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Abstract The Qinling Mountains in China frequently experience geological disasters, with large‐scale landslides being particularly prominent, causing severe economic losses to the local area. To gain a comprehensive understanding of the geological disaters distribution in the region, we conducted extensive research on the entire Qinling Mountains, covering an area of approximately 380,000 km2. By employing methods such as literature review, data collection, and interpretation of remote sensing images, we have successfully created a database of landslides. The inventory of landslides includes a total of 169,888 large‐scale landslides, covering a combined area of approximately 1575 km2. The average size of these landslides is approximately 92,734 m2. The scale of these landslides varies widely, with the smallest individual landslide covering an area of 166.25 m2 and the largest reaching 12.9 km2. Upon examining areas with frequent landslides, it was observed that landslides are usually densely distributed along riverbanks or within valleys. Landslide development is also dense in areas prone to frequent historical earthquakes. This comprehensive database provides essential data to support the analysis of spatial distribution patterns of large‐scale landslides in the Qinling Mountains. It also facilitates landslide assessments and serves as a reference for the prevention and control of landslide disasters in the area.

BackgroundUC patients suffer more from colorectal cancer (CRC) than the general population, which increases with disease duration. Early colonoscopy is difficult because ulcerative colitis-associated colorectal cancer (UCAC) lesions are flat and multifocal. Our study aimed to identify promising UCAC biomarkers that are complementary endoscopy strategies in the early stages.MethodsThe datasets may be accessed from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The co-expressed modules of UC and CRC were determined via weighted co-expression network analysis (WGCNA). The biological mechanisms of the shared genes were exported for analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To identify protein interactions and hub genes, a protein-protein interaction network and CytoHubba analysis were conducted. To evaluate gene expression, external datasets and experimental validation of human colon tissues were utilized. The diagnostic value of core genes was examined through receiver operating characteristic (ROC) curves. Immune infiltration analysis was employed to investigate the associations between immune cell populations and hub genes.ResultsThree crucial modules were identified from the WGCNA of UC and CRC tissues, and 33 coexpressed genes that were predominantly enriched in the NF-κB pathway were identified. Two biomarkers (CXCL1 and BCL6) were identified via Cytoscape and validated in external datasets and human colon tissues. CRC patients expressed CXCL1 at the highest level, whereas UC and CRC patients showed higher levels than the controls. The UC cohort expressed BCL6 at the highest level, whereas the UC and CRC cohorts expressed it more highly than the controls. The hub genes exhibited significant diagnostic potential (ROC curve > 0.7). The immune infiltration results revealed a correlation among the hub genes and macrophages, neutrophils and B cells.ConclusionsThe findings of our research suggest that BCL6 and CXCL1 could serve as effective biomarkers for UCAC surveillance. Additionally, they demonstrated a robust correlation with immune cell populations within the CRC tumour microenvironment (TME). Our findings provide a valuable insight about diagnosis and therapy of UCAC.

Abstract Background Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. Methods CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. Results Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin–proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. Conclusion Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin–proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression.

Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti-HCC activity (IC50 value of 2.082 μM) against human HCC HepG2 cells. Moreover, compound 8 significantly suppressed the HepG2 cell multiplication, and triggered G2/M phase arrest of HepG2 cells and their apoptosis. Further mechanistic investigations revealed that compound 8 suppressed tubulin polymerization by directly binding to the colchicine binding site of β-tubulin. Additionally, compound 8 significantly inhibited tumor growth with low toxicity in nude HepG2 tumor-bearing mice, achieving an approximate inhibition rate of 45.73 %. Therefore, compound 8 represents a promising pharmaceutical candidate for HCC management.

IntroductionPaeonia lactiflora contains diverse active constituents and exhibits various pharmacological activities. However, only partial identification of biologically active substances from P. lactiflora has been achieved using low-throughput techniques. Here, the roots of P. lactiflora, namely, Fenyunu (CK), Dafugui (DFG), and Red Charm (HSML), were studied. The primary and secondary metabolites were investigated using ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESIMS/MS).MethodsThe chemical compounds and categories were detected using broadly targeted UPLC-MS/MS. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and hierarchical clustering analysis (HCA) were carried out for metabolites of different varieties of P. lactiflora.ResultsA total of 1237 compounds were detected and classified into 11 categories. HCA, PCA, and OPLS-DA of these metabolites indicated that each variety of P. lactiflora was clearly separated from the other groups. Differential accumulated metabolite analysis revealed that the three P. lactiflora varieties contained 116 differentially activated metabolites (DAMs) involved in flavonoid, flavone, and flavonol metabolism. KEGG pathway analysis revealed that, in 65 pathways, 336 differentially abundant metabolites (DMs) were enriched in the CK and DFG groups; moreover, the type and content of terpenoids were greater in the CK group than in the DFG group. The CK and HSML groups contained 457 DMs enriched in 61 pathways; the type and amount of flavonoids, terpenoids, and tannins were greater in the CK group than in the HSML group. The DFG and HSML groups contained 497 DMs enriched in 65 pathways; terpenoids and alkaloids were more abundant in the HSML variety than in the DFG variety.ConclusionsA total of 1237 compounds were detected, and the results revealed significant differences among the three P. lactiflora varieties. Among the three P. lactiflora varieties, phenolic acids and flavonoids composed the largest and most diverse category of metabolites, and their contents varied greatly. Therefore, CK is suitable for medicinal plant varieties, and DFG and HSML are suitable for ornamental plant varieties. Twelve proanthocyanidin metabolites likely determined the differences in color among the three varieties.

