[Scale Effects of Landscape Pattern on Impacts of River Water Quality： A Meta-analysis].

The landscape pattern determines water pollution source and sink processes and plays an important role in regulating river water quality. Due to scale effects, studies on the relationship between landscape pattern and river water quality showed variance at different scales. However, there is still a lack of integrated study on the scale effect of landscape pattern and river water quality dynamics. This study collected 4 041 data from results of previous publications to address the characteristics of landscape pattern and river water quality dynamics at different scales and to identify the key temporal and spatial scales as well as landscape pattern indices for regulating river water quality. The results indicated that, compared to precipitation events, base flow periods, and interannual scales, the high-flow period was the key temporal scale for linking landscape pattern on river water quality. Compared to the watershed scale, the landscape pattern of buffer zones had a greater impact on river water quality. The high-flow period-buffer zone scale was the key spatiotemporal coupling scale for linking landscape pattern and river water quality. Compared to croplands, water bodies, grasslands, and the overall landscape of the watershed, the landscape pattern of forests and urban areas had a greater impact on river water quality. Fragmentation degree was the most important landscape pattern factor regulating river water quality. In river water quality management, it is important to focus on the landscape configuration of buffer zones, increase forest area, reduce patch density of forests and water bodies, and decrease the aggregation degree of urban areas.

[Nitrate Pollution Characteristics and Its Quantitative Source Identification of Major River Systems in China].

Accurate source identification/apportionment is essential for optimizing water NO3--N pollution control strategies. This study conducted a meta-analysis based on data from 167 rivers across China from 2000 to 2022 to analyze the spatial and temporal variation patterns of nitrate pollution in seven major river systems and to quantitatively identify the source composition of riverine nitrate. The average ρ（NO3--N） in the seven major river systems was （4.54±3.99） mg·L-1， with 9.6% of river ρ（NO3--N） exceeding 10 mg·L-1. The riverine ρ（NO3--N） in eastern China were higher than that in western China， and the highest concentration was observed in the Haihe River system. Additionally， tributaries experienced more serious NO3--N pollution than that in the main stream. The ρ（NO3--N） in most river systems in the dry season was higher than that in the wet season， except in the Yellow River system. There was significant nitrification in the Pearl River system， the middle and lower reaches of the Yellow River system， the middle reaches of the Liaohe River system， the Songhua River system， and the Haihe River system， whereas there was significant denitrification in the Yangtze River system， the Huaihe River system， and the lower reaches of the Pearl River system. Based on the dual stable isotopes-based MixSIAR model， the major NO3--N source was sewage/manure （ > 50%） in the Yangtze River system， Haihe River system， Liaohe River system， and Southeast River system. Soil nitrogen was the main NO3--N source in the Songhua River system （56.4%）， and the contribution of fertilizer nitrogen， soil nitrogen， and sewage/manure to NO3--N pollution in the Pearl River system， Huai River system， and Yellow River system was 20%-40%. The contribution rate of sewage/manure to NO3--N in the tributaries was higher than that in the main stream， whereas the contribution rate of soil nitrogen to NO3--N in the main stream was higher than that in the tributaries. The contribution rate of soil nitrogen， fertilizer nitrogen， and atmospheric deposition nitrogen to nitrate nitrogen in the wet season was higher than that in the dry season， whereas the contribution rate of sewage/manure to NO3--N pollution in the dry season was higher than that in the wet season. Therefore， point source pollution such as domestic and production sewage discharge should be controlled in the Haihe River system， the Yangtze River system， the Liaohe River system， the tributaries and the downstream main stream areas of Yellow River system， and the downstream area of the Pearl River system， whereas non-point source pollution caused by the loss of fertilizer and soil nitrogen should be controlled in the Huaihe River system， the Songhua River system， the middle reaches of the main stream area of the Yellow River system， and the middle and upper reaches of the Pearl River system. The results can provide a scientific basis for the effective control of nitrate pollution in the river systems in China.

High-Precision Printing of Flexible MXene Patterns for Dynamically Tunable Electromagnetic Interference Shielding Performance.

Smart electromagnetic interference (EMI) shielding materials are of great significance in coping with the dynamic performance demands of cutting-edge electronic devices. However, smart EMI shielding materials are still in their infancy and face a variety of challenges (e.g., large thickness, limited tunable range, poor reversibility, and unclear mechanisms). Here, we report a method for controllable shielding electromagnetic (EM) waves through subwavelength structure changes regulated by the customized structure via a direct printing route. The highly conductive MXene ink is regulated with metal ions (Al3+ ions), giving superb metallic conductivity (∼5000 S cm-1) for the printed lines without an annealing treatment. The reversible tunability of EMI shielding effectiveness (SE) ranging from 8.2 dB ("off" state) to 34 dB ("on" state) is realized through the controllable modulation of subwavelength structure driven by stress. This work provides a feasible strategy to develop intelligent shielding materials and EM devices.

