bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the three-station interferometry method to improve urban DAS ambient noise tomography
Authors: Song Zhenghong , Zeng Xiangfang , Chi Benxin , Bao Feng , Osotuyi Abayomi Gaius
Published: September 2022

Distributed acoustic sensing (DAS) is a novel seismological observation technology based on the fiber-optic sensing method, and can transform existing urban fiber-optic cables into ultra-dense array for urban seismological researches, thus opening abundant opportunities for resolving fine details of near surface structures. While high frequency ambient noise recorded on DAS has been applied in surface wave tomography, it is often difficult to extract a clear dispersion curve for the data recorded by urban internet cable because of the effect of precursor signals on noise correlation functions due to uneven distribution of noise sources, and weak coupling between the cable and the solid earth. In this study, we investigate the performance of the three-station interferometry method for improving the noise cross-correlation functions of the linear array. We applied this method to a DAS dataset acquired in an urban area, suppressed the precursor signal, improved the measurement of the dispersion curve, and constructed a 2D S-wave profile that reveals the hidden fault beneath the city. We also observed that the convergence of noise cross-correlation functions with weak coupling was significantly accelerated using this method. We employed this method to improve the signal quality of surface waves at far offset for the long segment, thus obtaining a more accurate dispersion curve. In conclusion, the three-station interferometry is an effective method to enhance the surface wave signal and suppress the precursor signal retrieved from the data recorded by urban internet cable, which could help in providing high resolution images of shallow structures in built-up areas.
Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial
Authors: Zhang Jiaqi , Xing Chuan , Cheng Xiangyi , He Bing
Published: September 2022

Objectives

Canagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy’s efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS).

Methods

Fifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated.

Results

Compared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively.

Conclusions

In overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy.

Trial registration

ClinicalTrials.gov, NCT04973891.
Optimal scheduling strategy of grid-connected microgrid with ladder-type carbon trading based on Stackelberg game
Authors: Fu Xiuwei , Zeng Guohui , Zhu Xiangchen , Zhao Jinbin , Huang Bo , Liu Jin
Published: September 2022

Aiming at the problems of promoting new energy consumption, reducing carbon emissions, load fluctuations, and multi-agent conflict of interests in the networked microgrid system, this article proposes a microgrid optimization operation strategy based on demand response and reward-penalty ladder-type carbon trading mechanism. First, in order to determine the electricity sales price of the system, an optimal scheduling model for microgrid operators is established, including gas cost, electricity profit for users, and surplus power supply network profit. Second, a demand response strategy on electricity price and low-carbon compensation incentives is proposed on the user side. The transaction model is embedded between microgrid operators and users into the master–slave game framework, and a multi-slave game collaborative optimization model is established with microgrid operators as leaders and users as followers. The existence and uniqueness of Stackelberg game are proved, and the differential evolution algorithm and CPLEX solver are used to solve the proposed model. Finally, an example of a microgrid system including three community users is provided to show the effectiveness of the proposed model and strategy.
RETRACTED: Rethinking sustainable energy development for green energy recovery: Empirical dynamism of oil prices shock
Authors: Leng Feng
Published: September 2022

The purpose of the study is to test the role of market timing between oil price shock and energy efficiency mitigation in ASEAN countries. To achieve the study objective, a persistence econometric modeling technique is applied. The results revealed that oil prices are now the other main source of energy efficiency mitigation in ASEAN economies. Market timing-based factors are replaced with for oil price shock to increase, warranting a collaborative environment. Moreover, green financing loan schemes invest both public and private funds in energy efficiency mitigation to capitalize on a cleaner environment by controlling the oil price shock. The consideration and application of financial consideration for sustainable innovation-financing projects or companies is limitless. Providing for screening CO2 emission reduction and cooperation proposals with speedy greenhouse gas reduction rates might have large opportunity costs. There may be a case for governments to increase industrial growth, improve resource efficiency, and increase factor productivity while tackling energy efficiency. Economic growth in ASEAN may have an even greater influence on greenhouse gas reduction than in other countries. On such points, there is a need to pay attention. If the suggested policy suggestions are implemented successfully, they would help enhance the scope of financing considerations for sustainable innovation to uplift energy efficiency mitigation through market timing-based mechanisms.
Decoupling of greenhouse gas emissions from livestock industrial development: Evidence from China Agricultural Green Development Modern Zone
Authors: Liu Zixuan , Ahmad Mahmood , Li Guojing , Yang Yadong , Liu Yang , Gao Mingjie , Luo Qiyou
Published: September 2022

