Energy efficient and sustainable design of a multi-story building based on embodied energy and cost.

Sustainable multi-story building designs are gaining increasing attention in light of the green development of the building industry. Recently, many studies have been conducted to determine the optimized embodied energy considering size of structural members and materials strength using a single objective function. In this context, the current study adopted a multi-objective function based on cost and Embodied Energy (EE) for the sustainable design of the entire multi-story building. A BuildingEnergy computer program is used to assess the energy consumption performance of a multi-story reinforcement cement concrete building. Based on the proposed method, an analysis is carried out to compare the optimal solutions for multi-story building. Furthermore, a detailed parametric study was conducted to explore the main factors for energy-efficient column and beam design. The results revealed that with a comparison of the most "carbon-friendly" and "cost-friendly" solutions, an added cost of 6-7% can contribute up to a 13% emission reduction. The sectional dimensions, steel rebar, concrete strengths, cost ratio, building height, and eccentricity remarkably influence sustainable design, cost optimization, and minimum carbon emission. Overall, this study could help to define cost-effective and energy-efficient structural members. Eventually, the EE is confirmed to be a feasible parameter for designing more sustainable multi-story RCC buildings.

A comparative analysis of RCC and composite buildings using the new plastic deformation (PD) method.

Low computational efficiency and non-linearity behaviour make the simulation of the overall building structure problematic to attain with a single dynamic or static method. Thus, this paper uses a plastic deformation (PD) method based on concrete plasticity theory (CPT) for comparative analysis of multi-storey reinforcement cement concrete (RCC) and composite buildings under common and rare earthquake loads. For this purpose, a 15-storey tall building was selected for analysis using ABAQUS software. At first, a possible building model was created and then plastic deformation analysis was performed using the new PD method under both common and rare earthquakes. After that, a nonlinear time history analysis was conducted, and the results of plastic strain distribution, lateral displacement, peak acceleration, storey stiffness, shear force, storey drift, normalised shear, and top deflection of the RCC and composite buildings were studied deeply. The fundamental time period of the RCC model was found to be 5.2 s while the fundamental time period of the composite model was 6 s. Under common and rare earthquake leads, the peak acceleration of the RCC building was 19% and 22% higher than composite buildings, respectively. Under common and rare seismic loads, the top deflections of the composite building were 33% and 36% higher than those of RCC buildings, respectively. In the case of the RCC building, it was found in this study that higher peak acceleration (PA) of the ground motion led to higher storey top displacement, storey drift, shear force and top deflection under both ground motions. Numerical results suggested that the use of composite structure is more durable than RCC structure. It was also concluded that the PD method could also be effectively used for the analysis of RCC and composite buildings under dynamic loads.

Cell density impacts the susceptibility to ferroptosis by modulating IRP1-mediated iron homeostasis.

Ferroptosis has been implicated in several neurological disorders and may be therapeutically targeted. However, the susceptibility to ferroptosis varies in different cells, and inconsistent results have been reported even using the same cell line. Understanding the effects of key variables of in vitro studies on ferroptosis susceptibility is of critical importance to facilitate drug discoveries targeting ferroptosis. Here, we showed that increased cell seeding density leads to enhanced resistance to ferroptosis by reducing intracellular iron levels. We further identified iron-responsive protein 1 (IRP1) as the key protein affected by cell density, which affects the expression of ferroportin or transferrin receptor and results in altered iron levels. Such observations were consistent across different cell lines, indicating that cell density should be tightly controlled in studies of ferroptosis. Since cell densities vary in different brain regions, these results may also shed light on selective regional vulnerability observed in neurological disorders.

DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion.

Traumatic brain injury (TBI) leads to progressive neurodegeneration that may be caused by chronic traumatic encephalopathy (CTE). However, the precise mechanism remains unclear. Herein, the study identifies a crucial protein, axonemal dynein light intermediate polypeptide 1 (DNALI1), and elucidated its potential pathogenic role in post-TBI neurodegeneration. The DNALI1 gene is systematically screened through analyses of Aging, Dementia, and TBI studies, confirming its elevated expression both in vitro and in vivo. Moreover, it is observed that altered DNALI1 expression under normal conditions has no discernible effect. However, upon overexpression, DNALI1 inhibits autophagosome-lysosome fusion, reduces autophagic flux, and exacerbates cell death under pathological conditions. DNALI1 silencing significantly enhances autophagic flux and alleviates neurodegeneration in a CTE model. These findings highlight DNALI1 as a potential key target for preventing TBI-related neurodegeneration.

Correlation of glymphatic system abnormalities with Parkinson's disease progression: a clinical study based on non-invasive fMRI.

