bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and temporal variation of genetic diversity and genetic differentiation in Daphnia galeata populations in four large reservoirs in southern China
Authors: Huang Qi , Xu Lei , Xie Lili , Liu Ping , Rizo Eric Zeus C. , Han Bo-Ping
Published: November 2022

Daphnia galeatais a common and dominant species in warmer waters, and has a strong top-down effect on both phytoplankton and bacteria. The knowledge of its temporal and spatial patterns of genetic diversity is fundamental in understanding its population dynamics and potential ecological function in ecosystems. Its population genetics have been investigated at regional scales but few within regions or at smaller spatial scales. Here, we examined the fine-scale spatial genetic variation ofD. galeatawithin four large, deep reservoirs in wet and dry seasons and the six-year variation of genetic diversity in one of the reservoirs by using cytochrome c oxidase subunit I and microsatellites (simple sequence repeat). Our study shows that fine-scale spatial genetic variation commonly occurred within the reservoirs, indicating strong environmental selection at least in the two of reservoirs with strong longitudinal gradients. Since the environmental gradients established in the dry season was largely reduced in the wet season, the fine-scale spatial genetic variation was much higher in the dry season. The dynamics of local genetic diversity did not follow the theoretical pattern of rapid erosion but peaked in mid or mid-late growth season. The local genetic diversity ofD. galeataappears to be shaped and maintained not only by recruitment from resting egg banks but also by gene flow within reservoirs. The temporal and fine-scale genetic variation within a water body suggests that it is necessary to pay attention to sampling periods and locations of a given water body in regional studies.
Case report: Acute Talaromyces marneffei mediastinitis in an HIV-negative patient
Authors: Chen Liangyu , Zhang Meichun , Guo Weihong , Ding Wenshuang , Tan Jinwen , Du Hong , Zhao Ziwen , Zhong Weinong
Published: November 2022

Talaromyces marneffei (T. marneffei) is one of the most important opportunistic human pathogens endemic in Southeast Asia. Talaromycosis, which was once regarded as an opportunistic infectious disease in patients with acquired immunodeficiency syndrome, is being increasingly reported in HIV-negative populations. Since T. marneffei infection can be localized or disseminated, patients may present with a variety of symptoms. However, mediastinal infection attributed to T. marneffei is extremely rare. We report the case of a 32-year-old female who manifested a large mediastinal mass and was eventually diagnosed as acute T. marneffei mediastinitis. The patient was HIV-negative and had no direct contact with intermediate hosts. We successfully managed to treat the patient with inhaled amphotericin B deoxycholate and observed lesion absorption in subsequent CT examinations. To our knowledge, this is the first published case of T. marneffei mediastinitis and first use of inhaled antifungal monotherapy on patients with T. marneffei infection.
Key infection stages defending heat stress in high-temperature-resistant Blumeria graminis f. sp. tritici isolates
Authors: Zhang Meihui , Wang Aolin , Zhang Cheng , Xu Fei , Liu Wei , Fan Jieru , Ma Zhanhong , Zhou Yilin
Published: November 2022

With the increase of temperature in the winter wheat-growing regions in China, the high-temperature-resistant Blumeria graminis f. sp. tritici (Bgt) isolates developed in the fields. To clarify the key infection stages and the roles of heat shock protein (HSP) genes of high-temperature-resistant Bgt isolates defending high temperature, 3 high-temperature-resistant and 3 sensitive Bgt isolates were selected from 55 isolates after determination of temperature sensitivity. And then they were used to investigate the infection stages and the expression levels of HSP genes, including Bgthsp60, Bgthsp70, Bgthsp90, and Bgthsp104, at 18°C and 25°C. The formation frequency of abnormal appressoria and inhibition rate of haustoria formation of high-temperature-resistant isolates at 25°C were lower than those of high-temperature-sensitive isolates, while major axis of microcolonies of high-temperature-resistant isolates was higher than those of high-temperature-sensitive isolates at 25°C. The results indicated that haustoria formation and hyphal expansion were the key infection stages of defense against heat stress in high-temperature-resistant isolates. Further analyses of HSP genes found the expression levels of Bgthsp60 and Bgthsp70c were upregulated at 24 and 72 h post-inoculation in high-temperature-resistant isolates, while no significant difference was observed for Bgthsp90 and Bgthsp104 genes. Taken together, the basis of high-temperature-resistant Bgt isolates is associated with induced expression of Bgthsp60 and Bgthsp70c response to heat stress in haustoria formation and hyphal expansion stages.
A preliminary study on the possibility of fermented pineapple peel residue partially replacing whole corn silage in feeding Chuanzhong black goats
Authors: Yang Chuang , Zhao Weiran , Tian Hanchen , Wang Mingyue , Gao Chongya , Guo Yongqing , Sun Baoli
Published: November 2022

