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With the aggravation of energy shortage and ecological deterioration, it becomes more and more essential for China to improve energy efficiency and realize the targets of energy conservation and emission reduction. This paper focuses on the measurement of the total factor energy efficiency (TFEE), the potentials of energy conservation and emission reduction, and the influencing factors of TFEE in China. Firstly, the model of Gray Weight Slack-Based Measure (GW-SBM) is established, with the weights of the indicators obtained via the grey relational analysis method, to calculate the TFEE of thirty provinces and six regions in China from 2009 to 2019. Then, the potentials of energy conservation and emission reduction are analyzed on the basis of TFEE measurements. Finally, the influencing factors of TFEE are identified via the truncated bootstrap model. The findings show that the TFEE values of 30 provinces fluctuate in the range of 0.20 and 1.0, varying significantly among provinces. Energy conservation potential reached 8.7490 million tons of standard coal (potential 39.06%), which means that more than one-third of energy consumption is inefficient. The top two factors in the TFEE measurement identified by the truncated bootstrap model, are energy consumption structure and environmental protection expenditure. Based on the research conclusions, this paper puts forward some countermeasures and suggestions.

PandaOmics is a cloud-based software platform that applies artificial intelligence and bioinformatics techniques to multimodal omics and biomedical text data for therapeutic target and biomarker discovery. PandaOmics generates novel and repurposed therapeutic target and biomarker hypotheses with the desired properties and is available through licensing or collaboration. Targets and biomarkers generated by the platform were previously validated in both in vitroand in vivostudies. PandaOmics is a core component of Insilico Medicine’s Pharma.ai drug discovery suite, which also includes Chemistry42 for the de novogeneration of novel small molecules, and inClinico─a data-driven multimodal platform that forecasts a clinical trial’s probability of successful transition from phase 2 to phase 3. In this paper, we demonstrate how the PandaOmics platform can efficiently identify novel molecular targets and biomarkers for various diseases.

The mediator kinases CDK8 and CDK19 control the dynamic transcription of selected genes in response to various signals and have been shown to be hijacked to sustain hyperproliferation by various solid and liquid tumors. CDK8/19 is emerging as a promising anticancer therapeutic target. Here, we report the discovery of compound 12, a novel small molecule CDK8/19 inhibitor. This molecule demonstrated not only decent enzymatic and cellular activities but also remarkable selectivity in CDK and kinome panels. Besides, compound 12also displayed favorable ADME profiles including low CYP1A2 inhibition, acceptable clearance, and high oral bioavailability in multiple preclinical species. Robust in vivo PD and efficacy studies in mice models further demonstrated its potential use as mono- and combination therapy for the treatment of cancers.

Solid-liquid phase-change materials (PCMs) offer exciting prospects for thermal energy conservation, whose performance is greatly affected by the carrier materials. Using expanded vermiculite (EV) as frameworks, carbon nanotube arrays (CNTs) were grown between EV layers by chemical vapor deposition (CVD). Then, the paraffin (PA) was loaded on the EV@CNTs composite by vacuum impregnation to prepare composite PCMs (PA/EV@CNTs), where the PA is organic carrier and the EV@CNTs acts as porous supports with high structural strength. The loading capacity of PA is further regulated by the hydrotropism of CNTs which effectively prevents the leakage of molten PA. The in-situ grown CNTs significantly improves the thermal conductivity of PCMs, improving the efficiency of energy conversion. With maximum PA loading capacity of 95 wt%, the thermal conductivity of PA/EV@CNTs-95% reaching 0.7176 W/mK, which was 1.73 and 2.96 times higher than that of pristine EV and PA. The phase change latent heat of PA/EV@CNTs-95% was measured to be 168.54 J/g, which is 1.48 times higher than that of PA/EV. After 100 cycles, the PA/EV@CNTs still maintains excellent thermal stability, and the enthalpy retention rate is 98.73%. The incorporation of high thermal conductivity amphipathicity CNTs in these PCMs makes them promising candidate for various applications such as energy-efficient buildings, thermal management in electronic devices, and self-cleaning materials.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen–carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus(MRSA) and ampicillin-resistant Escherichia coli(AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Stabilization of hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase domain enzymes (PHDs) represents a breakthrough in treating anemia associated with chronic kidney disease. Here, we identified a novel scaffold for noncarboxylic PHD inhibitors by utilizing structure-based drug design (SBDD) and generative models. Iterative optimization of potency and solubility resulted in compound 15which potently inhibits PHD thus stabilizing HIF-α in vitro. X-ray cocrystal structure confirmed the binding model was distinct from previously reported carboxylic acid PHD inhibitors by pushing away the R383 and Y303 residues resulting in a larger inner subpocket. Furthermore, compound 15demonstrated a favorable in vitro/in vivoabsorption, distribution, metabolism, and excretion (ADME) profile, low drug–drug interaction risk, and clean early safety profiling. Functionally, oral administration of compound 15at 10 mg/kg every day (QD) mitigated anemia in a 5/6 nephrectomy rat disease model.

