bluuebunny/crossref_metadata_2025 huggingface dataset:
How elevated nitrogen load affects bacterial community structure and nitrogen cycling services in coastal water
Authors: Lo Linus Shing Him , Xu Zhimeng , Lee Sangwook Scott , Lau Wing Keung , Qiu Jian-Wen , Liu Hongbin , Qian Pei-Yuan , Cheng Jinping
Published: December 2022

Nutrient pollution in the coastal environment has been accelerated by progressively intensifying aquaculture activities. Excessive nutrients can lead to coastal eutrophication with serious economic and ecological consequences. In this study, we studied coastal planktonic microbial community over a year to understand the aquaculture impact on coastal water quality and function. We observed increased total inorganic nitrogen concentrations in active fish farms to favor the diverse Alpha- and Gammaproteobacteria. Bacterial community alpha diversity in fish farms was positively correlated with total inorganic nitrogen, and active fish farming co-influenced the bacterial structural composition and regional beta diversity. By analyzing the nitrogen cycle-related functional compositions and pathways using PICRUSt2 prediction on inferred genomes, we identified the contribution of over 600 bacterial species to four major pathways. Enhanced nitrogen load in active fish farms was positively correlated with elevated dissimilatory nitrate reduction and denitrification pathway abundances. Fallowed fish farms were characterized by a predicted high abundance of nirA and narB genes contributing to assimilatory nitrate reduction pathway due to the prevalence of Cyanobacteria. Overall, these results suggested active operation and short hiatus in coastal aquaculture practices could rapidly impact planktonic bacterial communities and further influence nitrogen cycling and associated processes. These findings will improve the understanding of the responses and interactions between microbiome and aquaculture activities. In a world of increasing aquaculture demands, this work has important implications for sustainable water resource management and development.
A diagnostic accuracy study comparing RNA LAMP, direct LAMP, and rapid antigen testing from nasopharyngeal swabs
Authors: Cao Guojun , Lin Ke , Ai Jingwen , Cai Jianpeng , Zhang Haocheng , Yu Yiqi , Liu Qihui , Zhang Xinyun , Zhang Yi , Fu Zhangfan , Song Jieyu , Wang Hongyu , Yuan Guanmin , Wang Sen , Guan Ming , Zhang Wenhong
Published: December 2022

Introduction

During the coronavirus disease 2019 (COVID-19) pandemic, the early detection and isolation of individuals infected with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) through mass testing can effectively prevent disease transmission. SARS-CoV-2 nucleic acid rapid detection based on loop-mediated isothermal amplification (LAMP) may be appropriate to include in testing procedures.

Methods

We used 860 nasopharyngeal specimens from healthcare workers of Huashan Hospital and COVID-19 patients collected from April 7th to 21st, 2022, to assess the clinical diagnostic performance of the LAMP assay marketed by Shanghai GeneSc Biotech and compared it to the result of a rapid antigen test (RAT) head-to-head.

Results

Overall, the diagnostic performance of LAMP assay and RAT were as follows. The LAMP assay represented higher sensitivity and specificity than RAT, especially in the extracted RNA samples. The sensitivity was 70.92% and 92.91% for direct LAMP and RNA-LAMP assay, respectively, while the specificity was 99.86% and 98.33%. The LAMP assay had overall better diagnostic performance on the specimens with relatively lower Ct values or collected in the early phase (≤7 days) of COVID-19. The combination of LAMP assay and RAT improved diagnostic efficiency, providing new strategies for rapidly detecting SARS-CoV-2.

Conclusion

The LAMP assay are suitable for mass screenings of SARS-CoV-2 infections in the general population.
Soybean continuous cropping affects yield by changing soil chemical properties and microbial community richness
Authors: Li Yan , Shi Chuanqi , Wei Dan , Gu Xuejia , Wang Yufeng , Sun Lei , Cai Shanshan , Hu Yu , Jin Liang , Wang Wei
Published: December 2022

In agroecosystems, different cropping patterns cause changes in soil physicochemical properties and thus in microbial communities, which in turn affect crop yields. In this study, the yields of soybean continuous cropping for 5 years (C5), 10 years (C10), and 20 years (C20) and of soybean-corn rotational cropping (R) treatments were determined, and samples of the tillage layer soil were collected. High-throughput sequencing technology was used to analyze the diversity and composition of the soil bacterial and fungal communities. The factors influencing microbial communities, along with the effects of these communities and those of soil chemical indexes on yield, were further evaluated. The results showed that the community richness index of bacteria was higher in C20 than in R and that of fungi was highest in C5. The differences in the bacterial and fungal communities diversity indexes were not significant among the different continuous cropping treatments, respectively. The soil microbial community composition of all continuous cropping treatments differed significantly from R. The dominant bacterial phylum was Actinobacteriota and the dominant fungal phylum was Ascomycota. The relative abundance of Fusarium did not differ significantly among the continuous cropping treatments, while that of the plant pathogen fungi Lectera sp., Plectosphaerella sp., and Volutella sp. increased with continuous cropping years. Soil pH, SOM, N, and TP had significant effects on both bacterial and fungal communities, and TK and C/N had highly significant effects on fungal communities. The yield of C5 was significantly lower than that of R, and the differences in yield between C10, C20, and R were not significant. TN, TP, and pH had significant effects on yield, and fungal community abundance had a greater negative effect on yield than bacterial community abundance.
The COVID-19 explorer—An integrated, whole patient knowledge model of COVID-19 disease
Authors: Brock Stephan , Soldatos Theodoros G. , Jackson David B. , Diella Francesca , Hornischer Klaus , Schäfer Anne , Hoerstrup Simon P. , Emmert Maximilian Y.
Published: December 2022

