bluuebunny/crossref_metadata_2025 huggingface dataset:
Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link
Authors: Qing Jianbo , Hu Xueli , Li Changqun , Song Wenzhu , Tirichen Hasna , Yaigoub Hasnaa , Li Yafeng
Published: August 2022

Background

IgA nephropathy (IgAN) is an autoimmune disease that affects people of any age and is an important cause of end-stage renal disease. However, the pathogenesis and pathophysiology of IgAN is not clear. This article aimed to explore the immune-mediated inflammation and genetic mechanisms in IgAN.

Methods

The transcriptome sequencing data of IgAN glomeruli in the Gene Expression Omnibus database were downloaded. Single-sample gene set enrichment analysis was used to estimate the immune microenvironment of the merged microarray data and GSE141295. IgAN samples were divided into two clusters by cluster analysis. “limma” and “DEseq2” package in R were used to identify differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules related to inflammation in IgAN. R software package “clusterProfiler” was used for enrichment analysis, whereas Short Time-Series Expression Miner (STEM) analysis was used to identify the trend of gene expression. Machine-learn (ML) was performed using the shiny app. Finally, Drug Signatures Database (DSigDB) was used to identify potential molecules for treating IgAN.

Results

The infiltration of macrophages in IgAN glomeruli was increased, whereas CD4+ T cells, especially inducedregulatory T cells (iTregs) were decreased. A total of 1,104 common DEGs were identified from the merged data and GSE141295. Brown module was identified to have the highest inflammatory correlation with IgAN using WGCNA, and 15 hub genes were screened from this module. Among these 15 hub genes, 14 increased with the severity of IgAN inflammation based on STEM analysis. Neural network (nnet) is considered as the best model to predict the severity of IgAN. Fucose identified from DSigDB has a potential biological activity to treat IgAN.

Conclusion

The increase of macrophages and the decrease of iTregs in glomeruli represent the immune-mediated inflammation of IgAN, and fucose may be a potential therapeutic molecule against IgAN because it affects genes involved in the severe inflammation of IgAN.
Immunosenescence in atherosclerosis: A role for chronic viral infections
Authors: Ghamar Talepoor Atefe , Doroudchi Mehrnoosh
Published: August 2022

Immune system is a versatile and dynamic body organ which offers survival and endurance of human beings in their hostile living environment. However, similar to other cells, immune cells are hijacked by senescence. The ageing immune cells lose their beneficial functions but continue to produce inflammatory mediators which draw other immune and non-immune cells to the senescence loop. Immunosenescence has been shown to be associated with different pathological conditions and diseases, among which atherosclerosis has recently come to light. There are common drivers of both immunosenescence and atherosclerosis; e.g. inflammation, reactive oxygen species (ROS), chronic viral infections, genomic damage, oxidized-LDL, hypertension, cigarette smoke, hyperglycaemia, and mitochondrial failure. Chronic viral infections induce inflammaging, sustained cytokine signaling, ROS generation and DNA damage which are associated with atherogenesis. Accumulating evidence shows that several DNA and RNA viruses are stimulators of immunosenescence and atherosclerosis in an interrelated network. DNA viruses such as CMV, EBV and HBV upregulate p16, p21 and p53 senescence-associated molecules; induce inflammaging, metabolic reprogramming of infected cells, replicative senescence and telomere shortening. RNA viruses such as HCV and HIV induce ROS generation, DNA damage, induction of senescence-associated secretory phenotype (SASP), metabolic reprogramming of infected cells, G1 cell cycle arrest, telomere shortening, as well as epigenetic modifications of DNA and histones. The newly emerged SARS-CoV-2 virus is also a potent inducer of cytokine storm and SASP. The spike protein of SARS-CoV-2 promotes senescence phenotype in endothelial cells by augmenting p16, p21, senescence-associated β-galactosidase (SA-β-Gal) and adhesion molecules expression. The impact of SARS-CoV-2 mega-inflammation on atherogenesis, however, remains to be investigated. In this review we focus on the common processes in immunosenescence and atherogenesis caused by chronic viral infections and discuss the current knowledge on this topic.
Hindrance effect of tides on water exchanges between the Red Sea and the Gulf of Aden
Authors: Guo Daquan , Yao Fengchao , Zhan Peng , Krokos George , Hoteit Ibrahim
Published: August 2022

As a semienclosed marginal sea, the Red Sea connects with the open ocean through a narrow strait at its southern end, known as the Bab-al-Mandeb (BAM) strait. The water exchange between the Red Sea and the Gulf of Aden at the BAM strait is crucial for the water mass transformations and thermohaline circulation in the Red Sea as well as for nutrient supply to the open ocean. In this study, a three-dimensional high-resolution nonhydrostatic MIT general circulation model (MITgcm) was used to investigate the tidal influence on the water exchange in the BAM strait through simulations with and without tidal forcing. We found that the tidal effects on the water exchange in winter were insignificant; however, the summer intrusion of the Gulf of Aden Intermediate Water (GAIW) was strongly affected. When the simulation includes tidal forcing, the along-axis northern extension of the GAIW intrusion is reduced by u to 100 km and the monthly mean volume transport is decreased by 20% on average. Two actors that possibly contribute to the hindrance effects of tides in summer are (i) the tidal residual currents that propagate in a direction opposite to the pathway of the GAIW intrusion currents nd (ii) the enhanced vertical mixing at the pycnocline and near the benthic topography of the BAM strait, which triggers more instabilities along the pathway of the intrusion.
Warm bias of cold sea surface temperatures in the East Sea (Japan Sea)
Authors: Yoon Seung-Tae , Park JongJin
Published: August 2022

