bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases
Authors: Gao Han , He Chengwei , Hua Rongxuan , Guo Yuexin , Wang Boya , Liang Chen , Gao Lei , Shang Hongwei , Xu Jing-Dong
Published: March 2022

The endoplasmic reticulum, a vast reticular membranous network from the nuclear envelope to the plasma membrane responsible for the synthesis, maturation, and trafficking of a wide range of proteins, is considerably sensitive to changes in its luminal homeostasis. The loss of ER luminal homeostasis leads to abnormalities referred to as endoplasmic reticulum (ER) stress. Thus, the cell activates an adaptive response known as the unfolded protein response (UPR), a mechanism to stabilize ER homeostasis under severe environmental conditions. ER stress has recently been postulated as a disease research breakthrough due to its significant role in multiple vital cellular functions. This has caused numerous reports that ER stress-induced cell dysfunction has been implicated as an essential contributor to the occurrence and development of many diseases, resulting in them targeting the relief of ER stress. This review aims to outline the multiple molecular mechanisms of ER stress that can elucidate ER as an expansive, membrane-enclosed organelle playing a crucial role in numerous cellular functions with evident changes of several cells encountering ER stress. Alongside, we mainly focused on the therapeutic potential of ER stress inhibition in gastrointestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer. To conclude, we reviewed advanced research and highlighted future treatment strategies of ER stress-associated conditions.
First Principles Calculation of Protein–Protein Dimer Affinities of ALS-Associated SOD1 Mutants
Authors: Hsueh Shawn C. C. , Nijland Mark , Peng Xubiao , Hilton Benjamin , Plotkin Steven S.
Published: March 2022

Cu,Zn superoxide dismutase (SOD1) is a 32 kDa homodimer that converts toxic oxygen radicals in neurons to less harmful species. The dimerization of SOD1 is essential to the stability of the protein. Monomerization increases the likelihood of SOD1 misfolding into conformations associated with aggregation, cellular toxicity, and neuronal death in familial amyotrophic lateral sclerosis (fALS). The ubiquity of disease-associated mutations throughout the primary sequence of SOD1 suggests an important role of physicochemical processes, including monomerization of SOD1, in the pathology of the disease. Herein, we use a first-principles statistical mechanics method to systematically calculate the free energy of dimer binding for SOD1 using molecular dynamics, which involves sequentially computing conformational, orientational, and separation distance contributions to the binding free energy. We consider the effects of two ALS-associated mutations in SOD1 protein on dimer stability, A4V and D101N, as well as the role of metal binding and disulfide bond formation. We find that the penalty for dimer formation arising from the conformational entropy of disordered loops in SOD1 is significantly larger than that for other protein–protein interactions previously considered. In the case of the disulfide-reduced protein, this leads to a bound complex whose formation is energetically disfavored. Somewhat surprisingly, the loop free energy penalty upon dimerization is still significant for the holoprotein, despite the increased structural order induced by the bound metal cations. This resulted in a surprisingly modest increase in dimer binding free energy of only about 1.5 kcal/mol upon metalation of the protein, suggesting that the most significant stabilizing effects of metalation are on folding stability rather than dimer binding stability. The mutant A4V has an unstable dimer due to weakened monomer-monomer interactions, which are manifested in the calculation by a separation free energy surface with a lower barrier. The mutant D101N has a stable dimer partially due to an unusually rigid β-barrel in the free monomer. D101N also exhibits anticooperativity in loop folding upon dimerization. These computational calculations are, to our knowledge, the most quantitatively accurate calculations of dimer binding stability in SOD1 to date.
Long-Term Social Isolation-Induced Autophagy Inhibition and Cell Senescence Aggravate Cognitive Impairment in D(+)Galactose-Treated Male Mice
Authors: Wang Bin , Ntim Michael , Xia Min , Wang Ying , Lu Jin-cheng , Yang Jin-Yi , Li Shao
Published: March 2022

Aging is associated with physiological and pathological changes and presents health complications, such as dementia. Isolation has also been associated with the experience of growing old. Both have been linked individually to the incidence of cognitive decline. In this present study, the effects of these two phenomena have been looked at in animal models where aging was induced with D(+)Galactose in mice who underwent long-term post-weaned social isolation (L-PWSI). Assessing cognitive function using Y-maze, Morris water maze (MWM), and passive avoidance tests (PATs) confirmed that cognition is impaired in either of the treatments but worsened when the D(+)Galactose mice were subjected to L-PWSI. Moreover, a synaptic protein, PSD95, and dendritic spines density were significantly reduced in the L-PWSI and D(+)Galactose-treated mice. Our previous study revealed that autophagy deficit is involved in cognitive impairment in the L-PWSI model. Here, we first report the inhibited cell cycle in L-PWSI, combined with the decreased autophagy, aggravates cognitive impairment in D(+)Galactose-treated mice. Beyond these, the autophagy and cell cycle mechanisms that link isolation and aging have been explored. The close association between isolation and aging in humans is very real and needs much research attention going forward for possible therapeutic interventions.
Body Complexion and Circulating Lipids in the Risk of TDP-43 Related Disorders
Authors: Esteban-García Noelia , Fernández-Beltrán Luis C. , Godoy-Corchuelo Juan Miguel , Ayala Jose L. , Matias-Guiu Jordi A. , Corrochano Silvia
Published: March 2022

Objective

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two distinct degenerative disorders with overlapping genetics, clinical manifestations, and pathology, including the presence of TDP-43 aggregates in nearly 50% of patients with FTD and 98% of all patients with ALS. Here, we evaluate whether different genetically predicted body lipid metabolic traits are causally associated with the risk of FTD with TDP-43 aggregates, compare it to their causal role in the risk of ALS, and identify genetic variants shared between these two TDP43 related disorders in relation to lipid metabolic traits.