Abstract Objective The safety and efficacy of drug-eluting balloon on the treatment of intracranial atherosclerotic stenosis (ICAS) remain unclear. Here, we present our observation in a cohort study on the safety and efficacy of rapamycin-eluting balloon for patients with ICAS. Methods A total of 80 ICAS patients with stenosis degree of 70–99% were included. All patients were treated with rapamycin-eluting balloon and were followed up for 12 months after operation. Results All patients were successfully treated, where the mean stenosis severity reduced from 85.1 ± 7.6 to 6 ± 4.9%. 8 patients experienced immediate post-operational complications. Two patients passed away during the first month of the follow-up period. Recurrent ischemic syndrome and angiographic restenosis only appeared 7 days after operation. During later follow-up period, none of the patients had clinical angiographic restenosis or needed target vessel revascularization. Conclusion Our data suggest that intracranial stenting with rapamycin-eluting balloon seems to be safe and effective, although more clinical data are needed to support this notion.

This study investigates the prioritization and resource allocation strategies adopted by the coastal local governments of Qingdao, Dalian, and Xiamen in the context of marine regulatory reform aimed at enhancing regulatory efficiency. Data on relevant opinions, departmental requirements, and existing resource allocations were collected through a questionnaire survey. A backpropagation (BP) neural network was then applied to analyze the survey data, prioritize regulatory tasks, and propose resource allocation schemes. The findings demonstrate that integrating machine learning into marine regulation can significantly improve resource utilization efficiency, optimize task execution sequences, and enhance the scientific and refined nature of regulatory work. The BP neural network model exhibited strong predictive capabilities on the training set and demonstrated good generalization abilities on the test set. The performance of the BP neural network model varied slightly across different management levels. For the management level, the accuracy, precision, and recall rates were 85%, 88%, and 82%, respectively. For the supervisory level, these metrics were 81%, 83%, and 78%, respectively. At the employee level, the accuracy, precision, and recall rates were 79%, 81%, and 76%, respectively. These results indicate that the BP neural network model can provide differentiated resource allocation recommendations based on the needs of different management levels. Additionally, the model’s performance was assessed based on the employees’ years of experience. For employees with 0–5 years of experience, the accuracy, precision, and recall rates were 82%, 84%, and 79%, respectively. For those with 5–10 years of experience, the metrics were 83%, 86%, and 80%, respectively. For employees with over 10 years of experience, the accuracy, precision, and recall rates were 85%, 88%, and 82%, respectively. These data further confirm the applicability and effectiveness of the BP neural network model across different experience groups. Thus, the adoption of machine learning technologies for optimizing marine regulatory resources holds significant practical value, aiding in the enhancement of regulatory capacity and effectiveness within coastal local governments.

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

The high-value-added compounds of sea cucumber (Stichopus japonicus) intestine have not been exploited in sea cucumber processing. Here, low molecular weight peptides from the sea cucumber intestine (SCIP) were prepared using papain, and the effect of SCIP on promoting cartilage callus formation and their underlying mechanisms were studied. The results exhibited that the SCIP supplement markedly increased the area of the cartilage callus and ameliorated the early inflammatory environment at the fracture site by modulating the levels of inflammatory factors. Furthermore, SCIP promoted the polarization of M1 to M2 macrophages and finally promoted the differentiation of mesenchymal stem cells into chondrocytes at the fracture site through M2-like macrophage-mediated TGF-family factors and secretion of exosomes. This is the first report that SCIP can promote cartilage callus formation in mice with tibial fractures by promoting the polarization of M1 to M2 macrophages. SCIP might be considered raw material for developing nutraceutical additives.

Background: Hepatocellular carcinoma (HCC), a malignancy with high mortality and recurrence rates, has very limited options for treatment strategies. Dehydrocostus lactone (DL) is the principal quality marker extracted from Aucklandia lappa Decne. and has been demonstrated to possess excellent anticancer activity. The key purpose of this study was to explore the therapeutic effects and potential mechanisms of DL on HCC. Methods: The effect of DL on the cell viability of HCC cell lines (HepG2 and SK-HEP-1) and normal human hepatocyte cell line (L-O2) was examined by CCK8, colony formation, and BeyoClickTMEdU-488 assays; Hoechst 33,258 staining and flow cytometry were utilized to determine the impact of DL on apoptosis; the sensitivity of HCC cells to DL was explored by adding Z-VAD-fmk. In addition, the expression of apoptosis-related proteins Bax, Bcl-2, and PARP was detected by western blotting; the expression of p-H2AX was investigated by western blotting and immunofluorescence staining; cell cycle distribution was observed using flow cytometry; the migration ability and invasiveness of HCC cells were assessed by wound healing assay and transwell assay; immunoblotting was applied to visualize the levels of EMT markers in the two HCC cell lines. Transcriptome sequencing was performed to reveal the underlying mechanisms of DL anti-tumor; western blotting and qRT-PCR were employed to verify the mRNA and protein abundance of p53, p21, and CDK2; HepG2 xenograft in mice was used to test the anti-tumor effects of DL in vivo. Results: DL suppressed the proliferation of HCC cell lines (HepG2 and SK-HEP-1) but had little effect on a normal human liver cell line (L-O2). In addition, DL also induced apoptotic death of the HCC cells by activating Bax and downregulating Bcl-2. The antiproliferative effects of DL could be attributed to increased DNA damage and G1-phase cell cycle arrest. Moreover, DL inhibited HCC cell invasiveness and migration in vitro by decreasing the levels of β-catenin, N-cadherin, and TCF8/ZEB1, and increasing the E-cadherin level. RNA sequencing indicated that DL exerted its anti-hepatoma effects partly via regulation of p53-p21-CDK2 signaling. These results were validated by our in vivo experiments, in which DL markedly suppressed the growth of HepG2 xenografts in a mouse model without any toxic side effects, which corresponded to decreased expression of Ki67 and MMP9 in the tumor tissues. Conclusion: DL has significant anti-cancer effects in both in vivo and in vitro HCC models, and therefore could be further developed as a promising drug for the treatment of HCC.

