bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Method for Identifying Essential Proteins Based on Non-negative Matrix Tri-Factorization
Authors: Zhang Zhihong , Jiang Meiping , Wu Dongjie , Zhang Wang , Yan Wei , Qu Xilong
Published: August 2021

Identification of essential proteins is very important for understanding the basic requirements to sustain a living organism. In recent years, there has been an increasing interest in using computational methods to predict essential proteins based on protein–protein interaction (PPI) networks or fusing multiple biological information. However, it has been observed that existing PPI data have false-negative and false-positive data. The fusion of multiple biological information can reduce the influence of false data in PPI, but inevitably more noise data will be produced at the same time. In this article, we proposed a novel non-negative matrix tri-factorization (NMTF)-based model (NTMEP) to predict essential proteins. Firstly, a weighted PPI network is established only using the topology features of the network, so as to avoid more noise. To reduce the influence of false data (existing in PPI network) on performance of identify essential proteins, the NMTF technique, as a widely used recommendation algorithm, is performed to reconstruct a most optimized PPI network with more potential protein–protein interactions. Then, we use the PageRank algorithm to compute the final ranking score of each protein, in which subcellular localization and homologous information of proteins were used to calculate the initial scores. In addition, extensive experiments are performed on the publicly available datasets and the results indicate that our NTMEP model has better performance in predicting essential proteins against the start-of-the-art method. In this investigation, we demonstrated that the introduction of non-negative matrix tri-factorization technology can effectively improve the condition of the protein–protein interaction network, so as to reduce the negative impact of noise on the prediction. At the same time, this finding provides a more novel angle of view for other applications based on protein–protein interaction networks.
Mitochondrial Reactive Oxygen Species Are Essential for the Development of Psoriatic Inflammation
Authors: Mizuguchi Soichi , Gotoh Kazuhito , Nakashima Yuya , Setoyama Daiki , Takata Yurie , Ohga Shouichi , Kang Dongchon
Published: August 2021

Psoriasis is a common immune-mediated, chronic, inflammatory skin disease that affects approximately 2–3% of the population worldwide. Although there is increasing evidence regarding the essential roles of the interleukin (IL)-23/IL-17 axis and dendritic cell (DC)-T cell crosstalk in the development of skin inflammation, the contributions of mitochondrial function to psoriasis are unclear. In a mouse model of imiquimod (IMQ)-induced psoriasiform skin inflammation, we found that hematopoietic cell-specific genetic deletion of p32/C1qbp, a regulator of mitochondrial protein synthesis and metabolism, protects mice from IMQ-induced psoriatic inflammation. Additionally, we demonstrate that p32/C1qbp is an important regulator of IMQ-induced DC activation, both in vivo and in vitro. We also found that p32/C1qbp-deficient DCs exhibited impaired production of IL-1β, IL-23, and mitochondrial reactive oxygen species (mtROS) after IMQ stimulation. Because the inhibition of mtROS suppressed IMQ-induced DC activation and psoriatic inflammation, we presume that p32/C1qbp and mtROS can serve as therapeutic targets in psoriasis.
An Experimental Study on Strength Characteristics and Hydration Mechanism of Cemented Ultra-Fine Tailings Backfill
Authors: Deqing Gan , Hongbao Li , Chao Chen , Hongjian Lu , Youzhi Zhang
Published: August 2021

In order to study the strength characteristics and hydration mechanism of the cemented ultra-fine tailings backfill (CUTB), the uniaxial compressive strength (UCS) tests of CUTB and cemented classified tailings backfill (CCTB) with cement-tailing ratio (C/T ratio) of 1:4 and 1:6 and curing ages of 3, 7, 14 and 28 days were carried out. The hydration products and morphology of the cemented paste backfill (CPB) were analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM). The results show that the UCS of the CUTB is significant compared to the CCTB under the same conditions; the greater the C/T ratio and curing age, the greater the UCS difference value. The UCS growth curve of the CUTB is approximately S-shaped, and there is a relationship between the UCS and curing age. The ultra-fine tailings particles in the CUTB have potential activity; in the alkaline environment–generated cement hydration, active SiO2 and Al2O3 particles undergo secondary hydration reaction, resulting in no or very little Ca (OH)2 crystals generated in the CUTB, and the hydration products and morphology are also different.
Spectrum of Microorganisms, Antibiotic Resistance Pattern, and Treatment Outcomes Among Patients With Empyema Thoracis: A Descriptive Cross-Sectional Study From the Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan
Authors: Atif Muhammad , Naseem Mehwish , Sarwar Sajjad , Mukhtar Saba , Malik Iram , Hassan Muhammad Rauf ul , Iqbal Muhammad Nouman , Ahmad Nafees
Published: August 2021

Background: This study involves the analysis of spectrum of microorganisms, antibiotic resistance pattern, and treatment outcomes among empyema thoracis patients. This study also analyzes the factors associated with unsuccessful treatment outcome and duration of hospital stay among the patients.