Breast and gynecological cancers are among the leading causes of death in women worldwide, illustrating the urgent need for innovative treatment options. We identified MYT1 as a promising new therapeutic target for breast and gynecological cancer using PandaOmics, an AI-driven target discovery platform. The synthetic lethal relationship of MYT1 in tumor cell lines with CCNE1 amplification enhanced this rationale. Through structure-based drug design, we developed a series of novel, potent, and highly selective inhibitors specifically targeting MYT1. Importantly, our lead compound, featuring a tetrahydropyrazolopyrazine ring, exhibits remarkable selectivity over WEE1, a related kinase associated with bone marrow suppression upon inhibition. Optimization of potency and physical properties resulted in the discovery of compound 21, a novel MYT1 inhibitor, exhibiting optimal pharmacokinetic properties and promising in vivo antitumor efficacy.

Scandate cathodes have received widespread attention due to the high emission current density, existing results have shown that the content of strontium in impregnant has a certain degree of impact on the emission property of scandate cathodes. In this work, the mechanism by how strontium affects the emission property was investigated through experiments and theoretical analysis. Five precursor powders with different strontium element contents were prepared by freeze-drying method, and the impregnant was obtained after sintering. Then composition analysis was conducted on the impregnant and prepared experimental cathodes for emission performance testing, also the surface emission structure of cathode was established for density functional theory (DFT) calculations. The experimental results indicated that the variation in strontium content can alter the material composition of the impregnant and have impact on cathode emission performance. During the process of increasing strontium content from 0 to 12 atom%, the emission performance of the experimental cathodes increased first and then decreased. Under a testing temperature of 1100 $^{\circ }\text{C}_{\text {b}}$ , the cathodes with 6 atom% Sr have the highest emission current density of 34.9 A/cm2 at 260 V dc and 523.2 A/cm2 at 2000 V pulse voltage among the five experimental cathodes, and this cathode exhibits good emission uniformity. DFT results indicate that strontium does not directly participate in reducing the work function of cathode surface. It can be considered that strontium has a promoting effect on the formation of active substance, an appropriate amount of strontium promotes the formation of emitting active substance Ba2ScAl5 during the preparation process of the impregnant, thus promoting the improvement of cathode emission performance; while excessive strontium can lead to the generation of impurities that lower the emission performance of cathodes.

Currently, mainstream lanthanide probes with fluorescence located in the second near-infrared subwindow of 1500–1700 nm (NIR-IIb) are predominantly Er(III)-based nanoparticles (NPs). Here we report a newly developed NIR-IIb fluorescent nanoprobe, α-Tm NP (cubic-phase NaYF4@NaYF4:Tm@NaYF4), with an emission at 1630 nm. We activate the 1630 nm emission of Tm(III) in α-Tm NP through the large spread of the Stark split sublevels induced by the crystal-field effect of the α-NaYF4host. Further, we systematically investigated the effect of crystalline structure of the host NaYF4NP (cubic phase (α) or hexagonal phase (β)), the type and concentrations of dopants (Yb(III), Tm(III), and Ca(II) ions) in the α-phase host, and the thicknesses of the interlayer and inert shell on the NIR-IIb fluorescence of Tm(III). The ultimate nanostructure presents a significant enhancement factor of the NIR-IIb photoluminescence intensity of Tm(III) up to ∼315. With this bright NIR-IIb fluorescent nanoprobe, we demonstrate high-spatial-resolution time-coursing imaging of breast cancer bone metastasis.

The surface nano-crystallization of lightweight Fe–28Mn–8Al–1C steel was achieved via the supersonic fine particle bombardment (SFPB) technique. The effects of impact time of SFPB and gas pressure on the surface morphology, microstructure, and mechanical properties were systematically investigated. The results indicated that SFPB treatment can form a gradient nanostructure on the surface of the lightweight Fe–28Mn–8Al–1C steel. With a gas pressure of 1.0 MPa and an impact time of 60 s, the surface roughness was minimized, and the corresponding strength parameters reached their highest values. With increases in the impact time and gas pressure, the grain size of the surface nanocrystalline layer gradually decreased, whereas the surface microhardness and the depth of the severe plastic deformation layer increased. However, excessively long impact time or excessively high gas pressure led to the formation of microcracks, resulting in a decrease in the strength. After SFPB treatment, lightweight Fe–28Mn–8Al–1C steel still exhibited good plasticity with elongation above 46 %, but the tensile fracture morphology changed from ductile fracture (before SFPB) to mixed ductile and brittle fracture (after SFPB).

Fe–Mn–Al–C austenitic steels have promising prospects for lightweight applications, due to their low density, excellent strength, and ductility. But the specific strength ratio of these alloys are still low as compared to other alloys. Herein, an orthogonal rolling (OR) process was used to improve the mechanical strength of a Fe–28Mn–8Al–1C low-density steel. The effect of this deformation method on the microstructural evolution and mechanical properties was studied by means of microscopy techniques, e.g. optic, scanning and transmission electron microscope, electron backscattered diffraction, X-ray diffraction, micro hardness and tensile test measurements. Microstructural characterization results show that OR significantly promotes the activation of multiple slip systems within grains in the material. The development of more uniform deformation microstructure, compared with that that after unidirectional cold rolling to the same strain was mainly due the improvement of the uniformity of strain distribution by rolling deformation in multiple directions. It resulted in an average 84.5 nm sized ultrafine grain structures after 8-pass OR. The tensile and yield strengths were significantly increased to 1813 MPa and 1798 MPa, respectively. Despite of the still-exiting strength-ductility trade-off, a much higher elongation at tensile failure of 9.6% was achieved, compared to only 5.2% of unidirectional cold rolled material. This superior strength and ductility combination was likely promoted by the increased dislocation density and deformation substructures in forms of dislocation cells, and deformation twins induced by OR.

