bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1
Authors: Tang Yuyan , Zhu Yifan , He Haidong , Peng Yinshun , Hu Ping , Wu Jiajun , Sun Weiqian , Liu Ping , Xiao Yong , Xu Xudong , Wei Minggang
Published: July 2022

Background

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.

Methods

Thirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.

Results

In patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932–1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.

Conclusion

The urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.
Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury
Authors: Deng Junhui , Wu Zhifen , He Yun , Lin Lirong , Tan Wei , Yang Jurong
Published: July 2022

A growing number of studies have confirmed that immune cells play various key roles in the pathophysiology of acute kidney injury (AKI) development. After the resident immune cells and intrinsic renal cells are damaged by ischemia and hypoxia, drugs and toxins, more immune cells will be recruited to infiltrate through the release of chemokines, while the intrinsic cells promote macrophage polarity conversion, and the immune cells will promote various programmed deaths, phenotypic conversion and cycle arrest of the intrinsic cells, ultimately leading to renal impairment and fibrosis. In the complex and dynamic immune microenvironment of AKI, the bidirectional interaction between immune cells and intrinsic renal cells affects the prognosis of the kidney and the progression of fibrosis, and determines the ultimate fate of the kidney.
Metabolomics-Driven Exploration of the Antibacterial Activity and Mechanism of 2-Methoxycinnamaldehyde
Authors: Qian Chunguo , Jin Lu , Zhu Longping , Zhou Yang , Chen Jing , Yang Depo , Xu Xinjun , Ding Ping , Li Runnan , Zhao Zhimin
Published: July 2022

Methicillin-resistant Staphylococcus epidermidis (MRSE) is one of the most commonly found pathogens that may cause uncontrollable infections in immunocompromised and hospitalized patients. Compounds isolated from cinnamon such as cinnamaldehyde and cinnamic acid showed promising anti-oxidant, anti-tumor, and immunoregulatory effects; more importantly, these compounds also possess promising broad-spectrum antibacterial activity. In this study, the potential antibacterial activity of 2-methoxycinnamaldehyde (MCA), another compound in cinnamon, against MRSE was investigated. Combining the broth microdilution test, live/dead assay, and biofilm formation assay, we found MCA was able to inhibit the proliferation, as well as the biofilm formation of MRSE, indicating MCA could not only affect the growth of MRSE but also inhibit the pathogenic potential of this bacterium. Additionally, the results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that MCA caused morphological changes and the leakage of DNA, RNA, and cellular contents of MRSE. Due to the close relationship between cell wall synthesis, ROS formation, and cell metabolism, the ROS level and metabolic profile of MRSE were explored. Our study showed MCA significantly increased the ROS production in MRSE, and the following metabolomics analysis showed that the increased ROS production may partially be due to the increased metabolic flux through the TCA cycle. In addition, we noticed the metabolic flux through the pentose phosphate pathway (PPP) was upregulated accompanied by elevated ROS production. Therefore, the alterations in cell metabolism and increased ROS production could lead to the damage of the cell wall, which in turn decreased the proliferation of MRSE. In conclusion, MCA seemed to be a promising alternative antimicrobial agent to control MRSE infections.
Effect of Doxycycline Use in the Early Broiler Production Cycle on the Microbiome
Authors: Greene Genevieve , Koolman Leonard , Whyte Paul , Burgess Catherine , Lynch Helen , Coffey Aidan , Lucey Brigid , O’Connor Lisa , Bolton Declan
Published: July 2022

16S rRNA amplicon sequencing was used to investigate changes in the broiler gastrointestinal tract (GIT) microbiota throughout the rearing period and in combination with antibiotic treatment. Thirty birds (from a commercial flock) were removed at multiple points throughout the rearing period on days 13, 27, and 33, euthanised, and their GIT aseptically removed and divided into upper (the crop, proventriculus, and the gizzard), middle (the duodenum, jejunum, and ileum) and lower (the large intestine, the caeca, and the cloaca) sections. In a separate commercial flock, on the same farm with similar husbandry practices and feed, doxycycline (100 mg/ml per kg body weight) was administered in drinking water between day 8 and 12 (inclusive) of the production cycle. Birds were removed on days, 13, 27, and 33 and GIT samples prepared as above. The contents of three merged samples from each GIT section were pooled (n = 60), the DNA extracted and analysed by 16S rRNA amplicon metagenomic sequencing and analysed. Major changes in the broiler microbiota were observed as the birds aged particularly with the Firmicutes/Bacteroidetes ratio (F:B) of the lower GIT. Moreover, Chao1, ACE, and Shannon indices showed the antibiotic treatment significantly altered the microbiota, and this change persisted throughout the rearing period. Further research is required to investigate the effect of these changes on bird performance, susceptibility to infections and Campylobacter carriage.
The Impact of Nontuberculous Mycobacteria Species on Mortality in Patients With Nontuberculous Mycobacterial Lung Disease
Authors: Wang Ping-Huai , Pan Sheng-Wei , Wang Su-Mei , Shu Chin-Chung , Chang Chin-Hao
Published: July 2022

