bluuebunny/crossref_metadata_2025 huggingface dataset:
Stably transmitted defined microbial community in honeybees preserves Hafnia alvei inhibition by regulating the immune system
Authors: Wang Jieni , Lang Haoyu , Zhang Wenhao , Zhai Yifan , Zheng Li , Chen Hao , Liu Yan , Zheng Hao
Published: December 2022

The gut microbiota of honeybees is highly diverse at the strain level and essential to the proper function and development of the host. Interactions between the host and its gut microbiota, such as specific microbes regulating the innate immune system, protect the host against pathogen infections. However, little is known about the capacity of these strains deposited in one colony to inhibit pathogens. In this study, we assembled a defined microbial community based on phylogeny analysis, the ‘Core-20’ community, consisting of 20 strains isolated from the honeybee intestine. The Core-20 community could trigger the upregulation of immune gene expressions and reduce Hafnia alvei prevalence, indicating immune priming underlies the microbial protective effect. Functions related to carbohydrate utilization and the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS systems) are represented in genomic analysis of the defined community, which might be involved in manipulating immune responses. Additionally, we found that the defined Core-20 community is able to colonize the honeybee gut stably through passages. In conclusion, our findings highlight that the synthetic gut microbiota could offer protection by regulating the host immune system, suggesting that the strain collection can yield insights into host-microbiota interactions and provide solutions to protect honeybees from pathogen infections.
Parapoxvirus-based therapy eliminates SARS-CoV-2-loaded fine aerosol and blocks viral transmission in hamster models
Authors: Cui Huan , Zhao Kui , Zhang Cheng , Lin Jing , Sun Shihui , Li Qi , Du Le , Zhang Chunmao , Liu Juxiang , Gao Feng , He Wenqi , Gao Yuwei , Guo Zhendong , Guan Jiyu
Published: December 2022

Currently, it is believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne virus, and virus-containing aerosol particles have been found concurrent with the onset of COVID-19, which may contribute to the noncontact transmission of SARS-CoV-2. Exploring agents to block SARS-CoV-2 transmission is of great importance to prevent the COVID-19 pandemic. In this study, we found that inactivated Parapoxvirus ovis (iORFV), a kind of immunomodulator, could compress the proportion of small particle aerosols exhaled by Syrian golden hamsters. Notably, the concentration of SARS-CoV-2 RNA-containing aerosol particles was significantly reduced by iORFV in the early stages after viral inoculation. Importantly, smaller aerosol particles (<4.7 μm) that carry infectious viruses were completely cleared by iORFV. Consistently, iORFV treatment completely blocked viral noncontact (aerosol) transmission. In summary, iORFV may become a repurposed agent for the prevention and control of COVID-19 by affecting viral aerosol exhalation and subsequent viral transmission.
Horizontal gene transfer via OMVs co-carrying virulence and antimicrobial-resistant genes is a novel way for the dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae
Authors: Li Ping , Luo Wanying , Xiang Tian-Xin , Jiang Yuhuan , Liu Peng , Wei Dan-Dan , Fan Linping , Huang Shanshan , Liao Wenjian , Liu Yang , Zhang Wei
Published: December 2022

Introduction

The rapidly increased isolation rate of CR-HvKP worldwide has brought great difficulties in controlling clinical infection. Moreover, it has been demonstrated that the transmission of drug-resistant genes among bacteria can be mediated by outer membrane vesicles (OMVs), which is a new way of horizontal gene transfer (HGT). The transmission of virulence genes among bacteria has also been well studied; however, it remains unclear whether virulence and drug-resistant genes can be co-transmitted simultaneously. Co-transmission of virulence and drug-resistant genes is essential for the formation and prevalence of CR-HvKP.

Methods

First, we isolated OMVs from CR-HvKP by cushioned-density gradient ultracentrifugation (C-DGUC). TEM and DLS were used to examine the morphology and size of bacterial OMVs. OMV-mediated gene transfer in liquid cultures and the acquisition of the carbapenem gene and virulence gene was confirmed using colony-PCR. Antimicrobial susceptibility testing, mCIM and eCIM were conducted for the resistance of transformant. Serum killing assay, assessment of the anti-biofilm effect and galleria mellonella infection model, mucoviscosity assay, extraction and quantification of capsules were verified the virulence of transformant. Pulsed-field gel electrophoresis (PFGE), S1 nuclease-pulsed-field gel electrophoresis (S1-PFGE), Southern blotting hybridization confirmed the plasmid of transformant.

Results

Firstly, OMVs were isolated from CR-HvKP NUHL30457 (K2, ST86). TEM and DLS analyses revealed the spherical morphology of the vesicles. Secondly, our study demonstrated that CR-HvKP delivered genetic material, incorporated DNA within the OMVs, and protected it from degradation by extracellular exonucleases. Thirdly, the vesicular lumen DNA was delivered to the recipient cells after determining the presence of virulence and carbapenem-resistant genes in the CR-HvKP OMVs. Importantly, S1-PFGE and Southern hybridization analysis of the 700603 transformant strain showed that the transformant contained both drug-resistant and virulence plasmids.

