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Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.

IntroductionDeep vein thrombosis (DVT) is a common venous thromboembolic disease with an unclear pathogenesis. miR-10b-5p expression was increased in DVT patients and this study aims to determine the functional mechanism of miR-10b-5p in DVT development.Material and methodsRats were injected with miR-10b-5p and MFG-E8 related plasmids before DVT model establishment. The thrombus length, weight and size were measured. TUNEL staining was used to detect apoptosis of vascular endothelial cells. Cell transfection on HUVECs was performed to achieve miR-10b-5p suppression or/and MFG-E8 suppression. The cell viability, migration, angiogenesis ability and cell apoptosis of HUVECs were measured. The expression levels of miR-10b-5p, MFG-E8, JAK/STAT signal pathway related proteins in peripheral blood of DVT patients, rats, and HUVECs were detected by RT-qPCR and Western blot.ResultsDVT patients increased expression of miR-10b-5p and decreased expression of MFG-E8. miR-10b-5p expression was negatively correlated with MFG-E8. Rats with inhibition of miR-10b-5p or overexpression of MFG-E8 had less deteriorated thrombus, decreased thrombus length and weight, cell apoptosis and suppressed ratio of p-JAK/JAK and p-STAT3/STAT3. miR-10b-5p can negatively regulate and target MFG-E8 in HUVECs. HUVECs transfected with miR-10b-5p inhibitor had increased cell viability, migration and angiogenesis ability as well as suppressed cell apoptosis and decreased p-JAK/JAK and p-STAT3/STAT3 ratio, while co-transfection of miR-10b-5p inhibitor and MFG-E8 suppression can partially counteract the miR-10b-5p inhibitor.ConclusionsElevated expression of miR-10b-5p and decreased MFG-E8 expression were found in peripheral blood of DVT patient and inhibition on miR-10b-5p or overexpression of MFG-E8 can attenuate DVT in rat models.

Background Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease with high genetic heterogeneity. SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles, dysphagia, lingual fibrillation, pyramidal tract sign, and extrapyramidal system sign. However, it rarely has clinical manifestations similar to Parkinson-like symptoms, and is even rarer in patients sensitive to dopamine. We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing, which was completely different from the initial diagnosis. Case summary A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility. At the beginning of the disease, she presented with anxiety and sleep disorder. At the later stage, she presented with gait disorder, which was similar to Parkinson's disease. Her medical history was unremarkable, but her mother, grandmother, and uncle all had similar illnesses and died due to inability to take care of themselves and related complications. Laboratory and imaging examinations showed no abnormalities, but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm, respectively. Her symptoms fluctuated during the daytime, and we initially diagnosed her with dopamine-responsive dystonia. After treatment with low-dose levodopa, the patient's symptoms were significantly improved, but the final genetic diagnosis was SCA3. Conclusion SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.

Background Inflammation is an essential component of liver diseases. Paeoniflorin (PF), a monoterpenoid component derived from peony root (Paeonia lactiflora Pall.), has anti-inflammatory, immunoregulatory, and hepatoprotective activities. However, whether PF affects liver inflammation and its underlying mechanisms is unclear. In this study, we investigated the effects of PF on lipopolysaccharide (LPS)-induced inflammation in LO2 cells and the underlying molecular mechanism. Methods LPS was used to induce inflammation. After PF pretreatment for 2 h, the cells were treated with PF and LPS. Cell counting kit-8 was used to measure cell viability. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were tested by Enzyme-linked immunosorbent assay. Western blot was used to evaluate TNF-α, Ras homolog family member A (RhoA), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1β proteins expression. Results In LPS-induced LO2 cells, PF reduced TNF-α and IL-6 inflammatory cytokine production in a dose-dependent manner. LPS-induced TNF-α expression was also suppressed by PF. In addition, PF significantly inhibited LPS-induced RhoA activation (P = .0014). Finally, PF suppressed LPS-induced NLRP3 inflammasome activation by downregulating NLRP3, ASC, caspase-1, and IL-1β expression. Conclusion These findings suggest that PF alleviates inflammation induced by LPS and further suggest the anti-inflammatory effect of PF may follow via reduced RhoA and NLRP3 inflammasome activity.

