Simulating arsenic discharge flux at a relic smelting site in Guangxi Zhuang Autonomous Region, China.

Anthropogenic groundwater arsenic (As) pollution is common in many aquifers in Southwest China. It is concerned that long-term random disposal of As smelting slag could induce the transport of high-As groundwater into previously uncontaminated aquifers. Here, we used HELP-MODFLOW-MT3DMS model simulations to integrate the percolation, groundwater flow, and solute transport processes at an aquifer at site scale, constrained by weather, hydrogeology, and monitoring data. Our simulations provide a new method framework of the simulated percolation by HELP model and have induced As spatiotemporal distribution in the aquifer. According to the HELP model simulation results, percolation volume accounts for 24% of rainfall over 18 years. This work determined that the As discharge trend was fitted by double-constants kinetics based on the leaching experiment. And this work calculates total mass distribution of As in the aquifer over 18 years. We have found that the sustained As pollution relies on the rainfall that acts as the primary contributor of elevated As concentrations. Model simulation results suggest that 51.70% of the total As mass (1.96 × 104 kg) was fixed in low permeability solid media. The total As mass discharged into groundwater reached 9.3 × 103 kg, accounting for 24.68%. The accumulative outflow mass of arsenic was 8.0 × 103 kg, accounting for 21.62%.

A Biodegradable Nucleotide Coordination Polymer for Enhanced NSCLC Therapy in Combination with Metabolic Modulation.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC) still face challenges of acquired resistance and non-negligible side effects. To overcome these limitations, a biodegradable coordination polymer using guanine deoxynucleotide and ferrous iron (dGNP) is developed for targeted delivery of EGFR-TKIs. dGNPs can efficiently target nucleoside transporters in tumor cells that are regulated by fasting-mimicking diet (FMD). Meanwhile, FMD can augment the therapeutic efficacy of EGFR-TKIs by suppressing EGFR tyrosine kinase phosphorylation and related downstream pathways. In vivo results demonstrate that EGFR-TKIs-laden dGNPs combined with FMD treatment exhibit superior antitumor efficacy and reduced side effect. This study provides an innovative approach to enhance the therapeutic efficacy of EGFR-TKIs through nucleotide nanocarrier and metabolic modulation.

Persistent Degradation of HER2 Protein by Hybrid nanoPROTAC for Programmed Cell Death.

Proteolysis-targeting chimera (PROTAC) has emerged as a promising strategy for degrading proteins of interest. Peptide-based PROTACs offer several advantages over small-molecule-based PROTACs, such as high specificity, low toxicity, and large protein-protein interaction surfaces. However, peptide-based PROTACs have several intrinsic shortcomings that strongly limit their application including poor cell permeability and low stability and potency. Herein, we designed a nanosized hybrid PROTAC (GNCTACs) to target and degrade human epidermal growth factor receptor 2 (HER2) in tumor cells. Gold nanoclusters (GNCs) were utilized to connect HER2-targeting peptides and cereblon (CRBN)-targeting ligands. GNCTACs could overcome the intrinsic barriers of peptide-based PROTACs, efficiently delivering HER2-targeting peptides in the cytoplasm and protecting them from degradation. Furthermore, a fasting-mimicking diet was applied to enhance the cellular uptake and proteasome activity. Consequently, more than 95% of HER2 in SKBR3 cells was degraded by GNCTACs, and the degradation lasted for at least 72 h, showing a catalytic-like reaction.

Förster Resonance Energy Transfer Nanobullet for Photoacoustic Imaging and Amplified Photothermal-Photodynamic Therapy of Cancer.

Synergistic photodynamic and photothermal therapy (PDT-PTT) has emerged as an appealing effective antitumor approach. However, clinical utilization of PDT-PTT is plagued by aggregation-caused photobleaching, sequential double irradiations, unsatisfying balance between single oxygen (1 O2 ) quantum yield and photothermal conversion efficiency. Here, an anchored tumor-homing cell-penetrating peptide (PEGA-pVEC) and PANI-ES/HMME loaded FRET nanobullet (AHP-P) are reported. Within nanobullet, HMME (donor) and PANI-ES (acceptor) spontaneously form a förster resonance energy transfer (FRET) pair. Upon 660 nm laser irradiation, HMME convert near-infrared fluorescence (NIRF) to PANI, thus produce FRET-amplified photoacoustic imaging guided PTT. In addition, AHP-P with pH-sensitivity can gradually release HMME within acidic tumor environment, boosts the 1 O2 regeneration alongside with highly efficient photothermal conversion for photoinduced cancer PTT-PDT. Furthermore, the AHP-P nanobullet can home in on the tumor site and penetrate into cytoplasm through PEGA-pVEC, inducing remarkable tumor regression with an ≈80% tumor volume reduction and decreased skin phototoxicity in vivo during FRET-amplified PTT-PDT.