BACKGROUND: The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). METHODS: Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. RESULTS: The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. CONCLUSION: The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.

Comparative study on gene expression in psoriatic lesions versus chronic wound healing processes.

Psoriasis and chronic ulcers not only significantly impair quality of life but also pose a challenge in dermatological treatment. This study aimed to identify new therapeutic targets and biomarkers for psoriasis and chronic ulcers by comparing their gene expression profiles. The gene expression profiles of psoriatic, wound and chronic ulcer patients, as well as healthy controls, were determined via RNA extraction and next-generation sequencing of biopsies. In order to identify biomarkers, functional enrichment, differential expression analysis and machine learning algorithms were implemented. It is worth mentioning that the genes IL17A, TNF, KRT16, MMP9, and CD44 exhibited substantial correlations with the pathogenesis of the conditions being studied. As evidenced by their AUC-ROC values approaching 0.90, machine learning models accurately identified these biomarkers. The differential gene expression was consequently validated via qRT-PCR, which highlighted the increased expression of matrix remodelling enzymes and inflammatory cytokines. Additionally, genes essential for maintaining epidermis integrity and facilitating wound healing exhibited downregulation. These insights into the molecular mechanisms of psoriasis and chronic ulcers pave the way for the development of targeted therapies, offering hope for improved treatment strategies.

Leucine-rich repeat kinase 2 (LRRK2) inhibition upregulates microtubule-associated protein 1B to ameliorate lysosomal dysfunction and parkinsonism.

Mutations in LRRK2 (encoding leucine-rich repeat kinase 2 protein, LRRK2) are the most common genetic risk factors for Parkinson's disease (PD), and increased LRRK2 kinase activity was observed in sporadic PD. Therefore, inhibition of LRRK2 has been tested as a disease-modifying therapeutic strategy using the LRRK2 mutant mice and sporadic PD. Here, we report a newly designed molecule, FL090, as a LRRK2 kinase inhibitor, verified in cell culture and animal models of PD. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice and SNCA A53T transgenic mice, FL090 ameliorated motor dysfunctions, reduced LRRK2 kinase activity, and rescued loss in the dopaminergic neurons in the substantia nigra. Notably, by RNA-Seq analysis, we identified microtubule-associated protein 1 (MAP1B) as a crucial mediator of FL090's neuroprotective effects and found that MAP1B and LRRK2 co-localize. Overexpression of MAP1B rescued 1-methyl-4-phenylpyridinium induced cytotoxicity through rescuing the lysosomal function, and the protective effect of FL090 was lost in MAP1B knockout cells. Further studies may be focused on the in vivo mechanisms of MAP1B and microtubule function in PD. Collectively, these findings highlight the potential of FL090 as a therapeutic agent for sporadic PD and familial PD without LRRK2 mutations.

Hetong decoction relieves loperamide-induced constipation in rats by regulating expression of aquaporins.

OBJECTIVE: To investigate whether Hetong decoction (, HTT) alleviates constipation via regulating AQPs expression. METHODS: Constipation in rats was induced by loperamide, and rats were randomly assigned into model (saline), HHT-low (95 g/kg), HTT-medium (190 g/kg), HTT-high (380 g/kg) and positive control (mosapride) groups. Then the defecation function, the concentration of serum arginine vasopressin (AVP) and cyclic adenosine monophosphate (cAMP), and the expression of AQP3 and AQP8 in colon tissues were assessed. NCM460 colon cells with AQP3 and AQP8 knockdown or overexpression were exposed to serum from rats that received low or high dose of HTT, followed by detection of AQP3 and AQP8 expression. RESULTS: The model group showed lower fecal weight and water content, weaker intestinal transit, higher serum concentration of AVP and cAMP, increased proximal and distal AQP8 expression, increased proximal but decreased distal AQP3 expression. However, these trends were reversed in both the HTT group (low, medium and high dose) and the positive control group. In NCM460 cells, HTT dose-dependently stabilized AQP3 and AQP8 expression under AQP3/8 plasmid interference or overexpression. CONCLUSIONS: HTT relieves constipation in rats through regulating AQP3 and AQP8 expression.

Corrigendum: Probiotics for the treatment of docetaxel-related weight gain of breast cancer patients-A single-center, randomized, double-blind, and placebo-controlled trial.

[This corrects the article DOI: 10.3389/fnut.2021.762929.].

Tau suppresses microtubule-regulated pancreatic insulin secretion.

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.

Diagnostic Value of CT Delayed Phase Images Added to Gd-EOB-DTPA MRI for HCC Diagnosis in LR-3/4 Lesions.