This study aims to assess the effects of the partial replacement of whole corn silage (WCS) with fermented pineapple peel residue (FPPR) on growth, serological parameters, muscle quality, rumen microorganisms, and fecal microorganisms. A total of 24 Chuanzhong black goats weighing 10.23 ± 1.42 kg were evaluated in a randomized complete trial design in accordance with the following treatments: (1) 0% FPPR in the diet, (2) 25% FPPR in the diet, and (3) 50% FPPR in the diet. In goats, the partial substitution of FPPR for WCS increased the abundance of probiotics, such as Blautia, Butyrivibrio fibrisolvens, and Ruminococcus albus, and did not exert significant effects on overall serological parameters and muscle quality. In conclusion, the partial substitution of FPPR for WCS in the diet did not impair or affect the productive performance of goats.
The impact of Traditional Chinese Medicine on mouse gut microbiota abundances and interactions based on Granger causality and pathway analysis
Authors: Zhang Yi , Zhang Dahan , Bai Xiaogang , Chen Yang , Qiu Qinwei , Shang Xiaoxiao , Deng Yusheng , Yang Hongyan , Fang Xiaodong , Yang Zhimin , Han Lijuan
Published: November 2022

Objectives

The intestinal microbiota is essential in absorbing nutrients and defending against pathogens and is associated with various diseases, including obesity, type 2 diabetes, and hypertension. As an alternative medicine, Traditional Chinese Medicine (TCM) has long been used in disease treatment and healthcare, partly because it may mediate gut microbiota. However, the specific effects of TCM on the abundance and interactions of microbiota remain unknown. Moreover, using TCM ingredients and data detailing changes in the abundance of gut microorganisms, we developed bioinformatic methods that decipher the impact of TCM on microorganism interactions.

Methods

The dynamics of gut microorganisms affected by TCM treatments is explored using a mouse model, which provided the abundance of 70 microorganisms over time. The Granger causality analysis was used to measure microorganism interactions. Novel “serial connection” and “diverging connection” models were used to identify molecular mechanisms underlying the impact of TCM on gut microorganism interactions, based on microorganism proteins, TCM chemical ingredients, and KEGG reaction equations.

Results

Codonopsis pilosula (Dangshen), Cassia twig (Gui Zhi), Radices saussureae (Mu Xiang), and Sijunzi Decoction did not cause an increase in the abundance of harmful microorganisms. Most TCMs decreased the abundance of Bifidobacterium pseudolongum, suggesting a Bifidobacterium pseudolongum supplement should be used during TCM treatment. The Granger causality analysis indicated that TCM treatment changes more than half the interactions between the 70 microorganisms, and “serial connection” and “diverging connection” models suggested that changes in interactions may be related to the reaction number connecting species proteins and TCM ingredients. From a species diversity perspective, a TCM decoction is better than a single herb for healthcare. The Sijunzi Decoction only significantly increased the abundance of Bifidobacterium pseudolongum and did not cause a decrease in the abundance of other species but was found to improve the alpha diversity with the lowest replacement rate.

Conclusions

Because most of the nine TCMs are medicinal and edible plants, we expect the methods and results presented can be used to optimize and integrate microbiota and TCMs into healthcare processes. Moreover, as a control study, these results can be combined with future disease mouse models to link variations in species abundance with particular diseases.
Peroxisome proliferator-activated receptor-γ as the gatekeeper of tight junction in Clostridioides difficile infection
Authors: Lai Yi-Hsin , Wu Tai-Chieh , Tsai Bo-Yang , Hung Yuan-Pin , Lin Hsiao-Ju , Tsai Yau-Sheng , Ko Wen-Chien , Tsai Pei-Jane
Published: November 2022

Clostridioides difficile is a major causative pathogen of nosocomial antibiotic-associated diarrhea and severe colitis. Despite the use of vancomycin and fidaxomicin as standard drugs for the treatment of C. difficile infection (CDI), clinical relapse rates remain high. Therefore, new alternative therapeutics to treat CDI are urgently required. The nuclear receptor, peroxisome proliferator-activated receptor-γ (PPAR-γ), is mainly expressed in the adipose tissue and modulates lipid metabolism and insulin sensitization. Previous studies have shown that PPAR-γ is highly expressed in colonic tissues and regulates tight junction function in epithelial cells. However, the role of PPAR-γ in CDI pathogenesis remains unclear. In this study, we used a mouse model of CDI and found that both expression levels of PPAR-γ and the tight junction protein, occludin, were decreased in colonic tissues. Furthermore, to investigate the role of PPAR-γ in CDI, we used PPAR-γ defective mice and found that intestinal permeability and bacterial dissemination in these mice were significantly higher than those in wild-type mice during CDI. Administration of the PPAR-γ agonist, pioglitazone, to activate PPAR-γ activity improved the phenotypes of CDI, including bodyweight loss, inflammation, and intestinal integrity. Taken together, these results demonstrate that PPAR-γ is a potential therapeutic target in CDI, as it modulates colonic inflammation and integrity.
Late-long-term potentiation magnitude, but not Aβ levels and amyloid pathology, is associated with behavioral performance in a rat knock-in model of Alzheimer disease
Authors: Yesiltepe Metin , Yin Tao , Tambini Marc D. , Breuillaud Lionel , Zehntner Simone P. , D’Adamio Luciano
Published: November 2022

