Search

Abstract Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells’ migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Abstract Background Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. Methods The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. Results After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. Conclusions In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

ObjectiveIn recent years, there has been a significant increase in the severity of leaf diseases in maize, with a noticeable trend of mixed occurrence. This poses a serious threat to the yield and quality of maize. However, there is a lack of studies that combine the identification of different types of leaf diseases and their severity classification, which cannot meet the needs of disease prevention and control under the mixed occurrence of different diseases and different severities in actual maize fields.MethodsA method was proposed for identifying the types of typical leaf diseases in maize and classifying their severity using hyperspectral technology. Hyperspectral data of three leaf diseases of maize: northern corn leaf blight (NCLB), southern corn leaf blight (SCLB) and southern corn rust (SCR), were obtained through greenhouse pathogen inoculation and natural inoculation. The spectral data were preprocessed by spectral standardization, SG filtering, sensitive band extraction and vegetation index calculation, to explore the spectral characteristics of the three leaf diseases of maize. Then, the inverse frequency weighting method was utilized to balance the number of samples to reduce the overfitting phenomenon caused by sample imbalance. Relief-F and variable selection using random forests (VSURF) method were employed to optimize the sensitive spectral features, including band features and vegetation index features, to construct models for disease type identification based on the full stages of disease development (including all disease severities) and for individual disease severities using several representative machine learning approaches, demonstrating the effectiveness of the research method. Furthermore, the study individual occurrence severity classification models were also constructed for each single maize leaf disease, including the NCLB, SCLB and SCR severity classification models, respectively, aiming to achieve full-process recognition and disease severity classification for different leaf diseases. Overall accuracy (OA) and Macro F1 were used to evaluate the model accuracy in this study.Results and DiscussionThe research results showed significant spectrum changes of three kinds of maize leaf diseases primarily focusing on the visible (550-680 nm), red edge (740-760 nm), near-infrared (760-1 000 nm) and shortwave infrared (1 300-1 800 nm) bands. Disease-specific spectral features, optimized based on disease spectral response rules, effectively identified disease species and classify their severity. Moreover, vegetation index features were more effective in identifying disease-specific information than sensitive band features. This was primarily due to the noise and information redundancy present in the selected hyperspectral sensitive bands, whereas vegetation index could reduce the influence of background and atmospheric noise to a certain extent by integrating relevant spectral signals through band calculation, so as to achieve higher precision in the model. Among several machine learning algorithms, the support vector machine (SVM) method exhibited better robustness than random forest (RF) and decision tree (DT). In the full stage of disease development, the optimal overall accuracy (OA) of the disease classification model constructed by SVM based on vegetation index reached 77.51%, with a Macro F1 of 0.77, representing a 28.75% increase in OA and 0.30 higher of Macro F1 compared to the model based on sensitive bands. Additionally, the accuracy of the disease classification model with a single severity of the disease increased with the severity of the disease. The accuracy of disease classification during the early stage of disease development (OA=70.31%) closely approached that of the full disease development stage (OA=77.51%). Subsequently, in the moderate disease severity stage, the optimal accuracy of disease classification (OA=80.00%) surpassed the optimal accuracy of disease classification in the full disease development stage. Furthermore, the optimal accuracy of disease classification under severe severity reached 95.06%, with a Macro F1 of 0.94. This heightened accuracy during the severity stage can be attributed to significant changes in pigment content, water content and cell structure of the diseased leaves, intensifying the spectral response of each disease and enhancing the differentiation between different diseases. In disease severity classification model, the optimal accuracy of the three models for maize leaf disease severity all exceeded 70%. Among the three kinds of disease severity classification results, the NCLB severity classification model exhibited the best performance. The NCLB severity classification model, utilizing SVM based on the optimal vegetation index features, achieved an OA of 86.25%, with a Macro F1 of 0.85. In comparison, the accuracy of the SCLB severity classification model (OA=70.35%, Macro F1=0.70) and SCR severity classification model (OA=71.39%, Macro F1=0.69) were lower than that of NCLB.ConclusionsThe aforementioned results demonstrate the potential to effectively identify and classify the types and severity of common leaf diseases in maize using hyperspectral data. This lays the groundwork for research and provides a theoretical basis for large-scale crop disease monitoring, contributing to precision prevention and control as well as promoting green agriculture.

