bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker
Authors: Tang Qikai , Chen Zhengxin , Xie Jiaheng , Mo Chuangqi , Lu Jiacheng , Zhang Qixiang , Wang Zhangjie , Wu Wei , Wang Huibo
Published: June 2022

Background

Glioma, the most frequent malignant tumor of the neurological system, has a poor prognosis and treatment problems. Glioma’s tumor microenvironment is also little known.

Methods

We downloaded glioma data from the TCGA database. The patients in the TCGA database were split into two groups, one for training and the other for validation. The ubiquitination genes were then evaluated in glioma using COX and Lasso regression to create a ubiquitination-related signature. We assessed the signature’s predictive usefulness and role in the immune microenvironment after it was generated. Finally, in vitro experiment were utilized to check the expression and function of the signature’s key gene, USP4.

Results

This signature can be used to categorize glioma patients. Glioma patients can be separated into high-risk and low-risk groups in both the training and validation cohorts, with the high-risk group having a significantly worse prognosis (P<0.05). Following further investigation of the immune microenvironment, it was discovered that this risk grouping could serve as a guide for glioma immunotherapy. The activity, invasion and migration capacity, and colony formation ability of U87-MG and LN229 cell lines were drastically reduced after the important gene USP4 in signature was knocked down in cell tests. Overexpression of USP4 in the A172 cell line, on the other hand, greatly improved clonogenesis, activity, invasion and migration.

Conclusions

Our research established a foundation for understanding the role of ubiquitination genes in gliomas and identified USP4 as a possible glioma biomarker.
Effects of Mixing and Stratification on the Vertical Distribution and Size Spectrum of Zooplankton on the Shelf and Slope of the Northern South China Sea
Authors: Chen Kaixuan , Zhou Meng , Zhong Yisen , Waniek Joanna J. , Shan Congwen , Zhang Zhaoru
Published: June 2022

The northern shelf and off-shelf regions of the South China Sea (SCS) present a stark contrast between being eutrophic from terrestrial runoffs of nutrients and biota and being oligotrophic with multiple nutrient limitations due to the distance to land sources and stable permanent stratification. The abundance, size, and trophic structures of plankton in the shelf and off-shelf regions were studied in a joint Sino-German cruise conducted between September 1 and 24, 2018. A laser optical plankton counter was mounted on a water sampler-CTD (conductivity–temperature–depth) system for studying the horizontal and vertical distributions of plankton structures in a size range between 0.1 and 35 mm and their relationships with hydrographic and biological features in the northern SCS and its shelf region. Results revealed the subsurface chlorophyll maximum layer (SCM) below the pycnocline and plankton aggregation near the SCM about a depth of 50–60 m. The distributions of small plankton between 0.1 and 0.5 mm were strongly correlated with stratification and SCM compared to those of large plankton. Analyzing the intercept and slope of a normalized biovolume spectrum (NBVS) as an indicator for abundance and size structure of a plankton community, results revealed that in the shelf region, the slopes exhibited no significant vertical variations in the water column regardless of stratification and SCM. In contrast, in the off-shelf stratified water column, the intercepts and slopes were lower and flatter in the surface layer, higher and steeper in the SCM layer, and the lowest and flattest in the deep layer. Stirring by the typhoon also altered both the abundances and size structures of the plankton communities, with significant regional differences. This study elucidates the variances of plankton abundances, distributions, NBVS slopes, and intercepts among different water column structures in both shelf and off-shelf regions of the northern SCS.
Pore Structure and Permeability of Cementitious Materials Containing a Carboxylic Acid Type Hydrophobic Agent
Authors: Zhang Hao , Zhou Ying , Mu Song , Cai Jingshun , Hong Jinxiang , Liu Jianzhong , Zhao Yongqiang
Published: June 2022

Integral hydrophobic treatment is the most effective method to prolong the service life of the concrete by resisting the transport of water containing aggressive ions. The hydrophobicity phenomenon of cementitious materials with carboxylic acid type admixture has been presented, and experimental studies, including water adsorption, amount of hydration products, and pore system, are conducted to reveal the hydrophobicity mechanism. It is reported that cementitious materials containing hydrophobic admixture present excellent water resistance ability, and the experimental results of nitrogen adsorption isotherm show that carboxylic acid type admixture addition increases pore volume and surface area of cement pastes. In addition, the fractal geometry theory is applied to reveal the relation between the pore structure and the permeability coefficient of cement pastes with a hydrophobic agent. In conclusion, the high tortuosity fractal dimension and the hydrophobicity of the pore surface result in water resistance when the cementitious system is mixed with a new type of hydrophobic admixture.
Structural Design and Assessing of Recombinantly Expressed African Swine Fever Virus p72 Trimer in Saccharomyces cerevisiae
Authors: Meng Kaiwen , Zhang Yueping , Liu Qi , Huyan Yangnan , Zhu Wenzhuang , Xiang Ye , Meng Geng
Published: June 2022

