bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis
Authors: Américo Monique Ferrary , Freitas Andria dos Santos , da Silva Tales Fernando , de Jesus Luís Cláudio Lima , Barroso Fernanda Alvarenga Lima , Campos Gabriela Munis , Santos Rhayane Cristina Viegas , Gomes Gabriel Camargos , Assis Rafael , Ferreira Ênio , Mancha-Agresti Pamela , Laguna Juliana Guimarães , Chatel Jean-Marc , Carvalho Rodrigo Dias de Oliveira , Azevedo Vasco
Published: April 2023

Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.
Enriching the endophytic bacterial microbiota of Ginkgo roots
Authors: Zhang Shuangfei , Sun Chongran , Liu Xueduan , Liang Yili
Published: April 2023

Bacterial endophytes of Ginkgo roots take part in the secondary metabolic processes of the fossil tree and contribute to plant growth, nutrient uptake, and systemic resistance. However, the diversity of bacterial endophytes in Ginkgo roots is highly underestimated due to the lack of successful isolates and enrichment collections. The resulting culture collection contains 455 unique bacterial isolates representing 8 classes, 20 orders, 42 families, and 67 genera from five phyla: Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Deinococcus-Thermus, using simply modified media (a mixed medium without any additional carbon sources [MM)] and two other mixed media with separately added starch [GM] and supplemented glucose [MSM]). A series of plant growth-promoting endophytes had multiple representatives within the culture collection. Moreover, we investigated the impact of refilling carbon sources on enrichment outcomes. Approximately 77% of the natural community of root-associated endophytes were predicted to have successfully cultivated the possibility based on a comparison of the 16S rRNA gene sequences between the enrichment collections and the Ginkgo root endophyte community. The rare or recalcitrant taxa in the root endosphere were mainly associated with Actinobacteria, Alphaproteobacteria, Blastocatellia, and Ktedonobacteria. By contrast, more operational taxonomic units (OTUs) (0.6% in the root endosphere) became significantly enriched in MM than in GM and MSM. We further found that the bacterial taxa of the root endosphere had strong metabolisms with the representative of aerobic chemoheterotrophy, while the functions of the enrichment collections were represented by the sulfur metabolism. In addition, the co-occurrence network analysis suggested that the substrate supplement could significantly impact bacterial interactions within the enrichment collections. Our results support the fact that it is better to use the enrichment to assess the cultivable potential and the interspecies interaction as well as to increase the detection/isolation of certain bacterial taxa. Taken together, this study will deepen our knowledge of the indoor endophytic culture and provide important insights into the substrate-driven enrichment.
Assembly strategies for polyethylene-degrading microbial consortia based on the combination of omics tools and the “Plastisphere”
Authors: Zhang Chengxiao , Mu Yulin , Li Taihua , Jin Feng-Jie , Jin Chun-Zhi , Oh Hee-Mock , Lee Hyung-Gwan , Jin Long
Published: April 2023

Numerous microorganisms and other invertebrates that are able to degrade polyethylene (PE) have been reported. However, studies on PE biodegradation are still limited due to its extreme stability and the lack of explicit insights into the mechanisms and efficient enzymes involved in its metabolism by microorganisms. In this review, current studies of PE biodegradation, including the fundamental stages, important microorganisms and enzymes, and functional microbial consortia, were examined. Considering the bottlenecks in the construction of PE-degrading consortia, a combination of top-down and bottom-up approaches is proposed to identify the mechanisms and metabolites of PE degradation, related enzymes, and efficient synthetic microbial consortia. In addition, the exploration of the plastisphere based on omics tools is proposed as a future principal research direction for the construction of synthetic microbial consortia for PE degradation. Combining chemical and biological upcycling processes for PE waste could be widely applied in various fields to promote a sustainable environment.
Incorporating neurological and behavioral mechanisms of sociality into predator-prey models
Authors: Lichtenstein James L. L. , Schmitz Oswald J.
Published: April 2023

