furthermore, reactors with biochar also enhanced the thermodynamically favourable acetoclastic methanogenic pathway due to the higher abundance of Methanosarcina., 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 © 2020 Elsevier Ltd. All rights reserved.)

This study evaluated the efficacy of Lactobacillus acidophilus YT1 (MENOLACTO) for alleviating menopausal symptoms. This study was a multi-center, randomized, double-blinded, placebo-controlled clinical trial involving female subjects (ages: 40-60 years) with menopausal symptoms and a Kupperman index (KMI) score ≥ 20. Subjects were administered 1 × 10 8 CFU/day MENOLACTO or placebo, with the primary endpoint being total KMI score, and the effect of secondary endpoints on alleviating menopausal symptoms according to individual categories of the modified KMI, as well as a quality of life questionnaire (MENQOL questionnaire). After 12 weeks, total KMI scores decreased significantly, demonstrating improved menopausal symptoms relative to placebo along with improved modified KMI scores. Additionally, quality of life, according to the MENQOL questionnaire, significantly improved in all four symptoms-physical, psychosocial, vasomotor, and sexual symptoms. Moreover, we observed no significant difference between the two groups or significant changes in blood follicle-stimulating hormone and estradiol levels or endometrial thickness. These results demonstrated that MENOLACTO alleviated menopausal symptoms without notable side effects and improved quality of life, suggesting its efficacy as an alternative supplement to alleviate menopausal symptoms in women ineligible for hormonal therapy.

HCMV infection, reinfection or reactivation occurs in 60% of untreated solid organ transplant (SOT) recipients. Current clinical approaches to HCMV management include pre-emptive and prophylactic antiviral treatment strategies. The introduction of immune monitoring to better stratify patients at risk of viraemia and HCMV mediated disease could improve clinical management. Current approaches quantify T cell IFNγ responses specific for predominantly IE and pp65 proteins ex vivo , as a proxy for functional control of HCMV in vivo . However, these approaches have only a limited predictive ability. We measured the IFNγ T cell responses to an expanded panel of overlapping peptide pools specific for immunodominant HCMV proteins IE1/2, pp65, pp71, gB, UL144, and US3 in a cohort of D+R- kidney transplant recipients in a longitudinal analysis. Even with this increased antigen diversity, the results show that while all patients had detectable T cell responses, this did not correlate with control of HCMV replication in some. We wished to develop an assay that could directly measure anti-HCMV cell-mediated immunity. We evaluated three approaches, stimulation of PBMC with (i) whole HCMV lysate or (ii) a defined panel of immunodominant HCMV peptides, or (iii) fully autologous infected cells co-cultured with PBMC or isolated CD8 + T cells or NK cells. Stimulation with HCMV lysate often generated non-specific antiviral responses while stimulation with immunodominant HCMV peptide pools produced responses which were not necessarily antiviral despite strong IFNγ production. We demonstrated that IFNγ was only a minor component of secreted antiviral activity. Finally, we used an antiviral assay system to measure the effect of whole PBMC, and isolated CD8 + T cells and NK cells to control HCMV in infected autologous dermal fibroblasts. The results show that both PBMC and especially CD8 + T cells from HCMV seropositive donors have highly specific antiviral activity against HCMV. In addition, we were able to show that NK cells were also antiviral, but the level of this control was highly variable between donors and not dependant on HCMV seropositivity. Using this approach, we show that non-viraemic D+R+ SOT recipients had significant and specific antiviral activity against HCMV., (Copyright © 2020 Houldcroft, Jackson, Lim, Sedikides, Davies, Atkinson, McIntosh, Remmerswaal, Okecha, Bemelman, Stanton, Reeves and Wills.)

While CD8+ T cells specific for human cytomegalovirus (HCMV) have been extensively studied in both healthy HCMV seropositive carriers and patients undergoing immunosuppression, studies on the CD4+ T cell response to HCMV had lagged behind. However, over the last few years there has been a significant advance in our understanding of the importance and contribution that CMV-specific CD4+ T cells make, not only to anti-viral immunity but also in the potential maintenance of latently infected cells. During primary infection with HCMV in adults, CD4+ T cells are important for the resolution of symptomatic disease, while persistent shedding of HCMV into urine and saliva is associated with a lack of HCMV specific CD4+ T cell response in young children. In immunosuppressed solid organ transplant recipients, a delayed appearance of HCMV-specific CD4+ T cells is associated with prolonged viremia and more severe clinical disease, while in haematopoietic stem cell transplant recipients, it has been suggested that HCMV-specific CD4+ T cells are required for HCMV-specific CD8+ T cells to exert their anti-viral effects. In addition, adoptive T-cell immunotherapy in transplant patients has shown that the presence of HCMV-specific CD4+ T cells is required for the maintenance of HCMV-specific CD8+ T cells. HCMV is a paradigm for immune evasion. The presence of viral genes that down-regulate MHC class II molecules and the expression of viral IL-10 both limit antigen presentation to CD4+ T cells, underlining the important role that this T cell subset has in antiviral immunity. This review will discuss the antigen specificity, effector function, phenotype and direct anti-viral properties of HCMV specific CD4+ T cells, as well as reviewing our understanding of the importance of this T cell subset in primary infection and long-term carriage in healthy individuals. In addition, their role and importance in congenital HCMV infection and during immunosuppression in both solid organ and haemopoietic stem cell transplantation is considered., (Copyright © 2020 Lim, Jackson and Wills.)