China Agricultural Green Development Modern Zone (CAGDMZ) constitute a demonstration area for achieving green and sustainable development of Chinese agriculture. It plays a role in demonstrating high-quality agricultural development and environmental protection. As a result, a coordinated interaction among livestock greenhouse gas (GHG) emissions and rapid industrial livestock evolution in the CAGDMZ is of great concern to China’s government. In this paper, we were the first to research the decoupling relationship between livestock GHG emissions and industrial development by using data from 165 CAGDMZ of China from 2010 to 2019 at different regional scales and long time series. On this basis, we further explored the factors affecting livestock GHG emissions by using the Logarithmic Mean Divisia Index method (LMDI). Our analysis revealed that the amount of GHG emissions from livestock in the CAGDMZ showed a rising and then declining trend. Pigs, nondairy cattle and sheep were the main targets of livestock GHG emission reductions. There were obvious spatial differences in livestock GHG emissions. 17 provinces’CAGDMZ achieved emissions reductions, but 14 provinces’ CAGDMZ increased livestock GHG emissions. The Northeast CAGDMZ had the highest livestock GHG emissions and the Eastern CAGDMZ had the largest livestock GHG deceleration. Furthermore, the decoupling status in the CAGDMZ were unstable. Most provinces or regions of the CAGDMZ maintained the economic growth of livestock while curbing the excessive growth of GHG emissions. Only a few of them achieved a win-win situation of livestock output value increase while GHG emission reduction. Moreover, the comprehensive effect showed an inverted “U” trend. Production efficiency was the most major contributor to livestock GHG emissions reductions. Economic development factor and labor scale factor were the main driving factors for increasing GHG emissions. Industrial structure factor shifted from promotion to suppression of livestock GHG emissions. Therefore, some policies to accomplish the CAGDMZ’s long-term development were proposed.
Ecosystems Services Provided by Bats Are at Risk in Brazil
Authors: Brasileiro Lais A. M. , Machado Ricardo B. , Aguiar Ludmilla M. S.
Published: September 2022

Ecosystem services (ES) are essential for human society worldwide. ES originate from ecological processes commonly occurring in well-preserved regions. Bats play an essential role in providing such services, primarily insect suppression, plant pollination, and seed dispersal. Human activities have affected Earth’s systems, compromising species and ecosystems and, consequently, the ES provision. Brazil is a country with many bat species but is also one of the world’s leaders in deforestation. Here we aimed to identify regions with high potential for bats ecosystem services provision, assuming that the predicted presence of the species represents the existence of the services. First, we used a Maximum Entropy algorithm to model the distribution of 128 bat species, which correspond to 71% of the Brazilian species. We classify all species into 10 different groups, which resulted from a combination of three body sizes and four predominant trophic guilds (i.e., frugivores, insectivores, nectarivores, and carnivores). The guilds were associated with services of seed dispersion, pest control, pollination, and animal control. Then, we created a 0.5 × 0.5-degree grid to represent an index of ES per guild, which is defined by the sum of the product of the bat’s size weight (1, 2, or 3) by the area occupied of each species in each cell. For comparison, the index was normalized and scaled from 0 to 1. Finally, we used a map of current land use to compare the effects of natural area suppression on the provision of ES in each cell. Our results indicate a substantial reduction in the provision of ES by bats in extensive parts of the central and eastern parts of Brazil, but changes in ES varies among biomes. While the loss of species is an important factor affecting the provision of ES in the Atlantic Forest and the Cerrado, the reduction of species occurrence is most important factor in Amazonia, Caatinga, or Pantanal regions. We suggest that degraded area restoration should be promoted in areas with high ES values and areas near cities and croplands and that a precautionary approach of promoting the conservation of high provider richness should be applied to protect the continuation of bat’s ES.
Agrobacterium- and a single Cas9-sgRNA transcript system-mediated high efficiency gene editing in perennial ryegrass
Authors: Kumar Rahul , Kamuda Troy , Budhathoki Roshani , Tang Dan , Yer Huseyin , Zhao Yunde , Li Yi
Published: September 2022