Byline: Hua. Qiu, Ren-Feng. Shan, Jun-Hua. Ai, Shan-Ping. Ye, Jun. Shi Objective: The purpose of this study was to investigate the rate and reasons and also the risk factors for [...]

Byline: Hua. Qiu, Jun-Hua. Ai, Jun. Shi, Ren-Feng. Shan, Dong-Jun. Yu Gastrectomy is considered the gold standard treatment for gastric cancer patients. Currently, there are two minimally invasive surgical methods [...]

De novo drug design with desired biological activities is crucial for developing novel therapeutics for patients. The drug development process is time- and resource-consuming, and it has a low probability of success. Recent advances in machine learning and deep learning technology have reduced the time and cost of the discovery process and therefore, improved pharmaceutical research and development. In this paper, we explore the combination of two rapidly developing fields with lead candidate discovery in the drug development process. First, artificial intelligence has already been demonstrated to successfully accelerate conventional drug design approaches. Second, quantum computing has demonstrated promising potential in different applications, such as quantum chemistry, combinatorial optimizations, and machine learning. This article explores hybrid quantum-classical generative adversarial networks (GAN) for small molecule discovery. We substituted each element of GAN with a variational quantum circuit (VQC) and demonstrated the quantum advantages in the small drug discovery. Utilizing a VQC in the noise generator of a GAN to generate small molecules achieves better physicochemical properties and performance in the goal-directed benchmark than the classical counterpart. Moreover, we demonstrate the potential of a VQC with only tens of learnable parameters in the generator of GAN to generate small molecules. We also demonstrate the quantum advantage of a VQC in the discriminator of GAN. In this hybrid model, the number of learnable parameters is significantly less than the classical ones, and it can still generate valid molecules. The hybrid model with only tens of training parameters in the quantum discriminator outperforms the MLP-based one in terms of both generated molecule properties and the achieved KL divergence. However, the hybrid quantum-classical GANs still face challenges in generating unique and valid molecules compared to their classical counterparts.

Cyclin-dependent kinase 8 (CDK8), as a kinase subunit of the Mediator complex, is involved in the regulation of RNA polymerase II-mediated transcription, thereby modulating multiple signaling pathways and multiple transcription factors involved in oncogenic control. CDK8 deregulation has been implicated in human diseases, particularly in acute myeloid leukemia (AML) and advanced solid tumors, where it has been reported as a putative oncogene. Here, we report the successful optimization of an azaindole series of CDK8 inhibitors that were identified and further progressed through a structure-based generative chemistry approach. In several optimization cycles, we improved in vitro microsomal stability, kinase selectivity, and in vivo pharmacokinetic profile cross-species, leading to the discovery of compound 23, which demonstrated robust tumor growth inhibition in multiple in vivo efficacy models after oral administration.

This article investigates the effect of a synthetic jet (SJ) on the flow over a backward-facing step (BFS) in the weakly turbulent flow regime using the lattice Boltzmann method. The SJ operates with various momentum coefficients Cμand forcing frequencies fjet*. As Cμincreases, the reattachment length decreases, whereas increasing fjet*causes the reattachment length at first decrease and then increase. A minimum reattachment length appears at Cμ= 0.3125, fjet*= 1.6, corresponding to a 40% reduction compared with the uncontrolled case. Two mechanisms for the mediated flow are found: (1) A suitable control frequency leads to a lock-on state that prompts vertical momentum transfer and laminarizes the flow near the separation point, (2) Regular vortices emerge after wall reattachment in controlled cases. Fast Fourier and wavelet transform of the velocity near the separation point reveal that the monitored frequency becomes locked-on when fjet*> 1.6, making the flow quasi-periodic and dramatically reducing the reattachment length. Turbulent kinetic energy spectra indicate that the monitored frequencies are dominated by the forcing frequency and that active control laminarizes the local flow. Proper orthogonal decomposition is used to extract coherent structures at multiple scales. In the dominant mode, reattaching wake vortices are regulated by active control. In the second mode, irregular wake vortices emerge after fjet*= 2, which attenuates the SJ forcing and increases the reattachment length. This study provides insights on typical flows past a BFS and will shed more light on the design of closed-loop control strategies for separation flows.

As an electro-optic signal modulation device, the Mach-Zehnder (MZ) electro-optic modulator has potential applications in electrocardiogram (ECG) weak signal modulation. We propose a hybrid silicon/polymer asymmetric MZ electro-optic modulator that has the advantages of low half-wave voltages and low loss. The proposed modulator functions in the 1550 nm band, and it is mainly composed of two 3 dB multimode interference couplers, a bent waveguide, a modulation waveguide and a phase shifter. The loss of the multimode interference coupler is −0.43 dB at a device size of 4 $\mu \text{m}\,\,\times19.3\,\,\mu \text{m}$ . The core device size is 160 $\mu \text{m}\,\,\times700\,\,\mu \text{m}$ . The initial working state of the modulator is in the linear region, which can directly realize the linear modulation of voltage. Under the simulation condition of $\gamma _{33} =18.3$ pm/V, the results show that the modulator has a low loss of −3.4 dB and a low half-wave voltage amplitude of 3.0 V.