In an effort to control the outbreak of the African Swine Fever Virus (ASFV), there is an urgent need to develop an effective method to prevent the pandemic, including vaccines and diagnostic methods. The major capsid protein of ASFV p72 (B646L), which forms a trimer with each monomer adopting a double jelly roll fold, is the main component of the virus particle and major antigen of ASFV. Thus, the p72 protein may be considered an antigen candidate for vaccine and diagnostic development. However, the development of ASFV p72 trimer for the industry application, including veterinary usage, faces unavoidable challenges: firstly, the low cost of the antigen production is required in vaccine and diagnostic application; and, secondly, whether produced antigen folds in its native conformation. Here, based on the information provided by the atomic structure of p72, we have successfully performed rational mutagenesis on p72 trimers and expressed it in Saccharomyces cerevisiae with high yields. The cryo-EM structure of recombinant expressed p72 trimer is determined at 4.18 Å in resolution. The correlation coefficient between this structure and the ASFV virus structure is 0.77, suggesting a highly similar fold of this trimer with the native protein on the virus particle.
Biodegradation of Polyester Polyurethane by Embarria clematidis
Authors: Khruengsai Sarunpron , Sripahco Teerapong , Pripdeevech Patcharee
Published: June 2022

Polyester urethanes (PUR) are widely used in industries and have led to a worldwide plastic waste problem. Thus, novel solutions for PUR degradation are required to reduce environmental pollution. This work investigates the PUR biodegradation efficiency of 33 fungal species using a polyester-polyurethane colloid branded Impranil DLN (Impranil) compared to Aspergillus niger, which served as the positive control. The biodegradation is evaluated based on its ability to clear Impranil in media. Eleven fungi can clear Impranil in both solid- and liquid-medium assays. The highest degradation was attributed to Embarria clematidis cultured with Impranil as a carbon source. The degradation was confirmed by the Sturm test, Fourier-transform infrared (FTIR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). From the Sturm test, CO2 at a concentration of 0.85 g/L was found in E. clematidis cultured with 150 mL of Impranil solution after a 2-week incubation period while the CO2 at a concentration of 0.53 g/L was detected from A. niger in the same conditions. The biodegradation was further confirmed by evaluating the clearance percentage of supernatant of E. clematidis and A. niger culturing with Impranil from the Sturm test. The clearance percentage of E. clematidis and A. niger supernatant was 88.84 and 48.97%, respectively. Moreover, the degradation of soft segment and breakdown of ester linkages were observed, as evidenced by the decrease of the carbonyl (1,715 cm–1) and N-H stretching (1,340 cm–1 and 1,020 cm–1) FTIR spectral peaks, respectively. GC-MS detected 3Z-heptenol, 5Z-octenol, 2E,4E-hexadienol acetate, and 3E,6Z-nonadienol as degradation products from the E. clematidis culture supernatant. This fungus was screened for its ability to produce extracellular esterase, protease, and urease enzymes. Extracellular esterase, very low urease, and no protease activities were detected in the culture supernatant of E. clematidis in the presence of Impranil. E. clematidis can degrade Impranil partially via hydrolysis of ester linkages by cell-bound esterases at a considerable rate without any prior treatment. This fungus not only degraded Impranil but also mineralized them into CO2 and H2O. E. clematidis can be applied in the process of biochemical depolymerization of PUR for the pure monomers recycling.
Copper Acts Synergistically With Fluconazole in Candida glabrata by Compromising Drug Efflux, Sterol Metabolism, and Zinc Homeostasis
Authors: Gaspar-Cordeiro Ana , Amaral Catarina , Pobre Vânia , Antunes Wilson , Petronilho Ana , Paixão Paulo , Matos António P. , Pimentel Catarina
Published: June 2022

The synergistic combinations of drugs are promising strategies to boost the effectiveness of current antifungals and thus prevent the emergence of resistance. In this work, we show that copper and the antifungal fluconazole act synergistically against Candida glabrata, an opportunistic pathogenic yeast intrinsically tolerant to fluconazole. Analyses of the transcriptomic profile of C. glabrata after the combination of copper and fluconazole showed that the expression of the multidrug transporter gene CDR1 was decreased, suggesting that fluconazole efflux could be affected. In agreement, we observed that copper inhibits the transactivation of Pdr1, the transcription regulator of multidrug transporters and leads to the intracellular accumulation of fluconazole. Copper also decreases the transcriptional induction of ergosterol biosynthesis (ERG) genes by fluconazole, which culminates in the accumulation of toxic sterols. Co-treatment of cells with copper and fluconazole should affect the function of proteins located in the plasma membrane, as several ultrastructural alterations, including irregular cell wall and plasma membrane and loss of cell wall integrity, were observed. Finally, we show that the combination of copper and fluconazole downregulates the expression of the gene encoding the zinc-responsive transcription regulator Zap1, which possibly, together with the membrane transporters malfunction, generates zinc depletion. Supplementation with zinc reverts the toxic effect of combining copper with fluconazole, underscoring the importance of this metal in the observed synergistic effect. Overall, this work, while unveiling the molecular basis that supports the use of copper to enhance the effectiveness of fluconazole, paves the way for the development of new metal-based antifungal strategies.
Melatonin Rhythm and Its Relation to Sleep and Circadian Parameters in Children and Adolescents With Autism Spectrum Disorder
Authors: Martinez-Cayuelas Elena , Gavela-Pérez Teresa , Rodrigo-Moreno María , Merino-Andreu Milagros , Vales-Villamarín Claudia , Pérez-Nadador Iris , Garcés Carmen , Soriano-Guillén Leandro
Published: June 2022

Introduction

Sleep problems are prevalent among individuals with autism spectrum disorder (ASD), and a role has been attributed to melatonin in this multifactorial comorbidity.