Genome editing technologies provide a powerful tool for genetic improvement of perennial ryegrass, an important forage and turfgrass species worldwide. The sole publication for gene editing in perennial ryegrass used gene-gun for plant transformation and a dual promoter based CRISPR/Cas9 system for editing. However, their editing efficiency was low (5.9% or only one gene-edited plant produced). To test the suitability of the maize Ubiquitin 1 (ZmUbi1) promoter in gene editing of perennial ryegrass, we produced ZmUbi1 promoter:RUBY transgenic plants. We observed that ZmUbi1 promoter was active in callus tissue prior to shoot regeneration, suggesting that the promoter is suitable for Cas9 and sgRNA expression in perennial ryegrass for high-efficiency production of bi-allelic mutant plants. We then used the ZmUbi1 promoter for controlling Cas9 and sgRNA expression in perennial ryegrass. A ribozyme cleavage target site between the Cas9 and sgRNA sequences allowed production of functional Cas9 mRNA and sgRNA after transcription. Using Agrobacterium for genetic transformation, we observed a 29% efficiency for editing the PHYTOENE DESATURASE gene in perennial ryegrass. DNA sequencing analyses revealed that most pds plants contained bi-allelic mutations. These results demonstrate that the expression of a single Cas9 and sgRNA transcript unit controlled by the ZmUbi1 promoter provides a highly efficient system for production of bi-allelic mutants of perennial ryegrass and should also be applicable in other related grass species.
Exploration of differentially expressed mRNAs and miRNAs for pediatric acute myeloid leukemia
Authors: Wang Qing , Yue Chao , Liu Qin , Che Xuchun
Published: September 2022

Background: To establish a comprehensive differential gene profile for pediatric acute myeloid leukemia patients (pAML) based on two independent databases and verify the differentially expressed genes using in vitro and in vivo analyses.

Methods: The mRNA and miRNA sequencing information of GSE2191 and GSE35320, clinically recruited pAML individuals, and human AML cell line (NB4 cells) were utilized in the study.

Results: Compared with the control sample, pAML patients demonstrated a total of 778 differentially expressed genes, including 565 upregulated genes and 213 downregulated genes. The genes including ZC3H15, BCLAF1, PPIG, DNTTIP2, SRSF11, KTN1, UBE3A, PRPF40A, TMED5, and GNL2 were the top 10 potential hub genes. At the same time, 12 miRNAs demonstrated remarkable differential expressions in pAML individuals compared with control individuals, as five upregulated and seven downregulated miRNAs. The hsa-miR-133, hsa-miR-181, and hsa-miR-195 were significantly downregulated. Building a miRNA–mRNA regulatory network, hsa-miR-133 regulated ZC3H15, BCLAF1, SRSF11, KTN1, PRPF40A, and GNL2. Using the NB4 cell model, hsa-miR-133 treatment inhibited cell proliferation capacity, which could be attenuated by a single mRNA transfection or a combination of ZC3H15 and BCLAF1. At the same time, hsa-miR-133 mimic treatment could significantly accelerate cell apoptosis in NB4 cells, which was also ZC3H15- and BCLAF1-dependent. The concentrations of ZC3H15 and BCLAF1 were investigated in peripheral blood using the ELISA method for the clinical control and pAML samples. In pAML samples, the expression levels of ZC3H15 and BCLAF1 were significantly enhanced (p < 0.01), regardless of the classification.

Conclusion: Collectively, this study hypothesized several promising candidates for pAML formation.
Identification of a signature of evolutionarily conserved stress-induced mutagenesis in cancer
Authors: Cisneros Luis H. , Vaske Charles , Bussey Kimberly J.
Published: September 2022

The clustering of mutations observed in cancer cells is reminiscent of the stress-induced mutagenesis (SIM) response in bacteria. Bacteria deploy SIM when faced with DNA double-strand breaks in the presence of conditions that elicit an SOS response. SIM employs DinB, the evolutionary precursor to human trans-lesion synthesis (TLS) error-prone polymerases, and results in mutations concentrated around DNA double-strand breaks with an abundance that decays with distance. We performed a quantitative study on single nucleotide variant calls for whole-genome sequencing data from 1950 tumors, non-inherited mutations from 129 normal samples, and acquired mutations in 3 cell line models of stress-induced adaptive mutation. We introduce statistical methods to identify mutational clusters, quantify their shapes and tease out the potential mechanism that produced them. Our results show that mutations in both normal and cancer samples are indeed clustered and have shapes indicative of SIM. Clusters in normal samples occur more often in the same genomic location across samples than in cancer suggesting loss of regulation over the mutational process during carcinogenesis. Additionally, the signatures of TLS contribute the most to mutational cluster formation in both patient samples as well as experimental models of SIM. Furthermore, a measure of cluster shape heterogeneity was associated with cancer patient survival with a hazard ratio of 5.744 (Cox Proportional Hazard Regression, 95% CI: 1.824–18.09). Our results support the conclusion that the ancient and evolutionary-conserved adaptive mutation response found in bacteria is a source of genomic instability in cancer. Biological adaptation through SIM might explain the ability of tumors to evolve in the face of strong selective pressures such as treatment and suggests that the conventional ‘hit it hard’ approaches to therapy could prove themselves counterproductive.
Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas
Authors: Yu Shirong , Zhang Jingzhan , Ding Yuan , Kang Xiaojing , Pu Xiongming
Published: September 2022

