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Background: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. Methods: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. Results: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. Conclusion: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

To further improve the strength of an Al–Ce alloy, the effects of electromagnetic stirring treatment, Sc–Zr microalloying, and their compound action on the microstructure and properties of the Al–8Ce alloy were investigated for the first time in this study. The results show that the primary α-Al becomes coarse, the eutectic Al11Ce3 phase is refined and the lamellar spacing increases significantly due to the combined effect of forced convection of electromagnetic field and dendrite fragmentation and nucleation in Al–8Ce alloy after electromagnetic stirring treatment. After the Sc–Zr microalloying treatment of the Al–8Ce alloy, the α-Al changes from a dendritic to fine round morphology, and the eutectic Al11Ce3 phase changes from lamellar to fibrous, which is due to the heterogeneous nucleation of Al3(Sc, Zr) phase and the adsorption refinement caused by the enrichment of Sc and Zr. The optimization effect of Sc–Zr microalloying on the mechanical properties of the Al–8Ce alloy was better than that of electromagnetic stirring and their synergistic treatment. The tensile strength and yield strength of Al–8Ce alloy with Sc–Zr additions were increased from 157 MPa to 85 MPa–192 MPa and 115 MPa, respectively, by 22.3 % and 35.3 %. After aging treatment, the tensile strength (from 192 to 272 MPa) and yield strength (from 115 to 221 MPa) significantly improved owing to the secondary precipitation of Al3(Sc, Zr) particles. The precipitation strengthening of the Al3(Sc, Zr) phase was the main contributor to the high yield strength of the alloy.

Abstract Unprecedented levels of seismicity have been seen in southern Sichuan, China, since the large‐scale exploitation of shale gas. Fluid and pore pressure transported through hydrological channel are thought as pivotal elements in the induction of earthquakes. Our high‐resolution tomography results reveal two inclined seismic anomalies featured by low Vs and high Vp/Vs at different depth range. The deeper anomaly extends 15 km from NE to SE and connects the well g048 from 3 km depth to the vicinity of the Ms 4.7 Gongxian earthquake 5.4 km deep, which is hinted to be a hydrological channel inferred from the high fluid overpressure of 28 Mpa calculated from focal mechanism solution. The injection operation of multiple shale gas wells along the channel may potentially accumulate the pore pressure and cause the fault near the end of the channel to reach critical stress state through various mechanisms.

Solar distillation is a sustainable and promising technique to generate fresh water. However, the solar vapor generation is a high energy consumption process, resulting in a low water yield under natural sunlight. Hence, developing of advanced evaporators that can simultaneously reduce the energy requirement of water vaporization and accelerate solar water evaporation remains a great challenge. In this study, we report the fabrication of a multifunctional hydrogel of HxMoO3/PNIPAM with PNIPAM as hydratable skeleton and HxMoO3 as the light-absorbing unit for solar water evaporation. The experimental results demonstrate that the as-prepared hydrogel owns excellent photothermal activity. Accurately, the fabricated hydrogel -based solar evaporators achieved high water evaporation rate of 1.65 kg m−2 h−1 with the energy conversion efficiency of 85.87% under 1 kW m−2 irradiation. The enhanced photothermal activity of HxMoO3/PNIPAM hydrogel can be attributed to the synergistic effects of the components composed in this hierarchical architecture that change the water state and further speed up water evaporation. The HxMoO3/PNIPAM evaporators indicate its great potential for practical implementation of solar water evaporation.

Abstract Gastrointestinal cancer (GIC) is a common malignant tumour of the digestive system that seriously threatens human health. Due to the unique organ structure of the gastrointestinal tract, endoscopic and MRI diagnoses of GIC in the clinic share the problem of low sensitivity. The ineffectiveness of drugs and high recurrence rates in surgical and drug therapies are the main factors that impact the curative effect in GIC patients. Therefore, there is an urgent need to improve diagnostic accuracies and treatment efficiencies. Nanotechnology is widely used in the diagnosis and treatment of GIC by virtue of its unique size advantages and extensive modifiability. In the diagnosis and treatment of clinical GIC, surface-enhanced Raman scattering (SERS) nanoparticles, electrochemical nanobiosensors and magnetic nanoparticles, intraoperative imaging nanoparticles, drug delivery systems and other multifunctional nanoparticles have successfully improved the diagnosis and treatment of GIC. It is important to further improve the coordinated development of nanotechnology and GIC diagnosis and treatment. Herein, starting from the clinical diagnosis and treatment of GIC, this review summarizes which nanotechnologies have been applied in clinical diagnosis and treatment of GIC in recent years, and which cannot be applied in clinical practice. We also point out which challenges must be overcome by nanotechnology in the development of the clinical diagnosis and treatment of GIC and discuss how to quickly and safely combine the latest nanotechnology developed in the laboratory with clinical applications. Finally, we hope that this review can provide valuable reference information for researchers who are conducting cross-research on GIC and nanotechnology. Graphical Abstract

Abstract A smart textile that could harvest mechanical‐energy for photo‐thermal energy utilization facilitates the development of a flexible self‐heating wearable device. This study presents novel triboelectric materials with a dynamic‐bond‐cross‐linking azobenzene‐based polymer (PAzo‐M) with diverse metal ions. The flexible nylon fabric coated with PAzo‐M (NF@PAzo‐M) serves as a friction layer of the photothermal triboelectric nanogenerator (PT‐TENG) to harvest human mechanical energy. The prepared PT‐TENG could exhibit a maximum open‐circuit voltage of up to 188.8 V with excellent electron loss capability because of its minimum vertical electron affinity of internal ion. And it can harvest mechanical energy from human motion (0.5–1 Hz) to drive the self‐powering irradiation of ultraviolet light or visible light, leading to the reversible isomerization of NF@PAzo‐M. The NF@PAzo‐M textile cyclically utilizes photo‐thermal energy for self‐heating. These results suggest new opportunities to harvest human mechanical energy for self‐powering multifunctional wearable devices for functions.