Since early 2020 the COVID-19 pandemic has paralyzed the world, resulting in more than half a billion infections and over 6 million deaths within a 28-month period. Knowledge about the disease remains largely disjointed, especially when considering the molecular mechanisms driving the diversity of clinical manifestations and symptoms. Despite the recent availability of vaccines, there remains an urgent need to develop effective treatments for cases of severe disease, especially in the face of novel virus variants. The complexity of the situation is exacerbated by the emergence of COVID-19 as a complex and multifaceted systemic disease affecting independent tissues and organs throughout the body. The development of effective treatment strategies is therefore predicated on an integrated understanding of the underlying disease mechanisms and their potentially causative link to the diversity of observed clinical phenotypes. To address this need, we utilized a computational technology (the Dataome platform) to build an integrated clinico-molecular view on the most important COVID-19 clinical phenotypes. Our results provide the first integrated, whole-patient model of COVID-19 symptomatology that connects the molecular lifecycle of SARS-CoV-2 with microvesicle-mediated intercellular communication and the contact activation and kallikrein-kinin systems. The model not only explains the clinical pleiotropy of COVID-19, but also provides an evidence-driven framework for drug development/repurposing and the identification of critical risk factors. The associated knowledge is provided in the form of the open source COVID-19 Explorer (https://covid19.molecularhealth.com), enabling the global community to explore and analyze the key molecular features of systemic COVID-19 and associated implications for research priorities and therapeutic strategies. Our work suggests that knowledge modeling solutions may offer important utility in expediting the global response to future health emergencies.
Biological age and environmental risk factors for dementia and stroke: Molecular mechanisms
Authors: Knobel Pablo , Litke Rachel , Mobbs Charles V.
Published: December 2022

Since the development of antibiotics and vaccination, as well as major improvements in public hygiene, the main risk factors for morbidity and mortality are age and chronic exposure to environmental factors, both of which can interact with genetic predispositions. As the average age of the population increases, the prevalence and costs of chronic diseases, especially neurological conditions, are rapidly increasing. The deleterious effects of age and environmental risk factors, develop chronically over relatively long periods of time, in contrast to the relatively rapid deleterious effects of infectious diseases or accidents. Of particular interest is the hypothesis that the deleterious effects of environmental factors may be mediated by acceleration of biological age. This hypothesis is supported by evidence that dietary restriction, which universally delays age-related diseases, also ameliorates deleterious effects of environmental factors. Conversely, both age and environmental risk factors are associated with the accumulation of somatic mutations in mitotic cells and epigenetic modifications that are a measure of “biological age”, a better predictor of age-related morbidity and mortality than chronological age. Here we review evidence that environmental risk factors such as smoking and air pollution may also drive neurological conditions, including Alzheimer’s Disease, by the acceleration of biological age, mediated by cumulative and persistent epigenetic effects as well as somatic mutations. Elucidation of such mechanisms could plausibly allow the development of interventions which delay deleterious effects of both aging and environmental risk factors.
Postoperative delirium in geriatric patients with hip fractures
Authors: Chen Yang , Liang Shuai , Wu Huiwen , Deng Shihao , Wang Fangyuan , Lunzhu Ciren , Li Jun
Published: December 2022

Postoperative delirium (POD) is a frequent complication in geriatric patients with hip fractures, which is linked to poorer functional recovery, longer hospital stays, and higher short-and long-term mortality. Patients with increased age, preoperative cognitive impairment, comorbidities, perioperative polypharmacy, and delayed surgery are more prone to develop POD after hip fracture surgery. In this narrative review, we outlined the latest findings on postoperative delirium in geriatric patients with hip fractures, focusing on its pathophysiology, diagnosis, prevention, and treatment. Perioperative risk prediction, avoidance of certain medications, and orthogeriatric comprehensive care are all examples of effective interventions. Choices of anesthesia technique may not be associated with a significant difference in the incidence of postoperative delirium in geriatric patients with hip fractures. There are few pharmaceutical measures available for POD treatment. Dexmedetomidine and multimodal analgesia may be effective for managing postoperative delirium, and adverse complications should be considered when using antipsychotics. In conclusion, perioperative risk intervention based on orthogeriatric comprehensive care is the most effective strategy for preventing postoperative delirium in geriatric patients with hip fractures.
Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions
Authors: Watanabe Kenya , Nakagawasai Osamu , Kanno Syu-ichi , Mitazaki Satoru , Onogi Hiroshi , Takahashi Kohei , Watanabe Kei-ichiro , Tan-No Koichi , Ishikawa Masaaki , Srivastava Lalit K. , Quirion Remi , Tadano Takeshi
Published: December 2022