Cleavage of Amyloid precursor protein by β- and γ-secretases lead to Aβ formation. The widely accepted pathogenic model states that these mutations cause AD via an increase in Aβ formation and accumulation of Aβ in Amyloid plaques. APP mutations cause early onset familial forms of Alzheimer’s disease (FAD) in humans. We generated App−Swedish (Apps) knock−in rats, which carry a pathogenic APP mutation in the endogenous rat App gene. This mutation increases β-secretase processing of APP leading to both augmented Aβ production and facilitation of glutamate release in Apps/s rats, via a β-secretase and APP−dependent glutamate release mechanism. Here, we studied 11 to 14-month-old male and female Apps/s rats. To determine whether the Swedish App mutation leads to behavioral deficits, Apps/s knock-in rats were subjected to behavioral analysis using the IntelliCage platform, an automated behavioral testing system. This system allows behavioral assessment in socially housed animals reflecting a more natural, less stress-inducing environment and eliminates experimenter error and bias while increasing precision of measurements. Surprisingly, a spatial discrimination and flexibility task that can reveal deficits in higher order brain function showed that Apps/s females, but not Apps/s male rats, performed significantly worse than same sex controls. Moreover, female control rats performed significantly better than control and Apps/s male rats. The Swedish mutation causes a significant increase in Aβ production in 14-month-old animals of both sexes. Yet, male and female Apps/s rats showed no evidence of AD−related amyloid pathology. Finally, Apps/s rats did not show signs of significant neuroinflammation. Given that the APP Swedish mutation causes alterations in glutamate release, we analyzed Long-term potentiation (LTP), a long-lasting form of synaptic plasticity that is a cellular basis for learning and memory. Strikingly, LTP was significantly increased in Apps/s control females compared to both Apps/s sexes and control males. In conclusion, this study shows that behavioral performances are sex and App-genotype dependent. In addition, they are associated with LTP values and not Aβ or AD-related pathology. These data, and the failures of anti-Aβ therapies in humans, suggest that alternative pathways, such as those leading to LTP dysfunction, should be targeted for disease-modifying AD therapy.
Keeping track of and recognizing the value of Public Involvement work in dementia research
Authors: Georges Jean , Diaz-Ponce Ana , Lamirel Daphne , Moradi-Bachiller Soraya , Gove Dianne
Published: November 2022

The Public Involvement (PI) of people with dementia is slowly but progressively moving from a “nice to have” to a “must have” element of good-quality dementia research. Research funders and ethics committees increasingly ask for evidence of the planning of such involvement. The actual conduct and outcome of PI are, however, unfortunately typically under or inadequately reported. In this article, we provide an overview of what PI is and why it is important to dementia research and Alzheimer Europe's approach to PI. We draw on our recent experience of compiling a set of examples of PI in different European projects in publicly available sources. This highlighted the difficulty of finding information about PI activities and the almost total lack of details of such activities in formal reports, official records, and/or public project websites. In this article, we emphasize gaps and call for more stringent conditions for the inclusion and reporting of PI work in the context of the approval and funding of dementia research projects. We call for the establishment of obligatory reporting on the nature, specific challenges, and impact of PI in dementia research in formal reports (e.g., to funders), in public project websites, and in peer-reviewed articles. Such reporting should cover several key factors such as who was involved, how they were involved, and what impact PI had on the research process.
Integrative interaction of emotional speech in audio-visual modality
Authors: Dong Haibin , Li Na , Fan Lingzhong , Wei Jianguo , Xu Junhai
Published: November 2022

Emotional clues are always expressed in many ways in our daily life, and the emotional information we receive is often represented by multiple modalities. Successful social interactions require a combination of multisensory cues to accurately determine the emotion of others. The integration mechanism of multimodal emotional information has been widely investigated. Different brain activity measurement methods were used to determine the location of brain regions involved in the audio-visual integration of emotional information, mainly in the bilateral superior temporal regions. However, the methods adopted in these studies are relatively simple, and the materials of the study rarely contain speech information. The integration mechanism of emotional speech in the human brain still needs further examinations. In this paper, a functional magnetic resonance imaging (fMRI) study was conducted using event-related design to explore the audio-visual integration mechanism of emotional speech in the human brain by using dynamic facial expressions and emotional speech to express emotions of different valences. Representational similarity analysis (RSA) based on regions of interest (ROIs), whole brain searchlight analysis, modality conjunction analysis and supra-additive analysis were used to analyze and verify the role of relevant brain regions. Meanwhile, a weighted RSA method was used to evaluate the contributions of each candidate model in the best fitted model of ROIs. The results showed that only the left insula was detected by all methods, suggesting that the left insula played an important role in the audio-visual integration of emotional speech. Whole brain searchlight analysis, modality conjunction analysis and supra-additive analysis together revealed that the bilateral middle temporal gyrus (MTG), right inferior parietal lobule and bilateral precuneus might be involved in the audio-visual integration of emotional speech from other aspects.
Braille letter reading: A benchmark for spatio-temporal pattern recognition on neuromorphic hardware
Authors: Müller-Cleve Simon F. , Fra Vittorio , Khacef Lyes , Pequeño-Zurro Alejandro , Klepatsch Daniel , Forno Evelina , Ivanovich Diego G. , Rastogi Shavika , Urgese Gianvito , Zenke Friedemann , Bartolozzi Chiara
Published: November 2022