The East/Japan Sea (ES) is regarded as a natural laboratory for predicting future changes in the global Meridional Overturning Circulation (MOC) under warming climates, as the ES MOC (EMOC) changes rapidly in comparison with the global MOC. Specifically, intermediate and deep-water masses of the ES are formed in its northern reaches via wind-driven subduction of surface water, and convection from the surface to deep layers during the winter. Accordingly, it is important to investigate the variation of winter sea surface temperatures (SSTs) for characterizing and predicting the EMOC; however, global SST products must be corrected and optimized for the ES, as they fail to incorporate the local marginal sea conditions. Here, a warm bias in cold SST was identified for three SST products, such as optimally interpolated sea surface temperatures (OISSTs), microwave SSTs, and operational SST and sea ice analysis products, suggesting the potential usefulness of a correction method incorporating Argo float data. When comparing OISSTs with 5 m temperature estimates from Argo float data during 2000–2020, under the assumption that the mixed layer depth is deeper than 8 m, a nearly normalized histogram of biases was produced, and the robust warm bias (mean = 0.9°C) was detected in the range of relatively cold SSTs (-2°C to 10°C), yet no significant bias in warm SSTs (> 10°C) was found. To minimize the warm bias in cold SSTs, OISSTs were corrected with an inverse 4th-order polynomial fitting method. Subsequently, the mean bias between the corrected SSTs and top depth temperatures of Argo float data was significantly reduced to less than 0.1°C. Moreover, the warm bias of cold SSTs resulted in severe underestimations of the outcropping area colder than 1°C over the northern region, as well as the occurrence period of 1°C to 5°C SSTs in the north-western ES. These results highlight the importance of local bias correction for SST products, and it is expected that the newly suggested correction method will improve model predictions of EMOC change by enhancing SST data quality in the northern ES.
Rapid and sensitive amplicon-based genome sequencing of SARS-CoV-2
Authors: Park Changwoo , Kim Kwan Woo , Park Dongju , Hassan Zohaib ul , Park Edmond Changkyun , Lee Chang-Seop , Rahman MD Tazikur , Yi Hana , Kim Seil
Published: August 2022

As SARS-CoV-2 variants of concern emerged, the genome sequencing of SARS-CoV-2 strains became more important. In this study, SARS-CoV-2 was sequenced using amplicon-based genome sequencing with MinION. The primer panel used in this study consisted of only 11 primer panels and the size of the amplicons was approximately 3 kb. Full genome sequences were obtained with a hundred copies of the SARS-CoV-2 genome, and 92.33% and 75.39% of the genome sequences were obtained with 10 copies of the SARS-CoV-2 genome. The few differences in nucleotide sequences originated from mutations in laboratory cultures and/or mixed nucleotide sequences. The quantification of the SARS-CoV-2 genomic RNA was done using RT-ddPCR methods, and the level of LoD indicated that this sequencing method can be used for any RT-qPCR positive clinical sample. The sequencing results of the SARS-CoV-2 variants and clinical samples showed that our methods were very reliable. The genome sequences of five individual clinical samples were almost identical, and the analysis of the sequence variance showed that most of these nucleotide substitutions were observed in the genome sequences of the other clinical samples, indicating this amplicon-based whole-genome sequencing method can be used in various clinical fields.
Thermal traits govern the response of microbial community dynamics and ecosystem functioning to warming
Authors: Garcia Francisca C. , Warfield Ruth , Yvon-Durocher Gabriel
Published: August 2022

Understanding the ecological processes that underpin the dynamics of community turnover in response to environmental change is critical to predicting how warming will influence ecosystem functioning. Here, we quantify the effect of changing temperature on community composition and ecosystem functioning via the action of ecological selection on population-level thermal traits. To achieve this, we use microbes isolated from a network of geothermal streams in Iceland where in situ temperatures span 8–38°C within a single catchment. We first quantified variability in thermal tolerance between taxa, and then assembled synthetic communities along a broad thermal gradient to explore how temperature-driven selection on thermal tolerance traits shaped the emergent community structures and functions. We found marked changes in community structure and composition with temperature, such that communities exposed to extreme temperatures (10, 35°C) had highly asymmetric biomass distributions and low taxonomic richness. Thermal optima were a good predictor of the presence and relative abundance of taxa in the high-temperature treatments. We also found that the evenness of the abundance distribution was related to ecosystem production, such that communities with more equitable abundance distribution were also the most productive. Our results highlight the utility of using a multi-level approach that links population-level traits with community structure and ecosystem functioning to better understand how ecological communities will respond to global warming.
The 5′-end motif of Senecavirus A cDNA clone is genetically modified in 36 different ways for uncovering profiles of virus recovery
Authors: Meng Hailan , Wang Qi , Liu Meiling , Li Ziwei , Hao Xiaojing , Zhao Di , Dong Yaqin , Liu Shuang , Zhang Feng , Cui Jin , Ni Bo , Shan Hu , Liu Fuxiao
Published: August 2022