Introduction Previous studies have explored factors that influence the occurrence of hypothermia in very low/extremely low birth weight (VLBW/ELBW) infants, but the factors associated with hypothermia in VLBW or ELBW infants remain inadequately evaluated due to limited prospective data and inconsistency in study populations. Therefore, it is necessary to systematically evaluate the risk factors of hypothermia in VLBW/ELBW infants in order to provide a theoretical basis for clinical practice. Methods PubMed and other databases were used to search for case-control or cohort studies on factors influencing the occurrence of hypothermia in VLBW/ELBW infants. The search time was set from database creation to June 30th, 2022. Literature screening, quality evaluation, and data extraction were performed independently by two investigators according to predefined inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3. Results A total of 10 papers were finally included in this study and 12 factors were established by meta-analysis: body weight (six papers), failure to keep warm in time (three papers), neonatal resuscitation (seven papers), gestational age (three papers), premature rupture of membranes (three papers), maternal combined complications (four papers), cesarean section (six papers), antenatal steroids (four papers), multiple birth (two papers), small for gestational age (two papers), 1 min Apgar score (three papers), and 5 min Apgar score (three papers). Since only one study included race, age (hour), socio-economic status, and spontaneous labor, these factors could not be fitted into RevMan 5.3 for the analysis. Conclusion Although there were differences in the study design of the included literature, the influencing factors described in each study were relatively similar. The influencing factors identified in this study may contribute to the construction of related intervention strategies for hypothermia in VLBW/ELBW infants.

Cropland-grassland use conversion analysis constitutes crucial research on regional land and global change science, having important implications for regional ecology, food security and the well-being of farmers and herders. However, relevant research is rare, and limited attention has been given to the Tibetan Plateau. Therefore, based on land use raster data, this study utilized the land use conversion matrix method to investigate the spatial and temporal patterns of cropland-grassland conversions during 1990–2020 in the agro-pastoral areas of the Tibetan Plateau.Then this research further identified the key natural geographical and socioeconomic driving forces of cropland-grassland conversions, and examined the mechanisms and spatial heterogeneity of their driving effects by using the geographically weighted regression model. The results showed that cropland-grassland conversions temporally presented the “slow-slow-rapid” changes in 1990–2020 and were spatially clustered in the eastern semipastoral areas. Through mechanisms of ecological equilibrium, resource carrying, population mobility, interest-driven and macroregulation, natural geographical and socioeconomic factors within the cropland-grassland conversion system interacted differently in direction and extent with obvious spatial heterogeneity. Regional increasing rainfall, temperature and topographic relief expanded the extent of cropland use, coupled with the effects of distance to transportation and water sources and increased rural employment, causing widespread and profound land reclamation of grassland-to-cropland, further encouraged by cropland balance policy, while climate change and distance from inhabited settlement and transportation promoted cropland-to-grassland conversion, exacerbated by policies on nature reserve designation and cropland balance, and the fact that rapidly increasing urbanisation in the east accelerated cropland abandonment by diversifying nonfarm employment livelihood strategies. Value added in agriculture and livestock and agricultural machinery inputs tended to restrict cropland-grassland conversions by promoting their internal tapping into intensive and potential use. “Key place-based” and differentiated management policies were proposed to promote sustainable cropland-grassland use conversions and regional development.

Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present study, a homogeneous exopolysaccharide from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ1-1, was obtained. The results of chemical and spectroscopic analyses showed that PJ1-1 was a novel galactomannan with a molecular weight of about 10.24 kDa. The backbone of PJ1-1 was composed of →2)-α-d-Manp-(1→, →4)-α-d-Manp-(1→, →3)-β-d-Galf-(1→ and →2)-β-d-Galf-(1→ units with partial glycosylation at C-3 of →2)-β-d-Galf-(1→ unit. PJ1-1 had a strong hypoglycemic activity in vitro, evaluated using the assay of α-glucosidase inhibition. The anti-diabetic effect of PJ1-1 in vivo was further investigated using mice with type 2 diabetes mellitus induced by a high-fat diet and streptozotocin. The results indicated that PJ1-1 markedly reduced blood glucose level and improved glucose tolerance. Notably, PJ1-1 increased insulin sensitivity and ameliorated insulin resistance. Moreover, PJ1-1 significantly decreased the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, enhanced the level of serum high-density lipoprotein cholesterol and alleviated dyslipidemia. These results revealed that PJ1-1 could be a potential source of anti-diabetic agent.