Safety and efficacy of immune checkpoint inhibitor rechallenge in advanced non-small cell lung cancer: a retrospective study.

We conducted a retrospective study to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in patients with advanced non-small cell lung cancer (NSCLC). The study included 111 patients who had previously received ICI therapy and experienced disease progression. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Our findings revealed that the ICI rechallenge showed promising results in improving patient outcomes. OS (r) is the time from rechallenging with immune checkpoint inhibitors to the last follow-up or death from any cause. The median OS (r) was 14.3 months (95% CI 11.3-17.3 months), with a median PFS (r) of 5.9 months (95% CI 4.1-7.7 months). The ORR was 17.1%; the DCR was 82.3%. Subgroup analysis demonstrated that patients without brain or liver metastases had a longer OS (r) compared to those with metastases (21.6 vs. 13.8 months, χ2 = 3.873, P = 0.046; 20.8 vs. 9.1 months, χ2 = 10.733, P = 0.001, respectively). Moreover, patients without driver gene mutations exhibited significantly longer OS than those with mutations or wild-type patients (22.9 vs. 16.1 vs. 7.5 months, χ2 = 10.710, P = 0.005). Notably, patients who switched to a different ICI during the rechallenge had shorter OS than those who did not change medications (10.4 vs. 21.1 months, χ2 = 9.014, P = 0.003). The incidence of immune-related adverse events did not significantly differ between the two treatment phases. These findings suggest that ICI rechallenge may be a viable therapeutic strategy for select NSCLC patients. Further prospective studies are needed to validate these results and guide treatment decisions for advanced NSCLC.

Biphasic GaIn Alloy Constructed Stable Percolation Network in Polymer Composites over Ultrabroad Temperature Region.

Flexible and adaptable polymer composites with high-performance reliability over wide temperature range are imperative for various applications. However, the distinct filler-matrix thermomechanical behaviors often cause severe structure damage and performance degradation upon large thermal shock. To address this issue, a general strategy is proposed to construct leakage-free, self-adaptive, stable percolation networks in polymer composites over wide temperature (77-473 K) with biphasic Ga35In65 alloy. The in situ micro-CT technology, for the first time, reveals the conformable phase transitions of Ga35In65 alloys in the polymer matrix that help repair the disruptive conductive networks over large temperature variations. The cryo-expanded Ga compensates the disruptive carbon networks at low temperatures, and flowable Ga and melted In at high temperatures conformably fill and repair the deboned interfaces and yielded crevices. As a proof-of-concept, this temperature-resistant composite demonstrates superb electrical conductivity and electromagnetic interference shielding properties and stability even after a large temperature shock (ΔT = 396 K). Furthermore, the superiority of the construction of temperature self-adaptive networks within the composite enables them for additive manufacturing of application-oriented components. This work offers helpful inspiration for developing high-performance polymer composites for extreme-temperature applications.

Developmental toxicity in Daphnia magna induced by environmentally relevant concentrations of carbon black: From the perspective of metabolomics and symbiotic bacteria composition.

The level of carbon black (CB) pollution in the environment is rapidly increasing, owing to the increase in natural and industrial emissions. The water environment has become an important sink for CB. However, studies on CB mainly focused on its impact on air pollution and phytoremediation applications, and the toxicity mechanism of CB in aquatic organisms is relatively limited. Thus, Daphnia magna was used as a model organism to explore the developmental toxicity of environmentally relevant concentrations of CB under a full life-cycle exposure. The toxicity mechanism of CB in aquatic organisms was investigated based on metabolomic and symbiotic microbial analyses. It was found that compared with the control group, the body length of exposed D. magna decreased, while the mortality and intestinal inflammation increased with increasing concentration of CB. The normal reproductive regularity of D. magna was disturbed, and the deformity and body length of the offspring increased and decreased, respectively, after CB exposure. Metabolomic analysis showed that the urea cycle metabolic pathway of exposed D. magna was increased significantly, suggesting a perturbation of N metabolism. In addition, two eicosanoids were increased, suggesting possible inflammation in D. magna. The levels of seven phospholipid metabolites decreased that might be responsible for offspring malformations. Microbiological analysis showed that the composition of the symbiotic microbial community of D. magna was disturbed, including microorganisms involved in carbon cycling, nitrogen cycling, and biodegradation of pollutants, as well as pathogenic microorganisms. Overall, this study found that the inflammatory related metabolites and symbiotic bacterial, as well as reproductive related metabolites, were disrupted after D. magna exposed to different concentrations of CB, which revealed a possible developmental toxicity mechanism of CB in D. magna. These findings provide a scientific basis for analyzing the risks of CB in aquatic environments.

Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson's disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

Three-Dimensional Mirror-Assisted and Concave Pyramid-Shaped Solar-Thermal Steam Generator for Highly Efficient and Stable Water Evaporation and Brine Desalination.

Although significant advances have been achieved in developing solar-driven water evaporators for seawater desalination, there is still room for simultaneously enhancing water evaporation efficiency, salt resistance, and utilization of solar energy. Herein, for the first time, we demonstrate a highly efficient three-dimensional (3D) mirror-assisted and concave pyramid-shaped solar-thermal water evaporation system for high-yield and long-term desalination of seawater and brine water, which consists of a 3D concave pyramid-shaped solar-thermal architecture on the basis of polypyrrole-coated nonwoven fabrics (PCNFs), a 3D mirror array, a self-floating polystyrene foam layer, and a tail-like PCNF for upward transport of water. The 3D concave pyramid-shaped solar-thermal architecture enables multiple solar light reflections to absorb more solar energy, while the 3D mirror-assisted solar light enhancement design can activate the solar-thermal energy conversion of the back side of the concave pyramid-shaped PCNF architecture to improve the solar-thermal energy conversion efficiency. Crucially, selective accumulation of the precipitated salts on the back side of the concave pyramid-shaped architecture is realized, ensuring a favorable salt-resistant feature. The 3D mirror-assisted and concave pyramid-shaped solar-driven water evaporation system achieves a record high water evaporation rate of 4.75 kg m-2 h-1 under 1-sun irradiation only and exhibits long-term desalination stability even when evaporating high-salinity brine waters, demonstrating its great applicability and reliability for high-yield solar-driven desalination of seawater and high-salinity brine water.

Two-Dimensional Janus MXene Inks for Versatile Functional Coatings on Arbitrary Substrates.

Solution processing of two-dimensional nanomaterial inks guarantees efficient, straightforward fabrication of functional films, coatings, flexible devices, etc. Despite the excellent solution processibility and viscoelasticity of MXene aqueous inks, formulation of nonaqueous MXene inks with great affinity to both hydrophilic and hydrophobic substrates has proven quite challenging, limiting the practical applications of MXenes in printing/coatings on various substrates. Here, MXene surface chemistry is manipulated by asymmetrically grafting polystyrene and further concentrating the flakes into additive-free Janus MXene organic inks. The modified MXene nanosheets exhibit hydrophilicity on one side and hydrophobicity on the other. As a result, Janus MXene nanosheets ensure broad dispersibility in polar and nonpolar solvents, which in turn greatly extends the ink shelf life by slowing down the oxidation kinetics. Janus MXene sheets dispersed in toluene at room temperature remain at 90% of the initial solids after 1 month of storage. Janus surface engineering on MXene flakes guarantees the straightforward formation of uniform yet firm, large-area coatings on hydrophilic or hydrophobic substrates. These coatings demonstrate improved photothermal properties and chemical stability as well as good electromagnetic interference shielding performance. This strategy provides a simple and cost-effective way to promote the performance of MXene electronics in a variety of applications.

Efficient Preconstruction of Three-Dimensional Graphene Networks for Thermally Conductive Polymer Composites.

Electronic devices generate heat during operation and require efficient thermal management to extend the lifetime and prevent performance degradation. Featured by its exceptional thermal conductivity, graphene is an ideal functional filler for fabricating thermally conductive polymer composites to provide efficient thermal management. Extensive studies have been focusing on constructing graphene networks in polymer composites to achieve high thermal conductivities. Compared with conventional composite fabrications by directly mixing graphene with polymers, preconstruction of three-dimensional graphene networks followed by backfilling polymers represents a promising way to produce composites with higher performances, enabling high manufacturing flexibility and controllability. In this review, we first summarize the factors that affect thermal conductivity of graphene composites and strategies for fabricating highly thermally conductive graphene/polymer composites. Subsequently, we give the reasoning behind using preconstructed three-dimensional graphene networks for fabricating thermally conductive polymer composites and highlight their potential applications. Finally, our insight into the existing bottlenecks and opportunities is provided for developing preconstructed porous architectures of graphene and their thermally conductive composites.

