bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Immune Responses Elicited by SARS-CoV-2 mRNA and Recombinant Protein Vaccine Candidates
Authors: Wu Yixin , Zhang Huicong , Meng Liuxian , Li Fusheng , Yu Changyuan
Published: May 2022

After the outbreak of COVID-19, billions of vaccines with different types have been administrated, including recombinant protein vaccines and mRNA vaccines. Although both types of SARS-CoV-2 vaccine can protect people from viral infection, their differences in humoral and cellular immune responses are still not clearly understood. In this study, we made a head-to-head comparison between an mRNA vaccine candidate and a recombinant protein vaccine we developed previously. Results demonstrated that both vaccine candidates could elicit high specific binding and neutralizing antibody titers in BALB/c mice, but with bias towards different IgG subtypes. Besides, the mRNA vaccine candidate induces higher cellular immune responses than the recombinant protein vaccine. To date, this is the first reported study to directly compare the immune responses of both arms between SARS-CoV-2 mRNA and recombinant vaccines.
Longitudinal Dynamics of Cellular Responses in Recovered COVID-19 Patients
Authors: Cheng Meng-Li , Liu Hui-Ying , Zhou Chao , Li Rui-Ting , Zheng Jing , Qin Yan-Hong , Yang Ning , Zhang Yue , Huang Juan-Juan , Zhu Zhu , Meng Qing-Yu , Wang Guo-Qing , Zhao Hui , Chen Yun , Bai Chang-Qing , Qin Cheng-Feng , Li Fan
Published: May 2022

Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.
Data-Driven Modeling of Dissolved Iron in the Global Ocean
Authors: Huang Yibin , Tagliabue Alessandro , Cassar Nicolas
Published: May 2022

The importance of dissolved Fe (dFe) in regulating ocean primary production and the carbon cycle is well established. However, the large-scale distribution and temporal dynamics of dFe remain poorly constrained in part due to incomplete observational coverage. In this study, we use a compilation of published dFe observations (n=32,344) with paired environmental predictors from contemporaneous satellite observations and reanalysis products to build a data-driven surface-to-seafloor dFe climatology with 1°×1° resolution using three machine-learning approaches (random forest, supper vector machine and artificial neural network). Among the three approaches, random forest achieves the highest accuracy with overall R2 and root mean standard error of 0.8 and 0.3 nmol L-1, respectively. Using this data-driven climatology, we explore the possible mechanisms governing the dFe distribution at various depth horizons using statistical metrics such as Pearson correlation coefficients and the rank of predictors importance in the model construction. Our results are consistent with the critical role of aeolian iron supply in enriching surface dFe in the low latitude regions and suggest a far-reaching impact of this source at depth. Away from the surface layer, the strong correlation between dFe and apparent oxygen utilization implies that a combination of regeneration, scavenging and large-scale ocean circulation are controlling the interior distribution of dFe, with hydrothermal inputs important in some regions. Finally, our data-driven dFe climatology can be used as an alternative reference to evaluate the performance of ocean biogeochemical models. Overall, the new global scale climatology of dFe achieved in our study is an important step toward improved representation of dFe in the contemporary ocean and may also be used to guide future sampling strategies.
Going With the Flow – Population Genetics of the Kelp Saccharina latissima (Phaeophyceae, Laminariales)
Authors: Ribeiro Pedro A. , Næss Tonje , Dahle Geir , Asplin Lars , Meland Kenneth , Fredriksen Stein , Sjøtun Kjersti
Published: May 2022

Saccharina latissimais the most important habitat-forming kelp in sheltered areas of North-Atlantic, and there is also an increasing interest in cultivation and utilization ofS. latissima. The cultivation activity may introduce a risk of “crop-to-wild” gene flow from the cultivated crops to natural populations. A baseline study to examine genetic structure and gene flow inS. latissimaalong the Norwegian coast was therefore done. Microsatellite analyses was carried out on samples from 21 stations, where 12 were in the coastal area from outer Oslofjord in the south to Porsanger in North-Norway, and 9 in the two longest fjords of Norway, Hardangerfjord and Sognefjord. In addition, a hydrographical model was applied, simulating the direction and potential rate of spore dispersal along the coast during the main period of spore release. The results showed a clear isolation by distance pattern along the coast, good connectivity and little genetic structure, except for a reduced connectivity between South- and North-Norway, probably due to the Lofoten archipelago representing a partial barrier for the northward dispersal of spores. In addition, indications of reduced connectivity between coastal stations and the innermost fjord stations were found. Analysing the material with and without one locus potentially under positive selection suggests some degree of genetic adaptation of sugar kelp populations in the Skagerrak area and in the two fjords. The results suggest that genetic connectivity between populations on the coast is strongly influenced by the Norwegian Coastal current.
Atlantic Cod Growth History in Flemish Cap Between 1981 and 2016: The Impact of Fishing and Climate on Growth Performance
Authors: Ruiz-Díaz Raquel , Dominguez-Petit Rosario , Saborido-Rey Fran
Published: May 2022