Landslide prediction is critical for the early warning of a landslide occurrence. Existing stepwise landslide displacement prediction methods are mostly data-driven approaches. However, these models are vulnerable to overfitting, and the low-dimensional numerical features with high numerical volatility prevent them from precisely quantifying the rapid increase in daily displacement in the acceleration phase. Therefore, we propose a semantic information-driven stepwise landslide displacement prediction model comprising an identifier in the displacement phase and a predictor in the acceleration phase. First, the raw landslide monitoring data are converted into text-based semantic information and the semantic features are fused. Subsequently, based on the daily displacement and velocity, we propose a sliding window phase division algorithm to divide the stepwise landslide phase into stationary and acceleration phases. Finally, the landslide displacement phase is identified, and the displacement during the acceleration phase is predicted. The experimental results of the model on the Xinpu and Qingshi landslides in Chongqing, China, show that the proposed model exploits the derived semantic information to identify the landslide acceleration phase qualitatively, and predict the daily displacement of the acceleration phase quantitatively. The proposed model provides a valuable reference for the early warning of stepwise landslides.

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking matched donors. To test whether pretransplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group ( 1000 ng/mL) and the high-SF group (≥ 1000 ng/mL). We found that SF ≥1000 ng/mL independently increased the risk of grade II-IV aGvHD (HR = 2.596; 95% CI, 1.304-5.167, P = 0.007) and grade III-IV aGvHD (HR = 3.350; 95% CI, 1.162-9.658, P = 0.025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, P = 0.168). The two-year overall survival (85.29 ± 3.89% vs 92.00% ± 3.84%, P = 0.746) and failure-free survival (83.23% ± 4.08% vs 83.37% ± 6.27%, P = 0.915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (P = 0.056). In conclusion, elevated pretransplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA.

To select adaptive InSAR data source for difficult area to improve the deformation results, an InSAR data selection strategy is proposed in this paper. The topographic factors and InSAR data source parameters are combined to integrate the sensor’s viewing angle, terrain slope and aspect into a local incident angle, then the backscattering coefficients from 8 scenes of Sentinel-1 data in the study area is extracted, and the average value of the backscattering coefficients according to the classification results of the local incident angle is calculated. By analyzing the relationship between the origin InSAR data and the local incident angles, a local incident angle threshold is obtained. Finally, the credible area which is the important evidence in data source selection is obtained, which can be used as the mask data in the subsequent data processing to assist in improving the accuracy of the monitoring result.

Tigecycline is one of important antimicrobial agents for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence and prevalence of plasmid-mediated tigecycline resistance gene

The emergence and prevalence of the tet(X) gene and its variants in the environment and in clinical settings constitute a growing concern for public health worldwide. Accordingly, the tigecycline resistance gene variant tet(X6) is widely detected in Proteus spp. and Acinetobacter spp. rather than Enterobacteriaceae, while the underpinning behind this phenomenon is still unclear. To investigate the mechanisms underlying this distinct phenomenon, we assessed the fitness of the engineered plasmid pBAD-tet(X6) in different host bacteria by monitoring their growth curves, relative fitness and the ability of biofilm formation, as well as virulence in a Galleria mellonella model. MIC and qRT-PCR analysis indicated the successful expression of the tet(X6) gene in these strains in the presence of l-arabinose. Furthermore, we found that pBAD-tet(X6) displayed the lowest fitness cost in P. mirabilis compared with that in E. coli or S. Enteritidis, suggesting the fitness difference of tet(X6)-bearing plasmids in different host bacteria. Consistently, the carriage of pBAD-tet(X6) remarkably reduced the biofilm production and virulence of E. coli or S. Enteritidis. These findings not only indicate that the fitness cost difference elicited by the tet(X6) gene may be responsible for its selectivity in host bacteria but also sheds new insight into the dissemination of antibiotic resistance genes (ARGs) in clinical and environmental isolates.

