bluuebunny/crossref_metadata_2025 huggingface dataset:
α1A-adrenaline receptors in dorsal horn inhibitory neurons have an inhibitory role in the regulation of chloroquine-induced itch in mice
Authors: Shiraishi Yuto , Koga Keisuke , Yamagata Ryo , Hatada Izuho , Shiratori-Hayashi Miho , Tsuda Makoto
Published: March 2021

Our previous study showed the intrinsic ability of descending noradrenergic neurons projecting from the locus coeruleus to the spinal dorsal horn (SDH) to suppress itch-related behaviors. Noradrenaline and α1A-adrenaline receptor (α1A-AR) agonist increase inhibitory synaptic inputs onto SDH interneurons expressing gastrin-releasing peptide receptors, which are essential for itch transmission. However, the contribution of α1A-ARs expressed in SDH inhibitory interneurons to itch-related behavior remains to be determined. In this study, RNAscope in situ hybridization revealed that Adra1a mRNA is expressed in SDH inhibitory interneurons that are positive for Slc32a1 mRNA (known as vesicular GABA transporter). Mice with conditional knock-out of α1A-ARs in inhibitory interneurons (Vgat-Cre;Adra1aflox/flox mice) exhibited an increase in scratching behavior when induced by an intradermal injection of chloroquine, but not compound 48/80, which are known as models of histamine-independent and dependent itch, respectively. Furthermore, knockout of inhibitory neuronal α1A-ARs in the SDH using the CRISPR–Cas9 system also increased the scratching behavior elicited by chloroquine but not compound 48/80. Our findings demonstrated for the first time that α1A-ARs in SDH inhibitory interneurons contribute to the regulation of itch signaling with preference for histamine-independent itch.
Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder
Authors: Kitagawa Kohei , Matsumura Kensuke , Baba Masayuki , Kondo Momoka , Takemoto Tomoya , Nagayasu Kazuki , Ago Yukio , Seiriki Kaoru , Hayata-Takano Atsuko , Kasai Atsushi , Takuma Kazuhiro , Hashimoto Ryota , Hashimoto Hitoshi , Nakazawa Takanobu
Published: March 2021

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.
LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1
Authors: Wang Conghui , Wang Jiaying , Shen Xiameng , Li Mingyue , Yue Yongfang , Cheng Xiaodong , Lu Weiguo , Wang Xinyu , Xie Xing
Published: March 2021

Background

Metastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis.

Methods

EVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesized and applied. Ovarian cancer orthotopic implantation mouse model was established in vivo.

Results

We found that ovarian cancer-secreted EVs could be taken into recipient mesothelial cells, induce the MMT phenotype and enhance cancer cell adhesion to mesothelial cells. Furthermore, SPOCD1-AS embedded in ovarian cancer-secreted EVs was transmitted to mesothelial cells to induce the MMT process and facilitate peritoneal colonization in vitro and in vivo. SPOCD1-AS induced the MMT process of mesothelial cells via interacting with G3BP1 protein. Additionally, G3BP1 interfering peptide based on the F380/F382 residues was able to block SPOCD1-AS/G3BP1 interaction, inhibit the MMT phenotype of mesothelial cells, and diminish peritoneal metastasis in vivo.

Conclusions

Our findings elucidate the mechanism associated with EVs and their cargos in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.
Identification of potential markers for differentiating epithelial ovarian cancer from ovarian low malignant potential tumors through integrated bioinformatics analysis
Authors: Hao Wende , Zhao Hongyu , Li Zhefeng , Li Jie , Guo Jiahao , Chen Qi , Gao Yan , Ren Meng , Zhao Xiaoting , Yue Wentao
Published: March 2021

Background

Epithelial ovarian cancer (EOC), as a lethal malignancy in women, is often diagnosed as advanced stages. In contrast, intermediating between benign and malignant tumors, ovarian low malignant potential (LMP) tumors show a good prognosis. However, the differential diagnosis of the two diseases is not ideal, resulting in delays or unnecessary therapies. Therefore, unveiling the molecular differences between LMP and EOC may contribute to differential diagnosis and novel therapeutic and preventive policies development for EOC.

Methods

In this study, three microarray data (GSE9899, GSE57477 and GSE27651) were used to explore the differentially expressed genes (DEGs) between LMP and EOC samples. Then, 5 genes were screened by protein–protein interaction (PPI) network, receiver operating characteristic (ROC), survival and Pearson correlation analysis. Meanwhile, chemical-core gene network construction was performed to identify the potential drugs or risk factors for EOC based on 5 core genes. Finally, we also identified the potential function of the 5 genes for EOC through pathway analysis.