The invasion of trophoblasts into the uterine decidua and decidual vessels is critical for the formation of placenta. The defects of placentation are related to the etiologies of preeclampsia (PE), fetal growth restriction (FGR), and small-for-gestational age (SGA) neonates. It is possible to predict significant vascular events during pregnancy through uterine artery Doppler (UAD). From the implantation stage to the end of pregnancy, detecting changes in uterine and placental blood vessels can provide a favorable diagnostic instrument for pregnancy complications. This review aims to collect literature about the roles of UAD in pregnancy complications. We consider all relevant articles in English from January 1, 1983 to October 30, 2021. Predicting pregnancy complications in advance allows practitioners to carry out timely interventions to avoid or lessen the harm to mothers and neonates. Administering low-dose aspirin daily before 16 weeks of pregnancy can significantly reduce the incidence of pregnancy complications. From early pregnancy to late pregnancy, UAD can combine with other maternal factors, biochemical indicators, and fetal measurement data to identify high-risk population. The identification of high-risk groups can also lessen maternal mortality. Besides, through moderate risk stratification, stringent monitoring for high-risk pregnant women can be implemented, decreasing the incidence of adversities.

Various long non-coding RNAs (lncRNAs) are closely associated with lung adenocarcinoma (LUAD), playing oncogenic or anti-oncogenic roles in tumorigenesis and progression. Herein, we report a novel lncRNA—long intergenic non-protein coding RNA 1426 (LINC01426)—that has not yet been characterized in LUAD. We note that LINC01426 expression was markedly upregulated in LUAD tissues, and that functional assays verified that LINC01426 knockdown markedly inhibited cell proliferation, migration, and invasion in vitro. Xenografts derived from A549 cells knocked down of LINC01426 had evidently lower tumor weights and smaller tumor volumes. Our study also found that LINC01426 bound to hsa-miR-30b-3p as a competitive endogenous RNA in LUAD. Moreover, LINC01426 affected LUAD wound healing by interacting and combining with AZGP1, and LINC01426 expression was significantly associated with tumor-node-metastasis (TNM) staging and prognosis in patients with LUAD. To summarize, our study elucidates the oncogenic roles of LINC01426 in LUAD tumorigenesis and progression. We think that LINC01426 can serve as a potential diagnostic biomarker and therapeutic target in patients with LUAD.

Abstract Background Treatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF‐MEK‐ERK and PI3K‐AKT‐mTOR. Methods Patients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5‐10.0 mg/d in a 14‐day run‐in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS‐mutated non–small‐cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG‐PET. Efficacy was assessed by CT scans every 6 weeks of combination. Results Of 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose‐limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III° and pneumonia III° occurring after the DLT interval. The metabolic response rate in FDG‐PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively. Conclusions Treatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG‐PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS‐mutant solid tumors.

To solve the disadvantages of the traditional Z-source inverter (ZSI), this paper investigates a series-type switched-inductor Z-source inverter (SSI-ZSI) topology. It not only preserves the advantages of the traditional ZSI, but also improves the voltage gain. On the condition of the same voltage gain, the capacitor voltage stress is reduced, the soft start characteristic can be achieved and the inverter can be immune to the damage of the inrush current. The circuit structure and operating principle are analyzed in detail; the simulation model and the experimental platform are built. The simulation and experimental results verify the rationality and superiority of the circuit topology.

ObjectivesThe aim of this study was to perform a bibliometric analysis of publications related to perinatal palliative care to identify scientific output and research trends at a global level.MethodsThe Web of Science Core Collection database was searched to retrieve publications focusing on perinatal palliative care published between 2001 and 2020. All retrieved publications were identified by title and abstract for their relevance to perinatal palliative care. These eligible publications were extracted from the following data: title, abstract, year, keywords, author, organization, journal and cited literature. VOSviewer software was used to conduct bibliographic coupling, coauthorship, and cooccurrence analyses and to detect publication trends in perinatal palliative care research.ResultsA total of 114 publications concerning perinatal palliative care were included. The annual number of publications has increased dramatically in recent years. The United States has made the largest contribution to this field with the majority of publications (68, 59.6%) and citations (1,091, 70.5%) and with close collaborations with researchers in Canada, Portugal and Australia. Wool C and her institution, York College of Pennsylvania, are the respectively, most prolific author and institution in this field, publishing 18 papers (15.8%). Journal of Palliative Medicine is the leading and main journal in this field. According to the cooccurrence network analysis, five main research topics were identified: the candidates for PPC, service models and forms, framework components, parental perspectives and satisfaction, and challenges and needs of health care providers.ConclusionThe findings of this bibliometric study illustrate the current state and global trends of perinatal palliative care for the past two decades, which will help researchers determine areas of research focus and explore new directions for future research in this field.

Dehydrocostus lactone (DL) is among the representative ingredients of traditional Chinese medicine (TCM), with excellent anticancer, antibacterial, and anti-inflammatory activities. In this study, an advanced strategy based on ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC–Q-Orbitrap HRMS) was integrated to comprehensively explore the metabolic fate of DL in rats. First, prior to data collection, all biological samples (plasma, urine, and feces) were concentrated and purified using solid-phase extraction (SPE) pre-treatment technology. Then, during data collection, in the full-scan (FS) data-dependent acquisition mode, FS-ddMS2 was intelligently combined with FS-parent ion list (PIL)-dynamic exclusion (DE) means for targeted monitoring and deeper capture of more low-abundance ions of interest. After data acquisition, data-mining techniques such as high-resolution extracted ion chromatograms (HREICs), multiple mass defect filters (MMDFs), diagnostic product ions (DPIs), and neutral loss fragments (NLFs) were incorporated to extensively screen and profile all the metabolites in multiple dimensions. As a result, a total of 71 metabolites of DL (parent drug included) were positively or tentatively identified. The results suggested that DL in vivo mainly underwent hydration, hydroxylation, dihydrodiolation, sulfonation, methylation, dehydrogenation, dehydration, N-acetylcysteine conjugation, cysteine conjugation, glutathione conjugation, glycine conjugation, taurine conjugation, etc. With these inferences, we successfully mapped the “stepwise radiation” metabolic network of DL in rats, where several drug metabolism clusters (DMCs) were discovered. In conclusion, not only did we provide a refined strategy for inhibiting matrix effects and fully screening major-to-trace metabolites, but also give substantial data reference for mechanism investigation, in vivo distribution visualization, and safety evaluation of DL.