Genetic studies in humans have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Furthermore, it has been suggested that NRG-1 is involved in regulating the expression and function of the N-methyl-D-aspartate receptor and the GABAA receptor in several brain areas, including the prefrontal cortex (PFC), the hippocampus, and the cerebellum. Neonatal ventral hippocampal lesioned (NVHL) rats have been considered as a putative model for schizophrenia with characteristic post-pubertal alteration in response to stress and neuroleptics. In this study, we examined NRG-1, erb-b2 receptor tyrosine kinase 4 (erbB4), and phospho-erbB4 (p-erbB4) levels in the PFC and the distribution of NRG-1 in the NVHL rats by using immunoblotting and immunohistochemical analyses. Neonatal lesions were induced by bilateral injection of ibotenic acid in the ventral hippocampus of postnatal day 7 Sprague-Dawley (SD)-rats. NVHL rats showed significantly decreased levels of NRG-1 and p-erbB4 in the PFC compared to sham controls at post-pubertal period, while the level of erbB4 did not differ between sham and NVHL rats. Moreover, microinjection of NRG-1 into the mPFC improved NVHL-induced prepulse inhibition deficits. Our study suggests PFC NRG-1 alteration as a potential mechanism in schizophrenia-like behaviors in the NVHL model.
fNIRS neuroimaging in olfactory research: A systematic literature review
Authors: Gunasekara Natalie , Gaeta Giuliano , Levy Andrew , Boot Eleanor , Tachtsidis Ilias
Published: December 2022

There are a number of key features which make olfaction difficult to study; subjective processes of odor detection, discrimination and identification, and individualistic odor hedonic perception and associated odor memories. In this systematic review we explore the role functional near-infrared spectroscopy (fNIRS) has played in understanding olfactory perception in humans. fNIRS is an optical neuroimaging technique able to measure changes in brain hemodynamics and oxygenation related to neural electrical activity. Adhering to PRISMA guidelines, results of this search found that generally the majority of studies involving healthy adult subjects observed increased activity in response to odors. Other population types were also observed, such as infants, individuals with autism, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), mild cognitive impairment (MCI) and dysosmia. fNIRS coverage heavily favored the prefrontal cortex, temporal and parietal regions. This review finds that odor induced cortical activation is dependent on multiple factors, such as odorant type, gender and population type. This review also finds that there is room for improvement in areas such as participant diversity, use of wearable fNIRS systems, physiological monitoring and multi-distance channels.
Continuous mode adaptation for cable-driven rehabilitation robot using reinforcement learning
Authors: Yang Renyu , Zheng Jianlin , Song Rong
Published: December 2022

Continuous mode adaptation is very important and useful to satisfy the different user rehabilitation needs and improve human–robot interaction (HRI) performance for rehabilitation robots. Hence, we propose a reinforcement-learning-based optimal admittance control (RLOAC) strategy for a cable-driven rehabilitation robot (CDRR), which can realize continuous mode adaptation between passive and active working mode. To obviate the requirement of the knowledge of human and robot dynamics model, a reinforcement learning algorithm was employed to obtain the optimal admittance parameters by minimizing a cost function composed of trajectory error and human voluntary force. Secondly, the contribution weights of the cost function were modulated according to the human voluntary force, which enabled the CDRR to achieve continuous mode adaptation between passive and active working mode. Finally, simulation and experiments were conducted with 10 subjects to investigate the feasibility and effectiveness of the RLOAC strategy. The experimental results indicated that the desired performances could be obtained; further, the tracking error and energy per unit distance of the RLOAC strategy were notably lower than those of the traditional admittance control method. The RLOAC strategy is effective in improving the tracking accuracy and robot compliance. Based on its performance, we believe that the proposed RLOAC strategy has potential for use in rehabilitation robots.
Application of convolutional neural network in fusion and classification of multi-source remote sensing data
Authors: Ye Fanghong , Zhou Zheng , Wu Yue , Enkhtur Bayarmaa
Published: December 2022

Introduction

Through remote sensing images, we can understand and observe the terrain, and its application scope is relatively large, such as agriculture, military, etc.

Methods

In order to achieve more accurate and efficient multi-source remote sensing data fusion and classification, this study proposes DB-CNN algorithm, introduces SVM algorithm and ELM algorithm, and compares and verifies their performance through relevant experiments.

Results

From the results, we can find that for the dual branch CNN network structure, hyperspectral data and laser mines joint classification of data can achieve higher classification accuracy. On different data sets, the global classification accuracy of the joint classification method is 98.46%. DB-CNN model has the highest training accuracy and fastest speed in training and testing. In addition, the DB-CNN model has the lowest test error, about 0.026, 0.037 lower than the ELM model and 0.056 lower than the SVM model. The AUC value corresponding to the ROC curve of its model is about 0.922, higher than that of the other two models.