Discussion

In the present study, we aimed to clarify the role of CRHvKP-OMVs in transmitting CR-HvKP among K. pneumoniae. Collectively, our findings provided valuable insights into the evolution of CR-HvKP.
The influence of species identity and geographic locations on gut microbiota of small rodents
Authors: Wang Zhenyu , Zhang Chao , Li Guoliang , Yi Xianfeng
Published: December 2022

Although the correlation between gut microbiota, species identity and geographic locations has long attracted the interest of scientists, to what extent species identity and geographic locations influence the gut microbiota assemblages in granivorous rodents needs further investigation. In this study, we performed a survey of gut microbial communities of four rodent species (Apodemus agrarius, A. peninsulae, Tamias sibiricus and Clethrionomys rufocanus) distributed in two areas with great distance (> 600 km apart), to assess if species identity dominates over geographic locations in shaping gut microbial profiles using 16S rRNA gene sequencing. We found that gut microbiota composition varied significantly across host species and was closely correlated with host genetics. We identified strong species identity effects on gut microbial composition, with a comparatively weaker signal of geographic provenance on the intestinal microbiota. Specifically, microbiota of one species was on average more similar to that of conspecifics living in separate sites than to members of a closely related species living in the same location. Our study suggests that both host genetics and geographical variations influence gut microbial diversity of four rodent species, which merits further investigation to reveal the patterns of phylogenetic correlation of gut microbial community assembly in mammals across multiple habitats.
An AI-based approach for detecting cells and microbial byproducts in low volume scanning electron microscope images of biofilms
Authors: Abeyrathna Dilanga , Ashaduzzaman Md , Malshe Milind , Kalimuthu Jawaharraj , Gadhamshetty Venkataramana , Chundi Parvathi , Subramaniam Mahadevan
Published: December 2022

Microbially induced corrosion (MIC) of metal surfaces caused by biofilms has wide-ranging consequences. Analysis of biofilm images to understand the distribution of morphological components in images such as microbial cells, MIC byproducts, and metal surfaces non-occluded by cells can provide insights into assessing the performance of coatings and developing new strategies for corrosion prevention. We present an automated approach based on self-supervised deep learning methods to analyze Scanning Electron Microscope (SEM) images and detect cells and MIC byproducts. The proposed approach develops models that can successfully detect cells, MIC byproducts, and non-occluded surface areas in SEM images with a high degree of accuracy using a low volume of data while requiring minimal expert manual effort for annotating images. We develop deep learning network pipelines involving both contrastive (Barlow Twins) and non-contrastive (MoCoV2) self-learning methods and generate models to classify image patches containing three labels—cells, MIC byproducts, and non-occluded surface areas. Our experimental results based on a dataset containing seven grayscale SEM images show that both Barlow Twin and MoCoV2 models outperform the state-of-the-art supervised learning models achieving prediction accuracy increases of approximately 8 and 6%, respectively. The self-supervised pipelines achieved this superior performance by requiring experts to annotate only ~10% of the input data. We also conducted a qualitative assessment of the proposed approach using experts and validated the classification outputs generated by the self-supervised models. This is perhaps the first attempt toward the application of self-supervised learning to classify biofilm image components and our results show that self-supervised learning methods are highly effective for this task while minimizing the expert annotation effort.
Physical-model guided self-distillation network for single image dehazing
Authors: Lan Yunwei , Cui Zhigao , Su Yanzhao , Wang Nian , Li Aihua , Han Deshuai
Published: December 2022

Motivation

Image dehazing, as a key prerequisite of high-level computer vision tasks, has gained extensive attention in recent years. Traditional model-based methods acquire dehazed images via the atmospheric scattering model, which dehazed favorably but often causes artifacts due to the error of parameter estimation. By contrast, recent model-free methods directly restore dehazed images by building an end-to-end network, which achieves better color fidelity. To improve the dehazing effect, we combine the complementary merits of these two categories and propose a physical-model guided self-distillation network for single image dehazing named PMGSDN.

Proposed method

First, we propose a novel attention guided feature extraction block (AGFEB) and build a deep feature extraction network by it. Second, we propose three early-exit branches and embed the dark channel prior information to the network to merge the merits of model-based methods and model-free methods, and then we adopt self-distillation to transfer the features from the deeper layers (perform as teacher) to shallow early-exit branches (perform as student) to improve the dehazing effect.

Results

For I-HAZE and O-HAZE datasets, better than the other methods, the proposed method achieves the best values of PSNR and SSIM being 17.41dB, 0.813, 18.48dB, and 0.802. Moreover, for real-world images, the proposed method also obtains high quality dehazed results.