Cancer is a leading cause of death in worldwide. Growing evidence has shown that docosahexaenoic acid (DHA) has ameliorative effects on cancer. However, the effects of DHA-enriched phosphatidylcholine (DHA-PC) and efficacy differences between DHA-PC, DHA-triglyceride (DHA-TG), and DHA- ethyl esters (DHA-EE) on cancer cells had not been studied. In this study, 95D lung cancer cells in vitro were used to determine the effects and underlying mechanisms of DHA with different molecular forms. The results showed that DHA-PC and DHA-TG treatment significantly inhibited the growth of 95D cells by 53.7% and 33.8%, whereas DHA-EE had no significantly effect. Morphological analysis showed that DHA-PC and DHA-TG prompted promoted cell contraction, increased concentration of cell heterochromatin, vacuolization of cytoplasm, and edema of endoplasmic reticulum and mitochondria. TUNEL and AO/EB staining indicated that both DHA-PC and DHA-TG promoted cell apoptosis, in which DHA-PC performed better than DHA-TG. Mechanistically, DHA-PC and DHA-TG treatment up-regulated the PPARγ and RXRα signal, inhibited the expression of NF-κB and Bcl-2, and enhanced the expression of Bax and caspase-3, thereby promoting cell apoptosis. In conclusion, DHA-PC exerted superior effects to DHA-TG and DHA-EE in promoting apoptosis in 95D non-small-cell lung cancer cells. These data provide new evidence for the application of DHA in treatment of cancer.

A landslide susceptibility map, which describes the quantitative relationship between known landslides and control factors, is essential to link the theoretical prediction with practical disaster reduction measures. In this work, the artificial neural network (ANN) model, a promising tool for mapping landslide susceptibility, was adopted to evaluate the coseismic landslide susceptibility affected by the 2013 Minxian, Gansu, China, Mw5.9 earthquake. The evaluation was based on the landslide inventory of this event containing 6479 landslides, and the terrain, geological and seismic factors from database available. During the analyses, two ANN models were applied: considering the entire factors aforementioned (CS model) and excluding seismic factors above (ES model). The success and predictive rates of ANN models and the cumulative percentage curves of susceptibility maps obtained from the models all indicate that the CS model has a relatively better performance than the ES model. However, the comparison of overlapping susceptibility areas suggests that 52.8% of the very high susceptibility areas derived from the CS model coincide with the ES model; and for the very low susceptibility areas, this proportion is 73.55%. Thus, it can be concluded that the assessment based on existing earthquake-induced landslides and the ES model could provide better background information for seismic landslide susceptibility mapping and disaster prevention.

Successful exploitation of tight sandstone gas is one of the important means to ensure the “increasing reserves and production” of the oil and gas initiative and also one of the important ways to ensure national energy security. To further improve the accuracy of historical matching of field data such as gas production and bottom-hole pressure during the production process of this type of gas reservoir, in this study, a new expression of wellbore pressure for the uniform flow of vertical fractured wells in Laplace space based on the point sink function model of vertical fractures in tight sandstone gas reservoirs is constructed. This innovation is based on a typical production data analysis plot of the Blasingame type that uses the numerical inversion decoupling mathematical equation. After analyzing the pressure and pressure derivative characteristics of each flow stage in the typical curves, a new technique of type-curve matching was proposed. In order to verify the correctness of the model and the application value of the field, based on the previous production data of Sulige Gas Field in China, a new set of production data diagnostic chart of tight sandstone gas reservoir was formed. A case analysis showed that the application of the production data analysis method and data diagnosis plot in the field accurately evaluated the development effect of the tight sandstone gas reservoirs, clarified the scale of effective sand bodies, and provided technical support for optimizing and improving the well pattern and realizing the efficient development of gas fields.