Methods: This was a descriptive, cross-sectional study carried out in the Pulmonology Ward of the Bahawal Victoria hospital, Bahawalpur, Pakistan. All patients with empyema thoracis registered at the study site during the period of 1 year were included in the study. Multivariate regression analysis was used to analyze the factors associated with duration of hospital stay and unsuccessful treatment outcome among the patients.

Results: A total 110 patients were included in the study. Most of the patients (n = 73, 66.4%) were treated with piperacillin/tazobactam alone and in combination with either one or more than one antibiotics as an empiric therapy. Culture was positive in 58 (52.7%) patients and the most commonly identified organisms included, gram-negative Pseudomonas aeruginosa (n = 20; 18.8%) and Klebsiella sp. (n = 11, 10%) followed by same proportion of E. coli. The most commonly identified bacterial isolates showed high level of resistance against antibiotics used as an empiric therapy, while these showed low level of resistance against amoxicillin, clarithromycin, ertapenem, colistin, tigecycline, fosfomycin, rifampicin, and vancomycin. In this study, 82 (74.5%) patients successfully completed the treatment, while 12 (11%) showed no clinical improvement, 5 (4.5%) lost to follow up and 11 (10%) died. In multivariate binary logistic regression analysis, none of the patient attributes were significantly associated with unsuccessful treatment outcome, while in multivariate linear regression analysis, the factors which were significantly associated with duration of hospital stay included; duration of symptoms <2 weeks prior to admission (p = 0.008, beta = −0.247) and resistance to five antibiotic classes (p = 0.02, beta = 0.280).

Conclusion: Close to 25% of the patients did not complete the treatment successfully. Most of the common bacterial isolates showed high level of resistance against the broad-spectrum antibiotics used as an empiric therapy. This is alarming. However, better sensitivity of common bacterial isolates against standardized first line treatment for empyema thoracis is promising.
Nailfold Capillaroscopy With USB Digital Microscopy in Connective Tissue Diseases: A Comparative Study of 245 Patients and Healthy Controls
Authors: Chanprapaph Kumutnart , Fakprapai Wuttidej , Limtong Preeyachat , Suchonwanit Poonkiat
Published: August 2021

Background: Nailfold capillaroscopy (NFC) is a valuable tool to detect microcirculation abnormalities in connective tissue diseases (CTDs). However, whether the universal serial bus (USB) digital microscopy used as onychoscopy is as effective as the videocapillaroscopy in determining the diagnostic and prognostic values of CTDs remains to be determined.

Objective: This study aims to investigate NFC features of systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc) patients and compare with normal controls as well as examine which feature could differentiate among CTDs. Furthermore, we aim to explore different capillaroscopic abnormalities and their association with disease activity.

Methods: Nailfold images were taken from patients and healthy controls using a USB digital microscopy. Patterns on the capillary morphology, diameter, architecture, and density were recorded and compared. We further determined the NFC findings in SLE, DM, and SSc and corresponded to their respective disease activity scoring system.

Results: A total of 245 participants, consisting of 54 SLE, 32 DM, and 51 SSc patients, as well as 108 controls, were enrolled. All capillaroscopic features, except for tortuous capillaries, were significantly more common in CTDs than healthy control (all p < 0.05). A multinomial logistic regression analysis revealed that bushy capillaries had significantly higher odds for both SLE and DM than SSc (OR: 4.10, 95% confidence interval (CI): 1.71–9.81, p = 0.002 and OR: 7.82, 95% CI, 2.86–21.38, p < 0.001, respectively). Elongated capillaries demonstrated significant odds for SLE compared with SSc (OR: 3.35, 95% CI: 1.005–11.20, p = 0.049), while prominent subpapillary plexus showed greater odds for SLE compared with both DM and SSc (OR: 2.75, 95% CI: 1.07–7.02, p = 0.03 and OR: 5.78, 95% CI: 2.29–14.58, p < 0.001, respectively). The presence of hemorrhage, enlarged capillaries, and the low-density index had significantly higher odds in favor of SSc than SLE. Bushy capillaries were the only pattern with a strong association for DM over SSc. The presence of enlarged capillaries indicated higher SLE severity, but no specific finding was related to DM or SSc skin scores.