Results

Two hundred thirty-four DEGs were successfully screened, including 81 up-regulated genes and 153 down-regulated genes. Then, 5 core genes (CCNB1, KIF20A, ASPM, AURKA, and KIF23) were identified through PPI network analysis, ROC analysis, survival and Pearson correlation analysis, which show better diagnostic efficiency and higher prognostic value for EOC. Furthermore, NetworkAnalyst was used to identify top 15 chemicals that link with the 5 core genes. Among them, 11 chemicals were potential drugs and 4 chemicals were risk factors for EOC. Finally, we found that all 5 core genes mainly regulate EOC development via the cell cycle pathway by the bioinformatic analysis.

Conclusion

Based on an integrated bioinformatic analysis, we identified potential biomarkers, risk factors and drugs for EOC, which may help to provide new ideas for EOC diagnosis, condition appraisal, prevention and treatment in future.
Kssd: sequence dimensionality reduction by k-mer substring space sampling enables real-time large-scale datasets analysis
Authors: Yi Huiguang , Lin Yanling , Lin Chengqi , Jin Wenfei
Published: March 2021

Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can be used for large-scale dataset comparisons at population resolution on simulated and real data. Using Kssd, we prioritize references for all 1,019,179 bacteria whole genome sequencing (WGS) runs from NCBI Sequence Read Archive and find misidentification or contamination in 6164 of these. Additionally, we analyze WGS and exome runs of samples from the 1000 Genomes Project.
A U.S. isolate of Theileria orientalis, Ikeda genotype, is transmitted to cattle by the invasive Asian longhorned tick, Haemaphysalis longicornis
Authors: Dinkel Kelcey D. , Herndon David R. , Noh Susan M. , Lahmers Kevin K. , Todd S. Michelle , Ueti Massaro W. , Scoles Glen A. , Mason Kathleen L. , Fry Lindsay M.
Published: March 2021

Background

Theileria orientalis is a tick-borne hemoparasite that causes anemia, ill thrift, and death in cattle globally. The Ikeda strain of T.orientalis is more virulent than other strains, leading to severe clinical signs and death of up to 5% of affected animals. Within the Asia–Pacific region, where it affects 25% of Australian cattle, T.orientalis Ikeda has a significant economic impact on the cattle industry. In 2017, T.orientalis Ikeda was detected in a cattle herd in Albermarle County, Virginia, United States. Months earlier, the U.S. was alerted to the invasion of the Asian longhorned tick, Haemaphysalis longicornis, throughout the eastern U.S. Abundant H.longicornis ticks were identified on cattle in the T.orientalis-affected herd in VA, and a subset of ticks from the environment were PCR-positive for T.orientalis Ikeda. A strain of T.orientalis from a previous U.S. outbreak was not transmissible by H.longicornis; however, H.longicornis is the primary tick vector of T.orientalis Ikeda in other regions of the world. Thus, the objective of this study was to determine whether invasive H.longicornis ticks in the U.S. are competent vectors of T.orientalis Ikeda.

Methods

Nymphal H.longicornis ticks were fed on a splenectomized calf infected with the VA-U.S.-T.orientalis Ikeda strain. After molting, a subset of adult ticks from this cohort were dissected, and salivary glands assayed for T.orientalis Ikeda via qPCR. The remaining adult ticks from the group were allowed to feed on three calves. Calves were subsequently monitored for T.orientalis Ikeda infection via blood smear cytology and PCR.

Results

After acquisition feeding on a VA-U.S.-T.orientalis Ikeda-infected calf as nymphs, a subset of molted adult tick salivary glands tested positive by qPCR for T.orientalis Ikeda. Adult ticks from the same cohort successfully transmitted T.orientalis Ikeda to 3/3 naïve calves, each of which developed parasitemia reaching 0.4–0.9%.

Conclusions

Our findings demonstrate that U.S. H.longicornis ticks are competent vectors of the VA-U.S.-T.orientalis Ikeda strain. This data provides important information for the U.S. cattle industry regarding the potential spread of this parasite and the necessity of enhanced surveillance and control measures.