Methods

We conducted two-sample Mendelian randomization analyses (2SMR) to evaluate the causal association of 9 body complexion and 9 circulating lipids traits with the risk of FTD with TDP-43 aggregates and the risk of ALS. The inverse-variance weighted method was the primary analysis, followed by secondary sensitive analyses. We then looked for common genetic variants between FTD and ALS in relation to lipid metabolic traits.

Results

Genetically increased trunk-predicted mass, fat-free mass, and higher circulating triglycerides levels were suggestively associated with a higher risk of FTD with TDP-43 aggregates. Circulating lipids, mainly LDL cholesterol, were causally associated with a higher risk of ALS. We identified two genetic variants, EIF4ENIF1 and HNRNPK, in relation to body complexion and circulating lipids shared between FTD with TDP-43 aggregates and ALS.

Conclusion

This work provides evidence that body complexion and circulating lipids traits impact differentially on the risk of FTD and ALS, suggesting new and specific interventional approaches in the control of body lipid metabolism for FTD and ALS, and identified HNRNPK as a potential link between circulating lipids levels and these disorders.
Expression of SH3 and Multiple Ankyrin Repeat Domains Protein 3 in Mouse Retina
Authors: Xu Yue , Wang Ya’nan , Tong Guang’an , Li Lin , Cheng Juan , Zhang Lesha , Xu Qi , Wang Liecheng , Zhang Pingping
Published: March 2022

Synapse-associated gene mutations of SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) may lead to autism spectrum disorder (ASD). In some ASD cases, patients may also have vision disorders. However, the effects of SHANK3 in the retina are barely mentioned in the literature. In this study, we used wild-type mice to systematically map the distribution of SHANK3 expression in entire mouse retinas. Using Western blot analysis and immunofluorescence double labeling, we identified a large number of prominent cells expressing high levels of SHANK3 in the inner retina, in particular, the ganglion cell layer (GCL) and inner nucleus layer. The inner plexiform layer and outer nucleus layer were also exhibited positive SHANK3 signals. In the inner layer, GABAergic amacrine cells (ACs) labeled by glutamate decarboxylase were colocalized with SHANK3-positive cells. Dopaminergic ACs (labeled by tyrosine hydroxylase) and cholinergic ACs (labeled by choline acetyltransferase) were also found to contain SHANK3-positive signals. Additionally, most GCs (labeled by Brn3a) were also found to be SHANK3 positive. In the outer retina, bipolar cells (labeled by homeobox protein ChX10) and horizontal cells (labeled by calbindin) were SHANK3 positive. In the outer nucleus layers, the somata of blue cones (labeled by S-opsin) were weekly co-labeled with SHANK3. The inner segments of blue cones and the outer segments of red/green cones (labeled by L/M-opsin) were partially colocalized with SHANK3 and the outer segments of rods (labeled by Rho4D2) were partially SHANK3 positive too. Moreover, SHANK3-positive labeling was also observed in Müller cells (labeled by cellular retinaldehyde-binding protein). These wide expression patterns indicate that SHANK3 may play an important role in the visual signaling pathway.
Nuclear Magnetic Resonance Treatment Accelerates the Regeneration of Dorsal Root Ganglion Neurons in vitro
Authors: Mann Anda , Steinecker-Frohnwieser Bibiane , Naghilou Aida , Millesi Flavia , Supper Paul , Semmler Lorenz , Wolf Sonja , Marinova Lena , Weigl Lukas , Weiss Tamara , Radtke Christine
Published: March 2022

Functional recovery from peripheral nerve injuries depends on a multitude of factors. Schwann cells (SCs) are key players in the regenerative process as they develop repair-specific functions to promote axon regrowth. However, chronically denervated SCs lose their repair phenotype, which is considered as a main reason for regeneration failure. Previous studies reported a modulatory effect of low nuclear magnetic resonance therapy (NMRT) on cell proliferation and gene expression. To provide first insight into a possible effect of NMRT on cells involved in peripheral nerve regeneration, this study investigated whether NMRT is able to influence the cellular behavior of primary SC and dorsal root ganglion (DRG) neuron cultures in vitro. The effect of NMRT on rat SCs was evaluated by comparing the morphology, purity, proliferation rate, and expression levels of (repair) SC associated genes between NMRT treated and untreated SC cultures. In addition, the influence of (1) NMRT and (2) medium obtained from NMRT treated SC cultures on rat DRG neuron regeneration was examined by analyzing neurite outgrowth and the neuronal differentiation status. Our results showed that NMRT stimulated the proliferation of SCs without changing their morphology, purity, or expression of (repair) SC associated markers. Furthermore, NMRT promoted DRG neuron regeneration shown by an increased cell survival, enhanced neurite network formation, and progressed neuronal differentiation status. Furthermore, the medium of NMRT treated SC cultures was sufficient to support DRG neuron survival and neurite outgrowth. These findings demonstrate a beneficial impact of NMRT on DRG neuron survival and neurite formation, which is primarily mediated via SC stimulation. Our data suggest that NMRT could be suitable as a non-invasive auxiliary treatment option for peripheral nerve injuries and encourage future studies that investigate the effect of NMRT in a physiological context.
Closed-Loop Tracking and Regulation of Emotional Valence State From Facial Electromyogram Measurements
Authors: Branco Luciano R. F. , Ehteshami Arian , Azgomi Hamid Fekri , Faghih Rose T.
Published: March 2022