Spatio-temporal pattern recognition is a fundamental ability of the brain which is required for numerous real-world activities. Recent deep learning approaches have reached outstanding accuracies in such tasks, but their implementation on conventional embedded solutions is still very computationally and energy expensive. Tactile sensing in robotic applications is a representative example where real-time processing and energy efficiency are required. Following a brain-inspired computing approach, we propose a new benchmark for spatio-temporal tactile pattern recognition at the edge through Braille letter reading. We recorded a new Braille letters dataset based on the capacitive tactile sensors of the iCub robot's fingertip. We then investigated the importance of spatial and temporal information as well as the impact of event-based encoding on spike-based computation. Afterward, we trained and compared feedforward and recurrent Spiking Neural Networks (SNNs) offline using Backpropagation Through Time (BPTT) with surrogate gradients, then we deployed them on the Intel Loihi neuromorphic chip for fast and efficient inference. We compared our approach to standard classifiers, in particular to the Long Short-Term Memory (LSTM) deployed on the embedded NVIDIA Jetson GPU, in terms of classification accuracy, power, and energy consumption together with computational delay. Our results show that the LSTM reaches ~97% of accuracy, outperforming the recurrent SNN by ~17% when using continuous frame-based data instead of event-based inputs. However, the recurrent SNN on Loihi with event-based inputs is ~500 times more energy-efficient than the LSTM on Jetson, requiring a total power of only ~30 mW. This work proposes a new benchmark for tactile sensing and highlights the challenges and opportunities of event-based encoding, neuromorphic hardware, and spike-based computing for spatio-temporal pattern recognition at the edge.
Effect of mixture design approach on nutritional characteristics and sensory evaluation of steamed bread added rice flour
Authors: Tian Shuangqi , Wei Yichun , Chen Zhicheng
Published: November 2022

This study was designed to evaluate the effects of different rice nutrient compounds on steamed bread’s nutritional characteristics and sensory evaluation. The mixture design approach was used to research the interactions between different rice flours and wheat flours on the sensory evaluation of steamed bread. The arginine content of different rice flour (long-grained rice, polished round-grained rice, and black rice) was higher at 44.19, 21.74, and 34.78% than that of the common wheat, respectively. When the added amount of mixed rice flours exceeds 15%, the steamed bread gradually reduces its elasticity, and sensory score, and has a smaller specific volume. Rice is a widely consumed grain product, which provides energy and nutrients for more than half of humanity, especially in Asia. Different rice varieties have received increased attention from researchers for their high bioactive substances and other health benefits. The results of the current study provide a theoretical basis for the nutritional steamed bread and noodle industries to use different rice flour as an ingredient for enhancing or to improving the nutritional value of flour products.
Global trends and hotspots in research of robotic surgery in oncology: A bibliometric and visual analysis from 2002 to 2021
Authors: Lu Hua , Han Tingliang , Li Fangcun , Yang Jiali , Hou Zhaomeng
Published: November 2022

Background

With the development of robotic surgery in the field of oncology, an increasing number of relevant research papers have been published. In order to explore the research hotspots and trends in this field, a bibliometric and visual analysis was performed for the first time.

Methods

The literature records related to oncology robotic surgery were obtained from the Web of Science Core Collection database and imported into the software VOSviewer 1.6.18, CiteSpace 6.1.R3, and the Bibliometric Online Analysis Platform for analysis.

Results

A total of 6,964 publications, including 5,635 articles and 1,329 reviews, were included in this study. Over the past 20 years, annual publications and citations have experienced rapid growth, particularly in the last two years. The United States was the country with the most publications, while Yonsei University in South Korea was the most productive institution. The Journal of Robotic Surgery and the Journal of Urology were the journals with the most publications and citations, respectively. Mottrie A from Belgium and Ficarra V from Italy were the authors with the highest number of publications and citations, respectively. The keywords “robotic surgical procedure”, “laparoscopic surgery”, “prostate cancer”, “colorectal cancer”, “gastric cancer”, “resection”, “complications classification”, “open surgery”, “transoral robotic surgery”, “pathological outcomes”, and “robot-assisted surgery” reflect the research hotspots and trends of oncology robotic surgery.

Conclusion

The therapeutic advantages of robotic surgery in oncology are not yet prominent, and further randomized controlled trials with multicenter and large samples are needed to evaluate the advantages of robotic surgery compared with laparoscopic surgery and open surgery in the treatment of tumors from multiple outcome indicators.
Contouring the accessory parotid gland and major parotid glands as a single organ at risk during nasopharyngeal carcinoma radiotherapy
Authors: Cai Xin-Ling , Hu Jiang , Shi Jun-Tian , Chen Jin-Shu , Bai Shou-Min , Liu Yi-Min , Yu Xiao-Li
Published: November 2022

Background and purpose

No research currently exists on the role of the accessory parotid gland (APG) in nasopharyngeal carcinoma (NPC). We thereby aimed to assess the effects of APG on the dosimetry of the parotid glands (PGs) during NPC radiotherapy and evaluate its predictive value for late xerostomia.

Material and methods

The clinical data of 32 NPC patients with radiological evidence of the APG treated at Sun Yat-sen Memorial Hospital between November 2020 and February 2021 were retrospectively reviewed. Clinically approved treatment plans consisted of only the PGs as an organ at risk (OAR) (Plan1), while Plan2 was designed by considering the APG as a single organ at risk (OAR). The APG on Plan1 was delineated, and dose–volume parameters of the PGs alone (PG-only) and of the combined structure (PG+APG) were analyzed in both plans. The association of such dosimetric parameters in Plan1 with xerostomia at 6–9 months post-radiotherapy was further explored.

