bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between plankton dynamics and growth of the long-lived clam Arctica islandica on the Faroe shelf
Authors: Matras Una , Salter Ian , Larsen Karin Margretha H. , Gaard Eilif , Steingrund Petur
Published: August 2022

Marine ecosystem dynamics can vary on timescales ranging from months to centuries, but many observational data are limited to just a few decades. The bivalveArctica islandicamay live up to five centuries depositing annual growth increments in its shells which can serve as an indicator for ecosystem productivity. In the present study, 154 specimens ofA. islandicawere collected on the Faroe Shelf and standardised annual growth increments for 143 of them – 44 from coastal stations and 99 from shelf stations – were compared with climatic, oceanographic and biological variables.A. islandicagrowth from coastal and shelf stations was not correlated with basin-scale climate indices (the AMO index, the NAO index, the AO index or the subpolar gyre index) or, more locally, with windspeed or sea surface temperature on the Faroe Shelf. For the shelf stations there was a significant negative correlation betweenA. islandicagrowth and the volume transport of the Faroe Current flowing just north of Faroe Islands (r = -0.62). There was a weak nonsignificant positive correlation with an index of primary production on the Faroe Shelf (r = 0.31) and a strong negative correlation with a zooplankton biomass index in mid-summer (r = -0.76). There was also a strong positive correlation betweenA. islandicagrowth and the biomass of the bottom-feeding fish speciesMelanogrammus aeglefinustwo years later (r = 0.62). These results seem to suggest thatA. islandicagrowth may represent the amount of fresh phytoplankton that reaches the near-bottom water layers and could probably be regarded as a proxy for the strength of pelagic-benthic coupling that is modulated through phytoplankton-zooplankton interactions in the overlying water. Our results highlight the potential forA. islandicato serve as a long-term proxy for linking variability in pelagic ecosystem dynamics to demersal fish stocks.
Habitat value of subsea wells and pipelines for fishery target species in Australia
Authors: McLean Dianne , Speed Conrad W. , Birt Matthew Jon , Colquhoun Jamie , Case Mark , Stowar Marcus , Bond Todd , Ierodiaconou Daniel , Whitmarsh Sasha K. , Taylor Michael D. , Wines Sam , Booth David John , Fowler Ashley M. , Vaughan Brigit I.
Published: August 2022

Subsea pipelines and wells installed to support the oil and gas industry represent some of the most extensive and numerous anthropogenic structures throughout global marine ecosystems. There remains a paucity of information on the habitat value of these structures for fishery target species and, as a result, little understanding of how decommissioning should be conducted to minimise impacts to populations of these economically and socially important species. We assess the diversity and abundance of species that are targets of recreational and commercial fisheries on 33 subsea wells and 17 pipelines across the tropical northwest and temperate southeast marine regions of Australia. We examine relationships between fish identity and abundance and a range of environmental (e.g., depth, location), infrastructure-specific (e.g., pipeline position, diameter, age, length of pipeline, height of well, position on well), and biological (% cover of epibiota) variables using video filmed by remotely operated vehicles during their routine offshore inspection and maintenance campaigns. A total of 100 fishery target species were observed across subsea well and pipeline infrastructure, 56 species uniquely observed on pipelines and nine unique to wells. The families Lutjanidae (snapper), Serranidae (rock cods, groupers, perch), and Carangidae (trevallies) were most common and abundant on both wells and pipelines. In the northwest, lutjanids were most abundant around the base of wells, in shallow depths, on shorter wells, and where pipelines spanned the seafloor. A greater number of fishery target species and abundance of ocean perch (Helicolenus spp.) were also associated with pipelines that spanned the seafloor in temperate southeast Australia. The combined biomass of three species of snapper on wells in the northwest was 1,270 kg, with production levels for these species on each well estimated to be 105.2 g m2 year-1. The present study serves as an important reference point for informing decommissioning decisions for pipeline and well infrastructure and demonstrates the utility of industry-held data for science. We suggest that key predictor variables identified here be incorporated into comprehensive before-after-control-impact scientific studies for specific fields/assets to enable the prediction of potential impacts of decommissioning scenarios on marine communities present and quantification of such impacts after the decommissioning activity has occurred.
Effects of sea urchin feces on behaviors, digestion ability, growth, and resistance of the sea cucumber Apostichopus japonicus
Authors: Yu Yushi , Qiao Yihai , Ding Peng , Tian Ruihuan , Sun Jiangnan , Hu Fangyuan , Wu Guo , Chang Yaqing , Zhao Chong
Published: August 2022