Conclusion

Experimental results on both synthetic and real-world images demonstrate that the proposed PMGSDN can effectively dehaze images, resulting in dehazed results with clear textures and good color fidelity.
Siamese hierarchical feature fusion transformer for efficient tracking
Authors: Dai Jiahai , Fu Yunhao , Wang Songxin , Chang Yuchun
Published: December 2022

Object tracking is a fundamental task in computer vision. Recent years, most of the tracking algorithms are based on deep networks. Trackers with deeper backbones are computationally expensive and can hardly meet the real-time requirements on edge platforms. Lightweight networks are widely used to tackle this issue, but the features extracted by a lightweight backbone are inadequate for discriminating the object from the background in complex scenarios, especially for small objects tracking task. In this paper, we adopted a lightweight backbone and extracted features from multiple levels. A hierarchical feature fusion transformer (HFFT) was designed to mine the interdependencies of multi-level features in a novel model—SiamHFFT. Therefore, our tracker can exploit comprehensive feature representations in an end-to-end manner, and the proposed model is capable of handling small target tracking in complex scenarios on a CPU at a rate of 29 FPS. Comprehensive experimental results on UAV123, UAV123@10fps, LaSOT, VOT2020, and GOT-10k benchmarks with multiple trackers demonstrate the effectiveness and efficiency of SiamHFFT. In particular, our SiamHFFT achieves good performance both in accuracy and speed, which has practical implications in terms of improving small object tracking performance in the real world.
Endothelin-1, over-expressed in SOD1G93A mice, aggravates injury of NSC34-hSOD1G93A cells through complicated molecular mechanism revealed by quantitative proteomics analysis
Authors: Zhang Yingzhen , Chen Lin , Li Zhongzhong , Li Dongxiao , Wu Yue , Guo Yansu
Published: December 2022

Endothelin-1 (ET-1), a secreted signaling peptide, is suggested to be involved in multiple actions in various tissues including the brain, but its role in amyotrophic lateral sclerosis (ALS) remains unknown. In this study, we detected the expression changes as well as the cellular localization of ET-1, endothelin A (ET-A) and endothelin B (ET-B) receptors in spinal cord of transgenic SOD1-G93A (TgSOD1-G93A) mice, which showed that the two ET receptors (ET-Rs) expressed mainly on neurons and decreased as the disease progressed especially ET-B, while ET-1 expression was up-regulated and primarily localized on astrocytes. We then explored the possible mechanisms underlying the effect of ET-1 on cultured NSC34-hSOD1G93A cell model. ET-1 showed toxic effect on motor neurons (MNs), which can be rescued by the selective ET-A receptor antagonist BQ-123 or ET-B receptor antagonist BQ-788, suggesting that clinically used ET-Rs pan-antagonist could be a potential strategy for ALS. Using proteomic analysis, we revealed that 110 proteins were differentially expressed in NSC34-hSOD1G93A cells after ET-1 treatment, of which 54 were up-regulated and 56 were down-regulated. Bioinformatic analysis showed that the differentially expressed proteins (DEPs) were primarily enriched in hippo signaling pathway-multiple species, ABC transporters, ErbB signaling pathway and so on. These results provide further insights on the potential roles of ET-1 in ALS and present a new promising therapeutic target to protect MNs of ALS.
Improved neuron protection following cortical injury in the absence of Semaphorin4B
Authors: Sweetat Sahar , Casden Natania , Behar Oded
Published: December 2022

Injury to the central nervous system induces neuronal cell death and astrogliosis, an astrocyte-mediated response that has both a beneficial and detrimental impact on surrounding neuronal cells. The circumstance however, in which astrogliosis improves neuronal survival after an injury is not fully characterized. We have recently shown that Semaphorin4B (Sema4B) in the cortex is mostly expressed by astrocytes, and in its absence, astrocyte activation after an injury is altered. Here we find that in Sema4B knockout mice, neuronal cell death is reduced; as a result, more neurons survive near the injury site. Sema4B protein applied directly to neurons does not affect neuronal survival. In contrast, survival of wild-type neurons is increased when plated on glial culture isolated from the Sema4B knockout mice, as compared to Sema4B heterozygous cultures. Furthermore, this increased survival is also observed with conditioned medium collected from glial cultures of Sema4B knockout mice compared to heterozygous mice. This indicates that the increased survival is glial cell-dependent and mediated by a secreted factor(s). Together, our results imply that following injury, the lack of Sema4B expression in glial cells improves neuronal survival either as a result of reduced toxic factors, or perhaps increased survival factors under these conditions.
Elderly onset of MELAS in a male: A case report
Authors: Diao Sheng-Peng , Chen Song-Fa , Liu Ai-Qun , Zhou Zhi-Hua , Peng Zhong-Xing , Hong Ming-Fan
Published: December 2022

Background

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common maternally inherited mitochondrial diseases which rarely affects elderly people.