Knockdown of tankyrase 1 inhibits the progression of gastric adenocarcinoma via regulating human telomerase reverse transcriptase and telomeric repeat binding factor 1.

Background: Gastric cancer is one of the most lethal cancers. Aberrant expression levels of genes are frequently associated with cell immortalization and the occurrence of tumors. In this study, we aimed to investigate the role of tankyrase 1 (TANK1) in gastric adenocarcinoma and clarify the underlying mechanism. Methods: The messenger RNA (mRNA) levels of TANK1, human telomerase reverse transcriptase (h-TERT), and telomeric repeat binding factor 1 (TRF1) in clinical specimens and SGC-7901 cells were measured via real-time quantitative polymerase chain reaction (RT-qPCR). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry (IHC) assays were utilized to observe the cell apoptosis as well as Ki67 and h-TERT expression in tumor-bearing models. The effects of TANK1 antisense oligonucleotides (TANK1 ASODN) on viability and apoptosis of SGC 7901 cells were evaluated by cell counting kit-8 and flow cytometry analysis. Results: We found that TANK1 and h-TERT were both increased in gastric adenocarcinoma, while TRF1 was decreased. Tumor-bearing models demonstrated that TANK1 ASODN appeared to be effective in inhibiting tumor growth and decreasing the expression of h-TERT. Additionally, TANK1 ASODN inhibited the viability and promoted apoptosis of SGC-7901 cells. Moreover, the mRNA levels of h-TERT and TRF1 were modulated by TANK1 ASODN. Conclusions: This study revealed that TANK1 ASODN inhibits the proliferation and induced the apoptosis of gastric adenocarcinoma cells via manipulating the expression levels of h-TERT and TRF1.

Super-Tough and Environmentally Stable Aramid. Nanofiber@MXene Coaxial Fibers with Outstanding Electromagnetic Interference Shielding Efficiency.

Although electrically conductive and hydrophilic MXene sheets are promising for multifunctional fibers and electronic textiles, it is still a challenge to simultaneously enhance both conductivity and mechanical properties of MXene fibers because of the high rigidity of MXene sheets and insufficient inter-sheet interactions. Herein, we demonstrate a core-shell wet-spinning methodology for fabricating highly conductive, super-tough, ultra-strong, and environmentally stable Ti3C2Tx MXene-based core-shell fibers with conductive MXene cores and tough aramid nanofiber (ANF) shells. The highly orientated and low-defect structure endows the ANF@MXene core-shell fiber with super-toughness of ~ 48.1 MJ m-3, high strength of ~ 502.9 MPa, and high conductivity of ~ 3.0 × 105 S m-1. The super-tough and conductive ANF@MXene fibers can be woven into textiles, exhibiting an excellent electromagnetic interference (EMI) shielding efficiency of 83.4 dB at a small thickness of 213 µm. Importantly, the protection of the ANF shells provides the fibers with satisfactory cyclic stability under dynamic stretching and bending, and excellent resistance to acid, alkali, seawater, cryogenic and high temperatures, and fire. The oxidation resistance of the fibers is demonstrated by their well-maintained EMI shielding performances. The multifunctional core-shell fibers would be highly promising in the fields of EMI shielding textiles, wearable electronics and aerospace.

[Estimation of Nitrous Oxide Emission from River System Based on Water Discharge and Dissolved Nitrous Oxide Concentration].

Due to increasing active nitrogen pollution loads, river systems have become an important source of nitrous oxide (N2O) in many areas. Due to the lack of monitoring data in many studies as well as the difficulty in estimating intermediate parameters and expressing temporal-spatial variability in current methods, a high level of uncertainty remains in the estimates of riverine N2O emission quantity. Based on the monthly monitoring efforts conducted for 10 sampling sites across the Yonganxi River system in Zhejiang Province from June 2016 to July 2019, the temporal and spatial dynamics of riverine N2O dissolved concentrations ρ(N2O), N2O fluxes, and their influencing factors were addressed. A multiple regression model was then developed for predicating riverine N2O emission flux to estimate annual N2O emission quantity for the entire river system. The results indicated that observed riverine ρ(N2O) (0.03-2.14 µg·L-1) and the N2O fluxes[1.32-82.79 µg·(m2·h)-1] varied by 1-2 orders of magnitude of temporal-spatial variability. The temporal and spatial variability of ρ(N2O) were mainly influenced by the concentrations of nitrate, ammonia, and dissolved organic carbon, whereas the N2O emission fluxes were mainly affected by river water discharges and ρ(N2O). A multiple regression model that incorporates variables of river water discharge and ρ(N2O) could explain 90% of the variability in riverine N2O emission fluxes and has high accuracy. The model estimated N2O emission quantity from the entire Yonganxi River system of 3.67 t·a-1, with 29% from the main stream and 71% from the tributaries. The IPCC default emission factor method might greatly overestimate and underestimate N2O emission quantities for rivers impacted by low and high pressures of human activities, respectively. This study advances our quantitative understanding of N2O emission for the entire river system and provides a reference method for estimating riverine N2O emission with more accuracy.