Consumer-resource population models drive progress in predicting and understanding predation. However, they are often built by averaging the foraging outcomes of individuals to estimate per capita functional responses (functions that describe predation rate). Reliance on per-capita functional responses rests on the assumption that that individuals forage independently without affecting each other. Undermining this assumption, extensive behavioral neuroscience research has made clear that facilitative and antagonistic interactions among conspecifics frequently alter foraging through interference competition and persistent neurophysiological changes. For example, repeated social defeats dysregulates rodent hypothalamic signaling, modulating appetite. In behavioral ecology, similar mechanisms are studied under the concept of dominance hierarchies. Neurological and behavioral changes in response to conspecifics undoubtedly play some sort of role in the foraging of populations, but modern predator-prey theory does not explicitly include them. Here we describe how some modern approaches to population modeling might account for this. Further, we propose that spatial predator-prey models can be modified to describe plastic changes in foraging behavior driven by intraspecific interaction, namely individuals switching between patches or plastic strategies to avoid competition. Extensive neurological and behavioral ecology research suggests that interactions among conspecifics help shape populations’ functional responses. Modeling interdependent functional responses woven together by behavioral and neurological mechanisms may thus be indispensable in predicting the outcome of consumer–resource interactions across systems.
Effect of gait training using Welwalk on gait pattern in individuals with hemiparetic stroke: a cross-sectional study
Authors: Ii Takuma , Hirano Satoshi , Imoto Daisuke , Otaka Yohei
Published: April 2023

Introduction

We aimed to explore the effect of gait training using Welwalk on gait patterns by comparing differences in gait patterns between robotic-assisted gait training using Welwalk and gait training using an orthosis in individuals with hemiparetic stroke.

Methods

This study included 23 individuals with hemiparetic stroke who underwent gait training with Welwalk combined with overground gait training using an orthosis. Three-dimensional motion analysis on a treadmill was performed under two conditions for each participant: during gait training with Welwalk and with the ankle-foot orthosis. The spatiotemporal parameters and gait patterns were compared between the two conditions.

Results

The affected step length was significantly longer, the step width was significantly wider, and the affected single support phase ratio was significantly higher in the Welwalk condition than in the orthosis condition. The index values of abnormal gait patterns were significantly lower while using Welwalk than in the orthosis condition. The following four indices were lower in the Welwalk condition: contralateral vaulting, insufficient knee flexion, excessive hip external rotation during the paretic swing phase, and paretic forefoot contact.

Discussion

Gait training using Welwalk increased the affected step length, step width, and single support phase while suppressing abnormal gait patterns as compared to gait training using the ankle-foot orthosis. This study suggests that gait training using Welwalk may promote a more efficient gait pattern reacquisition that suppresses abnormal gait patterns.

Trial registration

Prospectively registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp; jRCTs042180152).
Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity
Authors: Dane Therese L. , Gill Anna L. , Vieira Fernando G. , Denton Kyle R.
Published: April 2023

Introduction

Intronic repeat expansions in the C9orf72 gene are the most frequent known single genetic causes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeat expansions are believed to result in both loss-of-function and toxic gain-of-function. Gain-of-function results in the production of toxic arginine-rich dipeptide repeat proteins (DPRs), namely polyGR and polyPR. Small-molecule inhibition of Type I protein arginine methyltransferases (PRMTs) has been shown to protect against toxicity resulting from polyGR and polyPR challenge in NSC-34 cells and primary mouse-derived spinal neurons, but the effect in human motor neurons (MNs) has not yet been explored.

Methods

To study this, we generated a panel of C9orf72 homozygous and hemizygous knockout iPSCs to examine the contribution of C9orf72 loss-of-function toward disease pathogenesis. We differentiated these iPSCs into spinal motor neurons (sMNs).

Results

We found that reduced levels of C9orf72 exacerbate polyGR15 toxicity in a dose-dependent manner. Type I PRMT inhibition was able to partially rescue polyGR15 toxicity in both wild-type and C9orf72-expanded sMNs.

Discussion

This study explores the interplay of loss-of-function and gain-of-function toxicity in C9orf72 ALS. It also implicates type I PRMT inhibitors as a possible modulator of polyGR toxicity.
Thalamocortical circuits for the formation of hierarchical pathways in the mammalian visual cortex
Authors: Murakami Tomonari , Ohki Kenichi
Published: April 2023

