bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling cascades in the failing heart and emerging therapeutic strategies
Authors: He Xin , Du Tailai , Long Tianxin , Liao Xinxue , Dong Yugang , Huang Zhan-Peng 
Published: April 2022

AbstractChronic heart failure is the end stage of cardiac diseases. With a high prevalence and a high mortality rate worldwide, chronic heart failure is one of the heaviest health-related burdens. In addition to the standard neurohormonal blockade therapy, several medications have been developed for chronic heart failure treatment, but the population-wide improvement in chronic heart failure prognosis over time has been modest, and novel therapies are still needed. Mechanistic discovery and technical innovation are powerful driving forces for therapeutic development. On the one hand, the past decades have witnessed great progress in understanding the mechanism of chronic heart failure. It is now known that chronic heart failure is not only a matter involving cardiomyocytes. Instead, chronic heart failure involves numerous signaling pathways in noncardiomyocytes, including fibroblasts, immune cells, vascular cells, and lymphatic endothelial cells, and crosstalk among these cells. The complex regulatory network includes protein–protein, protein–RNA, and RNA–RNA interactions. These achievements in mechanistic studies provide novel insights for future therapeutic targets. On the other hand, with the development of modern biological techniques, targeting a protein pharmacologically is no longer the sole option for treating chronic heart failure. Gene therapy can directly manipulate the expression level of genes; gene editing techniques provide hope for curing hereditary cardiomyopathy; cell therapy aims to replace dysfunctional cardiomyocytes; and xenotransplantation may solve the problem of donor heart shortages. In this paper, we reviewed these two aspects in the field of failing heart signaling cascades and emerging therapeutic strategies based on modern biological techniques.
Microbiota in health and diseases
Authors: Hou Kaijian , Wu Zhuo-Xun , Chen Xuan-Yu , Wang Jing-Quan , Zhang Dongya , Xiao Chuanxing , Zhu Dan , Koya Jagadish B. , Wei Liuya , Li Jilin , Chen Zhe-Sheng 
Published: April 2022

AbstractThe role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.
Trophic interactions between predatory protists and pathogen-suppressive bacteria impact plant health
Authors: Guo Sai , Tao Chengyuan , Jousset Alexandre , Xiong Wu , Wang Zhe , Shen Zongzhuan , Wang Beibei , Xu Zhihui , Gao Zhilei , Liu Shanshan , Li Rong , Ruan Yunze , Shen Qirong , Kowalchuk George A , Geisen Stefan 
Published: April 2022

AbstractPlant health is strongly impacted by beneficial and pathogenic plant microbes, which are themselves structured by resource inputs. Organic fertilizer inputs may thus offer a means of steering soil-borne microbes, thereby affecting plant health. Concurrently, soil microbes are subject to top-down control by predators, particularly protists. However, little is known regarding the impact of microbiome predators on plant health-influencing microbes and the interactive links to plant health. Here, we aimed to decipher the importance of predator-prey interactions in influencing plant health. To achieve this goal, we investigated soil and root-associated microbiomes (bacteria, fungi and protists) over nine years of banana planting under conventional and organic fertilization regimes differing in Fusarium wilt disease incidence. We found that the reduced disease incidence and improved yield associated with organic fertilization could be best explained by higher abundances of protists and pathogen-suppressive bacteria (e.g. Bacillus spp.). The pathogen-suppressive actions of predatory protists and Bacillus spp. were mainly determined by their interactions that increased the relative abundance of secondary metabolite Q genes (e.g. nonribosomal peptide synthetase gene) within the microbiome. In a subsequent microcosm assay, we tested the interactions between predatory protists and pathogen-suppressive Bacillus spp. that showed strong improvements in plant defense. Our study shows how protistan predators stimulate disease-suppressive bacteria in the plant microbiome, ultimately enhancing plant health and yield. Thus, we suggest a new biological model useful for improving sustainable agricultural practices that is based on complex interactions between different domains of life.
Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis
Authors: Tung Min-Che , Lin Yung-Wei , Lee Wei-Jiunn , Wen Yu-Ching , Liu Yu-Cheng , Chen Ji-Qing , Hsiao Michael , Yang Yi-Chieh , Chien Ming-Hsien 
Published: April 2022