Case presentation

We reported the case of a 61-year-old male patient with MELAS. He was experiencing acute migraine-like headaches as the first symptoms. Laboratory data showed elevated lactate and creatine kinase levels. Brain magnetic resonance imaging (MRI) found a high signal intensity lesion in the left occipital-temporal-parietal lobe on diffusion-weighted imaging (DWI). Magnetic resonance angiography (MRA) revealed reversible vasoconstriction of the middle cerebral arteries and superficial temporal arteries. A muscle biopsy suggested minor muscle damage. A genetic study revealed a mitochondrial DNA A3243G mutation.

Conclusion

Elderly onset of MELAS is rare and easily misdiagnosed as an ischemic stroke. MELAS with the onset of stroke-like episodes should be considered in adult or elderly patients with imaging findings that are atypical for cerebral infarction. The use of multimodal MRI in the clinical diagnosis of MELAS could be extremely beneficial.
Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia
Authors: Xu Minjie , Gao Ying , Zhang Hua , Zhang Binlong , Lyu Tianli , Tan Zhongjian , Li Changming , Li Xiaolin , Huang Xing , Kong Qiao , Xiao Juan , Kranz Georg S. , Li Shuren , Chang Jingling
Published: December 2022

Introduction

Post-stroke aphasia (PSA) is a language disorder caused by left hemisphere stroke. Electroacupuncture (EA) is a minimally invasive therapeutic option for PSA treatment. Tongli (HT5) and Xuanzhong (GB39), two important language-associated acupoints, are frequently used in the rehabilitation of patients with PSA. Preliminary evidence indicated functional activation in distributed cortical areas upon HT5 and GB39 stimulation. However, research on the modulation of dynamic and static functional connectivity (FC) in the brain by EA in PSA is lacking.

Method

This study aimed to investigate the PSA-related effects of EA stimulation at HT5 and GB39 on neural processing. Thirty-five participants were recruited, including 19 patients with PSA and 16 healthy controls (HCs). The BOLD signal was analyzed by static independent component analysis, generalized psychophysiological interactions, and dynamic independent component analysis, considering variables such as age, sex, and years of education.

Results

The results revealed that PSA showed activated clusters in the left putamen, left postcentral gyrus (PostCG), and left angular gyrus in the salience network (SN) compared to the HC group. The interaction effect on temporal properties of networks showed higher variability of SN (F = 2.23, positive false discovery rate [pFDR] = 0.017). The interaction effect on static FC showed increased functional coupling between the right calcarine and right lingual gyrus (F = 3.16, pFDR = 0.043). For the dynamic FC, at the region level, the interaction effect showed lower variability and higher frequencies of circuit 3, with the strongest connections between the supramarginal gyrus and posterior cingulum (F = 5.42, pFDR = 0.03), middle cingulum and PostCG (F = 5.27, pFDR = 0.036), and triangle inferior frontal and lingual gyrus (F = 5.57, pFDR = 0.026). At the network level, the interaction effect showed higher variability in occipital network–language network (LN) and cerebellar network (CN) coupling, with stronger connections between the LN and CN (F = 4.29, pFDR = 0.042). Dynamic FC values between the triangle inferior frontal and lingual gyri were anticorrelated with transcribing, describing, and dictating scores in the Chinese Rehabilitation Research Center for Chinese Standard Aphasia Examination.

Discussion

These findings suggest that EA stimulation may improve language function, as it significantly modulated the nodes of regions/networks involved in the LN, SN, CN, occipital cortex, somatosensory regions, and cerebral limbic system.
Treatment recommendations for non-HIV associated cryptococcal meningoencephalitis including management of post-infectious inflammatory response syndrome
Authors: Ssebambulidde Kenneth , Anjum Seher H. , Hargarten Jessica C. , Chittiboina Prashant , Shoham Shmuel , Seyedmousavi Seyedmojtaba , Marr Kieren A. , Hammoud Dima A. , Billioux Bridgette Jeanne , Williamson Peter R.
Published: December 2022

Cryptococcal meningoencephalitis (CM) continues to cause major morbidity and mortality in a range of patients such as those immunosuppressed from HIV and with biologic immunosuppressants, including treatments of autoimmunity, malignancies, and conditioning regimens for transplantation. It is currently the most common cause of non-viral meningitis in the United States. Infections in previously healthy patients also develop with autoantibodies to granulocyte-macrophage colony stimulating factor or with monogenetic defects. In all populations, mortality and significant long-term morbidity occur in 30–50% despite therapy, and immune reconstitution and post-infectious inflammatory response syndromes complicate management. To help with these difficult cases, we present here a practical tutorial of the care of a range of patients with CM in the absence of HIV/AIDS.
Sleep deprivation induces delayed regeneration of olfactory sensory neurons following injury
Authors: Han Bing , Kikuta Shu , Kamogashira Teru , Kondo Kenji , Yamasoba Tatsuya
Published: December 2022