Cutaneous T-cell lymphomas (CTCLs) are a kind of non-Hodgkin lymphoma that originates from skin, which is difficult to treat with traditional drugs. Human histone deacetylase inhibitors (HDACi) targeted therapy has become a promising treatment strategy in recent years, but some patients can develop resistance to the drug, leading to treatment failure. There are no public reports on whether alternative splicing (AS) and RNA binding proteins (RBP) affect the efficacy of targeted therapy. Using data from the Gene Expression Omnibus (GEO) database, we established a co-change network of AS events and RBP in CTCLs for the first time, and analyzed the potential regulatory effects of RBP on HDACi-related AS events. The dataset GSE132053, which contained the RNA sequence data for 17 HDACi samples, was downloaded and clean reads were aligned to the human GRCh38 genome by hierarchical indexing for spliced alignment of the transcripts, allowing four mismatches. Gene expression levels were evaluated using exons per million fragments mapped for each gene. Student’s t-tests were performed to evaluate the significance of changes in ratios for AS events, and regulated alternative splicing events (RASEs) were defined as events with p values less than 0.05. To sort the differentially expressed genes functional categories, Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were identified using the KOBAS 2.0 server. The regulatory mechanisms of the RASEs and RBPs were evaluated using Pearson’s correlation coefficient. Seven indirect events of HDACi resistance or sensitivity were identified: NIR_5151_RP11-977G19.10, NIR_4557_IRAG2, NIR_11870_SUMO1, NIR_5347_ING4, NIR_17935_DNAJC2, NIR_17974_CBLL1, and NIR_422_SLC50A1. The potential regulatory relationships between RBPs and HDACi-sensitive RASEs were also analyzed. LEPR and HNRNPAO significantly affected NIR_11870_SUMO1, suggesting a potential regulatory relationship. Additionally, CNN1 may regulate NIR_5347_ING4, CNOT3 may regulate NIR_17935_DNAJC2, and DQX1 and LENG9 may regulate NIR_422_SLC5A1. Overall, our findings establish a theoretical foundation for the precise targeted treatment of CTCLs with HDACi.
Establishment of an endoplasmic reticulum stress-related signature predicting outcomes of gastric adenocarcinoma patients
Authors: Gong Meiyuan , Wang Jingtao , Gao Wenfang , Liu Qian , Chen Jiaxing , Wang Guojun , Zhang Qi
Published: September 2022

Background: Gastric adenocarcinoma (GAC) is a common clinical malignancy with a poor prognosis. Endoplasmic reticulum (ER) stress plays important roles in the progression, immune filtration, and chemoresistance of cancers. However, whether ER stress-related gene signatures can predict the prognosis of GAC patients remains unknown.

Methods: GAC patient RNA-seq data downloaded from The Cancer Genome Atlas and gastric cancer patient microarray data from Gene Expression Omnibus datasets were analyzed using LASSO regression to construct an ER stress-related signature. Survival analysis, time-dependent receiver operating characteristic (ROC) curves, and Cox regression analysis were used to verify the efficacy of the signature. Immune infiltration, somatic mutation, immune checkpoint, and copy number variation analyses were utilized to explore the potential biological significance of the signature.

Results: In the present study, eight ER stress-related gene signatures were constructed. Survival analysis showed that patients in the high-risk group had a significantly worse prognosis. The area under the time-dependent ROC curves was 0.65, 0.70, and 0.63 at 1, 3, and 5 years, respectively, in the training cohort. Cox regression analysis showed that the signature is an independent prognostic factor. To predict GAC patients’ prognosis meeting individual needs, a nomogram was constructed with good accuracy. In addition, gene set enrichment and immune infiltration analyses showed that the ER stress-related signature is associated with cancer-related pathway activation and an immunosuppressive tumor microenvironment in GAC.