Development of a bioavailable Hg(II) sensing system based on MerR-regulated visual pigment biosynthesis.

Engineered microorganisms have proven to be a highly effective and robust tool to specifically detect heavy metals in the environment. In this study, a highly specific pigment-based whole-cell biosensor has been investigated for the detection of bioavailable Hg(II) based on an artificial heavy metal resistance operon. The basic working principle of biosensors is based on the violacein biosynthesis under the control of mercury resistance (mer) promoter and mercury resistance regulator (MerR). Engineered biosensor cells have been demonstrated to selectively respond to Hg(II), and the specific response was not influenced by interfering metal ions. The response of violacein could be recognized by the naked eye, and the time required for the maximum response of violacein (5 h) was less than that of enhanced green fluorescence protein (eGFP) (8 h) in the single-signal output constructs. The response of violacein was almost unaffected by the eGFP in a double-promoter controlled dual-signals output construct. However, the response strength of eGFP was significantly decreased in this genetic construct. Exponentially growing violacein-based biosensor detected concentrations as low as 0.39 µM Hg(II) in a colorimetric method, and the linear relationship was observed in the concentration range of 0.78-12.5 µM. Non-growing biosensor cells responded to concentrations as low as 0.006 µM Hg(II) in a colorimetric method and in a Hg(II) containing plate sensitive assay, and the linear relationship was demonstrated in a very narrow concentration range. The developed biosensor was finally validated for the detection of spiked bioavailable Hg(II) in environmental water samples.

Anisotropic CoFe2O4@Graphene Hybrid Aerogels with High Flux and Excellent Stability as Building Blocks for Rapid Catalytic Degradation of Organic Contaminants in a Flow-Type Setup.

Macroscopic three-dimensional catalytic materials could overcome the poor operability and avoid secondary pollution of common powdery counterparts, especially in flow-type setups. However, conventional isotropic graphene-based aerogels and foams have randomly distributed graphene sheets, which may cause stream erosion and reduce the flux seriously. Herein, for the first time, we design and fabricate a novel anisotropic CoFe2O4@graphene hybrid aerogel (CFO@GA-A) with a hydrothermal synthesis followed by directional-freezing and freeze-drying for a tube-like flow-type setup analogous to a wastewater discharge pipeline. The long and vertically aligned pores inside the aerogel provide an exceptional flux of 1100 L m-2 h-1, 450% higher than that of the rough and zigzag paths in the isotropic CoFe2O4@graphene hybrid aerogel (CFO@GA-I), and the leaching of metal ions is obviously inhibited by relieving the erosion of CoFe2O4. Besides, the CFO@GA-A could sustain the scour of high-speed flowing wastewater and maintain its structural stability. Therefore, organic contaminants of indigo carmine, methyl orange, orange II, malachite green, phenol, and norfloxacin could readily flow over the nanocatalysts and be degraded rapidly within 7.5-12.5 min at varied flow rates from 60 to 120 mL h-1. The CFO@GA-A also exhibits a much better long-term stability with removal efficiencies toward indigo carmine at 100%, 91%, and 85% for at least 30 h (60 mL h-1), 25 h (90 mL h-1), and 21 h (120 mL h-1), respectively. On the contrary, the CFO@GA-I exhibits unsatisfactory removal efficiencies of <40%. Interestingly, CFO@GA-A could also serve as building blocks to stack on each other for degrading intense flowing wastewater, exhibiting an outstanding composability. The high-flux and long-term stability make the CFO@GA-A promising as an ideal catalytic material for wastewater treatments.

Hollow-structured MXene-PDMS composites as flexible, wearable and highly bendable sensors with wide working range.