External sensory inputs propagate from lower-order to higher-order brain areas, and the hierarchical neural network supporting this information flow is a fundamental structure of the mammalian brain. In the visual system, multiple hierarchical pathways process different features of the visual information in parallel. The brain can form this hierarchical structure during development with few individual differences. A complete understanding of this formation mechanism is one of the major goals of neuroscience. For this purpose, it is necessary to clarify the anatomical formation process of connections between individual brain regions and to elucidate the molecular and activity-dependent mechanisms that instruct these connections in each areal pair. Over the years, researchers have unveiled developmental mechanisms of the lower-order pathway from the retina to the primary visual cortex. The anatomical formation of the entire visual network from the retina to the higher visual cortex has recently been clarified, and higher-order thalamic nuclei are gaining attention as key players in this process. In this review, we summarize the network formation process in the mouse visual system, focusing on projections from the thalamic nuclei to the primary and higher visual cortices, which are formed during the early stages of development. Then, we discuss how spontaneous retinal activity that propagates through thalamocortical pathways is essential for the formation of corticocortical connections. Finally, we discuss the possible role of higher-order thalamocortical projections as template structures in the functional maturation of visual pathways that process different visual features in parallel.
Comparison of neostigmine and sugammadex for hemodynamic parameters in neurointerventional anesthesia
Authors: Tsai Yu-Hsun , Chen Chun-Yu , Wong Ho-Fai , Chou An-Hsun
Published: April 2023

Introduction

Hemodynamic stability is important during neurointerventional procedures. However, ICP or blood pressure may increase due to endotracheal extubation. The aim of this study was to compare the hemodynamic effects of sugammadex and neostigmine with atropine in neurointerventional procedures during emergence from anesthesia.

Methods

Patients undergoing neurointerventional procedures were allocated to the sugammadex group (Group S) and the neostigmine group (Group N). Group S was administered IV 2 mg/kg sugammadex when a train-of-four (TOF) count of 2 was present, and Group N was administered neostigmine 50 mcg/kg with atropine 0.2 mg/kg at a TOF count of 2. We recorded heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure (MAP), and peripheral arterial oxygen saturation during administration of the reverse agent and at 2, 5, 10, 15, 30, 120 min, and 24 h thereafter. The primary outcome was blood pressure and heart rate change after the reversal agent was given. The secondary outcomes were systolic blood pressure variability standard deviation (a measure of the amount of variation or dispersion of a set of values), systolic blood pressure variability-successive variation (square root of the average squared difference between successive blood pressure measurements), nicardipine use, time-to-TOF ratio ≥0.9 after the administration of reversal agent, and time from the administration of the reversal agent to tracheal extubation.

Results

A total of 31 patients were randomized to sugammadex, and 30 patients were randomized to neostigmine. Except for anesthesia time, there were no significant differences in any of the clinical characteristics between the two groups. The results demonstrated that the increase in MAP from period A to B was significantly greater in Group N than in Group S (regression coefficient = −10, 95% confidence interval = −17.3 to −2.7, P = 0.007). The MAP level was significantly increased from period A to B in the neostigmine group (95.1 vs. 102.4 mm Hg, P = 0.015), but it was not altered in Group S. In contrast, the change in HR from periods A to B was not significantly different between groups.

Conclusion

We suggest that sugammadex is a better option than neostigmine in interventional neuroradiological procedures due to the shorter extubation time and more stable hemodynamic change during emergence.
Review of rehabilitation protocols for brachial plexus injury
Authors: Li Haijun , Chen Jinxiu , Wang Juehan , Zhang Tianfang , Chen Zuobing
Published: April 2023

Brachial plexus injury (BPI) is one of the most serious peripheral nerve injuries, resulting in severe and persistent impairments of the upper limb and disability in adults and children alike. With the relatively mature early diagnosis and surgical technique of brachial plexus injury, the demand for rehabilitation treatment after brachial plexus injury is gradually increasing. Rehabilitation intervention can be beneficial to some extent during all stages of recovery, including the spontaneous recovery period, the postoperative period, and the sequelae period. However, due to the complex composition of the brachial plexus, location of injury, and the different causes, the treatment varies. A clear rehabilitation process has not been developed yet. Rehabilitation therapy that has been widely studied focusing on exercise therapy, sensory training, neuroelectromagnetic stimulation, neurotrophic factors, acupuncture and massage therapy, etc., while interventions like hydrotherapy, phototherapy, and neural stem cell therapy are less studied. In addition, rehabilitation methods in some special condition and group often neglected, such as postoperative edema, pain, and neonates. The purpose of this article is to explore the potential contributions of various methods to brachial plexus injury rehabilitation and to provide a concise overview of the interventions that have been shown to be beneficial. The key contribution of this article is to form relatively clear rehabilitation processes based on different periods and populations, which provides an important reference for the treatment of brachial plexus injuries.
Case report: Novel compound heterozygous variants in the PANK2 gene in a Chinese patient diagnosed with ASD and ADHD
Authors: Dong Siqi , Tuo Ya , Qi Zihan , Zhang Yuanfeng , Liu Xiaoni , Huang Ping , Chen Xiangjun
Published: April 2023