Flemish Cap cod collapsed in the early 90’s after facing multiple threats due to climate variability and anthropogenic pressures. A master 35-year cod growth chronology was reconstructed in the present study by using sclerochronology techniques. Three additional chronologies were developed to account for the age-dependent effect of maturity and fishing intensity on growth. All chronologies showed that cod growth has decreased over the years and it is currently at the minimum level in the historic of data series. Hierarchical mixed-effects models were applied to the master chronology to identify extrinsic drivers of growth. The master chronology was divided into 3 periods: Premoratorium (1988-1998), Moratorium (1999-2009), and Postmoratorium (2010-2019). Our results showed that drivers of cod growth in the Flemish Cap varied between periods (Premoratorium: bottom temperature and fishing mortality, Moratorium: cod and pandalus abundance, and Postmoratorium: cod abundance and thickness of the cold intermediate layer). Our results suggest that density-dependence processes, food availability, and global warming may be behind the lack of recovery of the Flemish Cap cod stock. The Flemish Cap cod growth chronology shows variations on growth over time and identifies its drivers, having the potential to be included in the NAFO stock assessments or to be used to set dynamic reference points that guarantees the stock sustainability.
Resistivity of Surface Steps in Bulk-Insulating Topological Insulators
Authors: Ko Wonhee , Hus Saban , Kim Hoil , Kim Jun Sung , Zhang Xiao-Guang , Li An-Ping
Published: May 2022

Electron transport in topological insulators usually involves both topologically protected surface states and trivial electronic states in the bulk material. The surface transport is particularly interesting; however, it is also susceptible to atomic defects on the surfaces, such as vacancies, impurities, and step edges. Experimental determination of scattering effects of these surface defects requires both nanoscale spatial resolution and the ability to decipher surface transport from bulk transport. Here we directly measure the resistivity of individual surface steps in the surface dominating transport process of topological insulator Bi2Te2Se. A variable probe-spacing transport spectroscopy with a multiprobe scanning tunneling microscope is used to differentiate the surface conductance from bulk conductance, allowing the identification of a surface dominant transport regime. The technique also reveals a deviation from ideal 2D transport at atomic steps. Then, a multi-probe scanning tunneling potentiometry is employed to visualize the electrochemical potentials across individual step edges. A quantitative analysis of the potential distributions enables us to acquire a resistivity of 0.530 mΩ · cm for the one quintuple-layer atomic step. The result indicates that atomic defects, despite preserving the time-reversal symmetry, can still significantly affect the transport in topological insulators.
Tri-Band Negative Modulus Acoustic Metamaterial With Nested Split Hollow Spheres
Authors: Hao Limei , Li Yujia , Yan Xiaole , Yang Xiao , Guo Xueyi , Xie You , Pang Shaofang , Chen Zhi , Zhu Weiren
Published: May 2022

We presented tri-band negative modulus acoustic metamaterials (AM), whose operation characteristics could be flexibly designed by changing the three hole sizes (i.e., a1, a2, and a3) of the tri-layer nested split hollow spheres (NSHSs). We demonstrate numerically that tri-band negative modulus can be obtained and each resonant frequency corresponds to the hole size of each split hollow sphere. However, for the case when a1> a2> a3, the negative modulus band in the high frequency region vanishes. An effective sound-force analogue model with coupling interaction is further developed for the accurate prediction of the three resonant frequencies based on equating the tri-layer NSHSs to three spring oscillators in series. As a result of the analytical formulas, three resonant frequencies could be precisely controlled, and a nested AM with a tri-band negative modulus can be flexibly constructed. The proposed AM could be easily extended to multiple operation bands and can be further coupled with negative mass density structures for constructing multi-band double-negative AMs.
Oblique Lateral Interbody Fusion vs. Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Spinal Stenosis: A Retrospective Cohort Study
Authors: Gao Quan-You , Wei Fei-Long , Li Tian , Zhu Kai-Long , Du Ming-Rui , Heng Wei , Yang Fan , Gao Hao-Ran , Qian Ji-Xian , Zhou Cheng-Pei
Published: May 2022

Background

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an effective surgical option for lumbar spinal stenosis (LSS) with spondylolisthesis. However, few studies have discussed oblique lateral interbody fusion (OLIF) with MIS-TLIF.

Objective

To evaluate postoperative improvements, complications, and reoperation rates between patients with LSS undergoing OLIF or MIS-TLIF.

Methods

We retrospectively studied 113 LLS patients who underwent OLIF (53) or MIS-TLIF (60) with percutaneous pedicle screw fixation between January 2016 and December 2018. We measured estimated blood loss, operative time, hospital stay, reoperation, and complication incidence, visual analog scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopedic Association (JOA), and Short Form-36 (SF-36) scores, discal and foraminal height and lumbar lordotic angle.