AbstractRenal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies with poor prognoses, since it is largely resistant to chemotherapy, radiotherapy, and targeted therapy. The persistence of cancer stem cells (CSCs) is the major cause of treatment failure with RCC. Recent evidence showed that dopamine receptor D2 (DRD2)-targeting antipsychotic drugs such as penfluridol exert oncostatic effects on several cancer types, but the effect of penfluridol on RCC remains unknown. Here, we uncovered penfluridol suppressed in vitro cell growth and in vivo tumorigenicity of various RCC cell lines (Caki-1, 786-O, A498, and ACHN) and enhanced the Sutent (sunitinib)-triggered growth inhibition on clear cell (cc)RCC cell lines. Mechanistically, upregulation of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) was critical for autophagy-mediated apoptosis induced by penfluridol. Transcriptional inhibition of OCT4 and Nanog via inhibiting GLI1 was important for penfluridol-induced stemness and proliferation inhibition. The anticancer activities of penfluridol on ccRCC partially occurred through DRD2. In clinical ccRCC specimens, positive correlations of DRD2 with GLI1, OCT4, and Nanog were observed and their expressions were correlated with worse prognoses. Summarizing, DRD2 antagonists such as penfluridol induce UPR signaling and suppress the GLI1/OCT4/Nanog axis in ccRCC cells to reduce their growth through inducing autophagy-mediated apoptosis and stemness inhibition. These drugs can be repurposed as potential agents to treat ccRCC patients.
A novel oncogenic seRNA promotes nasopharyngeal carcinoma metastasis
Authors: Tan Yuan , Jiang Chonghua , Jia Qunying , Wang Jing , Huang Ge , Tang Faqing 
Published: April 2022

AbstractNasopharyngeal carcinoma (NPC) is a common malignant cancer in southern China that has highly invasive and metastatic features and causes high mortality, but the underlying mechanisms of this malignancy remain unclear. In this study, we utilized ChIP-Seq to identify metastasis-specific super enhancers (SEs) and found that the SE of LOC100506178 existed only in metastatic NPC cells and powerfully aggravated NPC metastasis. This metastatic SE transcribed into lncRNA LOC100506178, and it was verified as a seRNA through GRO-Seq. Furthermore, SE-derived seRNA LOC100506178 was found to be highly expressed in metastatic NPC cells and NPC lymph node metastatic tissues. Knockdown of seRNA LOC100506178 arrested the invasion and metastasis of NPC cells in vitro and in vivo, demonstrating that seRNA LOC100506178 accelerates the acquisition of NPC malignant phenotype. Mechanistic studies revealed that seRNA LOC100506178 specifically interacted with the transcription factor hnRNPK and modulated the expression of hnRNPK. Further, hnRNPK in combination with the promoter region of MICAL2 increased Mical2 transcription. Knockdown of seRNA LOC100506178 or hnRNPK markedly repressed MICAL2, Vimentin and Snail expression and upregulated E-cadherin expression. Overexpression of seRNA LOC100506178 or hnRNPK markedly increased MICAL2, Vimentin and Snail expression and decreased E-cadherin expression. Therefore, seRNA LOC100506178 may promote MICAL2 expression by upregulating hnRNPK, subsequently enhancing EMT process and accelerating the invasion and metastasis of NPC cells. seRNA LOC100506178 has the potential to serve as a novel prognostic biomarker and therapeutic target in NPC patients.
Proximal tubular RAGE mediated the renal fibrosis in UUO model mice via upregulation of autophagy
Authors: Liu Bohao , Sun Tianshi , Li Huiling , Qiu Shuangfa , Li Yijian , Zhang Dongshan 
Published: April 2022

Abstract
Previous studies reported that RAGE participated in the process of kidney fibrosis, but the function and regulation pathway of RAGE in proximal tubular cells in this process remains unclear. Here, we found that expression of RAGE was increased by TGF-β1 treatment and unilateral ureteral obstruction (UUO). Knock down of RAGE ameliorated renal fibrosis by TGF-β1 treatment, the expression of vimentin, Collagen I&III, and fibronectin are decreased. Mechanistically, RAGE mediated TGF-β1-induced phosphorylation of Stat3 and directly upregulated the Atg7 to increase the level of autophagy, and ultimately resulting in renal fibrosis. Furthermore, PT-RAGE-KO mice reduced kidney fibrosis in UUO model via inhibiting Stat3/Atg7 axis by knocking down RAGE. Furthermore, the above findings were confirmed in kidney of patients with obstructive nephropathy. Collectively, RAGE in proximal tubular cells promotes the autophagy to increase renal fibrosis via upregulation of Stat3/Atg7 axis.
PINK1 ameliorates acute-on-chronic liver failure by inhibiting apoptosis through mTORC2/AKT signaling
Authors: Yin Xuehong , Xue Ran , Wu Jing , Wu Muchen , Xie Bangxiang , Meng Qinghua 
Published: April 2022