Conclusions: Nailfold capillaroscopic examination using a digital microscope is a valuable method for the diagnosis of SLE, DM, and SSc. Several morphologic patterns can help differentiate among CTDs; however, the prognostic significance of this method requires further investigations.
Case Report: Acute Onset Fear of Falling and Treatment With “Cognitive Physical Therapy”
Authors: Castro Patricia , Vadera Shree , Bancroft Matthew James , Buttell Joseph , Kaski Diego
Published: August 2021

Fear of falling (FoF) is prevalent in older adults, especially those with previous falls, and typically starts insidiously. We present a 78-year-old woman with an abrupt onset FoF and no history of falls, balance problems, vertigo, oscillopsia, psychiatric or psychological issues to account for this. These cognitive changes led to a behavioural alteration of her gait that became slow and wide-based, with her gaze fixed on the floor. She began a tailored program of “Cognitive Physical Therapy (CPT)” combining cognitive behavioural therapy (CBT) and physical rehabilitation. 1 month later her 6 m walk time and steps were reduced by a 25 and 35%, respectively, and the stride length increased by 34%, with further improvement 2 months later. We postulate that the abrupt onset of symptoms triggered a central shift toward postural hypervigilance and anxiety, suppression of anticipatory (feed forward) postural adjustments (APA) leading to FoF. CPT improved objective gait parameters related to FoF and reduced postural anxiety suggesting that early diagnosis and prompt treatment may avoid chronic symptoms and social isolation.
Optical Mapping of Brain Activity Underlying Directionality and Its Modulation by Expertise in Mandarin/English Interpreting
Authors: He Yan , Hu Yinying , Yang Yaxi , Li Defeng , Hu Yi
Published: August 2021

Recent neuroimaging research has suggested that unequal cognitive efforts exist between interpreting from language 1 (L1) to language 2 (L2) compared with interpreting from L2 to L1. However, the neural substrates that underlie this directionality effect are not yet well understood. Whether directionality is modulated by interpreting expertise also remains unknown. In this study, we recruited two groups of Mandarin (L1)/English (L2) bilingual speakers with varying levels of interpreting expertise and asked them to perform interpreting and reading tasks. Functional near-infrared spectroscopy (fNIRS) was used to collect cortical brain data for participants during each task, using 68 channels that covered the prefrontal cortex and the bilateral perisylvian regions. The interpreting-related neuroimaging data was normalized by using both L1 and L2 reading tasks, to control the function of reading and vocalization respectively. Our findings revealed the directionality effect in both groups, with forward interpreting (from L1 to L2) produced more pronounced brain activity, when normalized for reading. We also found that directionality was modulated by interpreting expertise in both normalizations. For the group with relatively high expertise, the activated brain regions included the right Broca’s area and the left premotor and supplementary motor cortex; whereas for the group with relatively low expertise, the activated brain areas covered the superior temporal gyrus, the dorsolateral prefrontal cortex (DLPFC), the Broca’s area, and visual area 3 in the right hemisphere. These findings indicated that interpreting expertise modulated brain activation, possibly because of more developed cognitive skills associated with executive functions in experienced interpreters.
The Impact of Motor Imageries on Aesthetic Judgment of Chinese Calligraphy: An fMRI Study
Authors: He Mingcheng , Zhang Wei , Shahid Hira , Liu Yushan , Liang Xiaoling , Duan Yan , Wang Hua , He Xianyou
Published: August 2021

Previous behavioral studies on aesthetics demonstrated that there was a close association between perceived action and aesthetic appreciation. However, few studies explored whether motor imagery would influence aesthetic experience and its neural substrates. In the current study, Chinese calligraphy was used as the stimuli to explore the relationship between the motor imagery and the aesthetic judgments of a participant using functional magnetic resonance imaging. The imaging results showed that, compared with the baseline, the activation of the brain regions [e.g., anterior cingulate cortex (ACC), putamen, and insula] involved in perceptual processing, cognitive judgments, aesthetic emotional, and reward processing was observed after the participants performed motor imagery tasks. The contrast analyses within aesthetic judgments showed that the kinesthetic imagery significantly activated the middle frontal gyrus, postcentral gyrus, ACC, and thalamus. Generally, these areas were considered to be closely related to positive aesthetic experience and suggested that motor imagery, especially kinesthetic imagery, might be specifically associated with the aesthetic appreciation of Chinese calligraphy.
Inhibitory and Agonistic Autoantibodies Directed Against the β2-Adrenergic Receptor in Pseudoexfoliation Syndrome and Glaucoma
Authors: Hohberger Bettina , Schlötzer-Schrehard Ursula , Mardin Christian , Lämmer Robert , Munoz Luis , Kunze Rudolf , Herrmann Martin , Wallukat Gerd
Published: August 2021

Pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG) are assumed to be caused by a generalized elastosis leading to the accumulation of PEX material in ocular as well as in extraocular tissues. The exact pathophysiology of PEXS is still elusive. PEXG, the most common type of secondary open-angle glaucoma (OAG), is characterized by large peaks of intraocular pressure (IOP) with a progressive loss of the visual field. Agonistic autoantibodies (agAAbs) against the β2-adrenergic receptor (AR) have been shown to be present in sera of patients with primary and secondary OAG and ocular hypertension and are seemingly linked to IOP. In the present study, we investigated the autoantibodies directed against the β2-AR in sera of patients with PEXS and PEXG. We recruited 15, 10, and 15 patients with PEXG, PEXS, and primary OAG, respectively. Ten healthy individuals served as controls. All patients underwent standard ophthalmological examination with Octopus G1 perimetry. agAAbs prepared from serum samples were analyzed in a rat cardiomyocyte–based bioassay for the presence of agAAbs. We identified the interacting loop of the β2-AR and the immunoglobulin G (IgG) subclasses using synthetic peptides corresponding to the extracellular loops of the receptors and enzyme-linked immunosorbent assay, respectively. None of the controls were β2-agAAb–positive (0.2 ± 0.5 U). No β2-agAAbs (0.2 ± 0.4 U), but inhibitory β2-AAbs were observed in 80% of the patients that partially blocked the drug-induced β2-adrenergic stimulation; 5.8 ± 1.7 U vs. 11.1 ± 0.9 U for clenbuterol in the absence and the presence of sera from patients with PEXS, respectively. Epitope analyses identified the third extracellular loop of the β2-AR as the target of the inhibitory β2-AAbs, being of IgG3 subtype in PEXS patients. In contrast, patients with PEXG showed β2-agAAbs (5.6 ± 0.9 U), but no inhibitory ones. The β2-agAAbs levels of patients with PEXG and primary OAG patients (3.9 ± 2.8 U; p > 0.05) were at a similar level. In two cases of PEXG, the β2-agAAbs exert synergistic effects with clenbuterol. The activity increased from 11.5 ± 0.3 (clenbuterol only) to 16.3 ± 0.9 U. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma, agonistic and inhibitory β2-AAbs seem to be a part of this multifactorial interplay.
Emerging Artificial Neuron Devices for Probabilistic Computing
Authors: Li Zong-xiao , Geng Xiao-ying , Wang Jingrui , Zhuge Fei
Published: August 2021

In recent decades, artificial intelligence has been successively employed in the fields of finance, commerce, and other industries. However, imitating high-level brain functions, such as imagination and inference, pose several challenges as they are relevant to a particular type of noise in a biological neuron network. Probabilistic computing algorithms based on restricted Boltzmann machine and Bayesian inference that use silicon electronics have progressed significantly in terms of mimicking probabilistic inference. However, the quasi-random noise generated from additional circuits or algorithms presents a major challenge for silicon electronics to realize the true stochasticity of biological neuron systems. Artificial neurons based on emerging devices, such as memristors and ferroelectric field-effect transistors with inherent stochasticity can produce uncertain non-linear output spikes, which may be the key to make machine learning closer to the human brain. In this article, we present a comprehensive review of the recent advances in the emerging stochastic artificial neurons (SANs) in terms of probabilistic computing. We briefly introduce the biological neurons, neuron models, and silicon neurons before presenting the detailed working mechanisms of various SANs. Finally, the merits and demerits of silicon-based and emerging neurons are discussed, and the outlook for SANs is presented.
Robust Prognostic Subtyping of Muscle-Invasive Bladder Cancer Revealed by Deep Learning-Based Multi-Omics Data Integration
Authors: Zhang Xiaolong , Wang Jiayin , Lu Jiabin , Su Lili , Wang Changxi , Huang Yuhua , Zhang Xuanping , Zhu Xiaoyan
Published: August 2021

Muscle-invasive bladder cancer (MIBC) is the most common urinary system carcinoma associated with poor outcomes. It is necessary to develop a robust classification system for prognostic prediction of MIBC. Recently, increasing omics data at different levels of MIBC were produced, but few integration methods were used to classify MIBC that reflects the patient’s prognosis. In this study, we constructed an autoencoder based deep learning framework to integrate multi-omics data of MIBC and clustered samples into two different subgroups with significant overall survival difference (P= 8.11 × 10-5). As an independent prognostic factor relative to clinical information, these two subtypes have some significant genomic differences. Remarkably, the subtype of poor prognosis had significant higher frequency of chromosome 3p deletion. Immune decomposition analysis results showed that these two MIBC subtypes had different immune components including macrophages M1, resting NK cells, regulatory T cells, plasma cells, and naïve B cells. Hallmark gene set enrichment analysis was performed to investigate the functional character difference between these two MIBC subtypes, which revealed that activated IL-6/JAK/STAT3 signaling, interferon-alpha response, reactive oxygen species pathway, and unfolded protein response were significantly enriched in upregulated genes of high-risk subtype. We constructed MIBC subtyping models based on multi-omics data and single omics data, respectively, and internal and external validation datasets showed the robustness of the prediction model as well as its ability of prognosis (P< 0.05 in all datasets). Finally, through bioinformatics analysis and immunohistochemistry experiments, we found that KRT7 can be used as a biomarker reflecting MIBC risk.
Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020
Authors: Hou Zan , Xie Jiaqing , Zhang Li , Dai Gangyi , Chen Yuanhang , He Lang
Published: August 2021

Objectives

We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.