Patients with nontuberculous mycobacterial lung disease (NTM-LD) have increased mortality. The impact of NTM species on the risk of mortality remains unclear, especially that of death by non-cancer causes. We conducted a retrospective cohort study from 2006 to 2018 in a tertiary-care hospital in Taiwan. We enrolled patients who fulfilled the microbiological diagnostic criteria of NTM-LD. The mortality causes within 8 years after diagnosis were identified, and the Cox proportional hazard regression was performed for risk factors of mortality. A total of 1,652 subjects with NTM-LD were included. Among them, 723 (43.8%) were infected by Mycobacterium avium complex (MAC), 408 (24.7%) by M. abscessus complex (MABC), 120 (7.3%) by Mycobacterium kansasii (MK), 304 (18.4%) by other rapid-growing mycobacteria (RGM), and 97 (5.9%) by other slow-growing mycobacteria (SGM) groups. The 8-year all-cause mortality was 45.2% for all and the highest in the MK-LD group (59.2%), followed by the MABC-LD and MAC-LD groups. The adjusted hazard ratios were 2.20 (95% confidence interval: 1.40–3.46) in the MK-LD, 1.85 (1.54–2.22) in the MABC-LD, and 1.65 (1.12–2.41) in the MAC-LD groups for all-cause mortality, compared with the SGM group. Kaplan–Meier survival curves showed that all-cause mortality, non-cancer mortality, and mortality due to chronic airway diseases were significantly correlated with NTM species (log-rank p = 0.0031, < 0.001, and 0.001, respectively). High 8-year mortality rates were found in patients with NTM-LDs according to different NTM species. Notably, the difference was significant in non-cancer mortality causes, especially in chronic airway diseases.
Structural and Potential Functional Properties of Alkali-Extracted Dietary Fiber From Antrodia camphorata
Authors: Xia Yongjun , Meng Peng , Liu Shaodong , Tan Zhuoming , Yang Xi , Liang Lihong , Xie Fan , Zhang Hui , Wang Guangqiang , Xiong Zhiqiang , Lo Jenyu , Ai Lianzhong
Published: July 2022

Antrodia camphorata is rich in a variety of bioactive ingredients; however, the utilization efficiency of the residue of A. camphorata is low, resulting in serious waste. It is necessary to deeply study the functional components of A. camphorata residues to achieve high-value utilization. In this study, the components, structural characteristics, and functional properties of alkali-extracted dietary fiber extracted from residues of A. camphorata (basswood and dish cultured fruiting body, respectively) were investigated. There were similar components and structural characteristics of ACA-DK (extract from basswood cultured) and ACA-DF (extract from dish cultured). The two alkali-extracted dietary fiber were composed of mainly cellulose and xylan. However, ACA-DK has better adsorption capacities than ACA-DF on lipophilic substances such as oil (12.09 g/g), cholesterol (20.99 mg/g), and bile salts (69.68 mg/g). In vitro immunomodulatory assays stated that ACA-DK had a good effect on promoting the proliferation of RAW 264.7 cells and can activate cell phagocytosis, NO synthesis, and other immune capabilities. The edible fungus A. camphorata is a good source of functional dietary fiber. The alkali-extracted dietary fiber of A. camphorata might be used as a functional ingredient in the medicine and food industry.
Lagovirus Non-structural Protein p23: A Putative Viroporin That Interacts With Heat Shock Proteins and Uses a Disulfide Bond for Dimerization
Authors: Smertina Elena , Carroll Adam J. , Boileau Joseph , Emmott Edward , Jenckel Maria , Vohra Harpreet , Rolland Vivien , Hands Philip , Hayashi Junna , Neave Matthew J. , Liu Jian-Wei , Hall Robyn N. , Strive Tanja , Frese Michael
Published: July 2022

The exact function(s) of the lagovirus non-structural protein p23 is unknown as robust cell culture systems for the Rabbit haemorrhagic disease virus (RHDV) and other lagoviruses have not been established. Instead, a range of in vitro and in silico models have been used to study p23, revealing that p23 oligomerizes, accumulates in the cytoplasm, and possesses a conserved C-terminal region with two amphipathic helices. Furthermore, the positional homologs of p23 in other caliciviruses have been shown to possess viroporin activity. Here, we report on the mechanistic details of p23 oligomerization. Site-directed mutagenesis revealed the importance of an N-terminal cysteine for dimerization. Furthermore, we identified cellular interactors of p23 using stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics; heat shock proteins Hsp70 and 110 interact with p23 in transfected cells, suggesting that they ‘chaperone’ p23 proteins before their integration into cellular membranes. We investigated changes to the global transcriptome and proteome that occurred in infected rabbit liver tissue and observed changes to the misfolded protein response, calcium signaling, and the regulation of the endoplasmic reticulum (ER) network. Finally, flow cytometry studies indicate slightly elevated calcium concentrations in the cytoplasm of p23-transfected cells. Taken together, accumulating evidence suggests that p23 is a viroporin that might form calcium-conducting channels in the ER membranes.
Impact of Bioconjugation on Structure and Function of Antibodies for Use in Immunoassay by Hydrogen-Deuterium Exchange Mass Spectrometry
Authors: Luckau Luise , Groves Kate , Blencowe Chris , Scrimshaw Sam , Dent Alastair , Quaglia Milena
Published: July 2022

