3,3'-((3,4,5-trifluoropHenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) inhibit lung cancer cell proliferation and migration.

Lung cancer is a major public health challenge and, despite therapeutic improvements, is the first leading cause of cancer worldwide. The current cure rate from advanced cancer treatment is excessively low. Therefore, it is of great importance to identify novel, potent and less toxic anticancer agents for the treatment of lung cancer. The aim of our research is to synthesize a new biscoumarin 3,3'-((3,4,5-trifluorop -phenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) (C35) as an anticancer agent. C35 was simply prepared by 4-hydroxycoumarin and 3,4,5-trifluorobenzaldehyde under ethanol and its structure was analyzed by spectroscopic analyses. The anti-proliferation effect of C35 was detected using CCK-8 assay. Migration abilities were measured by Transwell assay. The expression of correlated proteins was determined by Western blot. The results showed that C35 displayed strong cytostatic effects on lung cancer cell proliferation. In addition, C35 possessed a significant inhibition of migration by reducing the expression of matrix metalloproteinases-2 (MMP-2) and MMP-9 in lung cancer cells. Furthermore, C35 treatment suppressed the phosphorylation of p38 in lung cancer cells. Moreover, in vivo experiments were carried out, in which we treated Lewis tumor-bearing C57 mice via intraperitoneal injection of C35. Results showed that C35 inhibited tumor growth in vivo. In conclusion, our study demonstrated the anticancer activity of C35 via suppression of lung cancer cell proliferation and migration, which is possibly involved with the inhibition of the p38 pathway.

Upgrading Passenger Vehicle Emission Standard Helps to Reduce China's Air Pollution Risk from Uncertainty in Electrification.

Upgrading to the CHINA 7 standard is crucial for managing air pollution from passenger vehicles in China. Meanwhile, China aims to achieve carbon neutrality by 2060, which necessitates large-scale replacement of gasoline vehicles with electric vehicles in the future. Consequently, the public might view upgrading gasoline vehicles to the CHINA 7 standard as redundant. However, the emission reduction benefits of upgrading standards in the context of uncertain electrification ambitions have not received adequate attention. Here, we show that upgrading standards will compensate for the absence of emissions reductions due to hindered electrification efforts. In the best scenario, China's CO2 emissions can be reduced to 0.047 Gt and NOx to 8.2 × 103 t in 2050. In nonextreme electrification scenarios with CHINA 7 standard, the emission intensity reduction will remain the main driver for emission reductions, outweighing the electrification contribution. In extreme electrification scenarios, upgrading standards will tackle the increased emissions from plug-in hybrid electric vehicles. Our fleet-level results advocate for early standards upgrades to enhance resilience against air pollution risks arising from uncertainties in electrification. Our evidence from China, with one of the most stringent emission standards, can provide a reference point for the world on the upgrading passenger vehicle emission standard issue.

Rethinking industrial land-use in American rust cities towards sustainability based on a block-level model.

Urban land is a fundamental but scarce resource that carries intensive human socio-economic activities. The demographic decline and housing vacancy issues that emerged with de-industrialization have raised concerns regarding the sustainable utilization of urban land resources, particularly in the American Rust Belt region. In this context, a comprehensive analysis of industrial land use can offer valuable insights to support the sustainable planning of shrinking cities. However, existing urban land research exhibits insufficient resolution at the sectoral scale and impedes the evaluation of industrial land use efficiency within the urban context. To address this gap, we established an integrated land use estimation framework for economic sectors based on multi-source data, which enables the assessment of land use efficiency at a finer sectoral scale. The method was then applied to the city of Detroit, Cleveland, and Pittsburgh. The results demonstrate that the current industrial land mix in the three cities is dominated by service-providing industries, but the land usage by goods-producing sectors in these cities presents a relatively high level of efficiency. The Moran's I value indicates a clustered tendency for the main economic sectors. The land use area results reveal that Other Services occupies the most land area in Detroit (2.29 million m2) and Cleveland (2.04 million m2). While in Pittsburgh, Professional Scientific and Technical Services (1.44 million m2) is the largest. In terms of the economic output, Management of Companies and Enterprises is the most efficient sector in Detroit (20.28 thousand $/m2) and Cleveland (29.43 thousand $/m2), while Pittsburgh's Public Administration (11.73 thousand $/m2) is the most efficient. As many other cities in the world are about to enter the era of de-industrialization or low growth, the outcomes can also serve as a reference to guide their sustainable revitalization in line with the SDGs.