The PANK2 gene, which encodes mitochondrial pantothenate kinase 2 protein, is the disease-causing gene for pantothenate kinase-associated neurodegeneration (PKAN). We report a case of atypical PKAN with autism-like symptoms presenting with speech difficulties, psychiatric symptoms, and mild developmental retardation. Magnetic resonance imaging (MRI) of the brain showed the typical “eye-of-the-tiger” sign. Whole-exon sequencing revealed PANK2 p.Ile501Asn/p.Thr498Ser compound heterozygous variants. Our study highlights the phenotypic heterogeneity of PKAN, which can be confused with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) and requires careful clinical identification.
Does MRI add value in selecting patients for thrombectomy beyond the 6 h window? A matched-control analysis
Authors: Cheng Huiran , Yu Zequan , Ma Gaoting , Wang Anxin , Jia Baixue , Tong Xu , Ma Ning , Gao Feng , Mo Dapeng , Song Ligang , Xuan Sun , Huo Xiaochuan , Zhang Zi-Xian , Ren Zeguang , Miao Zhongrong
Published: April 2023

Background

Controversy exists regarding the need of advanced imaging for patient selection in the extended window.

Aims

To analyze the effect of initial imaging modalities on clinical outcomes of patients underwent MT in the extended window.

Methods

This was a retrospective analysis of a prospective registry, the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry which was conducted at 111 hospitals between November 2017 and March 2019 in China. Primary study cohort and Guideline like cohort were identified, in each cohort, two imaging modalities for patient selection in 6 to 24 h window were defined: (1) NCCT ± CTA, (2) MRI. Guideline-like cohort were further screened based on key features of the DAWN and DEFUSE 3 trials. The primary outcome was 90 day mRS. The safety outcomes were sICH, any ICH and 90-day mortality.

Results

After adjusting for covariates, there were no significant differences in 90 day mRS or any safety outcomes between two imaging modalities groups in both cohorts. All outcome measures of mixed-effects logistic regression model were consistent with propensity score matching model.

Conclusion

Our results indicate that patients presented with anterior large vessel occlusion in the extended time window can potentially benefit from MT even in the absence of MRI selection. This conclusion needs to be verified by the prospective randomized clinical trials.
Genetics of Spontaneous Intracerebral Hemorrhage: Risk and Outcome
Authors: Guo Hongxiu , You Mingfeng , Wu Jiehong , Chen Anqi , Wan Yan , Gu Xinmei , Tan Senwei , Xu Yating , He Quanwei , Hu Bo
Published: April 2023

Spontaneous intracerebral hemorrhage (ICH) is a common fatal event without an effective therapy. Of note, some familial aggregation and inherited tendency is found in ICH and heritability estimates indicate that genetic variations contribute substantially to ICH risk and outcome. Thus, identification of genetic variants that affect the occurrence and outcome may be helpful for ICH prevention and therapy. There are several reviews summarizing numerous genetic variants associated with the occurrence of ICH before, but genetic variants contributing to location distribution and outcome have rarely been introduced. Here, we summarize the current knowledge of genetic variants and pay special attention to location distribution and outcome. So far, investigations have reveled variations in APOE, GPX1, CR1, ITGAV, PRKCH, and 12q21.1 are associated with lobar ICH (LICH), while ACE, COL4A2, 1q22, TIMP1, TIMP2, MMP2, MMP9, and TNF are associated with deep ICH (DICH). Moreover, variations in APOE, VWF, 17p12, HP, CFH, IL6ST, and COL4A1 are possible genetic contributors to ICH outcome. Furthermore, the prospects for ICH related genetic studies from the bench to the bed were discussed.
Whole-brain imaging of freely-moving zebrafish
Authors: Hasani Hamid , Sun Jipeng , Zhu Shuyu I. , Rong Qiangzhou , Willomitzer Florian , Amor Rumelo , McConnell Gail , Cossairt Oliver , Goodhill Geoffrey J.
Published: April 2023