Reported herein is a novel palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, bridged olefins, and dimethyl squarate allowing the construction of chromone-containing polycyclic compounds in good to high yields. Importantly, dimethyl squarate is first employed as the solid C1 source in organic synthesis. Gram-scale experiments, late-stage modification of natural products, as well as transformations of products show potential for further synthetic elaborations.

Near‐infrared‐II (NIR‐II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post‐modifications convenience. In related preparation, enhancement of NIR‐II tail emission from NIR‐I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR‐I dyes is a convenient protocol. However, present TICT‐type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR‐I dyes, etc. Herein, the synthesis of stable small‐sized polymer NIR‐II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR‐II emission is reported. Strong enhanced emissions can be obtained from various NIR‐I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd‐DTPA/IR‐808 sample). The fluorophore provides high‐resolution angiography, with high‐contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long‐term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR‐II fluoroprobes. The IR‐808 and Nd3+co‐conjugated polymer NIR‐II fluoroprobes with twisted intramolecular charge transfer state and Förster resonance energy transfer process are demonstrated for boosting NIR‐II tail emission. The probes with rapid renal clearance are employed for angiography, middle cerebral artery occlusion mice imaging, and prognosis of acute kidney injury mice.

Bismuth vanadate is a promising semiconductor in photoelectrochemical (PEC) water oxidation due to its suitable band gap (∼2.4 eV) for absorption of solar spectrum. Nevertheless, low charge mobility and poor photogenerated carrier separation efficiency of BiVO4lead to unsatisfactory photocurrent densities and poor PEC performance. Here, we report an innovative method of introducing bulk oxygen vacancies into BiVO4film through helium ion irradiation to improve the transfer and separation efficiency by improving the bulk conductivity. The result indicates that the highest photocurrent density of the ion-irradiated BiVO4reaches 1.33 mA cm–2at 1.2 V vs RHE, which is about 70% higher than that of the un-irradiated one (∼0.77 mA cm–2). The corresponding highest IPCE reaches 40% around 400 nm, which is double compared with that of the un-irradiated BiVO4. Therefore, ion irradiation is an effective and precise method to improve the photoelectrochemical performance by inducing bulk oxygen vacancies into BiVO4. It can also be extended to other photoelectrode materials.

Scattering can seriously affect the highly sensitive detection and quantitative analysis of chemical substances in scattering media and becomes a significant challenge for in vivo application of Raman spectroscopy. In this study, we demonstrated a proof of concept for using the self-reconstructing Bessel beam for Raman spectroscopic sensing of the chemicals in the handmade scattering media and biological tissue slices. The homebuilt Bessel beam Raman spectroscopy (BRS) was capable of accurately detecting the Raman spectra of the chemicals buried in the scattering media, and had a superiority in quantitative analysis. The feasibility of the developed technique was verified by detecting the Raman spectra of pure samples in air. Compared with the spectra acquired by the Gaussian beam Raman spectroscope, the performance of the BRS system in terms of Raman spectrum detection and Raman peak recognition was confirmed. Subsequently, by employing the technique for the detection of acetaminophen buried in the scattering media, the application of the new technology in detecting and quantitating the chemicals in the scattering media were underlined, offering greater detection depth and better linear quantification capability than the conventional Gaussian beam Raman spectroscopy. Finally, we explored the potential of the BRS system for chemical sensing of acetaminophen in biological tissue slices, indicating a significant development towards the evaluation of drug in vivo.

AISI 310S stable austenitic stainless steel was subjected to 90% cryorolling and then annealed at 800 °C for 2–60 min. The effect of annealing time on the microstructure and mechanical properties was studied by optical microscopy, scanning electron microscopy, transmission electron microscopy, microhardness and tensile test. The results show that the grain size of AISI 310S stainless steel is refined to the nanometer level after 90% cryorolling, and the grain size is approximately 20 nm. With the increase in annealing time, the degree of grain recrystallization occurs more fully and completely, as the grain begins to grow and then tends to stabilize. The strength and hardness of the annealed specimens decrease with increasing annealing time, while elongation tends to increase. When the annealing time is 10 min, the yield strength increases by about 2 times compared to that of the original austenite (unrolled), and the elongation is also above 20%, which is the best preparation process for ultra-fine grain austenitic stainless steel under this experimental condition. As the annealing time treatment increases, the fracture morphology changes from mixed quasi-cleavage and ductile fracture (after cryorolling) to ductile fracture (after annealing).

Historical political science, in its exploration of the frontiers of current Chinese political science, needs to pay tribute to similar intellectual contributions in modern Chinese academic tradition, and draw nourishment from its tortuous gains and losses. Liang Qichao was one of the pioneers of modern Chinese political science, and his introduction to Western studies with the aspiration of Enlightenment laid the modern foundation of this discipline. The maturity of his experience as a modern state-builder gave birth to Liang’s enlightenment reflection in his middle and later years. Liang’s conscious promotion of the inherent historical and civilized dimensions of political science constitutes one of the modern sources of historical political science. Qian Mu speaks highly of Liang’s “epiphany in his later years”, where he proposes more systematically a series of academic concepts and topics of comparative political significance according to the Chinese historical tradition. This created a modern political science tradition based on the awareness of Chinese civilization. It is necessary to establish an effective connection between political practice and historical tradition to develop historical political science in the context of the modern republic, toward achieving a more creative and meaningful second voyage.