Improving the aquaculture production efficiency by appropriate diets is an essential approach to meeting the increasing market demand for sea cucumbers. The feces of sea urchins, which contains various enzymes and microorganisms, is a potentially cost-effective food for sea cucumbers. To assess the usability of the fecal diet, a five-week laboratory simulation is conducted to investigate behaviors, digestion ability, growth and resistance ability of the sea cucumber Apostichopus japonicus fed with fecal diet at water temperatures of 15°C and 5°C. In the present study, A. japonicus fed with fecal diet shows an obvious preference to fecal diet rather than prepared feed at water temperatures of both 15°C and 5°C, which suggests that the feces is an applicable diet for A. japonicus. Furthermore, small A. japonicus fed with feces (group F) shows significant advantages in intestinal community richness, community diversity and intestine protease activity to A. japonicus fed with prepared feed (group S) at 15°C. These results indicate that the fecal diet provides benefits to digestion ability of small A. japonicus at 15°C. Weight gaining rate is significantly higher in the A. japonicus fed with feces than that in A. japonicus that were fed with feed or not fed with food (group C), which suggests that the direct improvement of the production efficiency at 15°C. The advantages in intestinal bacteria, protease activity, and growth are consistently found in group F compared with group S at 5°C. In addition, the composition of intestinal bacteria indicates that sea cucumbers may inherit the intestinal bacteria of sea urchins through fecal consumption. This suggests that the fecal diet enhances the digestion ability and enzyme activity at low water temperature and thus improves the growth of sea cucumbers. Furthermore, sea cucumbers fed with sea urchin feces have the highest survival rate among the three groups in exposure to an acute salinity decrease at both 5 and 15°C, indicating a better resistance to low salinity. This provides a new insight into the geographical expansion to low-salinity areas in sea cucumber aquaculture. In conclusion, the present study suggests that sea urchin feces have a great potential for the application in improving the production efficiency of sea cucumber aquaculture.
Acute oxalate nephropathy: A potential cause of acute kidney injury in diabetes mellitus—A case series from a single center
Authors: Bao Daorina , Wang Yu , Yu Xiaojuan , Zhao Minghui
Published: August 2022

Background

Acute oxalate nephropathy (AON) is an uncommon condition that causes acute kidney injury (AKI), characterized by the massive deposition of calcium oxalate crystals in the renal parenchyma. In previous studies, urinary oxalate excretion has been found to be increased in patients with diabetes mellitus (DM). Here, we report a case series of diabetic patients with AKI with biopsy-proven AON, aiming to alert physicians to the potential of AON as a trigger of AKI in diabetic patients in clinical practice.

Materials and methods

Cases with pathological diagnosis of AON who presented with AKI clinically and had DM between January 2016 and December 2020 were retrospectively enrolled. Their clinical and pathological manifestations, treatment, and prognosis were collected.

Results

Six male patients with biopsy-proven AON out of a total of 5,883 native kidney biopsies were identified, aged 58.3 ± 9.1 years at the time of kidney biopsy. Only one patient who had received Roux-en-Y gastric bypass surgery took oxalate-rich food before the onset of the disease. None of them had clinical features of enteric malabsorption. Three patients were currently on renin-angiotensin system inhibitor treatment for hypertension, and 5 of them received non-steroidal anti-inflammatory drugs. Three patients presented with oliguria and 4 patients needed dialysis at the beginning with none requiring dialysis at discharge. Four patients received a course of corticosteroid treatment empirically. Among them, two patients had estimated glomerular filtration rate (eGFR) recovered to over 60 ml/min/1.73 m2, while the other two patients remained with kidney dysfunction at the last follow-up. In two patients without corticosteroid treatment, one patient fully recovered with eGFR over 90 ml/min/1.73 m2 and the other patient remained with kidney dysfunction at the last follow-up.

Conclusion

AON might be a rare but potentially trigger of AKI in patients with DM. A kidney biopsy could help physicians to make the correct diagnosis. The proper treatment to alleviate oxalate-induced injury needs to be further studied.
Insertion site of central venous catheter among hospitalized adult patients: A systematic review and network meta-analysis
Authors: Sakuraya Masaaki , Okano Hiromu , Yoshihiro Shodai , Niida Shoko , Kimura Keina
Published: August 2022

Introduction

Central venous catheterization is a commonly performed procedure, accounting for approximately 8% of hospitalized patients. Based on the current literatures, the most acceptable site for central venous catheterization is inconclusive, considering various complications in hospitalized patients. Herein, we conducted a network meta-analysis to assess the clinically important complications among internal jugular, subclavian, femoral, and peripheral insertion.

Materials and methods

The Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Ichushi databases, Clinicaltrials.gov, and International Clinical Trials Registry Platform were searched. Studies including adults aged ≥ 18 years and randomized control trials that compared two different insertion sites (internal jugular, subclavian, femoral, and peripheral vein) were selected. The primary outcomes were clinically important infectious, thrombotic, and mechanical complications.

Results

Among the 5,819 records initially identified, 13 trials (6,201 patients) were included for a network meta-analysis. For clinically important infectious complication, subclavian insertion decreased the complication risk, compared with internal jugular [risk ratio (RR), 0.30; 95% confidence interval (CI), 0.11–0.81; moderate certainty], and femoral insertion increased than subclavian insertion (RR 2.56; 95% CI, 1.02–6.44; moderate certainty). Peripheral insertion was also significantly associated with a lower risk compared with internal jugular (RR 0.06; 95% CI, 0.01–0.32; low certainty); subclavian (RR 0.21; 95% CI, 0.05–0.77; moderate certainty); and femoral insertion (RR 0.08; 95% CI, 0.02–0.40; low certainty). For clinically important thrombotic complication, we did not find significant differences between insertion sites. For clinically important mechanical complication, femoral insertion decreased the complication risk, compared with internal jugular (RR 0.42; 95% CI, 0.21–0.82; moderate certainty) and subclavian insertion (RR 0.33; 95% CI, 0.16–0.66; moderate certainty). Peripheral insertion was also associated with the lower complication risk compared with internal jugular (RR 0.39; 95% CI, 0.18–0.85; low certainty) and subclavian insertion (RR 0.31; 95% CI, 0.13–0.75; moderate certainty).