Monoclonal antibodies (mAbs) are widely used as analytical components in immunoassays to detect target molecules in applications such as clinical diagnostics, food analysis and drug discovery. Functional groups are often conjugated to lysine or cysteine residues to aid immobilization of mAbs or to enable their detection in an antibody antigen complex. Good assay performance depends on the affinity and specificity of the mAbs for the antigen. The conjugation reaction however can cause higher order structural (HOS) changes and ultimately affect the assay performance. In this study, four differently conjugated mAbs were selected as model systems and characterized by mass spectrometry. Particularly, intact protein analysis by liquid-chromatography mass-spectrometry (LC-MS) was performed to determine the amount and distribution of conjugation. Hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments were carried out for the structural characterization of the conjugated mAbs. Immunoassay experiments were performed to monitor the effects of conjugation on the binding properties of the antibodies selected. Good agreement between the mass spectrometry and binding experiment results was found. Particularly, it was noted that the overall structural flexibility of the antibodies increases upon cysteine conjugation and decreases for lysine conjugation. The conjugation of mAbs with bulky functional groups tends to decrease the deuterium uptake kinetics due to induced steric effects. Overall, this study shows correlations between conjugation, structure and function of immunoassay antibodies and the benefits of mass spectrometry to improve understanding of the conjugation reaction and provide insights that can predict immunoassay performance.
Propranolol Administration Modulates Neural Activity in the Hippocampal Hilus During Fear Retrieval
Authors: Leal Santos Sofia , Chen Briana K. , Pereira Guilherme R. , Pham Vananh , Denny Christine A.
Published: July 2022

Altered fear learning is a strong behavioral component of anxiety disorders such as post-traumatic stress disorder (PTSD). Recent efforts have attempted to combine exposure therapies with drugs that target fear memory retrieval and memory reconsolidation, in order to improve treatment efficacy. The noradrenergic (NA) signaling system is of particular interest, due to its role in regulating the stress response and its involvement in fear and learning processes. Importantly, propranolol (P), a non-selective β-adrenergic antagonist, has shown the potential in decreasing exaggerated fear in both humans and animal models. In a previous study, we utilized an activity-dependent tagging murine model to determine the neural mechanisms by which propranolol attenuates learned fear. We found that propranolol acutely decreased memory trace reactivation specifically in the dorsal dentate gyrus (dDG), but not in CA3 or CA1. Here, we extended our previous study by investigating whether propranolol additionally altered activity in the hilus, a polymorphic layer that consists of neurons, mossy cells, and GABAergic interneurons. We found that propranolol acutely reduced overall hilar activity in both the dorsal and ventral hilus. Moreover, we report that propranolol significantly altered the activity of parvalbumin (PV)+ cells in the ventral (vDG), but not dorsal DG (dDG). Together, these results suggest that a β-adrenergic blockade may affect the activity of excitatory and inhibitory cell types in the hilar layer of the DG, and that these alterations may contribute to manipulating fear memory traces.
Dopamine D1/D5 Receptors in the Retrosplenial Cortex Are Necessary to Consolidate Object Recognition Memory
Authors: de Landeta Ana Belén , Medina Jorge H. , Katche Cynthia
Published: July 2022

The retrosplenial cortex (RSC) has been widely related to spatial and contextual memory. However, we recently demonstrated that the anterior part of the RSC (aRSC) is required for object recognition (OR) memory consolidation. In this study, we aimed to analyze the requirement of dopaminergic inputs into the aRSC for OR memory consolidation in male rats. We observed amnesia at 24-h long-term memory when we infused SCH23390, a D1/D5 dopamine receptors antagonist, into aRSC immediately after OR training session. However, the same infusion had no effect on OR short-term memory. Then, we analyzed whether the ventral tegmental area (VTA) is necessary for OR consolidation. VTA inactivation by intra-VTA administration of muscimol, a GABAA agonist, immediately after an OR training session induced amnesia when animals were tested at 24 h. Moreover, we observed that this VTA inactivation-induced amnesia was reversed by the simultaneous intra-aRSC delivery of SKF38393, a D1/D5 receptor agonist. Altogether, our results suggest that VTA dopaminergic inputs to aRSC play an important modulatory role in OR memory consolidation.
The Role of Transposable Elements in Sexual Development
Authors: Chiang Vic Shao-Chih , DeRosa Holly , Park Jin Ho , Hunter Richard G.
Published: July 2022