Affective studies provide essential insights to address emotion recognition and tracking. In traditional open-loop structures, a lack of knowledge about the internal emotional state makes the system incapable of adjusting stimuli parameters and automatically responding to changes in the brain. To address this issue, we propose to use facial electromyogram measurements as biomarkers to infer the internal hidden brain state as feedback to close the loop. In this research, we develop a systematic way to track and control emotional valence, which codes emotions as being pleasant or obstructive. Hence, we conduct a simulation study by modeling and tracking the subject's emotional valence dynamics using state-space approaches. We employ Bayesian filtering to estimate the person-specific model parameters along with the hidden valence state, using continuous and binary features extracted from experimental electromyogram measurements. Moreover, we utilize a mixed-filter estimator to infer the secluded brain state in a real-time simulation environment. We close the loop with a fuzzy logic controller in two categories of regulation: inhibition and excitation. By designing a control action, we aim to automatically reflect any required adjustments within the simulation and reach the desired emotional state levels. Final results demonstrate that, by making use of physiological data, the proposed controller could effectively regulate the estimated valence state. Ultimately, we envision future outcomes of this research to support alternative forms of self-therapy by using wearable machine interface architectures capable of mitigating periods of pervasive emotions and maintaining daily well-being and welfare.
Forgetting Enhances Episodic Control With Structured Memories
Authors: Yalnizyan-Carson Annik , Richards Blake A.
Published: March 2022

Forgetting is a normal process in healthy brains, and evidence suggests that the mammalian brain forgets more than is required based on limitations of mnemonic capacity. Episodic memories, in particular, are liable to be forgotten over time. Researchers have hypothesized that it may be beneficial for decision making to forget episodic memories over time. Reinforcement learning offers a normative framework in which to test such hypotheses. Here, we show that a reinforcement learning agent that uses an episodic memory cache to find rewards in maze environments can forget a large percentage of older memories without any performance impairments, if they utilize mnemonic representations that contain structural information about space. Moreover, we show that some forgetting can actually provide a benefit in performance compared to agents with unbounded memories. Our analyses of the agents show that forgetting reduces the influence of outdated information and states which are not frequently visited on the policies produced by the episodic control system. These results support the hypothesis that some degree of forgetting can be beneficial for decision making, which can help to explain why the brain forgets more than is required by capacity limitations.
Case Report: Roxadustat in Combination With Rituximab Was Used to Treat EPO-Induced Pure Red Cell Aplasia
Authors: You Xiaoe , Guo Baochun , Wang Zhen , Ma Hualin , Zhou Ru , Liu Lixia , Zhang Xinzhou
Published: March 2022

Recombinant human erythropoietin (rHuEPO) is a drug given to patients who have low hemoglobin related to chronic kidney disease or other anemia-related diseases. Some patients who receive rHuEPO repeatedly develop anti-rHuEPO-neutralizing antibodies, leading to the occurrence of pure red cell aplasia (PRCA). PRCA associated with rHuEPO includes severe rHuEPO resistance, blood transfusion dependence, high serum ferritin, severe reticulocytopenia, and presence of anti-rHuEPO antibody. However, the optimal treatment of erythropoietin (EPO)-induced PRCA is unclear. Therapeutic options against it remain a major clinical challenge. Herein we report on 2 male patients with PRCA during rHuEPO treatment, who received a combination therapy of roxadustat plus rituximab but had completely different clinical outcomes. The results obtained in this study show that roxadustat in combination with rituximab could be one of the treatment options for EPO-induced PRCA, but the treatment efficacy can vary from one individual to another. Additionally, we recommend starting reticulocyte monitoring and immunosuppressive agent therapy as early as possible to shorten the course of the disease and improve the outcomes of the patients.
Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session
Authors: He Jia-Kai , Jia Bao-Hui , Wang Yu , Li Shao-Yuan , Zhao Bin , Zhou Zeng-Guang , Bi Yan-Zhi , Wu Mo-Zheng , Li Liang , Zhang Jin-Ling , Fang Ji-Liang , Rong Pei-Jing
Published: March 2022

Objectives

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear.

Methods

Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes.

Results

The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment.