Conclusion

The insertion site of the central venous catheter, which is most likely to cause the fewest complications, should be selected. Our findings can provide the rationale for deciding the insertion site for a central venous catheter.

Systematic review registration

[www.protocols.io], identifier [61375].
Phylogrouping and characterization of Escherichia coli isolated from colonic biopsies and fecal samples of patients with flare of inflammatory bowel disease in Iran
Authors: Nadalian Banafsheh , Nadalian Bahareh , Houri Hamidreza , Shahrokh Shabnam , Abdehagh Mohammad , Yadegar Abbas , Ebrahimipour Gholamhossein
Published: August 2022

Background

Although the etiopathogenesis of inflammatory bowel disease (IBD) is still poorly understood, Escherichia coli has been described as a potential causative microorganism in IBD pathogenesis and also disease progression, offering a potential therapeutic target for disease management. Therefore, we conducted this study to investigate the pathotypes, phylogenetic groups, and antimicrobial resistance of E. coli isolates from patients with IBD in Iran.

Methods

Fecal and biopsy colonic samples were collected from IBD patients experiencing flare-up episodes referred to Taleghani hospital in Tehran, Iran, between August 2020 and January 2021. Identification of E. coli strains was performed based on biochemical and molecular methods. Antibiotic susceptibility testing was performed as recommended by the Clinical and Laboratory Standards Institute. Phylogrouping and pathotyping of each isolate were carried out using polymerase chain reaction (PCR) and multilocus sequence typing (MLST) assays.

Results

A total of 132 non-duplicate E. coli strains were isolated from 113 IBD patients, including 96 ulcerative colitis (UC), and 17 Crohn’s disease (CD) patients. In our study, 55% of CD-related E. coli and 70.5% of UC-related isolates were non-susceptible to at least three or more unique antimicrobial classes, and were considered as multidrug-resistant (MDR) strains. E. coli strains exhibited a high level of resistance to cefazolin, ampicillin, tetracycline, ceftazidime, ciprofloxacin, and cefotaxime. Enterotoxigenic E. coli (ETEC) and diffusely adherent E. coli (DAEC) were the most prevalent pathotypes, and groups B2 and D were the predominant phylogroups.

Conclusion

In the present study, we found that E. coli strains that colonize the gut of Iranian patients with IBD most frequently belonged to phylogenetic groups B2 and D. We also conclude that E. coli isolates from IBD patients have been revealed to be resistant to commonly used antibiotics, in which most of them harbored strains that would be categorized as MDR.
Human immunodeficiency virus-1 core: The Trojan horse in virus–host interaction
Authors: Wang Wei , Li Yan , Zhang Zhe , Wei Wei
Published: August 2022

Human immunodeficiency virus-1 (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDs) worldwide. In HIV-1 infection, innate immunity is the first defensive line for immune recognition and viral clearance to ensure the normal biological function of the host cell and body health. Under the strong selected pressure generated by the human body over thousands of years, HIV has evolved strategies to counteract and deceive the innate immune system into completing its lifecycle. Recently, several studies have demonstrated that HIV capsid core which is thought to be a protector of the cone structure of genomic RNA, also plays an essential role in escaping innate immunity surveillance. This mini-review summarizes the function of capsid in viral immune evasion, and the comprehensive elucidation of capsid-host cell innate immunity interaction could promote our understanding of HIV-1’s pathogenic mechanism and provide insights for HIV-1 treatment in clinical therapy.
A photosynthetic bacterial inoculant exerts beneficial effects on the yield and quality of tomato and affects bacterial community structure in an organic field
Authors: Lee Sook-Kuan , Chiang Ming-Shu , Hseu Zeng-Yei , Kuo Chih-Horng , Liu Chi-Te
Published: August 2022

Plant growth-promoting rhizobacteria (PGPR) are microorganisms that promote plant health and play a critical role in sustainable agriculture. As a PGPR, Rhodopseudomonas palustris strain PS3, when applied as a microbial inoculant, exhibited beneficial effects on a variety of crops. In this study, we investigated the effects of PS3 on tomato growth, soil properties, and soil microbiota composition in an organic field. The results demonstrated that PS3 inoculation significantly improved the yield of marketable tomato fruit (37%) and the postharvest quality (e.g., sweetness, taste, vitamin C, total phenolic compounds, and lycopene). Additionally, soil nutrient availability (35–56%) and enzymatic activities (13–62%) also increased. We detected that approximately 107 CFU/g soil of R. palustris survived in the PS3-treated soil after harvest. Furthermore, several bacterial genera known to be associated with nutrient cycling (e.g., Dyella, Novosphingobium, Luteimonas, Haliangium, and Thermomonas) had higher relative abundances (log2 fold change >2.0). To validate the results of the field experiment, we further conducted pot experiments with field-collected soil using two different tomato cultivars and obtained consistent results. Notably, the relative abundance of putative PGPRs in the genus Haliangium increased with PS3 inoculation in both cultivars (1.5 and 34.2%, respectively), suggesting that this genus may have synergistic interactions with PS3. Taken together, we further demonstrated the value of PS3 in sustainable agriculture and provided novel knowledge regarding the effects of this PGPR on soil microbiota composition.
Effect of long-term temperature stress on the intestinal microbiome of an invasive snail
Authors: Li Shuxian , Qian Zijin , Gao Shuo , Shen Wenjia , Li Xuexia , Li Hong , Chen Lian
Published: August 2022