Methods

We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.

Results

A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25).

Conclusions

HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.
Activation of FcRn Mediates a Primary Resistance Response to Sorafenib in Hepatocellular Carcinoma by Single-Cell RNA Sequencing
Authors: Guan Xin , Wu Yi , Zhang Shuqin , Liu Zhiyi , Fan Qingjie , Fang Shuai , Qiao Sennan , Sun Fei , Liang Chongyang
Published: August 2021

Sorafenib is the first-line therapeutic option for advanced hepatocellular carcinoma (HCC). Many patients exhibit a primary resistance (PR) response after initial treatment. In previous studies, compared to acquired resistance, the mechanism of PR is unclear. The present study aimed to evaluate the response of patient samples to sorafenib by patient-derived xenograft (PDX) models, and the differences at the transcriptome level between the sorafenib PR group and the sorafenib sensitive group were analyzed by single-cell sequencing technology. A specific cell cluster may be differentiated by the liver bud hepatic cells, and the JUN transcription factors in this cell cluster were highly activated. The albumin is secreted by other cell clusters, and the cluster stimulates the FcRn complex receptor to activate the HIF pathway and cell proliferation, resulting in a poor response to sorafenib. These findings are validated by both cell communication analysis and experiments. Thus, the current studies provided a novel approach for the treatment of sorafenib-resistant HCC.
Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression
Authors: Yang Junfa , Wu Maomao , Fang Hui , Su Yue , Zhang Lingling , Zhou Huan
Published: August 2021

Puerarin, an isoflavone component extracted from herb radix puerariae, is widely used in China in the treatment of immune diseases and inflammation. Previous studies have demonstrated that puerarin prevented acute lung injury by regulating inflammatory responses. However, the effect of puerarin on acute liver injury (ALI) was unclear. The purpose of this study was to explore the beneficial effects of puerarin when applied to ALI. We found that puerarin inhibited liver injury and inflammatory cell infiltration in lipopolysaccharide (LPS)/D-galactose (D-Gal)-induced acute liver failure and the liver pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in liver tissues with ALI and LPS-induced L-02 cells but upregulated the expression level of zinc finger E-box-binding homeobox 2 (ZEB2). Significantly, the results of this study showed that the inhibition of liver pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) production in LPS-induced L-02 cells was caused by ZEB2 overexpression. However, knocking down ZEB2 promoted LPS-mediated secretion of liver pro-inflammatory cytokines in L-02 cells. Additional experiments showed that puerarin inhibited the activation of the NF-κB signaling pathway by elevating ZEB2 expression in L-02 cells. In summary, puerarin most likely prevented activation of the pro-inflammatory factors and reduced LPS/D-Gal-induced liver injury by enhancing the ZEB2 expression level and, consequently, blocking activation of the NF-κB signaling pathway in the liver.
Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose
Authors: Yu Yuan-Yuan , Liu Qiu-Ping , Li Meng-Ting , An Pei , Chen Yu-Ying , Luan Xin , Lv Chao , Zhang Hong
Published: August 2021

Background: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved. Methods: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) in vitro. The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics. Results: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs. Conclusions: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.
Changes in Oxidative and Nitrosative Stress Indicators and Vascular Endothelial Growth Factor After Maximum-Intensity Exercise Assessing Aerobic Capacity in Males With Type 1 Diabetes Mellitus
Authors: Tota Łukasz , Matejko Bartłomiej , Morawska-Tota Małgorzata , Pilch Wanda , Mrozińska Sandra , Pałka Tomasz , Klupa Tomasz , Malecki Maciej T.
Published: August 2021

In type 1 diabetes mellitus (T1DM), chronic hyperglycemia causes reactive oxygen and nitrogen species production. Exercise alters the oxidant-antioxidant balance. We evaluated the aerobic capacity and oxidant-antioxidant balance changes after maximum-intensity exercise in T1DM patients. The study involved 30 T1DM participants and 23 controls. The patients’ average age was 23.4 ± 5.1 years, with a body mass index of 24.3 ± 3.1 kg m–2 and with satisfactory glycemic control. Among the controls, the respective values equaled 24.7 ± 2.9 years and 22.9 ± 2.1 kg m–2. Aerobic capacity was assessed with a treadmill test. Peak minute oxygen uptake was significantly lower in T1DM compared with the controls (44.7 ± 5.7 vs. 56.0 ± 7.3 mL kg–1 min–1). The total oxidant capacity measured by total oxidative status/total oxidative capacity (TOS/TOC) equaled 321.5 ± 151 μmol L–1 before and 380.1 ± 153 μmol L–1 after exercise in T1DM, and 164.1 ± 75 and 216.6 ± 75 μmol L–1 in the controls (p < 0.05 for all comparisons). A significant difference in the ratio of total antioxidant status/total antioxidant capacity (TAS/TAC) between the groups after the treadmill test was observed (p < 0.05). Nitrosative stress indicators where significantly higher in the T1DM group both before and after the exercise. In conclusion, diabetic patients demonstrated a lower aerobic capacity. The TOS/TOC and nitrosative stress indicators were significantly higher in T1DM before and after the test.
Genome-Wide Association Study Reveals Key Genes for Differential Lead Accumulation and Tolerance in Natural Arabidopsis thaliana Accessions
Authors: Busoms Sílvia , Pérez-Martín Laura , Llimós Miquel , Poschenrieder Charlotte , Martos Soledad
Published: August 2021