Enhancing Biochar-Based Nonradical Persulfate Activation Using Data-Driven Techniques.

Converting biomass into biochar (BC) as a functional biocatalyst to accelerate persulfate activation for water remediation has attracted much attention. However, due to the complex structure of BC and the difficulty in identifying the intrinsic active sites, it is essential to understand the link between various properties of BC and the corresponding mechanisms promoting nonradicals. Machine learning (ML) recently demonstrated significant potential for material design and property enhancement to help tackle this problem. Herein, ML techniques were applied to guide the rational design of BC for the targeted acceleration of nonradical pathways. The results showed a high specific surface area, and O% values can significantly enhance nonradical contribution. Furthermore, the two features can be regulated by simultaneously tuning the temperatures and biomass precursors for efficient directed nonradical degradation. Finally, two nonradical-enhanced BCs with different active sites were prepared based on the ML results. This work serves as a proof of concept for applying ML in the synthesis of tailored BC for persulfate activation, thereby revealing the remarkable capability of ML for accelerating bio-based catalyst development.

Enhanced Sensitivity of Tumor Cells to Autophagy Inhibitors Using Fasting-Mimicking Diet and Targeted Lysosomal Delivery Nanoplatform.

Autophagy is one of the key pathways for tumor cell survival and proliferation. Therefore, inhibition of autophagy has been extensively studied for cancer therapy. However, current autophagy inhibitors lack specificity and are ineffective in limiting tumor progression. Herein, we report a nanoplatform for tumor-site-targeted delivery of hydroxychloroquine (HCQ) using insulin-like growth factors 2 receptor (IGF2R)-targeted liposomes (iLipo-H). A fasting-mimicking diet (FMD) is used to increase the autophagy levels in tumor cells, thereby increasing the sensitivity of tumor cells to HCQ. In addition, FMD treatment upregulates the expression of IGF2R in tumor cells, but not normal cells. Consequently, iLipo-H nanoparticles efficiently accumulate at the tumor site under FMD condition. In vivo studies demonstrate that iLipo-H nanoparticles efficiently inhibit 4T1 tumor growth without obvious side effects, especially under FMD condition. This study provides a promising strategy to increase the sensitivity of tumor cells to autophagy inhibitors for effective cancer therapy.

Effect of cyclodextrin glucosyltransferase extracted from Bacillus xiaoxiensis on wheat dough and bread properties.

In this study, the cyclodextrin glucosyltransferase (CGTase) was extracted from Bacillus xiaoxiensis. CGTase had negative effects on dough viscoelastic properties and gluten strength but had positive effects on bread baking qualities and anti-staling properties. Adding an appropriate amount of CGTase (less than 0.3 U/g) could improve the specific volume, crumb texture, crust color, moisture content, and crumb hardness of bread. The bread crumb with 0.4 U/g CGTase (based on flour weight) had the lowest retrogradation enthalpy of 0.53 ± 0.10 J/g and the lowest relative crystallinity of 16.1%, which indicated the alleviating effect of amylopectin crystallization. Moreover, CGTase reduced the moisture from forming crystal lattices and limited starch molecule migration. The T2 transverse relaxation results showed that the increase of immobilized water content in the bread with CGTase was lower than the control after 5 days of storage, which implied the water-holding capacity of the bread was enhanced and provided information on the inhibition of water migration. Hence, the CGTase could be a potential bread improver.

Direct Presentation of Tumor-Associated Antigens to Induce Adaptive Immunity by Personalized Dendritic Cell-Mimicking Nanovaccines.