Background It has been reported that long non-coding RNA (lncRNA) LIPCAR is involved in the progression of atherosclerosis. However, the mechanism underlying the effects of LIPCAR on regulating the occurrence and development of atherosclerosis remains unclear. Methods Reverse transcription-quantitative PCR was performed to detect the levels of LIPCAR in the plasma of patients with atherosclerosis and in THP-1 macrophages. THP-1 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) to induce foam cell formation. Furthermore, Transwell assay was carried out to evaluate the migration ability of vascular smooth muscle cells (VSMCs). Results The expression of LIPCAR in the plasma of patients with atherosclerosis was significantly higher compared with that in healthy subjects, while LIPCAR knockdown notably reversed ox-LDL-induced THP-1 cell apoptosis. In addition, LIPCAR was upregulated in exosomes derived from THP-1 cells treated with ox-LDL (THP-1/ox-LDL Exo). Furthermore, THP-1/ox-LDL Exo significantly increased the expression levels of CDK2 and proliferative cell nuclear antigen in human VSMCs, while these effects were reversed following LIPCAR silencing. Conclusion The results of the present study suggested that exosomal lncRNA LIPCAR derived from ox-LDL modified THP-1 cells could promote the progression of atherosclerosis. Therefore, LIPCAR may be considered as a novel biomarker for the development of new strategies to treat atherosclerosis.

To investigate the mechanism underpinning the effect of Chaihu Shugan San ( CHSGS) on major depressive disorder (MDD).We searched the compound components of from seven herbal ingredients of CHSGS from TCMSP, SymMap, ETCM, NPASS databases, and the chemical structure of the compound from PubChem, and collected the compound targets from TCMSP and TargetNet databases, and MDD-related targets from DiseaseGene Network. We established protein-protein interaction in the STRING database. Through gene mapping, topology analysis and enrichment analysis, the core targets and pathways of CHSGS for MDD, and the involved biological processes (BP), cell components (CC), and molecular functions (MF) were predicted.We collected a total of 1135 CHSGS compounds. After screening by ADME standards and the five rules of Ribinski, we obtained 99 different chemical components with different chemical structures, and related targets of 183 different CHSGS compounds. In the DiseaseGene Network, a total of 740 relevant targets for MDD were collected. Through gene mapping and topological analysis, 62 related targets of CHSGS for MDD, 24 targets with topological Chinese herbal medicine were obtained. Through enrichment analysis, 10 relevant pathways and 3 core pathways were obtained with the involvement of 127 BP, 27 CC, and 43 MF.There are multiple targets and signaling pathways are involved in the action of CHSGS in the treatment of MDD.

To investigate the targets and mechanisms of action of Qingkailing injection (，QKL) in the treatment of cholestatic hepatitis.A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis, respectively. The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit. The org.Hs.eg.db and clusterProfiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which explored biological functions and pathways of potential targets. Targets were then visualized using Cytoscape 3.6.0 software.We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis. QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms, 15 cellular component and 29 molecular function terms. The mechanism of QKL action was mainly related to tumor necrosis factor, mitogen-activated protein kinase, and PI3K-Akt signaling pathways.The treatment of cholestatic hepatitis by QKL involved multiple targets, biological functions, and signaling pathways that are closely associated with the disease.