Senecavirus A (SVA) is an emerging picornavirus. Its genome is one positive-sense, single-stranded RNA. The viral protein (VPg) is covalently linked to the extreme 5′ end of the SVA genome. A complex hairpin-pseudoknot-hairpin (HPH) RNA structure was computationally predicted to form at the 5′ end of the SVA genome. A total of three extra “U” residues (UUU) served as a linker between the HPH structure and the VPg, causing putative UUU–HPH formation at the extreme 5′ end of the SVA genome. It is unclear how the UUU–HPH structure functions. One SVA cDNA clone (N0) was constructed previously in our laboratory. Here, the N0 was genetically tailored for reconstructing a set of 36 modified cDNA clones (N1 to N36) in an attempt to rescue replication-competent SVAs using reverse genetics. The results showed that a total of nine viruses were successfully recovered. Out of them, five were independently rescued from the N1 to N5, reconstructed by deleting the first five nucleotides (TTTGA) one by one from the extreme 5′ end of N0. Interestingly, these five viral progenies reverted to the wild-type or/and wild-type-like genotype, suggesting that SVA with an ability to repair nucleotide defects in its extreme 5′ end. The other four were independently rescued from the N26 to N29, containing different loop-modifying motifs in the first hairpin of the HPH structure. These four loop-modifying motifs were genetically stable after serial passages, implying the wild-type loop motif was not a high-fidelity element in the first hairpin during SVA replication. The other genetically modified sequences were demonstrated to be lethal elements in the HPH structure for SVA recovery, suggesting that the putative HPH formation was a crucial cis-acting replication element for SVA propagation.
Advances for the treatment of lower extremity arterial disease associated with diabetes mellitus
Authors: Pan Yang , Luo Yuting , Hong Jing , He Huacheng , Dai Lu , Zhu Hong , Wu Jiang
Published: August 2022

Lower extremity arterial disease (LEAD) is a major vascular complication of diabetes. Vascular endothelial cells dysfunction can exacerbate local ischemia, leading to a significant increase in amputation, disability, and even mortality in patients with diabetes combined with LEAD. Therefore, it is of great clinical importance to explore proper and effective treatments. Conventional treatments of diabetic LEAD include lifestyle management, medication, open surgery, endovascular treatment, and amputation. As interdisciplinary research emerges, regenerative medicine strategies have provided new insights to treat chronic limb threatening ischemia (CLTI). Therapeutic angiogenesis strategies, such as delivering growth factors, stem cells, drugs to ischemic tissues, have also been proposed to treat LEAD by fundamentally stimulating multidimensional vascular regeneration. Recent years have seen the rapid growth of tissue engineering technology; tissue-engineered biomaterials have been used to study the treatment of LEAD, such as encapsulation of growth factors and drugs in hydrogel to facilitate the restoration of blood perfusion in ischemic tissues of animals. The primary purpose of this review is to introduce treatments and novel biomaterials development in LEAD. Firstly, the pathogenesis of LEAD is briefly described. Secondly, conventional therapies and therapeutic angiogenesis strategies of LEAD are discussed. Finally, recent research advances and future perspectives on biomaterials in LEAD are proposed.
Targeting extracellular Hsp90: A unique frontier against cancer
Authors: Sager Rebecca A. , Khan Farzana , Toneatto Lorenzo , Votra SarahBeth D. , Backe Sarah J. , Woodford Mark R. , Mollapour Mehdi , Bourboulia Dimitra
Published: August 2022

The molecular chaperone Heat Shock Protein-90 (Hsp90) is known to interact with over 300 client proteins as well as regulatory factors (eg. nucleotide and proteins) that facilitate execution of its role as a chaperone and, ultimately, client protein activation. Hsp90 associates transiently with these molecular modulators during an eventful chaperone cycle, resulting in acquisition of flexible structural conformations, perfectly customized to the needs of each one of its client proteins. Due to the plethora and diverse nature of proteins it supports, the Hsp90 chaperone machinery is critical for normal cellular function particularly in response to stress. In diseases such as cancer, the Hsp90 chaperone machinery is hijacked for processes which encompass many of the hallmarks of cancer, including cell growth, survival, immune response evasion, migration, invasion, and angiogenesis. Elevated levels of extracellular Hsp90 (eHsp90) enhance tumorigenesis and the potential for metastasis. eHsp90 has been considered one of the new targets in the development of anti-cancer drugs as there are various stages of cancer progression where eHsp90 function could be targeted. Our limited understanding of the regulation of the eHsp90 chaperone machinery is a major drawback for designing successful Hsp90-targeted therapies, and more research is still warranted.
Research advances in the study of sleep disorders, circadian rhythm disturbances and Alzheimer’s disease
Authors: Xiong Xiangyang , Hu Tianpeng , Yin Zhenyu , Zhang Yaodan , Chen Fanglian , Lei Ping
Published: August 2022