Up to 50% of most mammalian genomes are made up of transposable elements (TEs) that have the potential to mobilize around the genome. Despite this prevalence, research on TEs is only beginning to gain traction within the field of neuroscience. While TEs have long been regarded as “junk” or parasitic DNA, it has become evident that they are adaptive DNA and RNA regulatory elements. In addition to their vital role in normal development, TEs can also interact with steroid receptors, which are key elements to sexual development. In this review, we provide an overview of the involvement of TEs in processes related to sexual development- from TE activity in the germline to TE accumulation in sex chromosomes. Moreover, we highlight sex differences in TE activity and their regulation of genes related to sexual development. Finally, we speculate on the epigenetic mechanisms that may govern TEs’ role in sexual development. In this context, we emphasize the need to further the understanding of sexual development through the lens of TEs including in a variety of organs at different developmental stages, their molecular networks, and evolution.
Detection of Brain Network Communities During Natural Speech Comprehension From Functionally Aligned EEG Sources
Authors: Zhou Di , Zhang Gaoyan , Dang Jianwu , Unoki Masashi , Liu Xin
Published: July 2022

In recent years, electroencephalograph (EEG) studies on speech comprehension have been extended from a controlled paradigm to a natural paradigm. Under the hypothesis that the brain can be approximated as a linear time-invariant system, the neural response to natural speech has been investigated extensively using temporal response functions (TRFs). However, most studies have modeled TRFs in the electrode space, which is a mixture of brain sources and thus cannot fully reveal the functional mechanism underlying speech comprehension. In this paper, we propose methods for investigating the brain networks of natural speech comprehension using TRFs on the basis of EEG source reconstruction. We first propose a functional hyper-alignment method with an additive average method to reduce EEG noise. Then, we reconstruct neural sources within the brain based on the EEG signals to estimate TRFs from speech stimuli to source areas, and then investigate the brain networks in the neural source space on the basis of the community detection method. To evaluate TRF-based brain networks, EEG data were recorded in story listening tasks with normal speech and time-reversed speech. To obtain reliable structures of brain networks, we detected TRF-based communities from multiple scales. As a result, the proposed functional hyper-alignment method could effectively reduce the noise caused by individual settings in an EEG experiment and thus improve the accuracy of source reconstruction. The detected brain networks for normal speech comprehension were clearly distinctive from those for non-semantically driven (time-reversed speech) audio processing. Our result indicates that the proposed source TRFs can reflect the cognitive processing of spoken language and that the multi-scale community detection method is powerful for investigating brain networks.
Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum
Authors: Tábuas-Pereira Miguel , Santana Isabel , Gibbons Elizabeth , Paquette Kimberly , Almeida Maria Rosário , Baldeiras Inês , Bras Jose , Guerreiro Rita
Published: July 2022

Introduction

Frontotemporal dementia (FTD) is considered to be part of a continuum with amyotrophic lateral sclerosis (ALS). Many genes are associated with both ALS and FTD. Yet, many genes associated with ALS have not been shown to cause FTD. We aimed to study a Portuguese cohort of FTD patients, searching for variants in genes associated with both FTD and/or ALS.

Methods

We included 57 thoroughly characterized index FTD patients from our memory clinic, who were not carriers of pathogenic variants in GRN, MAPT or C9orf72. We performed exome sequencing and 1) prioritized potential FTD and ALS causing variants by using Exomiser to annotate and filter results; and 2) looked specifically at rare variability in genes associated with FTD (excluding GRN, MAPT and C9ORF72) and/or ALS.

Results

We identified 13 rare missense variants in 10 patients (three patients had two variants) in the following genes: FUS, OPTN, CCNF, DCTN1, TREM2, ERBB4, ANG, CHRNA4, CHRNB4 and SETX. We found an additional frameshift variant on GLT8D1 in one patient. One variant (ERBB4 p.Arg1112His) gathered enough evidence to be classified as likely pathogenic by the ACMG criteria.

Discussion

We report, for the first time, an expanded study of genes known to cause FTD-ALS, in the Portuguese population. Potentially pathogenic variants in ERBB4, FUS, SETX, ANG, CHRNA4 and CHRNB4 were identified in FTD patients. These findings provide additional evidence for the potential role of rare variability in ALS-associated genes in FTD, expanding the genetic spectrum between the two diseases.
RETRACTED: Do Surrounding People's Emotions Affect Judgment of the Central Person's Emotion? Comparing Within Cultural Variation in Holistic Patterns of Emotion Perception in the Multicultural Canadian Society
Authors: Masuda Takahiko , Shi Shuwei , Varma Pragya , Fisher Delaney , Shirazi Safi
Published: July 2022