Objective: To explore the potential value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC) in LR-3/4 lesions by adding computed tomography (CT) delayed images based on the Liver Imaging Reporting And Data System (LI-RADS). Methods: The differences in clinical and imaging characteristics between hepatocellular carcinoma and non-HCC were compared, and logistic regression was used to analyze the imaging risk factors for the diagnosis of HCC. Based on the main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, the HCC diagnostic model 1 was established, and the diagnostic efficacy was analyzed. Based on model 1, delayed phase CT images were added to establish model 2 to find reliable predictors of HCC diagnosis. Receiver operating characteristic (ROC) analysis and the DeLong test were used to compare the two models. Results: There was a significant difference in serum AFP between HCC and non-HCC (P = 0.008). Based on main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, enhancing capsule (OR = 0.197, 95% CI = 0.06-0.595, P = 0.005) and washout (OR = 10.345, 95% CI = 3.460-30.930, P < 0.001) were independent risk factors in Model 1. After adding CT delayed-phase images to build model 2, enhancing capsule (OR = 0.132, 95% CI = 0.139-0.449, P = 0.001), MRI and (or) CT washout (OR = 0.052, 95% CI = 0.016-0.172, P < 0.001) were reliable predictors for HCC diagnosis. The AUC of model 1 was 0.808, sensitivity was 63.46%, and specificity was 85.00%. The AUC of model 2 was 0.854, the sensitivity was 71.20%, and the specificity was 85.00%. DeLong test (P = 0.040) demonstrated the diagnostic efficacy of model 2 significantly superior than model 1. Conclusion: Tumor washout and enhanced capsule are reliable factors for the diagnosis of HCC. Gd-EOB-DTPA MRI with delayed phase CT images can improve the sensitivity and diagnostic efficiency of HCC in LR-3/4 lesions on the premise of maintaining high specificity. Future studies are required to reinforce our finding.

Iron, ferroptosis, and ischemic stroke.

Over 30 million people suffer from the consequences of ischemic stroke. The precise molecular mechanism of neuronal damage during ischemic stroke remains unclear; therefore, the effective treatment of post-ischemic stroke remains a critical challenge. Recently, iron has emerged as a crucial factor in post-reperfusion injuries, participating in cell peroxidation, excitotoxicity, and a distinctive cell death pathway, namely, ferroptosis. Since iron is tightly regulated in the brain and important for brain functions, the imbalance of its metabolism, including its overload and deficiency, has been shown to impact ischemic stroke outcomes. This review summarizes the current understanding of pathological events associated with iron in ischemic stroke and discusses relevant drug development.

Parkin regulates neuronal lipid homeostasis through SREBP2-lipoprotein lipase pathway-implications for Parkinson's disease.

Abnormal lipid homeostasis has been observed in the brain of Parkinson's disease (PD) patients and experimental models, although the mechanism underlying this phenomenon is unclear. Notably, previous studies have reported that the PD-linked protein Parkin functionally interacts with important lipid regulators, including Sterol Regulatory Element-Binding Proteins (SREBPs) and cluster of differentiation 36 (CD36). Here, we demonstrate a functional relationship between Parkin and lipoprotein lipase (LPL), a triglyceride lipase that is widely expressed in the brain. Using a human neuroblastoma cell line and a Parkin knockout mouse model, we demonstrate that Parkin expression level positively correlates with neuronal LPL protein level and activity. Importantly, our study identified SREBP2, a major regulator of sterol and fatty acid synthesis, as a potential mediator between Parkin and LPL. Supporting this, SREBP2 genetic ablation abolished Parkin effect on LPL expression. We further demonstrate that Parkin-LPL pathway regulates the formation of intracellular lipid droplets, and that this pathway is upregulated upon exposure to PD-linked oxidative stress induced by rotenone. Finally, we show that inhibition of either LPL or SREBP2 exacerbates rotenone-induced cell death. Taken together, our findings reveal a novel pathway linking Parkin, SREBP2 and LPL in neuronal lipid homeostasis that may be relevant to the pathogenesis of PD.

Anna Livia Plurabelle's normless interactions in Finnegans Wake.

The complex structure and characterization of James Joyce's Finnegans Wake present a normless environment for its female characters, specifically Anna Livia Plurabelle (ALP). This paper explores ALP's normlessness in her social interactions using Karen Horney's theory of neurosis as a methodological device to reveal ALP's detached personality. Horney considers normlessness a trend of "Moving Away from People," also known as a detached personality. According to Horney, "self-sufficiency," "perfection," and "narrow limits in life" are the three neurotic factors that produce a detached personality, all of which are apparent in ALP's personality. In this novel, ALP is portrayed as neurotic to demonstrate her dependence on men and how she coopts male power in favor of her needs.