Tungsten (W) as plasma facing material (PFM) needs to face an unprecedented harsh environment in the fusion reactor, which puts forward high requirements for its radiation tolerance. Among the many challenges, the rapid accumulation of helium (He) atoms to form numerous bubbles or even “fuzzy” nanostructure leads to swelling and embrittlement of W matrix and seriously shorten its service life, which is one of the most serious problems faced by PFM-W at present. In this review, we summarize the recent works on the nanochannel W films with high surface-to-volume ratio deposited by magnetron sputtering, and the behaviors of He in the nanochannel W films at different fusion-related irradiation environment. Experimental and simulation results showed that the nanochannel W films have better radiation tolerance performance in managing He behaviors than that of commercial bulk W.

Although multivalent glycosidase inhibitors have shown enhanced glycosidase inhibition activities, further applications and research directions need to be developed in the future. In this paper, two positional isomeric perylene bisimide derivatives (PBI-4DNJ-1and PBI-4DNJ-2) with 1-deoxynojirimycin conjugated were synthesized. Furthermore, PBI-4DNJ-1and PBI-4DNJ-2showed positional isomeric effects on the optical properties, self-assembly behaviors, glycosidase inhibition activities, and hypoglycemic effects. Importantly, PBI-4DNJ-1exhibited potent hypoglycemic effects in mice with 41.33 ± 2.84 and 37.45 ± 3.94% decreases in blood glucose at 15 and 30 min, respectively. The molecular docking results showed that the active fragment of PBI-4DNJ-1has the highest binding energy (9.649 kcal/mol) and the highest total hydrogen bond energy (62.83 kJ/mol), which were related to the positional isomeric effect on the hypoglycemic effect in mice. This work introduced a new means to develop antihyperglycemic agents in the field of multivalent glycomimetics.

LncRNA dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitroand in vivo.

The development of green, renewable energy conversion and storage systems is an urgent task to address the energy crisis and environmental issues in the future. To achieve high performance, stable, and safe operation of energy conversion and storage systems, energy materials need to be modified and fabricated through rationalization. Among various modification and fabrication strategies, ion beam technology has been widely used to introduce various defects/dopants into energy materials and fabricate various nanostructures, where the structure, composition, and property of prefabricated materials can be further accurately tailored to achieve better performance. In this paper, we review the recent progress in the application of ion beam technology in material modification and fabrication, focusing on nanostructured energy materials for energy conversion and storage including photo- (electro-) water splitting, batteries (solar cells, fuel cells, and metal-ion batteries), supercapacitors, thermoelectrics, and hydrogen storage. This review first provides a brief basic overview of ion beam technology and describes the classification and technological advantages of ion beam technology in the modification and fabrication of materials. Then, modification of energy materials by ion beams is reviewed mainly concerning doping and defect introduction. Fabrication of energy materials is also discussed mainly in terms of heterojunctions, nanoparticles, nanocavities, and other nanostructures. In particular, we emphasize the advantages of ion beam technology in improving the performance of energy materials. Finally, we point out our understanding of challenges and future perspectives in applying ion beam technology for the modification and fabrication of energy materials.

Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement. Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.

Thirty-two new diosgenin derivatives were designed, synthesized, and evaluated for their cytotoxic activities in three human cancer cell lines (A549, MCF-7, and HepG2) and normal human liver cells (L02) using an MTT assay in vitro. Most compounds, especially 8, 18, 26, and 30, were more potent when compared with diosgenin. The structure–activity relationship results suggested that the presence of a succinic acid or glutaric acid linker, a piperazinyl amide terminus, and lipophilic cations are all beneficial for promoting cytotoxic activity. Notably, compound 8displayed excellent cytotoxic activity against HepG2 cells (IC50= 1.9 μM) and showed relatively low toxicity against L02 cells (IC50= 18.6 μM), showing some selectivity between normal and tumor cells. Studies on its cellular mechanism of action showed that compound 8induces G0/G1 cell cycle arrest and apoptosis in HepG2 cells. Predictive studies indicated that p38α mitogen-activated protein kinase (MAPK) is the optimum target of 8based on its 3D molecular similarity, and docking studies showed that compound 8fits well into the active site of p38α-MAPK and forms relatively strong interactions with the surrounding amino acid residues. Accordingly, compound 8may be used as a promising lead compound for the development of new antitumor agents.

Developing outstanding radiation-resistant materials with excellent thermal and mechanical properties and self-healing ability remains a great challenge for advanced nuclear energy systems. Here, we incorporate three-dimensional (3D) carbon nanotube (CNT) networks into iron nanocrystals (Fe NCs) to obtain functional bulk Fe-CNT nanocomposites, exhibiting much higher thermal conductivity and mechanical properties than the Fe NCs without sacrificing strength. Irradiations by energetic helium (He) and krypton ions show that 3D CNT networks act as gigantic-capacity “nano-dustbins” to collect and store He atoms and defects via a “loading-transporting-unloading” mechanism in the grain boundary-CNT (GB-CNT) configuration, thus greatly enhancing their radiation tolerance compared with the Fe NC counterparts. The energetic landscape of interactions of He/defects with the GBs and the Fe-CNT interfaces in the nanocomposites are revealed by first-principles calculations. This work offers a promising strategy for material design of high-performance structural materials for future advanced nuclear reactors.