Previous studies in cultural psychology have suggested that when assessing a target person's emotion, East Asians are more likely to incorporate the background figure's emotion into the judgment of the target's emotion compared to North Americans. The objective of this study was to further examine cultural variation in emotion perception within a culturally diverse population that is representative of Canada's multicultural society. We aimed to see whether East-Asian Canadians tended to keep holistic tendencies of their heritage culture regarding emotion perception. Participants were presented with 60 cartoon images consisting of a central figure and four surrounding figures and were then asked to rate the central figure's emotion; out of the four cartoon figures, two were female and two were male. Each character was prepared with 5 different emotional settings with corresponding facial expressions including: extremely sad, moderately sad, neutral, moderately happy, and extremely happy. Each central figure was surrounded by a group of 4 background figures. As a group, the background figures either displayed a sad, happy, or neutral expression. The participant's task was to judge the intensity of the central figures' happiness or sadness on a 10-point Likert scale ranging from 0 (not at all) to 9 (extremely). For analysis, we divided the participants into three groups: European Canadians (N = 105), East Asian Canadians' (N = 104) and Non-East Asian/Non-European Canadians (N = 161). The breakdown for the Non-East Asian/Non-European Canadian group is as follows: 94 South Asian Canadians, 25 Middle Eastern Canadians, 23 African Canadians, 9 Indigenous Canadians, and 10 Latin/Central/South American Canadians. Results comparing European Canadians and East Asian Canadians demonstrated cultural variation in emotion judgment, indicating that East Asian Canadians were in general more likely than their European Canadian counterparts to be affected by the background figures' emotion. The study highlights important cultural variations in holistic and analytic patterns of emotional attention in the ethnically diverse Canadian society. We discussed future studies which broaden the scope of research to incorporate a variety of diverse cultural backgrounds outside of the Western educational context to fully comprehend cultural variations in context related attentional patterns.
Transcranial Magnetic Stimulation for Long-Term Smoking Cessation: Preliminary Examination of Delay Discounting as a Therapeutic Target and the Effects of Intensity and Duration
Authors: Shevorykin Alina , Carl Ellen , Mahoney Martin C. , Hanlon Colleen A. , Liskiewicz Amylynn , Rivard Cheryl , Alberico Ronald , Belal Ahmed , Bensch Lindsey , Vantucci Darian , Thorner Hannah , Marion Matthew , Bickel Warren K. , Sheffer Christine E.
Published: July 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for smoking cessation and delay discounting rate is novel therapeutic target. Research to determine optimal therapeutic targets and dosing parameters for long-term smoking cessation is needed. Due to potential biases and confounds introduced by the COVID-19 pandemic, we report preliminary results from an ongoing study among participants who reached study end prior to the pandemic.

Methods

In a 3 × 2 randomized factorial design, participants (n = 23) received 900 pulses of 20 Hz rTMS to the left dorsolateral prefrontal cortex (PFC) in one of three Durations (8, 12, or 16 days of stimulation) and two Intensities (1 or 2 sessions per day). We examined direction and magnitude of the effect sizes on latency to relapse, 6-month point-prevalence abstinence rates, research burden, and delay discounting rates.

Results

A large effect size was found for Duration and a medium for Intensity for latency to relapse. Increasing Duration increased the odds of abstinence 7–8-fold while increasing Intensity doubled the odds of abstinence. A large effect size was found for Duration, a small for Intensity for delay discounting rate. Increasing Duration and Intensity had a small effect on participant burden.

Conclusion

Findings provide preliminary support for delay discounting as a therapeutic target and for increasing Duration and Intensity to achieve larger effect sizes for long-term smoking cessation and will provide a pre-pandemic comparison for data collected during the pandemic.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03865472].
Oxytocin Dynamics in the Body and Brain Regulated by the Receptor for Advanced Glycation End-Products, CD38, CD157, and Nicotinamide Riboside
Authors: Higashida Haruhiro , Furuhara Kazumi , Lopatina Olga , Gerasimenko Maria , Hori Osamu , Hattori Tsuyoshi , Hayashi Yasuhiko , Cherepanov Stanislav M. , Shabalova Anna A. , Salmina Alla B. , Minami Kana , Yuhi Teruko , Tsuji Chiharu , Fu PinYue , Liu Zhongyu , Luo Shuxin , Zhang Anpei , Yokoyama Shigeru , Shuto Satoshi , Watanabe Mizuki , Fujiwara Koichi , Munesue Sei-ichi , Harashima Ai , Yamamoto Yasuhiko
Published: July 2022