The gut microbiome is vital to the physiological and biochemical functions of the host, and changes in the composition of these microbial communities may affect growth and adaptability to the environment. Pomacea canaliculata is an invasive freshwater snail which has become a serious agricultural pest. Temperature adaptation is considered an important reason for the widespread distribution of this species. To date, the contribution of the gut microbes to host fitness of P. canaliculata during long-term temperature stress is not well understood. In this study, the morphological changes and intestinal microbiome of P. canaliculata under long-term stress at low temperature (15°C) and high temperature (35°C) were investigated with laboratory experiments. Compared with control group (25°C), the alpha diversity increased and pathogenic bacteria enriched changed under high and low temperature stress. The effect of high temperature stress on the intestinal microbiome of P. canaliculata was more significant than that of low temperature stress. A sustained high temperature environment led to an increase in the abundance of pathogenic bacteria, such as Aeromonas and Enterobacter, and a decrease in the abundance of immune-related bacteria such as Bacteroidetes, Firmicutes, and Lactococcus. These intestine microbiome changes can increase the risk of diseases like intestinal inflammation, and lead to more deaths at high temperature environments. In addition, with the extension of stress time from 14 to 28 days, the beneficial bacteria such as Bacteroidetes, Firmicutes, and Lactococcus were significantly enriched, while potential pathogenic bacteria such as Pseudomonas, Acinetobacter, Shivalella, and Flavobacterium decreased, suggesting that intestinal microbiota may play an important role in host response to heat stress. These results are consistent with previously reported results that the survival rate of both male and female P. canaliculata no longer significantly reduced after 21 days of high temperature stress, suggesting that the surviving P. canaliculata had gradually adapted to high temperature environments under long-term high temperature stress.
Cinnamaldehyde derivatives act as antimicrobial agents against Acinetobacter baumannii through the inhibition of cell division
Authors: Chai Wern Chern , Whittall Jonathan J. , Polyak Steven W. , Foo Klyie , Li Xin , Dutschke Cameron J. , Ogunniyi Abiodun D. , Ma Shutao , Sykes Matthew J. , Semple Susan J. , Venter Henrietta
Published: August 2022

Acinetobacter baumannii is a pathogen with high intrinsic antimicrobial resistance while multidrug resistant (MDR) and extensively drug resistant (XDR) strains of this pathogen are emerging. Treatment options for infections by these strains are very limited, hence new therapies are urgently needed. The bacterial cell division protein, FtsZ, is a promising drug target for the development of novel antimicrobial agents. We have previously reported limited activity of cinnamaldehyde analogs against Escherichia coli. In this study, we have determined the antimicrobial activity of six cinnamaldehyde analogs for antimicrobial activity against A. baumannii. Microscopic analysis was performed to determine if the compounds inhibit cell division. The on-target effect of the compounds was assessed by analyzing their effect on polymerization and on the GTPase activity of purified FtsZ from A. baumannii. In silico docking was used to assess the binding of cinnamaldehyde analogs. Finally, in vivo and in vitro safety assays were performed. All six compounds displayed antibacterial activity against the critical priority pathogen A. baumannii, with 4-bromophenyl-substituted 4 displaying the most potent antimicrobial activity (MIC 32 μg/mL). Bioactivity was significantly increased in the presence of an efflux pump inhibitor for A. baumannii ATCC 19606 (up to 32-fold) and significantly, for extensively drug resistant UW 5075 (greater than 4-fold), suggesting that efflux contributes to the intrinsic resistance of A. baumannii against these agents. The compounds inhibited cell division in A. baumannii as observed by the elongated phenotype and targeted the FtsZ protein as seen from the inhibition of polymerization and GTPase activity. In silico docking predicted that the compounds bind in the interdomain cleft adjacent to the H7 core helix. Di-chlorinated 6 was devoid of hemolytic activity and cytotoxicity against mammalian cells in vitro, as well as adverse activity in a Caenorhabditis elegans nematode model in vivo. Together, these findings present halogenated analogs 4 and 6 as promising candidates for further development as antimicrobial agents aimed at combating A. baumannii. This is also the first report of FtsZ-targeting compounds with activity against an XDR A. baumannii strain.
Micellization: A new principle in the formation of biomolecular condensates
Authors: Yamazaki Tomohiro , Yamamoto Tetsuya , Hirose Tetsuro
Published: August 2022

