bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Two‐Layer Numerical Model for Coastal Sheet‐Flow Sediment Transport
Authors: Tan Weikai , Yuan Jing 
Published: June 2021

AbstractSheet‐flow sediment transport is an important topic for coastal sediment research. In this study, a two‐layer numerical model is proposed for coastal sheet‐flow sediment transport. The bottom pick‐up layer, in which sediment motion is usually treated as bedload transport, is resolved in an empirical way, so no bedload model is required. For the suspension layer, the model solves the turbulent diffusion equation for sediment concentration, while the hydrodynamic part is described by Reynolds‐averaged Navier‐Stokes equations. The damping of turbulence due to concentration gradient and the hindered settling effect due to particle‐particle interactions are both incorporated in the present model. A predetermined erosion depth is taken as an input for determining the no‐motion sand bed level. This two‐layer model is capable of describing the detailed spatial‐temporal variations of flow velocity and sediment concentration within the sheet‐flow layer, and the model's fidelity is comparable to that of some two‐phase‐flow models. A large campaign of model validation is carried out to demonstrate that the models works well for wave‐driven sheet‐flow sediment transport.
Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner
Authors: Moreno-Fernandez Maria E. , Sharma Vishakha , Stankiewicz Traci E. , Oates Jarren R. , Doll Jessica R. , Damen Michelle S. M. A. , Almanan Maha A. T. A. , Chougnet Claire A. , Hildeman David A. , Divanovic Senad 
Published: June 2021

Abstract
Background
Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice.

Methods
Here, using chow- or high fat diet (HFD)-feeding regimens at standard (TS) and thermoneutral (TN) housing temperatures, the latter to model obesity in female mice, we examined the impact of gender and aging on obesity-associated metabolic derangements and immune responsiveness. Analysis included quantification of: (i) weight gain and adiposity; (ii) the development and severity of glucose dysmetabolism and non-alcoholic fatty liver disease (NAFLD); and (iii) induction of inflammatory pathways related to metabolic dysfunction.

Results
We show that under chow diet feeding regimen, aging was accompanied by increased body weight and white adipose tissue (WAT) expansion in a gender independent manner. HFD feeding regimen in aged, compared to young, male mice at TS, resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under TS housing conditions only aged, but not young, HFD fed female mice developed obesity. At TN however, both young and aged HFD fed female mice developed severe obesity. Independent of gender or housing conditions, aging attenuated the severity of metabolic derangements in HFD-fed obese mice. Tempered severity of metabolic derangements in aged mice was associated with increased splenic frequency of regulatory T (Treg) cells, Type I regulatory (Tr1)-like cells and circulating IL-10 levels and decreased vigor of HFD-driven induction of inflammatory pathways in adipose and liver tissues.

Conclusion
Our findings suggest that aging-associated altered immunological profile and inflammatory vigor may play a dominant role in the attenuation of obesogenic diet-driven metabolic dysfunction.
Drivers and implications of distance decay differ for ectomycorrhizal and foliar endophytic fungi across an anciently fragmented landscape
Authors: Bowman Elizabeth A , Arnold A Elizabeth 
Published: June 2021

Abstract
Fungal communities associated with plants often decrease in similarity as the distance between sampling sites increases (i.e., they demonstrate distance decay). In the southwestern USA, forests occur in highlands separated from one another by warmer, drier biomes with plant and fungal communities that differ from those at higher elevations. These disjunct forests are broadly similar in climate to one another, offering an opportunity to examine drivers of distance decay in plant-associated fungi across multiple ecologically similar yet geographically disparate landscapes. We examined ectomycorrhizal and foliar endophytic fungi associated with a dominant forest tree (Pinus ponderosa) in forests across ca. 550 km of geographic distance from northwestern to southeastern Arizona (USA). Both guilds of fungi showed distance decay, but drivers differed for each: ectomycorrhizal fungi are constrained primarily by dispersal limitation, whereas foliar endophytes are constrained by specific environmental conditions. Most ectomycorrhizal fungi were found in only a single forested area, as were many endophytic fungi. Such regional-scale perspectives are needed for baseline estimates of fungal diversity associated with forest trees at a landscape scale, with attention to the sensitivity of different guilds of fungal symbionts to decreasing areas of suitable habitat, increasing disturbance, and related impacts of climate change.
TRPM2 promotes pancreatic cancer by PKC/MAPK pathway
Authors: Lin Rui , Bao Xunxia , Wang Hui , Zhu Sibo , Liu Zhongyan , Chen Quanning , Ai Kaixing , Shi Baomin 
Published: June 2021