ObjectiveTo explore the effect of the family-centered empowerment model (FECM) on reducing anxiety, improving care ability, and readiness for hospital discharge of main caregivers of preterm infants.MethodsThe primary caregivers of preterm infants who were admitted to the Neonatal intensive care Unit (NICU) of our center from September 2021 to April 2022 were selected as the research objects. According to the wishes of the primary caregivers of preterm infants, they were divided into group A (FECM group) and group B (non-FECM group). The intervention effects were evaluated with the Anxiety Screening Scale (GAD-7), the Readiness for Hospital Discharge Scale-Parent Version (RHDS-Parent Form), and the Primary Caregivers of Premature Infants Assessment of Care Ability Questionnaire.ResultsBefore the intervention, there was no statistically significant difference in the general information, anxiety screening, the scores of each dimension, and total score of the comprehensive ability of the main caregivers, and the score of caregiver preparedness between the two groups (P > 0.05). After the intervention, there were statistically significant differences in the anxiety screening, the total score and total score of each dimension of the care ability, and the score of caregiver preparedness between the two groups (P

Abstracts: The effects of Sc and Zr on the microstructure and properties of Al–3Fe alloys were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and mechanical property testing. The results show that the Al3(Sc, Zr) phases with a L12 structure are formed with the addition of Sc and Zr, which promotes the heterogeneous nucleation, reduces the segregation and improve columnar grains. In the process of iron-rich phase nucleation and growth, Sc and Zr atoms are adsorbed around iron-rich phases, which prevents the growth of iron-rich intermetallics and makes the needle-like primary Al3Fe phases gradually change to short rod-like, butterfly-like and flower-like morphologies. Additionally, the fibrous eutectic Al6Fe phases are also observed. With increasing the Sc and Zr contents from 0 to 0.35 wt% and 0 to 0.14 wt%, respectively, the strength of the alloy increases and the elongation decreases. The Al–3Fe alloy with the addition of 0.16 wt% Sc and 0.06 wt% Zr has a tensile strength of 160.8 MPa and a yield strength of 132.4 MPa. During aging process, fine, dispersed and coherent nanoscale secondary Al3(Sc, Zr) (L12 structure) phases are formed in the α-Al matrix to promote precipitation strengthening. When the addition of Sc and Zr is 0.35 wt% and 0.14 wt%, respectively, the refinement effect on the macrostructure and the second phase is most obvious. After aging, the tensile strength reaches 233 MPa and the yield strength reaches 200 MPa.

This paper applies Reynolds-averaged Navier-Stokes (RANS) method to study propulsion performance in head and oblique waves. Finite volume method (FVM) is employed to discretize the governing equations and SST k-ω model is used for modeling the turbulent flow. The free surface is solved by volume of fluid (VOF) method. Sliding mesh technique is used to enable rotation of propeller. Propeller open water curves are determined by propeller open water simulations. Calm water resistance and wave added resistances are obtained from towing computations without propeller. Self-propulsion simulations in calm water and waves with varying loads are performed to obtain self-propulsion point and thrust identify method is use to predict propulsive factors. Regular head waves with wavelengths varying from 0.6 to 1.4 times the length of ship and oblique waves with incident directions varying from 0° to 360° are considered. The influence of waves on propulsive factors, including thrust deduction and wake fraction, open water, relative rotative, hull and propulsive efficiencies are discussed.

Abstract The September 2022 Ms 6.8 Luding earthquake broke more than 230 years of seismic calm on the Moxi fault, providing a unique opportunity to understand its seismogenic environment, rupture dynamics, and seismic hazard. Using teleseismic body waves, regional strong‐motion observations, GNSS, and InSAR data, we decipher the spatiotemporal rupture evolution of the mainshock. Combining the elastic dislocation model with surface creep, we find that the coseismic slip correlates closely with a locked patch with a loading rate of 9.7 mm/yr, but the creeping rate is insufficient to make up the shallow slip deficit. Notably, the Luding earthquake ruptured only ∼1/4 of the Moxi seismic gap, and it further increased the stress in the unruptured northern part. We thus argue that the Moxi fault has the potential for magnitude 7+ earthquakes in the near future, although geodetic prediction may overestimate the actual seismic moment released by the coseismic rupture.

ObjectiveThis study aims to explore the effect of perceived social support on college students’ autonomous fitness behavior, and the mediating role of mental toughness and exercise self-efficacy.MethodologyA survey participated by 985 college Students (average age, 19.55) was conducted by applying the following scales: The Perceived Social Support Scale, the Adolescent Self-Government Behavior Scale, the Mental Toughness Scale, and the Exercise Self-efficacy Scale (ESES).Results(1) Perceived social support can directly and positively predict autonomous fitness behavior, mental toughness, and exercise self-efficacy; mental toughness can directly and positively predict exercise self-efficacy. Likewise, perceived social support, mental toughness, and exercise self-efficacy can positively predict autonomous fitness behavior. (2) The indirect effect of the path with mental toughness as the mediating variable is 0.078, the indirect effect of the path with exercise self-efficacy as the mediating variable is 0.122, and the indirect effect of the path with mental toughness and exercise self-efficacy as the mediating variable is 0.082. (3) The total of all indirect effects is 0.282, and the effects of the three indirect pathways account for 18.25, 28.62, and 19.37% of the total, respectively.ConclusionThe perceived social support can indirectly predict college students’ autonomous fitness behavior through the independent mediating effect of mental toughness and self-efficacy, as well as the chain mediating effect of the two. The claim that mental toughness and exercise self-efficacy perform a chain-mediate role in the positive effect brought by perceived social support on autonomous fitness behavior has been supported. This study revealed the relationship and mechanism between perceived social support and college students’ autonomous fitness behavior and further improved the research on the impact of perceived social support on college students’ autonomous fitness behavior.

Aqueous proton batteries (APBs) have aroused attention because of the proton as charge carrier with smaller ionic size and faster kinetics when compared to the metallic ions in aqueous solutions. Although phenazine-based organic compounds with available redox-active sites are considered as promising organic electrode materials, the comprehensive study of their proton-storage behaviors and APB applications is still lacking so far. Herein, a rod-like diquinoxalino-phenazine (DPZ) organic compound is designed and synthetized via a facile dehydration approach. In-situ Raman investigation and theoretical calculation are conducted to probe into the proton redox process of DPZ organic electrode for the first time. It is demonstrated that three CN electroactive regions in each DPZ molecular unit could be simultaneously coordinated with two protons and the redox reaction between CN and CN bonds is highly reversible upon proton insertion/extraction. As expected, the DPZ organic electrode delivers a large proton-storage capacity of ∼ 218 mAh/g and long-term cycle performance without obvious dissolubility in acidic aqueous electrolyte. For real applications, soft-package and wire-shaped APBs based on such DPZ organic electrode are constructed, and they both achieve outstanding electrochemical characteristics, revealing their great potential applications in low-cost, high-safety, and high-performance energy technologies and portable/wearable electronics.

