bluuebunny/crossref_metadata_2025 huggingface dataset:
Short X···N Halogen Bonds With Hexamethylenetetraamine as the Acceptor
Authors: Anyfanti Goulielmina , Bauzá Antonio , Gentiluomo Lorenzo , Rodrigues João , Portalone Gustavo , Frontera Antonio , Rissanen Kari , Puttreddy Rakesh
Published: April 2021

Hexamethylenetetramine (HMTA) and N-haloimides form two types of short (imide)X···N and X–X···N (X = Br, I) halogen bonds. Nucleophilic substitution or ligand-exchange reaction on the peripheral X of X–X···N with the chloride of N-chlorosuccinimide lead to Cl–X···N halogen-bonded complexes. The 1:1 complexation of HMTA and ICl manifests the shortest I···N halogen bond [2.272(5) Å] yet reported for an HMTA acceptor. Two halogen-bonded organic frameworks are prepared using 1:4 molar ratio of HMTA and N-bromosuccinimide, each with a distinct channel shape, one possessing oval and the other square grid. The variations in channel shapes are due to tridentate and tetradentate (imide)Br···N coordination modes of HMTA. Density Functional Theory (DFT) studies are performed to gain insights into (imide)X···N interaction strengths (ΔEint). The calculated ΔEint values for (imide)Br···N (−11.2 to −12.5 kcal/mol) are smaller than the values for (imide)I···N (−8.4 to −29.0 kcal/mol). The DFT additivity analysis of (imide)Br···N motifs demonstrates Br···N interaction strength gradually decreasing from 1:1 to 1:3 HMTA:N-bromosuccinimide complexes. Exceptionally similar charge density values ρ(r) for N–I covalent bond and I···N non-covalent bond of a (saccharin)N–I···N motif signify the covalent character for I···N halogen bonding.
A Synthetic Phospholipid Derivative Mediates Ion Transport Across Lipid Bilayers
Authors: Wang Chenxi , Yang Huiting , Xiang Yanxin , Pang Shihao , Bao Chunyan , Zhu Linyong
Published: April 2021

Inspired by the natural phospholipid structures for cell membrane, a synthetic phospholipid LC with an ion recognition group benzo-18-crown-6 (B18C6) moiety was prepared which has been demonstrated to be able to transport ions across the lipid bilayers. Fluorescent vesicle assay shows that LC has an excellent transport activity, and the EC50 value for K+ is 11.2 μM. The voltage clamp measurement exhibits regular square-like current signals with considerably long opening times, which indicates that LC achieves efficient ion transport through a channel mechanism and its single channel conductivity is 17 pS. Both of the vesicle assay and patch clamp tests indicate that LC has selectivity for Rb+, whose ionic radius is larger than the cavity of crown ether. It suggests that the sandwich interaction may play a key role in the ion transport across lipid bilayers. All these results help us to speculate that LC transports ions via a channel mechanism with a tetrameric aggregate as the active structure. In addition, LC had obvious toxicity to HeLa cells, and the IC50 was 100.0 μM after coculture for 36 h. We hope that this simple synthetic phospholipid will offer novel perspectives in the development of more efficient and selective ion transporters.
Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer via Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier
Authors: Zhu Huai-Chang , Jia Xiao-Kang , Fan Yong , Xu Shao-Hua , Li Xiao-Yan , Huang Ming-Qing , Lan Meng-Liu , Xu Wen , Wu Shui-Sheng
Published: April 2021

Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis‐associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in Alismatis rhizoma which is well known for dietary herb. Alismatis rhizoma is often used clinically to treat gastrointestinal diseases in China. In this study, we investigated the potential prevention of AB23A in male mouse models of azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC. AB23A intervention alleviated the body weight loss, disease activity index, colon tumor load, tissue injury, and inflammatory cytokine changes in CAC mice. AB23A intervention leads to remarkable reductions in the activation of TLR, NF-κB and MAPK. AB23A significantly decreased the phosphorylation of p38, ERK, and JNK and up-regulated mucin-2 and the expression of tight junction proteins. The gut microbiota of AB23A-interfered mice was characterized with high microbial diversity, the reduced expansion of pathogenic bacteria, such as Klebsiella, Citrobacter, and Akkermansia, and the increased growth of bacteria including Bacteroides, Lactobacillus, and Alloprevotella. These data reveal that AB23A has the potential to be used to treat CAC in the future.
Why Should Scientists be on YouTube? It’s all About Bamboo, Oil and Ice Cream
Authors: Brennan Eric B.
Published: April 2021