Conclusions

It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.
Genetic Study of Cerebral Small Vessel Disease in Chinese Han Population
Authors: Wang Yunchao , Shi Changhe , Li Yusheng , Yu Wenkai , Wei Sen , Fan Yu , Mao Chengyuan , Yang Zhihua , Yu Lulu , Zhao Zichen , Li Shanshan , Gao Yuan , Xu Yuming
Published: March 2022

Cerebral small vessel disease (CSVD) is a syndrome of clinical, neuroimaging, and neuropathological manifestations caused by disorders that affect small cerebral vessels. Although the pathogenesis of the disease remains unclear, some studies have demonstrated that genetic variants contribute to the development of CSVD. Our study aimed to explore the genetic characteristics of CSVD in the Chinese Han population. We enrolled 182 sporadic CSVD Chinese Han patients whose magnetic resonance imaging results showed grade 2-3 white matter lesions. Target region sequencing of seven monogenic CSVD-related genes, including NOTCH3, HTRA1, COL4A1, COL4A2, GLA, TREX1, and CTSA, was performed, and we identified pathogenic variants by screening the sequencing results and functional predictive analysis. All variants were predicted to be pathogenic by the SIFT Score, Polymorphism Phenotyping-2 score, Mutation Taster, Splice site score calculation, and MaxEntScan. All variants were validated in 300 healthy controls. In total, eight variants were identified in patients with CSVD, including five novel variants, c.1774C>T (NOTCH3), c.3784C>T (NOTCH3), c. 1207C>T (HTRA1), and c. 1274+1G> A (HTRA1), c.1937G>C (COL4A1) and three reported mutations. None of these variants were present in 300 healthy controls. No pathogenic variants in COL4A2, GLA, TREX1, and CTSA were detected. This study identified five novel variants in CSVD-related genes in Chinese Han patients with sporadic CSVD. Our results expand the genetic profile of CSVD.
The Smoking Paradox in Stroke Patients Under Reperfusion Treatment Is Associated With Endothelial Dysfunction
Authors: Iglesias-Rey Ramón , Custodia Antía , Alonso-Alonso Maria Luz , López-Dequidt Iria , Rodríguez-Yáñez Manuel , Pumar José M. , Castillo José , Sobrino Tomás , Campos Francisco , Silva-Candal Andres da , Hervella Pablo
Published: March 2022

Objective

This study aimed to explore the association between smoking habit and the serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), in relation with the functional outcome of patients with acute ischemic stroke undergoing reperfusion treatment.

Methods

Observational and retrospective study of a series of patients with acute ischemic stroke subjected to reperfusion treatments. Clinical, analytical, and neuroimaging parameters were analyzed. The main endpoint was the functional outcome at 3 months, measured by the modified Ranking Scale (mRS). Logistic regression models were used to analyze the association between smoking and sTWEAK levels with functional outcome and leukoaraiosis.

Results

The results showed that smoking habit was associated with a good functional outcome at 3 months in patients with stroke (OR: 3.52; 95% CI: 1.03–11.9; p = 0.044). However, this independent association was lost after adjusting by sTWEAK levels (OR 1.73; 95% CI: 0.86–13.28; p = 0.116). sTWEAK levels were significantly lower in smoker patients [4015.5 (973.66–7921.83) pg/ml vs. 5,628 (2,848–10,202) pg/ml, p < 0.0001], while sTWEAK levels were significantly higher in patients with poor functional outcomes at 3 months [10,284 (7,388–13.247) pg/ml vs. 3,405 (2,329–6,629) pg/ml, p < 0.0001].

Conclusion

The decrease in sTWEAK levels was associated with a good functional outcome in smoker patients with stroke undergoing reperfusion therapy.
Effects of Traditional Chinese Exercises on Cognitive Function in Older Adults With Mild Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Zhou Kaixiang , Liu Meng , Bao Dapeng , Zhou Junhong
Published: March 2022

Background

Recently, considerable research has been conducted to study the effects of traditional Chinese exercises (TCEs) on cognitive function in older adults with MCI. We completed a comprehensive systematic review and meta-analysis to assess the efficacy of TCEs on cognitive function in this population.

Methods

A search strategy based on the PICOS principle was used to find the literatures in the databases of PubMed, Web of Science, MEDLINE, SPORT-Discus, PsycINFO, Cochrane Central Register of Controlled Trials, Ovid. The quality and risk of bias in the studies were independently assessed by two researchers.

Results

Nine trials with 1,290 participants were included. The effect size of TCEs on global cognitive function was small (SMD = 0.29, 95% CI 0.15–0.44, p < 0.001) when compared to the active control and was moderate (SMD = 0.58, 95% CI 0.21–0.94, p = 0.002) compared to the inactive control; statistically significant effects were also found for short-term memory (SMD = 0.22, 95% CI 0.05–0.39, p = 0.013), long-term memory (SMD = 0.53, 95% CI 0.20–0.86, p = 0.002), shifting (SMD = −0.39, 95% CI −0.54 to −0.25, p < 0.001), language ability (SMD = 0.32, 95% CI 0.13–0.51, p = 0.001), visuospatial perception (SMD = 0.31, 95% CI 0.15–0.46, p < 0.001).