Investigating the neurocircuit and synaptic sites of action of oxytocin (OT) in the brain is critical to the role of OT in social memory and behavior. To the same degree, it is important to understand how OT is transported to the brain from the peripheral circulation. To date, of these, many studies provide evidence that CD38, CD157, and receptor for advanced glycation end-products (RAGE) act as regulators of OT concentrations in the brain and blood. It has been shown that RAGE facilitates the uptake of OT in mother’s milk from the digestive tract to the cell surface of intestinal epithelial cells to the body fluid and subsequently into circulation in male mice. RAGE has been shown to recruit circulatory OT into the brain from blood at the endothelial cell surface of neurovascular units. Therefore, it can be said that extracellular OT concentrations in the brain (hypothalamus) could be determined by the transport of OT by RAGE from the circulation and release of OT from oxytocinergic neurons by CD38 and CD157 in mice. In addition, it has recently been found that gavage application of a precursor of nicotinamide adenine dinucleotide, nicotinamide riboside, for 12 days can increase brain OT in mice. Here, we review the evaluation of the new concept that RAGE is involved in the regulation of OT dynamics at the interface between the brain, blood, and intestine in the living body, mainly by summarizing our recent results due to the limited number of publications on related topics. And we also review other possible routes of OT recruitment to the brain.
Nobiletin Attenuates Anesthesia/Surgery-Induced Neurocognitive Decline by Preserving the Expression of Clock Genes in Mice
Authors: Sun Zhuonan , Yang Ning , Jia Xixi , Song Yanan , Han Dengyang , Wang Xiaoxiao , Sun Jie , Li Zhengqian , Zuo Zhiyi , Guo Xiangyang
Published: July 2022

Postoperative cognitive dysfunction (POCD) is commonly observed during the postoperative period and significantly affects the prognosis of patients. Neuroinflammation plays a vital role in the pathogenesis of POCD. Despite laboratory and clinical research over the past decades, practical pharmacological strategies for the treatment and prevention of POCD are not yet available currently. Nobiletin (NOB) is a natural polymethoxylated flavone. As an enhancer of the clock protein retinoic acid receptor-related orphan receptors (RORs), NOB has been shown to attenuate inflammation and improve cognitive decline. We speculate that NOB is a candidate for the treatment and prevention of POCD. In this study, we investigated whether and how NOB affected surgery-induced neuroinflammation and POCD in adult CD1 mice. NOB pretreatment suppressed exploratory laparotomy-induced systemic inflammation and neuroinflammation in a dose-dependent manner (< 50 mg/kg), and attenuated POCD. Moreover, NOB dose-dependently reversed the decrease of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1, also known as Arntl) and Rors expression induced by exploratory laparotomy. The expression of Bmal was negatively correlated with tumor necrosis factor-α (TNF-α). Our results suggest that NOB attenuated POCD, possibly via preserving the expression of Bmal and Rors and inhibiting inflammation.
The Predictive Potential of Altered Voxel-Based Morphometry in Severely Obese Patients With Meibomian Gland Dysfunction
Authors: Li Le-Yan , Wang Yuan-Yuan , Gao Jun-Wei , Chen Jun , Kang Min , Ying Ping , Liao Xulin , Wang Yixin , Zou Jie , Su Ting , Wei Hong , Shao Yi
Published: July 2022

Objective

To investigate voxel-based morphometry (VBM) by using magnetic resonance imaging (MRI) in meibomian gland dysfunction patients with severe obesity (PATs) and to explore the application of VBM in the early diagnosis, prevention of cognitive impairment and targeted treatment of this disease.

Methods

Sixteen PATs and 12 healthy controls (HCs) were enrolled and underwent MRI. Whole-head images were analyzed using VBM and data were compared between groups using an independent samples t-test. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic value of this approach. Mini-mental state examination (MMSE) scores were used to assess cognitive impairment and were analyzed using an independent samples t-test.

Results

Compared with HCs, the VBM values in PATs were reduced in the left cerebellum and right thalamus but increased in the right brainstem, right precuneus and right paracentral lobule. The results of ROC curve analysis indicated that VBM may be useful in meibomian gland disease diagnosis. Comparison of MMSE scores between groups showed mild cognitive impairment in PATs.

Conclusion

PATs showed altered VBM values in some brain areas. These findings may provide information about the pathophysiology of meibomian gland dysfunction and may help to explain the underlying mechanisms of clinical manifestations in PATs, such as cognitive impairment. Abnormal VBM values in these brain areas may serve as predictive factors for development of meibomian gland disease in severely obese people and as indicators for individualized treatment.
Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms
Authors: Han Haijun , Xu Mengxiang , Wen Li , Chen Jiali , Liu Qiang , Wang Ju , Li Ming D. , Yang Zhongli
Published: July 2022