Results

The mean age was 58.81 ± 0.9 years. The TLIF group had increased operation time, blood loss, and hospital stays (p = 0.007, 0.001, and 0.016, respectively). Postoperatively, VAS and ODI scores significantly decreased while JOA and SF-36 scores significantly increased. The postoperative differences in main outcomes between the groups were insignificant (all p > 0.05). The OLIF group had the lowest rates of overall (9.8% OLIF vs. 12.9% MIS-TLIF), intraoperative (3.9% OLIF vs. 4.8% MIS-TLIF), and postoperative complications (5.9% OLIF vs. 8.1% MIS-TLIF), but the differences were insignificant (p = 0.607, 0.813, and 0.653, respectively). The reoperation rate did not differ significantly (3.8% OLIF vs. 3.3% MIS-TLIF) (p = 0.842). OLIF restored disc height (74.4 vs. 32.0%), foraminal height (27.4 vs. 18.2%), and lumbar lordotic angle (3.5 vs. 1.1%) with greater success than did MIS-TLIF.

Conclusion

Patients undergoing OLIF with LSS improved similarly to MIS-TLIF patients. OLIF restored disc height, foraminal height and lumbar lordotic angle more successfully than did MIS-TLIF.
Management of Medicines Wastage, Returned Medicines and Safe Disposal in Malaysian Community Pharmacies: A Qualitative Study
Authors: Chong Kah Mun , Rajiah Kingston , Chong David , Maharajan Mari Kannan
Published: May 2022

Introduction

In supplying medicines to patients and consumers waste can occur in prescribing, dispensing, and leftover stages. Pharmacists in community pharmacies play a crucial role in dispensing and should share information on appropriate medicines disposal with consumers. This qualitative study explored how Malaysian community pharmacists manage medication wastage, returned medicines, and medicines disposal by eliciting their opinions on medicines wastage, the challenges faced, and feasibility of medicine return and safe medicine disposal in the setting of Malaysian community pharmacy.

Methods

Telephonic interviews were conducted using a pre-validated interview guide among community pharmacists. Purposive sampling was used to ensure heterogeneity of participants in terms of gender, age, and position in the pharmacy. The interview was conducted until a point where no new information was obtained. Interview data were thematically analyzed.

Results

The analysis identified nine themes organized into four domains. The results revealed that pharmacists have positive perceptions of the safe disposal of medicines. Pharmacists mentioned that medicine returns to service in community pharmacies are not common due to a lack of facilities in the management of unwanted, expired, and returned medicines. As such pharmacists have suggested a few ways to minimize medicinal wastage.

Conclusions

Respondents aimed to minimize medicines wastage (unused medicines) in order to minimize loss of revenue. Respondents did not usually accept returned medicines due to the operational costs of safe disposal. Disposal of unused medicines was undertaken by centralizing the stocks at an organization facility before being disposed of by outsourced waste management companies.
Deep Sequencing of Plasma Exosomal microRNA Level in Psoriasis Vulgaris Patients
Authors: Chen Xiu-Min , Yao Dan-Ni , Wang Mao-Jie , Wu Xiao-Dong , Deng Jing-Wen , Deng Hao , Huang Run-Yue , Lu Chuan-Jian
Published: May 2022

Psoriasis is a chronic skin disease affecting 1% to 3% of the world population. Psoriasis vulgaris (PV) is the most common form of psoriasis. PV patients suffer from inflamed, pruritic and painful lesions for years (even a lifetime). However, conventional drugs for PV are costly. Considering the need for long-term treatment of PV, it is urgent to discover novel biomarkers and therapeutic targets. Plasma exosomal miRNAs have been identified as the reliable biomarkers and therapy targets of human diseases. Here, we described the levels of plasma exosomal miRNAs in PV patients and analyzed the functional features of differently expressed miRNAs and their potential target genes for the first time. We identified 1,182 miRNAs including 336 novel miRNAs and 246 differently expressed miRNAs in plasma exosomes of healthy people and PV patients. Furthermore, the functional analysis found differently expressed miRNA-regulated target genes enriched for specific GO terms including primary metabolic process, cellular metabolic process, metabolic process, organic substance metabolic process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway containing cellular processes, human diseases, metabolic pathways, metabolism and organismal systems. In addition, we found that some predicted target genes of differentially expressed miRNAs, such as CREB1, RUNX2, EGFR, are both involved in inflammatory response and metabolism. In summary, our study identifies many candidate miRNAs involved in PV, which could provide potential biomarkers for diagnosis of PV and targets for clinical therapies against PV.
Emergence of blaNDM– 1-Carrying Aeromonas caviae K433 Isolated From Patient With Community-Acquired Pneumonia
Authors: Luo Xinhua , Mu Kai , Zhao Yujie , Zhang Jin , Qu Ying , Hu Dakang , Jia Yifan , Dai Piaopiao , Weng Jian , Wang Dongguo , Yu Lianhua
Published: May 2022