Conclusion

This meta-analysis provides clinicians with moderate evidence to recommend that TCEs hold potential to enhance both global cognitive function and multiple domains of cognitive function, which, however, needs to be confirmed and further examined in futures studies. The results of this work provide critical knowledge for the design of future studies implementing TCEs as well as its clinical practice. Future RCTs with rigorous designs are needed to help obtain more definitive conclusions on the effects of TCEs on cognitive function in older adults with MCI.
Toward a Multidimensional Understanding of Misophonia Using Cluster-Based Phenotyping
Authors: Norris Jordan E. , Kimball Suzanne H. , Nemri Danna C. , Ethridge Lauren E.
Published: March 2022

Misophonia is a condition characterized by hypersensitivity and strong emotional reactivity to specific auditory stimuli. Misophonia clinical presentations are relatively complex and reflect individualized experiences across clinical populations. Like some overlapping neurodevelopmental and neuropsychiatric disorders, misophonia is potentially syndromic where symptom patterns rather than any one symptom contribute to diagnosis. The current study conducted an exploratory k-means cluster analysis to evaluate symptom presentation in a non-clinical sample of young adult undergraduate students (N = 343). Individuals participated in a self-report spectrum characteristics survey indexing misophonia, tinnitus severity, sensory hypersensitivity, and social and psychiatric symptoms. Results supported a three-cluster solution that split participants on symptom presentation: cluster 1 presented with more severe misophonia symptoms but few overlapping formally diagnosed psychiatric co-occurring conditions; cluster 3 was characterized by a more nuanced clinical presentation of misophonia with broad-band sensory hypersensitivities, tinnitus, and increased incidence of social processing and psychiatric symptoms, and cluster 2 was relatively unaffected by misophonia or other sensitivities. Clustering results illustrate the spectrum characteristics of misophonia where symptom patterns range from more “pure” form misophonia to presentations that involve more broad-range sensory-related and psychiatric symptoms. Subgroups of individuals with misophonia may characterize differential neuropsychiatric risk patterns and stem from potentially different causative factors, highlighting the importance of exploring misophonia as a multidimensional condition of complex etiology.
Neurotechnological Approaches to the Diagnosis and Treatment of Alzheimer’s Disease
Authors: Ning Shen , Jorfi Mehdi , Patel Shaun R. , Kim Doo Yeon , Tanzi Rudolph E.
Published: March 2022

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, clinically defined by progressive cognitive decline and pathologically, by brain atrophy, neuroinflammation, and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Neurotechnological approaches, including optogenetics and deep brain stimulation, have exploded as new tools for not only the study of the brain but also for application in the treatment of neurological diseases. Here, we review the current state of AD therapeutics and recent advancements in both invasive and non-invasive neurotechnologies that can be used to ameliorate AD pathology, including neurostimulation via optogenetics, photobiomodulation, electrical stimulation, ultrasound stimulation, and magnetic neurostimulation, as well as nanotechnologies employing nanovectors, magnetic nanoparticles, and quantum dots. We also discuss the current challenges in developing these neurotechnological tools and the prospects for implementing them in the treatment of AD and other neurodegenerative diseases.
Daily Food Insecurity Predicts Lower Positive and Higher Negative Affect: An Ecological Momentary Assessment Study
Authors: Na Muzi , Dou Nan , Liao Yujie , Rincon Sara Jimenez , Francis Lori A. , Graham-Engeland Jennifer E. , Murray-Kolb Laura E. , Li Runze
Published: March 2022

Food insecurity (FI) is a dynamic phenomenon, and its association with daily affect is unknown. We explored the association between daily FI and affect among low-income adults during a 2-seasonal-month period that covered days both pre- and during the COVID-19 pandemic. A total of 29 healthy low-income adults were recruited during fall in 2019 or 2020, 25 of whom were followed in winter in 2020 or 2021. Daily FI (measured once daily) and affect (measured 5 times daily) were collected over the 2nd−4th week in each month. Time-Varying-Effect-Models were used to estimate the association between daily FI and positive/negative affect (PA/NA). Overall, 902 person-days of daily-level data were collected. Daily FI was associated with lower PA in the 3rd and 4th week of fall and winter and with higher NA in the second half of winter months. Similar patterns of FI-affect relations were found pre- and during COVID-19 in the second half of a given month, while unique patterns of positive affect scores in the 2nd week and negative scores in the 1st week were only observed during COVID days. Our study supports a time-varying association between FI and affect in low-income adults. Future large studies are needed to verify the findings; ultimately, better understanding such associations may help identify, target, and intervene in food insecure adults to prevent adverse mental health outcomes.
Association of Ratio of Apolipoprotein B to Apolipoprotein A1 With Survival in Peritoneal Dialysis
Authors: Yu Jing , Xia Xi , Huang Na-Ya , Qiu Ya-Gui , Yang Xiao , Mao Hai-Ping , Chen Wei , Huang Feng-Xian
Published: March 2022

Background

Although the ratio of apolipoprotein B (apo B) to apolipoprotein A1 (apo A1) (apo B/apo A1) seems to be associated with mortality in hemodialysis (HD) patients, the association of apo B/apo A1 ratio with death remains not clear in peritoneal dialysis (PD) patients.

Aims

The study targets to examine the relationship of apo B/apo A1 ratio with survival in patients receiving PD treatment.

Methods

In this single-center prospective observational cohort study, we enrolled 1,616 patients receiving PD treatment with a median follow-up time of 47.6 months. We used a multivariable Cox proportional hazards model to examine the relationship between apo B/apo A1 ratio and cardiovascular (CV) and all-cause mortality. The association of apo B/apo A1 ratio with atherosclerotic and non-atherosclerotic CV mortality was further evaluated by competing risk regression models.