One of the holy grails of neuroscience is to record the activity of every neuron in the brain while an animal moves freely and performs complex behavioral tasks. While important steps forward have been taken recently in large-scale neural recording in rodent models, single neuron resolution across the entire mammalian brain remains elusive. In contrast the larval zebrafish offers great promise in this regard. Zebrafish are a vertebrate model with substantial homology to the mammalian brain, but their transparency allows whole-brain recordings of genetically-encoded fluorescent indicators at single-neuron resolution using optical microscopy techniques. Furthermore zebrafish begin to show a complex repertoire of natural behavior from an early age, including hunting small, fast-moving prey using visual cues. Until recently work to address the neural bases of these behaviors mostly relied on assays where the fish was immobilized under the microscope objective, and stimuli such as prey were presented virtually. However significant progress has recently been made in developing brain imaging techniques for zebrafish which are not immobilized. Here we discuss recent advances, focusing particularly on techniques based on light-field microscopy. We also draw attention to several important outstanding issues which remain to be addressed to increase the ecological validity of the results obtained.
Functional connectivity changes are correlated with sleep improvement in chronic insomnia patients after rTMS treatment
Authors: Zhu Lin , Dang Ge , Wu Wei , Zhou Junhong , Shi Xue , Su Xiaolin , Ren Huixia , Pei Zian , Lan Xiaoyong , Lian Chongyuan , Xie Peng , Guo Yi
Published: April 2023

Background

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.

Objective

This study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.

Methods

Thirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).

Results

After treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8–10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.

Conclusion

Based on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.
The effects of blurred visual inputs with different levels on the cerebral activity during free level walking
Authors: Ao Mingxin , Ren Shuang , Yu Yuanyuan , Huang Hongshi , Miao Xin , Ao Yingfang , Wang Wei
Published: April 2023

Objective

The aim of this study was to evaluate the effects of blurred vision on electrocortical activities at different levels during walking.

Materials and methods

A total of 22 healthy volunteers (all men; mean age: 24.4 ± 3.9 years) underwent an electroencephalography (EEG) test synchronous with free level walking. Visual status was simulated by goggles covered by the occlusion foil targeted at a Snellen visual acuity of 20/60 (V0.3), 20/200 (V0.1), and light perception (V0). At each of these conditions, the participants completed barefoot walking for five blocks of 10 m. The EEG signals were recorded by a wireless EEG system with electrodes of interest, namely, Cz, Pz, Oz, O1, and O2. The gait performances were assessed by the Vicon system.

Results

During walking with normal vision (V1.0), there were cerebral activities related to visual processing, characterized as higher spectral power of delta (Oz and O2 vs. Cz, Pz, and O1, p ≤ 0.033) and theta (Oz vs. Cz and O1, p = 0.044) bands in occipital regions. Moderately blurred vision (V0.3) would attenuate the predominance of delta- and theta-band activities at Oz and O2, respectively. At the statuses of V0.1 and V0, the higher power of delta (at V0.1 and V0, Oz, and O2 vs. Cz, Pz, and O1, p ≤ 0.047) and theta bands (at V0.1, Oz vs. Cz, p = 0.010; at V0, Oz vs. Cz, Pz, and O1, p ≤ 0.016) emerged again. The cautious gait pattern, characterized by a decrease in gait speed (p < 0.001), a greater amplitude of deviation from the right ahead (p < 0.001), a prolonged stance time (p = 0.001), a restricted range of motion in the hip on the right side (p ≤ 0.010), and an increased knee flexion during stance on the left side (p = 0.014), was only detected at the status of V0. The power of the alpha band at the status of V0 was higher than that at V1.0, V0.3, and V0.1 (p ≤ 0.011).

Conclusion

Mildly blurred visual inputs would elicit generalization of low-frequency band activity during walking. In circumstance to no effective visual input, locomotor navigation would rely on cerebral activity related to visual working memory. The threshold to trigger the shift might be the visual status that is as blurred as the level of Snellen visual acuity of 20/200.
Peroxisomal defects in microglial cells induce a disease-associated microglial signature
Authors: Raas Quentin , Tawbeh Ali , Tahri-Joutey Mounia , Gondcaille Catherine , Keime Céline , Kaiser Romain , Trompier Doriane , Nasser Boubker , Leoni Valerio , Bellanger Emma , Boussand Maud , Hamon Yannick , Benani Alexandre , Di Cara Francesca , Truntzer Caroline , Cherkaoui-Malki Mustapha , Andreoletti Pierre , Savary Stéphane
Published: April 2023

Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders.
Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1
Authors: Peng Mei , Wu Jintao , Wang Weifan , Liao Tianlong , Xu Simeng , Xiao Di , He Zuping , Yang Xiaoping
Published: April 2023

Purpose

Spermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. B-lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both in vitro and in vivo.

Methods

Methyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2′-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality in vivo.

Results

Analysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209.