Although numerous susceptibility loci for depression have been identified in recent years, their biological function and molecular mechanism remain largely unknown. By using an exome-wide association study for depressive symptoms assessed by the Center for Epidemiological Studies Depression (CES-D) score, we discovered a novel missense single nucleotide polymorphism (SNP), rs61753730 (Q152E), located in the fourth exon of the frizzled class receptor 6 gene (FZD6), which is a potential causal variant and is significantly associated with the CES-D score. Computer-based in silico analysis revealed that the protein configuration and stability, as well as the secondary structure of FZD6 differed greatly between the wild-type (WT) and Q152E mutant. We further found that rs61753730 significantly affected the luciferase activity and expression of FZD6 in an allele-specific way. Finally, we generated Fzd6-knockin (Fzd6-KI) mice with rs61753730 mutation using the CRISPR/Cas9 genome editing system and found that these mice presented greater immobility in the forced swimming test, less preference for sucrose in the sucrose preference test, as well as decreased center entries, center time, and distance traveled in the open filed test compared with WT mice after exposed to chronic social defeat stress. These results indicate the involvement of rs61753730 in depression. Taken together, our findings demonstrate that SNP rs61753730 is a novel functional variant and plays an important role in depressive symptoms.
Depression in Adolescence and Brain-Derived Neurotrophic Factor
Authors: Lee Boyoung , Shin Eunjin , Song Inwoong , Chang Bomi
Published: July 2022

The incidence of depression among adolescents has been rapidly increasing in recent years. Environmental and genetic factors have been identified as important risk factors for adolescent depression. However, the mechanisms underlying the development of adolescent depression that are triggered by these risk factors are not well understood. Clinical and preclinical studies have focused more on adult depression, and differences in depressive symptoms between adolescents and adults make it difficult to adequately diagnose and treat adolescent depression. Brain-derived neurotrophic factor (BDNF) is known to play a critical role in the pathophysiology of many psychiatric disorders, including depression. However, there are still few studies on adolescent depression. Therefore, in this review paper, the causes and treatment of adolescent depression and the function of BDNF are investigated.
Driving Distance and Food Accessibility: A Geospatial Analysis of the Food Environment in the Navajo Nation and Border Towns
Authors: Bennion Natalie , Redelfs Alisha H. , Spruance Lori , Benally Shelby , Sloan-Aagard Chantel
Published: July 2022

The Navajo Nation, an area home to approximately 173,000 people in the southwest United States, experiences the highest rates of food insecurity in the United States and is classified as a food desert. The present study assessed the accessibility to food outlets (grocery stores, convenience stores, and restaurants) as measured by driving time on the Navajo Nation and in selected surrounding border towns. Food outlets located in neighboring border towns were examined using network analysis tools in ArcGIS Pro to calculate driving distance and examine the potential impact of driving time within the Navajo Nation on accessibility to nutritious foods. There were 14 grocery stores, 21 convenience stores, and 65 restaurants identified in the Navajo Nation using Mergent Intellect, a proprietary database, as compared to border towns which had a total of 542 grocery stores, 762 convenience stores, and 3,329 restaurants equaling a ratio of about 50:1 (grocery, 39:1; convenience, 36:1; restaurants, 51:1) when comparing food outlets nearby versus on the Navajo Nation. This ecological study presents a visual representation of driving time and food accessibility, revealing geographic areas within the Navajo Nation where access to border town food stores is sparse, and food insecurity may be elevated.
Dietary Acid Load (DAL), Glycated Hemoglobin A1c (HbA1c), and Metabolic Syndrome (MeS) Mediate the Association of the Adherence to the Dietary Approaches to Stopping Hypertension (DASH) and Mediterranean Diet (MeD) With Nonalcoholic Fatty Liver Disease
Authors: Doustmohammadian Azam , Nouri Saeidlou Sakineh , Esfandyari Saeed , Gholizadeh Esmaeel , Maadi Mansooreh , Motamed Nima , Ajdarkosh Hossein , Khoonsari Mahmoodreza , Clark Cain C. T. , Zamani Farhad
Published: July 2022

The study aimed to investigate the association of adults adhering to Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet (MeD) with nonalcoholic fatty liver disease (NAFLD) using structural equation modeling (SEM) in Iran. In this population-based cross-sectional study, 3,220 adults (44.65% female) aged ≥18 years were selected from the Amol Cohort Study (AmolCS). The dietary intakes were assessed by a validated 168-item semi-quantitative food-frequency questionnaire (FFQ). Residual method energy adjustment of MeD and DASH scores were calculated. Demographic characteristics and anthropometric and laboratory measurements were collected. NAFLD was diagnosed by an expert radiologistviaultrasound sonography. Based on the primary hypothesis, DASH, MeD, and NAFLD were fitted into models. Metabolic syndrome (MeS) as a potential risk factor directly affected NAFLD risk in all these models. In both genders, the higher adherence to DASH negatively affected NAFLD risk indirectly through the two following paths. (1) Dietary acid load (DAL) and metabolic syndrome (2) DAL and hemoglobin A1c (HbA1c). In addition, the higher DAL positively affected NAFLD risk among male participants indirectlyviaincreasing HbA1c level and MeS (from DAL to HbA1c: β = 0.07,P< 0.001; from HbA1c to MeS: β = 0.10,P< 0.001). Similarly, in both genders, the relationship between MeD and NAFLD was mediated through (1) DAL, HbA1c, and MeS and (2) DAL and MeS. Further, among male participants, the MeD and NAFLD risk were also associatedviathe mediators of HbA1c and MeS. In female participants, the higher MeD score was directly associated with a reduction of NAFLD risk (β = −0.07,P= 0.008). The present study found three important mediators, including DAL, HbA1c, and MeS, in the association of DASH and MeD scores with NAFLD risk. Preventive and therapeutic interventions should target the mediators, including DAL, HbA1c, MeS, and its components, to reduce NAFLD incidence in the general population.
A Sustainable and Antimicrobial Food Packaging Film for Potential Application in Fresh Produce Packaging
Authors: An Ling , Hu Xinzhong , Perkins Phil , Ren Tian
Published: July 2022