Results

Fifty APGs were found, with a mean volume of 3.3 ± 0.2 ml. Significant differences were found in all dosimetric parameters between Plan1 and Plan2. The mean dose and percentage of OAR volumes receiving more than 30 Gy significantly reduced in Plan1 itself (PG-only vs. PG+APG, 39.55 ± 0.83 Gy vs. 37.71 ± 0.75 Gy, and 62.00 ± 2.00% vs. 57.41 ± 1.56%, respectively; p < 001) and reduced further in Plan2 (PG+APG, 36.40 ± 0.74 Gy, and 55.54 ± 1.61%, respectively; p < 0.001). Three additional patients met the dose constraint in Plan1, which increased to seven in Plan2. With APG included, the predictive power of the dosimetric parameters for xerostomia tended to improve, although no significant differences were observed.

Conclusion

APG is anatomically similar to the PGs. Our findings suggest the potential benefits of treating the APG and PGs as a single OAR during radiotherapy (RT) of NPC by improving PG sparing.
Automatic segmentation of nasopharyngeal carcinoma on CT images using efficient UNet‐2.5D ensemble with semi‐supervised pretext task pretraining
Authors: Domoguen Jansen Keith L. , Manuel Jen-Jen A. , Cañal Johanna Patricia A. , Naval Prospero C.
Published: November 2022

Nasopharyngeal carcinoma (NPC) is primarily treated with radiation therapy. Accurate delineation of target volumes and organs at risk is important. However, manual delineation is time-consuming, variable, and subjective depending on the experience of the radiation oncologist. This work explores the use of deep learning methods to automate the segmentation of NPC primary gross tumor volume (GTVp) in planning computer tomography (CT) images. A total of sixty-three (63) patients diagnosed with NPC were included in this study. Although a number of studies applied have shown the effectiveness of deep learning methods in medical imaging, their high performance has mainly been due to the wide availability of data. In contrast, the data for NPC is scarce and inaccessible. To tackle this problem, we propose two sequential approaches. First we propose a much simpler architecture which follows the UNet design but using 2D convolutional network for 3D segmentation. We find that this specific architecture is much more effective in the segmentation of GTV in NPC. We highlight its efficacy over other more popular and modern architecture by achieving significantly higher performance. Moreover to further improve performance, we trained the model using multi-scale dataset to create an ensemble of models. However, the performance of the model is ultimately dependent on the availability of labelled data. Hence building on top of this proposed architecture, we employ the use of semi-supervised learning by proposing the use of a combined pre-text tasks. Specifically we use the combination of 3D rotation and 3D relative-patch location pre-texts tasks to pretrain the feature extractor. We use an additional 50 CT images of healthy patients which have no annotation or labels. By semi-supervised pretraining the feature extractor can be frozen after pretraining which essentially makes it much more efficient in terms of the number of parameters since only the decoder is trained. Finally it is not only efficient in terms of parameters but also data, which is shown when the pretrained model with only portion of the labelled training data was able to achieve very close performance to the model trained with the full labelled data.
Effects of antenatal corticosteroids on neonatal blood glucose fluctuation in late-preterm infants
Authors: Zhou Cailing , Zheng Wanli , Zhang Meixian , Tung Tao-Hsin , Wang Linghua , Wang Lizhen
Published: November 2022

Objective

To evaluate the effects of antenatal corticosteroids (ACS) on blood glucose fluctuations in late-preterm neonates.

Methods

A retrospective study was performed on 236 neonates with gestational age of 34+0 to 36+6 weeks who were admitted to the neonatology department of a tertiary general hospital in China's Zhejiang Province between April 2020 and February 2022. The neonates were divided into three groups: complete course, partial course, and control. Primary outcome was the neonatal blood glucose levels within the first 48 h of life.

Results

134 (56.8%) newborns were exposed to a complete course of ACS, 56 (23.7%) had a to a partial course of ACS, and 46 (19.5%) had no exposure to ACS. The patients in the complete course group had the highest proportion of neonatal hypoglycemia (16.4% vs. 3.6% and 6.5%).The patients exposed to a complete course of dexamethasone had significantly lower blood glucose levels within 12 h of birth than the control group, although no significant differences were observed after 24 h. Differences in blood glucose levels were more significant among male infants, although blood glucose curves of the male and female infants remained close to the overall trend.

Conclusions

Blood glucose levels in late-preterm neonates may decrease after ACS administration, especially after exposure to a complete course. The effects are more pronounced in the first 12 h of life, with males being more severely affected; however, the effects on blood glucose levels were not significant 24 h after birth. This can provide a reference for future clinical studies.
Application of amide proton transfer imaging for the diagnosis of neonatal hypoxic–ischemic encephalopathy
Authors: Chen Sijin , Liu Xilong , Lin Jie , Mei Yingjie , Deng Kan , Xue Qiao , Song Xiaoyan , Xu Yikai
Published: November 2022

Objective

This study aimed to evaluate cerebral amide proton transfer signal intensity (SI) among controls, hypoxic–ischemic encephalopathy (HIE) neonates with normal conventional magnetic resonance imaging (HIE/MRI−) findings, and HIE neonates with abnormal conventional MRI (HIE/MRI+) findings.