The salt overly sensitive (SOS) signal transduction pathway is one of the most highly studied salt tolerance pathways in plants. However, the molecular mechanism of the salt stress response in Tamarix hispida has remained largely unclear. In this study, five SOS genes (ThSOS1–ThSOS5) from T. hispida were cloned and characterized. The expression levels of most ThSOS genes significantly changed after NaCl, PEG6000, and abscisic acid (ABA) treatment in at least one organ. Notably, the expression of ThSOS3 was significantly downregulated after 6 h under salt stress. To further analyze ThSOS3 function, ThSOS3 overexpression and RNAi-mediated silencing were performed using a transient transformation system. Compared with controls, ThSOS3-overexpressing transgenic T. hispida plants exhibited greater reactive oxygen species (ROS)-scavenging capability and antioxidant enzyme activity, lower malondialdehyde (MDA) and H2O2 levels, and lower electrolyte leakage rates under salt stress. Similar results were obtained for physiological parameters in transgenic Arabidopsis, including H2O2 and MDA accumulation, superoxide dismutase (SOD) and peroxidase (POD) activity, and electrolyte leakage. In addition, transgenic Arabidopsis plants overexpressing ThSOS3 displayed increased root growth and fresh weight gain under salt stress. Together, these data suggest that overexpression of ThSOS3 confers salt stress tolerance on plants by enhancing antioxidant enzyme activity, improving ROS-scavenging capability, and decreasing the MDA content and lipid peroxidation of cell membranes. These results suggest that ThSOS3 might play an important physiological role in salt tolerance in transgenic T. hispida plants. This study provides a foundation for further elucidation of salt tolerance mechanisms involving ThSOSs in T. hispida.

The mining and reforestation plan is of great significance for mines re green and environmental protection, and the three-dimensional visualization and quantitative assessment play an important role in the effective evaluation of the mining plan. In this paper, aiming at breaking through the limitation of the traditional two-dimensional design and plan, making up for the defect of the planning based on virtual reality technology, a new planning method is proposed utilizing the UAV oblique photography and the 3D geographic information technology. Moreover, through the secondary development, the design scheme and plan are integrated with the 3D real scene mining model. Based on the visual and quantitative comparison and analysis of the mining scheme, a reasonable mining and re green scheme is arranged, providing a more intuitive and reliable qualitative and quantitative analysis method for objective evaluation and comparison of the optimal mining and reforestation decision making.

In this paper, we propose a method for building extraction, mainly focusing on the large density variety in terrestrial laser scanning (TLS) data. The density of projected points is calculated based on the polar grid instead of the commonly used regular grid and adaptive thresholds are generated for each cell to filter non-building cells and avoid parameter tuning. The points in the remaining cells are grouped into different clusters and the planar ratio of each cluster is calculated based on dimensionality features. Finally, the points in the clusters with planar ratio larger than 75% are recognized as building points. The method is compared with a regular grid based method in an urban TLS data with the buildings distributed at a distance of 60 to 350m and the results show that the proposed method has a better performance on the detection of buildings which are more than 200 meters away in this data.

Highlights ● The functional characterization of ThSOS genes were investigated by bioinformatics analysis and molecular characterization. ● ThSOS genes can respond to abiotic stresses (salt and drought) and hormone treatment (ABA). ● ThSOS3 gene overexpression increased ROS-scavenging capability and decreasing lipid peroxidation in cell membrane. ● ThSOS3 could effectively enhance the tolerance of transgenic T. hispida and Arabidopsis to salt stress.

We consider the Fife-Greenlee problem \begin{document}$e^2\triangle u + \bigl(u-\mathbf{a}(y)\bigr)(1-u^2) =0 ~~~ \mbox{in}\ Ω,~~~~~~~\frac{\partial u}{\partialν} = 0 ~~~ \mbox{on}\ \partialΩ,$ \end{document} where \begin{document}$Ω$\end{document} is a bounded domain in \begin{document}${\mathbb R}^2$\end{document} with smooth boundary, \begin{document}$\epsilon>0$\end{document} is a small parameter, \begin{document}$ν$\end{document} denotes the unit outward normal of \begin{document}$\partialΩ$\end{document} . Let \begin{document}$Γ = \{y∈ Ω: \mathbf{a}(y) = 0 \}$\end{document} be a simple smooth curve intersecting orthogonally with \begin{document}$\partialΩ$\end{document} at exactly two points and dividing \begin{document}$Ω$\end{document} into two disjoint nonempty components. We assume that \begin{document}$-1\, on \begin{document}$Ω$\end{document} and \begin{document}$\triangledown\mathbf{a}≠ 0$\end{document} on \begin{document}$Γ$\end{document} , and also some admissibility conditions between the curves \begin{document}$Γ$\end{document} , \begin{document}$\partialΩ$\end{document} and the inhomogeneity \begin{document}${\mathbf a}$\end{document} hold at the connecting points. We can prove that there exists a solution \begin{document}$u_{\epsilon}$\end{document} such that: as \begin{document}$\epsilon → 0$\end{document} , \begin{document}$u_{\epsilon}$\end{document} approaches \begin{document}$+1$\end{document} in one part, while tends to \begin{document}$-1$\end{document} in the other part, except a small neighborhood of \begin{document}$Γ$\end{document} .