Highlights The cationic waterborne polyurethanes microspheres with Diels-Alder bonds were synthesized for the first time. The electrostatic attraction not only endows the composite with segregated structure to gain high electromagnetic-interference shielding effectiveness, but also greatly enhances mechanical properties. Efficient healing property was realized under heating environment. Abstract It is still challenging for conductive polymer composite-based electromagnetic interference (EMI) shielding materials to achieve long-term stability while maintaining high EMI shielding effectiveness (EMI SE), especially undergoing external mechanical stimuli, such as scratches or large deformations. Herein, an electrostatic assembly strategy is adopted to design a healable and segregated carbon nanotube (CNT)/graphene oxide (GO)/polyurethane (PU) composite with excellent and reliable EMI SE, even bearing complex mechanical condition. The negatively charged CNT/GO hybrid is facilely adsorbed on the surface of positively charged PU microsphere to motivate formation of segregated conductive networks in CNT/GO/PU composite, establishing a high EMI SE of 52.7 dB at only 10 wt% CNT/GO loading. The Diels–Alder bonds in PU microsphere endow the CNT/GO/PU composite suffering three cutting/healing cycles with EMI SE retention up to 90%. Additionally, the electrostatic attraction between CNT/GO hybrid and PU microsphere helps to strong interfacial bonding in the composite, resulting in high tensile strength of 43.1 MPa and elongation at break of 626%. The healing efficiency of elongation at break achieves 95% when the composite endured three cutting/healing cycles. This work demonstrates a novel strategy for developing segregated EMI shielding composite with healable features and excellent mechanical performance and shows great potential in the durable and high precision electrical instruments.

The Chaiwopu Sag of Junggar Basin experienced a major breakthrough in oil and gas exploration for the first time in the late 1980s, however, the exploration effect in this area is still restricted by the complexity of faults and the uneven distribution of oil and gas. As the main body of the sag, the Dabancheng subsag has been strongly extruded by the Bogda Mountain thrust belt to the south, the Yilian Habirga Mountain (abbreviated as Yishan) thrust belt to the northeast, and the Heishan Mountain to the northwest since Permian. A compressive and narrow ramp structural system superimposed by multiple stress fields was developed, which led to the complexity and particularity of fault characteristics and evolution in the Dabancheng subsag. Approaches including logging, seismic and field geological survey data were applied to study the fault systems in the subsag, including the Southern Bogda Mountain fault system, the Yishan fault system and the Heishan fault system. The Southern Bogda Mountain fault system has a shallow detachment surface, which belongs to an orogenic wedge structure with plastic detachment layers. The Yishan fault system is a basement-involved structure. The Late Hercynian, Indosinian, Yanshanian and Himalayan tectonic movements have geological records in this area, forming different scales of faults. The late Hercynian period is a breakup stage, the Indosinian-Yanshanian period is a fault-shaping period, and the Himalayan period is a fault adjustment period. The distribution of detachment belt in the Southern Bogda Mountain fault system is consistent with that of the Middle-Lower Permian source rocks. Combined with the analyses of tectonic movement period, stratigraphic characteristics and fault systems, the Southern Bogda Mountain fault system is a potential oil and gas accumulation area.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions is a rare subtype of renal tumor. This entity predominantly occurs in juveniles, but rarely in adults. Xp11.2 translocation RCC (tRCC) patients with lymph node or organ metastasis are associated with poor prognosis, and the strategy remains controversial. Herein, we presented our experience with the diagnosis and treatment of an adult case of Xp11.2 tRCC. In our clinical practice, a 32-year-old male manifested fever and right flank paroxysmal blunt pain, and computed tomography showed an inhomogeneous mass, 6 cm in diameter, in the right kidney. Then right partial nephrectomy (PN) and renal hilar lymph node dissection by laparoscopic surgery were performed. Pathology revealed that the tumor cells were positive for TFE3 immunohistologically and positive for TFE3 break-apart fluorescence in situ hybridization assay. A splice site mutation c.1544-1G>T of protein tyrosine phosphatase receptor delta (PTPRD) was detected by next-generation sequencing and weak PTPRD expression was confirmed in tumor tissues compared to tumor periphery. This patient was diagnosed with stage III RCC and received immune checkpoint inhibitor (camrelizumab) in combination with tyrosine kinase inhibitor (axitinib) treatment for 1 year. He achieved a clinical complete response with no sign of recurrence or metastasis. PTPRD mutation might be a favorable indicator for Xp11.2 tRCC patients managed by PN and followed by the adjuvant therapy of immune checkpoint inhibitor and tyrosine kinase inhibitor.

Free running model tests and a system-based method are employed to evaluate maneuvering performance for a Small Waterplane Area Twin Hull (SWATH) ship in this paper. A 3 degrees of freedom Maneuvering Modeling Group (MMG) model is implemented to numerically simulate the maneuvering motions in calm water. Virtual captive model tests are performed by using a Reynolds-averaged Navier-Stokes (RANS) method to acquire hydrodynamic derivatives, after a convergence study to check the numerical accuracy. The turning and zigzag maneuvers are simulated by solving the maneuvering motion model and the predicted results agree well with the experimental data. Moreover, free running model tests are carried out for three lateral separations and the influence of the lateral separations on maneuvering performance is investigated. The research results of this paper will be helpful for the maneuvering prediction of the small waterplane area twin hull ship.

The Cambrian source rock is a key indicator that will guide future hydrocarbon explorations in ultra-deep strata. Despite its importance, the characteristics of paleotopography on the Precambrian basement and the distribution of source rocks above it remain unclear. The seismic and borehole data, isopach data, and the unconformity analysis are used to study the relations of the Cambrian source rock distribution to the paleotopography. The consistency of the strata thickness distribution maps of the Nanhua–Cambrian sequences show that the extensive thermal subsidence lasted the whole Sinian period, and makes the paleotopography of the Precambrian basement inherited from the landform after the Nanhua continental rifting. A major transgression caused by rapid subsidence of the Tarim Basin took place during the Cambrian. Shales were deposited offshore along the slopes of a paleo-uplift on the inherited paleotopography and formed the onlap in seismic profiles. The onlap on the inherited paleotopography reflects the distribution range of Yuertusi source rocks in the Cambrian.