Prominent Josephson tunneling between twisted single copper oxide planes of Bi2Sr2-xLaxCuO6+y.

Josephson tunneling in twisted cuprate junctions provides a litmus test for the pairing symmetry, which is fundamental for understanding the microscopic mechanism of high temperature superconductivity. This issue is rekindled by experimental advances in van der Waals stacking and the proposal of an emergent d+id-wave. So far, all experiments have been carried out on Bi2Sr2CaCu2O8+x (Bi-2212) with double CuO2 planes but show controversial results. Here, we investigate junctions made of Bi2Sr2-xLaxCuO6+y (Bi-2201) with single CuO2 planes. Our on-site cold stacking technique ensures uncompromised crystalline quality and stoichiometry at the interface. Junctions with carefully calibrated twist angles around 45° show strong Josephson tunneling and conventional temperature dependence. Furthermore, we observe standard Fraunhofer diffraction patterns and integer Fiske steps in a junction with a twist angle of 45.0±0.2°. Together, these results pose strong constraints on the d or d+id-wave pairing and suggest an indispensable isotropic pairing component.

A synthetic biscoumarin suppresses lung cancer cell proliferation and induces cell apoptosis by increasing expression of RIP1.

Coumarin has a variety of biological activities and widely exists in plants. Biscoumarin, derived from coumarin, their synthetic methods and bioactivities of biscoumarins is the hotspot of the current research. In this study, we evaluated for the first time the anticancer of a synthetic biscoumarin (3,3'-(4-chlorophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one, C3) on lung cancer cells and explored the related mechanism. C3 was simply prepared by 4-hydroxycoumarin and 4-chlorobenzaldehyde under ethanol. The structure of C3 was elucidated by various spectroscopic analyses. The antiproliferation effect of C3 was evaluated by the cell counting kit-8 assay. Cell cycle and apoptosis analysis were detected by flow cytometry. The expression of correlated proteins was determined using Western blotting. The result showed that C3 displayed a strong cytostatic effect on Lewis lung cancer (LLC) cells. C3 inhibited the proliferation of LLC cells, and induced G2/M phase cell cycle arrest. In addition, C3 possessed a significant reduction on cell apoptosis by increasing of RIP1 expression. Our data showed that C3 suppresses lung cancer cell proliferation and induces cell apoptosis, which is possibly involved with the RIP1.

Applications and Biocompatibility of Mesoporous Silica Nanocarriers in the Field of Medicine.

Mesoporous silica nanocarrier (MSN) preparations have a wide range of medical applications. Studying the biocompatibility of MSN is an important part of clinical transformation. Scientists have developed different types of mesoporous silica nanocarriers (MSNs) for different applications to realize the great potential of MSNs in the field of biomedicine, especially in tumor treatment. MSNs have achieved good results in diagnostic bioimaging, tissue engineering, cancer treatment, vaccine development, biomaterial application and diagnostics. MSNs can improve the therapeutic efficiency of drugs, introduce new drug delivery strategies, and provide advantages that traditional drugs lack. It is necessary not only to innovate MSNs but also to comprehensively understand their biological distribution. In this review, we summarize the various medical uses of MSN preparations and explore the factors that affect their distribution and biocompatibility in the body based on metabolism. Designing more reasonable therapeutic nanomedicine is an important task for the further development of the potential clinical applications of MSNs.

Protective effect and mechanism of chitooligosaccharides on acetaminophen-induced liver injury.

Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is N-acetyl-L-cysteine (NAC), which has many side effects. Chitooligosaccharides (COS) are processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. In this study, we constructed in vitro and in vivo models of APAP-induced liver injury to study COS of two molecular weights (MWs), which are COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM can significantly reduce the levels of serum ALT and AST and liver MDA, TNF-α, IL-1ß and IL-6, and increase the levels and activity of GSH, SOD, GSH-Px and CAT. A mechanistic study found that COST and COSM can significantly reduce the expression of liver CYP2E1, Keap1, p-ASK1/ASK1, p-MKK4/MKK4, p-JNK/JNK, Caspase-3 and Bax and increase the expression of Nrf2, HO-1, eNOS, SOD and Bcl-XL. COST and COSM can inhibit toxic APAP metabolism, inhibit oxidative damage and the apoptosis pathway, increase activation of the liver antioxidant pathway, and ultimately ameliorate APAP-induced liver oxidative damage.