To demonstrate the detailed genetic characteristics of a blaNDM–1-carrying multidrug-resistant Aeromonas caviae strain, the complete genome of the A. caviae strain K433 was sequenced by Illumina HiSeq and Oxford nanopore platforms, and mobile genetic elements associated with antibiotic resistance genes were analyzed by a series of bioinformatics methods. A. caviae K433 which was determined to produce class B carbapenemase, was resistant to most antibiotics tested except amikacin. The genome of K433 consisted of a chromosome cK433 (6,482-kb length) and two plasmids: pK433-qnrS (7.212-kb length) and pK433-NDM (200.855-kb length), the last being the first investigated blaNDM-carrying plasmid from Aeromonas spp. By comparison of the backbone and MDR regions from the plasmids studied, they involved a highly homologous sequence structure. This study provides in-depth genetic insights into the plasmids integrated with blaNDM-carrying genetic elements from Aeromonas spp.
A 16S rRNA Gene-Based Metabarcoding of Phosphate-Rich Deposits in Muierilor Cave, South-Western Carpathians
Authors: Haidău Catalina , Năstase-Bucur Ruxandra , Bulzu Paul , Levei Erika , Cadar Oana , Mirea Ionuţ Cornel , Faur Luchiana , Fruth Victor , Atkinson Irina , Constantin Silviu , Moldovan Oana Teodora
Published: May 2022

Muierilor Cave is one of Romania’s most important show caves, with paleontological and archeological deposits. Recently, a new chamber was discovered in the cave, with unique yellow calcite crystals, fine-grained crusts, and black sediments. The deposits in this chamber were related to a leaking process from the upper level that contains fossil bones and a large pile of guano. Samples were taken from the new chamber and another passage to investigate the relationship between the substrate and microbial community. Chemical, mineralogical, and whole community 16S rRNA gene-based metabarcoding analyses were undertaken, and the base of the guano deposit was radiocarbon dated. Our study indicated bacteria linked to the presence of high phosphate concentration, most likely due to the nature of the substrate (hydroxyapatite). Bacteria involved in Fe, Mn, or N cycles were also found, as these elements are commonly identified in high concentrations in guano. Since no bat colonies or fossil bones were present in the new chamber, a high concentration of these elements could be sourced by organic deposits inside the cave (guano and fossil bones) even after hundreds of years of their deposition and in areas far from both deposits. Metabarcoding of the analyzed samples found that ∼0.7% of the identified bacteria are unknown to science, and ∼47% were not previously reported in caves or guano. Moreover, most of the identified human-related bacteria were not reported in caves or guano before, and some are known for their pathogenic potential. Therefore, continuous monitoring of air and floor microbiology should be considered in show caves with organic deposits containing bacteria that can threaten human health. The high number of unidentified taxa in a small sector of Muierilor Cave indicates the limited knowledge of the bacterial diversity in caves that can have potential applications in human health and biotechnology.
Diversity Shifts in the Root Microbiome of Cucumber Under Different Plant Cultivation Substrates
Authors: Zhou Fangyuan , Wu Xiaoqing , Gao Yunxiao , Fan Susu , Zhou Hongzi , Zhang Xinjian
Published: May 2022

Application of plant artificial cultivation substrates lead to alteration of rhizosphere environment. Whether this alteration could lead to root microbiome variation was limitedly investigated. This work aims to determine the diversity shifts in the root microbiome of cucumber under different plant cultivation substrates and predict corresponding function of these different root bacterial microbiota. Cucumber root samples cultivated with two artificial cultivation substrates and greenhouse soils were prepared. Subsequently, high throughput sequencing and bioinformatics analysis were applicated to compare the root bacterial diversity of cucumber cultivated in different substrates and their corresponding function. In total, 311,039 sequences were obtained, and they were annotated to 42 operational taxonomic units (OTUs), belonging to 28 genera, 18 families, 12 orders, four classes, and three phyla. The α and β diversity of samples from the two cultivation substrates and greenhouse soils were significantly different. Only 2–3 bacterial species were found to be discrepancy between cucumber root samples from artificial cultivation substrates and from greenhouse soils. The relative abundance of genus Asticcacaulis, Methylophilus, Massilia, Dyella, and Devosia in samples of artificial cultivation substrates was significantly higher than that of soils, while the relative abundance of genus Phenylobacterium, Noviherbaspirillum, and Arenimonas was significantly lower than that of soils. Besides, compared to cucumber root bacterial community cultivated in soils, the abundance of synthetic pathways for flavonoids and flavonols, bile acids, indole alkaloids, lactose, and neolactose increased by 41.6-, 28.7-, 5.9-, and 5.5-fold, respectively, in the bacterial community of the substrate 1-cultivated roots, and the abundance of clavulanic acid, receptor interaction, sesquiterpenoid, bile acid, flavonoid and flavonol, indole alkaloid, lactose, and neolactose synthetic pathways increased by 42.3-, 32.4-, 32.4-, 13.9-, 10.3-, 6.3-, and 5.2-fold, respectively, in the bacterial community of the substrate two-cultivated roots. This paper verified the diversity shifts in the root microbiome of cucumber under different plant cultivation substrates. Besides, the corresponding function difference of these different root bacterial microbiota was predicted. This work would provide theoretical support for discovering microbial resources and building artificial microbial flora.
Could a Focus on the “Why” of Taxonomy Help Taxonomy Better Respond to the Needs of Science and Society?
Authors: Pritchard Leighton , Brown C. Titus , Harrington Bailey , Heath Lenwood S. , Pierce-Ward N. Tessa , Vinatzer Boris A.
Published: May 2022