Methods

A cross-sectional study was conducted on 41 autistic children and adolescents (9.9 ± 3.02) and 24 children and adolescents with a normal intellectual function (8.42 ± 2.43) were used as controls. Subjects were matched for sex, body mass index, and pubertal stage, and all were drug-naive. Circadian and sleep parameters were studied using an ambulatory circadian monitoring (ACM) device, and saliva samples were collected around the onset of sleep to determine dim light melatonin onset (DLMO).

Results

Prepubertal individuals with ASD presented later DLMO and an earlier decline in melatonin during adolescence. A relationship was found between melatonin and both sleep and circadian parameters. Participants and controls with later DLMOs were more likely to have delayed sleep onset times. In the ASD group, subjects with the later daytime midpoint of temperature had a later DLMO. Later melatonin peak time and DLMO time were related to lower general motor activity and lower stability of its rhythms.

Conclusion

The melatonin secretion pattern was different in individuals with ASD, and it showed a relationship with sleep and circadian parameters. Alterations in DLMO have not been previously reported in ASD with the exception of more variable DLMO timing; however, high variability in the study design and sample characteristics prevents direct comparison. The ACM device enabled the measurement of circadian rhythm, a scarcely described parameter in autistic children. When studied in combination with other measures such as melatonin, ACM can offer further knowledge on sleep problems in ASD.
Early Onset Diffusion Abnormalities in Refractory Headache Disorders
Authors: Santoro Jonathan D. , Moon Peter K. , Han Michelle , McKenna Emily S. , Tong Elizabeth , MacEachern Sarah J. , Forkert Nils D. , Yeom Kristen W.
Published: June 2022

Objective

This study sought to determine if individuals with medically refractory migraine headache have volume or diffusion abnormalities on neuroimaging compared to neurotypical individuals.

Background

Neuroimaging biomarkers in headache medicine continue to be limited. Early prediction of medically refractory headache and migraine disorders could result in earlier administration of high efficacy therapeutics.

Methods

A single-center, retrospective, case control study was performed. All patients were evaluated clinically between 2014 and 2018. Individuals with medically refractory migraine headache (defined by ICDH-3 criteria) without any other chronic medical diseases were enrolled. Patients had to have failed more than two therapeutics and aura was not exclusionary. The initial MRI study for each patient was reviewed. Multiple brain regions were analyzed for volume and apparent diffusion coefficient values. These were compared to 81 neurotypical control patients.

Results

A total of 79 patients with medically refractory migraine headache were included and compared to 74 neurotypical controls without headache disorders. Time between clinical diagnosis and neuroimaging was a median of 24 months (IQR: 12.0–37.0). Comparison of individuals with medically refractory migraine headache to controls revealed statistically significant differences in median apparent diffusion coefficient (ADC) in multiple brain subregions (p < 0.001). Post-hoc pair-wise analysis comparing individuals with medically refractory migraine headache to control patients revealed significantly decreased median ADC values for the thalamus, caudate, putamen, pallidum, amygdala, brainstem, and cerebral white matter. No volumetric differences were observed between groups.

Conclusions

In individuals with medically refractory MH, ADC changes are measurable in multiple brain structures at an early age, prior to the failure of multiple pharmacologic interventions and the diagnosis of medically refractory MH. This data supports the hypothesis that structural connectivity issues may predispose some patients toward more medically refractory pain disorders such as MH.
Effects of Physical and Mental Fatigue on Postural Sway and Cortical Activity in Healthy Young Adults
Authors: Gebel Arnd , Busch Aglaja , Stelzel Christine , Hortobágyi Tibor , Granacher Urs
Published: June 2022