Phase separation is a fundamental mechanism for compartmentalization in cells and leads to the formation of biomolecular condensates, generally containing various RNA molecules. RNAs are biomolecules that can serve as suitable scaffolds for biomolecular condensates and determine their forms and functions. Many studies have focused on biomolecular condensates formed by liquid-liquid phase separation (LLPS), one type of intracellular phase separation mechanism. We recently identified that paraspeckle nuclear bodies use an intracellular phase separation mechanism called micellization of block copolymers in their formation. The paraspeckles are scaffolded by NEAT1_2 long non-coding RNAs (lncRNAs) and their partner RNA-binding proteins (NEAT1_2 RNA-protein complexes [RNPs]). The NEAT1_2 RNPs act as block copolymers and the paraspeckles assemble through micellization. In LLPS, condensates grow without bound as long as components are available and typically have spherical shapes to minimize surface tension. In contrast, the size, shape, and internal morphology of the condensates are more strictly controlled in micellization. Here, we discuss the potential importance and future perspectives of micellization of block copolymers of RNPs in cells, including the construction of designer condensates with optimal internal organization, shape, and size according to design guidelines of block copolymers.
The effects of different types of Tai Chi exercises on motor function in patients with Parkinson's disease: A network meta-analysis
Authors: Lei Honghui , Ma Zhen , Tian Kexin , Liu Ke , Wang Jiaying , Zhu Xiangyu , Mi Baohong , Chen Ying , Yang Qihao , Jiang Huili
Published: August 2022

Background

Tai Chi can show improvement in balance and motor ability of elderly patients with PD. However, there were few reports on differences in outcomes associated with different types of Tai Chi on improving exercise capacity in elderly patients with PD. We compared the improvement of motor function in Parkinson's patients with different types of Tai Chi, for finding an optimal intervention.

Methods

The following databases were searched from the beginning of the establishment of each database to 10 January 2022: PubMed, EMBASE, The Cochrane Library, CNKI, Wanfang Database, and VIP Database. Randomized controlled trials incorporating different types of Tai Chi for PD were included. The outcome measures were UPDRSIII and BBS. NMA was conducted using Stata 15.0 based on a frequentist framework.

Results

A total of twenty trials were eligible, including 996 participants. In conventional meta-analysis, as for the UPDRSIII scale, 24-form simplified Tai Chi (SMD = −1.272, 95% CI [−2.036, −0.508], P < 0.05, I2 > 50%), Tai Chi exercise program (SMD = −0.839, 95% CI [−1.828, 0.151], P > 0.05, I2 > 50%), 8-form simplified Yang style Tai Chi (SMD = −0.325, 95% CI [−1.362, 0.713], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (SMD = −0.28, 95% CI [−0.97, 0.42], P > 0.05, I2 > 50%) were statistically more efficient than the control group. For BBS outcome, 24-form simplified Tai Chi (MD = 3.979, 95% CI [3.364, 4.595], P < 0.05, I2 <50%), Tai Chi exercise program (MD = 5.00, 95% CI [2.07, 7.93], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (MD = 1.25, 95% CI [0.52, 1.98], P < 0.05, I2 > 50%) were better than the control group. In the network meta-analysis, the results of UPDRSIII were as follows: 24-form > TCEP > 8-form YS > 8-form CS > control. The ranking probability of BBS was as follows: TCEP > 24-form > 8-form CS > control.

Conclusion

Among the four treatments studied, 24-form Tai Chi and Tai Chi exercise programs have shown better efficacy than other types. Our study provides new insights into exercise therapy for PD and may contribute to the formulation of a clinical exercise prescription.

Systematic review registration

Identifier: CRD42021285005.
Small extracellular vesicles derived from mesenchymal stem cell facilitate functional recovery in spinal cord injury by activating neural stem cells via the ERK1/2 pathway
Authors: Hu Xinyuan , Liu Zhong , Zhou Xinru , Jin Qian , Xu Wenrong , Zhai Xiao , Fu Qiang , Qian Hui
Published: August 2022

Spinal cord injury (SCI) causes severe neurological dysfunction leading to a devastating disease of the central nervous system that is associated with high rates of disability and mortality. Small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hucMSC-sEVs) have been explored as a promising strategy for treating SCI. In this study, we investigated the therapeutic effects of the intralesional administration of hucMSC-sEVs after SCI and determined the potential mechanisms of successful repair by hucMSC-sEVs. In vivo, we established the rat model of SCI. The Basso, Beattie, Bresnahan (BBB) scores showed that hucMSC-sEVs dramatically promoted the recovery of spinal cord function. The results of the hematoxylin–eosin (HE) staining, Enzyme-Linked Immunosorbent Assay (ELISA), and immunohistochemistry showed that hucMSC-sEVs inhibited inflammation and the activation of glia, and promoted neurogenesis. Furthermore, we studied the effect of hucMSC-sEVs on neural stem cells(NSCs) in vitro. We found that hucMSC-sEVs did not improve the migration ability of NSCs, but promoted NSCs to proliferate and differentiate via the ERK1/2 signaling pathway. Collectively, these findings suggested that hucMSC-sEVs promoted the functional recovery of SCI by activating neural stem cells via the ERK1/2 pathway and may provide a new perspective and therapeutic strategy for the clinical application of hucMSC-sEVs in SCI treatment.
Simplex cerebral cavernous malformations with MAP3K3 mutation have distinct clinical characteristics
Authors: Huo Ran , Wang Jie , Sun Ying-Fan , Weng Jian-Cong , Li Hao , Jiao Yu-Ming , Xu Hong-Yuan , Zhang Jun-Ze , Zhao Shao-Zhi , He Qi-Heng , Wang Shuo , Zhao Ji-Zong , Cao Yong
Published: August 2022

Objectives

To investigate the clinical characteristics of cerebral cavernous malformations (CCMs) with MAP3K3 somatic mutation.