Graphical Abstract
MiR-4448 is involved in deltamethrin resistance by targeting CYP4H31 in Culex pipiens pallens
Authors: Li Xixi , Hu Shengli , Yin Haitao , Zhang Hongbo , Zhou Dan , Sun Yan , Ma Lei , Shen Bo , Zhu Changliang
Published: March 2021

Background

Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens.

Methods

We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levels. The regulatory functions of miR-4448 and CYP4H31 were assessed using dual-luciferase reporter assays. Then, oral feeding, RNA interference, and the American Centers for Disease Control and Prevention bottle bioassay were used to determine miR-4448’s association with deltamethrin resistance by targeting CYP4H31in vivo. Cell Counting Kit-8 (CCK-8) was also used to detect the viability of pIB/V5-His-CYP4H31-transfected C6/36 cells after deltamethrin treatment in vitro.

Results

MiR-4448 was downregulated in the deltamethrin-resistant strain (DR strain), whereas CYP4H31 was downregulated in deltamethrin-susceptible strain. CYP4H31 expression was downregulated by miR-4448 recognizing and binding to its 3′ untranslated region. Functional verification experiments showed that miR-4448 overexpression resulted in lower expression of CYP4H31. The mortality of miR-4448 mimic-injected DR strain mosquitoes was higher than that of the controls. CCK-8 assays showed that CYP4H31 decreased cellular resistance to deltamethrin in vitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo.

Conclusions

In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.

Graphical Abstract
Positive feedback regulation between USP15 and ERK2 inhibits osteoarthritis progression through TGF-β/SMAD2 signaling
Authors: Wang Wenjuan , Zhu Yanhui , Sun Zhenyu , Jin Chen , Wang Xiang
Published: March 2021

Background

The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). However, the specific mechanism of non-SMAD and classical SMAD signaling interactions is still unclear, which needs to be further explored.

Methods

In ATDC5 cells, USP15 overexpression and knockout were performed using the transfected lentivirus USP15 and Crispr/Cas9. Western blotting and immunofluorescence staining were used to test p-SMAD2 and cartilage phenotype-related molecular markers. In rat OA models, immunohistochemistry, hematoxylin and eosin (HE)/Safranin-O fast green staining, and histology were used to examine the regulatory activity of USP15 in TGF-β/SMAD2 signaling and the cartilage phenotype. Then, ERK2 overexpression and knockout were performed. The expressions of USP15, p-SMAD2, and the cartilage phenotype were evaluated in vitro and in vivo. To address whether USP15 is required for ERK2 and TGF-β/SMAD2 signaling, we performed rescue experiments in vitro and in vivo. Immunoprecipitation and deubiquitination assays were used to examine whether USP15 could bind to ERK2 and affect the deubiquitination of ERK2. Finally, whether USP15 regulates the level of p-ERK1/2 was evaluated by western blotting, immunofluorescence staining, and immunohistochemistry in vitro and in vivo.

Results

Our results indicated that USP15 stimulated TGF-β/SMAD2 signaling and the cartilage phenotype. Moreover, ERK2 required USP15 to influence TGF-β/SMAD2 signaling for regulating the cartilage phenotype in vivo and in vitro. And USP15 can form a complex with ERK2 to regulate ubiquitination of ERK2. Interestingly, USP15 did not regulate the stability of ERK2 but increased the level of p-ERK1/2 to further enhance the TGF-β/SMAD2 signaling pathway.

Conclusions

Taken together, our study revealed positive feedback regulation between USP15 and ERK2, which played a critical role in TGF-β/SMAD2 signaling to inhibit OA progression. Therefore, this specific mechanism can guide the clinical treatment of OA.
Prevalence of thinness and its effect on height velocity in schoolchildren
Authors: Narchi Hassib , Alblooshi Afaf , Altunaiji Maisoon , Alali Nawal , Alshehhi Latifa , Alshehhi Huda , Almazrouei Asma , Alsuwaidi Ahmed R. , Souid Abdul-Kader
Published: March 2021

Objective

In contrast to childhood obesity, studies involving thin children are much fewer, especially in developed countries. Furthermore, most reports do not address the impact of childhood thinness on height velocity. This study investigated the prevalence of thinness and its effect on height velocity in schoolchildren in the United Arab Emirates (UAE). Weight and height were measured in 29,410 schoolchildren (50.5% females), as part of the health assessment (academic year 2014–2015). The body mass index (BMI) was classified as normal, thinness, overweight, or obese using cutoffs established by the International Obesity Task Force (IOTF), World Health Organization, and Centers for Disease Control.