The 2015 Mw 7.8 Gorkha earthquake in Nepal and the Mw 7.3 aftershock triggered at least 22,914 landslides that each had areas ≥500 m2 and lengths and widths ≥20 m. Amongst these landslides, 2,059 had areas >10,000 m2. Analyses of the landslide geometry, using length (L), width (W), height (H, from the crown to toe), reach angle (arctan value of H/L), and aspect ratio (L/W), show that most of the landslides have aspect ratios of 1.6–3.6 and reach angles of 35–45°. The fitting relationship between H and L is H = 0.87L − 11.11. The steep topography is likely the main factor that controls the landslide runout and planar shape. The landslides are divided into 3 geomorphometric categories using the aspect ratio: LS1 (L/W ≤ 2); LS2 (2 < L/W ≤ 4); and LS3 (L/W > 4). Statistical analyses of these categories with the control factors show that the landslide distribution does not relate to the three large-scale geologic faults that traverse the region, roads, accumulative precipitation before the earthquakes, and the small earthquakes that occurred during the 2012–2015 pre-monsoons in the study area. The 3 landslide categories are sensitive to similar conditions related to curvature, slope position, lithology, and peak ground acceleration. In contrast, the effects of elevation, slope angle, slope aspect, and streams on landslide distribution differ. Moreover, massive landslides (with areas >10,000 m2) are more likely to occur on the steeper hill slopes that in the higher elevation settings, which provide more substantial gravitational potential energy and long-runout space. As landslides with different geomorphometric shapes have various susceptible conditions, examining the landslide distribution based on their geometric characteristics provides a new way to study the landslide extent and mechanism.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, which ranks the third leading cause of cancer-related death worldwide. The screening of anti-HCC drug with high efficiency and low toxicity from traditional Chinese medicine (TCM) has attracted more and more attention. As a TCM, Chinese dragon’s blood has been used for the treatment of cardiovascular illness, gynecological illness, skin disorder, otorhinolaryngological illness, and diabetes mellitus complications for many years. However, the anti-tumor effect and underlying mechanisms of Chinese dragon’s blood remain ill-defined. Herein we have revealed that Chinese dragon’s blood EtOAc extract (CDBEE) obviously suppressed the growth of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, CDBEE inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, CDBEE displayed good in vitro anti-angiogenic activity. Importantly, CDBEE treatment significantly blunted the oncogenic capability of HepG2 cells in nude mice. Mechanistically, CDBEE inhibited Smad3 expression in human hepatoma cells and tumor tissues from nude mice. Using RNA interference, we demonstrated that CDBEE exerted anti-hepatoma activity partially through down-regulation of Smad3, one of major members in TGF-β/Smad signaling pathway. Therefore, CDBEE may be a promising candidate drug for HCC treatment, especially for liver cancer with aberrant TGF-β/Smad signaling pathway.

This paper conducted the shale hydration experiments by using four different types of shale outcrop samples. The microscopic pore structure variations before and after hydration were recorded, compared and analyzed through Field Emission Scanned Electronic Microscope (FESEM) with fixed-point observation technique. The results showed that higher content of montmorillonite and carbonate minerals would contribute to the form of dissolution pores and looseness of mineral grains; some critical factors also include original alignment and cementation of mineral grains, and distribution of natural microfractures. Hydration doesn't change the organic pore structure. Almost all dissolution pores originated from mineral intergranular and intragranular pores in matrix, and the dissolution of matrix pores also lead to mineral particles to loose and fall off. When the mineral grains are aligned and compacted along with the bedding-parallel planes, the density of dissolution pores and the number of dissolution pores of small size in bedding-vertical specimens are usually larger than that in bedding-parallel specimens. For the shale samples with few natural microfractures, carbonate minerals may contribute to the generation and propagation of microfractures during hydration. Key words: shale, hydration, microscopic pore structure, mineral component, fixed-point observation

Abstract Background The Gorkha, Nepal Mw 7.8 earthquake of 25 April 2015 triggered a large number of coseismic landslides in a broad area. Two highways, Araniko Highway and Pasang Lhamu Highway, that connect Tibet of China and Nepal, were affected seriously by these landslides. The purpose of this study was to investigate the landslide damage along the two highways, construct a detailed and complete inventory of coseismic landslides in the 5-km buffer area of the Araniko Highway, and perform a regional assessment of landslide hazard in the affected area. Findings Based on visual interpretation of high-resolution satellite images, field investigations, and GIS technology, we investigated the coseismic landslides along the Araniko Highway and Pasang Lhamu Highway. A detailed point-based inventory of coseismic landslides was constructed and spatial distributions of the landslides were analyzed. Correlations between the landslides and five controlling factors, i.e. elevation, slope angle, slope aspect, lithology, and seismic intensity, were illustrated statistically which permitted to assess landslides hazard in a larger rectangle area. Conclusions We examined the coseismic landslides of the 2015 Gorkha earthquake that blocked or damaged the Araniko Highway (117.3 km) and Pasang Lhamu Highway (139.3 km) in Nepal. Results show 35 coseismic landslides damaged the Araniko Highway along a total length 1,415 m. The total volume of them was estimated to be 0.37 million m3. We delineated 89 coseismic landslides that damaged the Pasang Lhamu Highway, where the total length of the damaged or buried roads is about 2,842 m and the total volume of the 89 landslides is about 1.47 million m3. In the 5-km buffer area along the Araniko Highway, we mapped 3,005 landslides caused by the Gorkha earthquake. The landslide number density of the study area is 2.925 km-2. The places with elevations 2,000-2,500 m have the highest landslide concentration. Landslide number density values increase with the slope angle. The slope aspects E and SE correspond to the highest concentrations of coseismic landslides. The underlying bedrock of Precambrian rocks-1 (Pc1) registered the largest landslide number density. The area of seismic intensity IX has a much higher LND value than that of the intensity VIII. We used the weigh index method to perform landslide hazard assessment in the 5-km buffer area on either side of the highway, which shows a success ratio of 85.9%. This method has been applied to a larger area mainly encompassing Rasuwa and Sindhupalchok counties of Nepal.

High salinity in the sewage discharged by coal chemistry companies has become the bottleneck to the development of this industry. In response to the zero discharge standard specified by the Ministry of Environmental Protection, this paper sheds new light on the development of low-cost zero discharge sewage treatment strategy for the coal chemistry industries based on coal chemistry brine TMC hot film coupling separation technology. A pretreatment test is conducted to determine the dosing conditions for any component. On this basis, taking a coal chemistry company as a study case, we conduct a pilot study on the evaporation and crystallization of industrial strong brine on the field. The findings show that PAC and FeSO4 can act as the best flocculant, while the optimal doses of Na2CO3, MgO, CaO, PAM and PAC are 70mg/L, 2500ug/L, 80mg/L, 2mg/L and 120mg/L, respectively; the purity of brine after evaporative crystallization reaches above 95%; the total treatment cost per ton brine is RMB 50.32 /t, so that the economic effect seems obvious. This study provides the clues for coal chemistry companies to reach the zero discharge of sewage and promote the steady development of the coal chemical industry.