Although versatile piezoresistive pressure sensors show a great potential as human motion detection and wearable smart devices, it is still an issue to widen their working range and enhance their sensitivity. Herein, hollow-structured MXene-polydimethylsiloxane composites (MPCs) are fabricated by utilizing nickel foam as the three-dimensional substrate for dip-coating of MXene sheets followed by infiltrating of polydimethylsiloxane and etching of the nickel foam substrate. The resultant MPC performs a wide working range with bending angles of 0° to 180°, an excellent long-term reliability up to 1000 cycles under the bending angles of 15°, 30° and 150°, and a stable durability with a bending angle of 30° in a frequency range from 0.05 to 2 Hz as a bendable piezoresistive pressure sensor, which is attributed to the formation of dense conduction paths due to the interconnection of MXene sheets during the deformation of MPC. The sensor also exhibits an extremely low detection limit of 10 mg for pressure detection. Interestingly, the slippage of adjacent MXene sheets is beneficial for monitoring slight vibration of equipments and detecting subtle human motions. Thus, the MPC sensor could be applied for stereo sound and ultrasonic vibration monitoring, swallowing, facial muscle movement, and various intense motion detections, demonstrating its great potential as wearable smart devices.

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway.

Tumor cell migration is a critical step in cancer metastasis. Over-activated Notch pathway can promote the migration of cancer cells, especially in the breast cancer. However, the underlying mechanism of non-canonical Notch signaling in modulating the migration has not yet been clearly characterized. Here we demonstrated that DAPT, a gamma secretase inhibitor, inhibited protrusion formation and cell motility, and then reduced the migration of triple-negative breast cancer cells, through increasing the activity of Cdc42 by non-canonical Notch pathway. Phosphorylation of AKT on S473 was surprisingly increased when Notch signaling was inhibited by DAPT. Inhibition of PI3K and AKT by LY294002 and MK2206, respectively, or knockdown of AKT expression by siRNA blocked DAPT-induced activation of Cdc42. Moreover, immunofluorescence staining further showed that DAPT treatment reduced the formation of lamellipodia and induced actin cytoskeleton remodeling. Taken together, these results indicated that DAPT inhibited Notch signaling and consequently activated PI3K/AKT/Cdc42 signaling by non-canonical pathway, facilitated the formation of filopodia and inhibited the assembly of lamellipodia, and finally resulted in the decrease of migration activity of breast cancer cells.

Highly sensitive, reliable and flexible piezoresistive pressure sensors featuring polyurethane sponge coated with MXene sheets.

Flexible pressure sensors still face a great challenge to combine fast frequency response, wide pressure range, multiple detection modes, satisfactory mechanical and environmental stability, and simple fabrication process into a sensor. Herein, flexible piezoresistive pressure sensors are fabricated by treating the backbone of polyurethane (PU) sponge with chitosan (CS) to obtain positively charged CS@PU sponge, followed by dip-coating of negatively charged Ti3C2Tx MXene sheets. The resulting MXene@CS@PU sponge-based sensor provides a versatile sensing platform with potentials for detecting both small and large pressure signals. Due to the highly compressive resilience of the PU sponge and its polar interaction with the MXene sheets, the MXene@CS@PU sensor has high compressibility and stable piezoresistive response for compressive strains of up to 85% with a stress of 245.7 kPa, and it also exhibits a satisfactory reproducibility for 5000 compression-release cycles. Even after washing in water for 1 h, the sensor still shows good performances. With a rapid response time of only 19 ms and a low detection limit of 30 µN corresponding to a pressure of 9 Pa, the MXene sponge sensor is promising for detecting human physiological signals and insect movements. In addition to the contact mode detection, the sponge sensor could detect voices and human breaths by a non-contact detection mode.

Efficacy and safety of external application of Traditional Chinese Medicine for the treatment of acute gouty arthritis: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA). METHODS: Six electronic data bases were retrieved from their inception to march 2017. 15 randomized controlled clinical trials (RCTs) were included. The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software; and related data was counted using Stata14.0 software. RESULTS: There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD = 1.093, 95% CI (－2.514, 4.701); P = 0.553)]. In terms of overall efficacy, the EATCM's treatment group was significantly superior to control group [(OR = 3.692; 95% CI (2.408, 5.661); P < 0.001)]. The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR = 0.135; 95% CI (0.067, 0.274); P < 0.001)]. All these funnel plots showed unlikelihood of publishing bias. But due to excessive heterogeneity, the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain. CONCLUSION: The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions, although the evidence is weak owing to the low methodological quality and the small number of the included trials.