Results

The median age was 10.2 years (range, 3–19). Using the IOTF scale, one-quarter of the children aged 4–6 years and one-third of the children aged 7–9 years were thin (BMI ≤ 18.5 kg/m2). Thinness was less prevalent (8–10%) in adolescents. Group peak height velocity was delayed 1–3 years in thin children and was higher in children with excess body fat. In conclusion thinness was the highest (25–33%) in children aged 4–9 years of age and their peak height velocity was delayed 1–3 years when compared to the other children.
Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans
Authors: Ammous Farah , Zhao Wei , Ratliff Scott M. , Mosley Thomas H. , Bielak Lawrence F. , Zhou Xiang , Peyser Patricia A. , Kardia Sharon L. R. , Smith Jennifer A.
Published: March 2021

Background

Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention.

Results

Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22–2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS andP = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040–0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006–0.064).

Conclusions

Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.
Additive interaction of mid- to late-life depression and cerebrovascular disease on the risk of dementia: a nationwide population-based cohort study
Authors: Jang Yoo Jin , Kang Cinoo , Myung Woojae , Lim Shinn-Won , Moon Young Kyung , Kim Ho , Kim Doh Kwan
Published: March 2021

Background

Dementia is a progressive neurocognitive disease with a substantial social burden. No apparent breakthroughs in treatment options have emerged so far; thus, disease prevention is essential for at-risk populations. Depression and cerebrovascular disease (CVD) are independent risk factors for dementia, but no studies have examined their interaction effect on dementia risk. This study aimed to identify the association of depression and CVD with the risk of dementia and evaluate whether dementia risk among patients with comorbid depression and CVD is higher than the sum of the individual risk due to each condition.

Methods

A population-based cohort study was conducted to analyze the Korean National Health Insurance Service-National Sample Cohort data of all individuals over 50 years of age. Individuals who had not been diagnosed with dementia at baseline were included and followed up from January 1, 2005, to December 31, 2013. A time-varying Cox proportional hazard regression model adjusted for potential confounding factors was used for the analysis. The interaction between depression and CVD was estimated based on the attributable proportion (AP), relative excess risk due to interaction (RERI), synergy index (SI), and multiplicative-scale interaction.

Results

A total of 242,237 participants were included in the analytical sample, of which 12,735 (5.3%) developed dementia. Compared to that for participants without depression or CVD, the adjusted hazard ratio for the incidence of dementia for those with depression alone was 2.35 (95% confidence interval [CI] 2.21–2.49), CVD alone was 3.25 (95% CI 3.11–3.39), and comorbid depression and CVD was 5.02 (95% CI 4.66–5.42). The additive interaction between depression and CVD was statistically significant (AP—0.08, 95% CI 0.01–0.16; RERI—0.42, 95% CI 0.03–0.82; SI—1.12, 95% CI 1.01–1.24). The multiplicative interaction was significant too, but the effect was negative (0.66, 95% CI 0.60–0.73).

Conclusions

In this population-based nationwide cohort with long-term follow-up, depression and CVD were associated with an increased risk of dementia, and their coexistence additively increased dementia risk more than the sum of the individual risks.
Fibrolamellar hepatocellular carcinoma treated with atezolizumab and bevacizumab: two case reports
Authors: AL Zahrani Ali , Alfakeeh Ali
Published: March 2021

Background

Fibrolamellar hepatocellular carcinoma is a unique tumor of the liver that differs from the classical hepatocellular carcinoma in diagnosis, behavior, and possibly treatment. There is usually absent underlying liver disease, and it usually occurs in young patients. The survival outcomes in localized fibrolamellar hepatocellular carcinoma are perhaps better than in classical hepatocellular carcinoma if treated early and radically. On the other hand, the prognosis remains poor for locally advanced and metastatic fibrolamellar hepatocellular carcinoma. Many reports suggested a limited benefit from systemic chemotherapy. Sorafenib also did not show major effects on fibrolamellar hepatocellular carcinoma. Given the rarity of fibrolamellar hepatocellular carcinoma, lack of large studies, and absence of standard treatment, the treatment decisions rely on case reports, previously reported cases series, and expert opinions. Recent studies have shown promising effects of immunotherapy with checkpoint inhibitors in the first- and second-line therapy of hepatocellular carcinoma. Atezolizumab with bevacizumab regimen has been approved recently as a first-line treatment for classical hepatocellular carcinoma. Currently, there are no reports yet on the use of atezolizumab with bevacizumab for fibrolamellar hepatocellular carcinoma.