Although polypyrrole (PPy) has been recognized as a promising organic electrode for rechargeable aqueous batteries (RABs), the practical application is still restricted by its rapid capacity fading after repeated cycles. Herein, a multilayer structural MXene-stabilized PPy (MXene@PPy) composite has been purposefully designed via a facile dip-coating approach, wherein the MXene coating effectively inhibits the structural degradation and irreversible redox reaction of PPy during the electrochemical process, demonstrated by electrochemical measurements combined with in-situ Raman investigation. Density functional theory (DFT) calculation further confirms the obvious electron transfer from MXene to PPy, leading to the formation of electron-rich region on PPy and hole-rich region on MXene, thereby promoting the redox reaction of PPy in the MXene@PPy composite with increased density of states (DOS). As an electrode, the MXene@PPy composite exhibits a large specific capacity of 124.9 mAh g−1 at 1.0 mA cm−2, high coulombic efficiency of ∼100%, superior charge-transfer capability, excellent rate performance and long-term cycling stability with high capacity retention of ∼80.3% over 2500 cycles in acidic aqueous electrolyte. For real application, a high-performance flexible RAB device constructed with such MXene@PPy composite electrode has been substantiated as the efficient power source, revealing its potential applications in high-safety portable/wearable electronics.

In order to explore the contextual factors that may influence Chinese early study abroad students’ acculturation experiences in Canada, we conducted in-depth interviews with 20 Chinese early study abroad students and 6 Chinese parents. Using Oppedal and Toppelberg’s acculturation development model as the analytical framework, we identify six microsystem factors (parents, host family, custodian, overseas-study service agent, friends, and church), two mesosystem factors (parents-custodian relationship and custodian-host family relationship), three exosystem factors (social services, public safety, and immigration policies), one majority culture macro factor (multiculturalism), and the time dimension are related to Chinese early study abroad students’ acculturation experiences. In addition to these factors, locosystem factors such as geography, physical environment, and climate of the city in which they live are also important. Based on these findings, we advise all stakeholders to create a supportive and sustainable environment for Chinese early study abroad students to live in Canada.

Core drilling has been widely used in mineral exploration with diamond-impregnated drilling technology. Automation is a critical technology in improving core drilling efficiency and reducing core drilling costs, but there is no complete automation that can control the entire core drilling process. In this paper, an electric drive laboratory drilling system was established using programmable logic controller (PLC) technology. A proportional integration differentiation (PID) control algorithm was developed to achieve closed-loop control of the weight-on-bit (WOB) during the drilling process. Four drilling modes were developed for the drilling system, and their performances were verified by drilling test. A constant-speed mode is proposed as the most suitable mode for the system. The recommended rate of penetration (ROP) of the rock sample and bit used in the experiment was obtained through the power optimization drilling test. The results show that the optimal rotation speed ranged from 700 to 1000 rpm, and the optimal ROP ranged from 2.0 to 2.6 m/h.

Chimeric antigen receptor (CAR)-expressing macrophages (CAR-M) have a great potential to improve cancer therapy, as shown from several recent preclinical studies. However, unlike CAR-T cell therapy, which has been widely studied, the efficacy and limitations of CAR-M cells remain to be established. To address this issue, in the present study, we compared three intracellular signaling domains (derived from common γ subunit of Fc receptors (FcRγ), multiple EGF-like-domains protein 10 (Megf10), and the CD19 cytoplasmic domain that recruits the p85 subunit of phosphoinositide-3 kinase (PI3K), respectively) for their ability to promote primary CAR-M functions, and investigated the potential synergistic effect between CAR-M and CAR-T cells in their ability to kill tumor cells. We found that CAR-MFcRγ exerted more potent phagocytic and tumor-killing capacity than CAR-MMegf10 and CAR-MPI3K. CAR-M and CAR-T demonstrated synergistic cytotoxicity against tumor cells in vitro. Mechanistically, the inflammatory factors secreted by CAR-T increased the expression of costimulatory ligands (CD86 and CD80) on CAR-M and augmented the cytotoxicity of CAR-M by inducing macrophage M1 polarization. The upregulated costimulatory ligands may promote the fitness and activation of CAR-T cells in turn, achieving significantly enhanced cytotoxicity. Taken together, our study demonstrated for the first time that CAR-M could synergize with CAR-T cells to kill tumor cells, which provides proof-of-concept for a novel combinational immunotherapy.

Construction of segregated structures within conductive polymer composites (CPCs) is a prospective strategy to enhance electromagnetic interference (EMI) shielding effectiveness (SE). However, the CPCs of segregated structures frequently experience worsened mechanical performances due to weak interface reactions between adjacent polymer domains, which are hindered by conductive fillers. Herein, 3D-printed segregated carbon nanotube (CNT)/polylactic acid (PLA) composite was firstly exploited to develop high mechanical properties while achieving good performance for electromagnetic interference shielding. Within the final 3D-printed CNT/PLA composite, CNTs coated on 3D-printed PLA scaffold were translated to interconnected conductive network after compression. Thus, EMI SE of composite was as high as 67.0 dB when 5.0 wt% CNTs were loaded. Furthermore, 3D-printed PLA scaffold with a highly continuous structure also benefited the mechanical robustness of the segregated composite, revealing the bending strength (87.8 MPa) and Young's modulus (4.43 GPa), which were 101% and 43% higher than 43.7 MPa and 3.08 GPa for the conventional CNT/PLA composite. Moreover, the regulation of 3D-printed PLA scaffolds results in promising CNT/PLA composites with tunable EMI SE. This work suggests that 3D printing technology is an effective and easy approach to develop the outperformance of CPCs for different radiation source fields and electronic devices.