BackgroudIn recent years, as the number of people with obesity has surged, the number of morbidly obese patients has also grown. The pathophysiological changes in morbid obesity can lead to combined lung diseases, which may result in hypoventilation, hypoxemia, acute upper airway obstruction, acute respiratory distress syndrome, and sleep apnea syndrome, posing serious challenges to anesthesia management. Here, we describe a case of the administration of remimazolam combined with remifentanil in a patient with morbid obesity undergoing gastroscopy. This has rarely been reported in clinical practice, and we present our management experience here with the aim of providing a reference for clinical work.Case presentationWe report the case of a 32-year-old male hypertensive patient with a height of 180 cm, weight of 145 kg, and body mass index of 44.8 kg/m2. The patient’s main complaint was intermittent hunger pain for more than 1 year, and duodenal polyps were found. Considering the patient’s morbid obesity and the combination of sleep apnea syndrome and hypertension, we administered remimazolam along with remifentanil to ensure perioperative safety.ConclusionThe procedure lasted 30 min, and the anesthesia was satisfactory with no complications. Remimazolam combined with remifentanil intravenous anesthesia is safe for short gastroscopy in patients with morbidly obesity. The administration of a small dose of split-titration delivery facilitates the maintenance of stable vital signs.

A novel tungsten carbide (WC)-reinforced nickel (Ni)-based laser cladding layer was prepared through an in-situ synthesis process. The mechanism of the effect of scanning rates and laser power on the microstructures, wear and corrosion resistance of in-situ synthesized WC-reinforced Ni-based cladding layer were analyzed. The results revealed that the optimal in-situ synthesized WC laser cladding process entailed a scan rate of 3 mm/s and a laser power of 3000 W. The generation of WC phase has a significant strengthening effect on the cladding layer, which exhibits outstanding hardness (1261HV0.2). There is no clear linear relationship between scanning rate and abrasion resistance, and the coating abrasion resistance increased with increasing laser power. Furthermore, increasing the laser power improves the corrosion resistance of the cladding layer, while the scanning speed has a minimal effect on corrosion resistance.

With the increasing importance of the stock market, it is of great practical significance to accurately describe the systemic risk of the stock market and conduct more accurate early warning research on it. However, the existing research on the systemic risk of the stock market lacks multi-dimensional factors, and there is still room for improvement in the forecasting model. Therefore, to further measure the systemic risk profile of the Chinese stock market, establish a risk early warning system suitable for the Chinese stock market, and improve the risk management awareness of investors and regulators. This paper proposes a combination model of EEMD-LSTM, which can describe the complex nonlinear interaction. Firstly, 35 stock market systemic risk indicators are selected from the perspectives of macroeconomic operation, market cross-contagion and the stock market itself to build a comprehensive indicator system that conforms to the reality of China. Furthermore, based on TEI@I complex system methodology, an EEMD-LSTM model is proposed. The EEMD method is adopted to decompose the composite index sequence into intrinsic mode function components (IMF) of different scales and one trend term. Then the LSTM algorithm is used to predicted and model the decomposed sub-sequences. Finally, the forecast result of the composite index is obtained through integration. The empirical results show that the stock market systemic risk index constructed in this paper can effectively identify important risk events within the sample period. In addition, compared with the benchmark model, the EEMD-LSTM model constructed in this paper shows a stronger early warning ability for systemic financial risks in the stock market.