Results

During the follow-up, 508 (31.4%) patients died, 249 (49.0%) died from CV events, of which 149 (59.8%) were atherosclerotic CV mortality. In multivariable models, for 1-SD increase in apo B/apo A1 ratio level, the adjusted hazard ratios for CV and all-cause mortality were 1.26 [95% confidence interval (CI), 1.07–1.47; P = 0.005] and 1.20 (95% CI, 1.07–1.35; P = 0.003), respectively. The adjusted subdistribution hazard ratios for atherosclerotic and non-atherosclerotic CV mortality were 1.43 (95% CI, 1.19–1.73; P < 0.001) and 0.85 (95% CI, 0.64–1.13; P = 0.256), respectively. For quartile analysis, patients in quartile 4 had higher CV, all-cause, and atherosclerotic CV mortality compared with those in quartile 1. Moreover, apo B/apo A1 ratio had a diabetes-related difference in CV, all-cause, and atherosclerotic CV mortality.

Conclusion

Elevated apo B/apo A1 ratio level was significantly associated with CV, all-cause, and atherosclerotic CV mortality in patients undergoing PD. Moreover, the association was especially statistically significant in patients with diabetes.
Molecular Authentication of Twelve Meat Species Through a Promising Two-Tube Hexaplex Polymerase Chain Reaction Technique
Authors: Cai Zhendong , Zhong Guowei , Liu Qianqian , Yang Xingqiao , Zhang Xiaoxia , Zhou Song , Zeng Xiaoqun , Wu Zhen , Pan Daodong
Published: March 2022

Frequent meat frauds have aroused significant social attention. The aim of this study is to construct a two-tube hexaplex polymerase chain reaction (PCR) method offering accurate molecular authentication of twelve meat species in actual adulteration event. Deoxyribonucleic acid (DNA) sequencing demonstrates that designed primers can specifically amplify target species from genomic DNA mixture of six species in each tube reaction, which showed 100% accuracy of horse (148 bp), pigeon (218 bp), camel (283 bp), rabbit (370 bp), ostrich (536 bp), and beef (610 bp) as well as turkey (124 bp), dog (149 bp), chicken (196 bp), duck (277 bp), cat (380 bp), and goose (468 bp). A species-specific primer pair produced the target band in the presence of target genomic DNA but not non-target species. Through multiplex PCR assays with serial concentration of the DNA mixture of six species in each PCR reaction, the detection limit (LOD) of the two-tube hexaplex PCR assay reached up to 0.05–0.1 ng. Using genomic DNA isolated from both boiled and microwave-cooked meat as templates, PCR amplification generated expected PCR products. These findings demonstrate that the proposed method is specific, sensitive and reproducible, and is adequate for food inspection. Most importantly, this method was successfully applied to detect meat frauds in commercial meat products. Therefore, this method is of great importance with a good application foreground.
Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein
Authors: Murray Margaret , Coughlan Melinda T. , Gibbon Anne , Kumar Vinod , Marques Francine Z. , Selby-Pham Sophie , Snelson Matthew , Tsyganov Kirill , Williamson Gary , Woodruff Trent M. , Wu Tong , Bennett Louise E.
Published: March 2022

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fermentation metabolites, and the biomarkers of health status in pigs as a model of human digestion and metabolism. Weanling pigs were fed with standard or resistant protein diets for 4 weeks. The resistant protein, approximately half as digestible as the standard protein, was designed to enter the colon for microbial fermentation. Fecal and blood samples were collected to assess the microbiome and circulating metabolites and biomarkers. The resistant protein diet group consumed less feed and grew to ~50% of the body mass of the standard diet group. The diets had unique effects on the fecal microbiome, as demonstrated by clustering in the principal coordinate analysis. There were 121 taxa that were significantly different between groups (adjusted-p < 0.05). Compared with control, plasma tri-methylamine-N-oxide, homocysteine, neopterin, and tyrosine were increased and plasma acetic acid was lowered following the resistant protein diet (all p < 0.05). Compared with control, estimated glomerular filtration rate (p < 0.01) and liver function marker aspartate aminotransferase (p < 0.05) were also lower following the resistant protein diet. A resistant protein diet shifted the composition of the fecal microbiome. The microbial fermentation of resistant protein affected the levels of circulating metabolites and the biomarkers of health status toward a profile indicative of increased inflammation and the risk of chronic kidney disease.
Non-linear Associations Between Visceral Adipose Tissue Distribution and Anthropometry-Based Estimates of Visceral Adiposity
Authors: Scafoglieri Aldo , Van den Broeck Jona , Cattrysse Erik , Bautmans Ivan , Heymsfield Steven B.
Published: March 2022

Background

Recent evidence suggests that excess visceral adipose tissue (VAT) is associated with future loss of subcutaneous adipose tissue (SAT) and skeletal muscle (SM) with aging. In clinical settings (abdominal) circumferences are commonly used to estimate body composition (BC). We aimed to study the linearity of VAT distribution ratios (i.e., VAT/SAT ratio and VAT/SM ratio), waist-to-hip ratio (WHR) and waist circumference (WC) with age and the relationship of VAT distribution ratios with anthropometry (i.e., WHR and WC).

Materials and Methods

BC was determined using whole body magnetic resonance imaging in a large multi-ethnic group of 419 adults (42% white, 30% black, 15% Hispanic, 13% Asian, 1% other) with a BMI ranging from 15.9 to 40.8kg/m2. Linear and non-linear regression analysis was used to examine the linearity of VAT distribution ratios and anthropometry from 18 to 88 years. The relation between VAT distribution ratios and anthropometry was assessed separately.

