Explore the vast range of titles available.

Background Diabetic patients have a higher risk factor for colorectal cancer (CRC) metastasis. Stearoyl-CoA desaturase 1 (SCD1) , the main enzyme responsible for producing monounsaturated fatty acids(MUFA) from saturated fatty acids, is frequently deregulated in both diabetes and CRC . The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown. Methods SCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer.ucsc.edu/ ). CRC cell lines stably transfected with SCD1 shRNAs or vector were established to investigate the role of SCD1 in modulating migration and invasion of CRC cells. A glucose concentration gradient was set to investigate regulation of SCD1 in CRC relevant to diabetic conditions. Results The clinical data analysis showed high expression of SCD1 in CRC tissues with a negative correlation with the prognosis of CRC. In vitro experiments revealed that SCD1 increased CRC progression through promoting epithelial–mesenchymal transition (EMT) . Lipidomic analysis demonstrated that SCD1 increased MUFA levels and MUFA administration could rescue migration and invasion defect of CRC cells induced by SCD1 knockdown. Furthermore, SCD1-mediated progression of CRC was promoted by carbohydrate response-element binding protein (ChREBP) in response to high glucose. Mechanistically, hyperglycemia-SCD1-MUFA induced CRC cell migration and invasion by regulating PTEN. Conclusions Our findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.

ObjectiveThis study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy.MethodsInitially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis.ResultsIn 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb–IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions.ConclusionPerioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients’ recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions.Trial registration numberNCT04297202.

Climate change (CC) and land use/cover change (LUCC) are the main drivers of streamflow change. In this study, the effects of CC and LUCC on streamflow regime as well as their spatial variability were examined by using the Distributed Hydrology Soil Vegetation Model (DHSVM) for the Beichuan River Basin in the northeast Tibetan Plateau. The results showed that CC increased annual and maximum streamflow in the upstream but decreased them in the downstream. CC also enhanced minimum streamflow in the whole river basin and advanced the occurrence of daily minimum streamflow. Temperature change exerted greater influence on streamflow regime than wind speed change did in most situations, but the impact of wind speed on streamflow reflected the characteristics of accumulative effects, which may require more attention in future, especially in large river basins. As for LUCC, cropland expansion and reservoir operation were the primary reasons for streamflow reduction. Cropland expansion contributed more to annual mean streamflow change, whereas reservoir operation greatly altered monthly streamflow pattern and extreme streamflow. Reservoir regulation also postponed the timing of minimum streamflow and extended durations of average, high, and low streamflow. Spatially, CC and LUCC played predominant roles in the upstream and the downstream, respectively.

Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 ( NRP1 ) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.

Figure S3 Effect of glucose on SCD1-induced migration and invasion ability of SW116 cells. Figure S3 Effect of glucose on SCD1-induced migration and invasion ability of SW116 cells. Incorrect Fig. 7 Fig. 7 figure 1 PTEN plays an important role in SCD1-induced migration and invasion of CRC cells. a, b Representative Western blot and quantification data of PTEN proteins of OA-treated HCT116 (a) and Caco2 (b) cells. c Representative Western blot and quantification data of PTEN in HCT116 cells transfected with siRNAs for PTEN (si1 and si2) or Caco2 cells ectopically expressing PTEN. d Representative photographs of transwell assays of shSCD1 or shNC-transfected HCT116 after being transfected with PTEN siRNAs (siPTEN) or negative control scramble siRNAs (siNC). The scale bar is 100 μm. h, i Histograms show the number of migrated (h) and invasive (i) Caco2 cells Full size image Correct Fig. 7 Fig. 7 figure 2 PTEN plays an important role in SCD1-induced migration and invasion of CRC cells. a, b Representative Western blot and quantification data of PTEN proteins of OA-treated HCT116 (a) and Caco2 (b) cells. c Representative Western blot and quantification data of PTEN in HCT116 cells transfected with siRNAs for PTEN (si1 and si2) or Caco2 cells ectopically expressing PTEN. d Representative photographs of transwell assays of shSCD1 or shNC-transfected HCT116 after being transfected with PTEN siRNAs (siPTEN) or negative control scramble siRNAs (siNC). Figure S3 Effect of glucose on SCD1-induced migration and invasion ability of SW116 cells. Figure S3 Effect of glucose on SCD1-induced migration and invasion ability of SW116 cells.