Pre-harvest yield prediction of ratoon rice is critical for guiding crop interventions in precision agriculture. However, the unique agronomic practice (i.e., varied stubble height treatment) in rice ratooning could lead to inconsistent rice phenology, which had a significant impact on yield prediction of ratoon rice. Multi-temporal unmanned aerial vehicle (UAV)-based remote sensing can likely monitor ratoon rice productivity and reflect maximum yield potential across growing seasons for improving the yield prediction compared with previous methods. Thus, in this study, we explored the performance of combination of agronomic practice information (API) and single-phase, multi-spectral features [vegetation indices (VIs) and texture (Tex) features] in predicting ratoon rice yield, and developed a new UAV-based method to retrieve yield formation process by using multi-temporal features which were effective in improving yield forecasting accuracy of ratoon rice. The results showed that the integrated use of VIs, Tex and API (VIs & Tex + API) improved the accuracy of yield prediction than single-phase UAV imagery-based feature, with the panicle initiation stage being the best period for yield prediction (R2 as 0.732, RMSE as 0.406, RRMSE as 0.101). More importantly, compared with previous multi-temporal UAV-based methods, our proposed multi- temporal method (multi-temporal model VIs & Tex: R2 as 0.795, RMSE as 0.298, RRMSE as 0.072) can increase R2 by 0.020–0.111 and decrease RMSE by 0.020–0.080 in crop yield forecasting. This study provides an effective method for accurate pre-harvest yield prediction of ratoon rice in precision agriculture, which is of great significance to take timely means for ensuring ratoon rice production and food security.

The survival rate of Castanopsis kawakamii from seed to seedling is relatively low, leading to difficulties in the regeneration of its natural forests. Forest gaps play a vital role in plant regeneration and biodiversity maintenance in forest ecosystems. Unfortunately, our understanding of the effects of gap size and within-gap position on the seed germination and radicle growth of C. kawakamii is still limited. In particular, our knowledge on the relationship between gap size and environmental factors and their influence on seed germination and radicle growth is incomplete. In the present study, we studied the influences of forest gaps and within-gap position on seed regeneration on the germination and radicle growth of an endangered species C. kawakamii in a subtropical natural forest in China. We selected three large gaps (LG, gap size above 200 m2), three medium gaps (MG, gap size 50–100 m2), three small gaps (SG, gap size 30–50 m2), and non-gap (NG), and planted the seeds of C. kawakamii in five positions within each gap. The results showed that (1) the influence of forest gaps on seed germination rate was, from highest to lowest, medium gaps (51%), non-gap (47%), small gaps (40%) and large gaps (17%), and the seed germination rate was the highest in all positions in medium gaps, with the exception of the east position. (2) Radicle length in forest gaps was, from highest to lowest, medium gaps, small gaps, large gaps and non-gap, and it was the highest in the east, south, west and north positions of medium gaps. (3) Canopy openness (gap size) and air temperature were the main factors influencing seed germination and radicle growth of C. kawakamii. We concluded that medium-sized gaps were the most suitable for seed germination and radicle growth of C. kawakamii, and they promote the regeneration of this endangered species in the investigated natural forest.

The role of lncRNA Gm20743 in the development of diabetic sarcopenia is explored using a mouse model.

Metabolic syndromes (Mets) is a high-risk factor for a series of cardiovascular diseases. Changes in iodine nutritional status can directly mediate the occurrence of insulin resistance, affect glucose and lipid metabolism and the regulation of blood pressure and also,may contribute to the pathogenesis of Mets by regulating thyroid function. Exploring the role of iodine in the occurrence and development of Mets can provide new ideas for the prevention and treatment of Mets.

In-plane anisotropy (IPA) due to asymmetry in lattice structures provides an additional parameter for the precise tuning of characteristic polarization-dependent properties in two-dimensional (2D) materials, but the narrow range within which such method can modulate properties hinders significant development of related devices. Herein we present a novel periodic phase engineering strategy that can remarkably enhance the intrinsic IPA obtainable from minor variations in asymmetric structures. By introducing alternant monoclinic and rutile phases in 2D VO2 single crystals through the regulation of interfacial thermal strain, the IPA in electrical conductivity can be reversibly modulated in a range spanning two orders of magnitude, reaching an unprecedented IPA of 113. Such an intriguing local phase engineering in 2D materials can be well depicted and predicted by a theoretical model consisting of phase transformation, thermal expansion, and friction force at the interface, creating a framework applicable to other 2D materials. Ultimately, the considerable adjustability and reversibility of the presented strategy provide opportunities for future polarization-dependent photoelectric and optoelectronic devices.