Physical fatigue (PF) negatively affects postural control, resulting in impaired balance performance in young and older adults. Similar effects on postural control can be observed for mental fatigue (MF) mainly in older adults. Controversial results exist for young adults. There is a void in the literature on the effects of fatigue on balance and cortical activity. Therefore, this study aimed to examine the acute effects of PF and MF on postural sway and cortical activity. Fifteen healthy young adults aged 28 ± 3 years participated in this study. MF and PF protocols comprising of an all-out repeated sit-to-stand task and a computer-based attention network test, respectively, were applied in random order. Pre and post fatigue, cortical activity and postural sway (i.e., center of pressure displacements [CoPd], velocity [CoPv], and CoP variability [CV CoPd, CV CoPv]) were tested during a challenging bipedal balance board task. Absolute spectral power was calculated for theta (4–7.5 Hz), alpha-2 (10.5–12.5 Hz), beta-1 (13–18 Hz), and beta-2 (18.5–25 Hz) in frontal, central, and parietal regions of interest (ROI) and baseline-normalized. Inference statistics revealed a significant time-by-fatigue interaction for CoPd (p = 0.009, d = 0.39, Δ 9.2%) and CoPv (p = 0.009, d = 0.36, Δ 9.2%), and a significant main effect of time for CoP variability (CV CoPd: p = 0.001, d = 0.84; CV CoPv: p = 0.05, d = 0.62). Post hoc analyses showed a significant increase in CoPd (p = 0.002, d = 1.03) and CoPv (p = 0.003, d = 1.03) following PF but not MF. For cortical activity, a significant time-by-fatigue interaction was found for relative alpha-2 power in parietal (p < 0.001, d = 0.06) areas. Post hoc tests indicated larger alpha-2 power increases after PF (p < 0.001, d = 1.69, Δ 3.9%) compared to MF (p = 0.001, d = 1.03, Δ 2.5%). In addition, changes in parietal alpha-2 power and measures of postural sway did not correlate significantly, irrespective of the applied fatigue protocol. No significant changes were found for the other frequency bands, irrespective of the fatigue protocol and ROI under investigation. Thus, the applied PF protocol resulted in increased postural sway (CoPd and CoPv) and CoP variability accompanied by enhanced alpha-2 power in the parietal ROI while MF led to increased CoP variability and alpha-2 power in our sample of young adults. Potential underlying cortical mechanisms responsible for the greater increase in parietal alpha-2 power after PF were discussed but could not be clearly identified as cause. Therefore, further future research is needed to decipher alternative interpretations.
Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates Cognitive Function Related to Motor Execution During Sequential Task: A Randomized Control Study
Authors: Yamamoto Satoshi , Ishii Daisuke , Ishibashi Kiyoshige , Kohno Yutaka
Published: June 2022

In daily life, we perform a variety of sequential tasks while making cognitive decisions to achieve behavioral goals. If transcranial direct current electrical stimulation (tDCS) can be used to modulate cognitive functions involved in motor execution, it may provide a new rehabilitation method. In the present study, we constructed a new task in which cognitive decisions are reflected in motor actions and investigated whether the performance of the task can be improved by tDCS of the left dorsolateral prefrontal cortex (DLPFC). Forty healthy participants were randomly assigned to a real or sham tDCS group. The anode electrode was placed at F3 (left DLPFC), and the cathode electrode was positioned in the contralateral supraorbital area. Participants underwent one session of tDCS (1.5 mA, 20 min) and a sequential non-dominant hand task was performed for nine trials before and after tDCS. The task consisted of S1 (a manual dexterity task) and S2 (a manual dexterity task requiring a decision). The results showed the S2 trajectory length was significantly shorter after real tDCS than after sham tDCS (p = 0.017), though the S1 trajectory length was not significant. These results suggest that a single tDCS session of the left DLPFC can improve the performance of cognitive tasks complementary to motor execution, but not on dexterity tasks. By elucidating the modulating effect of tDCS on cognitive functions related to motor execution, these results may be used to improve the performance of rehabilitation patients in the future.
Syllable-Initial Phonemes Affect Neural Entrainment to Consonant-Vowel Syllables
Authors: Cucu M. Oana , Kazanina Nina , Houghton Conor
Published: June 2022

Neural entrainment to speech appears to rely on syllabic features, especially those pertaining to the acoustic envelope of the stimuli. It has been proposed that the neural tracking of speech depends on the phoneme features. In the present electroencephalography experiment, we examined data from 25 participants to investigate neural entrainment to near-isochronous stimuli comprising syllables beginning with different phonemes. We measured the inter-trial phase coherence of neural responses to these stimuli and assessed the relationship between this coherence and acoustic properties of the stimuli designed to quantify their “edginess.” We found that entrainment was different across different classes of the syllable-initial phoneme and that entrainment depended on the amount of “edge” in the sound envelope. In particular, the best edge marker and predictor of entrainment was the latency of the maximum derivative of each syllable.
Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations
Authors: Zhang Wen , Ye Fanghua , Chen Shimeng , Peng Jing , Pang Nan , Yin Fei
Published: June 2022

CSNK2B has recently been identified as the causative gene for Poirier–Bienvenu neurodevelopmental syndrome (POBINDS). POBINDS is a rare neurodevelopmental disorder characterized by early-onset epilepsy, developmental delay, hypotonia, and dysmorphism. Limited by the scarcity of patients, the genotype–phenotype correlations in POBINDS are still unclear. In the present study, we describe the clinical and genetic characteristics of eight individuals with POBINDS, most of whom suffered developmental delay, generalized epilepsy, and hypotonia. Minigene experiments confirmed that two intron variants (c.367+5G>A and c.367+6T>C) resulted in the skipping of exon 5, leading to a premature termination of mRNA transcription. Combining our data with the available literature, the types of POBINDS-causing variants included missense, nonsense, frameshift, and splicing, but the variant types do not reflect the clinical severity. Reduced casein kinase 2 holoenzyme activity may represent a unifying pathogenesis. We also found that individuals with missense variants in the zinc finger domain had manageable seizures (p = 0.009) and milder intellectual disability (p = 0.003) than those with missense variants in other domains of CSNK2B. This is the first study of genotype–phenotype correlations in POBINDS, drawing attention to the pathogenicity of intron variants and expanding the understanding of neurodevelopmental disorders.
Offline Parietal Intermittent Theta Burst Stimulation or Alpha Frequency Transcranial Alternating Current Stimulation Has No Effect on Visuospatial or Temporal Attention
Authors: Moretti Jessica , Marinovic Welber , Harvey Alan R. , Rodger Jennifer , Visser Troy A. W.
Published: June 2022