Scientific information is a key ingredient needed to tackle global challenges like climate change, but to do this it must be communicated in ways that are accessible to diverse groups, and that go beyond traditional methods (peer-reviewed publications). For decades there have been calls for scientists to improve their communication skills—with each other and the public—but, this problem persists. During this time there have been astonishing changes in the visual communication tools available to scientists. I see video as the next step in this evolution. In this paper I highlight three major changes in the visual communication tools over the past 100 years, and use three memorable items—bamboo, oil and ice cream—and analogies and metaphors to explain why and how Do-it-Yourself (DIY) videos made by scientists, and shared on YouTube, can radically improve science communication and engagement. I also address practical questions for scientists to consider as they learn to make videos, and organize and manage them on YouTube. DIY videos are not a silver bullet that will automatically improve science communication, but they can help scientists to 1) reflect on and improve their communications skills, 2) tell stories about their research with interesting visuals that augment their peer-reviewed papers, 3) efficiently connect with and inspire broad audiences including future scientists, 4) increase scientific literacy, and 5) reduce misinformation. Becoming a scientist videographer or scientist DIY YouTuber can be an enjoyable, creative, worthwhile and fulfilling activity that can enhance many aspects of a scientist’s career.
Serum Complement C1q Activity Is Associated With Obstructive Coronary Artery Disease
Authors: Guo Shuren , Mao Xiaohuan , Li Xiaohua , Ouyang Huan , Gao Yuhua , Ming Liang
Published: April 2021

Background:Complement C1q plays a dual role in the atherosclerosis. Previous studies showed inconsistent results about the association of serum C1q levels and coronary artery disease (CAD). Here, we explored the associations of serum C1q activity with CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year restenosis after coronary artery revascularization.

Methods:We enrolled 956 CAD patients and 677 controls to evaluate the associations of serum complement C1q activity to the presence and severity of obstructive CAD and non-obstructive CAD. Serum C1q activity and the concentrations of laboratory markers were measured in all subjects. All the data were analyzed using SPSS22.0 software.

Results:Serum C1q activity in Obstructive CAD and Non-Obstructive CAD groups was significantly higher than the control group (195.52 ± 48.31 kU/L and 195.42 ± 51.25 kU/L vs. 183.44 ± 31.75 kU/L,P< 0.05). Greater C1q activity was significantly correlated with higher total cholesterol (TC) and triglyceride (TG) levels. C1q activity was associated with an increased Odds Ratio (OR) of CAD (OR = 1.322, 95% CI 1.168–1.496,P< 0.05) and 1-year restenosis after revascularization (the highest OR = 3.544, 95% CI 1.089–12.702,P< 0.05). Complement C1q activity was not correlated with Gensini score in the Obstructive CAD group after adjustment for confounders. C1q activity has low value in predicting the incidence of CAD.

Conclusion:Serum complement C1q activity is associated with obstructive CAD.
Safety and Efficacy of Vitamin K Antagonists vs. Novel Oral Anticoagulants in Patients With Left Ventricular Thrombus: A Meta-Analysis
Authors: Xuan He , Chen Yi-Ming , Dai Yun-Lang , Zhou Jing , Jiang Yu-Feng , Zhou Ya-Feng
Published: April 2021

Aims: A meta-analysis was conducted to evaluate the safety and efficacy of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with left ventricular thrombus (LVT).

Methods and Results: We searched PubMed, Web of Science, and Cochrane Library for cohort studies comparing the use of VKAs vs. NOACs for the treatment of LVT from the earliest date available to September 30, 2020. The predetermined efficacy and safety outcomes included thromboembolic events, resolution of LVT, clinically significant bleedings, and all-cause death. Fixed-effects model was used to estimate the pooled effects. Publication bias analyses and sensitivity analyses were conducted to check the robustness of results. A total of 6 studies enrolling 837 patients (mean age 60.2 ± 1.6 years; 77.2% were male) were included. We found no significant differences in thromboembolic events [relative risk (RR) 1.69, 95% confidence interval (CI) 0.94–3.06, P 0.08, I2 12.7%], the rate of resolution of thrombus (RR 1.08, 95% CI 0.96–1.21, P 0.21, I2 4.8%), and clinically significant bleedings (RR 0.70, 95% CI 0.37–1.32, P 0.27, I2 0%) between the VKAs and NOACs group. Additionally, no significant difference in all-cause mortality was found between the two groups (RR 1.24, 95% CI 0.79–1.96, P 0.35, I2 0.0%). Sensitivity analyses, using the “1-study removed” method, detected no significant differences.

Conclusion: NOACs and VKAs have similar efficacy and safety in treating LVT, prompting the inference that NOACs are the possible alternatives of VKAs in LVT therapy.
Mechanisms of Atherosclerosis Induced by Postprandial Lipemia
Authors: Zhao Yixi , Liu Longtao , Yang Shengjie , Liu Guijian , Pan Limin , Gu Chun , Wang Yang , Li Dan , Zhao Ran , Wu Min
Published: April 2021