Although there are still no satisfactory answers to the question of why we need to sleep, a better understanding of its function will help to improve societal attitudes toward sleep. Sleep disorders are very common in neurodegenerative diseases and are a key factor in the quality of life of patients and their families. Alzheimer’s disease (AD) is an insidious and irreversible neurodegenerative disease. Along with progressive cognitive impairment, sleep disorders and disturbances in circadian rhythms play a key role in the progression of AD. Sleep and circadian rhythm disturbances are more common in patients with AD than in the general population and can appear early in the course of the disease. Therefore, this review discusses the bidirectional relationships among circadian rhythm disturbances, sleep disorders, and AD. In addition, pharmacological and non-pharmacological treatment options for patients with AD and sleep disorders are outlined.
Investigating charge trapping in ferroelectric thin films through transient measurements
Authors: Lancaster Suzanne , Lomenzo Patrick D. , Engl Moritz , Xu Bohan , Mikolajick Thomas , Schroeder Uwe , Slesazeck Stefan
Published: August 2022

A measurement technique is presented to quantify the polarization loss in ferroelectric thin films as a function of delay time during the first 100s after switching. This technique can be used to investigate charge trapping in ferroelectric thin films by analyzing the magnitude and rate of polarization loss. Exemplary measurements have been performed on Hf0.5Zr0.5O2 (HZO) and HZO/Al2O3 films, as a function of pulse width and temperature. It is found that the competing effects of the depolarization field, internal bias field and charge trapping lead to a characteristic Gaussian dependence of the rate of polarization loss on the delay time. From this, a charge trapping and screening model could be identified which describes the dynamics of polarization loss on short timescales.
Single-sized metasurface for simultaneous pseudo-color nanoprinting and holographic image display
Authors: Li Jiaxin , Zhou Zhou , Li Zile , Zheng Guoxing
Published: August 2022

Metasurfaces provide a novel platform for multifunctional devices due to their incomparable competence for the manipulation of different optical properties. Recently, many works have emerged to merge distinct functions into a single metasurface, which effectively increase the information density and capacity of meta-devices. In this work, combining the dual-wavelength polarizer and the orientation degeneracy of the Malus law, we further exploit the design degree of freedom of the metasurface, and realize color control and phase manipulation simultaneously with single-sized nanostructures. We experimentally demonstrate our concept by integrating the function of pseudo-color nanoprinting and holographic image display together. Our research can effectively improve the functionalities of metasurface and promote advanced research of multimode displays, information encryption, optical multiplexing, and many other related fields.
Use of 18F-FDG-PET/CT in differential diagnosis of primary central nervous system lymphoma and high-grade gliomas: A meta-analysis
Authors: Zhang Guisheng , Li Jiuhong , Hui Xuhui
Published: August 2022

Background

Primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG) appear similar under imaging. However, since the two tumors vary in their treatment methods, their differential diagnosis is crucial. The use of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) imaging to effectively distinguish between the two tumors is not clear; therefore, a meta-analysis was carried out to determine its effectiveness.

Materials and methods

The databases PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, China Science, and Technology Journal Database (CQVIP) were exhaustively searched using stringent inclusion and exclusion criteria to select high-quality literature. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used for the qualitative assessment of the included literature. The bivariate effect model was used to combine statistics such as sensitivity (SEN) and specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) [95% confidence intervals (CI)], plot summary receiver operating characteristic (SROC) curve, and calculate the area under the curve (AUC) value. Sensitivity analysis was used to evaluate the stability of the results, and Deek's test was used to assess publication bias. Meta-regression and subgroup analysis was used to determine the sources of heterogeneity.

Results

A total of nine studies were included in this study. For differential diagnosis of PCNSL and HGG, the combined SEN was 0.91 (95% CI: 0.80–0.96; I2 = 46.73%), combined SPE was 0.88 (95% CI: 0.82–0.93; I2 = 56.30%), the combined PLR was 7.83 (95% CI: 4.96–12.37; I2 = 15.57%), combined NLR was 0.10 (95% CI: 0.05–0.23; I2 = 31.99%), combined DOR was 77.36 (95% CI: 32.74–182.77; I2 = 70.70%). The AUC of SROC was 0.95 (95% CI: 0.93–0.97). No publication bias was found and the sample size and different parameters were the primary reason for heterogeneity.

Conclusion

The 18F-FDG-PET/CT imaging technique has a high diagnostic accuracy in the differential diagnosis of PNCSL and HGG. Patients suspected to have the above two tumors are suggested to be examined by 18F-FDG-PET / CT to help in the clinical distinction and further treatment modalities.
Sudden sensorineural hearing loss as the initial symptom in patients with acoustic neuroma
Authors: Song Mengtao , Wang Dayong , Li Jin , Chen Guohui , Zhang Xiaolong , Wang Hongyang , Wang Qiuju
Published: August 2022

Background

Previous studies have shown that patients with acoustic neuroma (AN) sometimes present with sudden sensorineural hearing loss (SSNHL) as an initial symptom. The purpose of this research was to investigate the clinical characteristics, diagnosis, and treatment of AN in patients initially diagnosed with SSNHL.