Results

In both sexes non-linear relationships were found between BC estimates and age, and between BC measures mutually. The ratios of VAT/SAT and VAT/SM showed quadratic relationships with age. VAT distribution ratios showed exponential or quadratic relationships with anthropometry with coefficients of determination ranging between 18 and 55%.

Conclusion

In both sexes, VAT distribution ratios showed curvilinear relationships with age and with anthropometry. Given the sex differences in VAT distribution ratios, WHR and WC represent different BC proportions in men and women. These results emphasize the challenge when interpreting changes in BC based upon linear extrapolations in clinical practice.
Polyphenol Extracts From Germinated Mung Beans Can Improve Type 2 Diabetes in Mice by Regulating Intestinal Microflora and Inhibiting Inflammation
Authors: Shen Xinting , Jiang Xiujie , Qian Lili , Zhang Aiwu , Zuo Feng , Zhang Dongjie
Published: March 2022

Studies have shown that inhibiting inflammation and regulating intestinal microflora imbalance is a significant factor in controlling the development of type 2 diabetes mellitus (T2DM). This experiment studied the protective effect of polyphenol extract from germinated mung beans on diabetic C57BL/6 mice.

Results

Fasting blood glucose (FBG) was decreased, glucose tolerance was increased, insulin resistance was decreased, serum lipid indexes in T2DM mice were improved, and the enzyme activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced. Meanwhile, the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in serum were decreased, the concentration of interleukin 10 (IL-10) in serum was increased, inhibiting the inflammatory reaction induced by diabetes and repairing the morphology of mice liver tissue. At the same time, germinated mung bean polyphenol (GMP) can regulate the main intestinal flora, Firmicutes, Bacteroidetes, and Proteobacteria in diabetic mice and can also regulate species diversity and improve intestinal flora imbalance. Taken together, the experimental conclusion is a certain dose of polyphenol extract from germinated mung beans that can improve mouse T2DM by inhibiting inflammatory reaction and regulating intestinal microflora.
Dietary Medium-Chain Triglyceride Decanoate Affects Glucose Homeostasis Through GPR84-Mediated GLP-1 Secretion in Mice
Authors: Nonaka Hazuki , Ohue-Kitano Ryuji , Masujima Yuki , Igarashi Miki , Kimura Ikuo
Published: March 2022

Background

Dietary triglycerides are an important energy source; however, their excess intake causes metabolic diseases such as obesity and type 2 diabetes. Medium-chain triglycerides (MCTs) as triglyceride forms of medium-chain fatty acids (MCFAs) are applied to meet the energy demands of athletes, the elderly, and people with stunted growth, because MCFAs are efficiently converted into energy for immediate utilization by the organs and do not accumulate as fat. Although the intake of each MCT type (octanoate; C8:0, decanoate; C10:0, and dodecanoate; C12:0) exhibits beneficial metabolic effects, individual functional differences remain unclear.

Methods

MCTs or MCFAs were administrated to male GPR84-deficient mice with a C57BL/6J background and mouse enteroendocrine cell line STC-1, and the effects on glucose homeostasis and gut hormone GLP-1 secretion were evaluated.

Results

C10:0 intake improves glucose metabolism through the MCFA receptor GPR84-mediated GLP-1 secretion. Each MCT intake showed resistance to obesity and improved metabolic parameters compared with lard intake. Moreover, oral administration of MCTs enhanced glucose tolerance, especially C10:0 administration, which sufficiently increased plasma GLP-1 levels. Additionally, C10:0 stimulation promoted GLP-1 secretion via GPR84 in STC-1, enhanced glucose tolerance through GPR84-mediated GLP-1 secretion, and showed resistance to high-fat diet (HFD)-induced obesity in mice.

Conclusions

Dietary MCT (C10:0) intake efficiently may protect against obesity and improve insulin resistance via GLP-1 secretion.
Molecular Diagnostic of Ochratoxin A With Specific Aptamers in Corn and Groundnut via Fabrication of a Microfluidic Device
Authors: Shahdeo Deepshikha , Khan Azmat Ali , Alanazi Amer M. , Bajpai Vivek K. , Shukla Shruti , Gandhi Sonu
Published: March 2022

Ochratoxin A (OTA) is one of the predominant mycotoxins that contaminate a wide range of food commodities. In the present study, a 36-mer aptamer was used as a molecular recognition element coupled with gold nanoparticles (AuNPs) for colorimetric detection of OTA in a microfluidic paper-based analytical device (μPADs). The μPADs consisted of three zones: control, detection, and sample, interconnected by channels. UV-vis spectroscopy (UV-vis), Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM) were used for characterization of AuNPs and AuNPs/Aptamer. According to the colorimetric assay, limit of detection (LOD) was found to be 242, 545.45, and 95.69 ng/mL in water, corn, and groundnut, respectively. The HPLC detection method achieved acceptable coefficient in standard curves (r2 = 0.9995), improved detection range, and recovery rates in spiked corn and groundnut samples as 43.61 ± 2.18% to 87.10 ± 1.82% and 42.01 ± 1.31% to 86.03 ± 2.64% after multiple sample extractions and cleanup steps. However, the developed μPADs analytical device had the potent ability to rapidly detect OTA without any extraction pre-requirement, derivatization, and cleanup steps, thus illustrating its feasibility in the animal health sector, agricultural, and food industries.
Cardiac Toxicity From Adjuvant Targeting Treatment for Breast Cancer Post-Surgery
Authors: Fu Zhenkun , Lin Zhoujun , Yang Mao , Li Chenggang
Published: March 2022