Surface-enhanced Raman spectroscopy (SERS) technology has been regarded as a most efficient and sensitive strategy for the detection of pollutants at ultra-low concentrations. Fabrication of SERS substrates is of key importance in obtaining the homogeneous and sensitive SERS signals. Cellulose filter papers loaded with plasmonic metal NPs are well known as cost-effective and efficient paper-based SERS substrates. In this manuscript, face-to-face assembly of silver nanoplates via solvent-evaporation strategies on the cellulose filter papers has been developed for the SERS substrates. Furthermore, these developed paper-based SERS substrates are utilized for the ultra-sensitive detection of the rhodamine 6G dye and thiram pesticides. Our theoretical studies reveal the creation of high density hotspots, with a huge localized and enhanced electromagnetic field, near the corners of the assembled structures, which justifies the ultrasensitive SERS signal in the fabricated paper-based SERS platform. This work provides an excellent paper-based SERS substrate for practical applications, and one which can also be beneficial to human health and environmental safety.

Abstract Wearable strain sensors based on flexible conductive polymer composites (FCPCs) have attracted great attention due to their applications in the fields of human–machine interaction, disease diagnostics, human motion detection, and soft robotic skin. In recent decades, FCPC‐based strain sensors with high stretchability and sensitivity, short response time, and excellent stability have been developed, which are expected to be more versatile and intelligent. Smart strain sensors are required to provide wearable comfort, such as breathability, self‐cooling ability, and so forth. To adapt to the harsh environment, wearable strain sensors should also be highly adaptive to protect the skin and the sensor itself. In addition, portable power supply system, multisite sensing capability, and multifunctionality are crucial for the next generation of FCPC‐based strain sensor.

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens in sericulture and causes huge economic loss annually. The roles of N6-methyladenosine (m6A) modification in silkworms following BmNPV infection are currently unclear. Here, methylated RNA immunoprecipitation with next-generation sequencing were applied to investigate the m6A profiles in silkworm midgut following BmNPV infection. A total of 9144 and 7384 m6A peaks were identified from the BmNPV-infected (TEST) and uninfected silkworm midguts (CON), respectively, which were distributed predominantly near stop codons. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of common m6A peaks in nuclear genes revealed that these m6A-related transcripts were associated with crucial signaling pathways. Comparative transcriptome analysis showed that 1221 differential expressed m6A peaks were identified between TEST and CON, indicating that m6A modification is regulated following BmNPV infection. GO and KEGG pathway analysis of the differentially expressed m6A peaks showed their association with signal transduction, translation, and degradation. To understand further the effect of the m6A machinery on virus infection, expression levels of m6A-related genes were altered in silencing and overexpression experiments. Expression of viral structural protein VP39 was increased in BmN cells by siRNA-mediated depletion of methyltransferase-like (METTL) enzyme genes (BmMETTL3, BmMETTL14) and cytoplasmic YTH-domain family 3 (BmYTHDF3), while the reverse results were found after overexpression of the m6A-related enzymes in BmN cells. Overall, m6A modification might be a novel epigenetic mechanism that regulation BmNPV infection and interference with this mechanism may provide a novel antiviral strategy for preventing BmNPV disease.

Hand-foot-and-mouth disease (HFMD) caused by human enterovirus A71 (EV-A71) infection has been associated with severe neurological complications. With the lack of an internationally approved antiviral, coupled with a surge in outbreaks globally, EV-A71 has emerged as a neurotropic virus of high clinical importance. Andrographolide has many pharmacological effects including antiviral activity and its derivative, andrographolide sulfonate, has been used in China clinically to treat EV-A71 infections. This study sought to identify novel andrographolide derivatives as EV-A71 inhibitors and elucidate their antiviral mode of action. Using an immunofluorescence-based phenotypic screen, we identified novel EV-A71 inhibitors from a 344-compound library of andrographolide derivatives and validated them with viral plaque assays. Among these hits, ZAF-47, a quinolinoxy-andrographolide, was selected for downstream mechanistic studies. It was found that ZAF-47 acts on EV-A71 post-entry stages and inhibits EV-A71 protein expression. Subsequent luciferase studies confirm that ZAF-47 targets EV-A71 genome RNA replication specifically. Unsuccessful attempts in generating resistant mutants led us to believe a host factor is likely to be involved which coincide with the finding that ZAF-47 exhibits broad-spectrum antiviral activity against other enteroviruses (CV-A16, CV-A6, Echo7, CV-B5, CV-A24 and EV-D68). Furthermore, ZAF-46 and ZAF-47, hits from the screen, were derivatives of the same series containing quinolinoxy and olefin modifications, suggesting that an andrographolide scaffold mounted with these unique moieties could be a potential anti-EV-A71/HFMD strategy.

Thinned peach polyphenols (TPPs) were extracted by ultrasonic disruption and purified using macroporous resin. Optimized extraction conditions resulted in a TPPs yield of 1.59 ± 0.02 mg GAE/g FW, and optimized purification conditions resulted in a purity of 43.86% with NKA-9 resin. TPPs composition was analyzed by UPLC-ESI-QTOF-MS/MS; chlorogenic acid, catechin, and neochlorogenic acid were the most abundant compounds in thinned peaches. Purified TPPs exhibited scavenging activity on DPPH, ABTS, hydroxyl radical, and FRAP. TPPs inhibited α-amylase and α-glucosidase by competitive and noncompetitive reversible inhibition, respectively. TPPs also exhibited a higher binding capacity for bile acids than cholestyramine. In summary, TPPs from thinned peaches are potentially valuable because of their high antioxidant, hypoglycemic, and hypolipidemic capacities, and present a new incentive for the comprehensive utilization of thinned peach fruit.

The phylogenetic relationships of species in the Phasianidae, Order Galliformes, are the object of intensive study. However, convergent morphological evolution and rapid species radiation result in much ambiguity in the group. Further, matrilineal (mtDNA) genealogies conflict with trees based on nuclear DNA retrotransposable elements. Herein, we analyze 39 nearly complete mitochondrial genomes (three new) and up to seven nuclear DNA segments. We combine these multiple unlinked, more informative genetic markers to infer historical relationships of the major groups of phasianids. The nuclear DNA tree is largely congruent with the tree derived from mt genomes. However, branching orders of mt/nuclear trees largely conflict with those based on retrotransposons. For example, Gallus/Bambusicola/Francolinus forms the sister-group of Coturnix/Alectoris in the nuclear/mtDNA trees, yet the tree based on retrotransposable elements roots the former at the base of the tree and not with the latter. Further, while peafowls cluster with Gallus/Coturnix in the mt tree, they root at the base of the phasianids following Gallus in the tree based on retrotransposable elements. The conflicting branch orders in nuclear/mtDNA and retrotransposons-based trees in our study reveal the complex topology of the Phasianidae.