Methods

We performed a retrospective review of our CCMs database between May 2017 and December 2019. The patients with simplex CCMs identified to harbor a MAP3K3 or CCM gene somatic mutation were included. Clinical characteristics were recorded. Univariate and multivariate logistic analyses were used to assess the risk factors associated with hemorrhage events of CCMs. To explore the underlying mechanism, we transfected MEKK3-I441M-overexpressing and CCM2-knockdown lentiviruses into human umbilical vein endothelial cells (HUVECs) and investigated thrombomodulin (TM) and tight junctions (TJs) protein expression by western blotting and immunofluorescence. Finally, immunohistochemistry was used to validate TM and TJs protein expression in surgical samples.

Results

Fifty simplex CCMs patients were included, comprising 38 MAP3K3 mutations and 12 CCM gene mutations. Nine (23.7%) patients with MAP3K3 mutations and 11(91.7%) patients with CCM gene mutations exhibited overt hemorrhage, respectively. Multivariate logistic analyses revealed that MAP3K3 mutation was associated with a lower risk of hemorrhage events. In the vitro experiments, ZO-1 expression was not reduced in MEKK3-I441M-overexpressing HUVECs compared with wild type, whereas it was significantly decreased in CCM2-knockdown HUVECs compared with control. In the MEKK3-I441M-overexpressing HUVECs, TM expression was increased, and the NF-κB pathway was significantly activated. After treatment with an NF-κB signaling inhibitor, TM expression was further upregulated. Meanwhile, TM expression was increased, but the NF-κB pathway was not activated in CCM2-knockdown HUVECs. Accordingly, immunohistochemistry showed that ZO-1 expression in the MAP3K3-mutant samples was significantly higher than that in the CCM-mutant samples. TM expression in the MAP3K3-mutant lesions was significantly lower than that in the CCM-mutant samples.

Conclusion

Simplex CCMs with MAP3K3 mutation occasionally present with overt hemorrhage, which is associated with the biological function of MAP3K3 mutation.
Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations
Authors: Liu Yuefang , Liang Zhe , Cai Weili , Shao Qixiang , Pan Qiong
Published: August 2022

Introduction

TRIO and CNKSR2 have been demonstrated as the important regulators of RAC1. TRIO is a guanine exchange factor (GEF) and promotes RAC1 activity by accelerating the GDP to GTP exchange. CNKSR2 is a scaffold and adaptor protein and helps to maintain Rac1 GTP/GDP levels at a concentration conducive for dendritic spines formation. Dysregulated RAC1 activity causes synaptic function defects leading to neurodevelopmental disorders (NDDs), which manifest as intellectual disability, learning difficulties, and language disorders.

Case presentation

Here, we reported two cases with TRIO variation from one family and three cases with CNKSR2 variation from another family. The family with TRIO variation carries a novel heterozygous frameshift variant c.3506delG (p. Gly1169AlafsTer11), where a prenatal case and an apparently asymptomatic carrier mother with only enlarged left lateral ventricles were firstly reported. On the other hand, the CNKSR2 family carries a novel hemizygous non-sense variant c.1282C>T (p. Arg428*). Concurrently, we identified a novel phenotype never reported in known pathogenic CNKSR2 variants, that hydrocephalus and widening lateral ventricle in a 6-year-old male of this family. Furthermore, the genotype–phenotype relationship for TRIO, CNKSR2, and RAC1 was explored through a literature review.

Conclusion

The novel variants and unique clinical features of these two pedigrees will help expand our understanding of the genetic and phenotypic profile of TRIO- and CNKSR2-related diseases.
Influence of endothelial function and arterial stiffness on the behavior of cervicocephalic arterial dissections: An observational study
Authors: Lee Seong-Joon , Lee Jin Soo , Kim Min , Park So Young , Park Ji Hyun , Park Bumhee , Jung Woo Sang , Choi Jin Wook , Hong Ji Man
Published: August 2022

Background

The mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV).

Methods

From a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes.

Results

A total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 −10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07–94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis.

Conclusion

In spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.
Dynamic regional homogeneity alterations and cognitive impairment in patients with moderate and severe obstructive sleep apnea
Authors: Li Kunyao , Shu Yongqiang , Liu Xiang , Xie Wei , Li Panmei , Kong Linghong , Yu Pengfei , Zeng Yaping , Huang Ling , Long Ting , Zeng Li , Li Haijun , Peng Dechang
Published: August 2022

Background and purpose

Previous studies have found that abnormal local spontaneous brain activity in patients with obstructive sleep apnea (OSA) was associated with cognitive impairment, and dynamic functional connections can capture the time changes of functional connections during magnetic resonance imaging acquisition. The purpose of this study was to investigate the dynamic characteristics of regional brain connectivity and its relationship with cognitive function in patients with OSA and to explore whether the dynamic changes can be used to distinguish them from healthy controls (HCs).

Methods

Seventy-nine moderate and severe male OSA patients without any treatment and 84 HCs with similar age and education were recruited, and clinical data and resting functional magnetic resonance imaging data were collected. The dynamic regional homogeneity (dReHo) was calculated using a sliding window technique, and a double-sample t-test was used to test the difference in the dReHo map between OSA patients and HCs. We explored the relationship between dReHo and clinical and cognitive function in OSA patients using Pearson correlation analysis. A support vector machine was used to classify the OSA patients and HCs based on abnormal dReHo.