Materials and methods

We reviewed retrospectively the medical records of all patients who were treated as SSNHL initially and were later diagnosed with AN after undergoing magnetic resonance imaging (MRI) at our hospital between 2008 and 2021. Patient demographics, associated complaints (mostly tinnitus and vertigo), the severity of hearing loss, audiogram configurations, auditory brainstem response (ABR), and MRI examination were reviewed and analyzed. In addition, treatment outcomes and management protocols were also included in this study.

Results

A total of 10 (0.7%, 10/1,383) patients presented with SSNHL as the initial symptom and were diagnosed as AN by MRI finally. Of the 10 patients enrolled in this study, four were men and six were women. The average age at the time of diagnosis of SSNHL was 46.2 ± 13.16 years. These patients exhibited varying severity of hearing loss and a variety of audiogram configurations. All patients showed an abnormal ABR. According to the Koos grading standard, there were 5 grade I (intracanalicular [IAC]) tumors, 3 grade II tumors, and 2 grade III tumors. The treatment outcome revealed that 2 patients exhibited recovery of the average hearing of impaired frequency by more than 15 dB, and 6 patients showed no recovery. Furthermore, four patients were referred to undergo surgical treatment after being diagnosed with AN, 1 patient accepted stereotactic radiation therapy, and the remaining 5 patients were on a “wait and scan” strategy.

Conclusion

The hearing loss of patients with AN presented with SSNHL may improve with drug treatment. Hearing recovery for SSNHL does not exclude the presence of AN, and all patients initially diagnosed with SSNHL should undergo MRI and ABR to prevent misdiagnosis and delays in potential treatment.
Use of flow diverter device in basilar artery for aneurysm treatment: Case series and literature review
Authors: Wang Chuanchuan , Zhu Deyuan , Xu Xiaolong , Zhou Yu , Zhao Rui , Li Qiang , Yang Pengfei , Huang Qinghai , Xu Yi , Liu Jianmin , Fang Yibin
Published: August 2022

Background

Flow diverters (FDs) for the treatment of basilar artery (BA) aneurysms remain controversial. In this study, we report our initial experience of flow diversion for treatment of this pathology.

Methods

Consecutive patients with an aneurysm of the BA that was treated by implantation of the FD were included in our retrospective study. Procedural complications, aneurysm occlusion, and a functional outcome were evaluated. FD placement in BA for aneurysm treatment reported in the literature was also reviewed and summarized.

Results

Sixteen patients with 16 BA aneurysms were treated by FD implantation with (n = 8) or without (n = 8) adjunctive coiling. The Tubridge was used in 13 (81.3%) and Pipeline in 3 (18.8%) procedures. Average aneurysm size was 15.7 mm. Four aneurysms were located at the basilar apex, six at the basilar trunk, and six at the vertebrobasilar junction. Three patients experienced procedural complications (18.8%), including two ischemic strokes and one hydrocephalus, with resultant mortality in one case (6.3%). Median follow-up was 7.7 months and available for 15 aneurysms. Complete/near-complete occlusion was seen in 13 (86.7%) aneurysms.

Conclusion

In our initial experience, flow diversion is feasible and safe in the treatment of BA aneurysms with promising occlusion rates at mid-term follow-up. Larger cohort studies are required to validate these results.
Radon Concentrations in Indoor and Outdoor Environments of Atomic Energy Centre Dhaka, Bangladesh, and Concomitant Health Hazards
Authors: Pervin Shikha , Yeasmin Selina , Khandaker Mayeen Uddin , Begum Afia
Published: August 2022

Realizing the non-negligible health hazards due to radon exposure, the present study was carried out to measure the radon concentrations in indoor and outdoor environments of Atomic Energy Centre Dhaka (AECD), Bangladesh. A portable electrostatic radon-measuring device (RAD7) was used to determine the indoor radon levels in different laboratories of AECD, and a RAD7 detector with a stainless steel soil probe was employed to measure the soil gas radon in the surrounding areas of the AECD campus. The indoor radon concentration in various laboratories was found to vary from 11 ± 7 Bq/m3 to 360 ± 180 Bq/m3 with an average of 63 ± 33 Bq/m3. Overall, the average indoor radon level shows below the action level (300 Bq/m3) recommended by ICRP publication-126 for homes and workplaces. However, the laboratories having poor ventilation show a relatively higher radon level. The average soil gas radon concentration at different depths of 15 cm, 35 cm, and 55 cm was found to be 0.07 ± 0.01 kBq/m3, 2.31 ± 0.31 kBq/m3, and 22.5 ± 1.4 kBq/m3, respectively. The calculated average annual effective dose due to the inhalation of indoor radon in home and workplaces was found to be below the ICRP recommended value of 10 mSv/y. The present results could serve as a reference radon level in the indoor and outdoor environment in Dhaka city, Bangladesh.
Poria cocos polysaccharide prevents alcohol-induced hepatic injury and inflammation by repressing oxidative stress and gut leakiness
Authors: Jiang Yue-hang , Wang Lei , Chen Wei-dong , Duan Yu-ting , Sun Ming-jie , Huang Jia-jing , Peng Dai-yin , Yu Nian-jun , Wang Yan-yan , Zhang Yue
Published: August 2022