Conclusion: In the current study, we established an ER stress-related signature. This prognostic signature has good predictive power and could facilitate the development of novel strategies for the clinical treatment of GAC.
Potential gene identification and pathway crosstalk analysis of age-related macular degeneration
Authors: Ren Chengda , Yu Jing
Published: September 2022

Age-related macular degeneration (AMD), the most prevalent visual disorder among the elderly, is confirmed as a multifactorial disease. Studies demonstrated that genetic factors play an essential role in its pathogenesis. Our study aimed to make a relatively comprehensive study about biological functions of AMD related genes and crosstalk of their enriched pathways. 1691 AMD genetic studies were reviewed, GO enrichment and pathway crosstalk analyses were conducted to elucidate the biological features of these genes and to demonstrate the pathways that these genes participate. Moreover, we identified novel AMD-specific genes using shortest path algorithm in the context of human interactome. We retrieved 176 significantly AMD-related genes. GO results showed that the most significant term in each of these three GO categories was: signaling receptor binding (PBH = 4.835 × 10−7), response to oxygen-containing compound (PBH = 2.764 × 10−21), and extracellular space (PBH = 2.081 × 10−19). The pathway enrichment analysis showed that complement pathway is the most enriched. The pathway crosstalk study showed that the pathways could be divided into two main modules. These two modules were connected by cytokine-cytokine receptor interaction pathway. 42 unique genes potentially participating AMD development were obtained. The aberrant expression of the mRNA of FASN and LRP1 were validated in AMD cell and mouse models. Collectively, our study carried out a comprehensive analysis based on genetic association study of AMD and put forward several evidence-based genes for future study of AMD.
A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma
Authors: Huang Shenglan , Sun Liying , Hou Ping , Liu Kan , Wu Jianbing
Published: September 2022

Background

Actin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers.

Methods

The public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan–Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman’s correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells.

Results

ARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint–related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells.

Conclusions

ARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.
Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats
Authors: Rostevanov Ira S. , Betesh-Abay Batya , Nassar Ahmad , Rubin Elina , Uzzan Sarit , Kaplanski Jacob , Biton Linoy , Azab Abed N.
Published: September 2022

Background

Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes’ (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.

Objective

This study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats.

Methods

Depression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2.

Results

Overall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent.

Conclusion

Contrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment.
Effects of feed transition on digestive tract digestive enzyme, morphology and intestinal community in cuttlefish (Sepia pharaonis)
Authors: Jiang Maowang , Xiao Wencheng , Ye Jingtao , Xu Liting , Peng Ruibing , Han Qingxi , Lü Zhenming , Shi Huilai , Jiang Xiamin
Published: September 2022

Sepia pharaonis is an excellent candidate for aquaculture in China. However, the low survival rate during early feed transition is a bottleneck restricting industrial development. Understanding the changes in digestive physiology and intestinal microflora during feed transition should enable us to meet their nutritional needs to improve production. In this study, we investigate the digestive enzyme of S. pharaonis and undertake histological observations of the digestive gland and intestine. The intestinal microflora 16S rRNA genes were also analyzed using high-throughput sequencing of the pre, mid, and post-feed transition stages (20, 40, and 60 days post-hatching (DPH), respectively). The digestive enzymes from the digestive gland (trypsin and chymotrypsin) rapidly decrease at 40 DPH when compared to their levels at 20 DPH, but mostly recovered by 60 DPH. The alkaline phosphatase and lipase increased sharply by 40 DPH, then peaked at 60 DPH. The intestinal digestive enzymes followed similar trends during feed transition, except for lipase activity, which decreased after 20 DPH and remained low, even at 60 DPH. Feed transition affects the morphogenesis of the digestive tract and feed transition stress leads to the impairment of the digestive gland and intestinal morphology, which reduces the digestive capacity, but almost totally recovers by 60 DPH. Moreover, the comparison of the intestinal microbial composition during feed transition revealed that the dominant phylum Bacteroidetes gradually increased to a peak at 40 DPH and then decreased until 60 DPH. The microbial composition changed with the most abundant genus Pseudomonas being replaced by Acinetobacter. The phylum and family level investigation suggested the microbiota in the rearing water had limited influence on the intestinal microbiota. The intestinal microbiota diversity increased during feed transition. This study improves our understanding of changes and adaptations in cuttlefish during feed transition.
Effect of acupuncture at the sphenopalatine ganglion for the treatment of moderate to severe seasonal allergic rhinitis: Study protocol for a three-armed randomized controlled trial
Authors: Wang Weiming , Chen Hui , Gao Ning , Yu Shudan , Liao Jiahua , Wang Shijie , Gao Ziqi , Liu Zhishun
Published: September 2022