Dendritic cells (DCs)-based vaccines are an approved method for inducing potent antigen-specific immune responses to eliminate tumor cells. However, this promising strategy still faces challenges such as tumor-associated antigens (TAAs) loading, lymph node homing, quality control, and other limitations. Here, a personalized DC-mimicking nanovaccine (nanoDC) for stimulation of TAAs-specific T cell populations is developed. The nanoDCs are fabricated using nanoparticles with dendritic structure and membranes from mature bone-marrow-derived cells (BMDCs). Mature BMDCs are stimulated by nanostructures assembled from Escherichia coli and tumor cells to efficiently deliver TAAs and induce BMDCs maturation through the stimulator of interferon genes (STING) pathway. By maintaining co-stimulatory markers, molecules class I (MHC-I) antigen complexes and lymphocyte homing receptors, nanoDCs efficiently migrate to lymph nodes and generate potent antigen-specific T cell responses. Consequently, vaccination with nanoDCs strongly inhibits the tumor growth and metastases formation in vivo. In particular, nanoDCs can also induce memory T cells for long-term protective immunity. This study demonstrates that nanoDCs can trigger adaptive immune protection against tumors for personalized immunotherapy and precision medicine.

Synchronous removal of emulsions and soluble organic contaminants via a microalgae-based membrane system: performance and mechanisms.

In this study, we applied a flexible strategy to manufacture a microalgal biochar-based membrane (MBCM). Due to the hierarchical surface topography on a micro-nano scale, the MBCM was found to have both underwater superoleophobic and underoil superhydrophobic properties. Combining an underoil superhydrophobic oil-containing region (OCR) with an underwater superoleophobic water-containing region (WCR) achieved the successive filtration of multiphase emulsions. The MBCM also served as a high-performance carbocatalyst for advanced oxidation processes (AOPs), due to the N functionalities (5.08%) of the graphene-like structure. This was caused by the high-temperature pyrolysis of rich proteins and alkaline salts in the algal residue. As a result, the MBCM/AOPs system achieved greater than 99.5% emulsions separation efficiency in different emulsion mixtures, while also achieving an outstanding degradation rate (99.8%) of soluble organic contaminants (SOCs). This in-depth exploration resulted in a low-cost and green strategy for developing multifunctional membranes to treat complex wastewater. The paper explains the mechanisms used by MBCM to synchronously remove emulsions and SOCs from wastewater.

Separable Microneedle Patch to Protect and Deliver DNA Nanovaccines Against COVID-19.

The successful control of coronavirus disease 2019 (COVID-19) pandemic is not only relying on the development of vaccines, but also depending on the storage, transportation, and administration of vaccines. Ideally, nucleic acid vaccine should be directly delivered to proper immune cells or tissue (such as lymph nodes). However, current developed vaccines are normally treated through intramuscular injection, where immune cells do not normally reside. Meanwhile, current nucleic acid vaccines must be stored in a frozen state that may hinder their application in developing countries. Here, we report a separable microneedle (SMN) patch to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines and immune adjuvant for efficient immunization. Compared with intramuscular injection, SMN patch can deliver nanovaccines into intradermal for inducing potent and durable adaptive immunity. IFN-γ+CD4/8+ and IL-2+CD4/8+ T cells or virus specific IgG are significantly increased after vaccination. Moreover, in vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses. These features of nanovaccines-laden SMN patch are important for developing advanced COVID-19 vaccines with global accessibility.

Simulation of Lake-Groundwater Interaction under Steady-State Flow.

MODFLOW is one of the most popular groundwater simulation tools available; however, the development of lake modules that can be coupled with MODFLOW is lacking apart from the LAK3 package. This study proposes a new approach for simulating lake-groundwater interaction under steady-state flow, referred to as the sloping lakebed method (SLM). In this new approach, discretization of the lakebed in the vertical direction is independent of the spatial discretization of the aquifer system, which can potentially solve the problem that the lake and groundwater are usually simulated at different scales. The lakebed is generalized by a slant at the bottom of each lake grid cell, which can be classified as fully submerged, dry, and partly submerged. The SLM method accounts for all lake sources and sinks, establishing a governing equation that can be solved using Newton's method. A benchmarking case study was conducted using a modified model setup in the LAK3 user manual. It was found that when there is a sufficient number of layers at the top of the groundwater model, SLM simulates an almost identical groundwater head as the LAK3-based model; when the number of layers decreases, SLM is unaffected while LAK3 may be at a risk of giving unrealistic results. Additionally, the SLM can reflect the relationship between the simulated lake surface area and lake water depth more accurately. Therefore, the SLM method is a promising alternative to the LAK3 package when simulating lake-groundwater interaction.