The circadian system, which is essential for the alignment of sleep/wake cycles, modulates adult neurogenesis. The olfactory epithelium (OE) has the ability to generate new neurons throughout life. Loss of olfactory sensory neurons (OSNs) as a result of injury to the OE triggers the generation of new OSNs, which are incorporated into olfactory circuits to restore olfactory sensory perception. This regenerative potential means that it is likely that the OE is substantially affected by sleep deprivation (SD), although how this may occur remains unclear. The aim of this study is to address how SD affects the process of OSN regeneration following OE injury. Mice were subjected to SD for 2 weeks, which induced changes in circadian activity. This condition resulted in decreased activity during the night-time and increased activity during the daytime, and induced no histological changes in the OE. However, when subjected to SD during the regeneration process after OE injury, a significant decrease in the number of mature OSNs in the dorsomedial area of the OE, which is the only area containing neurons expressing NQO1 (quinone dehydrogenase 1), was observed compared to the NQO1-negative OE. Furthermore, a significant decrease in proliferating basal cells was observed in the NQO1-positive OE compared to the NQO1-negative OE, but no increase in apoptotic OSNs was observed. These results indicate that SD accompanied by disturbed circadian activity could induce structurally negative effects on OSN regeneration, preferentially in the dorsomedial area of the OE, and that this area-specific regeneration delay might involve the biological activity of NQO1.
Effect of face masks on speech perception in noise of individuals with hearing aids
Authors: Choi Jung Ho , Choi Hyo Jung , Kim Dong Hyun , Park Ji Hye , An Yong-Hwi , Shim Hyun Joon
Published: December 2022

Although several previous studies have confirmed that listeners find it difficult to perceive the speech of face-mask-wearing speakers, there has been little research into how masks affect hearing-impaired individuals using hearing aids. Therefore, the aim of this study was to compare the effects of masks on the speech perception in noise of hearing-impaired individuals and normal-hearing individuals. We also investigated the effect of masks on the gain conferred by hearing aids. The hearing-impaired group included 24 listeners (age: M = 69.5, SD = 8.6; M:F = 13:11) who had used hearing aids in everyday life for >1 month (M = 20.7, SD = 24.0) and the normal-hearing group included 26 listeners (age: M = 57.9, SD = 11.1; M:F = 13:13). Speech perception in noise was measured under no mask–auditory-only (no-mask–AO), no mask–auditory–visual (no-mask–AV), and mask–AV conditions at five signal-to-noise ratios (SNRs; −16, −12, −8, −4, 0 dB) using five lists of 25 monosyllabic Korean words. Video clips that included a female speaker’s face and sound or the sound only were presented through a monitor and a loudspeaker located 1 m in front of the listener in a sound-attenuating booth. The degree of deterioration in speech perception caused by the mask (no-mask–AV minus mask–AV) was significantly greater for hearing-impaired vs. normal-hearing participants only at 0 dB SNR (Bonferroni’s corrected p < 0.01). When the effects of a mask on speech perception, with and without hearing aids, were compared in the hearing-impaired group, the degree of deterioration in speech perception caused by the mask was significantly reduced by the hearing aids compared with that without hearing aids at 0 and −4 dB SNR (Bonferroni’s corrected p < 0.01). The improvement conferred by hearing aids (unaided speech perception score minus aided speech perception score) was significantly greater at 0 and −4 dB SNR than at −16 dB SNR in the mask–AV group (Bonferroni’s corrected p < 0.01). These results demonstrate that hearing aids still improve speech perception when the speaker is masked, and that hearing aids partly offset the effect of a mask at relatively low noise levels.
Characterisation of parasympathetic ascending nerves in human colon
Authors: Johnson Michaela E. , Humenick Adam , Peterson Rochelle A. , Costa Marcello , Wattchow David A. , Sia Tiong Cheng , Dinning Phil G. , Brookes Simon J. H.
Published: December 2022

Background

In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus (“hypogastric plexus”) and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming “ascending nerves” or “shunt fascicles” running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width.

Aim

To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon.

Methods

Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery (n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves.

Results

The rectosigmoid and rectal specimens had 6–11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1–3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres.

Conclusion

Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.
A developmental delay linked missense mutation in Kalirin-7 disrupts protein function and neuronal morphology
Authors: Parnell Euan , Voorn Roos A. , Martin-de-Saavedra M. Dolores , Loizzo Daniel D. , Dos Santos Marc , Penzes Peter
Published: December 2022