Conclusion

Analysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.
Measurement of sarcopenia in lung cancer inpatients and its association with frailty, nutritional risk, and malnutrition
Authors: Wang Fang , Zhen Hong-nan , Wang Han-ping , Yu Kang
Published: April 2023

Background

Sarcopenia, frailty, and malnutrition are associated with undesirable clinical outcomes in cancer patients. Sarcopenia-related measurements may be promising fast biomarkers for frailty. Our objectives were to assess the prevalence of nutritional risk, malnutrition, frailty, and sarcopenia in lung cancer inpatients, and describe the relationship of them.

Methods

Stage III and IV lung cancer inpatients were recruited before chemotherapy. The skeletal muscle index (SMI) was assessed by multi-frequency bioelectric impedance analysis (m-BIA). Sarcopenia, frailty, nutritional risk, and malnutrition were diagnosed according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019), Fried Frailty Phenotype (FFP), nutritional risk screening-2002 (NRS-2002), and Global Leadership Initiative on Malnutrition criteria (GLIM), and correlation analysis was performed between them with Pearson’s r correlation coefficients. A univariate and multivariate logistic regression analysis was conducted for all patients, gender and age-stratified subgroups to obtain odds ratios (ORs) and 95% confidence intervals (95%CIs).

Results

The cohort included 97 men (77%) and 29 women (23%), with mean age of 64.8 ± 8.7 years. Among the 126 patients, 32 (25.4%) and 41 (32.5%) had sarcopenia and frailty, and the prevalence of nutritional risk and malnutrition was 31.0% (n = 39) and 25.4% (n = 32). Adjusted for age and gender, SMI was correlated with FFP (r = −0.204, p = 0.027), and did not remain significantly when stratified by gender. Stratification according to age revealed in ≥65-years-old population, SMI and FFP were significantly correlated (r = −0.297, p = 0.016), which is not seen in <65-years-old group (r = 0.048, p = 0.748). The multivariate regression analysis showed FFP, BMI, and ECOG were the independent variables associated with sarcopenia (OR 1.536, 95%CI 1.062–2.452, p = 0.042; OR 0.625, 95%CI 0.479–0.815, p = 0.001; OR 7.286, 95%CI 1.779–29.838, p = 0.004).

Conclusion

Comprehensively assessed sarcopenia is independently associated with frailty based on FFP questionnaire, BMI, and ECOG. Therefore, sarcopenia assessment including m-BIA based SMI, and muscle strength and function could be used to indicate frailty to help select the targeting patients for care. Moreover, in addition to muscle mass, muscle quality should not be ignored in clinical practice.
Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects
Authors: Guo Bin , Chen Qian , Liu Zhicheng , Chen Xiaoping , Zhu Peng
Published: April 2023

Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
Application of family-centered empowerment model in primary caregivers of premature infants: A quasi-experimental study
Authors: Dai Kun , Fan Xinqi , Shi Huan , Xiong Xiaoju , Ding Lingli , Yu Yaqi , Yu Genzhen , Wang Suqing
Published: April 2023

Objective

To explore the effect of the family-centered empowerment model (FECM) on reducing anxiety, improving care ability, and readiness for hospital discharge of main caregivers of preterm infants.

Methods

The primary caregivers of preterm infants who were admitted to the Neonatal intensive care Unit (NICU) of our center from September 2021 to April 2022 were selected as the research objects. According to the wishes of the primary caregivers of preterm infants, they were divided into group A (FECM group) and group B (non-FECM group). The intervention effects were evaluated with the Anxiety Screening Scale (GAD-7), the Readiness for Hospital Discharge Scale-Parent Version (RHDS-Parent Form), and the Primary Caregivers of Premature Infants Assessment of Care Ability Questionnaire.

Results

Before the intervention, there was no statistically significant difference in the general information, anxiety screening, the scores of each dimension, and total score of the comprehensive ability of the main caregivers, and the score of caregiver preparedness between the two groups (P > 0.05). After the intervention, there were statistically significant differences in the anxiety screening, the total score and total score of each dimension of the care ability, and the score of caregiver preparedness between the two groups (P < 0.05).