Liver cancer is the fourth leading cause of cancer death worldwide, and hepatocellular carcinoma (HCC) accounts for the greatest proportion of these deaths. Baicalein, a flavonoid isolated from the root of Scutellariae radix, is considered a potential candidate to treat HCC. However, the underlying molecular mechanisms remain poorly understood. In the present study, a network pharmacological approach was combined with microarray data (GSE95504) acquired from the Gene Expression Omnibus database to reveal the therapeutic mechanisms of action of baicalein at a systemic level. We identified 38 baicalein targets and 76 differently expressed genes (DEGs) following treatment with baicalein, including 55 upregulated and 21 downregulated genes. The DEGs were significantly enriched in the biological functions of apoptosis, endoplasmic reticulum stress, and PERK-mediated unfolded protein response. Protein-protein interaction (PPI) network construction and topological screening revealed a core module of PPIs including two baicalein targets, TP53 and CDK1, and two downregulated DEGs, HSPA1A and HSPA1B. Expression and survival data for these genes in the module derived from Gene Expression Profiling Interactive Analysis (GEPIA) were subjected to Kaplan–Meier analysis of overall survival and disease-free survival. Overexpression of CDK1, BRCA1, TUBB, HSPA1A, HSPA1B, and HSPA4 was associated with significantly worse overall survival, while overexpression of CDK1, CLU7, BRCA1, and TUBB was associated with significantly worse disease-free survival. These data suggest that baicalein exerts therapeutic effects against HCC via a PPI network involving TP53, CDK1, HSPA1A, and HSPA1B.

Being influenced by fluctuating precipitation, long-term rainfall-induced landslide displacement prediction could be unstable. To solve this problem, a rainfall-induced landslide displacement prediction model based on Attention Mechanism Neural Network(AMNN) is proposed in this paper. Firstly, accumulative landslide displacement is decomposed into the trend term and the periodic term. Secondly, multivariate linear regression is adopted to fit the trend term and AMNN is used to predict the periodic term. Finally, the accumulative predicted displacement is given by summing the trend and the periodic displacement components. In this paper, one rainfall-induced landslide in Chongqing province, China was taken as an example to evaluate the designed model. Compared with some existing methods, the model proposed in this paper can captured the correlation between each feature sequence and the predicted term with higher prediction accuracy of 0.97 Goodness of Fit. The results of this paper are believed to be contributive to further rainfall-induced landslide forecast and early warning research.

Reasonable mining scheme is of great significance for safety and efficiency of mining activity and environmental protection. In view of the limitation that the traditional mine surveying and mapping method can’t provide accurate terrain data for the mining scheme design, moreover, the common mining design software can’t be combined with the 3D real scene mining situation for scheme analysis and evaluation, this paper proposed a design method based on 3D real scene model by combining the UAV Remote sensing technology and 3D geographic information technology. This method can make the mining design agree with the demand of mining efficiency and environmental protection, improving the rationality of mining design.

To relieve difficulties in traditional manual way of crag investigation in complex topographic area, this article supposed an unmanned aerial vehicle(UAV) oblique photography technique to acquire the accurate three dimensional (3D) spatial information of crags. Taking a crag on high steep mountain in southwest China as an example, using adapted UVA flight route plan to acquire oblique images, after data processing, the high precision 3D measurable model of the crag is produced. This method satisfies the need of constructing the real-time three-dimensional model of the crag with the non-contact data acquisition method, making up the limitation of the traditional ground investigation, providing a solution for the accurate investigation of the high steep crag.