Postprandial lipemia plays an important role in the formation, occurrence, and development of atherosclerosis, and it is closely related to coronary heart disease and other diseases involving endothelial dysfunction, oxidative stress, inflammation, and other mechanisms. Therefore, it has become a focus area for further research. The studies on postprandial lipemia mainly include TG, TRL, VLDL, CM, and remnant cholesterol. Diurnal triglyceride patterns and postprandial hyperlipidemia are very relevant and are now insufficiently covered. The possible mechanisms between postprandial lipemia and cardiovascular disease have been reviewed in this article by referring to relevant literature in recent years. The research progress on the effects of postprandial lipemia on endothelial function, oxidative stress, and inflammation is highlighted. The intervention of postprandial lipemia is discussed. Non-medicinal intervention such as diet and exercise improves postprandial lipemia. As medicinal intervention, statin, fibrate, ezetimibe, omega-3 fatty acids, and niacin have been found to improve postprandial lipid levels. Novel medications such as pemafibrate, PCSK9, and apoCIII inhibitors have been the focus of research in recent years. Gut microbiota is closely related to lipid metabolism, and some studies have indicated that intestinal microorganisms may affect lipid metabolism as environmental factors. Whether intervention of gut microbiota can reduce postprandial lipemia, and therefore against AS, may be worthy of further study.
Impact of Leaflet Tethering on Residual Regurgitation in Patients With Degenerative Mitral Disease After Interventional Edge-to-Edge Repair
Authors: Ge Zhenyi , Pan Wenzhi , Li Wei , Wei Lai , Kong Dehong , Pan Cuizhen , Zhou Daxin , Shu Xianhong , Ge Junbo
Published: April 2021

Background: Grade 2+ residual mitral regurgitation (MR 2+) is associated with the recurrence of MR and a lower survival rate in interventional mitral valve (MV) edge-to-edge (EE) repair. We sought to determine the MV anatomic factors affecting residual MR 2+ during interventional EE repair with the ValveClamp system in patients with degenerative MR (DMR).

Methods: In this multicenter study, 62 patients with significant (grade 3+ to 4+) DMR underwent ValveClamp implantation across eight centers from July 2018 to December 2019. Patient clinical, anatomical, and procedural characteristics were prospectively collected and retrospectively analyzed.

Results: A single clamp was implanted in 59 patients, and two clamps were implanted in three patients. Residual MR 2+ was found in 14 patients (22.6%) immediately after the ValveClamp procedure. Patients with residual MR 2+ showed significantly larger preoperative tenting sizes and annular dimensions than the residual MR ≤1+ group. Multivariate analysis identified tenting volume as the major determinant of residual MR 2+ after ValveClamp procedures (odds ratio, 1.410 per 0.1-mL/m2 increase; 95% confidence interval, 1.167–1.705; P < 0.001). Receiver operating characteristic curves identified a tenting volume index ≥0.82 mL/m2 as the optimal cutoff point to predict residual MR 2+ (area under curve, 0.84). Patients with a tenting volume index ≥0.82 mL/m2 were more likely to develop recurrent 3+ MR or undergo MV surgery during short-term follow-up (P < 0.001).

Conclusions: Preoperative assessment of the tenting volume index will help to predict intraoperative residual MR 2+ in patients with DMR receiving EE-based interventional repair. Improvements in the interventional strategy are warranted for sustained MR reduction in patients with DMR with unfavorable anatomy.
Prognostic Significance of B-Type Natriuretic Peptide in Patients With Left Ventricular Thrombus
Authors: An Zhixia , Gao Zhichun , Wang Luyu , Hou Changchun , Zhang Liying , Gong Siming , Rao Rongsheng , Li Chun , Qin Zhexue
Published: April 2021

Background and Aims: There is sparse information on the prognostic value of B-type natriuretic peptide (BNP) for the outcomes in patients with left ventricular thrombus (LVT).

Methods: Patients diagnosed with LVT by transthoracic echocardiography between November 2009 to July 2020 at our institution were included. The endpoints were all-cause mortality and systemic embolism.

Results: Ninety-two subjects were finally included in the study. The mean age of the cohort was 56.73 ± 14.12, and 80.4% of the patients were male. The median BNP (1st quartile−3rd quartile) was 437.5 (112.74–1317.5). The total all-cause mortality rate was 30.44% (28/92), and the 1-year, 2-year, and 3-year cumulative survival rates were 85.4, 75.5, and 66.5%, respectively. Systemic embolism was identified in 10 subjects. COX multivariate analysis showed that Log BNP (HR, 4.16; 95%CI, 1.81–9.56; P = 0.001) and BMI (HR, 0.86; 95%CI, 0.73–0.99; P = 0.048) were significantly associated with all-cause mortality. In addition, patients with BNP levels in the upper median (≥ 437.5 pg/ml) had significantly higher all-cause mortality rate compared to those with lower median BNP (<437.5 pg/ml; P = 0.004). The area under the receiver operating characteristic curve for BNP and all-cause mortality was 0.71. In the linear trend test, BNP quartiles were significantly related to all-cause mortality in all models, and the P-values for trend in models 1, 2, and 3 were 0.005, 0.006, and 0.048, respectively.