Graphitic nitride-catalyzed advanced oxidation processes (AOPs) for landfill leachate treatment: A mini review.

Landfill leachate poses significant risks to public health via the release of high-toxicity contaminants, including refractory organic compounds, ammonia-nitrogen compounds, and heavy metals. Significant efforts have been made to develop useful methods for leachate disposition and treatment. Advanced oxidation processes (AOPs) are one of the most promising methods, because they can rapidly degrade diverse pollutants and significantly improve the biodegradability of leachate. Graphitic carbon nitride (g-C3N4), a fascinating conjugated polymer, has become a hot topic in AOP research due to its metal-free benefits and high photosensitivity. Thus, combining AOPs with g-C3N4 achieves excellent degradation of refractory pollutants in leachate. Since the composition of leachate is complex in the practical conditions, the information reported by current studies of using g-C3N4 as a remediator is still incomplete and fragmented. Thus, in this review, the recent status of leachate treatment and approaches for its disposal has been summarized and some conclusions have been drawn. In addition, a brief introduction to g-C3N4 and its application in AOPs for leachate treatment have been critically discussed and with its future outlook assessed. Although the development of g-C3N4 in AOPs for leachate treatment is highly efficient and practical, comprehensive study about its application and technology expansion is urgently needed, based on the complex operating conditions. Perspectives on the treatment of leachate using g-C3N4-AOPs are also included. The information and perspectives provided in this review will provide guidance and novel understanding to accelerate the development of g-C3N4-based AOPs for leachate treatment.

Enhanced Directional Seawater Desalination Using a Structure-Guided Wood Aerogel.

Seawater desalination via solar energy has potential to alleviate freshwater scarcity. However, problems including insufficient air-water interface, large heat loss, and potential ecological impact have restricted its practical viability. Here, a novel wood-derived indirect-contact (hanging) photothermal evaporation system was designed. An evaporation rate of 1.351 kg·m-2·h-1 with efficiency up to 90.89% under one sun illumination (1 kW·m-2) was achieved, which is the highest record to the best of our knowledge. More importantly, a series of simulations and numerical modeling were carried out to analyze the main factors affecting seawater collection and evaporation, and the synergetic mechanisms of oriented seawater collection, photothermal thermogenesis, and natural convection were elucidated. Taken together, this study provides a new wood-derived hanging seawater desalination system with superior mechanical strength, good repeatability, great ecological security, and excellent thermal stability. The corresponding mechanisms of the whole process are shown, and the seawater evaporation efficiency approaching the real demand is maximized.

Interferon gamma inhibits CXCL8-CXCR2 axis mediated tumor-associated macrophages tumor trafficking and enhances anti-PD1 efficacy in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC. METHODS: BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ2 test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values. RESULTS: PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2+CD68+ macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2+CD68+ macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2+CD68+ macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2+CD68+ macrophages by blocking the CXCL8-CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68+ macrophages, which are associated with advanced tumor stage and poor prognosis. CONCLUSION: Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2+CD68+ macrophages via blocking the CXCL8-CXCR2 axis.

Knockdown of RAP2A gene expression suppresses cisplatin resistance in gastric cancer cells.

Cisplatin (DDP) resistance is closely associated with the failure of chemotherapy to manage various different types of human cancer. The GTPase protein Ras-related protein Rap-2a (RAP2A) regulates cancer cell proliferation, migration and invasion; however, little is currently known regarding its role in cancer cell resistance to chemotherapy. The present study investigated the potential roles of the RAP2A gene in gastric cancer cell resistance to DDP treatment. The DDP half maximal inhibitory concentration (IC50) values for the proliferation inhibition of MGC803 and MGC803/DDP gastric cancer cells were determined by treating the cells with a DDP concentration gradient and measuring their survival rates using the Cell Counting Kit-8 (CCK-8) assay; cell viability was also assessed using the CCK-8 assay. Cell migration and invasion were assessed using Transwell Matrigel assays, and apoptosis and DNA damage were evaluated using flow cytometry and Hoechst staining. RAP2A expression was knocked down by siRNA transfection, and RAP2A protein levels were examined using western blotting. The DDP IC50 values for DDP-resistant MGC803/DDP cells were greater than those for MGC803 cells. Furthermore, MGC803/DDP cells exhibited increased levels of viability, migration and invasion, and decreased levels of apoptosis and DNA damage during DDP treatment. Knockdown of RAP2A expression significantly promoted MGC803/DDP cell apoptosis and DNA damage, and decreased the viability and invasion capabilities of these cells following treatment with DDP. The results of the present study revealed that RAP2A expression promotes DDP resistance in gastric cancer cells by increasing their viability, migration and invasion capacities, and by suppressing apoptosis and DNA damage.