Result

Compared with HCs, OSA patients exhibited higher dReHo values in the right medial frontal gyrus and significantly lower dReHo values in the right putamen, right superior temporal gyrus, right cingulate gyrus, left insula and left precuneus. The correlation analysis showed that the abnormal dReHo values in multiple brain regions in patients with OSA were significantly correlated with nadir oxygen saturation, the oxygen depletion index, sleep period time, and Montreal cognitive assessment score. The support vector machine classification accuracy based on the dReHo difference in brain regions was 81.60%, precision was 81.01%, sensitivity was 81.01%, specificity was 82.14%, and area under the curve was 0.89.

Conclusion

The results of this study suggested that there was abnormal dynamic regional spontaneous brain activity in patients with OSA, which was related to clinical and cognitive evaluation and can be used to distinguish OSA patients from HCs. The dReHo is a potential objective neuroimaging marker for patients with OSA that can further the understanding of the neuropathological mechanism of patients with OSA.
The ventral striatum contributes to the activity of the motor cortex and motor outputs in monkeys
Authors: Suzuki Michiaki , Nishimura Yukio
Published: August 2022

The ventral striatum (VSt) is thought to be involved in the vigor of motivated behavior and is suggested to be a limbic-motor interface between limbic areas involved in motivational processes and neural circuits regulating behavioral outputs. However, there is little direct evidence demonstrating the involvement of the VSt in motor control for motivated behaviors. To clarify the functional role of the VSt in motor control, we investigated the effect of reversible pharmacological inactivation of the VSt on the oscillatory activity of the sensorimotor cortices and motor outputs in two macaque monkeys. VSt inactivation reduced movement-related activities of the primary motor cortex and premotor area at 15–120 Hz and increased those at 5–7 Hz. These changes were accompanied by reduced torque outputs but had no effect on the correct performance rate. The present study provides direct evidence that the VSt regulates activities of the motor cortices and motor output.
Molecular mechanisms of flavonoid accumulation in germinating common bean (Phaseolus vulgaris) under salt stress
Authors: Zhang Qi , Zheng Guangyue , Wang Qi , Zhu Jixing , Zhou Zhiheng , Zhou Wenshuo , Xu Junjie , Sun Haoyue , Zhong Jingwen , Gu Yanhua , Yin Zhengong , Du Yan-li , Du Ji-dao
Published: August 2022

Flavonoids are important secondary metabolites, active biomolecules in germinating beans, and have prominent applications in food and medicine due to their antioxidant effects. Rutin is a plant flavonoid with a wide biological activity range. In this study, flavonoid (rutin) accumulation and its related molecular mechanisms in germinating common bean (Phaseolus vulgaris) were observed at different time points (0–120 h) under salt stress (NaCl). The rutin content increased from germination onset until 96 h, after which a reducing trend was observed. Metabolome analysis showed that salt stress alters flavonoid content by regulating phenylpropanoid (ko00940) and flavonoid (ko00941) biosynthesis pathways, as well as their enzyme activities, including cinnamyl-alcohol dehydrogenase (CAD), peroxidase (POD), chalcone isomerase (CHI), and flavonol synthase (FLS). The RNA-seq and quantitative real-time PCR (qRT-PCR) analyses also showed that these two pathways were linked to changes in flavonoid content following salt treatment. These results reveal that salt stress effectively enhanced rutin content accumulation in germinating beans, hence it could be employed to enhance the functional quality of germinating common beans.
Association between serum vitamin D status and the anti-seizure treatment in Chinese children with epilepsy
Authors: Dong Na , Guo Hong-Li , Hu Ya-Hui , Yang Jiao , Xu Min , Ding Le , Qiu Jin-Chun , Jiang Zhen-Zhou , Chen Feng , Lu Xiao-Peng , Li Xiao-Nan
Published: August 2022

Objective

To compare the serum 25-OH-VitD levels, the major marker of vitamin D (VitD) status, between healthy children and children with epilepsy before initiation of and during anti-seizure medications (ASMs) treatment and to evaluate the potential influence factors on 25-OH-VitD levels. Another major aim was to assess the potential role of VitD supplementation.

Methods

For comparison, we finally enrolled and collected data from 6,338 healthy children presenting to Health Care Department and 648 children visiting primary care pediatricians with symptoms of epilepsy in Children’s Hospital of Nanjing Medical University from January 2019 to June 2021. The demographic and biochemical characteristics of each child were extracted from the hospital information system.

Results

Serum 25-OH-VitD levels in 648 children with epilepsy were significantly lower than those of 6,338 healthy children (P < 0.0001), and the percentage of VitD insufficiency and deficiency status in pediatric patients was 49.19%. Of note, the serum 25-OH-VitD levels in children with newly diagnosed epilepsy before receiving any ASMs treatment were also significantly lower than those in healthy controls. Interestingly, ASMs therapy, alone or in combination, did not consistently reduce baseline serum VitD levels in children with epilepsy. The lower serum VitD levels in pediatric patients than those in healthy children might be related to the disease itself, rather than the ASMs treatment. As expected, VitD supplementation substantially increased the serum 25-OH-VitD levels (P < 0.0001). More critically, children with epilepsy receiving VitD supplementation achieved good seizure control in our study.