Methods

Forty neonates diagnosed with neonatal HIE and sixteen normal neonates were evaluated. All neonates underwent conventional MRI scans and APT imaging. Cerebral APT SIs were compared to identify cerebral regions with significant APT changes among sixteen controls, thirteen HIE/MRI− patients, and twenty–seven HIE/MRI+ patients.

Results

Significantly increased APT SIs were observed in the HIE/MRI− group compared with controls, in the left insula, right occipital lobe, left cingulate gyrus (posterior part), and corpus callosum. Significantly increased APT SIs were found in the HIE/MRI+ group compared with controls, in the right anterior temporal lobe (medial part), anterior parts of the right parahippocampal and ambient gyri, left superior temporal gyrus (middle part), left insula, left cingulate gyrus (posterior part), and right lentiform nucleus. No significant APT SI differences were observed in the cerebellum and brainstem among the three groups.

Conclusion

Amide proton transfer imaging plays an important role in detecting hypoxic–ischemic encephalopathy regardless of conventional MRI findings. Changes in APT signal intensity may provide important insights into the characterization of the cerebral internal environment. This study suggests that APT imaging could be used as a complement to conventional MRI in the detection of hypoxic–ischemic encephalopathy in clinical practice.
Blockade of prostaglandin E2 receptor 4 ameliorates peritoneal dialysis-associated peritoneal fibrosis
Authors: Luo Qimei , Liu Mi , Tan Yanhong , Chen Jinzhong , Zhang Wei , Zhong Shaoxin , Pan Jianyi , Zheng Qingkun , Gong Lewei , Su Lijuan , Jia Zhanjun , Dou Xianrui
Published: November 2022

Inflammatory responses in the peritoneum contribute to peritoneal dialysis (PD)-associated peritoneal fibrosis. Results of our previous study showed that increased microsomal prostaglandin E synthase-1-mediated production of prostaglandin E2 (PGE2) contributed to peritoneal fibrosis. However, the role of its downstream receptor in the progression of peritoneal fibrosis has not been established. Here, we examined the role of PGE2 receptor 4 (EP4) in the development of peritoneal fibrosis. EP4 was significantly upregulated in peritoneal tissues of PD patients with ultrafiltration failure, along with the presence of an enhanced inflammatory response. In vitro experiments showed that exposure to high glucose concentrations enhanced EP4 expression in rat peritoneal mesothelial cells (RPMCs). High-glucose–induced expression of inflammatory cytokines (monocyte chemoattractant protein-1, tumour necrosis factor α, and interleukin 1β) was significantly reduced in RPMCs treated with ONO-AE3-208, an EP4 receptor antagonist. ONO-AE3-208 also significantly decreased the expression of extracellular matrix proteins induced by high glucose concentrations. Furthermore, ONO-AE3-208 blunted activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and phosphorylation of nuclear factor kappa B (NF-κB) (p-p65). To further investigate the functional role of EP4, ONO-AE3-208 was administrated for 4 weeks in a rat model of PD, the results of which showed that ONO-AE3-208 inhibited peritoneal fibrosis and improved peritoneal dysfunction. Additionally, inflammatory cytokines in the peritoneum of PD rats treated with ONO-AE3-208 were downregulated, in line with inhibition of the NLRP3 inflammasome and NF-κB phosphorylation. In conclusion, an EP4 antagonist reduced the development of peritoneal fibrosis, possibly by suppressing NLRP3 inflammasome- and p-p65–mediated inflammatory responses. Our findings suggest that an EP4 antagonist may be therapeutically beneficial for PD-associated peritoneal fibrosis.
Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation
Authors: Chan Shiu-Wan
Published: November 2022

Virus fusion process is evolutionarily conserved and provides a promising pan-viral target. Cell-cell fusion leads to syncytial formation and has implications in pathogenesis, virus spread and immune evasion. Drugs that target these processes can be developed into anti-virals. Here, we have developed sensitive, rapid, adaptable fusion reporter gene assays as models for plasma membrane and alternative fusion pathways as well as syncytial fusion in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have confirmed their specificity using neutralizing antibodies and specific protease inhibitors. The fusion report gene assays are more sensitive and unbiased than morphological fusion assay. The fusion assays can differentiate between transmembrane serine protease 2 (TMPRSS2)-dependency in TMPRSS2(+) cells and trypsin-dependency in angiotensin-converting enzyme 2 (ACE2)(+)TMPRSS2(-) cells. Moreover, we have identified putative novel fusion processes that are triggered by an acidic pH with and without trypsin. Coupled with morphological fusion criteria, we have found that syncytia formation is enhanced by TMPRSS2 or trypsin. By testing against our top drug hits previously shown to inhibit SARS-CoV-2 pseudovirus infection, we have identified several fusion inhibitors including structurally related lopsided kite-shaped molecules. Our results have important implications in the development of universal blockers and synergistic therapeutics and the small molecule inhibitors can provide important tools in elucidating the fusion process.
Review of preclinical data of PF-07304814 and its active metabolite derivatives against SARS-CoV-2 infection
Authors: Chen Wujun , Shao Yingchun , Peng Xiaojin , Liang Bing , Xu Jiazhen , Xing Dongming
Published: November 2022