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.
Bacillus subtilis M6 improves intestinal barrier, antioxidant capacity and gut microbial composition in AA broiler
Authors: Ji Linbao , Zhang Lian , Liu Hu , Shen Jiakun , Zhang Yu , Lu Lin , Zhang Xiujun , Ma Xi
Published: August 2022

Bacillus subtilis can secret a variety of substances to improve human and animal gut health via inhibiting the proliferation of pathogenic bacteria. In this study, a fast-growing and stress-resistant strain of Bacillus subtilis M6 (B. subtilis M6) were isolated, which showed a strong antibacterial activity to E. coli K88, S. typhimurium ATCC14028, and S. aureus ATCC25923 in vitro. In vivo studies showed that B. subtilis M6 can significantly improve the average daily gain (ADG) using an AA broiler model. Dietary B. subtilis M6 improved the intestinal morphology. The villus height of jejunum and ileum were significantly increased. The concentration of malondialdehyde (MDA) in the ileal mucosa was significantly reduced in B. subtilis M6 treatment group, which suggested the oxidative stress of the ileum was significantly relieved. Though the β diversity of treatments was not significantly, B. subtilis M6 improved the composition of intestinal microbes, especially at the level of caecum genus, the dominant genus was changed from Ruminococcus to Akkermansia, which indicated the change of intestinal carbohydrate nutrition. In conclusion, these data indicate that the B. subtilis M6 shows a probiotic potential to improve intestinal health via altering gut microbiota.
ACO1 and IREB2 downregulation confer poor prognosis and correlate with autophagy-related ferroptosis and immune infiltration in KIRC
Authors: Zhu Ting , Xiao Zhuoyu , Yuan Haoyu , Tian Hu , Chen Taoyi , Chen Qi , Chen Mingkun , Yang Jiankun , Zhou Qizhao , Guo Wenbin , Xue Kangyi , Xia Ming , Bao Jiming , Yang Cheng , Duan Haifeng , Wang Hongyi , Huang Zhipeng , Liu Cundong , Zhou Junhao
Published: August 2022

Background

ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism–linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers.

Methods

The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan–Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)–KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib.

Results

KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan–Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells.

Conclusion

ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.
Ginseng-derived nanoparticles inhibit lung cancer cell epithelial mesenchymal transition by repressing pentose phosphate pathway activity
Authors: Yang Lan , Jin Wen-qi , Tang Xiao-lei , Zhang Shuai , Ma Rui , Zhao Da-qing , Sun Li-wei
Published: August 2022

It is unclear whether ginseng-derived nanoparticles (GDNPs) can prevent tumor cell epithelial-mesenchymal transition (EMT). Here, we describe typical characteristics of GDNPs and possible underlying mechanisms for GDNP antitumor activities. First, GDNPs particle sizes and morphology were determined using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), respectively, while cellular uptake of PKH67-labeled GDNPs was also assessed. Next, we evaluated GDNPs antitumor effects by determining whether GDNPs inhibited proliferation and migration of five tumor cell lines derived from different cell types. The results indicated that GDNPs most significantly inhibited proliferation and migration of lung cancer-derived tumor cells (A549, NCI-H1299). Moreover, GDNPs treatment also inhibited cell migration, invasion, clonal formation, and adhesion tube formation ability and reduced expression of EMT-related markers in A549 and NCI-H1299 cells in a dose-dependent manner. Meanwhile, Kaplan-Meier analysis of microarray data revealed that high-level thymidine phosphorylase (TP) production, which is associated with poor lung cancer prognosis, was inhibited by GDNPs treatment, as reflected by decreased secretion of overexpressed TP and downregulation of TP mRNA-level expression. In addition, proteomic analysis results indicated that GDNPs affected pentose phosphate pathway (PPP) activity, with ELISA results confirming that GDNPs significantly reduced levels of PPP metabolic intermediates. Results of this study also demonstrated that GDNPs-induced downregulation of TP expression led to PPP pathway inhibition and repression of lung cancer cell metastasis, warranting further studies of nano-drugs as a new and promising class of anti-cancer drugs.
Primary intrathoracic liposarcomas: A clinicopathologic and molecular study of 43 cases in one of the largest medical centers of China
Authors: Xie You , Jing Wenyi , Zhao Wei , Peng Ran , Chen Min , Lan Ting , Peng Heng , He Xin , Chen Huijiao , Zhang Zhang , Zhang Hongying
Published: August 2022

Introduction

Primary intrathoracic liposarcoma is extremely rare, and most published series lack genetic analyses. The aim of our study is to better understand the clinicopathologic and genetic features of these rare lesions.

Materials and methods

Forty-three primary intrathoracic liposarcomas were identified and most cases were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), whole-exome sequencing (WES), and Sanger sequencing.