AbstractThe mechanism of pancreatic cancer (PA) is not fully understanded. In our last report, TRPM2 plays a promising role in pancreatic cancer. However, the mechanism of TRPM2 is still unknown in this dismal disease. This study was designed to investigate the role and mechanism of TRPM2 in pancreatic cancer. TRPM2 overexpressed and siRNA plasmid were created and transfected with pancreatic cancer cell line (BxPC-3) to construct the cell model. We employed CCK-8, Transwell, scratch wound, and nude mice tumor-bearing model to investigate the role of TRPM2 in pancreatic cancer. Besides, we collected the clinical data, tumor tissue sample (TT) and para-tumor sample (TP) from the pancreatic cancer patients treated in our hospital. We analyzed the mechanism of TRPM2 in pancreatic cancer by transcriptome analysis, western blot, and PCR. We blocked the downstream PKC/MEK pathway of TRPM2 to investigate the mechanism of TRPM2 in pancreatic cancer by CCK8, scratch wound healing, and transwell assays. Overexpressed TRPM2 could promote pancreatic cancer in proliferation, migration, and invasion ability in no matter the cell model or nude mice tumor-bearing model. TRPM2 level is highly negative correlated to the overall survival and progression-free survival time in PA patients, however, it is significantly increased in PA tissue as the tumor stage increases. The transcriptome analysis, GSEA analysis, western-blot, and PCR results indicate TRPM2 is highly correlated with PKC/MAPK pathways. The experiments of PKC/MEK inhibitors added to TRPM2 overexpressed BxPC-3 cell showed that significant inhibition of PA cells happened in CCK8, transwell, and wound-healing assay. TRPM2 may directly activate PKCα by calcium or indirectly activate PKCε and PKCδ by increased DAG in PA, which promote PA by downstream MAPK/MEK pathway activation.
Long noncoding RNA DGCR5 involves in tumorigenesis of esophageal squamous cell carcinoma via SRSF1-mediated alternative splicing of Mcl-1
Authors: Duan Yuqing , Jia Yunlong , Wang Jiali , Liu Tianxu , Cheng Zishuo , Sang Meixiang , lv Wei , Qin Jing , Liu Lihua 
Published: June 2021

AbstractLong noncoding RNAs (lncRNAs) emerge as essential roles in the regulation of alternative splicing (AS) in various malignancies. Serine- and arginine-rich splicing factor 1 (SRSF1)-mediated AS events are the most important molecular hallmarks in cancer. Nevertheless, the biological mechanism underlying tumorigenesis of lncRNAs correlated with SRSF1 in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we found that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) was upregulated in ESCC clinical samples, which associated with poor prognosis. Through RNA interference and overexpression approaches, we confirmed that DGCR5 contributed to promote ESCC cell proliferation, migration, and invasion while inhibited apoptosis in vitro. Mechanistically, DGCR5 could directly bind with SRSF1 to increase its stability and thus stimulate alternative splicing events. Furthermore, we clarified that SRSF1 regulated the aberrant splicing of myeloid cell leukemia-1 (Mcl-1) and initiated a significant Mcl-1L (antiapoptotic) isoform switch, which contributed to the expression of the full length of Mcl-1. Moreover, the cell-derived xenograft (CDX) model was validated that DGCR5 could facilitate the tumorigenesis of ESCC in vivo. Collectively, our findings identified that the key biological role of lncRNA DGCR5 in alternative splicing regulation and emphasized DGCR5 as a potential biomarker and therapeutic target for ESCC.
Multilevel regulation of Wnt signaling by Zic2 in colon cancer due to mutation of β-catenin
Authors: Xu Zhengshui , Zheng Jianbao , Chen Zilu , Guo Jing , Li Xiaopeng , Wang Xingjie , Qu Chao , Yuan Liyue , Cheng Chen , Sun Xuejun , Yu Junhui 
Published: June 2021