Effect of different bile acids on the intestine through enterohepatic circulation based on FXR.

Farnesoid X receptor (FXR) is a nuclear receptor for bile acids (BAs) that is widely expressed in the intestine, liver and kidney. FXR has important regulatory impacts on a wide variety of metabolic pathways (such as glucose, lipid, and sterol metabolism) and has been recognized to ameliorate obesity, liver damage, cholestasis and chronic inflammatory diseases. The types of BAs are complex and diverse. BAs link the intestine with the liver through the enterohepatic circulation. BAs derivatives have entered clinical trials for liver disease. In addition to the liver, the intestine is also targeted by BAs. This article reviews the effects of different BAs on the intestinal tract through the enterohepatic circulation from the perspective of FXR, aiming to elucidate the effects of different BAs on the intestinal tract and lay a foundation for new treatment methods.

Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer.

BACKGROUND: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. RESULTS: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15-25 nm) and inner diameter (7-8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. CONCLUSIONS: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.

Advances in the preparation and assessment of the biological activities of chitosan oligosaccharides with different structural characteristics.

Chitosan oligosaccharides (COSs) are widely used biopolymers that have been studied in relation to a variety of abnormal biological activities in the food and biomedical fields. Since different COS preparation technologies produce COS compounds with different structural characteristics, it has not yet been possible to determine whether one or more chito-oligomers are primarily responsible for the bioactivity of COSs. The inherent biocompatibility, mucosal adhesion and nontoxic nature of COSs are well documented, as is the fact that they are readily absorbed from the intestinal tract, but their structure-activity relationship requires further investigation. This review summarizes the methods used for COS preparation, and the research findings with regard to the antioxidant, anti-inflammatory, anti-obesity, bacteriostatic and antitumour activity of COSs with different structural characteristics. The correlation between the molecular structure and bioactivities of COSs is described, and new insights into their structure-activity relationship are provided.

Pathogenic Characteristics of and Variation in Vibrio parahaemolyticus Isolated from Acute Diarrhoeal Patients in Southeastern China from 2013 to 2017.

OBJECTIVE: Vibrio parahaemolyticus is a major diarrhoea-inducing pathogen in coastal areas. In this study, we analysed the pathogenic characteristics of and variation in V. parahaemolyticus isolated from acute diarrhoeal patients in seven hospitals in different areas of southeastern China from 2013 to 2017. METHODS: The fecal specimens of patients with acute diarrhoea were collected. The routine microbiological test procedure combining with MALDI Biotyper microbial identification system was carried out to identify the V. parahaemolyticus. Serum agglutination tests, PCR for the detection of virulence-related genes and the Kirby-Bauer method to test for antimicrobial sensitivity were performed. RESULTS: From 2013 to 2017 in southeastern China, a total of 1220 V. parahaemolyticus strains were isolated from 16,504 stool specimens collected from acute diarrhoeal patients, and the annual isolation rate fluctuated between 6.1% and 8.7%. In total, 96.7% of the V. parahaemolyticus isolates were isolated in summer and autumn, mainly in people aged 18-44. Fifty-nine serotypes were identified, and the agglutination rate of the O antigen was 98.5%. From 2014 to 2016, the dominant serotype was O3:K6, while in 2013 and 2017, it was O4:KUT. The serotypes of O3:K6, O4:KUT, O4:K8, O3:KUT, O10:K60, O1:KUT and O1:K36 appeared every year from 2013 to 2017. O4:K6 and OUT:K6 began to appear after 2014 and 2015, respectively. A total of 49.5% of the strains belonged to the pandemic group, which consisted of 26 serotypes. Most isolates were sensitive to common antibiotics, excluding ampicillin. CONCLUSION: V. parahaemolyticus is still present at a high level in southeastern China. Although the pandemic O3:K6 serotype is predominant, new serotypes continue to emerge, especially the O4:KUT serotype, which exceeded O3:K6 in prevalence in some years. Long-term surveillance is necessary to prevent the outbreak or transmission of this pathogen.