Conclusion: BNP level is a prognostic factor for all-cause mortality in LVT patients, and elevated BNP is indicative of a higher risk of LVT.
Late Cenozoic Denudation and Topographic Evolution History of the Lhasa River Drainage in Southern Tibetan Plateau: Insights From Inverse Thermal History Modeling
Authors: Cai Dongxu , Wang Xianyan , Li Guangwei , Zhu Wenbin , Lu Huayu
Published: April 2021

The interaction of surface erosion (e.g., fluvial incision) and tectonic uplift shapes the landform in the Tibetan Plateau. The Lhasa River flows toward the southwest across the central Gangdese Mountains in the southern Tibetan Plateau, characterized by a low-relief and high-elevation landscape. However, the evolution of low-relief topography and the establishment of the Lhasa River remain highly under debate. Here, we collected thermochronological ages reported in the Lhasa River drainage, using a 3D thermokinematic model to invert both late Cenozoic denudation and relief history of the Lhasa River drainage. Our results show that the Lhasa River drainage underwent four-phase denudation history, including two-stage rapid denudation at ∼25–16 Ma (with a rate of ∼0.42 km/Ma) and ∼16–12 Ma (with a rate of ∼0.72 km/Ma). In the latest Oligocene–early Miocene, uplift of the Gangdese Mountains triggered the rapid denudation and the formation of the current main drainage of the Lhasa River. In the middle Miocene, the second stage of the rapid denudation and the high relief were associated with intense incision of the Lhasa River, which is probably due to the enhanced Asian summer monsoon precipitation. This later rapid episode was consistent with the records of regional main drainage systems. After ∼12 Ma, the denudation rate decreases rapidly, and the relief of topography in the central Gangdese region was gradually subdued. This indicates that the fluvial erosion resulting from Asian monsoon precipitation increase significantly impacts on the topographic evolution in the central Gangdese region.
Unraveling Past Submarine Eruptions by Dating Lapilli Tuff-Encrusting Coralligenous (Actea Volcano, NW Sicilian Channel)
Authors: Lodolo Emanuele , Renzulli Alberto , Cerrano Carlo , Calcinai Barbara , Civile Dario , Quarta Gianluca , Calcagnile Lucio
Published: April 2021

The dating of young submarine volcanic eruptions, with their potential generation of tsunamigenic waves, is essential for a reliable hazard assessment. This is particularly relevant in highly populated coastal areas. The scarce knowledge of the underwater environment makes however, this reconstruction challenging. Our study is focused on the NW sector of the Sicilian Channel, where several small- and medium-size volcanic edifices are present. The only documented Surtseyan-type eruption occurred in A.D. 1831, forming the ephemeral Ferdinandea Island. Late Pleistocene to mid-Holocene eruptions have been up to now only hypothesized, and based solely on indirect data. Here we present the first radiocarbon dates of a coralligenous bioconstruction sampled at 34 m water depth from the summit of the Actea volcano, grown up progressively (up to nowadays) on a lapilli tuff deposit. Actea volcano is a recently discovered pyroclastic cone located at only four nautical miles off the SW coast of Sicily. The oldest age of the bioconstructions that started to encrustate the shallow water pyroclastics shortly after their emplacement (7,387 ± 175 cal years B.P.) represents a terminus ante quem, thus testifying a mid-Holocene submarine eruption in this sector of the Sicilian Channel. This method may be effectively used to bridge the gap between historical accounts and the geological record and thus may contribute to a better volcanic hazard assessment of submarine eruption and related phenomena such as tsunamis.
Terrestrial Signature of a Recently-Tidewater Glacier and Adjacent Periglaciation, Windy Glacier (South Shetland Islands, Antarctic)
Authors: Kreczmer Kacper , Dąbski Maciej , Zmarz Anna
Published: April 2021

Contemporary retreat of glaciers is well visible in the West Antarctic region. The aim of this study is to identify, map and quantify terrestrial glacial and periglacial landforms developed in front of Windy Glacier (Warszawa Icefield, King George Island, South Shetlands), which recently turned from being tidewater to land-terminating, and on near-by Red Hill. The study is based on an orthophoto map and a DEM elaborated with a use of images obtained during a UAV BVLOS photogrammetric survey in 2016, Google Earth Pro images from 2006 and an orthophoto map from 1978/1979. The geomorphological map obtained includes 31 types of landforms and water bodies, grouped into: (1) glacial depositional landforms, (2) fluvial and fluvioglacial landforms, (3) littoral and lacustrine landforms, (4) solifluction landforms, (5) other mass movement landforms, (6) patterned ground, (7) debris flows, landslides and mudflows, (8) water bodies, (9) other (bedrock, boulders, glacial ice, snow patches, and not recognized surface). Most area is occupied by glacial lagoon, fluvial and fluvioglacial landforms, not recognized surfaces and littoral landforms. Between 2006 and 2016 the glacier deposited a well-developed patch of fluted moraine with small drumlins. We recognize the glacial-periglacial transition zone between 41 and 47 m GPS height above which solifluction landforms and sorted patterned ground dominate. Advantages of UAV and BVLOS missions are highlighted and problems with vectorization of landforms are discussed. Distinction between flutes and small drumlins is shown on length-to-elongation and length-to-width diagrams and critical reference to previous geomorphological mappings on King George Island is presented.
Numerical Simulation on the Longitudinal Breach Process of Landslide Dams Using an Improved Coupled DEM-CFD Method
Authors: Li Dong-yang , Zheng De-feng , Wu Hao , Shen Yue-qiang , Nian Ting-kai
Published: April 2021