Case report

In this article, we present two Arabic patients with advanced fibrolamellar hepatocellular carcinoma who received atezolizumab and bevacizumab combinations but did not show any clinical benefits.

Conclusion

While atezolizumab and bevacizumab combinations had shown benefits in classical hepatocellular carcinoma, the current data showed a lack of benefit and tumor response in fibrolamellar hepatocellular carcinoma.
Gene engineered mesenchymal stem cells: greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury
Authors: Florian Maria , Wang Jia-Pey , Deng Yupu , Souza-Moreira Luciana , Stewart Duncan J. , Mei Shirley H. J.
Published: March 2021

Background

Acute lung injury (ALI) and in its severe form, acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance the potency of mesenchymal stem cells (MSCs) to develop more effective treatments. Genetic modification of MSCs has been demonstrated to significantly improve the therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off-target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration.

Methods

Here, we explored whether a minicircle DNA (MC) vector containing human angiopoietin 1 (MC-ANGPT1) can provide a more effective platform for gene-enhanced MSC therapy of ALI/ARDS.

Results

At 24 h after transfection, nuclear-targeted electroporation using an MC-ANGPT1 vector resulted in a 3.7-fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048 ± 567 pg/mL vs. 552.1 ± 33.5 pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSCs significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSCs reduced it by 71% (p < 0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSCs significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). pANGPT1-transfected MSCs significantly reduced BAL albumin levels by 71%, while MC-ANGPT1-transfected MSCs reduced it by 85%.

Conclusions

Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSCs and enhanced the therapeutic effect on the ALI model compared to plasmid. These results support the potential benefits of MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.
Chronic ethanol vapor exposure potentiates cardiovascular responses to acute stress in male but not in female rats
Authors: Bianchi Paula C. , Gomes-de-Souza Lucas , Costa-Ferreira Willian , Palombo Paola , Carneiro de Oliveira Paulo E. , Engi Sheila A. , Leão Rodrigo M. , Planeta Cleopatra S. , Crestani Carlos C. , Cruz Fabio C.
Published: March 2021

Background

Ethanol use is related to a wide variety of negative health outcomes, including cardiovascular diseases. Stress is also involved in numerous pathologies, such as cardiovascular diseases and psychiatric disorders. Sexual dimorphism is an important factor affecting cardiovascular response and has been proposed as a potential risk factor for sex-specific health problems in humans. Here, we evaluated the effect of prolonged ethanol vapor inhalation on arterial pressure, heart rate, and tail skin temperature responses to acute restraint stress, investigating differences between male and female rats.

Methods

We exposed male and female Long-Evans rats to ethanol vapor for 14 h, followed by ethanol withdrawal for 10 h, for 30 consecutive days, or to room air (control groups). The animals underwent surgical implantation of a cannula into the femoral artery for assessment of arterial pressure and heart rate values. The tail skin temperature was measured as an indirect measurement of sympathetic vasomotor response.

Results

Chronic ethanol vapor inhalation reduced basal heart rate in both female and male rats. Sex-related difference was observed in the decrease of tail cutaneous temperature evoked by stress, but not in the pressor and tachycardiac responses. Furthermore, prolonged ethanol inhalation enhanced the blood pressure and heart rate increase caused by acute restraint stress in male, but not in female rats. However, no effect of chronic ethanol vapor was observed in the tail cutaneous temperature response to restraint in either sex.

Conclusion

Chronic ethanol vapor exposure increased the cardiovascular reactivity to stress in male, but not in female rats.
Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids
Authors: Fang Ke-Ying , Cao Wen-Chao , Xie Tian-Ao , Lv Jie , Chen Jia-Xin , Cao Xun-Jie , Li Zhong-Wei , Deng Shu-Ting , Guo Xu-Guang
Published: March 2021

Background

In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people’s health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein–protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in.

Results

In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients.