Folate receptor (FR) overexpression occurs in a variety of cancers, including pancreatic cancer. In addition, enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer. Furthermore, the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer. In this study, a novel FR-directed, macropinocytosis-enhanced, and highly cytotoxic bioconjugate folate (F)-human serum albumin (HSA)-apoprotein of lidamycin (LDP)-active enediyne (AE) derived from lidamycin was designed and prepared. F-HSA-LDP-AE consisted of four moieties: F, HSA, LDP, and AE. F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells. Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells. By in vivo optical imaging, F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice, showing clear and lasting tumor localization for 360 h. In the MTT assay, F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines. It also induced apoptosis and caused G2/M cell cycle arrest. F-HSA-LDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice. At well-tolerated doses of 0.5 and 1 mg/kg, (i.v., twice), the inhibition rates were 91.2% and 94.8%, respectively (P

Diabetic kidney disease has obvious family aggregation and ethnic differences, some single nucleotide polymorphisms (SNPs) related to the susceptibility of diabetic kidney disease have been identified, especially engulfment and cell motility 1 (ELMO1) and solute carrier family 12 member 3(SLC12A3), which are related to the development of diabetic kidney disease in Chinese population. Meanwhile, inflammation plays a key role in the occurrence and development of diabetic kidney disease, including T cell and type-2 innate lymphoid cell(ILC2) promote chronic inflammatory response and fibrosis of kidney by secreting inflammatory factors.

Circular RNAs (circRNAs) are a new and large group of non-coding RNA molecules that are abundantly expressed in the central nervous system. However, very little is known about their roles in traumatic brain injury. In this study, we firstly screened differentially expressed circRNAs in normal and injured brain tissues of mice after traumatic brain injury. We found that the expression of circLphn3 was substantially decreased in mouse models of traumatic brain injury and in hemin-treated bEnd.3 (mouse brain cell line) cells. After overexpressing circLphn3 in bEnd.3 cells, the expression of the tight junction proteins, ZO-1, ZO-2, and occludin, was upregulated, and the expression of miR-185-5p was decreased. In bEnd.3 cells transfected with miR-185-5p mimics, the expression of ZO-1 was decreased. Dual-luciferase reporter assays showed that circLphn3 bound to miR-185-5p, and that miR-185-5p bound to ZO-1. Additionally, circLphn3 overexpression attenuated the hemin-induced high permeability of the in vitro bEnd.3 cell model of the blood-brain barrier, while miR-185-5p transfection increased the permeability. These findings suggest that circLphn3, as a molecular sponge of miR-185-5p, regulates tight junction proteins’ expression after traumatic brain injury, and it thereby improves the permeability of the blood-brain barrier. This study was approved by the Animal Care and Use Committee of Chongqing Medical University of China (approval No. 2021-177) on March 22, 2021.

Abstract Background Trehalose, an intracellular protective agent reported to mediate defense against many stresses, can alleviate high-temperature-induced damage in Pleurotus ostreatus. In this study, the mechanism by which trehalose relieves heat stress was explored by the addition of exogenous trehalose and the use of trehalose-6-phosphate synthase 1 (tps1) overexpression transformants. Results The results suggested that treatment with exogenous trehalose or overexpression of tps1 alleviated the accumulation of lactic acid under heat stress and downregulated the expression of the phosphofructokinase (pfk) and pyruvate kinase (pk) genes, suggesting an ameliorative effect of trehalose on the enhanced glycolysis in P. ostreatus under heat stress. However, the upregulation of hexokinase (hk) gene expression by trehalose indicated the involvement of the pentose phosphate pathway (PPP) in heat stress resistance. Moreover, treatment with exogenous trehalose or overexpression of tps1 increased the gene expression level and enzymatic activity of glucose-6-phosphate dehydrogenase (g6pdh) and increased the production of both the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), confirming the effect of trehalose on alleviating oxidative damage by enhancing PPP in P. ostreatus under heat stress. Furthermore, treatment with exogenous trehalose or overexpression of tps1 ameliorated the decrease in the oxygen consumption rate (OCR) caused by heat stress, suggesting a relationship between trehalose and mitochondrial function under heat stress. Conclusions Trehalose alleviates high-temperature stress in P. ostreatus by inhibiting glycolysis and stimulating PPP activity. This study may provide further insights into the heat stress defense mechanism of trehalose in edible fungi from the perspective of intracellular metabolism.