Results

This series included 27 males and 16 females (ratios, 1.68:1) aged 24-73 years (median, 53 years). Tumors mainly occurred in the mediastinum (n=23, 53.5%), followed by pleural cavity (n=16, 37.2%) and lung (n=4, 9.3%). The study included 21 well-differentiated liposarcomas (WDLs), 19 dedifferentiated liposarcomas (DDLs), 2 myxoid pleomorphic liposarcomas (MPLs) and 1 pleomorphic liposarcoma (PL), without identification of myxoid liposarcoma. FISH analysis identified MDM2 amplification in 17 of 18 WDLs (94.4%) and all DDLs (16/16, 100.0%). The MDM2-nonamplified WDL was CDK4-nonamplified but FRS2-amplified. WES and Sanger sequencing found somatic TP53 mutation in the 2 MPLs. Follow-up information was available for 33 of 38 cases (86.8%). Thirteen patients (39.4%) showed no evidence of disease, 10 patients (30.3%) were alive with disease, and 8 patients (24.2%) died of disease. Fourteen cases developed recurrence and 1 with metastasis.

Conclusions

WDL/DDL was the overwhelming subtype in this location, followed by MPL and PL. Analysis of the FRS2 gene, in combination with MDM2 and other genes of 12q13-15, may more precisely characterize WDL/DDLs. MPL is the most fatal subtype of this site. Further studies are needed to explore the role of TP53 in the pathogenesis of MPL.
Risk assessment and prediction model of renal damage in childhood immunoglobulin A vasculitis
Authors: Fu Ruqian , Yang Manqiong , Li Zhihui , Kang Zhijuan , Xun Mai , Wang Ying , Wang Manzhi , Wang Xiangyun
Published: August 2022

Objectives

To explore the risk factors for renal damage in childhood immunoglobulin A vasculitis (IgAV) within 6 months and construct a clinical model for individual risk prediction.

Methods

We retrospectively analyzed the clinical data of 1,007 children in our hospital and 287 children in other hospitals who were diagnosed with IgAV. Approximately 70% of the cases in our hospital were randomly selected using statistical product service soltions (SPSS) software for modeling. The remaining 30% of the cases were selected for internal verification, and the other hospital's cases were reviewed for external verification. A clinical prediction model for renal damage in children with IgAV was constructed by analyzing the modeling data through single-factor and multiple-factor logistic regression analyses. Then, we assessed and verified the degree of discrimination, calibration and clinical usefulness of the model. Finally, the prediction model was rendered in the form of a nomogram.

Results

Age, persistent cutaneous purpura, erythrocyte distribution width, complement C3, immunoglobulin G and triglycerides were independent influencing factors of renal damage in IgAV. Based on these factors, the area under the curve (AUC) for the prediction model was 0.772; the calibration curve did not significantly deviate from the ideal curve; and the clinical decision curve was higher than two extreme lines when the prediction probability was ~15–82%. When the internal and external verification datasets were applied to the prediction model, the AUC was 0.729 and 0.750, respectively, and the Z test was compared with the modeling AUC, P > 0.05. The calibration curves fluctuated around the ideal curve, and the clinical decision curve was higher than two extreme lines when the prediction probability was 25~84% and 14~73%, respectively.

Conclusion

The prediction model has a good degree of discrimination, calibration and clinical usefulness. Either the internal or external verification has better clinical efficacy, indicating that the model has repeatability and portability.

Clinical trial registration:

www.chictr.org.cn, identifier ChiCTR2000033435.
A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma
Authors: Wei Nan , Chao-yang Gong , Wen-ming Zhou , Ze-yuan Lei , Yong-qiang Shi , Shun-bai Zhang , Kai Zhang , Yan-chao Ma , Hai-hong Zhang
Published: August 2022

Background: Ubiquitination is medicated by three classes of enzymes and has been proven to involve in multiple cancer biological processes. Moreover, dysregulation of ubiquitination has received a growing body of attention in osteosarcoma (OS) tumorigenesis and treatment. Therefore, our study aimed to identify a ubiquitin-related gene signature for predicting prognosis and immune landscape and constructing OS molecular subtypes.

Methods: Therapeutically Applicable Research to Generate Effective Treatments (TARGET) was regarded as the training set through univariate Cox regression, Lasso Cox regression, and multivariate Cox regression. The GSE21257 and GSE39055 served as the validation set to verify the predictive value of the signature. CIBERSORT was performed to show immune infiltration and the immune microenvironment. The NMF algorithm was used to construct OS molecular subtypes.

Results: In this study, we developed a ubiquitin-related gene signature including seven genes (UBE2L3, CORO6, DCAF8, DNAI1, FBXL5, UHRF2, and WDR53), and the gene signature had a good performance in predicting prognosis for OS patients (AUC values at 1/3/5 years were 0.957, 0.890, and 0.919). Multivariate Cox regression indicated that the risk score model and prognosis stage were also independent prognostic prediction factors. Moreover, analyses of immune cells and immune-related functions showed a significant difference in different risk score groups and the three clusters. The drug sensitivity suggested that IC50 of proteasome inhibitor (MG-132) showed a notable significance between the risk score groups (p < 0.05). Through the NMF algorithm, we obtained the three clusters, and cluster 3 showed better survival outcomes. The expression of ubiquitin-related genes (CORO6, UBE2L3, FBXL5, DNAI1, and DCAF8) showed an obvious significance in normal and osteosarcoma tissues.