Shugan Jieyu capsule improve sleep and emotional disorder in coronavirus disease 2019 convalescence patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of the Shugan Jieyu capsule on improving sleep and emotional disorder during Coronavirus disease 2019 (COVID-19) convalescence. METHODS: We conducted a randomized, double-blind, placebo-controlled trial, and recruit 200 COVID-19 convalescence patients and then divide the subjects into two groups respectively: the experimental group ( 100) and the control group ( 100). Patients in the control group were given doses as a placebo, while those in the experimental group were given Shugan Jieyu capsule. The investigators mainly observed the differences between the two groups before and after treatment in terms of the rate of reduction and the rate of efficiency in Hamilton Depression Scale (HAMD-17) total scores from baseline, and recorded the scores of Hamilton Anxiety Scale (HAMA), Patient Health Questionnaire-15 (PHQ-15), Insomnia Severity Index (ISI) and Treatment Emergent Symptom Scale at 2 week, the 4 week and the 6 week respectively after treatment, and compared the differences between the groups. And the occurrence of adverse events was recorded. RESULTS: After 6-week treatment, there were statistically significant differences in the rate of reduction as well as efficiency in HAMD-17 scores, HAMA Total Scores, PHQ-15 Score, ISI Score from baseline in the experimental group and control group (< 0.05). There were 4 adverse events in the experimental group and 1 in the control group. CONCLUSION: Shugan Jieyu capsule could significantly improve sleep and emotional disorder in patients during COVID-19 convalescence.

Effect of cognitive behavioral intervention on anxiety, depression, and quality of life in patients with epilepsy.

OBJECTIVE: This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on quality of life, anxiety, and depression in patients with epilepsy. METHODS: Each study subject was randomly assigned to a CBT (n=46) or control (n=49) group (1:1 ratio), and the first group underwent an 8-week CBT treatment. Anxiety, depression, and quality of life (QOLIE-31) were assessed at both baseline and endpoint using the Self-Rating Anxiety Scale (SAS), Hamilton Depression Scale (HDMA) and quality of life in Epilepsy-31 (QOLIE-31) scales. The statistical analyses included between-and within-group comparisons of the effects of CBT on these measures and associations with demographic and clinical variables. RESULTS: No differences were found between variables at baseline (P>0.05). The repeated-measures analyses found that CBT group had greater improvement in depression score compared to the control group (P<0.05). The analysis of anxiety score showed that compared to the control group, CBT intervention had no statistical significance in the total anxiety population. However, the CBT intervention decreased anxiety in women and Combined-drug group (P<0.05). The CBT group had greater improvement in overall score, medication effect, and seizure worry score than the control group (P<0.05). Stratified analysis found total and medication effects score of CBT intervention group for the combined-drug group were higher than those of the single drug group (P<0.05). CONCLUSION: Increases in overall scores, seizure worry, cognitive functioning, and medication effect were better in the CBT group. CBT can improve anxiety, depression, and quality of life in patients with epilepsy. Women and combined-drug patients with epilepsy benefit most from CBT.

Loss of CaV1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory.

L-type CaV1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate CaV1.3 RNA editing, we demonstrate that unedited CaV1.3ΔECS mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of CaV1.3 RNA editing sites slows Ca2+-dependent inactivation to increase Ca2+ influx but reduces channel open probability to decrease Ca2+ influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited CaV1.3 channels permitted larger Ca2+ influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the CaV1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the CaV1.3 channel in brain function.

Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis.

While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.

Immobilization of hexavalent chromium in soil-plant environment using calcium silicate hydrate synthesized from coal gangue.

The presence of excessive hexavalent chromium (Cr(VI)) in the contaminated soils and plants has become a global environmental issue due to its toxicity and carcinogenicity. This work investigated the feasibility of immobilizing Cr(VI) in the soil-plant environment using calcium silicate hydrate (C-S-H) synthesized from coal gangue. The results revealed that the C-S-H amendment increased soil pH and organic matter (OM), which further promoted Cr(VI) immobilization. Results also revealed that exchangeable and carbonate bound fractions of Cr were either converted into Fe/Mn oxide and OM bound fractions of Cr or hardly released residual fraction of Cr due to C-S-H treatment. The C-S-H accelerated conversion of Cr(VI) into Cr(III) promoting plant growth and alleviating the toxic effect of Cr(VI). Cr(VI) was mainly immobilized and accumulated in the plant roots which resulted in comparatively lower Cr(VI) content in the edible part of plants. The exchangeable fraction of Cr in soil could be used as a bioavailability evaluation index of Cr(VI) in plants. In short, C-S-H was proved to be a practical and environmentally friendly amendment for in-situ immobilization of Cr(VI) contaminated soil.

Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.

Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.