Non-invasive brain stimulation is a growing field with potentially wide-ranging clinical and basic science applications due to its ability to transiently and safely change brain excitability. In this study we include two types of stimulation: repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). Single session stimulations with either technique have previously been reported to induce changes in attention. To better understand and compare the effectiveness of each technique and the basis of their effects on cognition we assessed changes to both temporal and visuospatial attention using an attentional blink task and a line bisection task following offline stimulation with an intermittent theta burst (iTBS) rTMS protocol or 10 Hz tACS. Additionally, we included a novel rTMS stimulation technique, low-intensity (LI-)rTMS, also using an iTBS protocol, which uses stimulation intensities an order of magnitude below conventional rTMS. Animal models show that low-intensity rTMS modulates cortical excitability despite sub-action potential threshold stimulation. Stimulation was delivered in healthy participants over the right posterior parietal cortex (rPPC) using a within-subjects design (n = 24). Analyses showed no evidence for an effect of any stimulation technique on spatial biases in the line bisection task or on magnitude of the attentional blink. Our results suggests that rTMS and LI-rTMS using iTBS protocol and 10 Hz tACS over rPPC do not modulate performance in tasks assessing visuospatial or temporal attention.
Value of Preoperative Imaging Results in Predicting Cochlear Nerve Function in Children Diagnosed With Cochlear Nerve Aplasia Based on Imaging Results
Authors: Chao Xiuhua , Wang Ruijie , Luo Jianfen , Wang Haibo , Fan Zhaomin , Xu Lei
Published: June 2022

This study aimed to assess the function of the cochlear nerve using electrically evoked compound action potentials (ECAPs) for children with cochlear implants who were diagnosed with cochlear nerve aplasia and to analyze the correlation between preimplantation imaging results and ECAP responses. Thirty-five children diagnosed with cochlear nerve aplasia based on magnetic resonance imaging (MRI) were included. Preimplantation MRI and high-resolution computed tomography (HRCT) images were reconstructed, and the width of the bone cochlear nerve canal (BCNC), the diameter of the vestibulocochlear nerve (VCN), and the diameter of the facial nerve (FN) were measured. ECAP input/output (I/O) functions were measured at three electrode locations along the electrode array for each participant. The relationship between ECAP responses (including ECAP threshold, ECAP maximum amplitude, and slope of ECAP I/O function) and sizes of the BCNC and VCN was analyzed using Pearson's correlation coefficients. Our analysis revealed that ECAP responses varied greatly among individual participants. Overall, ECAP thresholds gradually increased, while maximum amplitudes and ECAP I/O function slopes gradually decreased, as the electrode location moved from the basal to the apical direction in the cochlea. ECAP responses exhibited no significant correlations with BCNC width or VCN diameter. The ratio of the VCN to FN diameters was significantly correlated with the slope of the ECAP I/O function and the maximum amplitude. BCNC width could not predict the function of the cochlear nerve. Compared with the absolute size of the VCN, the size of the VCN relative to the FN may represent an indicator for predicting the functional status of the cochlear nerve in children diagnosed with cochlear nerve aplasia based on imaging results.
Characteristics and Mediating Effect of Gut Microbiota With Experience of Childhood Maltreatment in Major Depressive Disorder
Authors: Zhang Yanyan , Zhang Ruiyu , Liu Penghong , Wang Jizhi , Gao Mingxue , Zhang Jie , Yang Jun , Yang Chunxia , Zhang Yu , Sun Ning
Published: June 2022

Gut microbiota and childhood maltreatment are closely related to depressive symptoms. This study aimed to analyze the characteristics of gut microbiota in major depressive disorder (MDD) patients with childhood maltreatment experience and explore the correlation between gut microbiota, childhood maltreatment, and depressive symptoms. A total of 37 healthy controls (HCs) and 53 patients with MDD were enrolled, including 18 MDD patients without childhood maltreatment experience and 35 MDD patients with childhood maltreatment experience. The Hamilton’s Depression Scale (HAMD-24) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to evaluate their depressive symptoms and childhood maltreatment experience, respectively. The composition of gut microbiota was evaluated using 16S rRNA sequencing. Spearman’s correlation analysis was used to evaluate the correlation between different gut microbiota, depressive symptoms and childhood maltreatment. The mediation analysis was used to evaluate the mediating effect of gut microbiota. In the α-diversity analysis, we found that the Simpson index and Pielou’s Evenness index differed significantly between MDD patients without childhood maltreatment experience and HCs. In the β-diversity analysis, principal coordinate analysis (PCoA) showed significant differences between MDD patients without childhood maltreatment experience, MDD patients with childhood maltreatment experience and HCs. Twenty-seven different bacteria were identified through Linear discriminant analysis effect size (LEfSe) analysis at different levels of classification. The analysis of the correlation showed that Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium were significantly correlated with HAMD and CTQ-SF scores. The mediation analysis showed that childhood maltreatment had a significant direct effect on the patients’ depressive symptoms, and Blautia, Bifidobacterium, Roseburia had a significant mediating effect. The findings of this study suggested that MDD patients with childhood maltreatment experience had different gut microbiota, which might have a mediating effect on the influence of childhood maltreatment on depressive symptoms.
Aging-Dependent Altered Transcriptional Programs Underlie Activity Impairments in Human C9orf72-Mutant Motor Neurons
Authors: Sommer Daniel , Rajkumar Sandeep , Seidel Mira , Aly Amr , Ludolph Albert , Ho Ritchie , Boeckers Tobias M. , Catanese Alberto
Published: June 2022