AbstractZinc-finger of the cerebellum 2 (Zic2) is widely implicated in cancers, but the role of Zic2 in tumorigenesis is bilateral. A recent study indicated that Zic2 could render colon cancer cells more resistant to low glucose-induced apoptosis. However, the functional roles of Zic2 in colon cancer and the underlying molecular mechanism remain elusive. Herein, we demonstrated that Zic2 was highly expressed in colon cancer tissues and correlated with poor survival. Knockdown of Zic2 inhibited colon cancer cell growth, arrested the cell cycle transition from G0/G1 to S phase, and suppressed tumor sphere formation in vitro; in addition, silencing Zic2 retarded xenograft tumor formation in vivo. Consistently, ectopic expression of Zic2 had the opposite effects. Mechanistically, Zic2 executed its oncogenic role in colon cancer by enhancing Wnt/β-catenin signaling. Zic2 directly binds to the promoter of Axin2 and transcriptionally represses Axin2 expression and subsequently promotes the accumulation and nuclear translocation of β-catenin. Meanwhile, Zic2 could activate Wnt signaling by interacting with β-catenin. Intriguingly, in HCT116 cells with intrinsic Ser45 mutation of β-catenin, which blocks the degradation-related phosphorylation of β-catenin by CK1, modified Zic2 expression did not affect the protein level of β-catenin. Altogether, our findings uncover a novel multilevel mechanism for the oncogenic activity of Zic2 in colon cancer and suggest Zic2 as a potential therapeutic target for colon cancer patients.
HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3β/JNK signaling pathway
Authors: Lai Wenjie , Zhu Weian , Xiao Chutian , Li Xiaojuan , Wang Yu , Han Yuefu , Zheng Jiayu , Li Yingqiu , Li Mingqiang , Wen Xingqiao 
Published: June 2021

AbstractGenes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3β/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.
Effects of short-chain fatty acids in inhibiting HDAC and activating p38 MAPK are critical for promoting B10 cell generation and function
Authors: Zou Fagui , Qiu Yi , Huang Yilian , Zou Hang , Cheng Xiao , Niu Qingru , Luo Aoxiang , Sun Jianbo 
Published: June 2021

AbstractB10 cells are regulatory B cells capable of producing IL-10 for maintaining immune homeostasis. Dysregulation of B10 cells occurs in autoimmune and inflammatory diseases. Modulation or adoptive transfer of B10 cells is a promising therapeutic strategy. The short-chain fatty acids (SCFAs), the metabolites of microbiota, play a critical role in maintaining immune homeostasis and are the potential drugs for the modulation of B10 cells. It is not clear whether and how SCFAs upregulate the frequency of B10 cells. Here, we found that SCFAs could promote murine and human B10 cell generation in vitro. Upregulation of B10 cells by butyrate or pentanoate was also observed in either healthy mice, mice with dextran sodium sulfate (DSS)-induced colitis, or mice with collagen-induced arthritis. Moreover, SCFA treatment could ameliorate clinical scores of colitis and arthritis. Adoptive transfer of B cells pretreated with butyrate showed more alleviation of DSS-induced colitis than those without butyrate. A further study demonstrates that SCFAs upregulate B10 cells in a manner dependent on their histone deacetylase (HDAC) inhibitory activity and independent of the G-protein-coupled receptor pathway. Transcriptomic analysis indicated that the MAPK signaling pathway was enriched in B10 cells treated with butyrate. A study with inhibitors of ERK, JNK, and p38 MAPK demonstrated that activating p38 MAPK by butyrate is critical for the upregulation of B10 cells. Moreover, HDAC inhibitor has similar effects on B10 cells. Our study sheds light on the mechanism underlying B10 cell differentiation and function and provides a potential therapeutic strategy with SCFAs and HDAC inhibitors for inflammation and autoimmune diseases.
Are Shockley-Read-Hall and ABC models valid for lead halide perovskites?
Authors: Kiligaridis Alexander , Frantsuzov Pavel A. , Yangui Aymen , Seth Sudipta , Li Jun , An Qingzhi , Vaynzof Yana , Scheblykin Ivan G. 
Published: June 2021