Discussion

It can be seen that the method used in this paper can significantly improve the effect of multi-source remote sensing data fusion and classification, and has certain practical value.
Survival motor neuron protein and neurite degeneration are regulated by Gemin3 in spinal muscular atrophy motoneurons
Authors: Miralles Maria P. , Sansa Alba , Beltran Maria , Soler Rosa M. , Garcera Ana
Published: December 2022

Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder caused by reduction of the ubiquitously expressed protein Survival Motor Neuron (SMN). Low levels of SMN impact on spinal cord motoneurons (MNs) causing their degeneration and progressive muscle weakness and atrophy. To study the molecular mechanisms leading to cell loss in SMN-reduced MNs, we analyzed the NF-κB intracellular pathway in SMA models. NF-κB pathway activation is required for survival and regulates SMN levels in cultured MNs. Here we describe that NF-κB members, inhibitor of kappa B kinase beta (IKKβ), and RelA, were reduced in SMA mouse and human MNs. In addition, we observed that Gemin3 protein level was decreased in SMA MNs, but not in non-neuronal SMA cells. Gemin3 is a core member of the SMN complex responsible for small nuclear ribonucleoprotein biogenesis, and it regulates NF-κB activation through the mitogen-activated protein kinase TAK1. Our experiments showed that Gemin3 knockdown reduced SMN, IKKβ, and RelA protein levels, and caused significant neurite degeneration. Overexpression of SMN increased Gemin3 protein in SMA MNs, but did not prevent neurite degeneration in Gemin3 knockdown cells. These data indicated that Gemin3 reduction may contribute to cell degeneration in SMA MNs.
Postoperative red blood cell distribution width predicts functional outcome in aneurysmal subarachnoid hemorrhage after surgical clipping: A single-center retrospective study
Authors: Zhao Long , Zhang Yi , Lin Ping , Li Weida , Huang Xingyuan , Li Hangyang , Xia Mingkai , Chen Xinlong , Zhu Xi , Tang Xiaoping
Published: December 2022

Objective

Red blood cell (RBC) parameters are associated with outcomes following aneurysmal subarachnoid hemorrhage (aSAH), but their predictive value remains uncertain. This study aimed to detect the association between RBC parameters and functional outcome in aSAH patients undergoing surgical clipping.

Methods

This retrospective observational study included aSAH patients who underwent surgical clipping at Affiliated Hospital of North Sichuan Medical College between August 2016 and September 2019. The functional outcome following aSAH was assessed by modified Rankin Scale (mRS), and mRS 3–6 was defined as poor functional outcome.

Results

Out of 187 aSAH patients included (62% female, 51–66 years old), 73 patients had poor functional outcome. Multivariate logistic regression of admission parameters showed that World Federation of Neurosurgical Societies (WFNS) grade (odds ratio [95% CI]: 1.322 [1.023–1.707], p = 0.033) and white blood cell (WBC) (odds ratio [95% CI]: 1.136 [1.044–1.236], p = 0.003) were independently associated with poor functional outcome. In postoperative parameters, RBC distribution width (RDW) (odds ratio [95% CI]: 1.411 [1.095–1.818], p = 0.008), mean platelet volume (MPV, odds ratio [95% CI]: 1.253 [1.012–1.552], p = 0.039) and admission WFNS grade (odds ratio [95% CI]: 1.439 [1.119–1.850], p = 0.005) were independently associated with poor functional outcome. The predictive model including WFNS grade, admission WBC, and postoperative RDW and MPV had significantly higher predictive power compared to WFNS grade alone (0.787 [0.722–0.852] vs. 0.707 [0.630–0.784], p = 0.024). The combination of WFNS grade and WBC on admission showed the highest positive predictive value (75.5%) and postoperative RDW and MPV combined with admission WFNS grade and WBC showed the highest negative predictive value (83.7%).

Conclusion

Postoperative RDW is independently associated with poor functional outcome in aSAH patients undergoing surgical clipping. A combined model containing postoperative RDW may help predict good outcome in patients with aSAH after timely aneurysm clipping.
Too risky, too large, too late, or too mild—Reasons for not treating ischemic stroke patients and the related outcomes
Authors: Behrndtz Anne Brink , Damsbo Andreas Gammelgaard , Blauenfeldt Rolf Ankerlund , Andersen Grethe , Speiser Lasse Ole , Simonsen Claus Ziegler
Published: December 2022

Background

Despite effective treatments, many patients are still not offered reperfusion therapy for acute ischemic stroke.

Methods

We present a single-center observational study on acute ischemic stroke patients, who presented as candidates for reperfusion therapy but were deemed ineligible after work-up. Reasons for non-treatment were obtained by studying patient files and subsequently grouped into “too risky” (e.g., anticoagulant use, comorbidities), “too large” (large infarct), “too late” (late presentation of stroke and wake-up strokes), or “too mild” (clinically mild/remitting symptoms). Modified Rankin scale (mRS) score was prospectively collected in all patients by a structured telephone interview. All non-treated patients with a National Institute of Health Stroke Scale (NIHSS) score of 0–5 were compared with a similar cohort that was treated.

Results

Of 529 patients with acute ischemic stroke arriving as reperfusion therapy candidates, 198 (37.4%) were not treated. The majority (42%) were not treated due to admission outside the treatment window (too late) and 24% had absolute contraindications (too risky). Only 8% was excluded because their infarct was too large [median Alberta Stroke Program Early CT score 3 (2–4)]. In the “too mild” group (14%) the percentage of patients not being independent at 90 days was 30%. The adjusted odds ratio for a better outcome (lower mRS) among treated patients with NIHSS 0–5 compared with non-treated was 1.93 (95% confidence interval 1.15–3.23).