Main protease (Mpro) is a superior target for anti-SARS-COV-2 drugs. PF-07304814 is a phosphate ester prodrug of PF-00835231 that is rapidly metabolized into the active metabolite PF-00835231 by alkaline phosphatase (ALP) and then suppresses SARS-CoV-2 replication by inhibiting Mpro. PF-07304814 increased the bioavailability of PF-00835231 by enhancing plasma protein binding (PPB). P-glycoprotein (P-gp) inhibitors and cytochrome P450 3A (CYP3A) inhibitors increased the efficacy of PF-00835231 by suppressing its efflux from target cells and metabolism, respectively. The life cycle of SARS-CoV-2 is approximately 4 h. The mechanisms and efficacy outcomes of PF-00835231 occur simultaneously. PF-00835231 can inhibit not only cell infection (such as Vero E6, 293T, Huh-7.5, HeLa+angiotensin-converting enzyme 2 (ACE2), A549+ACE2, and MRC-5) but also the human respiratory epithelial organ model and animal model infection. PF-07304814 exhibits a short terminal elimination half-life and is cleared primarily through renal elimination. There were no significant adverse effects of PF-07304814 administration in rats. Therefore, PF-07304814 exhibits good tolerability, pharmacology, pharmacodynamics, pharmacokinetics, and safety in preclinical trials. However, the Phase 1 data of PF-07304814 were not released. The Phase 2/3 trial of PF-07304814 was also suspended. Interestingly, the antiviral activities of PF-00835231 derivatives (compounds 5–22) are higher than, similar to, or slightly weaker than those of PF-00835231. In particular, compound 22 exhibited the highest potency and had good safety and stability. However, the low solubility of compound 22 limits its clinical application. Prodrugs, nanotechnology and salt form drugs may solve this problem. In this review, we focus on the preclinical data of PF-07304814 and its active metabolite derivatives to hopefully provide knowledge for researchers to study SARS-CoV-2 infection.
Data mining and safety analysis of BTK inhibitors: A pharmacovigilance investigation based on the FAERS database
Authors: Wan Qing , Li Qiang , Lai Xin , Xu Tiantian , Hu Jinfang , Peng Hongwei
Published: November 2022

Objective: The introduction of Bruton’s tyrosine kinase (BTK) inhibitors was a milestone in the treatment of B-cell malignancies in recent years owing to its desired efficacy against chronic lymphocytic leukaemia and small cell lymphocytic lymphoma. However, safety issues have hindered its application in clinical practice. The current study aimed to explore the safety warning signals of BTK inhibitors in a real-world setting using the FDA Adverse Event Reporting System (FAERS) to provide reference for clinical rational drug use.

Methods: Owing to the short marketing time of other drugs (zanbrutinib and orelabrutinib), we only analysed ibrutinib and acalabrutinib in this study. All data were obtained from the FAERS database from January 2004 to December 2021. Disproportionality analysis and Bayesian analysis were utilised to detect and assess the adverse event (AE) signals of BTK inhibitors.

Results: In total, 43,429 reports of ibrutinib were extracted and 1527 AEs were identified, whereas 1742 reports of acalabrutinib were extracted and 220 AEs were identified by disproportionality analysis and Bayesian analysis. Among reports, males were more prone to develop AEs (58.2% for males vs. 35.6% for females treated with ibrutinib, and 55.9% vs. 31.9%, respectively, for acalabrutinib), and more than 30% of patients that suffered from AEs were over 65 years of age. Subsequently, we investigated the top 20 preferred terms (PTs) associated with the signal strength of ibrutinib and acalabrutinib, and our results identified 25 (13 vs. 12, respectively) novel risk signals. Among the top 20 PTs related to death reports, the terms infectious, pneumonia, pleural effusion, fall, asthenia, diarrhoea, and fatigue were all ranked high for these two BTK inhibitors. Further, cardiac disorders were also an important cause of death with ibrutinib.

Conclusion: Patients treated with ibrutinib were more prone to develop AEs than those treated with acalabrutinib. Importantly, infection-related adverse reactions, such as pneumonia and pleural effusion, were the most common risk signals related to high mortality associated with both BTK inhibitors, especially in elderly patients. Moreover, cardiovascular-related adverse reactions, such as atrial fibrillation and cardiac failure, were fatal AEs associated with ibrutinib. Our results provide a rationale for physicians to choose suitable BTK inhibitors for different patients and provide appropriate monitoring to achieve safer therapy and longer survival.
Design of novel disturbing peptides against ACE2 SARS-CoV-2 spike-binding region by computational approaches
Authors: Zareei Sara , Pourmand Saeed , Amanlou Massoud
Published: November 2022

The SARS-CoV-2, the virus which is responsible for COVID-19 disease, employs its spike protein to recognize its receptor, angiotensin-converting enzyme 2 (ACE2), and subsequently enters the host cell. In this process, the receptor-binding domain (RBD) of the spike has an interface with the α1-helix of the peptidase domain (PD) of ACE2. This study focuses on the disruption of the protein-protein interaction (PPI) of RBD-ACE2. Among the residues in the template (which was extracted from the ACE2), those with unfavorable energies were selected for substitution by mutagenesis. As a result, a library of 140 peptide candidates was constructed and the binding affinity of each candidate was evaluated by molecular docking and molecular dynamics simulations against the α1-helix of ACE2. Finally, the most potent peptides P23 (GFNNYFPHQSYGFMPTNGVGY), P28 (GFNQYFPHQSYGFPPTNGVGY), and P31 (GFNRYFPHQSYGFCPTNGVGY) were selected and their dynamic behaviors were studied. The results showed peptide inhibitors increased the radius, surface accessible area, and overall mobility of residues of the protein. However, no significant alteration was seen in the key residues in the active site. Meanwhile, they can be proposed as promising agents against COVID-19 by suppressing the viral attachment and curbing the infection at its early stage. The designed peptides showed potency against beta, gamma, delta, and omicron variants of SARS-CoV-2.
Locating and imaging composite damage based on frequency spectrum detection of lamb waves
Authors: Zhang Wenchao , Su Chenhui , Zhang Yuhang , Yang Hongjuan
Published: November 2022