Introduction

Seasonal allergic rhinitis (SAR) is a major health problem with a relatively high worldwide prevalence that severely limits the quality of life for sufferers. Acupuncture is widely used for SAR treatment in China; however, the evidence on the efficacy of acupuncture at the sphenopalatine ganglion (SPG) for SAR is inconclusive. Therefore, this study aims to investigate the efficacy and safety of acupuncture at the SPG acupoint for the treatment of SAR.

Methods and analysis

A total of 120 participants with SAR will be recruited and randomly assigned to the acupuncture group, placebo acupuncture (PA) group, or rescue medication (RM) group with a 1:1:1 allocation ratio. Participants in the acupuncture group and PA group will receive 8 sessions of acupuncture stimulus at the SPG plus RM or 8 sessions of shallow needling at the SPG acupoint plus RM for 4 weeks with a 4-week follow-up in the first year and a 1-week follow-up in the second year. Participants in the RM group will only receive RM throughout the study. The primary outcome is the change from baseline in the average daily combined symptoms and medication score (CSMS) over weeks 1–4. All analysis will be based on an intention-to-treat principle. All statistical tests will be two-sided and a p-value < 0.05 will be considered to be statistically significant.
Prospective association between sleep duration and cognitive impairment: Findings from the China Health and Retirement Longitudinal Study (CHARLS)
Authors: Liu Wenhua , Wu Qingsong , Wang Minghuan , Wang Peng , Shen Na
Published: September 2022

Objective

The association between sleep duration and cognition are inconclusive. Our study aimed to comprehensively investigate the effects of sleep duration on the risk of cognitive impairment in the middle-aged and older Chinese population.

Methods

We used the longitudinal cohort data from waves 1–4 (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). Self-reported exposures included total sleep duration, nocturnal sleep duration, post-lunch napping, and changes in sleep duration over time according to face-to-face interviews. Cognitive function was assessed by a Chinese version of the Modified Mini-Mental State Examination (MMSE).

Results

A total of 7,342 eligible participants were included. The mean age was 61.5 ± 6.5 years, and 48.9% (3,588/7,342) were male. We identified a U-shaped association of total sleep duration as well as nocturnal sleep duration with the risk of cognitive impairment. People with 7–8 h of total sleep duration and 6–7 h of nocturnal sleep had the lowest risk of cognitive impairment. Further results showed that post-lunch napping within 2 h was beneficial to cognition and 60 min was optimal. Moreover, analyses of changes in sleep duration further supported that sleeping less or more was harmful to cognition. Notably, those “excessive-change” sleepers (from ≤6 to ≥9 h, or from ≥9 to ≤6 h) had more risks.