The Rac1 guanine exchange factor Kalirin-7 is a key regulator of dendritic spine morphology, LTP and dendritic arborization. Kalirin-7 dysfunction and genetic variation has been extensively linked to various neurodevelopmental and neurodegenerative disorders. Here we characterize a Kalirin-7 missense mutation, glu1577lys (E1577K), identified in a patient with severe developmental delay. The E1577K point mutation is located within the catalytic domain of Kalirin-7, and results in a robust reduction in Kalirin-7 Rac1 Guanosine exchange factor activity. In contrast to wild type Kalirin-7, the E1577K mutant failed to drive dendritic arborization, spine density, NMDAr targeting to, and activity within, spines. Together these results indicate that reduced Rac1-GEF activity as result of E1577K mutation impairs neuroarchitecture, connectivity and NMDAr activity, and is a likely contributor to impaired neurodevelopment in a patient with developmental delay.
Glucosamine inhibits extracellular matrix accumulation in experimental diabetic nephropathy
Authors: Teuma Loic , Eshwaran Rachana , Tawokam Fongang Ulrich , Wieland Johanna , Shao Feng , Lagana Maria Luisa , Wang Yixin , Agaci Ane , Hammes Hans-Peter , Feng Yuxi
Published: December 2022

Introduction

Glucosamine, the intermediate metabolite of the hexosamine biosynthesis pathway (HBP), is widely used as a supplementary drug in patients with osteoarthritis. However, its consequences in such patients concomitantly suffering from diabetic nephropathy is unknown.

Methods

The aim of the study was to investigate the effect of exogenous administration of glucosamine in the diabetic kidney. A mouse model of streptozotocin-induced diabetic nephropathy in vivo and cultured endothelial cells in vitro were used in the study. The mice were treated with glucosamine for 6 months. Renal function was evaluated by metabolic cage, and histology of the kidney was estimated by periodic acid-schiff (PAS) staining. The expression of related genes was assessed by real-time PCR, immunofluorescence staining, immunoblotting and ELISA.

Results

There was no significant difference in urinary albumin secretion, relative kidney weight, or creatinine clearance between the groups treated with glucosamine and controls. Assessment of the kidney demonstrated reduction in mesangial expansion and fibronectin expression in the diabetic glomeruli treated with glucosamine. Glucosamine treatment significantly decreased α-smooth muscle actin (α-SMA) protein expression in both diabetic and control kidneys, whereas the expression of other fibrosis-related genes and inflammatory factors was unaltered. Moreover, α-SMA colocalized with the endothelial marker CD31 in the diabetic and control kidneys, and glucosamine reduced α-SMA+ ECs in the diabetic glomeruli. In addition, glucosamine suppressed α-SMA expression in endothelial cells treated with or without high glucose.

Discussion

In summary, this is the first report to show that glucosamine reduces mesangial expansion and inhibits endothelial-mesenchymal transition in diabetic nephropathy. The underlying mechanisms need to be further investigated.
Modulatory effect of camel milk on intestinal microbiota of mice with non-alcoholic fatty liver disease
Authors: Hao Shiqi , Ming Liang , Li Yafei , Lv Haodi , Li Lin , Jambal Tuyatsetseg , Ji Rimutu
Published: December 2022

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease of life, usually caused by unhealthy diet and lifestyle. Compared to normal individuals, the structure of the intestinal flora of NAFLD patients is altered accordingly. This study investigates the effect of camel milk on the regulation of intestinal flora structure in mice with high-fat diet-induced NAFLD. NAFLD model was established by feeding C57BL/6J mice a high-fat diet for 12 weeks, meanwhile camel milk (3.0 g/kg/d), cow milk (3.0 g/kg/d), and silymarin (200 mg/kg/d) were administered by gavage, respectively. Food intake and changes of physiological indexes in mice were observed and recorded. The 16S rRNA gene V3-V4 region was sequenced and the intestinal flora diversity and gene function were predicted in the colon contents of mice from different group. The results showed that camel milk enhanced glucolipid metabolism by downregulate the levels of blood glucose and triglyceride (TG) in serum, reduced lipid accumulation by downregulate the level of TG in the liver and improved liver tissue structure in NAFLD mice (p < 0.05). Meanwhile, camel milk had a positive modulatory effect on the intestinal flora of NAFLD mice, increasing the relative abundance of beneficial bacteria and decreasing the relative abundance of harmful bacteria in the intestinal flora of NAFLD mice, and silymarin had a similar modulatory effect. At the genus level, camel milk increased the relative abundance of Bacteroides, norank_f_Muribaculaceae and Alloprevotella and decreased the relative abundance of Dubosiella and Coriobacteriaceae_UCG-002 (p < 0.05). Camel milk also enhanced Carbohydrate metabolism, Amino acid metabolism, Energy metabolism, Metabolism of cofactors and vitamins and Lipid metabolism in NAFLD mice, thus reducing the degree of hepatic lipid accumulation in NAFLD mice and maintaining the normal structure of the liver. In conclusion, camel milk can improve the structure and diversity of intestinal flora and enhance the levels of substance and energy metabolism in NAFLD mice, which has a positive effect on alleviating NAFLD and improving the structure of intestinal flora.
Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017–2018
Authors: Tong Junlu , Zeng Yingjuan , Xie Jianhui , Xiao Kecen , Li Man , Cong Li
Published: December 2022

Background

Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD.

Purpose

To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population.