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease characterized by dysfunction and loss of upper and lower motor neurons (MN). Despite several studies identifying drastic alterations affecting synaptic composition and functionality in different experimental models, the specific contribution of impaired activity to the neurodegenerative processes observed in ALS-related MN remains controversial. In particular, contrasting lines of evidence have shown both hyper- as well as hypoexcitability as driving pathomechanisms characterizing this specific neuronal population. In this study, we combined high definition multielectrode array (HD-MEA) techniques with transcriptomic analysis to longitudinally monitor and untangle the activity-dependent alterations arising in human C9orf72-mutant MN. We found a time-dependent reduction of neuronal activity in ALSC9orf72 cultures occurring as synaptic contacts undergo maturation and matched by a significant loss of mutant MN upon aging. Notably, ALS-related neurons displayed reduced network synchronicity most pronounced at later stages of culture, suggesting synaptic imbalance. In concordance with the HD-MEA data, transcriptomic analysis revealed an early up-regulation of synaptic terms in ALSC9orf72 MN, whose expression was decreased in aged cultures. In addition, treatment of older mutant cells with Apamin, a K+ channel blocker previously shown to be neuroprotective in ALS, rescued the time-dependent loss of firing properties observed in ALSC9orf72 MN as well as the expression of maturity-related synaptic genes. All in all, this study broadens the understanding of how impaired synaptic activity contributes to MN degeneration in ALS by correlating electrophysiological alterations to aging-dependent transcriptional programs.
Use of Teduglutide in Children With Intestinal Failure: A Systematic Review
Authors: Gigola Francesca , Cianci Maria Chiara , Cirocchi Roberto , Ranucci Maria Chiara , Del Riccio Marco , Coletta Riccardo , Morabito Antonino
Published: June 2022

Background and Objectives

Short-bowel syndrome (SBS) results from the loss of a significant portion of the small intestine leading to a state of malabsorption. After an intestinal loss, there is a process of adaptation involving the Glucagon-Like Peptide-2 (GLP-2), an enteroendocrine peptide also involved in nutrient absorption. Teduglutide is a recombinant analog of GLP-2 approved in 2016 to treat selected SBS pediatric patients who are dependent on parenteral support. The present systematic review aims to evaluate the efficacy of Teduglutide in pediatric patients with SBS in reducing the need for parenteral nutrition (PN).

Materials and Methods

We performed a literature search on MEDLINE and Embase to include articles up to November 2021. We included articles that involved using Teduglutide in the SBS pediatric population to define its efficacy in reducing the need for PN. The key words used were GLP-2, teduglutide, child.

Results

Fourteen studies completely fulfilled the inclusion criteria. Two hundred 23 patients were treated with Teduglutide, and the median duration of treatment was 45 weeks (IQR: 36–52.5 weeks). One-hundred and fifty-two patients were treated with 0.05 mg/Kg/d of subcutaneous Teduglutide, 38 received 0.025 mg/Kg/d and 8 received either 0.125 mg/Kg/d or 0.20 mg/Kg/d. A total of 36 patients achieved enteral autonomy (EA) after a median of 24 weeks of treatment (IQR: 24–48 weeks) and 149 patients showed a reduction in PN needs in terms of volume, calories, or hours per day. Eleven studies reported complications: gastrointestinal were the most common, with 89 cases reported in treated patients and 11 in non-treated patients.

Conclusion

Teduglutide appears safe and effective in reducing PN requirements and improving EA in the pediatric population. However, more studies are needed to understand its efficacy in the long term and after discontinuation and possible complications.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022301593].
ERH Interacts With EIF2α and Regulates the EIF2α/ATF4/CHOP Pathway in Bladder Cancer Cells
Authors: Pang Kun , Dong Yang , Hao Lin , Shi Zhen-duo , Zhang Zhi-guo , Chen Bo , Feng Harry , Ma Yu-yang , Xu Hao , Pan Deng , Chen Zhe-sheng , Han Cong-hui
Published: June 2022

Background

There is a lack of research on the molecular interaction of the enhancers of rudimentary homolog (ERH) in bladder cancer (BC) cells. This study aimed to determine the interacting proteins of ERH in human T24 cells.