Variations in vegetation are closely related to climate change, but understanding of their characteristics and causes remains limited. As a typical semi-humid and semi-arid cold plateau region, it is important to understand the knowledge of long term Normalized Difference Vegetation Index (NDVI) variations and find the potential causes in the source region of the Yangtze River. Based on four tree-ring width chronologies, the regional mean NDVI for July and August spanning the period 1665–2013 was reconstructed using a regression model, and it explained 43.9% of the total variance during the period 1981–2013. In decadal, the reconstructed NDVI showed eight growth stages (1754–1764, 1766–1783, 1794–1811, 1828–1838, 1843–1855, 1862–1873, 1897–1909, and 1932–1945) and four degradation stages (1679–1698, 1726–1753, 1910–1923, and 1988–2000). And based on wavelet analysis, significant cycles of 2–3 yr and 3–8 yr were identified. In additional, there was a significant positive correlation between the NDVI and the Palmer Drought Severity Index (PDSI) during the past 349 yr, and they were mainly in phase. However, according to the results of correlation analysis between different grades of drought/wet and NDVI, there was significant asymmetry in extreme drought years and extreme wet years. In extreme drought years, NDVI was positively correlated with PDSI, and in extreme wet years they were negatively correlated.

Adjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative.

Tire wear particles (TWP), generated by the friction of vehicle tires against the road surface during driving, accelerating, and braking, are transferred to aquatic ecosystems via rainfall runoff. These particles exhibit toxicological effects on aquatic organisms and have become the focus of research in environment and health. Microalgae, as primary producers in the marine food web, play a crucial role in aquatic ecosystems and are inevitably affected by TWP. However, the toxic mechanisms by which TWP influences microalgae's normal physiological activities remain unclear. Given this, Microcystis aeruginosa , a common species in freshwater ecosystems, was selected as an experimental species in this study to investigate the effects of different concentrations of TWP (5, 25, 50, 100 mg/L) on its growth, chlorophyll a content, photosynthetic activity, extracellular polymer secretion (EPS), and oxidative stress. The results showed that TWP had a concentration-dependent inhibitory effect on the growth, chlorophyll content, and photosynthetic activity of Microcystis aeruginosa , with maximum inhibition rates reaching 89.4%, 98.44% and 92.9%, respectively. TWP stimulated the secretion of the EPS of Microcystis aeruginosa , and the secretion of the EPS increased with the increase of the concentration of TWP. TWP also promoted the polysaccharide-to-protein ratio in the EPS with a rise of 27.3–38.5%. Meanwhile, the three-dimensional fluorescence-area-integral analysis indicated that the ratio of the protein-like component was generally higher than the one of the humic-like component in the EPS of Microcystis aeruginosa . The significant increase in superoxide dismutase (SOD) activity under 50 and 100 mg/L TWP exposure predicted a substantial activation of oxidative stress. In contrast, the significant increase in the malondialdehyde (MDA) content indicated the overproduction of reactive oxygen species (ROS) and may lead to lipid peroxidation damage. These findings will help us better understand the toxic mechanisms by which TWP induces effects in microalgae.

Evaluating groundwater inflow is greatly significant for ensuring the safety and economy during foundation pit dewatering with suspended waterproof curtains. However, there are limited applicable methods to predict the groundwater inflow of circle foundation pit with waterproof curtains in deep unconfined aquifers. In this study, based on Darcy’s law and the continuity of water flow, the impact of suspended waterproof curtains on groundwater seepage was initially analyzed during circle foundation pit dewatering in deep unconfined aquifers. Furthermore, an analytical solution was proposed for groundwater inflow of circle foundation pit with suspended waterproof curtains in the unconfined aquifers. The effect of suspended waterproof curtains on seepage area, seepage direction, and seepage path were respectively considered by introducing the buried depth of waterproof curtain, the anisotropy coefficient, and the seepage path reduction coefficient. Finally, based on the self-conducted indoor seepage experiment and other cases (an indoor seepage experiment and two actual engineering projects), this proposed method was applied to conduct a comparative analysis with the existing methods. Results indicated that the proposed method can more reasonably evaluate the groundwater inflow of circle foundation pit with waterproof curtains in the unconfined aquifer, which can provide a better guidance for the groundwater inflow control in the practical dewatering projects.

This study describes the detailed investigation on dynamic swelling of biodegradable network system poly(N-isopropylacrylamide-co-N-maleylgelatin) P(NIPAAm-co-N-MAGEL) prepared by N-isopropylacrylamide (NIPAAm) and N-maleylgelatin (MAGEL) with N,N′-methylene bis(acrylamide) (BIS) as a cross-linking agent. Effects of MAGEL content on the swelling behavior were investigated. The results showed that the swelling kinetics were dependent on the content of MAGEL and the maximum swelling rate was observed at 30% content of MAGEL. The swelling process follows second-order kinetics, and the mechanism of water transport is pseudo-Fickian type of diffusion. Swelling kinetics under different concentrations of NaCl was also studied. The swelling rate decreased with increasing the concentration of NaCl.