Sequences of circular RNAs (circRNAs) produced from back-splicing of exon(s) completely overlap with those from cognate linear RNAs transcribed from the same gene loci with the exception of their back-splicing junction (BSJ) sites. Therefore, examination of global circRNA expression from RNA-seq datasets generally relies on the detection of RNA-seq fragments spanning BSJ sites, which is different from the quantification of linear RNA expression by normalized RNA-seq fragments mapped to whole gene bodies. Thus, direct comparison of circular and linear RNA expression from the same gene loci in a genome-wide manner has remained challenging. Here, we update the previously-reported CIRCexplorer pipeline to version 3 for circular and linear RNA expression analysis from ribosomal-RNA depleted RNA-seq (CIRCexplorer3-CLEAR). A new quantitation parameter, fragments per billion mapped bases (FPB), is applied to evaluate circular and linear RNA expression individually by fragments mapped to circRNA-specific BSJ sites or to linear RNA-specific splicing junction (SJ) sites. Comparison of circular and linear RNA expression levels is directly achieved by dividing FPBcirc by FPBlinear to generate a CIRCscore, which indicates the relative circRNA expression level using linear RNA expression level as the background. Highly-expressed circRNAs with low cognate linear RNA expression background can be readily identified by CIRCexplorer3-CLEAR for further investigation. CIRCexplorer3-CLEAR is publically available at https://github.com/YangLab/CLEAR. Keywords: Circular RNA, Back-splicing, Linear RNA, Pre-mRNA splicing, Ribo− RNA-seq

Real-time non-destructive monitoring of water use efficiency (WUE) is important for screening high-yielding high-efficiency varieties and determining the rational allocation of water resources in winter wheat production. Compared with vertical observation angles, multi-angle remote sensing provides more information on mid to lower parts of the wheat canopy, thereby improving estimates of physical and chemical indicators of the entire canopy. In this study, multi-angle spectral reflectance and the WUE of the wheat canopy were obtained at different growth stages based on field experiments carried out across 4 years using three wheat varieties under different water and nitrogen fertilizer regimes. Using appropriate spectral parameters and sensitive observation angles, the quantitative relationships with wheat WUE were determined. The results revealed that backward observation angles were better than forward angles, while the common spectral parameters Lo and NDDAig were found to be closely related to WUE, although with increasing WUE, both parameters tended to become saturated. Using this data, we constructed a double-ratio vegetation index (NDDAig/FWBI), which we named the water efficiency index (WEI), reducing the impact of different test factors on the WUE monitoring model. As a result, we were able to create a unified monitoring model within an angle range of −20–10°. The equation fitting determination coefficient (R2) and root mean square error (RMSE) of the model were 0.623 and 0.406, respectively, while an independent experiment carried out to test the monitoring models confirmed that the model based on the new index was optimal, with R2, RMSE, and relative error (RE) values of 0.685, 0.473, and 11.847%, respectively. These findings suggest that the WEI is more sensitive to WUE changes than common spectral parameters, while also allowing wide-angle adaptation, which has important implications in parameter design and the configuration of satellite remote sensing and UAV sensors.

Steam-assisted gravity drainage (SAGD) is an important method used in the development of heavy oil. A heat transfer model in the SAGD production process is established based on the heat transfer effect caused by the temperature difference at the front edge of the steam chamber and the heat convection effect caused by the pressure difference. The observation well temperature method is used in this model to calculate the horizontal expansion speed of the steam chamber. In this manner, an expansion speed model considering heat convection and heat conduction is established for a steam chamber with a steam-assisted gravity drainage system. By comparing this with the production data extracted from the Fengcheng Oilfield target block, it is verified that the model can be effectively applied for actual field development. Simultaneously, by using the derived model, the temperature distribution at the edge of the steam chamber and production forecast can be predicted. Sensitivity analysis of the expansion rate of the steam chamber demonstrates that the larger the thermal conductivity, the faster is the steam chamber horizontal expansion speed, and the two are positively correlated; the larger the reservoir heat capacity, the slower is the steam chamber horizontal expansion speed. A larger heat capacity of the convective liquid indicates that there are more water components in the convective liquid, the viscosity of the convective liquid is low, and the expansion speed of the steam chamber increases accordingly. This research closely integrates theory with actual field production and provides theoretical support for the development of heavy oil reservoirs.