Genomics has put prokaryotic rank-based taxonomy on a solid phylogenetic foundation. However, most taxonomic ranks were set long before the advent of DNA sequencing and genomics. In this concept paper, we thus ask the following question: should prokaryotic classification schemes besides the current phylum-to-species ranks be explored, developed, and incorporated into scientific discourse? Could such alternative schemes provide better solutions to the basic need of science and society for which taxonomy was developed, namely, precise and meaningful identification? A neutral genome-similarity based framework is then described that could allow alternative classification schemes to be explored, compared, and translated into each other without having to choose only one as the gold standard. Classification schemes could thus continue to evolve and be selected according to their benefits and based on how well they fulfill the need for prokaryotic identification.
Peptide Aptamer PA3 Attenuates the Viability of Aeromonas veronii by Hindering of Small Protein B-Outer Membrane Protein A Signal Pathway
Authors: Liu Peng , Chang Huimin , Xu Qi , Wang Dan , Tang Yanqiong , Hu Xinwen , Lin Min , Liu Zhu
Published: May 2022

The small protein B (SmpB), previously acting as a ribosome rescue factor for translation quality control, is required for cell viability in bacteria. Here, our study reveals that SmpB possesses new function which regulates the expression of outer membrane protein A (ompA) gene as a transcription factor in Aeromonas veronii. The deletion of SmpB caused the lower transcription expression of ompA by Quantitative Real-Time PCR (qPCR). Electrophoretic mobility shift assay (EMSA) and DNase I Footprinting verified that the SmpB bound at the regions of −46 to −28 bp, −18 to +4 bp, +21 to +31 bp, and +48 to +59 bp of the predicted ompA promoter (PompA). The key sites C52AT was further identified to interact with SmpB when PompA was fused with enhanced green fluorescent protein (EGFP) and co-transformed with SmpB expression vector for the fluorescence detection, and the result was further confirmed in microscale thermophoresis (MST) assays. Besides, the amino acid sites G11S, F26I, and K152 in SmpB were the key sites for binding to PompA. In order to further develop peptide antimicrobial agents, the peptide aptamer PA3 was screened from the peptide aptamer (PA) library by bacterial two-hybrid method. The drug sensitivity test showed that PA3 effectively inhibited the growth of A. veronii. In summary, these results demonstrated that OmpA was a good drug target for A. veronii, which was regulated by the SmpB protein and the selected peptide aptamer PA3 interacted with OmpA protein to disable SmpB-OmpA signal pathway and inhibited A. veronii, suggesting that it could be used as an antimicrobial agent for the prevention and treatment of pathogens.
A Critical Role of δ-Opioid Receptor in Anti-microglial Activation Under Stress
Authors: Xu Yuan , Zhi Feng , Peng Ya , Mao Jiahao , Balboni Gianfranco , Yang Yilin , Xia Ying
Published: May 2022

Microglia are involved in the regulation of cerebral homeostasis and pathogen confrontation. There is, however, evidence showing that excessive microglia activation is implicated in various age-related cerebral diseases. On the other hand, microglia may experience complex changes of polarization in pathological insults, i.e., from a proinflammatory M1 to an anti-inflammatory M2 phenotype, which differentially contribute to the exacerbation or alleviation of cellular injury. Remolding the phenotype of microglia or inhibiting the excessive activation of microglia seems to be a promising approach against neurodegenerative pathologies. Since δ-opioid receptor (DOR) activation exhibits a strong protective capacity against various neuronal injuries, especially the hypoxic/ischemic injury, we asked if the DOR-induced neuroprotection is associated with its effect on microglia. We explored this fundamental issue by using pharmacological and genetic approaches in the BV2 cell line, a general type of microglial cells. The results showed that DOR expression significantly increased in the activated microglial M2 phenotype, but slightly decreased in the microglial M1 phenotype. Hypoxia induced dual polarizations of BV2 cells with an increase in DOR expression. Administration of a specific DOR agonist, UFP-512, largely inhibited lipopolysaccharide (LPS) or hypoxia-induced microglial M1 activation and inflammatory activity with high concentrations of UFP-512 being effective to reverse the interleukin-4 (IL4)-induced microglial activation. Consistent with these observations, inhibiting DOR or knocking-down DOR promoted the excessive activation of BV2 cells in both M1 and M2 directions, while DOR overexpression did the opposite. Furthermore, the PC12 cells exposed to the conditioned medium of BV2 cells treated by UFP-512 grew better than those treated directly with UFP-512 under LPS or hypoxic insults. DOR inhibitor naltrindole could block all the effects of DOR activation. The medium from the BV2 cells with DOR knock-down decreased the viability of PC12 cell, while the medium from the BV2 cells with DOR overexpression largely attenuated LPS or hypoxic injury in the PC12 cells. These first data suggest a close linkage between DOR expression/function and microglial polarization and a critical role of DOR in negative controlling microglial activation. Our work provides a novel clue for new protective strategies against neurodegenerative pathophysiology through DOR-mediated regulation of microglia.
Is There an Association Between Untreated Hearing Loss and Psychosocial Outcomes?
Authors: Jayakody Dona M. P. , Wishart Justin , Stegeman Inge , Eikelboom Robert , Moyle Thomas C. , Yiannos Jessica M. , Goodman-Simpson Jack James , Almeida Osvaldo P.
Published: May 2022