A sustainable solution to plastics pollution: An eco-friendly bioplastic film production from high-salt contained Spirulina sp. residues.

Plastic products have become a major contaminant in environmental ecology due to their recalcitrant biodegradation, poor management and risky disposal. Therefore, much research attention has been paid to developing the biodegradable bio-based plastics. However, many of the substitute bioplastics derived from agricultural materials may present a potential threat to food security and eco-systems. Herein, we propose a sustainable, eco-friendly and simple procedure to convert the hazardous high-salt contained microalgal residues into bioplastic film. With 35 % poly (vinyl alcohol) (PVA) assistance, the composite bioplastic films achieved 22 MPa tensile strength under alkali condition and 77 % elongation at break under acidic condition. The average maximum contact angle of 94.4° confirmed a desirable water resistance potential. The synthesis mechanism demonstrated that the inorganic salts existed in microalgal residues could act as the filler in shape of sheets under alkali condition or as the cross linker under acidic condition, significantly enhancing the practical feasibility. This work demonstrates a promising biodegradable bioplastics formed from sustainable eco-friendly waste reutilization process, providing a new insight for fundamentally reducing the plastics pollution.

N-doped graphitic biochars from C-phycocyanin extracted Spirulina residue for catalytic persulfate activation toward nonradical disinfection and organic oxidation.

Biochars are low-cost and environmental-friendly materials, which are promising in wastewater treatment. In this study, biochars were manufactured from C-phycocyanin extracted (C-CP) Spirulina residue (SDBC) via thermal pyrolysis. Simultaneously, N-doping was also achieved from the protein in the algae for obtaining a high-performance carbocatalyst for peroxydisulfate (PDS) activation. The SDBC yielded large specific surface areas, nitrogen loading, and good conductivity, which demonstrated excellent oxidation efficiencies toward a wide array of aqueous microcontaminants. An in-depth mechanistic study was performed by integrating selective radical scavenging, solvent exchange (H2O to D2O), diverse organic probes, and electrochemical measurement, unveiling that SDBC/PDS did not rely on free radicals or singlet oxygen but a nonradical pathway. PDS intimately was bonded with a biochar (SDBC 900-acid, pyrolysis at 900 °C) to form a surface reactive complex that subsequently attacked an organic sulfamethoxazole (SMX) adsorbed on the biochar via an electron-transfer regime. During this process, the SDBC 900-acid played versatile roles in PDS activation, organic accumulation and mediating the electron shuttle from SMX to PDS. This nonradical system can maintain a superior oxidation efficiency in complicated water matrix and long-term stable operation. More importantly, the nonradical species in SDBC 900-acid/PDS system were capable of inactivating the bacteria (Escherichia coli) in wastewater. Therefore, the biochar based nonradical system can provide a mild and high-efficiency strategy for disinfection in waste and drinking water by green carbocatalysis. This study provides not only a value-added biochar catalyst for wastewater purification but also the first insight into the bacteria inactivation via nonradical oxidation.

The inhibitory role of recombinant P-selectin glycoprotein ligand immunoglobulin G on portal vein thrombosis based on a novel rat model.