Conclusions

In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.
Improving oxidation stability of 2D MXenes: synthesis, storage media, and conditions
Authors: Iqbal Aamir , Hong Junpyo , Ko Tae Yun , Koo Chong Min
Published: March 2021

Understanding and preventing oxidative degradation of MXene suspensions is essential for fostering fundamental academic studies and facilitating widespread industrial applications. Owing to their outstanding electrical, electrochemical, optoelectronic, and mechanical properties, MXenes, an emerging class of two-dimensional (2D) nanomaterials, show promising state-of-the-art performances in various applications including electromagnetic interference (EMI) shielding, terahertz shielding, electrochemical energy storage, triboelectric nanogenerators, thermal heaters, light-emitting diodes (LEDs), optoelectronics, and sensors. However, MXene synthesis using harsh chemical etching causes many defects or vacancies on the surface of the synthesized MXene flakes. Defective sites are vulnerable to oxidative degradation reactions with water and/or oxygen, which deteriorate the intrinsic properties of MXenes. In this review, we demonstrate the nature of oxidative degradation of MXenes and highlight the recent advancements in controlling the oxidation kinetics of MXenes with several promising strategic approaches, including careful control of the quality of the parent MAX phase, chemical etching conditions, defect passivation, dispersion medium, storage conditions, and polymer composites.
Immediate and legacy effects of snow exclusion on soil fungal diversity and community composition
Authors: Zhang Li , Ren Yuzhi , Yang Kaijun , Li Zhijie , Tan Bo , Liu Yang , Li Han , You Chengming , Liu Sining , Wang Lixia , Yin Rui , Zhang Jian , Xu Zhenfeng
Published: March 2021

Background

Soil fungi play crucial roles in ecosystem functions. However, how snow cover change associated with winter warming affects soil fungal communities remains unclear in the Tibetan forest.

Methods

We conducted a snow manipulation experiment to explore immediate and legacy effects of snow exclusion on soil fungal community diversity and composition in a spruce forest on the eastern Tibetan Plateau. Soil fungal communities were performed by the high throughput sequencing of gene-fragments.

Results

Ascomycota and Basidiomycota were the two dominant fungal phyla and Archaeorhizomyces, Aspergillus and Amanita were the three most common genera across seasons and snow manipulations. Snow exclusion did not affect the diversity and structure of soil fungal community in both snow-covered and snow-free seasons. However, the relative abundance of some fungal communities was different among seasons. Soil fungal groups were correlated with environmental factors (i.e., temperature and moisture) and soil biochemical variables (i.e., ammonium and enzyme).

Conclusions

These results suggest that the season-driven variations had stronger impacts on soil fungal community than short-term snow cover change. Such findings may have important implications for soil microbial processes in Tibetan forests experiencing significant decreases in snowfall.
Correction to: Species diversity and molecular analysis of opportunistic Mycobacterium, Nocardia and Rhodococcus isolated from the hospital environment in a developing country, a potential resources for nosocomial infection
Authors: Siavashifar Marzieh , Rezaei Fatemeh , Motallebirad Tahereh , Azadi Davood , Absalan Abdorrahim , Naserramezani Zahra , Golshani Mohadeseh , Jafarinia Morteza , Ghaffari Kazem
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
An improved in vivo tethering assay with single molecule FISH reveals that a nematode Nanos enhances reporter expression and mRNA stability
Authors: Doenier Jonathan , Lynch Tina R. , Kimble Judith , Aoki Scott T.
Published: March 2021

Robust methods are critical for testing the in vivo regulatory mechanism of RNA binding proteins. Here we report improvement of a protein–mRNA tethering assay to probe the function of an RNA binding protein in its natural context within the C. elegans adult germline. The assay relies on a dual reporter expressing two mRNAs from a single promoter and resolved by trans-splicing. The gfp reporter 3′UTR harbors functional binding elements for λN22 peptide, while the mCherry reporter 3′UTR carries mutated nonfunctional elements. This strategy enables internally controlled quantitation of reporter protein by immunofluorescence and mRNA by smFISH. To test the new system, we analyzed a C. elegans Nanos protein, NOS-3, which serves as a post-transcriptional regulator of germ cell fate. Unexpectedly, tethered NOS-3 enhanced reporter expression. We confirmed this enhancement activity with a second reporter engineered at an endogenous germline gene. NOS-3 enhancement of reporter expression was associated with its amino-terminal intrinsically disordered region, not its carboxy-terminal zinc fingers. RNA quantitation revealed that tethered NOS-3 enhances stability of the reporter mRNA. We suggest that this direct NOS-3 enhancement activity may explain a paradox: Classically Nanos proteins are expected to repress RNA, but nos-3 had been found to promote gld-1 expression, an effect that could be direct. Regardless, the new dual reporter dramatically improves in situ quantitation of reporter expression after RNA binding protein tethering to determine its molecular mechanism in a multicellular tissue.
COVID-19 related misconceptions among older adults in Bangladesh: findings from a cross-sectional study
Authors: Mistry Sabuj Kanti , Ali ARM Mehrab , Yadav Uday Narayan , Irfan Nafis Md. , Rayamajhee Binod , Stanners Melinda N.
Published: March 2021

Background

The COVID-19 has been appeared as the most remarkable global calamity of this century. Just as the COVID-19 spread throughout the world, so as the rumour and misconceptions related to it. The present study aimed to explore the prevalence of COVID-19 related misconceptions and its correlates among the older adults in Bangladesh.