Conclusions

FECM can effectively reduce the anxiety of primary caregivers of premature infants and improve their readiness for hospital discharge and care ability. To improve the quality of life of premature infants by implementing personalized training, care guidance, and peer support.
Predictive factors of extubation failure in pediatric cardiac intensive care unit: A single-center retrospective study from Thailand
Authors: Saengsin Kwannapas , Sittiwangkul Rekwan , Borisuthipandit Thirasak , Trongtrakul Konlawij , Tanasombatkul Krittai , Phanacharoensawad Thanaporn , Moonsawat Guanoon , Phinyo Phichayut
Published: April 2023

Introduction/objective

Extubation failure increases morbidity and mortality in pediatric cardiac patients, a unique population including those with congenital heart disease or acquired heart disease. This study aimed to evaluate the predictive factors of extubation failure in pediatric cardiac patients and to determine the association between extubation failure and clinical outcomes.

Methods

We conducted a retrospective study in the pediatric cardiac intensive care unit (PCICU) of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, from July 2016 to June 2021. Extubation failure was defined as the re-insertion of the endotracheal tube within 48 hours after extubation. Multivariable log-binomial regression with generalized estimating equations (GEE) was performed to explore the predictive factors associated with extubation failure.

Results

We collected 318 extubation events from 246 patients. Of these, 35 (11%) events were extubation failures. In physiologic cyanosis, the extubation failure group had significantly higher SpO2 than the extubation success group (P < 0.001). The predictive factors associated with extubation failure included a history of pneumonia before extubation (RR 3.09, 95% CI 1.54–6.23, P = 0.002), stridor after extubation (RR 2.57, 95% CI 1.44–4.56, P = 0.001), history of re-intubation (RR 2.24, 95% CI 1.21–4.12, P = 0.009), and palliative surgery (RR 1.87, 95% CI 1.02–3.43, P = 0.043).

Conclusion

Extubation failure was identified in 11% of extubation attempts in pediatric cardiac patients. The extubation failure was associated with a longer duration of PCICU stay but not with mortality. Patients with a history of pneumonia before extubation, history of re-intubation, post-operative palliative surgery, and post-extubation stridor should receive careful consideration before extubation and close monitoring afterward. Additionally, patients with physiologic cyanosis may require balanced circulation via regulated SpO2.
Establishment of a 7-gene prognostic signature based on oxidative stress genes for predicting chemotherapy resistance in pancreatic cancer
Authors: Zhang Shengmin , Yang Jianrong , Wu Hongsheng , Cao Tiansheng , Ji Tengfei
Published: April 2023

Background: Oxidative stress is involved in regulating various biological processes in human cancers. However, the effect of oxidative stress on pancreatic adenocarcinoma (PAAD) remained unclear.

Methods: Pancreatic cancer expression profiles from TCGA were downloaded. Consensus ClusterPlus helped classify molecular subtypes based on PAAD prognosis-associated oxidative stress genes. Limma package filtered differentially expressed genes (DEGs) between subtypes. A multi-gene risk model was developed using Lease absolute shrinkage and selection operator (Lasso)-Cox analysis. A nomogram was built based on risk score and distinct clinical features.

Results: Consistent clustering identified 3 stable molecular subtypes (C1, C2, C3) based on oxidative stress-associated genes. Particularly, C3 had the optimal prognosis with the greatest mutation frequency, activate cell cycle pathway in an immunosuppressed status. Lasso and univariate cox regression analysis selected 7 oxidative stress phenotype-associated key genes, based on which we constructed a robust prognostic risk model independent of clinicopathological features with stable predictive performance in independent datasets. High-risk group was found to be more sensitive to small molecule chemotherapeutic drugs including Gemcitabine, Cisplatin, Erlotinib and Dasatinib. The 6 of 7 genes expressions were significantly associated with methylation. Survival prediction and prognostic model was further improved through a decision tree model by combining clinicopathological features with RiskScore.

Conclusion: The risk model containing seven oxidative stress-related genes may have a greater potential to assist clinical treatment decision-making and prognosis determination.
Synergistic antitumor activity of regorafenib and rosuvastatin in colorectal cancer
Authors: Yuan Tao , Wu Ruilin , Wang Weihua , Liu Yue , Kong Wencheng , Yang Bo , He Qiaojun , Zhu Hong
Published: April 2023

Introduction: Colorectal cancer is one of the most prevalent life-threatening malignant tumors with high incidence and mortality. However, the efficacy of current therapeutic regimens is very limited. Regorafenib has been approved for second- or third-line treatment of patients who are refractory to standard chemotherapy diagnosed with metastatic colorectal cancer, but its clinical efficacy needs to be further improved. Accumulating evidence demonstrates that statins also possess potent anticancer activities. However, whether regorafenib and statins pose synergistic anticancer effects in colorectal cancer is still unclear.