Methods

First, the ERH gene was overexpressed in human T24 cells. Coimmunoprecipitation (co-IP) and shotgun mass spectrometry (MS) analyses were performed to obtain a list of proteins that interact with ERH. Subsequently, bioinformatic analyses with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) studies were performed to analyze the ERH-interactive protein list (ERH-IPL). Then, we selected one of the interacting proteins, EIF2α for verification. An immunofluorescence colocalization assay was performed to validate the co-expression of the selected protein, and the binding sites of the two proteins were predicted by ZDOCK technology. Finally, PCR analysis on the downstream molecules of the interacting protein was performed for verification.

Results

ERH protein was successfully overexpressed in human T24 cells. We obtained a list of 205 proteins that might directly or indirectly interact with the ERH protein by mass spectrometric analysis. The bioinformatic analysis showed that ERH-interacting proteins were related to “ribonucleoprotein complex”, “ATPase activity”, “nuclear speck”, and “translation factor activity, RNA binding”. We further identified one of the key genes, EIF2S1, and confirmed that the corresponding protein EIF2α is co-expressed and may bind with ERH in human T24 cells. The mRNA levels of molecules ATF4 and CHOP were found to be upregulated by ERH.

Conclusion

ERH protein affects “ribonucleoprotein complex”, “ATPase activity”, “nuclear speck”, and “translation factor activity, RNA binding”. The ERH protein can interact with EIF2α and regulate the EIF2α-ATF4/CHOP signaling pathway in human T24 cells.
Cordycepin Inhibits Triple-Negative Breast Cancer Cell Migration and Invasion by Regulating EMT-TFs SLUG, TWIST1, SNAIL1, and ZEB1
Authors: Wei Chunli , Khan Md. Asaduzzaman , Du Jiaman , Cheng Jingliang , Tania Mousumi , Leung Elaine Lai-Han , Fu Junjiang
Published: June 2022

Cancer metastasis is the most important cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) plays crucial roles in cancer metastasis. Cordycepin (CD) is highly enriched in the medicinally used Cordyceps mushroom. In this study, we conducted the antimetastatic activities of CD, specifically focusing on its regulatory effects on EMT-inducing transcription factors (EMT-TFs) in triple-negative breast cancer (TNBC). Our study showed CD to inhibit the growth, migration, and invasion of BT549 and 4T1 cancer cell lines, by employing cell viability assay and real-time cell analyses. The protein levels of N-Cadherin and E-Cadherin, as well as their transcription factors TWIST1, SLUG, SNAIL1, and ZEB1 in BT549 and 4T1 cells, were estimated by Western blot assays. Results from dual-luciferase reporter assays demonstrated that CD is capable of inactivating the EMT signaling pathway by inhibiting TWIST1 and SLUG expression. Furthermore, in vivo studies with mice carrying cancer cell-derived allograft tumors showed the inhibitory effect of CD on cancer cell growth and metastasis. Furthermore, the additive/synergistic anti-metastasis effect of CD and thymoquinone (TQ), another natural product with promising anticancer roles, was demonstrated by combinational treatment. The results from this research indicate that CD would be a promising therapeutic molecule against TNBC by targeting EMT-TFs, possibly in SLUG, TWIST1, SNAIL1, and ZEB1.
Social and Regional Disparities in Utilization of Maternal and Child Healthcare Services in India: A Study of the Post-National Health Mission Period
Authors: Bango Madhumita , Ghosh Soumitra
Published: June 2022

Background

India has enjoyed enhanced economic growth, but has fared poorly in human development indicators and health outcomes, over the last two decades. Significant health inequities and access to healthcare continue to exist and have widened within communities across states. This study examine the changes and disparities in maternal and child healthcare (MCH) among disadvantaged and advanced social groups in three states of India.

Data and Methods

Four rounds of National Family Health Survey data were used to measure infant mortality rate (IMR) and under-five mortality rate (U5MR) according to the social groups for the selected states. This study investigates the socio-economic inequities manifested into caste and class differentials and inequities in availability, utilization, and affordability of maternal and healthcare services. Descriptive statistics and the logistic regression model were used. Individual- and household-level covariates were employed to understand the differentials in healthcare utilization.

Results

The probability of not receiving full antenatal care (ANC) or full immunization for the children was highest among the Scheduled Caste/Scheduled Tribe (SC/ST) families, followed by economic class, mother's education and residence. Tamil Nadu showed the highest utilization of public health facilities, while Bihar was the poorest in terms of health outcomes and utilization of MCH care services even after the pre-National Health Mission (NHM) period. Bihar and West Bengal also showed private healthcare dependence.