Soil contamination by lead (Pb) has become one of the major ecological threats to the environment. Understanding the mechanisms of Pb transport and deposition in plants is of great importance to achieve a global Pb reduction. We exposed a collection of 360 Arabidopsis thaliana natural accessions to a Pb-polluted soil. Germination rates, growth, and leaf Pb concentrations showed extensive variation among accessions. These phenotypic data were subjected to genome wide association studies (GWAs) and we found a significant association on chromosome 1 for low leaf Pb accumulation. Genes associated with significant SNP markers were evaluated and we selected EXTENSIN18 (EXT18) and TLC (TRAM-LAG1-CLN8) as candidates for having a role in Pb homeostasis. Six Pb-tolerant accessions, three of them exhibiting low leaf Pb content, and three of them with high leaf Pb content; two Pb-sensitive accessions; two knockout T-DNA lines of GWAs candidate genes (ext18, tlc); and Col-0 were screened under control and high-Pb conditions. The relative expression of EXT18, TLC, and other genes described for being involved in Pb tolerance was also evaluated. Analysis of Darwinian fitness, root and leaf ionome, and TEM images revealed that Pb-tolerant accessions employ two opposing strategies: (1) low translocation of Pb and its accumulation into root cell walls and vacuoles, or (2) high translocation of Pb and its efflux to inactive organelles or intracellular spaces. Plants using the first strategy exhibited higher expression of EXT18 and HMA3, thicker root cell walls and Pb vacuolar sequestration, suggesting that these genes may contribute to the deposition of Pb in the roots. On the other hand, plants translocating high amounts of Pb showed upregulation of TLC and ABC transporters, indicating that these plants were able to properly efflux Pb in the aerial tissues. We conclude that EXT18 and TLC upregulation enhances Pb tolerance promoting its sequestration: EXT18 favors the thickening of the cell walls improving Pb accumulation in roots and decreasing its toxicity, while TLC facilitates the formation of dictyosome vesicles and the Pb encapsulation in leaves. These findings are relevant for the design of phytoremediation strategies and environment restoration.
High-Resolution X-Ray Computed Tomography: A New Workflow for the Analysis of Xylogenesis and Intra-Seasonal Wood Biomass Production
Authors: Lehnebach Romain , Campioli Matteo , Gričar Jozica , Prislan Peter , Mariën Bertold , Beeckman Hans , Van den Bulcke Jan
Published: August 2021

Understanding tree growth and carbon sequestration are of crucial interest to forecast the feedback of forests to climate change. To have a global understanding of the wood formation, it is necessary to develop new methodologies for xylogenesis measurements, valid across diverse wood structures and applicable to both angiosperms and gymnosperms. In this study, the authors present a new workflow to study xylogenesis using high-resolution X-ray computed tomography (HRXCT), which is generic and offers high potential for automatization. The HXRCT-based approach was benchmarked with the current classical approach (microtomy) on three tree species with contrasted wood anatomy (Pinus nigra, Fagus sylvatica, and Quercus robur). HRXCT proved to estimate the relevant xylogenesis parameters (timing, duration, and growth rates) across species with high accuracy. HRXCT showed to be an efficient avenue to investigate tree xylogenesis for a wide range of wood anatomies, structures, and species. HRXCT also showed its potential to provide quantification of intra-annual dynamics of biomass production through high-resolution 3D mapping of wood biomass within the forming growth ring.
The Thiamin-Requiring 3 Mutation of Arabidopsis 5-Deoxyxylulose-Phosphate Synthase 1 Highlights How the Thiamin Economy Impacts the Methylerythritol 4-Phosphate Pathway
Authors: Joshi Jaya , Mimura Manaki , Suzuki Masaharu , Wu Shan , Gregory Jesse F. , Hanson Andrew D. , McCarty Donald R.
Published: August 2021