Conclusions

Keeping 7–8 h per day was related to the lowest risk of cognitive impairment in midlife and late life, and an optimal post-lunch napping was 60 min for these stable sleepers. Especially, excessive changes in sleep duration over time led to poorer cognition. Our work highlights the importance of optimal sleep habits to cognitive function. The self-reported sleep measures limited our findings, and further studies are needed for verification.
Epitope mapping of severe acute respiratory syndrome coronavirus 2 neutralizing receptor binding domain-specific monoclonal antibodies
Authors: Maghsood Faezeh , Amiri Mohammad Mehdi , Zarnani Amir-Hassan , Salimi Vahid , Kardar Gholam Ali , Khoshnoodi Jalal , Mobini Maryam , Ahmadi Zare Hengameh , Ghaderi Abbas , Jeddi-Tehrani Mahmood , Schmidt Sylvie , Laumond Géraldine , Moog Christiane , Shokri Fazel
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the outbreak led to the coronavirus disease 2019 (COVID-19) pandemic. Receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 is considered as a major target for immunotherapy and vaccine design. Here, we generated and characterized a panel of anti-RBD monoclonal antibodies (MAbs) isolated from eukaryotic recombinant RBD-immunized mice by hybridoma technology. Epitope mapping was performed using a panel of 20-mer overlapping peptides spanning the entire sequence of the RBD protein from wild-type (WT) Wuhan strain by enzyme-linked immunosorbent assay (ELISA). Several hybridomas showed reactivity toward restricted RBD peptide pools by Pepscan analysis, with more focus on peptides encompassing aa 76–110 and 136–155. However, our MAbs with potent neutralizing activity which block SARS-CoV-2 spike pseudovirus as well as the WT virus entry into angiotensin-converting enzyme-2 (ACE2) expressing HEK293T cells showed no reactivity against these peptides. These findings, largely supported by the Western blotting results suggest that the neutralizing MAbs recognize mainly conformational epitopes. Moreover, our neutralizing MAbs recognized the variants of concern (VOC) currently in circulation, including alpha, beta, gamma, and delta by ELISA, and neutralized alpha and omicron variants at different levels by conventional virus neutralization test (CVNT). While the neutralization of MAbs to the alpha variant showed no substantial difference as compared with the WT virus, their neutralizing activity was lower on omicron variant, suggesting the refractory effect of mutations in emerging variants against this group of neutralizing MAbs. Also, the binding reactivity of our MAbs to delta variant showed a modest decline by ELISA, implying that our MAbs are insensitive to the substitutions in the RBD of delta variant. Our data provide important information for understanding the immunogenicity of RBD, and the potential application of the novel neutralizing MAbs for passive immunotherapy of SARS-CoV-2 infection.
Geraniol inhibits biofilm formation of methicillin-resistant Staphylococcus aureus and increase the therapeutic effect of vancomycin in vivo
Authors: Gu Kexin , Ouyang Ping , Hong Yuxin , Dai Yuyun , Tang Ting , He Changliang , Shu Gang , Liang Xiaoxia , Tang Huaqiao , Zhu Ling , Xu Zhiwen , Yin Lizi
Published: September 2022

Methicillin-resistant Staphylococcus aureus (MRSA) is among the common drug resistant bacteria, which has gained worldwide attention due to its high drug resistance and infection rates. Biofilms produced by S. aureus are known to increase antibiotic resistance, making the treatment of S. aureus infections even more challenging. Hence, inhibition of biofilm formation has become an alternative strategy for controlling persistent infections. In this study, we evaluated the efficacy of geraniol as a treatment for MRSA biofilm infection. The results of crystal violet staining indicated that 256 μg/mL concentration of geraniol inhibited USA300 biofilm formation by 86.13% and removed mature biofilms by 49.87%. Geraniol exerted its anti-biofilm effect by influencing the major components of the MRSA biofilm structure. We found that geraniol inhibited the synthesis of major virulence factors, including staphyloxanthin and autolysins. The colony count revealed that geraniol inhibited staphyloxanthin and sensitized USA300 cells to hydrogen peroxide. Interestingly, geraniol not only reduced the release of extracellular nucleic acids (eDNA) but also inhibited cell autolysis. Real-time polymerase chain reaction data revealed the downregulation of genes involved in biofilm formation, which verified the results of the phenotypic analysis. Geraniol increased the effect of vancomycin in eliminating USA300 biofilms in a mouse infection model. Our findings revealed that geraniol effectively inhibits biofilm formation in vitro. Furthermore, in combination with vancomycin, geraniol can reduce the biofilm adhesion to the implant in mice. This suggests the potential of geraniol as an anti-MRSA biofilm drug and can provide a solution for the clinical treatment of biofilm infection.
The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea
Authors: Li Ling , Yu Meng-xue , Guo Jian , Hao Zhong-na , Zhang Zhen , Lu Zi-qi , Wang Jiao-yu , Zhu Xue-ming , Wang Yan-li , Chen Jie , Sun Guo-Chang , Lin Fu-cheng
Published: September 2022

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.
Directional couplings between the respiration and parasympathetic control of the heart rate during sleep and wakefulness in healthy subjects at different ages
Authors: Borovkova Ekaterina I. , Prokhorov Mikhail D. , Kiselev Anton R. , Hramkov Aleksey N. , Mironov Sergey A. , Agaltsov Mikhail V. , Ponomarenko Vladimir I. , Karavaev Anatoly S. , Drapkina Oksana M. , Penzel Thomas
Published: September 2022