Feature selection has proved to be a beneficial tool in learning problems with the main advantages of interpretation and generalization. Most existing feature selection methods do not achieve optimal classification performance, since they neglect the correlations among highly correlated features which all contribute to classification. In this paper, a novel semisupervised feature selection algorithm based on support vector machine (SVM) is proposed, termed SENFS. In order to solve SENFS, an efficient algorithm based on the alternating direction method of multipliers is then developed. One advantage of SENFS is that it encourages highly correlated features to be selected or removed together. Experimental results demonstrate the effectiveness of our feature selection method on simulation data and benchmark data sets.

The ADF/cofilin family has been characterized as a group of actin-binding proteins critical for controlling the assembly of actin within the cells. In this study, the solution structure of the ADF/cofilin from Trypanosoma brucei (TbCof) was determined by NMR spectroscopy. TbCof adopts the conserved ADF/cofilin fold with a central β-sheet composed of six β-strands surrounded by five α-helices. Isothermal titration calorimetry experiments denoted a submicromolar affinity between TbCof and G-actin, and the affinity between TbCof and ADP-G-actin was five times higher than that between TbCof and ATP-G-actin at low ionic strength. The results obtained from electron microscopy and actin filament sedimentation assays showed that TbCof depolymerized but did not co-sediment with actin filaments and its ability of F-actin depolymerization was pH independent. Similar to actin, TbCof was distributed throughout the cytoplasm. All our data indicate a structurally and functionally conserved ADF/cofilin from Trypanosoma brucei.

Src homology 2 (SH2) domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1) via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode.Tensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five β-strands flanked by two α-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1) as well as phosphorylated ligand.We determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner.

Background Subarachnoid haemorrhage (SAH) can result in a highly unfavourable prognosis. In recent years, the study of SAH has focused on early brain injury (EBI), which is a crucial progress that contributes to adverse prognosis. SAH can lead to various complications, including mitochondrial dysfunction and DNA damage. Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein with multifaceted functionality integral to DNA repair and redox signalling. However, the role of APE1 in mitochondrial DNA damage repair after SAH is still unclear.Methods Our study involved an in vivo endovascular perforation model in rats and an in vitro neuron oxyhaemoglobin intervention. Then, the effects of APE1 on mitochondrial DNA damage repair were analysed by western blot, immunofluorescence, quantitative real-time PCR, mitochondrial bioenergetics measurement and neurobehavioural experiments.Results We found that the level of APE1 decreased while the mitochondria DNA damage and neuronal death increased in a rat model of SAH. Overexpression of APE1 improved short-term and long-term behavioural impairment in rats after SAH. In vitro, after primary neurons exposed to oxyhaemoglobin, APE1 expression significantly decreased along with increased mitochondrial DNA damage, a reduction in the subunit of respiratory chain complex levels and subsequent respiratory chain dysfunction. Overexpression of APE1 relieved energy metabolism disorders in the mitochondrial of neurons and reduced neuronal apoptosis.Conclusion In conclusion, APE1 is involved in EBI after SAH by affecting mitochondrial apoptosis via the mitochondrial respiratory chain. APE1 may potentially play a vital role in the EBI stage after SAH, making it a critical target for treatment.

The incidence of allergic diseases is gradually increasing， and multi-system allergic diseases often co-occur in the same patient. It is very important to conduct comprehensive diagnosis and treatment with high quality， high efficiency， reasonable and standardized. The multi-disciplinary diagnosis and treatment provides a new way to solve the complicated and difficult comorbidities of allergic comorbidity and multimorbidity， which is an effective supplement to the traditional diagnosis and treatment mode， and is also the development trend of the diagnosis and treatment of allergic diseases. At present， the multi-disciplinary treatment of allergic comorbidity and multimorbidity is still in the exploratory stage at home and abroad， and has not yet formed a mature system or a operation mode. Based on the clinical exploration and practical experience of allergic disease expert team of the Third Affiliated Hospital of Sun Yat-sen University， this paper expounds the construction and implementation of the multi-disciplinary treatment system for allergic comorbidity and multimorbidity from the aspects of implementation objectives， organizational structure， basic requirements， operation mode， procedure， system guarantee， quality control and so on. Establishing a standardized， mature and perfect multi-disciplinary treatment system for allergic comorbidity and multimorbidity and ensuring its effective operation and implementation will help to improve the level of multi-disciplinary diagnosis and treatment for allergic comorbidity and multimorbidity.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA)-caused infections greatly threaten public health. The discovery of natural-product-based anti-MRSA agents for treating infectious diseases has become one of the current research focuses. Objectives: This study aims to identify promising anti-MRSA agents with a clear mechanism based on natural norharmane modified by quaternization or dimerization. Methods: A total of 32 norharmane analogues were prepared and characterized. Their antibacterial activities and resistance development propensity were tested by the broth double-dilution method. Cell counting kit-8 and hemolysis experiments were used to assess their biosafety. The plasma stability, bactericidal mode, and biofilm disruption effects were examined by colony counting and crystal violet staining assays. Fluorescence microscopy, metabolomic analysis, docking simulation and spectra titration revealed its anti-MRSA mechanisms. The mouse skin infection model was used to investigate the in vivo efficacy. Results: Compound 5a was selected as a potential anti-MRSA agent, which exhibited potent anti-MRSA activity in vitro and in vivo, low cytotoxicity and hemolysis under an effective dose. Moreover, compound 5a showed good stability in 50% plasma, a low tendency of resistance development and capabilities to disrupt bacterial biofilms. The mechanism studies revealed that compound 5a could inhibit the biosynthesis of bacteria cell walls, damage the membrane, disturb energy metabolism and amino acid metabolism pathways, and interfere with protein synthesis and nucleic acid function. Conclusions: These results suggested that compound 5a is a promising candidate for combating MRSA infections, providing valuable information for further exploiting a new generation of therapeutic antibiotics.