Silencing of SENP2 in Multiple Myeloma Induces Bortezomib Resistance by Activating NF-κB Through the Modulation of IκBα Sumoylation.

The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However, its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study, by combining in silico analysis and sgRNA library based drug resistance screening assay, we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient's samples. Furthermore, down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis, whereas, overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated IκBα that resulted in the activation of NF-κB. Taken together, we report that silencing of SENP2 and consequent activation of NF-κB through the modulation of IκBα sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma.

Delivery of RIPK4 small interfering RNA for bladder cancer therapy using natural halloysite nanotubes.

RNA interference (RNAi) technology can specifically silence the expression of a target gene and has emerged as a promising therapeutic method to treat cancer. In the present study, we showed that natural halloysite nanotube (HNT)-assisted delivery of an active small interfering RNA (siRNA) targeting receptor-interacting protein kinase 4 ( RIPK4 ) efficiently silenced its expression to treat bladder cancer. The HNTs/siRNA complex increased the serum stability of the siRNA, increased its circulation lifetime in blood, and promoted the cellular uptake and tumor accumulation of the siRNA. The siRNA markedly down-regulated RIPK4 expression in bladder cancer cells and bladder tumors, thus inhibiting tumorigenesis and progression in three bladder tumor models (a subcutaneous model, an in situ bladder tumor model, and a lung metastasis model), with no adverse effects. Thus, we revealed a simple but effective method to inhibit bladder cancer using RIPK4 silencing, indicating a promising therapeutic method for bladder cancer.

Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer.

Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-ß1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-ß1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFß1-EMT axis.

Charge-Dependent Regulation in DNA Adsorption on 2D Clay Minerals.

DNA purification is essential for the detection of human clinical specimens. A non-destructive, controllable, and low reagent consuming DNA extraction method is described. Negatively charged DNA is absorbed onto a negatively charged montmorillonite to achieve non-destructive DNA extraction based on cation bridge construction and electric double layer formation. Different valence cation modified montmorillonite forms were used to validate the charge-dependent nature of DNA adsorption on montmorillonite. Electric double layer thickness thinning/thickening with the high/lower valence cations exists, and the minerals tended to be sedimentation-stable due to the Van der Waals attraction/electrostatic repulsion. Li-modified montmorillonite with the lowest charge states showed the best DNA adsorption efficiency of 8-10 ng/µg. Charge-dependent regulating research provides a new perspective for controllable DNA extraction and a deep analysis of interface engineering mechanisms.

Enhanced Thermoelectric Power in Graphene: Violation of the Mott Relation by Inelastic Scattering.

We report the enhancement of the thermoelectric power (TEP) in graphene with extremely low disorder. At high temperature we observe that the TEP is substantially larger than the prediction of the Mott relation, approaching to the hydrodynamic limit due to strong inelastic scattering among the charge carriers. However, closer to room temperature the inelastic carrier-optical-phonon scattering becomes more significant and limits the TEP below the hydrodynamic prediction. We support our observation by employing a Boltzmann theory incorporating disorder, electron interactions, and optical phonons.

Topological Protection from Random Rashba Spin-Orbit Backscattering: Ballistic Transport in a Helical Luttinger Liquid.

The combination of Rashba spin-orbit coupling and potential disorder induces a random current operator for the edge states of a 2D topological insulator. We prove that charge transport through such an edge is ballistic at any temperature, with or without Luttinger liquid interactions. The solution exploits a mapping to a spin 1/2 in a time-dependent field that preserves the projection along one randomly undulating component (integrable dynamics). Our result is exact and rules out random Rashba backscattering as a source of temperature-dependent transport, absent integrability-breaking terms.

Rigorous description of exchange-correlation energy of many-electron systems.

With the eigenfunctional theory, we study a general interacting electron system, and give a rigorous expression of its ground state energy, which is composed of two parts: one part is contributed by the non-interacting electrons, and the other one is represented by the correlation functions that are controlled by the electron correlation. Moreover, according to the rigorous expression of the ground state energy, an effective scheme beyond the local density approximation of the density functional theory is proposed. As a simple example for a spin-1/2 XXZ chain, under the linear approximation in solving the equation of the phase field, the ground state energy obtained by the present scheme is quite close to that of the Bethe ansatz.