The current study aimed to reveal a novel method for constructing a portal vein thrombosis (PVT) model in rats and to evaluate the inhibitory role of recombinant P-selectin glycoprotein ligand immunoglobulin G (rPSGL-Ig) on the formation of PVT. The PVT model was constructed in rats through intermittent portal vein obstruction (IPVO) combined with endangium destruction. A total of 4 mg/kg rPSGL-Ig was intraperitoneally pre-injected into rats 1 h prior to model construction. Changes in the thrombus size and vessel diameter were observed by B-scan ultrasonography. Histopathological changes in the portal vein, central hepatic vein and vasa intestini tenuis were observed using hematoxylin and eosin staining. Additionally, histopathological changes in the portal vein were observed by transmission electron microscopy. A total of 8 mg/kg rPSGL-Ig or 2×104 U/kg urokinase were used to compare the thrombolytic effects and thrombus sizes. The PVT model was successfully constructed in rats, and exhibited a significantly greater thrombus size and vessel diameter compared with the control group (P<0.05). Intervention with rPSGL-Ig significantly inhibited the formation of PVT, and resulted in a significantly lower thrombus size and vessel diameter compared with the model group (P<0.05). Additionally, histopathological changes in the portal vein, central hepatic vein and vasa intestini tenuis in PVT rats were considerably reversed following the intervention with rPSGL-Ig. rPSGL-Ig demonstrated a lower thrombolytic effect compared with that of URO. IPVO combined with endangium destruction effectively constructed a PVT model in rats. rPSGL-Ig effectively prevented PVT in rats. rPSGL-Ig may be used in future studies for the treatment of patients with PVT.

Identification of Key lncRNAs Associated With Atherosclerosis Progression Based on Public Datasets.

Atherosclerosis is one of the most common type of cardiovascular disease and the prime cause of mortality in the aging population worldwide. However, the detail mechanisms and special biomarkers of atherosclerosis remain to be further investigated. Lately, long non-coding RNAs (lncRNAs) has attracted much more attention than other types of ncRNAs. In our work, we found and confirmed differently expressed lncRNAs and mRNAs in atherosclerosis by analyzing GSE28829. We performed the weighted gene co-expression network analysis (WGCNA) by analyzing GSE40231 to confirm highly correlated genes. Gene Ontology (GO) analysis were utilized to assess the potential functions of differential expressed lncRNAs in atherosclerosis. Co-expression networks were also constructed to confirm hub lncRNAs in atherosclerosis. A total of 5784 mRNAs and 654 lncRNAs were found to be dysregulated in the progression of atherosclerosis. A total of 15 lncRNA-mRNA co-expression modules were identified in this study based on WGCNA analysis. Moreover, a few lncRNAs, such as ZFAS1, LOC100506730, LOC100506691, DOCK9-AS2, RP11-6I2.3, LOC100130219, were confirmed as important lncRNAs in atherosclerosis. Taken together, bioinformatics analysis revealed these lncRNAs were involved in regulating the leukotriene biosynthetic process, gene expression, actin filament organization, t-circle formation, antigen processing, and presentation, interferon-gamma-mediated signaling pathway, and activation of GTPase activity. We believed that this study would provide potential novel therapeutic and prognostic targets for atherosclerosis.

Deformation of the aquifer system under groundwater level fluctuations and its implication for land subsidence control in the Tianjin coastal region.

This study demonstrates characteristics and mechanisms of deformation of an aquifer system in response to seasonal fluctuations of groundwater level when groundwater pumping has been strictly regulated after experiencing longtime land subsidence. Two boreholes with depth of 1226 m (G2 site) and 905 m (G3 site) were drilled at the Tianjin coastal region where severe land subsidence had occurred since the 1950s. Extensometer/piezometer groups installed at the G2 site illustrate synchronized variations of compaction and groundwater level since 2010 in the aquifer system between depth of 100-400 m which contributes most groundwater pumpage. Monitored land subsidence demonstrates that the shallow aquifer has become the main contributor to the land subsidence, and inelastic compaction still occurred in the aquifers where groundwater level has recovered. Pre-consolidation stresses show that clayey soils in depth < 100 m are under-consolidated, and deep clayey soils show the state of normal- to over-consolidation. The effects of the cyclic groundwater level oscillation on deformation were investigated using repeated loading and unloading tests. Void ratio changes in loading/unloading cycles illustrate that inelastic deformation rate decreases gradually and elastic deformation rate remains almost unchanged with increases of cyclic numbers. The deformation of soil samples from 100 to 400 m is mostly elastic for loading stress in the over-consolidation stress range. These findings suggest that groundwater dewatering in the shallow (depth < 100 m) aquifer will be the primary target to control land subsidence. Groundwater level fluctuations higher than pre-consolidation value in 100-400 m only lead to elastic and recoverable deformation even small residual permanent deformation may continue for a long time. The results improve the understanding of deformation in complex urban aquifers affected by groundwater level fluctuations and highlight the importance of city planning management for controlling land subsidence in coastal cities.