Cardiorespiratory interactions are important, both for understanding the fundamental processes of functioning of the human body and for development of methods for diagnostics of various pathologies. The properties of cardiorespiratory interaction are determined by the processes of autonomic control of blood circulation, which are modulated by the higher nervous activity. We study the directional couplings between the respiration and the process of parasympathetic control of the heart rate in the awake state and different stages of sleep in 96 healthy subjects from different age groups. The detection of directional couplings is carried out using the method of phase dynamics modeling applied to experimental RR-intervals and the signal of respiration. We reveal the presence of bidirectional couplings between the studied processes in all age groups. Our results show that the coupling from respiration to the process of parasympathetic control of the heart rate is stronger than the coupling in the opposite direction. The difference in the strength of bidirectional couplings between the considered processes is most pronounced in deep sleep.
Correlation between heart rate variability and polysomnography-derived scores of obstructive sleep apnea
Authors: dos Santos Rafael Rodrigues , da Silva Thais Marques , Silva Luiz Eduardo Virgilio , Eckeli Alan Luiz , Salgado Helio Cesar , Fazan Rubens
Published: September 2022

Obstructive sleep apnea (OSA) is one of the most common sleep disorders and affects nearly a billion people worldwide. Furthermore, it is estimated that many patients with OSA are underdiagnosed, which contributes to the development of comorbidities, such as cardiac autonomic imbalance, leading to high cardiac risk. Heart rate variability (HRV) is a non-invasive, widely used approach to evaluating neural control of the heart. This study evaluates the relationship between HRV indices and the presence and severity of OSA. We hypothesize that HRV, especially the nonlinear methods, can serve as an easy-to-collect marker for OSA early risk stratification. Polysomnography (PSG) exams of 157 patients were classified into four groups: OSA-free (N = 26), OSA-mild (N = 39), OSA-moderate (N = 37), and OSA-severe (N = 55). The electrocardiogram was extracted from the PSG recordings, and a 15-min beat-by-beat series of RR intervals were generated every hour during the first 6 h of sleep. Linear and nonlinear HRV approaches were employed to calculate 32 indices of HRV. Specifically, time- and frequency-domain, symbolic analysis, entropy measures, heart rate fragmentation, acceleration and deceleration capacities, asymmetry measures, and fractal analysis. Results with indices of sympathovagal balance provided support to reinforce previous knowledge that patients with OSA have sympathetic overactivity. Nonlinear indices showed that HRV dynamics of patients with OSA display a loss of physiologic complexity that could contribute to their higher risk of development of cardiovascular disease. Moreover, many HRV indices were found to be linked with clinical scores of PSG. Therefore, a complete set of HRV indices, especially the ones obtained by the nonlinear approaches, can bring valuable information about the presence and severity of OSA, suggesting that HRV can be helpful for in a quick diagnosis of OSA, and supporting early interventions that could potentially reduce the development of comorbidities.
Prediction of risk factors for intraoperative hypotension during general anesthesia undergoing carotid endarterectomy
Authors: Jia Yitong , Feng Guang , Wang Zheng , Feng Yao , Jiao Liqun , Wang Tian-Long
Published: September 2022

Objective

Carotid endarterectomy (CEA) has been considered as “gold standard” treatment for patients with significant carotid stenosis Intra-operative hypotension was a risk factor for post-operative complications in patients undergoing CEA. This study aimed to investigate the predictors for intra-operative hypotension during CEA.

Methods

This retrospective study included consecutive patients underwent CEA from June 1, 2020 to May 31, 2021 in the neurosurgery department of Xuanwu Hospital, Capital Medical University. The intraoperative hypotension was defined as blood pressure (BP) of 20% below standard value for longer than 5 min. Univariable and multivariable analyses were performed to identify the prediction of risk factors for intraoperative hypotension.

Results

Overall, 367 patients were included, and 143 (39.0%) patients had hypotension during CEA procedure. Univariate analysis indicated Grade 3 hypertension (P = 0.002), peripheral artery disease (P = 0.006) and shunting (P = 0.049) were associated with occurrence of intraoperative hypotension during CEA procedure. On multivariable analysis, Grade 3 hypertension (P = 0.005), peripheral artery disease (P = 0.009), and shunting (P = 0.034) were all found to be independent predicting factors of hypotension during the CEA process.

Conclusion

Intraoperative hypotension is a dynamic phenomenon may be affected by patients with grade 3 hypertension, peripheral artery disease and intra-operative shunting. It is necessary to pay special attention to these patients, both intraoperatively and postoperatively, to improve the final clinical outcome.