Progressive Destabilization and Triggering Mechanism Analysis Using Multiple Data for Chamoli Rockslide of 7 February 2021

A catastrophic rockslide occurred on 7 February 2021 in Chamoli area in the high Himalaya. In the absence of field data, multiple satellites data of decade span have been used to investigate and understand the progressive destabilization of rockslide body. A 3D geometric model was developed using geospatial information about geology, terrain, and ice cover to understand the triggering mechanism. Several causes are uncovered as: the pronounced long-term change of land surface temperature facilitated local permafrost degradation and led to ice cover shrinking since 2010; the occurrence of ice avalanche nearby in 2016 accompanying with sidewall-to-bedrock fracturing enhanced the ice segregation beneath the rockslide body; and the development of side cracks in early February 2021 led to dropping of side support and percolating of surface water. Heavy precipitation several days before favoured the destabilization, top-corner cracks developing and top-side bergschrund breaking abruptly two days before, and ice strength reduction owing air temperature rising few hours before the event triggered finally the rockslide. The frequent disasters such as cloudburst, extreme precipitation, landslides, and snow avalanches responding to global warming and climate change in the Himalayan region needs immediate attention to the chain-like geohazards and collaborative observation with satellites and other platforms

Query translation from XPath to SQL in the presence of recursive DTDs

We study the problem of evaluating xpath queries over xml data that is stored in an rdbms via schema-based shredding. The interaction between recursion (descendants-axis) in xpath queries and recursion in dtds makes it challenging to answer xpath queries using rdbms. We present a new approach to translating xpath queries into sql queries based on a notion of extended XP ath expressions and a simple least fixpoint (lfp) operator. Extended xpath expressions are a mild extension of xpath, and the lfp operator takes a single input relation and is already supported by most commercial rdbms. We show that extended xpath expressions are capable of capturing both dtd recursion and xpath queries in a uniform framework. Furthermore, they can be translated into an equivalent sequence of sql queries with the lfp operator. We present algorithms for rewriting xpath queries over a (possibly recursive) dtd into extended xpath expressions and for translating extended xpath expressions to sql queries, as well as optimization techniques. The novelty of our approach consists in its capability to answer a large class of xpath queries by means of only low-end rdbms features already available in most rdbms, as well as its flexibility to accommodate existing relational query optimization techniques. In addition, these translation algorithms provide a solution to query answering for certain (possibly recursive) xml views of xml data. Our experimental results verify the effectiveness of our techniques. © 2009 Springer-Verlag

Identification of a regulatory pathway inhibiting adipogenesis via RSPO2

Healthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142$^{+}$ cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis

Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis

To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders. However, whether cells can directly sense FAs to maintain cellular lipid homeostasis is unknown. Here we report a sensing mechanism for cellular FAs based on peroxisomal degradation of FAs and coupled with reactive oxygen species (ROS) production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for non-alcoholic fatty liver disease progression using genetic and pharmacological approaches to alter ROS levels in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation-mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders

Mantle Flow Underneath the South China Sea Revealed by Seismic Anisotropy

It Has Long Been Established that Plastic Flow in the Asthenosphere Interacts Constantly with the overlying Lithosphere and Plays a Pivotal Role in Controlling the Occurrence of Geohazards Such as Earthquakes and Volcanic Eruptions. Unfortunately, Accurately Characterizing the Direction and Lateral Extents of the Mantle Flow Field is Notoriously Difficult, Especially in Oceanic Areas Where Deployment of Ocean Bottom Seismometers (OBSs) is Expensive and Thus Rare. in This Study, by Applying Shear Wave Splitting Analyses to a Dataset Recorded by an OBS Array that We Deployed between Mid-2019 and Mid-2020 in the South China Sea (SCS), We Show that the Dominant Mantle Flow Field Has a NNW-SSE Orientation, Which Can Be Attributed to Mantle Flow Extruded from the Tibetan Plateau by the Ongoing Indian-Eurasian Collision. in Addition, the Results Suggest that E-W Oriented Flow Fields Observed in South China and the Indochina Peninsula Do Not Extend to the Central SCS

The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway

Identification of pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis based on comprehensive bioinformatics analysis and machine learning

Objective:Bioinformatics methods were applied to investigate the pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis (ACAS) and provide new insights for the treatment of this disease.Methods:The study utilized five ACAS datasets (GSE100927, GSE11782, GESE28829, GSE41571, and GSE43292) downloaded from the NCBI GEO database. The first four datasets were combined as the training set (n = 99), while GSE43292 (n = 64) was used as the validation set. Difference analysis and functional enrichment analysis were then performed on the training set. The pathogenic targets of ACAS were screened by protein-protein interaction networks and MCODE analyses, combined with three machine learning algorithms. The results were next verified by analysis of inter-group differences and ROC curve analysis. Next, immune-related function and immune cell correlation analyses were performed, and plaques of human ACAS were applied to verify the results via immunohistochemistry (IH) and immunofluorescence (IF). Finally, the competing endogenous RNAs (ceRNA) and transcription factors (TFs) regulatory networks of the characterized genes were constructed.Results:A total of 177 differentially expressed genes were identified, including 67 genes downregulated and 110 genes upregulated. Gene set enrichment analysis revealed that five pathways were active in the experimental group, including xenograft rejection, autoimmune thyroid disease, graft-versus-host disease, leishmaniasis infection, and lysosomes. Four key genes were identified, with C3AR1 being upregulated and FBLN5, PPP1R12A, and TPM1 being downregulated. The analysis of inter-group differences demonstrated that the four characterized genes were differentially expressed in both the control and experimental groups. The ROC analysis showed that they had high AUC values in both the training and validation sets. Therefore, a predictive ACAS patient nomogram model based on the screened genes was established. Correlation analysis revealed a positive correlation between C3AR1 expression and neutrophils, which was further validated in IH and IF. One or multiple lncRNAs may compete with the characterized genes for binding miRNAs. Additionally, each characterized gene interacts with multiple TFs.Conclusion:Four pivotal genes were screened, and relevant ceRNA and TFs were predicted. These molecules may exert a crucial role in ACAS and serve as potential biomarkers and therapeutic targets

A Rice Gene of De Novo Origin Negatively Regulates Pathogen-Induced Defense Response

How defense genes originated with the evolution of their specific pathogen-responsive traits remains an important problem. It is generally known that a form of duplication can generate new genes, suggesting that a new gene usually evolves from an ancestral gene. However, we show that a new defense gene in plants may evolve by de novo origination, resulting in sophisticated disease-resistant functions in rice. Analyses of gene evolution showed that this new gene, OsDR10, had homologs only in the closest relative, Leersia genus, but not other subfamilies of the grass family; therefore, it is a rice tribe-specific gene that may have originated de novo in the tribe. We further show that this gene may evolve a highly conservative rice-specific function that contributes to the regulation difference between rice and other plant species in response to pathogen infections. Biologic analyses including gene silencing, pathologic analysis, and mutant characterization by transformation showed that the OsDR10-suppressed plants enhanced resistance to a broad spectrum of Xanthomonas oryzae pv. oryzae strains, which cause bacterial blight disease. This enhanced disease resistance was accompanied by increased accumulation of endogenous salicylic acid (SA) and suppressed accumulation of endogenous jasmonic acid (JA) as well as modified expression of a subset of defense-responsive genes functioning both upstream and downstream of SA and JA. These data and analyses provide fresh insights into the new biologic and evolutionary processes of a de novo gene recruited rapidly