Conclusion

Presenting outside the treatment window is still the most common reason for not receiving therapy. Our study suggests a benefit of thrombolysis for patients with mild symptoms.
Probing the deployment of peripheral visual attention during obstacle-crossing planning
Authors: Malik Raza N. , Marigold Daniel S. , Chow Mason , Lam Tania
Published: December 2022

Gaze is directed to one location at a time, making peripheral visual input important for planning how to negotiate different terrain during walking. Whether and how the brain attends to this input is unclear. We developed a novel paradigm to probe the deployment of sustained covert visual attention by testing orientation discrimination of a Gabor patch at stepping and non-stepping locations during obstacle-crossing planning. Compared to remaining stationary, obstacle-crossing planning decreased visual performance (percent correct) and sensitivity (d’) at only the first of two stepping locations. Given the timing of the first and second steps before obstacle crossing relative to the Gabor patch presentation, the results suggest the brain uses peripheral vision to plan one step at a time during obstacle crossing, in contrast to how it uses central vision to plan two or more steps in advance. We propose that this protocol, along with multiple possible variations, presents a novel behavioral approach to identify the role of covert visual attention during obstacle-crossing planning and other goal-directed walking tasks.
Effects of acute ischemic stroke on binaural perception
Authors: Dietze Anna , Sörös Peter , Bröer Matthias , Methner Anna , Pöntynen Henri , Sundermann Benedikt , Witt Karsten , Dietz Mathias
Published: December 2022

Stroke-induced lesions at different locations in the brain can affect various aspects of binaural hearing, including spatial perception. Previous studies found impairments in binaural hearing, especially in patients with temporal lobe tumors or lesions, but also resulting from lesions all along the auditory pathway from brainstem nuclei up to the auditory cortex. Currently, structural magnetic resonance imaging (MRI) is used in the clinical treatment routine of stroke patients. In combination with structural imaging, an analysis of binaural hearing enables a better understanding of hearing-related signaling pathways and of clinical disorders of binaural processing after a stroke. However, little data are currently available on binaural hearing in stroke patients, particularly for the acute phase of stroke. Here, we sought to address this gap in an exploratory study of patients in the acute phase of ischemic stroke. We conducted psychoacoustic measurements using two tasks of binaural hearing: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. The location of the stroke lesion was established by previously acquired MRI data. An additional general assessment included three-frequency audiometry, cognitive assessments, and depression screening. Fifty-five patients participated in the experiments, on average 5 days after their stroke onset. Patients whose lesions were in different locations were tested, including lesions in brainstem areas, basal ganglia, thalamus, temporal lobe, and other cortical and subcortical areas. Lateralization impairments were found in most patients with lesions within the auditory pathway. Lesioned areas at brainstem levels led to distortions of lateralization in both hemifields, thalamus lesions were correlated with a shift of the whole auditory space, whereas some cortical lesions predominantly affected the lateralization of stimuli contralateral to the lesion and resulted in more variable responses. Lateralization performance was also found to be affected by lesions of the right, but not the left, basal ganglia, as well as by lesions in non-auditory cortical areas. In general, altered lateralization was common in the stroke group. In contrast, deficits in tone-in-noise detection were relatively scarce in our sample of lesion patients, although a significant number of patients with multiple lesion sites were not able to complete the task.
Tuina for peripherally-induced neuropathic pain: A review of analgesic mechanism
Authors: Liu Zhi-Feng , Wang Hou-Rong , Yu Tian-Yuan , Zhang Ying-Qi , Jiao Yi , Wang Xi-You
Published: December 2022

Peripherally-induced neuropathic pain (pNP) is a kind of NP that is common, frequent, and difficult to treat. Tuina, also known as massage and manual therapy, has been used to treat pain in China for thousands of years. It has been clinically proven to be effective in the treatment of pNP caused by cervical spondylosis, lumbar disc herniation, etc. However, its analgesic mechanism is still not clear and has been the focus of research. In this review, we summarize the existing research progress, so as to provide guidance for clinical and basic studies. The analgesic mechanism of tuina is mainly manifested in suppressing peripheral inflammation by regulating the TLR4 pathway and miRNA, modulating ion channels (such as P2X3 and piezo), inhibiting the activation of glial cells, and adjusting the brain functional alterations. Overall, tuina has an analgesic effect by acting on different levels of targets, and it is an effective therapy for the treatment of pNP. It is necessary to continue to study the mechanism of tuina analgesia.
The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy model via mitophagy reduction
Authors: Zhong Fuxin , Gan Yunhao , Song Jiaqi , Zhang Wenbo , Yuan Shiyun , Qin Zhangjin , Wu Jiani , Lü Yang , Yu Weihua
Published: December 2022

Background

Epilepsy is a common neurological disease, and excessive mitophagy is considered as one of the major triggers of epilepsy. Mitophagy is a crucial pathway affecting reactive oxygen species. Phosphoglycerate mutase 5 (PGAM5) is a protein phosphatase present in mitochondria that regulates many biological processes including mitophagy and cell death. However, the mechanism of PGAM5 in epilepsy remains unclear. The purpose of the present study was to examine whether PGAM5 affects epilepsy through PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy.