The thiamin-requiring mutants of Arabidopsis have a storied history as a foundational model for biochemical genetics in plants and have illuminated the central role of thiamin in metabolism. Recent integrative genetic and biochemical analyses of thiamin biosynthesis and utilization imply that leaf metabolism normally operates close to thiamin-limiting conditions. Thus, the mechanisms that allocate thiamin-diphosphate (ThDP) cofactor among the diverse thiamin-dependent enzymes localized in plastids, mitochondria, peroxisomes, and the cytosol comprise an intricate thiamin economy. Here, we show that the classical thiamin-requiring 3 (th3) mutant is a point mutation in plastid localized 5-deoxyxylulose synthase 1 (DXS1), a key regulated enzyme in the methylerythritol 4-phosphate (MEP) isoprene biosynthesis pathway. Substitution of a lysine for a highly conserved glutamate residue (E323) located at the subunit interface of the homodimeric enzyme conditions a hypomorphic phenotype that can be rescued by supplying low concentrations of thiamin in the medium. Analysis of leaf thiamin vitamers showed that supplementing the medium with thiamin increased total ThDP content in both wild type and th3 mutant plants, supporting a hypothesis that the mutant DXS1 enzyme has a reduced affinity for the ThDP cofactor. An unexpected upregulation of a suite of biotic-stress-response genes associated with accumulation of downstream MEP intermediate MEcPP suggests that th3 causes mis-regulation of DXS1 activity in thiamin-supplemented plants. Overall, these results highlight that the central role of ThDP availability in regulation of DXS1 activity and flux through the MEP pathway.
Unsupervised Online Assessment of Visual Working Memory in 4- to 10-Year-Old Children: Array Size Influences Capacity Estimates and Task Performance
Authors: Ross-Sheehy Shannon , Reynolds Esther , Eschman Bret
Published: August 2021

The events of the COVID-19 Pandemic forced many psychologists to abandon lab-based approaches and embrace online experimental techniques. Although lab-based testing will always be the gold standard of experimental precision, several protocols have evolved to enablesupervisedonline testing for paradigms that require direct observation and/or interaction with participants. However, many tasks can be completed online in anunsupervisedway, reducing reliance on lab-based resources (e.g., personnel and equipment), increasing flexibility for families, and reducing participant anxiety and/or demand characteristics. The current project demonstrates the feasibility and utility of unsupervised online testing by incorporating a classic change-detection task that has been well-validated in previous lab-based research. In addition to serving as proof-of-concept, our results demonstrate that large online samples are quick and easy to acquire, facilitating novel research questions and speeding the dissemination of results. To accomplish this, we assessed visual working memory (VWM) in 4- to 10-year-old children in an unsupervised online change-detection task using arrays of 1–4 colored circles. Maximum capacity (max K) was calculated across the four array sizes for each child, and estimates were found to be on-par with previously published lab-based findings. Importantly, capacity estimates varied markedly across array size, with estimates derived from larger arrays systematically underestimating VWM capacity for our youngest participants. A linear mixed effect analysis (LME) confirmed this observation, revealing significant quadratic trends for 4- through 7-year-old children, with capacity estimates that initially increased with increasing array size and subsequently decreased, often resulting in estimates that werelowerthan those obtained from smaller arrays. Follow-up analyses demonstrated that these regressions may have been based on explicit guessing strategies for array sizes perceived too difficult to attempt for our youngest children. This suggests important interactions between VWM performance, age, and array size, and further suggests estimates such asoptimal array sizemight capture bothquantitativeaspects of VWM performance andqualitativeeffects of attentional engagement/disengagement. Overall, findings suggest that unsupervised online testing of VWM produces reasonably good estimates and may afford many benefits over traditional lab-based testing, though efforts must be made to ensure task comprehension and compliance.
Emotion Differentiation and Youth Mental Health: Current Understanding and Open Questions
Authors: Nook Erik C.
Published: August 2021

A growing body of research identifies emotion differentiation—the ability to specifically identify one’s emotions—as a key skill for well-being. High emotion differentiation is associated with healthier and more effective regulation of one’s emotions, and low emotion differentiation has been documented in several forms of psychopathology. However, the lion’s share of this research has focused on adult samples, even though approximately 50% of mental disorders onset before age 18. This review curates what we know about the development of emotion differentiation and its implications for youth mental health. I first review published studies investigating how emotion differentiation develops across childhood and adolescence, as well as studies testing relations between emotion differentiation and mental health in youth samples. Emerging evidence suggests that emotion differentiation actually falls across childhood and adolescence, a counterintuitive pattern that merits further investigation. Additionally, several studies find relations between emotion differentiation and youth mental health, but some instability in results emerged. I then identify open questions that limit our current understanding of emotion differentiation, including (i) lack of clarity as to the valid measurement of emotion differentiation, (ii) potential third variables that could explain relations between emotion differentiation and mental-health (e.g., mean negative affect, IQ, personality, and circularity with outcomes), and (iii) lack of clear mechanistic models regarding the development of emotion differentiation and how it facilitates well-being. I conclude with a discussion of future directions that can address open questions and work toward interventions that treat (or even prevent) psychopathology.
Supporting Team Reflexivity During the COVID-19 Lockdown: A Qualitative Study of Multi-Vision Groups In-person and Online
Authors: Parrello Santa , Fenizia Elisabetta , Gentile Rosa , Iorio Ilaria , Sartini Clara , Sommantico Massimiliano
Published: August 2021