Methods: Sulforhodamine B (SRB) assays were applied to evaluate the anti-proliferative activity of regorafenib or/and rosuvastatin in vitro, and immunoblotting analysis were applied to detect the effects of regorafenib/rosuvastatin combined treatment on mitogen-activated protein kinase (MAPK) signaling and apoptosis-related proteins. MC38 tumors were applied to investigate the synergistic anticancer effects of regorafenib in combination with rosuvastatin in vivo.

Results: We found that regorafenib in combination with rosuvastatin exerted significant synergistic inhibition against colorectal cancer growth in vitro and in vivo. Mechanistically, regorafenib and rosuvastatin combination synergistically suppressed MAPK signaling, a crucial signaling pathway promoting cell survival, as indicated by the reduction of phosphorylated MEK/ERK. In addition, regorafenib in combination with rosuvastatin synergistically induced the apoptosis of colorectal cancer in vitro and in vivo.

Discussion: Our study demonstrated the synergistic anti-proliferative and pro-apoptotic effects of regorafenib/rosuvastatin combined treatment in colorectal cancer in vitro/vivo and might potentially be evaluated as a novel combination regimen for clinical treatment of colorectal cancer.
Unraveling the mystery of canopy dieback caused by citrus disease Huanglongbing and its link to hypoxia stress
Authors: Shahzad Faisal , Tang Lisa , Vashisth Tripti
Published: April 2023

Devastating citrus disease Huanglongbing (HLB) is without existing cures. Herein, we present results demonstrating the possible mechanisms (hypoxia stress) behind HLB-triggered shoot dieback by comparing the transcriptomes, hormone profiles, and key enzyme activities in buds of severely and mildly symptomatic ‘Hamlin’ sweet orange (Citrus sinensis). Within six months (October – May) in field conditions, severe trees had 23% bud dieback, greater than mild trees (11%), with a concomitant reduction in canopy density. In February, differentially expressed genes (DEGs) associated with responses to osmotic stress, low oxygen levels, and cell death were upregulated, with those for photosynthesis and cell cycle downregulated in severe versus mild trees. For severe trees, not only were the key markers for hypoxia, including anaerobic fermentation, reactive oxygen species (ROS) production, and lipid oxidation, transcriptionally upregulated, but also alcohol dehydrogenase activity was significantly greater compared to mild trees, indicating a link between bud dieback and hypoxia. Tricarboxylic acid cycle revival, given the upregulation of glutamate dehydrogenase and alanine aminotransferase DEGs, suggests that ROS may also be generated during hypoxia-reoxygenation. Greater (hormonal) ratios of abscisic acid to cytokinins and jasmonates and upregulated DEGs encoding NADPH oxidases in severe versus mild trees indicate additional ROS production under limited oxygen availability due to stomata closure. Altogether, our results provided evidence that as HLB progresses, excessive ROS produced in response to hypoxia and during hypoxia-reoxygenation likely intensify the oxidative stress in buds leading to cell death, contributing to marked bud and shoot dieback and decline of the severely symptomatic sweet orange trees.
Predicting grade school scientific literacy from aspects of the early home science environment
Authors: Bae Jihye , Shavlik Margaret , Shatrowsky Christine E. , Haden Catherine A. , Booth Amy E.
Published: April 2023

Fostering scientific literacy has become an increasingly salient goal as evidence accumulates regarding the early emergence of foundational skills and knowledge in this domain, as well as their relation to long-term success and engagement. Despite the potential that the home context has for nurturing early scientific literacy, research specifying its role has been limited. In this longitudinal study, we examined associations between children’s early science-related experiences at home and their subsequent scientific literacy. Following on our previous work, we specifically considered parent causal-explanatory talk, as well as the degree to which parents facilitate access to science-related materials and experiences. A group of 153 children from diverse backgrounds were evaluated across 5 annual waves of data collection from preschool entry (Mage = 3.41) through first grade (Mage = 7.92). Results demonstrate that parent invitations for children to explain causal phenomena had strong concurrent relations to scientific literacy but showed little relation to subsequent literacy. In contrast, the broader home science environment at preschool entry, particularly in the form of exposure to science-related activities, predicted scientific literacy over the next 4 years. The directionality and specificity of these relations were clarified through the inclusion of measures of cognitive and broader home experiences as controls in regression analyses. Overall, our investigation revealed that exposure to science-related input provided by parents has particularly powerful potential for shaping scientific literacy when children are very young. Implications for parent-focused interventions that promote science literacy are discussed.