Methods

After the knockdown of PGAM5 expression by the adeno-associated virus, an epilepsy model was created by kainic acid. Next, the seizure activity was recorded by local field potentials before evaluating the level of mitochondrial autophagy marker proteins. Lastly, the ultrastructure of mitochondria, neuronal damage and oxidative stress levels were further observed.

Results

A higher PGAM5 level was found in epilepsy, and its cellular localization was in neurons. The interactions between PGAM5 and PINK1 in epilepsy were further found. After the knockdown of PGAM5, the level of PINK1 and light chain 3B was decreased and the expression of the translocase of the inner mitochondrial membrane 23 and translocase of the outer mitochondrial membrane 20 were both increased. Knockdown of PGAM5 also resulted in reduced neuronal damage, decreased malondialdehyde levels, decreased reactive oxygen species production and increased superoxide dismutase activity. In addition, the duration of spontaneous seizure-like events (SLEs), the number of SLEs and the time spent in SLEs were all reduced in the epilepsy model after inhibition of PGAM5 expression.

Conclusion

Inhibition of PGAM5 expression reduces seizures via inhibiting PINK1-mediated mitophagy.
TrkB signaling is correlated with muscular fatigue resistance and less vulnerability to neurodegeneration
Authors: Just-Borràs Laia , Cilleros-Mañé Víctor , Polishchuk Aleksandra , Balanyà-Segura Marta , Tomàs Marta , Garcia Neus , Tomàs Josep , Lanuza Maria A.
Published: December 2022

At the neuromuscular junction (NMJ), motor neurons and myocytes maintain a bidirectional communication that guarantees adequate functionality. Thus, motor neurons’ firing pattern, which is influenced by retrograde muscle-derived neurotrophic factors, modulates myocyte contractibility. Myocytes can be fast-twitch fibers and become easily fatigued or slow-twitch fibers and resistant to fatigue. Extraocular muscles (EOM) show mixed properties that guarantee fast contraction speed and resistance to fatigue and the degeneration caused by Amyotrophic lateral sclerosis (ALS) disease. The TrkB signaling is an activity-dependent pathway implicated in the NMJ well-functioning. Therefore, it could mediate the differences between fast and slow myocytes’ resistance to fatigue. The present study elucidates a specific protein expression profile concerning the TrkB signaling that correlates with higher resistance to fatigue and better neuroprotective capacity through time. The results unveil that Extra-ocular muscles (EOM) express lower levels of NT-4 that extend TrkB signaling, differential PKC expression, and a higher abundance of phosphorylated synaptic proteins that correlate with continuous neurotransmission requirements. Furthermore, common molecular features between EOM and slow soleus muscles including higher neurotrophic consumption and classic and novel PKC isoforms balance correlate with better preservation of these two muscles in ALS. Altogether, higher resistance of Soleus and EOM to fatigue and ALS seems to be associated with specific protein levels concerning the TrkB neurotrophic signaling.
Developmental pathways linked to the vulnerability of adult midbrain dopaminergic neurons to neurodegeneration
Authors: Prakash Nilima
Published: December 2022

The degeneration of dopaminergic and other neurons in the aging brain is considered a process starting well beyond the infantile and juvenile period. In contrast to other dopamine-associated neuropsychiatric disorders, such as schizophrenia and drug addiction, typically diagnosed during adolescence or young adulthood and, thus, thought to be rooted in the developing brain, Parkinson’s Disease (PD) is rarely viewed as such. However, evidences have accumulated suggesting that several factors might contribute to an increased vulnerability to death of the dopaminergic neurons at an already very early (developmental) phase in life. Despite the remarkable ability of the brain to compensate such dopamine deficits, the early loss or dysfunction of these neurons might predispose an individual to suffer from PD because the critical threshold of dopamine function will be reached much earlier in life, even if the time-course and strength of naturally occurring and age-dependent dopaminergic cell death is not markedly altered in this individual. Several signaling and transcriptional pathways required for the proper embryonic development of the midbrain dopaminergic neurons, which are the most affected in PD, either continue to be active in the adult mammalian midbrain or are reactivated at the transition to adulthood and under neurotoxic conditions. The persistent activity of these pathways often has neuroprotective functions in adult midbrain dopaminergic neurons, whereas the reactivation of silenced pathways under pathological conditions can promote the survival and even regeneration of these neurons in the lesioned or aging brain. This article summarizes our current knowledge about signaling and transcription factors involved in midbrain dopaminergic neuron development, whose reduced gene dosage or signaling activity are implicated in a lower survival rate of these neurons in the postnatal or aging brain. It also discusses the evidences supporting the neuroprotection of the midbrain dopaminergic system after the external supply or ectopic expression of some of these secreted and nuclear factors in the adult and aging brain. Altogether, the timely monitoring and/or correction of these signaling and transcriptional pathways might be a promising approach to a much earlier diagnosis and/or prevention of PD.
Prediction of prognosis and immunotherapy response of amino acid metabolism genes in acute myeloid leukemia
Authors: Zhou Hui , Wang Fengjuan , Niu Ting
Published: December 2022

Background

Amino acid (AA) metabolism plays a crucial role in cancer. However, its role in acute myeloid leukemia (AML) is still unavailable. We screened out AA metabolic genes, which related to prognosis, and analyzed their correlation with tumor immune microenvironment in AML.