Materials and methods

The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017–2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders.

Results

A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (Pinteraction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02).

Conclusion

MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.
Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: Association with insulin resistance and weight loss in a population with metabolic syndrome
Authors: Soldevila-Domenech Natalia , Pastor Antoni , Sala-Vila Aleix , Lázaro Iolanda , Boronat Anna , Muñoz Daniel , Castañer Olga , Fagundo Beatriz , Corella Dolores , Fernández-Aranda Fernando , Martínez-González Miguel Ángel , Salas-Salvadó Jordi , Fitó Montserrat , de la Torre Rafael
Published: December 2022

Background

Excess circulating endocannabinoids (eCBs) and imbalanced N-acylethanolamines (NAEs) related eCBs abundance could influence dietary weight loss success. We aimed to examine sex differences in the impact of a 3-years Mediterranean diet (MedDiet) intervention on circulating eCBs, NAEs and their precursor fatty acids, and to analyze the interplay between changes in eCBs or NAEs ratios, insulin resistance and the achievement of clinically meaningful weight reductions.

Methods

Prospective cohort study in a subsample of N = 105 participants (54.3% women; 65.6 ± 4.6 years) with overweight or obesity and metabolic syndrome that underwent a 3-years MedDiet intervention (PREDIMED-Plus study). Plasma eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), fatty acids, diet, glycemic homeostasis (including the assessment of insulin resistance-HOMA-IR), and cardiovascular risk markers were monitored (at 0-6-12-36 months).

Results

Mediterranean diet adherence increased in both sexes and remained high during the 3 years of follow-up. Reductions in body weight, glycemic and cardiovascular parameters were larger in men than in women. Women presented higher concentrations of NAEs than men throughout the study. In both sexes, AEA and other NAEs (including OEA, and PEA) decreased after 6 months (for AEA: −4.9%), whereas the ratio OEA/AEA increased after 1 year (+5.8%). Changes in 2-AG (−3.9%) and the ratio OEA/PEA (+8.2%) persisted over the 3 years of follow-up. In women, 6-months changes in AEA (OR = 0.65) and the ratio OEA/AEA (OR = 3.28) were associated with the achievement of 8% weight reductions and correlated with HOMA-IR changes (r = 0.29 and r = −0.34). In men, OEA/PEA changes were associated with 8% weight reductions (OR = 2.62) and correlated with HOMA-IR changes (r = −0.32).

Conclusion

A 3-years MedDiet intervention modulated plasma concentrations of eCBs and NAEs. Changes in AEA and in the relative abundance of NAEs were associated with clinically meaningful weight reductions. However, marked sex differences were identified in eCBs and NAEs, as well as in the efficacy of the intervention in terms of glycemic and cardiovascular parameters, which could be related to post-menopause alterations in glucose metabolism. These findings support a sex-balanced research strategy for a better understanding of the mechanisms underlying the regulation of body weight loss.
Case report: 10-year survival of a patient with a primary hepatic gastrointestinal stromal tumor
Authors: Lian Jie , Feng Meiyan , Zhang Shumei , Lu Haibo
Published: December 2022

Background

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Extra-gastrointestinal stromal tumors (EGISTs) predominantly arise outside the gastrointestinal tract, although primary hepatic GISTs are extremely rare. GISTs are highly aggressive; they often grow to a large size. Here, we report the 10-year survival of a patient with a primary hepatic GIST following sequential response therapy.

Case presentation

A 50-year-old Chinese man complained of fatigue and slight abdominal pain, and presented with a large lump in the liver, which was detected by computed tomography (CT). He was subsequently diagnosed with a primary hepatic GIST, based on CT-guided fine needle aspiration cytology and immunohistochemistry analyses. The presence of GIST or EGIST metastases was excluded using CT, esophagogastroduodenoscopy, colonoscopy, and ultrasound. Cytological examination showed that the tumor was composed of epithelioid and spindle cells. Immunohistochemistry analysis revealed positive staining for CD117 (KIT) and DOG1, and negative staining for CD34, S-100, and α-smooth muscle actin (SMA). Following tumor ablation with argon-helium cryosurgery, the patient received imatinib mesylate for 61 months. However, this treatment was discontinued because of disease progression, at which point interventional therapy was administered once. One month later, sunitinib malate was administered for 71 months. The patient achieved long-term survival for 135 months.

Conclusions

EGISTs can be easily misdiagnosed as other types of tumors because they have no specific characteristics to distinguish them during imaging examinations. However, our case study demonstrates that the long-term survival of patients with EGISTs can be achieved with molecular targeted therapy.
CD20 expression: A risk stratification factor for newly diagnosed multiple myeloma with t(11;14)
Authors: Jian Yuan , Zhang Zhiyao , Zhou Huixing , Yang Guangzhong , Geng Chuanying , Wang Huijuan , Gao Wen , Chen Wenming
Published: December 2022

Objective

Translocation (11;14) is one of the most frequent recurrent cytogenetic abnormalities in multiple myeloma (MM), while its clinical prognostic value remains controversial. CD20 expression is uncommon in MM while strongly associated with t(11;14). This study aimed to investigate whether CD20 could provide further prognostic value in MM patients harboring t(11;14).