The increasing world population necessitates the production of larger amounts of food in a safe and environmentally sustainable manner, while concomitantly managing an increasing amount of food waste similarly. These needs can theoretically be met by the recycling of the nutrients in food waste via anaerobic digestion, which also produces renewable energy. This hypothesis is proven by the growing of a commonly consumed leafy vegetable, xiao bai cai (Brassica rapa), by the addition of food waste anaerobic digestate in place of commercial fertilizer. Different concentrations of the digestate were tested, as well as different heat treatments to simulate hygienization, and the results for most part (aerial fresh weight, dry weight, chlorophyll content) are not significantly different from growth utilizing commercial inorganic 15:15:15 NPK fertilizer. Microbial analysis of the growth media was also carried out to explicate digestate effects and to show that some common foodborne disease pathogens were not detected., 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 © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: We investigated the prevalence of amyloid positivity and cerebral microbleeds (CMBs) in subjects with cognitive complaints with the aim of identifying differences in clinical parameters and cognitive function according to the pattern of coexistence., Methods: We retrospectively enrolled 200 subjects with memory impairment and applied both standardized ¹⁸F-florbetaben PET and brain MRI, including susceptibility-weighted imaging. The amyloid burden was visually classified as positive or negative, and the number and location of CMBs were also analyzed visually. Descriptive analysis was performed for the prevalence of amyloid positivity and CMBs. The relationship between the coexisting pattern of those two findings and clinical parameters including the results of neuropsychiatric tests was analyzed., Results: Positive amyloid PET scans were exhibited by 102 (51.5%) of the 200 patients, and 51 (25.5%) of them had CMBs, which were mostly located in lobar areas in the patients with positive amyloid scans. The patients with CMBs were older and had a higher burden of white-matter hyperintensities than the patients without CMBs. The patients with CMBs also performed worse in confrontation naming and frontal/executive function. When classified by topographical region, parietal CMBs (odds ratio=3.739, p =0.024) were significantly associated with amyloid positivity., Conclusions: The prevalence of CMBs was higher in patients with cognitive decline than in the general population. CMBs play distinctive roles in affecting clinical parameters and neuropsychological profiles according to the coexistence of amyloid pathology., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Human cytomegalovirus (HCMV) latency is an active process which remodels the latently infected cell to optimize latent carriage and reactivation. This is achieved, in part, through the expression of viral genes, including the G-protein-coupled receptor US28. Here, we use an unbiased proteomic screen to assess changes in host proteins induced by US28, revealing that interferon-inducible genes are downregulated by US28. We validate that major histocompatibility complex (MHC) class II and two pyrin and HIN domain (PYHIN) proteins, myeloid cell nuclear differentiation antigen (MNDA) and IFI16, are downregulated during experimental latency in primary human CD14 + monocytes. We find that IFI16 is targeted rapidly during the establishment of latency in a US28-dependent manner but only in undifferentiated myeloid cells, a natural site of latent carriage. Finally, by overexpressing IFI16, we show that IFI16 can activate the viral major immediate early promoter and immediate early gene expression during latency via NF-κB, a function which explains why downregulation of IFI16 during latency is advantageous for the virus. IMPORTANCE Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus which infects 50 to 100% of humans worldwide. HCMV causes a lifelong subclinical infection in immunocompetent individuals but is a serious cause of mortality and morbidity in the immunocompromised and neonates. In particular, reactivation of HCMV in the transplant setting is a major cause of transplant failure and related disease. Therefore, a molecular understanding of HCMV latency and reactivation could provide insights into potential ways to target the latent viral reservoir in at-risk patient populations., (Copyright © 2019 Elder et al.)

Background and Purpose: Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs)., Methods: We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons., Results: Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD., Conclusions: Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (© 2019 Korean Dementia Association.)

Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)-palmitic and oleic acid-and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.

Cnidium officinale , widely cultivated in East Asia, has been reported to exhibit pharmacological efficacy in various disorders. However, little has been reported on its role as a pain killer. In this study, we reveal that the C. officinale extract (COE) has great efficacy as a novel analgesic in various in vivo pain models. Administration of COE attenuated hypersensitivity in all postoperative, neuropathic, and menopausal pain models. Decreased hyperalgesia was confirmed by a mechanical withdrawal threshold assay and ultrasonic vocalization call analysis. In addition, application of COE inhibited the induction of the proinflammatory cytokines and calpain-3 on dorsal root ganglion neurons in a spared nerve injury rat model. Treatment with ferulic acid, which was identified as one of the components of COE by HPLC analysis, alleviated nociceptive behaviors. Our findings suggest that ferulic acid is an active compound from COE, and COE is a potential phytomedical source for pain relief by inhibiting the process of inflammation.