Methods

The study followed a cross-sectional design and was conducted among 1032 participants aged 60 years and above from Bangladesh. Information was collected on 14 different locally relevant misconceptions related to the spread, prevention, and treatment of COVID-19, scored each misconception as one, and obtained a cumulative score, ranging from 0 to 14, with a higher score indicating a higher level of misconceptions. A multiple linear regression model explored the factors associated with misconceptions.

Results

The most common misconceptions were, all returning migrants carrying COVID-19 (45.5%), wearing personal protective equipment (PPE) in outdoors (80.1%), not going to the funeral of people died of COVID-19 (45.2%), its prevention by nutritious food (57.6%) and drinking water (39.4%), and doctor can cure COVID-19 (49.9%). Misconceptions were higher among the participants who were living alone, whose family members were not responsive to their needs during COVID-19, and who received COVID-19 related information from Radio/TV and health workers. These misconceptions were less likely among those who were aged 70-79 years, who had pre-existing non-communicable chronic conditions, who were overwhelmed by COVID-19, and who felt themselves at highest risk of COVID-19.

Conclusion

Overall, we found that misconceptions were prevalent among the older adults in Bangladesh. Government and other relevant stakeholders should take immediate actions to address the prevalent misconceptions through using appropriate channels, media, and message delivery systems, and applying evidence-based risk communication methods.
Real-color displays realized by randomized polarization
Authors: Sasaki Shizuki , Udono Mariko , Koike Yasuhiro
Published: March 2021

This study achieves real-color displays using a randomizing effect based on the concept of “natural light.” At present, most displays emit linearly polarized light, which causes essential blackout and color degradation problems when the displays are viewed through polarizers such as sunglasses. To address this, complex polarization-control technologies are added to existing displays, but the problems remain unresolved. In contrast, this study randomizes the polarization using a polymer film called a random depolarization film (RDF) that is doped with specific birefringent crystal particles. The RDF placed on a display reproduces colors that are very close to the natural colors seen in reality without the need for complex polarization technologies. We believe that it has the potential to change the approach to color-reproducing technology for displays.
Multi-scale GCN-assisted two-stage network for joint segmentation of retinal layers and discs in peripapillary OCT images
Authors: Li Jiaxuan , Jin Peiyao , Zhu Jianfeng , Zou Haidong , Xu Xun , Tang Min , Zhou Minwen , Gan Yu , He Jiangnan , Ling Yuye , Su Yikai
Published: March 2021

An accurate and automated tissue segmentation algorithm for retinal optical coherence tomography (OCT) images is crucial for the diagnosis of glaucoma. However, due to the presence of the optic disc, the anatomical structure of the peripapillary region of the retina is complicated and is challenging for segmentation. To address this issue, we develop a novel graph convolutional network (GCN)-assisted two-stage framework to simultaneously label the nine retinal layers and the optic disc. Specifically, a multi-scale global reasoning module is inserted between the encoder and decoder of a U-shape neural network to exploit anatomical prior knowledge and perform spatial reasoning. We conduct experiments on human peripapillary retinal OCT images. We also provide public access to the collected dataset, which might contribute to the research in the field of biomedical image processing. The Dice score of the proposed segmentation network is 0.820 ± 0.001 and the pixel accuracy is 0.830 ± 0.002, both of which outperform those from other state-of-the-art techniques.
Time division ghost imaging
Authors: Torii Teruaki , Haruse Yuta , Sugimoto Shintaro , Kasaba Yusuke
Published: March 2021