After a major earthquake, the rapid identification and mapping of co-seismic landslides in the whole affected area is of great significance for emergency rescue and loss assessment of seismic hazards. In recent years, researchers have achieved good results in research on a small scale and single environment characteristics of this issue. However, for the whole earthquake-affected area with large scale and complex environments, the correct rate of extracting co-seismic landslides remains low, and there is no ideal method to solve this problem. In this paper, Planet Satellite images with a spatial resolution of 3 m are used to train a seismic landslide recognition model based on the deep learning method to carry out rapid and automatic extraction of landslides triggered by the 2018 Iburi earthquake, Japan. The study area is about 671.87 km2, of which 60% is used to train the model, and the remaining 40% is used to verify the accuracy of the model. The results show that most of the co-seismic landslides can be identified by this method. In this experiment, the verification precision of the model is 0.7965 and the F1 score is 0.8288. This method can intelligently identify and map landslides triggered by earthquakes from Planet images. It has strong practicability and high accuracy. It can provide assistance for earthquake emergency rescue and rapid disaster assessment.

The lipid-lowering effects of eicosapentaenoic acid-containing phosphatidylcholine (EPA-PC) from sea cucumber in rat models of non-alcoholic fatty liver disease (NAFLD) were investigated. Oral administration of EPA-PC to orotic acid (OA)-fed mice lowered the liver-to-body weight ratio, serum and hepatic triacylglycerol (TG) and total cholesterol (TC) levels, and high-density lipoprotein cholesterol (HDLC)/TC ratio. EPA-PC also increased the proportion of polyunsaturated fatty acids (PUFA) in serum and hepatic lipids. To elucidate the possible mechanism of action underlying the lipid-lowering effects of EPA-PC, the key enzymes and transcriptional factors involved in fatty acid biosynthesis, transport, and β-oxidation were investigated. The mRNA expressions of SREBP-1c, PPARα, and AMPK, as well as of their target genes, were detected. The results showed that EPA-PC could significantly ameliorate lipid accumulation by suppressing lipid biosynthesis and promoting fatty acid transport and β-oxidation. Overall, our findings revealed that EPA-PC could alleviate NAFLD.

Inflammatory bowel disease (IBD) has been gradually considered a public health challenge worldwide. Sulfated polysaccharides, extracted from seaweed, have been shown to have an anti-inflammatory effect on the disease. In this study, LMW-ulvan, a unique sulfate Ulva polysaccharide with low molecular weight, was prepared using the enzymatic method. The structural characterization of LMW-ulvan and its protective effect on colitis induced by dextran sulfate sodium (DSS) were studied. The results showed that LMW-ulvan with molecular weight of 2.56 kDa consists of 57.23% rhamnose (Rha), 28.76% xylose (Xyl), 7.42% glucuronic acid (GlcA), and 1.77% glucose (Glc). Its backbone contains (1→3,4)-linked Rha, (1→4)-linked Xyl, and (1→4)-linked GlcA with small amounts of (1→4)-linked Rha residues; sulfate substitution was at C-3 of Rha. LMW-ulvan was found to reduce DSS-induced disease activity index, colon shortening, and colonic tissue damage, which were associated with decreased oxidative stresses and inflammation, thus improving the expression of tight junction proteins. These results indicate that LMW-ulvan is able to improve colitis and may be a promising application for IBD.

Gadus morhua eggs contain several nutrients, including polyunsaturated fatty acids, lecithin and glycoproteins. A novel sialoglycopeptide from the eggs of G. morhua (Gm-SGPP) was extracted with 90% phenol and purified by Q Sepharose Fast Flow (QFF) ion exchange chromatography, followed by S-300 gel filtration chromatography. Gm-SGPP contained 63.7% carbohydrate, 16.2% protein and 18.6% N-acetylneuraminic acid. High-performance size exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that Gm-SGPP is a 7000-Da pure sialoglycopeptide. β-elimination reaction suggested that Gm-SGPP contained N-glycan units. Amino acid N-terminal sequence analysis indicated the presence of Ala-Ser-Asn-Gly-Thr-Gln-Ala-Pro amino acid sequence. Moreover, N-glycan was connected at the third Asn location of the peptide chain through GlcNAc. Gm-SGPP was composed of D-mannose, D-glucuronic acid and D-galactose. Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR) and methylation analysis were performed to reveal the structure profile of Gm-SGPP. In vitro results showed that the proliferation activity of MC3T3-E1 cells was significantly promoted by Gm-SGPP. In vivo data revealed that Gm-SGPP increased the calcium and phosphorus content of tibias and promoted longitudinal bone growth in adolescent rats.