Objective

Age-related hearing loss is one of the leading causes of disability in older adults. This cross-sectional study investigated the association between untreated hearing loss, social (perception of quality and quantity of social network) and emotional loneliness (perception of limited emotional support), social isolation (size of the social network), social support (actual or perceived availability of resources from the social network) and psychological discomfort (depression, anxiety, and stress) in older adults.

Study Design

Cross-sectional study design.

Methods

A total of 202 community derived sample of volunteers, age range 40–89 years, mean age (M) = 65.3 ± 11.0 years were recruited. Of these 115 were females (M = 63.2 ± 12.0 years) and 87 were males (M = 68.2 ± 8.9 years). All participants completed a hearing assessment, social interaction and support questionnaire and a social and emotional loneliness questionnaire.

Results

Hearing loss significantly contributed to both moderate [P < 0.001, B (95% CI): 0.01 (0.99–1.02)] and intense levels [P < 0.001, 0.02 (1.00–1.04)] of emotional loneliness. Depression was significantly associated with satisfaction with social support [P < 0.001; −0.17 (−0.23 to −0.11), social interaction [P = 0.01; −0.07 (−0.12 to −0.01)], and moderate [P < 0.001; 0.31 (1.22–1.53)] and intense [P < 0.001; 0.29 (1.20–1.50)] levels of emotional loneliness and intense levels of social loneliness [P = 0.01; 0.12 (1.05–1.21)].

Conclusion

Untreated hearing loss significantly increases the odds of being emotionally lonely. Depression significantly contributes to social and emotional loneliness, satisfaction with social support and social loneliness. Given the higher prevalence of loneliness and psychological discomfort and their associations with untreated hearing loss, hearing-impaired older adults are at significant risk of developing loneliness and psychological discomfort. Therefore, hearing health professionals should be aware of the psychosocial burden that may accompany hearing loss, in order to provide appropriate advice and support.
Microvascular Impairment in Patients With Cerebral Small Vessel Disease Assessed With Arterial Spin Labeling Magnetic Resonance Imaging: A Pilot Study
Authors: Neumann Katja , Günther Matthias , Düzel Emrah , Schreiber Stefanie
Published: May 2022

In this pilot study, we investigated microvascular impairment in patients with cerebral small vessel disease (CSVD) using non-invasive arterial spin labeling (ASL) magnetic resonance imaging (MRI). This method enabled us to measure the perfusion parameters, cerebral blood flow (CBF), and arterial transit time (ATT), and the effective T1-relaxation time (T1eff) to research a novel approach of assessing perivascular clearance. CSVD severity was characterized using the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) and included a rating of white matter hyperintensities (WMHs), lacunes, enlarged perivascular spaces (EPVSs), and cerebral microbleeds (CMBs). Here, we found that CBF decreases and ATT increases with increasing CSVD severity in patients, most prominent for a white matter (WM) region-of-interest, whereas this relation was almost equally driven by WMHs, lacunes, EPVSs, and CMBs. Additionally, we observed a longer mean T1eff of gray matter and WM in patients with CSVD compared to elderly controls, providing an indication of impaired clearance in patients. Mainly T1eff of WM was associated with CSVD burden, whereas lobar lacunes and CMBs contributed primary to this relation compared to EPVSs of the centrum semiovale. Our results complement previous findings of CSVD-related hypoperfusion by the observation of retarded arterial blood arrival times in brain tissue and by an increased T1eff as potential indication of impaired clearance rates using ASL.
Mesenchymal Stem Cells Improve Cognitive Impairment and Reduce Aβ Deposition via Promoting AQP4 Polarity and Relieving Neuroinflammation in Rats With Chronic Hypertension-Induced Cerebral Small-Vessel Disease
Authors: Liu Xiao lu , Ouyang Fu bing , Hu Liu ting , Sun Pei , Yang Jing , Sun Yuan jing , Liao Meng shi , Lan Lin fang , Pei Zhong , Fan Yu hua
Published: May 2022