Background: Spectroscopic imaging based on the spontaneous Raman scattering effects can provide unique fingerprint information in relation to the vibration bands of molecules. Due to its advantages of high chemical specificity, non-invasive detection capability, low sensitivity to water, and no special sample pretreatment, Raman Spectroscopic Imaging (RSI) has become an invaluable tool in the field of biomedicine and medicinal chemistry. Methods: There are three methods to implement RSI, including point scanning, line scanning and wide-field RSI. Point-scanning can achieve two-and three-dimensional imaging of target samples. High spectral resolution, full spectral range and confocal features render this technique highly attractive. However, point scanning based RSI is a time-consuming process that can take several hours to map a small area. Line scanning RSI is an extension of point scanning method, with an imaging speed being 300-600 times faster. In the wide-field RSI, the laser illuminates the entire region of interest directly and all the images then collected for analysis. In general, it enables more accurate chemical imaging at faster speeds. Results: This review focuses on the recent advances in RSI, with particular emphasis on the latest developments on instrumentation and the related applications in biomedicine and medicinal chemistry. Finally, we prospect the development trend of RSI as well as its potential to translation from bench to bedside. Conclusion: RSI is a powerful technique that provides unique chemical information, with a great potential in the fields of biomedicine and medicinal chemistry.

The effect of rolling reduction and annealing process on the microstructure and corrosion behavior of Mg−9Li−1Zn (LZ91) alloy was investigated. The test alloy sheets were cold rolled with the reduction of 50% and 75%, respectively, and then were annealed at 200 °C for 1 h. The microstructure of test alloys was observed by OM and SEM while the phase composition was determined by XRD. The corrosion property was evaluated by electrochemical measurements and immersion tests. The results show that LZ91 alloy sheet consists of α-Mg, β-Li and precipitated Mg−Li−Zn compounds (MgLi2Zn and MgLiZn phases). Dynamic recrystallization grains appear in β-Li phase during annealing process, leading to grain refinement. The results indicate that the increasing rolling reduction and performing the annealing process can enhance the corrosion resistance of LZ91 alloy. The 75% cold-rolled and annealed LZ91 alloy shows the best corrosion resistance.

A typical rare-earth element modified Ce-SAF 2507 super duplex stainless steel was isothermally hot-compressed to reach superior mechanic properties over its pristine and peers. Mechanical, macro- and micro-structural evolutions subjected to hot-modification were studied in detail toward an optimal hot working for the Ce-SAF2507. A dynamic softening phenomenon shows that the increase of hot deformation temperature and decrease of the strain rate were dominated by the dynamic recovery of ferrite at a high strain rate and low deformation temperature. The same phenomenon at a low strain rate but high deformation temperature was ruled by the dynamic recrystallization of austenite. These two processes determined significant phase transformations from austenite to ferrite under higher deformation temperature and strain rate. A hot deformation activation energy Q∼406kJmol−1was obtained through a unified strain-compensated constitutive equation for Ce-SAF2507. Quantitative grain size refinements further proved the above mechanisms deduced from mechanical and microscopic observations, while structure induced changes of mechanical properties were crosschecked with the microhardness. Insights of microstructure also demonstrated the existences of the Cr2N in both phases, grain boundaries, and α/γ interface. The overall deformation dynamics was explicated based on the structural and quantitative results.

ABSTRACTIntroduction: Disease-modifying treatment for Parkinson’s disease (PD) to halt or revert the disease progression remains an unmet medical need. LRRK2 kinase activity is abnormally elevated in PD patients carrying LRRK2 mutations, with G2019S as the most frequent one. Small molecules to inhibit LRRK2 kinase activity might provide a potential disease-modifying strategy for PD.Areas covered: This review provides an update of small molecule LRRK2 inhibitors in patents published from January 2014 to October 2019. The molecules are classified by their structural scaffolds.Expert opinion: Despite the tremendous efforts to push small molecule LRRK2 inhibitors toward clinical trials, the overall progress is somewhat disappointing due to the challenges in compound optimization and the putative concern of target-related adverse effects. It is challenging to optimize multiple parameters including kinase selectivity, CNS penetration, and unbound fraction in brain simultaneously. In addition, the on-target effect of morphologic changes observed in lung/kidney in pre-clinical studies for several frontrunner ATP-competitive inhibitors prevented their further development. With this regard, non-ATP-competitive inhibitors may provide a different safety profile for development. DNL201 and DNL151 have entered early clinical trials to evaluate tolerability and target engagement biomarkers. This will pave the way for the development for future LRRK2 inhibitors.

Persistent luminescence has shown great potential in anticounterfeiting technology benefiting from the feature of free background. However, current anticounterfeiting technology faces the challenges of low security and inconvenience, because these challenges are mainly based on visible light. Herein, we report the preparation of nanoscale Zn2Ga2Sn0.5O6:Yb3+-Ni2+(ZGSO:Yb–Ni) phosphors with strong invisible persistent luminescence in the second near-infrared (NIR-II) window to meet the challenge. The nanoscale ZGSO:Yb–Ni phosphors (50–500 nm) were successfully prepared through the combination of a modified hydrothermal method and a subsequent annealing process. The resultant nanoparticles exhibit an intense NIR-II fluorescence at 1349 nm under the excitation of 254 nm light, and the persistent luminescence can last for ∼5 min after the excitation is switched off. A phosphor-based pattern was fabricated with resultant NIR-II nanopowders, and it shows high concealment, flexibility, and signal-to-noise ratio in the proof-of-concept experiment. These results demonstrate that ZGSO:Yb–Ni phosphors have great potential in anticounterfeiting applications.