AbstractAcute-on-chronic liver failure (ACLF) is a lethal syndrome with a remarkable short-term death rate. Even worse, effective internal medicine therapies are currently lacking. Increasing evidence indicates apoptosis plays a critical role in the progression of liver failure. PINK1 has an essential function in maintaining cell survival. However, the role and underlying mechanism of PINK1 in apoptosis in ACLF are incompletely understood. Herein, our team discovered that PINK1 remarkably improved ACLF, featured by a reduction in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an amelioration in the gross and microscopy histopathology appearance of hepatic tissues. Meanwhile, PINK1 affected cleaved caspase-3 expression via mTORC2/AKT, and this effect was eliminated after further intervention with Rictor or AKT. Overall, these findings indicate that PINK1 participates in the regulation of multiple biological functions, including hepatic cell growth and apoptosis in ACLF via the mTORC2/AKT signaling pathway. The present research offers a solid theory-wise foundation for the clinic applications of PINK1 as a valid target for ACLF treatment to reverse or postpone the development of ACLF.
ANGPTL4 negatively regulates the progression of osteosarcoma by remodeling branched-chain amino acid metabolism
Authors: Lin Shanyi , Miao Yu , Zheng Xu , Dong Yang , Yang Qingcheng , Yang Quanjun , Du Silin , Xu Jun , Zhou Shumin , Yuan Ting 
Published: April 2022

AbstractAngiopoietin-like-4 (ANGPTL4), a secreted glycoprotein that is mainly known as a regulator in lipid metabolism, now, is also indicated to be involved in the regulation of cancer progression and metastasis. However, little is known about not only biological functions, but also underlying mechanism of ANGPTL4 in the progression of osteosarcoma (OS). Here, we discovered that ANGPTL4 is downregulated in OS, and is associated with branched-chain amino acid (BCAA) metabolism. The BCAAs (valine, leucine, and isoleucine) are essential amino acids that play an important role in metabolic regulation. Aberrant BCAA metabolism is also found in various cancers and is associated with tumor progression, including proliferation, invasion, and metastasis. In this study, we indicated that the negative relation between the expression of ANGPTL4 and BCAA catabolism in OS samples and cell lines. The knockdown of ANGPTL4 in OS cells resulted in the accumulation of BCAAs, which in turn activated the mTOR signaling pathway, enhancing OS cell proliferation. Thus, reduced expression of ANGPTL4 is associated with the progression of OS. Taken together, our results demonstrated that the ANGPTL4/BCAA/mTOR axis is an important pathway in OS progression and may be a potential therapeutic target to slow OS progression.
Hyperglycemia induces gastric carcinoma proliferation and migration via the Pin1/BRD4 pathway
Authors: Yu Jianjian , Hu Dan , Wang Laicheng , Fan Zongcheng , Xu Changsheng , Lin Yunchai , Chen Xin , Lin Jinxiu , Peng Feng 
Published: April 2022