Conclusion

This study detected the presence of significant caste/tribe differentials in the utilization of MCH care services in the selected states of India. Limited accessibility and unavailability of complete healthcare were the foremost reasons for the under-utilization of these services, especially for people from disadvantaged social groups. The result also suggested that it is perilous to confirm “Health for All” immediately. It will be the efficiency with which India addresses inequities in providing healthcare services and guarantees quality care of health services.
Exploration of Lamiaceae in Cardio Vascular Diseases and Functional Foods: Medicine as Food and Food as Medicine
Authors: Chakrabartty Ishani , Mohanta Yugal Kishore , Nongbet Amilia , Mohanta Tapan Kumar , Mahanta Saurov , Das Nibedita , Saravanan Muthupandian , Sharma Nanaocha
Published: June 2022

In the current scenario, cardiovascular disease (CVD) is one of the most life-threatening diseases that has caused high mortality worldwide. Several scientists, researchers, and doctors are now resorting to medicinal plants and their metabolites for the treatment of different diseases, including CVD. The present review focuses on one such family of medicinal plants, called Lamiaceae, which has relieving and preventive action on CVD. Lamiaceae has a cosmopolitan distribution and has great importance in the traditional system of medicine. Lamiaceae members exhibit a wide range of activities like antioxidant, antihyperlipidemic, vasorelaxant, and thrombolytic effect, both in vitro and in vivo–these are mechanisms that contribute to different aspects of CVD including stroke, heart attack, and others. These plants harbour an array of bioactive compounds like phenolic acids, flavonoids, alkaloids, and other phytochemicals responsible for these actions. The review also highlights that these plants are a rich source of essential nutrients and minerals like omega-3 and hence, can serve as essential sources of functional foods—this can have an additional role in the prevention of CVDs. However, limitations still exist, and extensive research needs to be conducted on the Lamiaceae family in the quest to develop new and effective plant-based drugs and functional foods that can be used to treat and prevent cardiovascular diseases worldwide.
Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities
Authors: Jadhav Nikita , Ajgaonkar Saiprasad , Saha Praful , Gurav Pranay , Pandey Amitkumar , Basudkar Vivek , Gada Yash , Panda Sangita , Jadhav Shashank , Mehta Dilip , Nair Sujit
Published: June 2022

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer’s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer’s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.
Detector Simulation Challenges for Future Accelerator Experiments
Authors: Apostolakis John , Bandieramonte Marilena , Banerjee Sunanda , Bartosik Nazar , Corti Gloria , Cosmo Gabriele , Elvira V. Daniel , Evans Thomas , Gheata Andrei , Pagan Griso Simone , Ivantchenko Vladimir , Jones Christopher , Klute Markus , Leggett Charles , Morgan Ben , Novak Tadej , Pedro Kevin , Paganetti Harald
Published: June 2022

Detector simulation is a key component for studies on prospective future high-energy colliders, the design, optimization, testing and operation of particle physics experiments, and the analysis of the data collected to perform physics measurements. This review starts from the current state of the art technology applied to detector simulation in high-energy physics and elaborates on the evolution of software tools developed to address the challenges posed by future accelerator programs beyond the HL-LHC era, into the 2030–2050 period. New accelerator, detector, and computing technologies set the stage for an exercise in how detector simulation will serve the needs of the high-energy physics programs of the mid 21st century, and its potential impact on other research domains.
N-3-Oxo-Octanoyl Homoserine Lactone Primes Plant Resistance Against Necrotrophic Pathogen Pectobacterium carotovorum by Coordinating Jasmonic Acid and Auxin-Signaling Pathways
Authors: Liu Fang , Zhao Qian , Jia Zhenhua , Zhang Siyuan , Wang Juan , Song Shuishan , Jia Yantao
Published: June 2022

Many Gram-negative bacteria use small signal molecules, such as N-acyl-homoserine lactones (AHLs), to communicate with each other and coordinate their collective behaviors. Recently, increasing evidence has demonstrated that long-chained quorum-sensing signals play roles in priming defense responses in plants. Our previous work indicated that a short-chained signal, N-3-oxo-octanoyl homoserine lactone (3OC8-HSL), enhanced Arabidopsis resistance to the hemi-biotrophic bacteria Pseudomonas syringae pv. tomato DC3000 through priming the salicylic acid (SA) pathway. Here, we found that 3OC8-HSL could also prime resistance to the necrotrophic bacterium Pectobacterium carotovorum ssp. carotovorum (Pcc) through the jasmonic acid (JA) pathway, and is dependent on auxin responses, in both Chinese cabbage and Arabidopsis. The subsequent Pcc invasion triggered JA accumulation and increased the down-stream genes’ expressions of JA synthesis genes (LOX, AOS, and AOC) and JA response genes (PDF1.2 and VSP2). The primed state was not observed in the Arabidopsis coi1-1 and jar1-1 mutants, which indicated that the primed resistance to Pcc was dependent on the JA pathway. The 3OC8-HSL was not transmitted from roots to leaves and it induced indoleacetic acid (IAA) accumulation and the DR5 and SAUR auxin-responsive genes’ expressions in seedlings. When Arabidopsis and Chinese cabbage roots were pretreated with exogenous IAA (10 μM), the plants had activated the JA pathway and enhanced resistance to Pcc, which implied that the JA pathway was involved in AHL priming by coordinating with the auxin pathway. Our findings provide a new strategy for the prevention and control of soft rot in Chinese cabbage and provide theoretical support for the use of the quorum-sensing AHL signal molecule as a new elicitor.