In the conventional ghost imaging, it requires to illuminate a large number of patterns in order to reconstruct a good quality image under a low signal-to-noise ratio. We propose a new method so called time division ghost imaging to improve the quality of the image in noisy environment. In this procedure, the total number of patterns in the calculation process of the correlation function are divided into the sub-units with fewer illuminated patterns. Then one calculates the correlation for each sub-unit, and synthesizes the intermediate images obtained at each sub-unit. The validation and effectiveness of this method are confirmed by simulation and experiment, showing the robustness to noise.
Monolithic AlGaAs second-harmonic nanoantennas: erratum
Authors: Gili V. F. , Carletti L. , Locatelli A. , Rocco D. , Finazzi M. , Ghirardini L. , Favero I. , Gomez C. , Lemaître A. , Celebrano M. , De Angelis C. , Leo G.
Published: March 2021

Figure 1(b) in [V. F. Gili et al, Opt. Express 24, 15965 (2016)10.1364/OE.24.015965] is corrupted and is corrected in this erratum.
Plasmon-driven light harvesting in poly(vinyl alcohol) films for precise surface topography modulation
Authors: Liu Hongfang , Fu Shencheng , Li Xin , Zhou Jiahui , Wang Yiqian , Zhang Xintong , Liu Yichun
Published: March 2021

Efficient light harvesting is essential for advanced photonic devices. Complex micro/nano surface relief structures can be produced via light-triggered mechanical movement, but limited in organic active molecular units. In this Letter, we propose to embed noble-metal particles into light-inactive polyvinyl alcohol matrix to construct a light harvesting system driven by plasmon for inscription of surface relief gratings. Ultra-small-sized silver nuclei are generated in the polymer by pre-thermal treatment, acting as an accelerator for the subsequent photoinduced particle growth, hydrogen group cleavage, and matrix softening. Based on such properties, a complex plasmonic array carrying ultra-high-density information is achieved with peristrophic multiplexing holography. This Letter paves a bright way to realize data storage, information encryption, and optical microcavity.
Gratingless integrated tunneling multiplexer for terahertz waves
Authors: Headland Daniel , Withayachumnankul Withawat , Fujita Masayuki , Nagatsuma Tadao
Published: March 2021

The arrayed waveguide grating (AWG) is a versatile and scalable passive photonic multiplexer that sees widespread usage. However, the necessity of a waveguide array engenders large device size, and gratings invariably commute finite power into undesired diffraction orders. Here, we demonstrate AWG-like functionality without a grating or waveguide array, yielding benefits to compactness, bandwidth, and efficiency. To this end, we exploit optical tunneling from a dielectric waveguide to an adjacent slab in order to realize a slab-confined frequency-scanning beam, which is manipulated using in-slab beamforming techniques that we have developed in order to separate distinct frequency bands. In this way, we devise an all-intrinsic-silicon integrated

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frequency-division terahertz multiplexer, which is shown to support aggregate data rates up to 48 Gbit/s with an on–off-keying modulation scheme, operating in the vicinity of 350 GHz. Our investigation targets the terahertz range, to provide a critical missing building block for future high-volume wireless communications networks.
High-resolution two-photon transcranial imaging of brain using direct wavefront sensing
Authors: Chen Congping , Qin Zhongya , He Sicong , Liu Shaojun , Lau Shun-Fat , Wu Wanjie , Zhu Dan , Ip Nancy Y. , Qu Jianan Y.
Published: March 2021

Imaging of the brain in its native state at high spatial resolution poses major challenges to visualization techniques. Two-photon microscopy integrated with the thinned-skull or optical clearing skull technique provides a minimally invasive tool for in vivo imaging of the cortex of mice without activating immune response and inducing brain injury. However, the imaging contrast and spatial resolution are severely compromised by the optical heterogeneity of the skull, limiting the imaging depth to the superficial layer. In this work, an optimized configuration of an adaptive optics two-photon microscope system and an improved wavefront sensing algorithm are proposed for accurate correction for the aberrations induced by the skull window and brain tissue. Using this system, we achieved subcellular resolution transcranial imaging of layer 5 pyramidal neurons up to 700 μm below pia in living mice. In addition, we investigated microglia–plaque interaction in living brain of Alzheimer’s disease and demonstrated high-precision laser dendrotomy and single-spine ablation.
Legal challenges of an open web index
Authors: Erenli Kai , Geminn Christian , Pfeiffer Leon
Published: March 2021

Calls for a European “third way” in matters of digital technology need to be put into action to achieve an actual change of the status quo. To achieve autonomy in the digital sphere, European alternatives to digital services and products need to be established. However, such efforts must also extend to the level of information technology infrastructure. To that end, decentralized indexing of the internet could significantly help to strengthen Europe’s digital sovereignty. Nevertheless, legal challenges need to be overcome to make that vision a reality.