AbstractMetal halide perovskites are an important class of emerging semiconductors. Their charge carrier dynamics is poorly understood due to limited knowledge of defect physics and charge carrier recombination mechanisms. Nevertheless, classical ABC and Shockley-Read-Hall (SRH) models are ubiquitously applied to perovskites without considering their validity. Herein, an advanced technique mapping photoluminescence quantum yield (PLQY) as a function of both the excitation pulse energy and repetition frequency is developed and employed to examine the validity of these models. While ABC and SRH fail to explain the charge dynamics in a broad range of conditions, the addition of Auger recombination and trapping to the SRH model enables a quantitative fitting of PLQY maps and low-power PL decay kinetics, and extracting trap concentrations and efficacies. However, PL kinetics at high power are too fast and cannot be explained. The proposed PLQY mapping technique is ideal for a comprehensive testing of theories and applicable to any semiconductor.
B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma
Authors: Ruffin Ayana T. , Cillo Anthony R. , Tabib Tracy , Liu Angen , Onkar Sayali , Kunning Sheryl R. , Lampenfeld Caleb , Atiya Huda I. , Abecassis Irina , Kürten Cornelius H. L. , Qi Zengbiao , Soose Ryan , Duvvuri Umamaheswar , Kim Seungwon , Oesterrich Steffi , Lafyatis Robert , Coffman Lan G. , Ferris Robert L. , Vignali Dario A. A. , Bruno Tullia C. 
Published: June 2021

AbstractCurrent immunotherapy paradigms aim to reinvigorate CD8+ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV+), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV+ HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV+ HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.
Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus
Authors: Hasni Sarfaraz A. , Gupta Sarthak , Davis Michael , Poncio Elaine , Temesgen-Oyelakin Yenealem , Carlucci Philip M. , Wang Xinghao , Naqi Mohammad , Playford Martin P. , Goel Rishi R. , Li Xiaobai , Biehl Ann J. , Ochoa-Navas Isabel , Manna Zerai , Shi Yinghui , Thomas Donald , Chen Jinguo , Biancotto Angélique , Apps Richard , Cheung Foo , Kotliarov Yuri , Babyak Ashley L. , Zhou Huizhi , Shi Rongye , Stagliano Katie , Tsai Wanxia Li , Vian Laura , Gazaniga Nathalia , Giudice Valentina , Lu Shajia , Brooks Stephen R. , MacKay Meggan , Gregersen Peter , Mehta Nehal N. , Remaley Alan T. , Diamond Betty , O’Shea John J. , Gadina Massimo , Kaplan Mariana J. 
Published: June 2021

AbstractIncreased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.
A small molecule HIF-1α stabilizer that accelerates diabetic wound healing
Authors: Li Guodong , Ko Chung-Nga , Li Dan , Yang Chao , Wang Wanhe , Yang Guan-Jun , Di Primo Carmelo , Wong Vincent Kam Wai , Xiang Yaozu , Lin Ligen , Ma Dik-Lung , Leung Chung-Hang 
Published: June 2021

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.
The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets
Authors: Nording Henry , Baron Lasse , Haberthür David , Emschermann Frederic , Mezger Matthias , Sauter Manuela , Sauter Reinhard , Patzelt Johannes , Knoepp Kai , Nording Anne , Meusel Moritz , Meyer-Saraei Roza , Hlushchuk Ruslan , Sedding Daniel , Borst Oliver , Eitel Ingo , Karsten Christian M. , Feil Robert , Pichler Bernd , Erdmann Jeanette , Verschoor Admar , Chavakis Emmanouil , Chavakis Triantafyllos , von Hundelshausen Philipp , Köhl Jörg , Gawaz Meinrad , Langer Harald F. 
Published: June 2021

AbstractPlatelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1−/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.
Replicate sequencing libraries are important for quantification of allelic imbalance
Authors: Mendelevich Asia , Vinogradova Svetlana , Gupta Saumya , Mironov Andrey A. , Sunyaev Shamil R. , Gimelbrant Alexander A. 
Published: June 2021

AbstractA sensitive approach to quantitative analysis of transcriptional regulation in diploid organisms is analysis of allelic imbalance (AI) in RNA sequencing (RNA-seq) data. A near-universal practice in such studies is to prepare and sequence only one library per RNA sample. We present theoretical and experimental evidence that data from a single RNA-seq library is insufficient for reliable quantification of the contribution of technical noise to the observed AI signal; consequently, reliance on one-replicate experimental design can lead to unaccounted-for variation in error rates in allele-specific analysis. We develop a computational approach, Qllelic, that accurately accounts for technical noise by making use of replicate RNA-seq libraries. Testing on new and existing datasets shows that application of Qllelic greatly decreases false positive rate in allele-specific analysis while conserving appropriate signal, and thus greatly improves reproducibility of AI estimates. We explore sources of technical overdispersion in observed AI signal and conclude by discussing design of RNA-seq studies addressing two biologically important questions: quantification of transcriptome-wide AI in one sample, and differential analysis of allele-specific expression between samples.