AbstractDiabetes is a potential risk factor for gastric cancer (GC). Pin1, a peptidyl–prolyl cis/trans isomerase, promotes GC cell proliferation and migration. The role and underlying mechanism of the Pin1/BRD4 axis in hyperglycemia-induced proliferation and migration of GC cells were analyzed in vivo and in vitro. Proliferation and migration of GC cells were measured; Pin1 and BRD4 expression of the cell cycle were determined. Pin1 and BRD4 were downregulated by transfecting Pin1 shRNA lentivirus into GC cells and JQ1-intervention GC cells. Tumor formation and lung metastasis were assessed in vivo. Inhibition of Pin1 and BRD4 significantly suppressed high-glucose (HG)-induced GC cell proliferation and migration. HG enhanced G1/S cell-cycle transition, associated with increased Pin1 and BRD4 expression. Silencing Pin1 significantly downregulated the expression of BRD4 and NAP1L1 and upregulated that of P21 in GC cells. In vivo studies indicated that hyperglycemia promotes tumor growth and lung metastasis by inducing Pin1 and BRD4 expression. Thus, Pin1/BRD4 plays an important role in hyperglycemia-promoted tumor growth. The significance of these findings toward improved prognosis of diabetic patients with GC cannot be underestimated.
IFN-γ+ cytotoxic CD4+ T lymphocytes are involved in the pathogenesis of colitis induced by IL-23 and the food colorant Red 40
Authors: Chen Lili , He Zhengxiang , Reis Bernardo S. , Gelles Jesse D. , Chipuk Jerry Edward , Ting Adrian T. , Spicer Julie A. , Trapani Joseph A. , Furtado Glaucia C. , Lira Sergio A. 
Published: April 2022

AbstractThe food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin (IL)-23. This immune response is mediated by CD4+ T cells, but mechanistic insights into how these CD4+ T cells trigger and perpetuate colitis have remained elusive. Here, using single-cell transcriptomic analysis, we found that several CD4+ T-cell subsets are present in the intestines of colitic mice, including an interferon (IFN)-γ-producing subset. In vivo challenge of primed mice with Red 40 promoted rapid activation of CD4+ T cells and caused marked intestinal epithelial cell (IEC) apoptosis that was attenuated by depletion of CD4+ cells and blockade of IFN-γ. Ex vivo experiments showed that intestinal CD4+ T cells from colitic mice directly promoted apoptosis of IECs and intestinal enteroids. CD4+ T cell-mediated cytotoxicity was contact-dependent and required FasL, which promoted caspase-dependent cell death in target IECs. Genetic ablation of IFN-γ constrained IL-23- and Red 40-induced colitis development, and blockade of IFN-γ inhibited epithelial cell death in vivo. These results advance the understanding of the mechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ+ cytotoxic CD4+ T cells as a new potential therapeutic target for colitis.
Combined levator and frontalis muscle advancement flaps for recurrent severe congenital ptosis
Authors: Diab Mostafa Mohammed M. , Abd-Elaziz Khaled , Allen Richard C. 
Published: April 2022

Abstract
Background
To evaluate the outcomes of combined levator resection and frontalis muscle advancement for surgical management of recurrent severe congenital ptosis.

Design
Retrospective, nonrandomized interventional case series.

Methods
A retrospective review was performed of patients who underwent combined levator resection and frontalis muscle advancement for recurrent congenital ptosis between 2017 and 2020. Inclusion criteria were levator function of 4 mm or less and margin reflex distance 1 (MRD1) of 0 mm or less. Main outcome measures were postoperative MRD 1, lagophthalmos, lash angle, and grades of eyelid contour and crease. The outcomes were assessed by reviewing medical charts and photographs.

Results
Thirty-one patients (35 eyelids) met the inclusion criteria. The mean preoperative MRD1 was −1.14 ± 1.56 mm, which improved to 3.93 ± 0.52 mm with an average lagophthalmos of 0.91 ± 0.74 mm at the last follow-up. A total of 91.4% of eyelids had excellent eyelid contour, crease, and eyelash angle at the final follow-up. One eyelid required revision surgery. There were no other significant complications.

Conclusions
For poor function recurrent congenital ptosis, combining levator resection and frontalis muscle advancement is an effective method that results in long-term correction with cosmetically pleasing outcomes and minimal complications.
Hotspots of the stokes rotating circulation in a large marginal sea
Authors: Gan Jianping , Kung Hiusuet , Cai Zhongya , Liu Zhiqiang , Hui Chiwing , Li Junlu 
Published: April 2022