Cerebral small-vessel disease (CSVD) is the main cause of vascular cognitive impairment (VCI), and the accumulation of amyloid β-protein (Aβ) may be significantly involved in CSVD-induced VCI. The imbalance between Aβ production and clearance is believed to be an important pathological mechanism of Aβ deposition in Alzheimer disease. In this study, we aimed to disclose the roles of aquaporin 4 (AQP4) and neuroinflammation in CSVD, which were the key factors for Aβ clearance and production, respectively, and the effect of mesenchymal stem cells (MSCs) on Aβ deposition and these two factors. The stroke-prone renovascular hypertensive (RHRSP) rats were grouped and received MSC and MSC + AS1517499 (an inhibitor of pSTAT6). The latter was used to explore the underlying mechanism. The cognitive function, white matter lesions, Aβ expression, expression, and polarity of AQP4, neuroinflammation and the STAT6 pathway were investigated. Compared with sham-operated rats, RHRSP rats showed spatial cognitive impairment, white matter lesions and Aβ deposition. Moreover, AQP4 polarity disorder and neuroinflammatory activation were found, which were linked to Aβ deposition. Treatment with MSCs markedly improved cognitive tasks and reduced Aβ deposition but failed to reduce white-matter lesions. Furthermore, MSCs not only promoted AQP4 polarity but also alleviated neuroinflammation probably through the STAT6 pathway. The present study demonstrated that Aβ deposition, AQP4 polarity disorder and neuroinflammation might be involved in CSVD and the regulatory effects of MSCs on them suggested potential therapeutic value for CSVD.
The Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction
Authors: Chen Xiaoshu , Pang Xinru , Yeo Abrey J. , Xie Siwen , Xiang Mengting , Shi Bin , Yu Gongchang , Li Chao
Published: May 2022

The blood-brain barrier (BBB) is a selective, semi-permeable layer of endothelial cells that protects the central nervous system from harmful substances circulating in blood. It is one of the important barriers of the nervous system. BBB dysfunction is an early pathophysiological change observed in nervous system diseases. There are few treatments for BBB dysfunction, so this motivates the review. Ferroptosis is a novel cell death mode caused by iron-mediated lipid peroxidation accumulation, which has recently attracted more attention due to its possible role in nervous system disorders. Studies have shown that lipid peroxidation and iron accumulation are related to the barrier dysfunction, especially the expression of tight junction proteins. Therefore, examination of the relationship between ferroptosis and BBB dysfunction may reveal new targets for the treatment of brain diseases.
Astrocytic Calcium and cAMP in Neurodegenerative Diseases
Authors: Sobolczyk Marta , Boczek Tomasz
Published: May 2022

It is commonly accepted that the role of astrocytes exceeds far beyond neuronal scaffold and energy supply. Their unique morphological and functional features have recently brough much attention as it became evident that they play a fundamental role in neurotransmission and interact with synapses. Synaptic transmission is a highly orchestrated process, which triggers local and transient elevations in intracellular Ca2+, a phenomenon with specific temporal and spatial properties. Presynaptic activation of Ca2+-dependent adenylyl cyclases represents an important mechanism of synaptic transmission modulation. This involves activation of the cAMP-PKA pathway to regulate neurotransmitter synthesis, release and storage, and to increase neuroprotection. This aspect is of paramount importance for the preservation of neuronal survival and functionality in several pathological states occurring with progressive neuronal loss. Hence, the aim of this review is to discuss mutual relationships between cAMP and Ca2+ signaling and emphasize those alterations at the Ca2+/cAMP crosstalk that have been identified in neurodegenerative disorders, such as Alzheimer's and Parkinson's disease.
Annual Trends in the Incidence and Prevalence of Alzheimer's Disease in South Korea: A Nationwide Cohort Study
Authors: Baek Min Seok , Kim Han-Kyeol , Han Kyungdo , Kwon Hyuk-Sung , Na Han Kyu , Lyoo Chul Hyoung , Cho Hanna
Published: May 2022

Despite recent studies suggesting a declining incidence and prevalence of dementia on a global scale, epidemiologic results with respect to Alzheimer's disease (AD) are lacking due to the methodological limitations inherent to conducting large-scale cohort investigations of this topic. The aim of the current study was to investigate the incidence and prevalence of AD in Korea. We conducted a secondary analysis within the National Health Insurance System (NHIS) database, a unique resource that reports medical information for the entire Korean population. AD diagnoses as well as evaluations of vascular risks were defined based on International Statistical Classification of Diseases (ICD-10) codes along with prescription records. The cut-off age for diagnosing AD was defined as the age of the patient's highest Youden index. In this study, the incidence and prevalence of AD in the Korean population aged 40 years or older showed an overall increase between 2006 and 2015. Although both older and younger age groups showed an increase in the incidence and prevalence of AD, the highest increase was observed in older age groups. Based on the highest Youden's index value (sensitivity + specificity – 1), the cut-off value for the diagnosis of AD was 69 years with an area under the curve (AUC) of 0.92. We found that the incidence of AD was higher in individuals with underlying vascular risks. However, in recent years, the prevalence of AD was conversely found to be lower in individuals with hypertension or dyslipidemia. Despite efforts toward reducing the number of AD cases through educational, policy, and various public health and preventive medicine interventions, the incidence and prevalence of AD continues to grow in Korea. Efforts aimed at early diagnosis and the modification of underlying risks may be critical to reducing the socioeconomic burden of AD.
Computational Mechanisms of Osmoregulation: A Reinforcement Learning Model for Sodium Appetite
Authors: Uchida Yuuki , Hikida Takatoshi , Yamashita Yuichi
Published: May 2022