Conclusion: We developed a novel ubiquitin-related gene signature which showed better predictive prognostic ability for OS and provided additional information on chemotherapy and immunotherapy. The OS molecular subtypes would also give a useful guide for individualized therapy.
The inhibitory effect of some pyrazole ligands and their Cu(II) complexes on the growth of Escherichia coli, Klebsiella–Enterobacter spp., and Staphylococcus aureus
Authors: Zaimović Majda Šahman , Kosović Perutović Milica , Jelušić Gordana , Radović Ana , Jaćimović Željko
Published: August 2022

The aim of this study was to evaluate the inhibitory activity of chemistry products against the growth of Escherichia coli, Klebsiella–Enterobacter spp., and Staphylococcus aureus. Pyrazole derivatives (4-bromo-2-(1H-pyrazol-3-yl)phenol, 4-nitro-3-pyrazolecarboxylic acid, N-(benzyloxycarbonyl)-1H-pyrazole-1-carboxamidine), 3-amino-5-hydroxypyrazole, 3,5-pyrazoledicarboxylic acid monohydrate, and selected complexes of Cu(II) with the mentioned pyrazoles as ligands were used as chemistry bioactives for antibacterial activity. The testing method was carried out according to the disc diffusion method. Some compounds have shown inhibitory effects against the growth of E. coli. A small number of compounds have shown inhibitory effects against the growth of Klebsiella–Enterobacter spp. but did not show inhibitory effects on Staphylococcus aureus compared to amoxicillin as a standard.
Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression?
Authors: Zhao Fangyi , Cheng Ziqian , Piao Jingjing , Cui Ranji , Li Bingjin
Published: August 2022

Dopamine and its receptors are currently recognized targets for the treatment of several neuropsychiatric disorders, including Parkinson’s disease, schizophrenia, some drug use addictions, as well as depression. Dopamine receptors are widely distributed in various regions of the brain, but their role and exact contribution to neuropsychiatric diseases has not yet been thoroughly studied. Based on the types of dopamine receptors and their distribution in different brain regions, this paper reviews the current research status of the molecular, cellular and circuit mechanisms of dopamine and its receptors involved in depression. Multiple lines of investigation of these mechanisms provide a new future direction for understanding the etiology and treatment of depression and potential new targets for antidepressant treatments.
Therapeutic effects of shaogan fuzi decoction in rheumatoid arthritis: Network pharmacology and experimental validation
Authors: Shi Lu , Zhao Yiying , Feng Chenran , Miao Feng , Dong Linlin , Wang Tianquan , Stalin Antony , Zhang Jingyuan , Tu Jingru , Liu Kexin , Sun Wenyan , Wu Jiarui
Published: August 2022

Shaogan Fuzi Decoction (SGFD), one of the classical prescriptions of Chinese Medicine, has a long history in the treatment of rheumatoid arthritis (RA), but definitive studies on its efficacy and mechanism of action are lacking. This study aims to elucidate the pharmacodynamic role of SGFD against RA and the potential mechanisms based on a combination of network pharmacology and experimental verification. The RA model in rats was induced by intradermal injection of bovine type Ⅱ collagen and incomplete Freund’s adjuvant at the tail root. SGFD was administered once a day by oral gavage for 4 weeks. After SGFD administration, rat’s arthritis index (AI) score and paw swelling decreased to some extent, and synovial inflammation, vascular hyperplasia, and cartilage destruction of the ankle joint were improved. Simultaneously, thymus and spleen index and serum levels of C-reactive protein (CRP) were lowered. Network pharmacology revealed that quercetin, kaempferol, naringenin, formononetin isorhamnetin and licochalcone A were the potentialiy active components, and IL6, TP53, TNF, PTGS2, MAPK3 and IL-1β were potential key targets for SGFD in the treatment of RA. Ingredients-targets molecular docking showed that the components had the high binding activity to these target proteins. The mechanism of SGFD for RA involves various biological functions and is closely correlated with TNF signaling pathway, Osteoclast differentiation, T cell receptor signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, NF-κB signaling pathway, toll-like receptor signaling pathway, and so on. Western blot and ELISA showed that the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated c-Jun N-terminal kinase (p-JNK), p-p38, phosphorylated extracellular regulated kinase (p-ERK) and TNF-α was significantly upregulated in the synovium of RA rats, and the levels of serum inflammatory factors were significantly increased. SGFD inhibits the activation of the TLR4/NF-κB/MAPK pathway and the expression/production of pro-inflammatory cytokines. In summary, SGFD could improve the symptoms and inflammatory response in collagen-induced arthritis (CIA) rat model. The mechanism might be related to the regulation of TLR4/MAPKs/NF-κB signaling pathway and the reduction of inflammatory factor release, which partially confirms the results predicted by network pharmacology.