Methods

CD20 expression detected by flow cytometry was retrospectively analyzed in 211 newly diagnosed MM patients with t(11;14). The clinical characteristics and outcomes were analyzed between CD20 positive and negative patients.

Results

CD20 expression was found in 34.6% (73/211) newly diagnosed MM (NDMM) patients with t(11;14), associated with lower serum creatine levels and lower incidence of plasmacytoma. Based on similar treatment regimens, CD20 positive patients had a comparable overall response rate to CD20 negative patients, whereas had a lower CR/sCR (complete response/stringent complete response) rate than the latter (31.4% vs. 46.4%, P =0.045). Nevertheless, CD20 positive patients had a longer tendency of progression-free survival (PFS) (59.0 vs. 29.0 months, P =0.163) and significantly longer overall survival (OS) (99.0 vs. 56.0 months, P=0.003) than CD20 negative patients. Further investigation among CD20 expression proportion showed that strong expression of CD20 (>80% of bone marrow plasma cells) exhibited the longest OS (median not reached, P =0.011). However, the favorable impact of CD20 expression on survival was eliminated with the contaminant presence of cytogenetic abnormalities besides t(11;14). Autologous stem cell transplantation (ASCT) could improve the prognosis of CD20 negative t(11;14) patients. Multivariate analysis confirmed that CD20 expression was an independent favorable indicator for longer OS in t(11;14) MM patients.

Conclusion

CD20 expression is a favorable prognostic factor in NDMM with t(11;14) and could provide further risk-stratification value in this heterogeneous disease subgroup.
Should we adopt an automated de-centralized model of chimeric antigen receptor- T cells manufacturing for low-and middle-income countries? A real world perspective
Authors: Ramakrishnan Sharanya , Kumar Jeevan , Datta Suvro Sankha , Radhakrishnan Vivek , Nair Reena , Chandy Mammen
Published: December 2022

Autologous chimeric antigen receptor-T (CAR-T) cell therapy has proven itself as an effective therapeutic modality for cancers, especially hematological malignancies and is emerging as a potential candidate for solid organ cancers as well. However, the accessibility to treatment has been limited due to complexities and costs associated with manufacturing a genetically modified autologous product. The centralized model of CAR-T manufacturing which has emerged as the dominant model in developed nations does not seem well-suited to the needs and realities of the developing economies. In this context, we explore the relative advantages and disadvantages of the two models from a developing nation’s perspective.
Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma
Authors: Song Jiaxun , Yuan Xiaofeng , Piao Lianhua , Wang Jiawen , Wang Pu , Zhuang Ming , Liu Jie , Liu Zhiwei
Published: December 2022

Although some advances have been made in the treatment of osteosarcoma in recent years, surgical resection remains the mainstream treatment. Initial and early diagnosis of osteosarcoma could be very difficult to achieve due to the insufficient sensitivity for the means of examination. The distal metastasis of osteosarcoma also predicts the poor prognosis of osteosarcoma. In order to solve this series of problems, people begin to discover a new method of diagnosing and treating osteosarcoma. Ubiquitination, as an emerging posttranslational modification, has been shown to be closely related to osteosarcoma in studies over the past decades. In general, this review describes the cellular functions and molecular mechanisms of ubiquitination during the development of osteosarcoma.
Personalized treatment of brain metastases: Evolving survival prediction models may benefit from evaluation of serum tumor markers (narrative review)
Authors: Nieder Carsten , Andratschke Nicolaus H. , Grosu Anca L.
Published: December 2022

Treatment of a limited number of brain metastases (oligometastases) might include complex and sometimes invasive approaches, e.g. neurosurgical resection followed by post-operative stereotactic radiotherapy, and thus, correct identification of patients who are appropriate candidates is crucial. Both, staging procedures that visualize the true number of metastastic lesions and prognostic assessments that identify patients with limited survival, who should be managed with less complex, palliative approaches, are necessary before proceeding with local treatment that aims at eradication of all oligometastases. Some of the prognostic models, e.g. the LabBM score (laboratory parameters in patients with brain metastases), include blood biomarkers believed to represent surrogate markers of disease extent. In a recent study, patients with oligometastases and a LabBM score of 0 (no abnormal biomarkers) had an actuarial 5-year survival rate of 27% after neurosurgical resection and 39% after stereotactic radiotherapy. Other studies have tied serum tumor markers such as carcinoembryonic antigen (CEA) to survival outcomes. Even if head-to-head comparisons and large-scale definitive analyses are lacking, the available data suggest that attempts to integrate tumor marker levels in blood biomarker-based survival prediction models are warranted.