Metallic multilayered nanofilms have been extensively studied owing to their unique physical properties and applications. However, studies on the thermal conductivity and electrical resistivity of metallic multilayered nanofilms, as their important physical properties, are seldom reported. In this work, Cu/W multilayered nanofilms with periodic thickness varying from 6 to 150 nm were deposited by magnetron sputtering. The resistivities of the Cu/W multilayered nanofilms increase with the decrease of periodic thickness, especially when the periodic thickness is smaller than 37 nm. The resistivities of the multilayered nanofilms fit well with the Fuchs–Sondheimer and Mayadas–Shatzkes (FS–MS) model, which considers both interface scattering and grain boundary scattering. The thermal conductivities of the Cu/W multilayered nanofilms were measured by the three-omega (3ω) method, which decrease with a decrease of periodic thickness initially and increase at the smallest periodic thickness of 6 nm. The Boltzmann transport equation (BTE)-based model was used, to explain the periodic thickness-dependent thermal conductivity of metallic multilayered nanofilms by considering the contributions from both phonon and electron heat transport processes, where the calculated thermal conductivities agree well with the measured ones. The electrical resistivity and thermal conductivity strongly depend on the microstructures of the multilayered nanofilms.

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF4nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitroand in vivosize-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm2. When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivoresult show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitroresult. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

Broadband absorption in the mid-infrared region is of significance for wide applications, such as photo/thermal detection, infrared stealth, and thermal imaging. Recently, metal-based plasmonic absorbers have been developed in the mid-infrared region. However, the fabrication cost, thickness, and bandwidth of these absorbers applied in aerospace still need to be improved. In this study, we propose and experimentally demonstrate a large-area, rather thin, metal-free absorber with broadband mid-infrared absorption based on a low-cost self-assembly process. The metal-free absorber is fabricated by spraying carbon black nanoparticles onto 5 μm-thick transferrable anodic aluminum oxide (AAO) templates on nanoporous Si graded-index films, which are fabricated by ion irradiation. Experimental results show that the average absorbance can reach 97.5% in the range of 2.5–15.3 μm. Full-wave numerical simulations show that the electromagnetic fields are greatly enhanced into pores, as these random carbon black particles serve as scatter centers and couple light into 5 μm-thick AAO templates, enhancing the interaction of light with carbon black significantly, and reveal that the high-performance broadband absorption is attributed to the light-trapping effect. The significant light absorption combined with a low-cost, high-production self-assembly technique suggests that the absorber can be used in the fields of optoelectronics and integrated photonics.

The metastasis of breast cancer mainly occurs through the axillary lymph node and blood circulation systems. It is extremely difficult to know when the cancer cells start to metastasize; however, early detection of breast cancer metastasis is crucial and challenging to enable surgical removal of the primary tumor and perform a systematic lymphadenectomy to eliminate invasion of the tumor. Herein, we report real-time tracking of the metastasis of orthotopic breast cancer with background-free near-infrared long-persistent luminescence (NIR-PL) imaging, and its guidance for the surgical removal of lymph nodes. The NIR-PL imaging is based on Cr3+/Nd3+codoped ZnGa2O4(A-ZGCN) nanoparticles with a superlong afterglow time of more than 15 days. We show that the detection sensitivity of metastasis of cancer cells with the NIR-PL imaging is higher than the classic bioluminescence imaging. We find that the metastasis of breast cancer cells to lymph nodes occurred as early as on the third day after orthotopic inoculation of breast cancer cells and followed an order of the proper axillary lymph node (PALN, day 3) > accessory axillary lymph node (AALN, day 6) > accessory mandibular lymph node (AMLN, day 9) > mandibular lymph node (MLN, day 25). In addition, we show that the NIR-PL nanoprobes (i.e., A-ZGCN NPs) displayed 17% radioenhancement, which was used for radiotherapy of orthotopic breast cancer to further prevent and reduce its metastasis to other organs. The radiotherapy treatment is superior to surgery for removal of the tumor accompanied by a NIR-PL imaging-guided lymphadenectomy. Our work demonstrates the great potential of NIR-PL imaging and the corresponding nanoprobes for tracking metastasis of cancer cells and for radiotherapy.

Background and Aims: It is urgent need to develop new-effective and well-tolerable medical treatment for endometriosis, but normal drug development is tedious, costly and time-consuming. Artificial intelligence (AI) is a powerful tool to drive discovery of novel druggable targets. Here we aim to use AI to identify novel therapeutic targets for endometriosis treatment.Method: Targets associated with endometriosis were prioritized by PandaOmics (a well-established AI-driven target identification platform). Expression levels of druggable targets were tested in human endometriotic lesions. Functional characterizations of the targets were performed by in-vitro and in-vivo endometriosis models. Viability, proliferation and apoptosis were examined.Results: Analysis of 11 public endometriosis bulk transcriptomics databases revealed 2 lists of high confidence and novel druggable targets. Tow novel targets ENDO01 and ENDO02 were selected based on ranking in PandaOmics, consistency of significant dysregulated expression across comparisons, as well as literature evidence relevant to disease-driving mechanisms. Differential expressions were confirmed in human endometriosis tissues. siRNA targeting ENDO01 and ENDO02 significantly reduced cell viability and proliferation, as well as enhanced apoptosis in endometriotic cells in-vitro; and significantly decreased lesion volume and weight with reduced proliferative and enhanced apoptosis in-vivo.Conclusion: Two novel targets for endometriosis were identified with AI and validated by in-vitro and in-vivo experiments within a short period. The study demonstrated how AI could speed up the novel target discovery process from years to months. For diseases remaining incurable or with high morbidity, the application of AI in target discovery could be a new therapeutic regimen that benefits patients.