Non-small cell lung cancer (NSCLC), the major form of primary lung cancer, is a common cause of cancer-related death worldwide. Cell adhesion-mediated drug resistance (CAM-DR), a form of chemotherapy resistance, has been reported to confer resistance to various chemotherapeutic agents. Integrin β1 signaling plays an important role in CAM-DR and has been proposed as a potential target for NSCLC. Wenxia Changfu Formula (WCF) is a Traditional Chinese Compound Prescription for the intervention treatment of NSCLC combined with cisplatin (DDP). This study aims to investigate the effect and mechanism of WCF combined with DDP in reversing CAM-DR. Firstly, the chemical profile of WCF was characterized by UPLC/Q-TOF-MS analysis. A total of 237 compounds with mzCloud Best Match of greater than 70 were identified by using the online database mzCloud. Secondly, we established A549 three-dimensional(3D) cells cultured in vitro and nude mice xenografts models of the A549 cell line with Integrin β1 overexpression. In vitro, the cell viability, migration and adhesion were measured though MTT Assay, Wound Healing Assay and Cell Adhesion Assay, the Integrin β1 expression of the A549 cells was assessed through immunocytochemistry; in vitro, the transplanted tumor morphology and the colocalization of Integrin β1 and its ligands were tested by HE staining and immunofluorescence. As a result, we found that the combination effectively reduced cell viability, suppressed migration and adhesion, and downregulated the protein level of Integrin β1 in three-dimensional cultured A549 cells. And the combination of WCF with DDP significantly inhibited tumor growth, increased organelle vacuolations and decreased colocalization of Integrin β1 and its ligands including fibulin-2 and laminin. Taken together, our results confirm that the combination of WCF with DDP could reverse the lung cancer CAM-DR through the Integrin β1 signaling pathway.

Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited. Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved. Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism. Results: FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01–47.70%). Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.

Four metal complexes based on quinoline carboxylate ligand from 2-(pyridin-4-yl)quinoline-4-carboxylic acid (HL), {[ML2(H2O)2]∙2H2O}n (M = MnII, 1; M = CoII, 2; M= CdII, 3) and {[Ag2L2(H2O)2]∙3H2O}n (4) have been synthesized under hydrothermal conditions. Their structures were determined by elemental analyses, IR spectra, and further characterized by single-crystal X-ray diffraction analysis. Complexes 1–3 feature a 1D chain structure which is further linked together to construct the 3D supramolecular network through hydrogen bonds. Complex 4 exhibits a 3D configuration. The fluorescent behavior and antibacterial activities of these compounds have been investigated.

To investigate the genetic diversity of an edible fungus Pleurotus ferulae, a total of 89 wild samples collected from six geographical locations in the Xinjiang Uygur Autonomous Region of China and two geographical locations in Italy, were analyzed using three DNA fragments including the translation elongation factor (EF1α), the second largest subunit of the RNA polymerase II (RPB2) and the largest subunit of the RNA polymerase II (RPB1). The results indicated relatively abundant genetic variability in the wild resources of P. ferulae. The analysis of molecular variance (AMOVA) showed that the vast majority of the genetic variation was found within geographical populations. Both the Chinese populations and the Italian populations of P. ferulae displayed a limited genetic differentiation. The degree of differentiation between the Chinese populations and the Italian populations was obviously higher than that between the populations from the same region, and moreover the genetic differentiation among all the tested populations was correlated to the geographical distance. The phylogeny analyses confirmed that samples from China and Italy belonged to another genetic group separated from Pleurotus eryngii. They were closely related to each other but were clustered according to their geographical origins, which implied the Chinese populations were highly differentiated from the Italian populations because of distance isolation, and the two populations from different regions might be still in the process of allopatric divergence.