Homeostatic control with oral nutrient intake is a vital complex system involving the orderly interactions between the external and internal senses, behavioral control, reward learning, and decision-making. Sodium appetite is a representative system and has been intensively investigated in animal models of homeostatic systems and oral nutrient intake. However, the system-level mechanisms for regulating sodium intake behavior and homeostatic control remain unclear. In the current study, we attempted to provide a mechanistic understanding of sodium appetite behavior by using a computational model, the homeostatic reinforcement learning model, in which homeostatic behaviors are interpreted as reinforcement learning processes. Through simulation experiments, we confirmed that our homeostatic reinforcement learning model successfully reproduced homeostatic behaviors by regulating sodium appetite. These behaviors include the approach and avoidance behaviors to sodium according to the internal states of individuals. In addition, based on the assumption that the sense of taste is a predictor of changes in the internal state, the homeostatic reinforcement learning model successfully reproduced the previous paradoxical observations of the intragastric infusion test, which cannot be explained by the classical drive reduction theory. Moreover, we extended the homeostatic reinforcement learning model to multimodal data, and successfully reproduced the behavioral tests in which water and sodium appetite were mediated by each other. Finally, through an experimental simulation of chemical manipulation in a specific neural population in the brain stem, we proposed a testable hypothesis for the function of neural circuits involving sodium appetite behavior. The study results support the idea that osmoregulation via sodium appetitive behavior can be understood as a reinforcement learning process, and provide a mechanistic explanation for the underlying neural mechanisms of decision-making related to sodium appetite and homeostatic behavior.
SCN1A-Related Epilepsy: Novel Mutations and Rare Phenotypes
Authors: Ma Rui , Duan Yiran , Zhang Liping , Qi Xiaohong , Zhang Lu , Pan Sipei , Gao Lehong , Wang Chaodong , Wang Yuping
Published: May 2022

Objectives

To expand the genotypes and phenotypes of sodium voltage-gated channel alpha subunit 1 (SCN1A)-related epilepsy.

Methods

We retrospectively collected the clinical and genetic information of 22 epilepsy patients (10 males, 12 females; mean: 9.2 ± 3.9 years; 3.9–20.3 years) carrying 22 variants of SCN1A. SCN1A mutations were identified by next-generation sequencing.

Results

Twenty-two variants were identified, among which 12 have not yet been reported. The median age at seizure onset was 6 months. Sixteen patients were diagnosed with Dravet syndrome (DS), two with genetic epilepsy with febrile seizures plus [one evolved into benign epilepsy with centrotemporal spikes (BECTS)], one with focal epilepsy, one with atypical childhood epilepsy with centrotemporal spikes (ABECTS) and two with unclassified epilepsy. Fourteen patients showed a global developmental delay/intellectual disability (GDD/ID). Slow background activities were observed in one patient and epileptiform discharges were observed in 11 patients during the interictal phase.

Significance

This study enriches the genotypes and phenotypes of SCN1A-related epilepsy. The clinical characteristics of patients with 12 previously unreported variants were described.
Neuroprotective Effects of the Pannexin-1 Channel Inhibitor: Probenecid on Spinal Cord Injury in Rats
Authors: Qi Qi , Wang Xiao-Xuan , Li Jing-Lu , Chen Yu-Qing , Chang Jian-Rong , Xi Jin , Lü He-Zuo , Zhang Yu-Xin
Published: May 2022

Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1β (IL-1β), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1β, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI.
The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms
Authors: Chapman Caitlyn A. , Nuwer Jessica L. , Jacob Tija C.
Published: May 2022

Synaptic plasticity is a critical process that regulates neuronal activity by allowing neurons to adjust their synaptic strength in response to changes in activity. Despite the high proximity of excitatory glutamatergic and inhibitory GABAergic postsynaptic zones and their functional integration within dendritic regions, concurrent plasticity has historically been underassessed. Growing evidence for pathological disruptions in the excitation and inhibition (E/I) balance in neurological and neurodevelopmental disorders indicates the need for an improved, more “holistic” understanding of synaptic interplay. There continues to be a long-standing focus on the persistent strengthening of excitation (excitatory long-term potentiation; eLTP) and its role in learning and memory, although the importance of inhibitory long-term potentiation (iLTP) and depression (iLTD) has become increasingly apparent. Emerging evidence further points to a dynamic dialogue between excitatory and inhibitory synapses, but much remains to be understood regarding the mechanisms and extent of this exchange. In this mini-review, we explore the role calcium signaling and synaptic crosstalk play in regulating postsynaptic plasticity and neuronal excitability. We examine current knowledge on GABAergic and glutamatergic synapse responses to perturbances in activity, with a focus on postsynaptic plasticity induced by short-term pharmacological treatments which act to either enhance or reduce neuronal excitability via ionotropic receptor regulation in neuronal culture. To delve deeper into potential mechanisms of synaptic crosstalk, we discuss the influence of synaptic activity on key regulatory proteins, including kinases, phosphatases, and synaptic structural/scaffolding proteins. Finally, we briefly suggest avenues for future research to better understand the crosstalk between glutamatergic and GABAergic synapses.