Abstract Background Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. Methods Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. Results The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p

Mycoplasma pneumoniae pneumonia （MPP） is a common cause of community-acquired pneumonia in children aged 5 and older in China. Although most affected children have favorable clinical prognosis， some cases can escalate into severe MPP due to risk factors such as pathogen resistance or co-infections， etc. These severe cases significantly jeopardize the lives of children and may lead to diverse long-term sequelae. In response to this challenge， the Children’s Medical Center of the Third Affiliated Hospital of Sun Yat-sen University， integrating current guidelines， expert consensus， and its extensive clinical experience， has devised the “412” cluster treatment strategy. This comprehensive approach encompasses treatments for anti-infection， anti-inflammatory storm， anticoagulation and antioxidant stress. Additionally， it seamlessly integrates traditional Chinese medicine with western therapies， featuring bundled respiratory management and follow-up care. This strategy provides a valuable reference for the diagnosis and treatment of severe MPP in children.

Fatty acids (FAs), which were initially recognized as energy sources and essential building blocks of biomembranes, serve as the precursors of important signaling molecules. Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events. Inspired by the advances in click chemistry for protein enrichment, we herein established a click chemistry-based enrichment (CCBE) strategy for tracing the cellular metabolism of eicosapentaenoic acid (EPA, 20:5 n-3) in neural cells. Terminal alkyne-labeled EPA (EPAA) used as a surrogate was incubated with N2a, mouse neuroblastoma cells, and alkyne-labeled metabolites (ALMs) were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment. After removing unlabeled metabolites, ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry (LC-MS) analysis. The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices. In addition, this method can overcome current detection limits by enhancing MS sensitivity of targets, improving the chromatographic separation of sn-position glycerophospholipid regioisomers, facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature, and providing versatile fluorescence detection of ALMs for cellular distribution. This CCBE strategy might be expanded to trace the metabolism of other FAs, small molecules, or drugs.

Abstract Mutations in AT‐rich interactive domain‐containing protein 1A (ARID1A) cause Coffin‐Siris syndrome (CSS), a rare genetic disorder that results in mild to severe intellectual disabilities. However, the biological role of ARID1A in the brain remains unclear. In this study, we report that the haploinsufficiency of ARID1A in excitatory neurons causes cognitive impairment and defects in hippocampal synaptic transmission and dendritic morphology in mice. Similarly, human embryonic stem cell‐derived excitatory neurons with deleted ARID1A exhibit fewer dendritic branches and spines, and abnormal electrophysiological activity. Importantly, supplementation of acetate, an epigenetic metabolite, can ameliorate the morphological and electrophysiological deficits observed in mice with Arid1a haploinsufficiency, as well as in ARID1A‐null human excitatory neurons. Mechanistically, transcriptomic and ChIP‐seq analyses demonstrate that acetate supplementation can increase the levels of H3K27 acetylation at the promoters of key regulatory genes associated with neural development and synaptic transmission. Collectively, these findings support the essential roles of ARID1A in the excitatory neurons and cognition and suggest that acetate supplementation could be a potential therapeutic intervention for CSS.

Upward depletion of ophiolitic mantle is produced by melt-peridotite reaction with lateral melt/rock ratio variations in an asthenospheric upwelling column, which flows to become the horizontal oceanic lithospheric mantle under spreading centers.

Abstract A diffuse magmatic province covering central‐eastern Asia continent displays a compositional transition at 120–100 Ma and probably reflects melting initiation in isotopically enriched lithospheric mantle, followed by melting of the asthenosphere. However, the cause for the transition across such a vast landmass remains poorly constrained. Here, analyses of newly found Chaoge basalts (∼95 Ma, central Asia) and compiled data from across the basaltic province are combined to reveal the factors controlling the basalt dichotomy. The Chaoge basalts are considered to originate from a hot pyroxenite‐bearing asthenosphere with potential temperatures of ∼1,450°C, overlapping the source thermochemical conditions for most post‐transition basaltic rocks. The asthenosphere in 120–100 Ma is suggested to be hotter and to have controlled the compositional transition in the studied basaltic province. We suggest that asthenospheric warming resulted from prolonged continental thermal blanketing and can account for other diffuse igneous provinces with similar compositional variations and tectonic histories.

Pyroptosis is a kind of programmed cell death mediated by the gasdermin protein, including the classical pathway that depends on caspase-1 and the non-classical pathway that depends on caspase-4, -5, and 11, accompanied by the release of a large number of inflammatory factors. Atherosclerosis, myocardial ischemia, heart failure and other cardiovascular diseases are closely related to inflammatory response. Pyroptosis, as a highly pro-inflammatory cell death, is also widely involved in the occurrence and development of the cardiovascular diseases, and plays an important role in these diseases.

Oceanic subduction is an important trigger for mantle heterogeneity, which further increases melt production and controls the compositions of intraplate basalts. Such a role played by the (Paleo-) Pacific subduction have been extensively studied and well constrained based on the widespread mantle xenoliths and intraplate magmatism in the eastern North China Craton. By contrast, the recycled materials from other Phanerozoic subducted slabs beneath the craton are relatively poorly recognized. Here, a reappraisal is made to the recently reported peridotite xenoliths and ~89 Ma host basalts from the Langshan area in the northwest North China Craton and regional data on xenoliths and basalts, with the emphasis on the mass transfer in the mantle wedge from the subducted Paleo-Asian oceanic slab. The Langshan peridotites are fertile in composition and record complex melt extraction and metasomatism. One episode of metasomatism is likely induced by silicate melts with concomitant enrichments in large ion lithophile elements and high field strength elements and positive Eu anomaly, suggestive of the contribution from recycled materials. This metasomatism should take place in Paleozoic according to the diffusion modelling. The host basalts are comparable with partial melts of pyroxenite under 2–3 GPa and have oceanic island basalts-like trace-element compositions. Positive Sr and Eu anomalies, low Rb/Sr and high Ba/Rb ratios, and the moderated depleted but slightly decoupled Sr–Nd isotopes suggest the involvement of subducted oceanic crustal materials in the mantle source. The Pb isotopic compositions are best modeled by the mixing between depleted mantle, altered oceanic crust with minor young (