An accurate investigation of the landslide dam breach process is crucial for the understanding the breach mechanism and disaster prediction. However, the numerical research on the landslide dam breach process to date is rarely reported, especially regarding the soil-water flow coupling effect incorporated in the erosion process. This paper presents a numerical investigation on the longitudinal breach process of landslide dams via a coupled discrete element method (DEM) and computational fluid dynamics (CFD) with the volume of fluid (VOF). Moreover, a virtual sphere model is proposed to overcome the computational instability caused by the particle size approaching the mesh size. The accuracy and validity of the improved coupled method are verified using a series of single particle sedimentation cases. By employing this method, the longitudinal breach process of landslide dams featuring different materials and hydrodynamic conditions has been simulated. It is found to satisfactorily reproduce the longitudinal breach process of landslide dams including surface flow erosion, backward erosion, head-cut erosion, and water and sediment rebalance or complete breach. The effects of the inflow discharges and dam materials on the erosion process are systematically resolved. The breach flow can cause the rotation trend of particles and lead to the increase of tangential contact force at the initial stage of the dam breaching. During the breach process, both the strength and density of the force chain continue to attenuate. The results obtained from the improved coupled DEM-CFD simulations can reasonably explain the particle-fluid interaction mechanisms, physical and morphological evolution and breach process at both macroscopic and mesoscopic scales.
Mesenchymal Stem Cell Exosomes as a New Strategy for the Treatment of Diabetes Complications
Authors: Xiong Jiachao , Hu Hao , Guo Rong , Wang Hui , Jiang Hua
Published: April 2021

Diabetes mellitus (DM) is a metabolic disease, now prevalent worldwide, which is characterized by a relative or absolute lack of insulin secretion leading to chronically increased blood glucose levels. Diabetic patients are often accompanied by multiple macrovascular complications, such as coronary heart disease, hypertension, macrovascular arteriosclerosis, and microvascular complications. Microvascular complications include diabetic kidney injury, diabetic encephalopathy, and diabetic foot, which reduce the quality of life and survival status of patients. Mesenchymal stem cell exosomes (MSC-Exos) possess repair functions similar to MSCs, low immunogenicity, and ease of storage and transport. MSC-Exos have been proven to possess excellent repair effects in repairing various organ damages. This study reviews the application of MSC-Exos in the treatment of DM and its common complications. MSC-Exos may be used as an effective treatment for DM and its complications.
Maternal and Neonatal Complications in Patients With Diminished Ovarian Reserve in In-Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles
Authors: Han Shuang , Zhai Yiwei , Guo Qingqing , Qin Yiming , Liu Peihao
Published: April 2021

Background

Diminished ovarian reserve (DOR) is one of the most intractable clinical issues in human reproduction and is reported to be associated with raised risk of recurrent pregnancy loss and aneuploid blastocysts. In this study, we aimed to explore whether DOR was also associated with maternal and neonatal complications in in-vitro fertilization/intracytoplasmic sperm injection cycles.

Methods

A retrospective cohort study including women below 40 years of age who achieved singleton live birth after fresh embryo transfer in in-vitro fertilization/intracytoplasmic sperm injection cycles in a single center from January 2012 to June 2019 was conducted. Participants with DOR, defined as basal follicle-stimulating hormone (FSH) ≥ 10IU/L and antimullerian hormone (AMH) < 1.2ng/ml, were enrolled as the study group. The controls were 1:2 matched by age and body mass index with FSH < 10IU/L and AMH ≥ 1.2ng/ml. Maternal and neonatal complications were compared between the DOR group and the controls.

Results

A total of 579 women, 193 in the DOR group and 386 matched as controls, were included in this study. Compared to controls, the incidence of hypertensive disorders of pregnancy was significantly increased in the DOR group (5.7% vs. 2.1%, P = 0.021). DOR patients also presented slightly higher incidences of preterm birth (10.9% vs. 7.5%, P = 0.174) and low birthweight (6.2% vs. 5.4%, P = 0.704) yet without statistical significances. The incidences of gestational diabetes mellitus and placenta previa were comparable between the two groups.

Conclusion

Compared to women with normal ovarian reserve, women with diminished ovarian reserve might have elevated incidence of hypertensive disorders of pregnancy. Patients with diminished ovarian reserve might need more strict antenatal care.
Development and Assessment of the Monthly Grid Precipitation Datasets in China
Authors: Peng Jiadong , Duan Lijie , Xu Wenhui , Li Qingxiang
Published: April 2021

Based on the high-quality homogenized precipitation data from all 2,419 national weather stations in China, the climatology and anomaly percentage fields are derived, and then the digital elevation model (DEM) is employed to reduce the influence of elevation on the spatial interpolation accuracy of precipitation due to the unique topography in China. Then, the gradient plus inverse distance squared (GIDS) method and the inverse distance squared (IDS) method are used to grid the climatology field and the anomaly percentage field, respectively, and the 0.5 × 0.5° gridded datasets during 1961–2018 in China are obtained by combining them together. The evaluation shows that the mean absolute error (MAE) between the analysis value and the observation is 15.8 mm/month. The MAE in South China is generally higher than that in North China, and the MAE is obviously larger in summer than in other seasons. Specifically, 94.6, 54.4, 4.6, and 53.8% of the MAE are below 10 mm/month in winter (DJF), spring (MAM), summer (JJA), and autumn (SON), respectively, and 99.5, 79.9, 22.8, and 82.1% of them are less than 20 mm/month. The MAE over China in four seasons is 3.8, 13.2, 33.5, and 12.7 mm/month, respectively. This dataset has the potential of broad application prospects in the evaluations of weather and climate models and satellite products.
RETRACTED: NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer
Authors: Jia Xinzhuan , Wei Lan , Zhang Zhengmao
Published: April 2021

Background

Accumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.