Significance

In this retrospective study, the childhood epilepsy before initiation of and during ASMs treatment decreased the serum 25-OH-VitD concentrations, suggesting a clear association between epileptic disease and the risk of VitD deficiency. ASMs coadministration and long-term valproic acid treatment did not worse VitD-deficiency status, but in the small group receiving VitD supplementation, there was a significant improvement in reduction of seizure frequency. Therefore, pediatric clinicians are urged to raise public awareness of epilepsy-associated VitD deficiency.
LncRNA GAS5 represses stemness and malignancy of gliomas via elevating the SPACA6-miR-125a/let-7e Axis
Authors: Wu Shuang , Ren Kaixi , Zhao Jing , Li Juan , Jia Bo , Wu Xiuquan , Dou Yanan , Fei Xiaowei , Huan Yu , He Xin , Wang Tingting , Lv Weihao , Wang Li , Wang Yan’gang , Zhao Junlong , Fei Zhou , Li Sanzhong
Published: August 2022

Glioblastoma (GBM) is a highly invasive neurological malignancy with poor prognosis. LncRNA-GAS5 (growth arrest-specific transcript 5) is a tumor suppressor involved in multiple cancers. In this study, we explored the clinical significance, biological function, and underlying mechanisms of GAS5 in GBM. We showed that lncRNA-GAS5 expression decreased in high-grade glioma tissues and cells, which might be associated with poor prognosis. GAS5 overexpression lowered cell viability, suppressed GBM cell migration and invasion, and impaired the stemness and proliferation of glioma stem cells (GSCs). We further discovered that GAS5 inhibited the viability of glioma cells through miR-let-7e and miR-125a by protecting SPACA6 from degradation. Moreover, GAS5 played an anti-oncogenic role in GBM through the combined involvement of let-7e and miR-125a in vivo and in vitro. Notably, these two miRNAs block the IL-6/STAT3 pathway in tumor tissues extracted from a xenograft model. Taken together, our study provides evidence for an important role of GAS5 in GBM by affecting the proliferation and migration of GSCs, thus providing a new potential prognostic biomarker and treatment strategy for GBM.
CRISPR-based knockout screening identifies the loss of MIEF2 to enhance oxaliplatin resistance in colorectal cancer through inhibiting the mitochondrial apoptosis pathway
Authors: Xie Chaozheng , Li Kang , Li Ya , Peng Xudong , Teng Biyun , He Kuan , Jin Aishun , Wang Wang , Wei Zhengqiang
Published: August 2022

The first-line anticancer agent oxaliplatin (OXL) is the preferred drug for treating colorectal cancer (CRC); however, the development of drug resistance is common in patients treated with OXL, which considerably reduces the efficacy of OXL-based regimens. By performing genome-wide CRISPR/Cas9 library knockdown screening, we found that mitochondrial elongation factor 2 (MIEF2) was among the top candidate genes. The OXL-resistant cell lines and organoids developed in the present study showed stable but low expression of MIEF2. Reduced MIEF2 expression may enhance CRC resistance to OXL by reducing mitochondrial stability and inhibiting apoptosis by decreasing cytochrome C release. In conclusion, among the different biomarkers of OXL resistance in CRC, MIEF2 may serve as a specific biomarker of OXL responsiveness and a potential target for the development of therapies to improve chemotherapeutic effectiveness.
Comprehensive analysis of tissue proteomics in patients with papillary thyroid microcarcinoma uncovers the underlying mechanism of lymph node metastasis and its significant sex disparities
Authors: Cao Zhen , Zhang Zejian , Tang Xiaoyue , Liu Rui , Wu Mengwei , Wu Jianqiang , Liu Ziwen
Published: August 2022

Background

Lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC) is associated with an increased risk of recurrence and poor prognosis. Sex has been regarded as a critical risk factor for LNM. The present study aimed to investigate the molecular mechanisms underlying LNM and its significant sex disparities in PTMC development.

Methods

A direct data-independent acquisition (DIA) proteomics approach was used to identify differentially expressed proteins (DEPs) in PTMC tumorous tissues with or without LNM and from male and female patients with LNM. The functional annotation of DEPs was performed using bioinformatics methods. Furthermore, The Cancer Genome Atlas Thyroid Carcinoma (TCGA-THCA) dataset and immunohistochemistry (IHC) were used to validate selected DEPs.

Results

The proteomics profile in PTMC with LNM differed from that of PTMC without LNM. The metastasis-related DEPs were primarily enriched in categories associated with mitochondrial dysfunction and may promote tumor progression by activating oxidative phosphorylation and PI3K/AKT signaling pathways. Comparative analyses of these DEPs revealed downregulated expression of specific proteins with well-established links to tumor metastasis, such as SLC25A15, DIRAS2, PLA2R1, and MTARC1. Additionally, the proteomics profiles of male and female PTMC patients with LNM were dramatically distinguishable. An elevated level of ECM-associated proteins might be related to more LNM in male PTMC than in female PTMC patients. The upregulated expression levels of MMRN2 and NID2 correlated with sex disparities and showed a positive relationship with unfavorable variables, such as LNMs and poor prognosis.

Conclusions

The proteomics profiles of PTMC show significant differences associated with LNM and its sex disparities, which further expands our understanding of the functional networks and signaling pathways related to PTMC with LNM.