Breast cancer is one of the most prevalent types of cancers worldwide, especially for females. Surgery is the preferred treatment for breast cancer, and various postoperative adjuvant therapies can be reasonably used according to different pathological characteristics, especially traditional radiotherapy, chemotherapy, and endocrine therapy. In recent years, targeting agent therapy has also become one of the selective breast cancer treatment strategies, including anti-HER-2 drugs, CDK4/6 inhibitor, poly ADP-ribose polymerase inhibitor, PI3K/AKT/mTOR pathway inhibitor, ER targeting drugs, and aromatase inhibitor. Because of the different pathologic mechanisms of these adjuvant therapies, each of the strategies may cause cardiotoxicity in clinic. The cardiac adverse events of traditional endocrine therapy, radiotherapy, and chemotherapy for breast cancer have been widely detected in clinic; however, the targeting therapy agents have been paid more attention with the extension of application. This review will summarize the cardiac toxicity of various adjuvant therapies for breast cancer, especially for targeting drug therapy.
Transient Receptor Potential Cation Channel Subfamily V Member 1 Expression Promotes Chemoresistance in Non-Small-Cell Lung Cancer
Authors: Li Li , Chen Cheng , Xiang Qin , Fan Songqing , Xiao Tian , Chen Yangchao , Zheng Duo
Published: March 2022

Approximately 85% of lung cancer cases are non-small-cell lung cancer (NSCLC). Chemoresistance is a leading cause of chemotherapy failure in NSCLC treatment. Transient receptor potential cation channel subfamily V, member 1 (TRPV1), a non-selective cation channel, plays multiple roles in tumorigenesis and tumor development, including tumor cell proliferation, death, and metastasis as well as the response to therapy. In this study, we found TRPV1 expression was increased in NSCLC. TRPV1 overexpression induced cisplatin (DDP) and fluorouracil (5-FU) resistance in A549 cells independent of its channel function. TRPV1 expression was upregulated in A549-DDP/5-FU resistant cells, and DDP/5-FU sensitivity was restored by TRPV1 knockdown. TRPV1 overexpression mediated DDP and 5-FU resistance by upregulation of ABCA5 drug transporter gene expression, thereby increasing drug efflux, enhancing homologous recombination (HR) DNA repair pathway to alleviate apoptosis and activating IL-8 signaling to promote cell survival. These findings demonstrate an essential role of TRPV1 in chemoresistance in NSCLC and implicate TRPV1 as a potential chemotherapeutic target.
Neoadjuvant Chemoradiotherapy for Oral Cavity Cancer: Predictive Factors for Response and Interim Analysis of the Prospective INVERT-Trial
Authors: von der Grün Jens , Winkelmann Ria , Burck Iris , Martin Daniel , Rödel Franz , Wild Peter Johannes , Bankov Katrin , Weigert Andreas , Kur Ivan-Maximiliano , Brandts Christian , Filmann Natalie , Issing Christian , Thönissen Philipp , Tanneberger Anna Maria , Rödel Claus , Ghanaati Shahram , Balermpas Panagiotis
Published: March 2022

Background

To study neoadjuvant chemoradiotherapy (nCRT) and potential predictive factors for response in locally advanced oral cavity cancer (LA-OCC).

Methods

The INVERT trial is an ongoing single-center, prospective phase 2, proof-of-principle trial. Operable patients with stage III-IVA squamous cell carcinomas of the oral cavity were eligible and received nCRT consisting of 60 Gy with concomitant cisplatin and 5-fluorouracil. Surgery was scheduled 6-8 weeks after completion of nCRT. Explorative, multiplex immunohistochemistry (IHC) was performed on pretreatment tumor specimen, and diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted prior to, during nCRT (day 15), and before surgery to identify potential predictive biomarkers and imaging features. Primary endpoint was the pathological complete response (pCR) rate.

Results

Seventeen patients with stage IVA OCC were included in this interim analysis. All patients completed nCRT. One patient died from pneumonia 10 weeks after nCRT before surgery. Complete tumor resection (R0) was achieved in 16/17 patients, of whom 7 (41%, 95% CI: 18-67%) showed pCR. According to the Clavien-Dindo classification, grade 3a and 3b complications were found in 4 (25%) and 5 (31%) patients, respectively; grade 4-5 complications did not occur. Increased changes in the apparent diffusion coefficient signal intensities between MRI at day 15 of nCRT and before surgery were associated with better response (p=0.022). Higher abundances of programmed cell death protein 1 (PD1) positive cytotoxic T-cells (p=0.012), PD1+ macrophages (p=0.046), and cancer-associated fibroblasts (CAFs, p=0.036) were associated with incomplete response to nCRT.

Conclusion

nCRT for LA-OCC followed by radical surgery is feasible and shows high response rates. Larger patient cohorts from randomized trials are needed to further investigate nCRT and predictive biomarkers such as changes in DW-MRI signal intensities, tumor infiltrating immune cells, and CAFs.