Purpose

Our aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.

Methods

The expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and SOX3. Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.

Results

In this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed in vivo. Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted SOX3 mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.

Conclusion

NEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/SOX3 pathway, showing that NEAT1 might be a potential target for OC resistance treatment.
Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region
Authors: Zodanu Gloria Kafui Esi , Oszlánczi Mónika , Havasi Kálmán , Kalapos Anita , Rácz Gergely , Katona Márta , Ujfalusi Anikó , Nagy Orsolya , Széll Márta , Nagy Dóra
Published: April 2021

Congenital heart defects (CHD) are the most common developmental abnormalities, affecting approximately 0.9% of livebirths. Genetic factors, including copy number variations (CNVs), play an important role in their development. The most common CNVs are found on chromosome 22q11.2. The genomic instability of this region, caused by the eight low copy repeats (LCR A-H), may result in several recurrent and/or rare microdeletions and duplications, including the most common, ∼3 Mb large LCR A-D deletion (classical 22q.11.2 deletion syndrome). We aimed to screen 22q11.2 CNVs in a large Hungarian pediatric and adult CHD cohort, regardless of the type of their CHDs. All the enrolled participants were cardiologically diagnosed with non-syndromic CHDs. A combination of multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis and droplet digital PCR methods were used to comprehensively assess the detected 22q11.2 CNVs in 212 CHD-patients. Additionally, capillary sequencing was performed to detect variants in the TBX1 gene, a cardinal gene located in 22q11.2. Pathogenic CNVs were detected in 5.2% (11/212), VUS in 0.9% and benign CNVs in 1.8% of the overall CHD cohort. In patients with tetralogy of Fallot the rate of pathogenic CNVs was 17% (5/30). Fifty-four percent of all CNVs were typical proximal deletions (LCR A-D). However, nested (LCR A-B) and central deletions (LCR C-D), proximal (LCR A-D) and distal duplications (LCR D-E, LCR D-H, LCR E-H, LCR F-H) and rare combinations of deletions and duplications were also identified. Segregation analysis detected familial occurrence in 18% (2/11) of the pathogenic variants. Based on in-depth clinical information, a detailed phenotype–genotype comparison was performed. No pathogenic variant was identified in the TBX1 gene. Our findings confirmed the previously described large phenotypic diversity in the 22q11.2 CNVs. MLPA proved to be a highly efficient genetic screening method for our CHD-cohort. Our results highlight the necessity for large-scale genetic screening of CHD-patients and the importance of early genetic diagnosis in their clinical management.
Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses
Authors: Qiu Xue , Lin Jinyan , Liang Bixiao , Chen Yanbing , Liu Guoqun , Zheng Jing
Published: April 2021

Objective

The aim of this study is the identification of hub genes associated with idiopathic pulmonary arterial hypertension (IPAH).

Materials and Methods

GSE15197 gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by screening IPAH patients and controls. The 5,000 genes with the greatest variances were analyzed using a weighted gene co-expression network analysis (WGCNA). Modules with the strongest correlation with IPAH were chosen, followed by a functional enrichment analysis. Protein–protein interaction (PPI) networks were constructed to identify hub gene candidates using calculated degrees. Real hub genes were found from the overlap of DEGs and candidate hub genes. microRNAs (miRNAs) targeting real hub genes were found by screening miRNet 2.0. The most important IPAH miRNAs were identified.

Results

There were 4,395 DEGs identified. WGCNA indicated that green and brown modules associated most strongly with IPAH. Functional enrichment analysis showed that green and brown module genes were mainly involved in protein digestion and absorption and proteoglycans in cancer, respectively. The top ten candidate hub genes in green and brown modules were identified, respectively. After overlapping with DEGs, 11 real hub genes were identified: EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1. These genes were expressed with significant differences in IPAH versus controls, indicating a high diagnostic ability. The miRNA–gene network showed that hsa-mir-1-3p could associate with IPAH.