Summary: EED (embryonic ectoderm development) is a core component of the Polycomb repressive complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27) during the process of self-renewal, proliferation, and differentiation of embryonic stem cells. However, its function in the mammalian nervous system remains unexplored. Here, we report that loss of EED in the brain leads to postnatal lethality, impaired neuronal differentiation, and malformation of the dentate gyrus. Overexpression of Sox11, a downstream target of EED through interaction with H3K27me1, restores the neuronal differentiation capacity of EED-ablated neural stem/progenitor cells (NSPCs). Interestingly, downregulation of Cdkn2a, another downstream target of EED which is regulated in an H3K27me3-dependent manner, reverses the proliferation defect of EED-ablated NSPCs. Taken together, these findings established a critical role of EED in the development of hippocampal dentate gyrus, which might shed new light on the molecular mechanism of intellectual disability in patients with EED mutations. : In this article, Chang-Mei Liu and colleagues show that EED is necessary for neuronal differentiation in the dentate gyrus, by targeting the downstream target Sox11 through interaction with H3K27me1. These data established a critical role of EED in the development of hippocampal dentate gyrus, which might shed new light on understanding molecular mechanism of intellectual disability in patients with EED mutations. Keywords: EED, PRC2, neural stem cells, dentate gyrus

Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage.

Kaempferol is a major flavonoid in Ginkgo Folium and other edible plants, which is being proposed here to have roles in angiogenesis. Angiogenesis is important in both physiological and pathological development. Here, kaempferol was shown to bind with vascular endothelial growth factor (VEGF), probably in the heparin binding domain of VEGF: this binding potentiated the angiogenic functions of VEGF in various culture models. Kaempferol potentiated the VEGF-induced cell motility in human umbilical vein endothelial cells (HUVECs), as well as the sub-intestinal vessel sprouting in zebrafish embryos and formation of microvascular in rat aortic ring. In cultured HUVECs, application of kaempferol strongly potentiated the VEGF-induced phosphorylations of VEGFR2, endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase (Erk) in time-dependent and concentration-dependent manners, and in parallel the VEGF-mediated expressions of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were significantly enhanced. In addition, the potentiation effect of kaempferol was revealed in VEGF-induced migration of skin cell and monocyte. Taken together, our results suggested the pharmacological roles of kaempferol in potentiating VEGF-mediated functions should be considered.

GA binding protein (GABP) is a ubiquitously expressed transcription factor that regulates the development of multiple cell types, including osteoblast, hematopoietic stem cells, B cells and T cells. However, so little is known about its biological function in the development of central nervous system. In this report, we show that GABP is highly expressed in neural stem/progenitor cells (NSPCs) and down-regulated in neurons, and that GABPβ1 is required for the proper proliferation of NSPCs. Knockdown of GABPα resulted in an elevated expression level of GABPβ1, and GABPβ1 down-regulation significantly decreased the proliferation of NSPCs, whereas GABPβ2 knockdown did not result in any changes in the proliferation of NSPCs. We observed that there was nearly a 21-fold increase of the GABPβ1S mRNA level in GABPβ1L KO NSPCs compared to WT cells, and knocking down of GABPβ1S in GABPβ1L KO NSPCs could further reduce their proliferation potential. We also found that knockdown of GABPβ1 promoted neuronal and astrocytic differentiation of NSPCs. Finally, we identified dozens of downstream target genes of GABPβ1, which are closely associated with the cell proliferation and differentiation. Collectively, our results suggest that both GABPβ1L and GABPβ1S play an essential role in regulating the proper proliferation and differentiation of NSPCs. Keywords: GABP, Neural stem cell, GABPβ1L, GABPβ1S, Cell proliferation, Neurogenesis

Piceatannol is also named as trans-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol on VEGF-mediated angiogenesis is not known. Here, the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis. In human umbilical vein endothelial cells (HUVECs), piceatannol markedly reduced the VEGF-induced cell proliferation, migration, invasion, as well as tube formation without affecting cell viability. Furthermore, piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo. In addition, we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions. Piceatannol was proposed to bind with VEGF, thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling, including expressions of phosphorylated eNOS, Erk and Akt. Furthermore, piceatannol visibly suppressed ROS formation, as triggered by VEGF. Moreover, we further determined the outcome of piceatannol binding to VEGF in cancer cells: piceatannol significantly suppressed VEGF-induced colon cancer proliferation and migration. Thus, these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors, thus affecting the related downstream signaling. Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases.

Histone demethylase UTX mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish a mechanistic switch to activate large sets of genes. Mutation of Utx has recently been shown to be associated with Kabuki syndrome, a rare congenital anomaly syndrome with dementia. However, its biological function in the brain is largely unknown. Here, we observe that deletion of Utx results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of Utx in the hippocampus leads to reduced long-term potentiation and amplitude of miniature excitatory postsynaptic current, aberrant dendrite development and defective synapse formation. Transcriptional profiling reveals that Utx regulates a subset of genes that are involved in the regulation of dendritic morphology, synaptic transmission, and cognition. Specifically, Utx deletion disrupts expression of neurotransmitter 5-hydroxytryptamine receptor 5B (Htr5b). Restoration of Htr5b expression in newborn hippocampal neurons rescues the defects of neuronal morphology by Utx ablation. Therefore, we provide evidence that Utx plays a critical role in modulating synaptic transmission and cognitive behaviors. Utx cKO mouse models like ours provide a valuable means to study the underlying mechanisms of the etiology of Kabuki syndrome.

Background: Based on our previous work, we found that 10-methoxycanthin-6-one displayed potential antibacterial activity and quaternization was an available method for increasing the antibacterial activity. Here, we explored the antibacterial activity of quaternized 10-methoxy canthin-6-one derivatives. Methods and Results: Twenty-two new 3-N-benzylated 10-methoxy canthin-6-ones were designed and synthesized through quaternization reaction. The in vitro antibacterial activity against three bacteria was evaluated by the double dilution method. Moreover, the structure–activity relationships (SARs) were carefully summarized in order to guide the development of antibacterial canthin-6-one agents. Two highly active compounds (6p and 6t) displayed 8-fold superiority (MIC = 3.91 µg/mL) against agricultural pathogenic bacteria R. solanacearum and P. syringae compared to agrochemical streptomycin sulfate, and showed potential activity against B. cereus. Moreover, these two compounds exhibited good “drug-like„ properties, low cytotoxicity, and no inhibition on seed germination. Conclusions: This work provides two new effective quaternized canthin-6-one derivatives as candidate bactericide, promoting the development of natural-sourced bactericides and preservatives.