Introduction:The professional self is often hindered by a lack of self-care and poor work-life balance, and cannot be considered an unlimited resource. Given this, the reflexive team is an important organizational tool for protecting workers' well-being. The non-profit organizationMaestri di Strada(MdS) (“Street Teachers”) conducts action research (AR) in the area of socio-education. The main tool used by the group to protect the well-being of its members is a guided reflexivity group, inspired by the Balint Group and termed the Multi-Vision Group (MG). In March 2020, because of the COVID-19 lockdown, the MdS team had to quickly revamp its working model, and MGs were held online for the first time.

Aim:Through qualitative research that takes a longitudinal approach, the aim of this study is to evaluate the efficacy of the MG in supporting the team's reflexivity in this new online format.

Methods:This article considers MGs during two different time periods: pre-pandemic (T1) and early pandemic (T2). During T1, the MdS team met 18 times in person, while during T2 the team met 12 times through an online platform (always under the guidance of a psychotherapist). During all sessions in both time periods, a silent observer was present in the meetings, and they subsequently compiled narrative reports. The textual corpora of the reports were submitted for a Thematic Analysis of Elementary Contexts through T-Lab Plus, in order to examine the main content of the groups' discourse.

Results:The results (five clusters in T1; and five in T2) show that, during T2, the group devoted considerable time to experiences tied to the pandemic (T21: schools facing the pandemic crisis; T2.2: the pandemic: death, inner worlds, and thought resistance; T2.3: kids' stories involving physical distancing and emotional proximity). The group also came up with innovative educational initiatives that defied the lockdown (T2.4: fieldwork: the delivery of “packages of food for thought”; T2.5: the MdS group: identity and separation). Based on these findings, the MG most likely contributed to the emergence of MdS as a “resilient community,” capable of absorbing the shock of the pandemic and realizing a fast recovery response.
Happiness Management: A Culture to Explore From Brand Orientation as a Sign of Responsible and Sustainable Production
Authors: Ravina-Ripoll Rafael , Nunez-Barriopedro Estela , Almorza-Gomar David , Tobar-Pesantez Luis-Bayardo
Published: August 2021

The overarching call to action represented by the sustainable development goals (SDGs) calls for new sustainable production and management models. Likewise, in periods of crisis, such as the current COVID-19 pandemic, companies are forced to develop competitive and sustainable development strategies to increase their brand value and achieve a good market position. Therefore, this work’s main objective is to design a structural equation modelling (SEM) to analyse the main critical dimensions of brand orientation to influence happiness in responsible and sustainable entities. For this purpose, a descriptive cross-sectional study was carried out based on primary data from a survey of a representative sample of 216 managers of small- and medium-sized enterprises in Andalusia (Spain) in the construction, industry and services sectors. The model results reveal significant dimensions of brand orientation and positively direct influence on happiness management. One of the significant managerial implications of this work is that the model allows for more responsible and sustainable management of entities by considering brand orientation about happiness.
Investigating Principal Working Memory Features in Generalized, Panic, and Social Anxiety Spectrum Disorders
Authors: Abushalbaq Oday M. , Khdour Hussain Y. , Abo Hamza Eid G. , Moustafa Ahmed A. , Herzallah Mohammad M.
Published: August 2021

Anxiety spectrum disorders are characterized by excessive and uncontrollable worrying about potential negative events in the short- and long-term future. Various reports linked anxiety spectrum disorders with working memory (WM) deficits despite conflicting results stemming from different study approaches. It remains unclear, however, how different anxiety spectrum disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD), differ in WM function. In this study, we utilized verbal, numerical, and sequential evaluations of WM to cover most possible facets of the WM data space. We used principal component analysis to extract the uncorrelated/whitened components of WM based on these measures. We evaluated medication-free patients with GAD, SAD, and PD patients as well as matched healthy individuals using a battery that measures WM duration and load. We found that patients with GAD and SAD, but not PD, exhibited poor performance only in the WM principal component that represents maintenance. There were no other significant differences between the four groups. Further, different WM components significantly predicted the severity of anxiety symptoms in the groups. We explored the clinical utility of WM components for differentiating patients with anxiety spectrum disorders from healthy individuals. By only using the WM components that represent maintenance and encoding, we managed to differentiate patients from controls in 84% of cases. For the first time, we present multiple novel approaches to examine cognitive function and design cognitive screening, and potentially diagnostics, for psychiatric disorders.