Conclusion

EP300, MMP2, CDH2, CDK2, GNG10, ALB, SMC2, DHX15, CUL3, BTBD1, and LTN1 may play essential roles in IPAH. Predicted miRNA hsa-mir-1-3p could regulate gene expression in IPAH. Such hub genes may contribute to the pathology and progression in IPAH, providing potential diagnostic and therapeutic opportunities for IPAH patients.
Senataxin: A New Guardian of the Female Germline Important for Delaying Ovarian Aging
Authors: Homer Hayden A.
Published: April 2021

Early decline in ovarian function known as premature ovarian aging (POA) occurs in around 10% of women and is characterized by a markedly reduced ovarian reserve. Premature ovarian insufficiency (POI) affects ~1% of women and refers to the severe end of the POA spectrum in which, accelerated ovarian aging leads to menopause before 40 years of age. Ovarian reserve refers to the total number of follicle-enclosed oocytes within both ovaries. Oocyte DNA integrity is a critical determinant of ovarian reserve since damage to DNA of oocytes within primordial-stage follicles triggers follicular apoptosis leading to accelerated follicle depletion. Despite the high prevalence of POA, very little is known regarding its genetic causation. Another little-investigated aspect of oocyte DNA damage involves low-grade damage that escapes apoptosis at the primordial follicle stage and persists throughout oocyte growth and later follicle development. Senataxin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage and is well-known for its roles in preventing neurodegenerative disease. Recent findings uncover an important role for SETX in protecting oocyte DNA integrity against aging-induced increases in oxidative stress. Significantly, this newly identified SETX-mediated regulation of oocyte DNA integrity is critical for preventing POA and early-onset female infertility by preventing premature depletion of the ovarian follicular pool and reducing the burden of low-grade DNA damage both in primordial and fully-grown oocytes.
Competing Endogenous RNA Networks in Glioma
Authors: Cen Liang , Liu Ruochen , Liu Wei , Li Qianqian , Cui Hongjuan
Published: April 2021

Gliomas are the most common and malignant primary brain tumors. Various hallmarks of glioma, including sustained proliferation, migration, invasion, heterogeneity, radio- and chemo-resistance, contribute to the dismal prognosis of patients with high-grade glioma. Dysregulation of cancer driver genes is a leading cause for these glioma hallmarks. In recent years, a new mechanism of post-transcriptional gene regulation was proposed, i.e., “competing endogenous RNA (ceRNA).” Long non-coding RNAs, circular RNAs, and transcribed pseudogenes act as ceRNAs to regulate the expression of related genes by sponging the shared microRNAs. Moreover, coding RNA can also exert a regulatory role, independent of its protein coding function, through the ceRNA mechanism. In the latest glioma research, various studies have reported that dysregulation of certain ceRNA regulatory networks (ceRNETs) accounts for the abnormal expression of cancer driver genes and the establishment of glioma hallmarks. These achievements open up new avenues to better understand the hidden aspects of gliomas and provide new biomarkers and potential efficient targets for glioma treatment. In this review, we summarize the existing knowledge about the concept and logic of ceRNET and highlight the emerging roles of some recently found ceRNETs in glioma progression.
Desmoglein-4 Deficiency Exacerbates Psoriasiform Dermatitis in Rats While Psoriasis Patients Displayed a Decreased Gene Expression of DSG4
Authors: Moreno-Sosa Tamara , Sánchez María Belén , Pietrobon Elisa Olivia , Fernandez-Muñoz Juan Manuel , Zoppino Felipe Carlos Martín , Neira Flavia Judith , Germanó María José , Cargnelutti Diego Esteban , Innocenti Alicia Carolina , Jahn Graciela Alma , Valdez Susana Ruth , Mackern-Oberti Juan Pablo
Published: April 2021

Desmogleins are involved in cell adhesion conferring structural skin integrity. However, their role in inflammation has been barely studied, and whether desmoglein-4 modulates psoriasis lesions is completely unknown. In this study, we assessed the impact of desmoglein-4 deficiency on the severity of imiquimod (IMQ)-induced skin inflammation and psoriasiform lesions. To this end, desmoglein-4−/− Oncins France Colony A (OFA) with Sprague–Dawley (SD) genetic background were used. Additionally, human RNA-Seq datasets from psoriasis (PSO), atopic dermatitis (AD), and a healthy cohort were analyzed to obtain a desmosome gene expression overview. OFA rats displayed an intense skin inflammation while SD showed only mild inflammatory changes after IMQ treatment. We found that IMQ treatment increased CD3+ T cells in skin from both OFA and SD, being higher in desmoglein-4-deficient rats. In-depth transcriptomic analysis determined that PSO displayed twofold less DSG4 expression than healthy samples while both, PSO and AD showed more than three-fold change expression of DSG3 and DSC2 genes. Although underlying mechanisms are still unknown, these results suggest that the lack of desmoglein-4 may contribute to immune-mediated skin disease progression, promoting leukocyte recruitment to skin. Although further research is needed, targeting desmoglein-4 could have a potential impact on designing new biomarkers for skin diseases.
Role of Tonsillar Chronic Inflammation and Commensal Bacteria in the Pathogenesis of Pediatric OSA
Authors: Sarmiento Varón Lindybeth , De Rosa Javier , Rodriguez Raquel , Fernández Pablo M. , Billordo L. Ariel , Baz Plácida , Beccaglia Gladys , Spada Nicolás , Mendoza F. Tatiana , Barberis Claudia M. , Vay Carlos , Arabolaza M. Elena , Paoli Bibiana , Arana Eloísa I.
Published: April 2021