N-halamines are a group of compounds containing one or more nitrogen-halogen covalent bond(s). This high-energy halide bond provides a strong oxidative state so that it is able to inactivate microorganisms effectively. In this study, a sustainable film was developed based on polylactic acid (PLA) with incorporated N-halamine compound 1-chloro-2,2,5,5-tetramethyl-4-imidazolidinone (MC), as a promising antimicrobial food packaging material. Results showed that the incorporation of MC prevented the crystallization of PLA and improved the physical properties of the films. In addition, both the moisture barrier and the oxygen permeability were improved with the presence of MC. Importantly, the antimicrobial film was able to inactivate inoculated microorganisms by a factor of seven log cycles in as little as 5 min of contact. Films that contained higher levels of MC further enhanced the antimicrobial efficacy. Fresh strawberries packed with the fabricated films maintained the quality for up to 5 days. Due to the ease of fabrication and the effective biocidal property, these films have a wide range of potential applications in the field of food packaging to extend the shelf life of fresh produce.
Active Consideration of Future Health Can Be Prompted by Simple Health Messages and Improves Nutritional Quality of Food Choices
Authors: Gustafson Christopher R.
Published: July 2022

Many choices that people face daily have implications for future health and well-being. Choices about what foods to purchase and consume are one of the most frequent—and universal choices—that people must make. The ongoing rise of overweight and obesity rates—and associated diet-related diseases—in the US and many other countries illustrates the future health consequences of low-quality dietary choices. While a large body of research shows that individuals with a tendency to consider the future make a wide range of healthier decisions, research on limited attention and exogenous factors influencing choice suggests that attention to the future consequences of choices may vary from one choice scenario to the next. In this research, we examine the impact of active consideration of future health impacts during a hypothetical online food choice experiment on the nutritional quality of food choices and on choice process variables—the set of products people choose to select from and the use of nutrition information during choice—during an online food choice task. Next, we examine the impact of exposure to a short message about the health benefits of fiber on consideration of future health impacts and on the nutritional quality of choices. We find that active consideration of future health impacts significantly improves the nutritional quality of choices—particularly among processed food products—and makes people more likely to pay attention to healthy foods and use nutrition information. Exposure to a short health message significantly increases the likelihood that individuals consider future health impacts during choice, which promotes healthier choices overall.
Preparation and Structure Characterization of High-Value Laminaria digitata Oligosaccharides
Authors: Cheong Kit-Leong , Li Jia-Kang , Zhong Saiyi
Published: July 2022

Algae-derived marine oligosaccharides have been reported to be promising bioactive compounds because of their various properties with health benefits and potential significance in numerous applications in industrial biotechnology. In this study, laminaran oligosaccharides (LOs) with varying degrees of polymerization were obtained through partial acid hydrolysis of laminaran derived from Laminaria digitata. Based on response surface methodology, the optimum LOs yield was obtained for acid hydrolysis laminaran at a hydrolysis time of 55 min, temperature of 71°C, and acid concentration of 1.00 mol/L. The size-exclusion resin Bio-Gel P-2 was considered to be a better option for LOs purification. The structure of the purified oligosaccharides was analyzed through mass spectrometry and nuclear magnetic resonance. They demonstrated the main oligosaccharide structure corresponding to the connection of glucose with β-D-Glcp-(1→3)-β-D-Glcp, which was identified as laminaribiose (DP2), laminaritriose (DP3), laminaritetrose (DP4), and laminaripentaose (DP5). LOs demonstrate excellent antioxidant activities, as evidenced from their reactions with oxidizing free radicals, 1, 1-diphenyl-2-picryl-hydrazyl, and 2, 2′-azino-bis (3-etilbenzotiazoline-6-sulfonic acid) radicals. LOs exhibited a prebiotic effect on the growth of Bifidobacterium adolescentis and Lactobacillus plantarum. Therefore, we propose the development of LOs as natural antioxidants and prebiotics in the functional food and pharmaceutical industries.
Association of Dietary Intake and Biomarker of α-Linolenic Acid With Incident Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Dai Ze-Bin , Ren Xiao-Li , Xue Yi-Lang , Tian Ya , He Bing-Bing , Xu Chang-Long , Yang Bo
Published: July 2022

Background and Objective

There is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts.

Methods

Pertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively.

Results

Over the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I2: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I2: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I2: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24).

Conclusions

Blood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.