Methods

We evaluated 472 amino acid metabolism-related genes in 132 AML patients. The predictive risk model was developed according to differentially expressed genes, univariate Cox and LASSO analyses. We validated the risk signature by survival analysis and independence tests. Single-sample gene set enrichment analysis (ssGSEA), tumor immune microenvironment (TME), tumor mutation burden (TMB), functional enrichment, and the IC50 of drugs were assessed to explore the correlations among the risk model, immunity, and drug sensitivity of AML.

Results

Six amino acid metabolism-related genes were confirmed to develop the risk model, including TRH, HNMT, TFEB, SDSL, SLC43A2, and SFXN3. The high-risk subgroup had an immune “hot” phenotype and was related to a poor prognosis. The high-risk group was also associated with more activity of immune cells, such as Tregs, had higher expression of some immune checkpoints, including PD1 and CTLA4, and might be more susceptible to immunotherapy. Xenobiotic metabolism, the reactive oxygen species (ROS) pathway, fatty acid metabolism, JAK/STAT3, and the inflammatory response were active in the high-risk subgroup. Furthermore, the high-risk subgroup was sensitive to sorafenib, selumetinib, and entospletinib. ssGSEA discovered that the processes of glutamine, arginine, tryptophan, cysteine, histidine, L-serine, isoleucine, threonine, tyrosine, and L-phenylalanine metabolism were more active in the high-risk subgroup.

Conclusion

This study revealed that AA metabolism-related genes were correlated with the immune microenvironment of AML patients and could predict the prognosis and immunotherapy response of AML patients.
Characterization, immunostimulatory and antitumor activities of a β-galactoglucofurannan from cultivated Sanghuangporus vaninii under forest
Authors: Cheng Junwen , Wang Yanbin , Song Jiling , Liu Yu , Ji Weiwei , He Liang , Wei Hailong , Hu Chuanjiu , Jiang Yihan , Xing Yiqi , Huang Xubo , Ding Hongmei , He Qinghai
Published: December 2022

A biomacromolecule, named as β-galactoglucofurannan (SVPS2), was isolated from the cultivated parts of Sanghuangporus vaninii under the forest. Its primary and advanced structure was analyzed by a series of techniques including GC-MS, methylation, NMR, MALS as well as AFM. The results indicated that SVPS2 was a kind of 1, 5-linked β-Glucofurannan consisting of β-glucose, β-galactose and α-fucose with 23.4 KDa. It exhibited a single-stranded chain with an average height of 0.72 nm in saline solution. The immunostimulation test indicated SVPS2 could facilitate the initiation of the immune reaction and promote the secretion of cytokines in vitro. Moreover, SVPS2 could mediate the apoptosis of HT-29 cells by blocking them in S phase. Western blot assay revealed an upregulation of Bax, Cytochrome c and cleaved caspase-3 by SVPS2, accompanied by a downregulation of Bcl-2. These results collectively demonstrate that antitumor mechanism of SVPS2 may be associated with enhancing immune response and inducing apoptosis of tumor cells in vitro. Therefore, SVPS2 might be utilized as a promising therapeutic agent against colon cancer and functional food with immunomodulatory activity.
Is there any association between dietary inflammatory index and quality of life? A systematic review
Authors: Golmohammadi Mona , Kheirouri Sorayya , Ebrahimzadeh Attari Vahideh , Moludi Jalal , Sulistyowati Reny , Nachvak Seyed Mostafa , Mostafaei Roghayeh , Mansordehghan Maryam
Published: December 2022

Background

The inflammatory potential of unhealthy diets can lead to the development of chronic diseases and also exacerbating their complications. Therefore, the present systematic review aimed to evaluate the association of dietary inflammatory index (DII) and quality of life (QOL) in human subjects.

Methods

A systematic search was conducted in PubMed, Web of Science, and Scopus databases, using the combination of all search terms related to DII and QOL until May 2022. All eligible human studies published in English were included.

Results

Three hundred twenty-seven studies were obtained from the first systematic search of the databases although, only eight studies were eligible for the evaluation. Seven studies reported that there was a significant reverse association between DII scores and overall QOL and/or its subscales in different populations including patients with asthma, osteoarthritis, hemodialysis patients, multiple sclerosis, obese women, and also in healthy subjects. While, one study on postmenopausal women found no evidence of this association.