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, inex vivocultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+cells, with some IgA+cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01
Authors: Pratoomwun Jirawat , Thomson Paul , Jaruthamsophon Kanoot , Tiyasirichokchai Rawiporn , Jinda Pimonpan , Rerkpattanapipat Ticha , Tassaneeyakul Wichittra , Nakkam Nontaya , Rerknimitr Pawinee , Klaewsongkram Jettanong , Srinoulprasert Yuttana , Pirmohamed Munir , Naisbitt Dean J. , Sukasem Chonlaphat
Published: April 2021

HLA-B*13:01-positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the HLA allele of interest, namely HLA-B*13:01. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive HLA-B*13:01-positive patients. Clones were characterized for antigen specificity and cross-reactivity with structurally related compounds by measuring proliferation and cytokine release. Surface marker expression was characterized via flow cytometry. Mechanistic studies were conducted to assess pathways of T cell activation in response to antigen stimulation. Peripheral blood mononuclear cells from all patients were stimulated to proliferate and secrete IFN-γ with nitroso sulfamethoxazole. All sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones expressed the CD4+ phenotype and strongly secreted IL-13 as well as IFN-γ, granzyme B and IL-22. No secretion of IL-17 was observed. A number of nitroso sulfamethoxazole-specific clones cross-reacted with nitroso dapsone but not sulfamethoxazole whereas sulfamethoxazole specific clones cross-reacted with nitroso sulfamethoxazole only. The nitroso sulfamethoxazole specific clones were activated in both antigen processing-dependent and -independent manner, while sulfamethoxazole activated T cell responses via direct HLA binding. Furthermore, activation of nitroso sulfamethoxazole-specific, but not sulfamethoxazole-specific, clones was blocked with glutathione. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones from hypersensitive patients were CD4+ which suggests that HLA-B*13:01 is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients.
Distinguishing Signal From Noise in Immunopeptidome Studies of Limiting-Abundance Biological Samples: Peptides Presented by I-Ab in C57BL/6 Mouse Thymus
Authors: Nanaware Padma P. , Jurewicz Mollie M. , Clement Cristina C. , Lu Liying , Santambrogio Laura , Stern Lawrence J.
Published: April 2021

Antigen presentation by MHC-II proteins in the thymus is central to selection of CD4 T cells, but analysis of the full repertoire of presented peptides responsible for positive and negative selection is complicated by the low abundance of antigen presenting cells. A key challenge in analysis of limiting abundance immunopeptidomes by mass spectrometry is distinguishing true MHC-binding peptides from co-eluting non-specifically bound peptides present in the mixture eluted from immunoaffinity-purified MHC molecules. Herein we tested several approaches to minimize the impact of non-specific background peptides, including analyzing eluates from isotype-control antibody-conjugated beads, considering only peptides present in nested sets, and using predicted binding motif analysis to identify core epitopes. We evaluated these methods using well-understood human cell line samples, and then applied them to analysis of the I-Ab presented immunopeptidome of the thymus of C57BL/6 mice, comparing this to the more easily characterized splenic B cell and dendritic cell populations. We identified a total of 3473 unique peptides eluted from the various tissues, using a data dependent acquisition strategy with a false-discovery rate of <1%. The immunopeptidomes presented in thymus as compared to splenic B cells and DCs identified shared and tissue-specific epitopes. A broader length distribution was observed for peptides presented in the thymus as compared to splenic B cells or DCs. Detailed analysis of 61 differentially presented peptides indicated a wider distribution of I-Ab binding affinities in thymus as compared to splenic B cells. These results suggest different constraints on antigen processing and presentation pathways in central versus peripheral tissues.
Identification of Immune-Related LncRNA Pairs for Predicting Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma
Authors: Wang Xueying , Cao Kui , Guo Erliang , Mao Xionghui , Guo Lunhua , Zhang Cong , Guo Junnan , Wang Gang , Yang Xianguang , Sun Ji , Miao Susheng
Published: April 2021

Long noncoding RNAs (lncRNAs) have multiple functions with regard to the cancer immunity response and the tumor microenvironment. The prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor currently, and it may be effective to predict the clinical outcome and immunotherapeutic response of HNSCC by immunogenic analysis. Therefore, by using univariate COX analysis and Lasso Cox regression, we identified a signature consisting of 21 immune-related lncRNA pairs (IRLPs) that predicted clinical outcome and Immunotherapeutic response in HNSCC. Specifically, it was associated with immune cell infiltration (i.e., T cells CD4 memory resting, CD8 T cells, macrophages M0, M2, and NK cells), and more importantly this signature was strongly related with immune checkpoint inhibitors (ICIs) [such as PDCD1 (r = -0.35, P < 0.001), CTLA4 (r = -0.26, P < 0.001), LAG3 (r = -0.22, P < 0.001) and HAVCR2 (r = -0.2, P < 0.001)] and immunotherapy-related biomarkers (MMR and HLA). The present study highlighted the value of the 21 IRLPs signature as a predictor of prognosis and immunotherapeutic response in HNSCC.