Herbaceous peony (Paeonia lactiflora Pall.) is a famous flower with medicinal values, and its flowers have a number of medicinal constituents, especially flavonoids. In this study, a P. lactiflora cultivar with double colors including white outer-petal and yellow inner-petal was used as the experimental materials to perform the qualitative and quantitative analysis of flavonoids by high-performance liquid chromatograph-electrospray ionization-mass spectrometry (HPLC-ESI-MSn) and investigate the expression patterns of flavonoid biosynthetic genes using real-time quantitative polymerase chain reaction (Q-PCR). The results showed that the colors of both petals gradually weakened with flower development. Moreover, one main anthocyanin composition (peonidin 3,5-di-O-glucoside) and five main anthoxanthin compositions (kaempferol di-hexo-side, kaempferol-3-O-malonylglucoside-7-O-glucoside, quercetin-3-O-galactoside, luteolin-7-O-glucoside and isorhamnetin-3-O-glucoside) were found in the both, differing significantly in their peak areas only. Total anthocyanin, anthoxanthin and flavonoid contents in white outer-petal and yellow inner-petal gradually decreased during flower development, and were consistently higher in white outer-petal. Furthermore, the expression patterns of nine structural genes in P. lactiflora flavonoid biosynthetic pathway showed that the expression levels of phenylalanine ammonialyase gene (PIPAL), chalcone synthase gene (PICHS), flavanone 3-hydroxylase gene (PIF3H), anthocyanidin synthase gene (PIANS) and UDP-glucoside: flavonoid 5-O-glucosyltransferase gene (PIF5GT) in two petals basically presented declined tendencies, and transcription levels of PIPAL, PICHS, PIANS, PIF3GT and PIF5GT also tended to be higher in white outer-petal, which was correlated with their flavonoid contents. These results would lay a solid foundation for the exploration and utilization of flavonoid resources in P. lactiflora flowers.

The aim of this study was to verify the applicability of the critical nitrogen concentration dilution curve (Nc) of wheat grown under different irrigation conditions in the field, and discuss the feasibility of using the N nutrition index (NNI) to optimize N fertilizer application. The high-yield, medium-protein wheat varieties Zhoumai 27 and Zhoumai 22 were used in field experiments in two different locations (Zhengzhou and Shangshui) in Huang-Huai, China. Plants were grown under rainfed and irrigation conditions, with five N application rates. Nc models of the leaves, stems, and whole plant were constructed, followed by establishment of an NNI model and accumulative N deficit model (Nand). As previous research reported, our results also showed that the critical N concentration and biomass formed a power function relationship (N = aDW−b). When the biomass was the same, the critical N concentration was higher under irrigation than rainfed treatment. Meanwhile, the fitting accuracy (R2) of the Nc model was also higher under irrigation than rainfed treatment in both sites, and was higher in the stems and whole plant. The NNI calculated using the Nc model increased with increasing N application, reflecting N deficiency. Moreover, there was a significant negative linear correlation between NNI and Nand, and both indices could be uniformly modeled between locations and water treatments. The accuracy of the Nand model was highest in the whole plant, followed by the leaves and stems. The models constructed in this paper provide a theoretical basis for accurate management of N fertilizer application in wheat production.

In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro- and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and V&Kgr; repertoire but exhibited an increased frequency of unique CDR3 in their V&Lgr; repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgM-expressing B cells that expressed &Lgr; chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.

In view of problems that present discriminated methods of water burst source ca't realize prediction of water burst and has long processing time and high complexity, the paper designed a water quality detection system which adopts laser induce fluorescence technology and uses FPGA as core processor. Through on-line detection of fluorescence spectrum, the system can real-timely monitor changes of chemical components of underground water and rapidly monitor movement precursor of the water burst source, so as to achieve forewarning of water burst. The test results show that the system has high detection precision and fast response speed.