Lamb wave is widely concerned in damage detection of composite structures due to its long propagation distance and strong sensitivity to damage. In order to solve the problem of damage information extraction, high-precision imaging positioning of damage is realized. A damage location imaging method based on lamb signal spectrum is proposed. The damage location imaging of composite materials is realized by simulation and experiment respectively. Firstly, the feasibility of the algorithm is verified by simulation. The circular sensor array is arranged in the structure. Each sensor acts as an actuator and rotates clockwise to generate Lamb waves, while other sensors collect signals. The frequency spectrum of the signal is extracted to calculate the damage factor, and the probability imaging algorithm is used to realize the single damage and multiple damage location imaging. Then, the damage imaging localization is realized through experiments. Finally, the resistant noise characteristic of the proposed algorithm is analyzed. The results show that both single damage and multiple damage can be located in strong noise environment. It shows that this method can realize damage imaging directly without preprocessing the original signal. It has great potential in damage location imaging under strong noise environment.
Two-dimensional Cr-based ferromagnetic semiconductor: Theoretical simulations and design
Authors: Tu Yufei , Liu Qingquan , Hou Lipeng , Shi Puyuan , Jia Chaobin , Su Jingjuan , Zhang Jiawen , Zhang Xiuyun , Wang Bing
Published: November 2022

Two-dimensional (2D) material is the promising for next-generation information technology. The recently discovered intrinsic magnetic crystals have simulated a renaissance in 2D spintronics, which provides an ideal platform for exploring novel physical phenomena. However, current experimental trial-and-error methods in discovering new spintronic material are still very expensive and challenging. In contrast, based on well-developed first-principles calculations, computationally designing the spintronic materials provides a more efficient way for exploring new ferromagnetic (FM) materials and understanding the nature of magnetic properties. Several predictions, such as CrI3 monolayer, CrGeTe3 bilayer, CrSBr monolayer, FeCl2 monolayer, and Fe3GeTe2 monolayer have been confirmed by experiments, showing the great performance of computational approaches. This minireview article attempts to give a brief of discovering intrinsic 2D spintronics from theoretical aspect, and in particular, we emphasize roles played by calculation based on first-principles methods in designing 2D FM materials and devices. The current challenges and proposals on future developments of 2D spintronics are also discussed.
Chronic heat stress part 1: Decrease in egg quality, increase in cortisol levels in egg albumen, and reduction in fertility of breeder pekin ducks
Authors: Oluwagbenga E. M. , Tetel V. , Schober J. , Fraley G. S.
Published: November 2022

Global warming poses detrimental effects on poultry production leading to substantial economic losses. The goal of our experiment was to test the hypothesis that heat stress (HS) would alter welfare and egg quality (EQ) of breeder ducks. Furthermore, we wanted to test if HS would increase cortisol levels in egg albumen. Adult Pekin ducks were randomly assigned to two different rooms at 85% lay with 60 hens and 20 drakes per room. Baseline data including body weight, body condition scores (BCS), and egg production/quality were collected the week preceding heat treatment. Ducks were subjected to cyclic HS of 35°C for 10h/day and 29.5°C for the remaining 14h/day for 3 weeks while the control room was maintained at 22°C. Eggs were collected daily and analyzed weekly for quality assessment, and for albumen glucocorticoid (GCs) levels using mass spectrometry. One week before the exposure to HS, 10 hens and 5 drakes were euthanized and the same number again after 3 weeks and birds necropsied. Data analyses were done by 1- or 2-way ANOVA as appropriate with a Tukey-Kramer post hoc test. BCS were analyzed using a chi-squared test. A p ≤ 0.05 was considered significant. Circulating levels of corticosterone were significantly (p < 0.01) elevated at week 1 only in the HS hens. The circulating levels of cortisol increased significantly at week 1 and 2 (p < 0.05), and week 3 (p < 0.01) in the hens and at weeks 2 and 3 only (p < 0.05) in the drakes. Feather quality scores (p < 0.01), feather cleanliness scores (p < 0.001) and footpad quality scores (p < 0.05) increased significantly in the HS group. HS elicited a significant (p < 0.001) decrease in egg production at weeks 1 and 3. Hens in the HS group showed significantly decreased BW (p < 0.001) and number of follicles (p < 0.05). Shell weight decreased significantly at week 1 only (p < 0.05) compared to controls. Yolk weight decreased significantly at week 3 (p < 0.01) compared to controls. HS elicited a significant increase in albumen cortisol levels at week 1 (p < 0.05) and week 3 (p < 0.05). Thus, cortisol may provide critical information to further understand and to improve welfare.