AIMS:In this study, we determined whether different subtypes of epidermal growth factor receptor (EGFR) exon19 mutation are associated with the therapeutic effect of EGFR-tyrosine kinase inhibitors (TKIs) on advanced non-small cell lung adenocarcinoma. METHODS:A total of 122 patients with stage III or IV non-small cell lung adenocarcinoma were retrospectively reviewed. Clinical characteristics of these patients, including progression-free survival (PFS) outcome for EGFR-TKI treatment, were analyzed. RESULTS:According to the mutation pattern, we classified the in-frame deletions detected on EGFR Exon19 into three different types: codon deletion (CD), with a deletion of one or more original codons; codon substitution and skipping (CSS), with a deletion of one or two nucleotides but the residues could be translated into a new amino acid without changing following amino acid sequence; CD or CSS plus single nucleotide variant (SNV) (CD/CSS+SNV), exclude CD or CSS, there's another SNV nearby the deletion region. The clinical characteristics of three groups were analyzed and as a result, no significant difference was found. By comparing the average number of missing bases and amino acids of the three mutation subtypes, it could be discovered that the number of missing bases and amino acids of the three mutation subtypes is diverse, and group CSS> group CD> group CD/CSS+SNV. Finally, survival analysis was performed between three groups of patients. The median PFS of group CD, group CSS and group CD/CSS+SNV was 11 months, 9 months and 14 months respectively. There was a distinct difference in the PFS between group CSS and group CD/CSS+SNV (P = 0.035

The 5 September 2018 (UTC time) Mw6.6 earthquake of Tomakomai, Japan has triggered about 10,000 landslides with high density, causing widespread concern. We attempted to establish a detailed inventory of this slope failure and use proper methods to assess landslide susceptibility in the entire affected area. To this end we applied the logistic regression (LR) and the support vector machine (SVM) for this study. Based on high-resolution (3 m) optical satellite images (planet image) before and after the earthquake, we delineated 9295 individual landslides triggered by the earthquake, occupying an area of 30.96 km2. Ten controlling factors were selected for susceptibility analysis, including elevation, slope angle, aspect, curvature, distances to faults, distances to the epicenter, Peak ground acceleration (PGA), distance to rivers, distances to roads and lithology. Using the LR and SVM, two landslide susceptibility maps were produced for the study area. The results show that in the LR model, the success rate is 84.7% between the landslide susceptibility map and the training dataset, and the prediction rate is 83.9% shown by comparing the test dataset and the landslide susceptibility map. In the SVM model, a success rate of 90.9% exists between the susceptibility map and the test samples, and a prediction rate of 87.1% from comparison of the test dataset and the landslides susceptibility map. In comparison, the performance of the SVM is slightly better than the LR model.

Great earthquakes occurring in mountainous areas can trigger large-scale landslides, leading to serious geological disasters. Thus, in recent years, especially after the 2008 Wenchuan earthquake, much attention has been focused on the research about regional risk assessment of seismic landslides in China and elsewhere in the world. Such study is based on the engineering geological analogy, and its purpose is to estimate the risks of earthquake-induced landslides for the regions with the same or similar environment. In light of previous work, such assessment includes 2 tasks: establishment of seismic landslide database and evaluation of potential landslides using mathematical statistics models. The interpretation of regional seismic landslides is the basis for building the landslide database. The common methods for risk assessment include the evidence-weight model, certainty factor method (CF)and information value model, logistic regression model (LR), artificial neural networks (ANN), support vector machine method (SVM), Newmark displacement model,analytic hierarchy process (AHP), and so forth. This paper presents a review on these methods, and an outlook on the advancement of this research field in the future.

Since landslide detection using the combination of AIRSAR data and GIS-based susceptibility mapping has been rarely conducted in tropical environments, the aim of this study is to compare and validate support vector machine (SVM) and index of entropy (IOE) methods for landslide susceptibility assessment in Cameron Highlands area, Malaysia. For this purpose, ten conditioning factors and observed landslides were detected by AIRSAR data, WorldView-1 and SPOT 5 satellite images. A spatial database was generated including a total of 92 landslide locations encompassing the same number of observed and detected landslides, which was divided into training (80%; 74 landslide locations) and validation (20%; 18 landslide locations) datasets. Results of the difference between observed and detected landslides using root mean square error (RMSE) indicated that only 16.3% error exists, which is fairly acceptable. The validation process was performed using statistical-based measures and the area under the receiver operating characteristic (AUROC) curves. Results of validation process indicated that the SVM model has the highest values of sensitivity (88.9%), specificity (77.8%), accuracy (83.3%), Kappa (0.663) and AUROC (84.5%), followed by the IOE model. Overall, the SVM model applied to detected landslides is considered to be a promising technique that could be tested and utilized for landslide susceptibility assessment in tropical environments.

Faba bean (Vicia faba L.), a partially allogamous species, is rich in protein. Condensed tannins limit the use of faba beans as food and feed. Two recessive genes, zt-1 and zt-2, control the zero tannin content in faba bean and promote a white flower phenotype. To determine the inheritance and develop a linkage map for the zt-1 gene in the faba bean germplasm M3290, F2 and F3 progenies were derived from the purple flower and high tannin content genotypes Qinghai12 and zt-1 line M3290, respectively. Genetic analysis verified a single recessive gene for zero tannin content and flower colour. In total, 596 SSR markers and 100 ISSR markers were used to test the polymorphisms between the parents and bulks for the contrasting flower colour via Bulked Segregant Analysis (BSA). Subsequently, six SSR markers and seven ISSR markers were used to genotype the entire 413 F2 population. Linkage analysis showed that the zt-1 gene was closely linked to the SSR markers SSR84 and M78, with genetic distances of 2.9 and 5.8 cM, respectively. The two flanked SSR markers were used to test 34 faba bean genotypes with different flower colours. The closely linked SSR marker SSR84 predicted the zt-1 genotypes with absolute accuracy. The results from the marker-assisted selection (MAS) from this study could provide a solid foundation for further faba bean breeding programmes.