AbstractMarginal seas, surrounded by continents with dense populations, are vulnerable and have a quick response to climate change effects. The seas typically have alternatively rotating layered circulations to regulate regional heat and biogeochemical transports. The circulations are composed of dynamically active hotspots and governed by the couplings between unique extrinsic inflow and intrinsic dynamic response. Ambiguities about the circulations’ structure, composition, and physics still exist, and these ambiguities have led to poor numerical simulation of the marginal sea in global models. The South China Sea is an outstanding example of a marginal sea that has this typical rotating circulation. Our study demonstrates that the rotating circulation is structured by energetic hotspots with large vorticity arising from unique dynamics in the marginal sea and is identifiable by the constraints of Stokes Theorem. These hotspots contribute most of the vorticity and most of energy needed to form and maintain the rotating circulation pattern. Our findings provide new insights on the distinguishing features of the rotating circulation and the dominant physics with the objectives of advancing our knowledge and improving modeling of marginal seas.
Defect-mediated ripening of core-shell nanostructures
Authors: Zhang Qiubo , Peng Xinxing , Nie Yifan , Zheng Qi , Shangguan Junyi , Zhu Chao , Bustillo Karen C. , Ercius Peter , Wang Linwang , Limmer David T. , Zheng Haimei 
Published: April 2022

AbstractUnderstanding nanostructure ripening mechanisms is desirable for gaining insight on the growth and potential applications of nanoscale materials. However, the atomic pathways of nanostructure ripening in solution have rarely been observed directly. Here, we report defect-mediated ripening of Cd-CdCl2 core-shell nanoparticles (CSN) revealed by in-situ atomic resolution imaging with liquid cell transmission electron microscopy. We find that ripening is initiated by dissolution of the nanoparticle with an incomplete CdCl2 shell, and that the areas of the Cd core that are exposed to the solution are etched first. The growth of the other nanoparticles is achieved by generating crack defects in the shell, followed by ion diffusion through the cracks. Subsequent healing of crack defects leads to a highly crystalline CSN. The formation and annihilation of crack defects in the CdCl2 shell, accompanied by disordering and crystallization of the shell structure, mediate the ripening of Cd-CdCl2 CSN in the solution.
Deletion and tandem duplications of biosynthetic genes drive the diversity of triterpenoids in Aralia elata
Authors: Wang Yu , Zhang He , Ri Hyok Chol , An Zeyu , Wang Xin , Zhou Jia-Nan , Zheng Dongran , Wu Hao , Wang Pengchao , Yang Jianfei , Liu Ding-Kun , Zhang Diyang , Tsai Wen-Chieh , Xue Zheyong , Xu Zhichao , Zhang Peng , Liu Zhong-Jian , Shen Hailong , Li Yuhua 
Published: April 2022

AbstractAraliaceae species produce various classes of triterpene and triterpenoid saponins, such as the oleanane-type triterpenoids in Aralia species and dammarane-type saponins in Panax, valued for their medicinal properties. The lack of genome sequences of Panax relatives has hindered mechanistic insight into the divergence of triterpene saponins in Araliaceae. Here, we report a chromosome-level genome of Aralia elata with a total length of 1.05 Gb. The loss of 12 exons in the dammarenediol synthase (DDS)-encoding gene in A. elata after divergence from Panax might have caused the lack of dammarane-type saponin production, and a complementation assay shows that overexpression of the PgDDS gene from Panax ginseng in callus of A. elata recovers the accumulation of dammarane-type saponins. Tandem duplication events of triterpene biosynthetic genes are common in the A. elata genome, especially for AeCYP72As, AeCSLMs, and AeUGT73s, which function as tailoring enzymes of oleanane-type saponins and aralosides. More than 13 aralosides are de novo synthesized in Saccharomyces cerevisiae by overexpression of these genes in combination. This study sheds light on the diversity of saponins biosynthetic pathway in Araliaceae and will facilitate heterologous bioproduction of aralosides.
Temperature estimation of a pair of trapped ions
Authors: de Sá Neto O. P. , Costa H. A. S. , Prataviera G. A. , de Oliveira M. C. 
Published: April 2022

AbstractWe apply estimation theory to a system formed by two interacting trapped ions. By using the Fisher matrix formalism, we introduce a simple scheme for estimation of the temperature of the longitudinal vibrational modes of the ions. We use the ions interaction to effectively infer the temperature of the individual ions, by optimising the interaction time evolution and by measuring only over one of the ions. We also investigate the effect of a non-thermal reservoir over the inference approach. The non-classicality of one of the ions vibrational modes, introduced due to a squeezed thermal reservoir, does not directly affect the inference of the individual temperatures, although allowing the modes to be entangled. To check actual experimental conditions, we analyze the temperature inference under heating due to surface-electrode noise.