Conclusion

This systematic review demonstrated that an anti-inflammatory diet might be associated with better QOL. However, future well-designed clinical trials can provide better conclusions especially regarding the quantifying of this relationship.
The mitigative effect of isorhamnetin against type 2 diabetes via gut microbiota regulation in mice
Authors: Li Jinjun , Yuan Huimin , Zhao Zhiqi , Li Li , Li Xiaoqiong , Zhu Liying , Wang Xin , Sun Ping , Xiao Yinping
Published: December 2022

In order to demonstrate the effects of isorhamnetin (IH) on the symptoms of type 2 diabetes mellitus (T2DM) and the role of gut microbiota in this process, an T2DM mouse model was established via a high-fat diet and streptozotocin. After 6 weeks of IH intervention and diabetes phenotype monitoring, the mice were dissected. We detected blood indicators and visceral pathology. Contents of the cecum were collected for 16S rRNA sequencing and short chain fatty acid (SCFAs) detection. The results showed that after IH intervention, the body weight of type 2 diabetic mice was gradually stabilized, fasting blood glucose was significantly decreased, and food intake was reduced (P < 0.05). Isorhamnetin significantly increased the level of SCFAs and decreased the levels of blood lipids and inflammatory factors in mice (P < 0.05). 16S rRNA sequencing results showed that Lactobacillus were significantly decreased and Bacteroidales S24-7 group_norank were significantly increased (P < 0.05). Interestingly, gut microbiota was significantly correlated with inflammatory factors, blood lipids, and SCFAs (P < 0.05). Taken together, our data demonstrated that isorhamnetin could improve the diabetic effects in T2DM mice, which might be mediated by gut microbiota.
Case report: Long-term clinical benefit of pyrotinib therapy following trastuzumab resistance in HER2-amplification recurrent mucinous ovarian carcinoma
Authors: Fang Xiangming , Mou Haibo , Ying Xinxin , Hou Xuehua , Wang Luo , Wu Ying , Yan Naimeng , Guo Lijie , Liao Qin
Published: December 2022

Advanced or recurrent mucinous carcinoma of the ovary minimally responds to current cytotoxic treatments and has a poor prognosis. Despite multimodal treatment with chemotherapy and surgery, most patients ultimately progress and require palliative systemic therapy. Anti-HER2 therapy has been demonstrated to be an effective strategy for the treatment of HER2-positive breast cancer. However, the role of anti-HER2 therapy in ovarian cancer remains largely unknown. Here, we report the case of a young woman with FIGO Stage IIIc recurrent mucinous ovarian carcinoma (MOC) who developed trastuzumab resistance and disease progression following cross-treatment with trastuzumab combined with pertuzumab. HER2 amplification was discovered using next-generation sequencing (NGS). The patient then received bevacizumab, and pyrotinib (an irreversible HER2 antagonist) plus capecitabine treatment, and achieved a long-term clinical benefit for 22 months. Pyrotinib combined with bevacizumab is a potential treatment for MOC patients who are heavily pretreated and harbor a HER2 amplification. Our case may provide valuable treatment information for patients with advanced or recurrent MOC.
Genome-wide association studies identify miRNA-194 as a prognostic biomarker for gastrointestinal cancer by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5
Authors: Huang Pan , Xia Lingyun , Guo Qiwei , Huang Congcong , Wang Zidi , Huang Yinxuan , Qin Shanshan , Leng Weidong , Li Dandan
Published: December 2022

Background

The dysregulated genes and miRNAs in tumor progression can be used as biomarkers for tumor diagnosis and prognosis. However, the biomarkers for predicting the clinical outcome of gastrointestinal cancer (GIC) are still scarce.

Methods

Genome-wide association studies were performed to screen optimal prognostic miRNA biomarkers. RNA-seq, Ago-HITS-CLIP-seq, western blotting and qRT-PCR assays were conducted to identify target genes of miR-194. Genome-wide CRISPR-cas9 proliferation screening analysis were conducted to distinguish passenger gene and driver gene.

Results

A total of 9 prognostic miRNAs for GIC were identified by global microRNA expression analysis. Among them, miR-194 was the only one miRNA that significantly associated with overall survival, disease-specific survival and progress-free interval in both gastric, colorectal and liver cancers, indicating miR-194 was an optimal prognostic biomarker for GIC. RNA-seq analysis confirmed 18 conservative target genes of miR-194. Four of them, including ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5, were directly targeted by miR-194 and required for cell proliferation. Cell proliferation assay validated that miR-194 inhibits cell proliferation by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5 in GIC.

Conclusion

In summary, miR-194 is an optimal biomarker for predicting the outcome of GIC. Our finding highlights that miR-194 exerts a tumor-suppressive role in digestive system cancers by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5.
The role and mechanism of claudins in cancer
Authors: Wang De-Wen , Zhang Wei-Han , Danil Galiullin , Yang Kun , Hu Jian-Kun
Published: December 2022

Claudins are a tetraspan membrane protein multigene family that plays a structural and functional role in constructing tight junctions. Claudins perform crucial roles in maintaining cell polarity in epithelial and endothelial cell sheets and controlling paracellular permeability. In the last two decades, increasing evidence indicates that claudin proteins play a major role in controlling paracellular permeability and signaling inside cells. Several types of claudins are dysregulated in various cancers. Depending on where the tumor originated, claudin overexpression or underexpression has been shown to regulate cell proliferation, cell growth, metabolism, metastasis and cell stemness. Epithelial-to-mesenchymal transition is one of the most important functions of claudin proteins in disease progression. However, the exact molecular mechanisms and signaling pathways that explain why claudin proteins are so important to tumorigenesis and progression have not been determined. In addition, claudins are currently being investigated as possible diagnostic and treatment targets. Here, we discuss how claudin-related signaling pathways affect tumorigenesis, tumor progression, and treatment sensitivity.