Black phosphorus (BP) nanostructures with unique layer-dependent properties have been extensively applied in the fields of electronic devices, energy conversion and storage, and nanomedicine. As a narrow band gap semiconductor, they are expected to show strong second near-infrared (NIR-II) fluorescence. However, there is no report on the NIR-II fluorescence of free-standing BP nanostructures, which have great potential in the NIR-II fluorescence bioimaging because of their excellent biocompatibility and biodegradability. Here, for the first time, we report that the BP nanoparticles modified with cholesterol exhibit strong NIR-II fluorescence and can be encapsulated with the PEGylated lipid to form BP@lipid-PEG nanospheres for in vitro and in vivo NIR-II imaging. The resultant BP@lipid-PEG nanospheres exhibit broad emissions from 900 to 1650 nm under excitation by an 808 nm laser and have 8% quantum yield of that of standard dye IR-26. We also show that the NIR-II fluorescence image acquired with emission beyond 1400 nm has the sharpest contrast and can be used to in situ measure the diameter of blood vessels. In addition to NIR-II fluorescence imaging, we also show the potential of BP@lipid-PEG nanospheres in photoacoustic (PA) imaging. Both the long-wavelength NIR-II fluorescence imaging and PA imaging reveal that the as-fabricated BP@lipid-PEG nanospheres can be gradually metabolized by the liver in 48 h, thus making them promising for bioapplications.

A hydrodynamic tunnel experimental investigation and analysis of vibration characteristics for a hydrofoil in a transient regime is considered. Tests are performed for NACA 0017 models with a non-uniform section at an angle of attack AOA = 5º and Reynolds numbers up to Re= 7.0 × 106. This study is related to a project design of experiments in a complex facility that involves several parameters. The analysis focuses on the vibrations of a hydrofoil for different values of the bracing stiffness kh, the torsional stiffness ka, and the locations of the elastic axis āand of the center of gravity xa. The structural bracing response is investigated via measurements of the displacement of the free tip section of the hydrofoil using a three-axis acceleration sensor, and the torsional response of the structure is analyzed via measurements of displacements with single-axis acceleration sensors. The hydrofoil is made of reinforced plastics without flexibility, and elastic functions are provided by a spring support mechanism combined with a torsional structure. The study shows that an increase of the velocity V∞results in different behaviors of the bracing and torsional amplitudes. Another notable result of the study is that the emergence of transition occurs simultaneously with additional peaks and changes of vibration amplitudes.

Flake graphite iron, compacted graphite iron and spheroidal graphite iron with various tensile strengths were cast. They were selected and grouped according to roughly the same tensile strength, and then the main cutting force in each group was measured and compared. The microstructures of different cast irons were characterized. The relationship between the cutting force and microstructure was established. Results show that the graphite morphology in cast irons determines the strength. In order to obtain the same strength of the cast iron with sharply edged graphite, more or finer pearlite in the matrix is needed. Graphitic cast irons with high pearlite content and smaller pearlite interlamellar spacing have higher hardness. For the cast irons with different graphite morphologies, but almost the same tensile strength, the main cutting force is obviously different, along with the hardness. Harder cast irons have a greater cutting force, but the difference in cutting force is not proportional to hardness.

Breast cancer remains to show high mortality and poor prognosis in women despite of significant progress in recent diagnosis and treatment. Herein, we report the rational design of a highly efficient ultrasmall nanotheranostic agent with excellent photodynamic therapy (PDT) performance to against breast cancer and its metastasis by eliciting antitumor immunity. The ultrasmall nanoagent (3.1 ± 0.4 nm) was fabricated from polyethylene glycol modified Cu2–xSe nanoparticles, β-cyclodextrin, and chlorin e6 under ambient conditions. The resultant nanoplatform (CS–CD–Ce6 NPs) can be passively accumulated into the tumor to exhibit dramatic antitumor efficacy through the excellent PDT effect under near-infrared irradiation. The excellent PDT performance of this nanoplatform is owing to its role as a Fenton-like Haber–Weiss catalyst for the efficient degradation of H2O2within the tumor to release hydroxyl radicals (·OH) and very toxic singlet oxygen (1O2) under irradiation. The generated vast amounts of reactive oxygen species not only killed primary tumor cells but also elicited immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) and induced proinflammatory M1-macrophages polarization. Thereby, antitumor immune responses against the metastasis of breast cancer were robustly evoked. Our work demonstrates that ultrasmall Cu2–xSe nanoparticle-based nanoplatform offers a promising way to prevent cancer metastasis via immunogenic effects through its excellent PDT performance.

Acute-on-chronic liver failure (ACLF) carries a significant burden on critical care services and health care resources. However, the exact pathogenesis of ACLF remains to be elucidated, and novel treatments are desperately required. In our previous work, we utilized mice subjected to acute insult in the context of hepatic fibrosis to simulate the development of ACLF and documented the favorable hepatoprotection conferred by M2-like macrophages in vivoand in vitro. In the present study, we focused on the phenotypic switch of human and mouse macrophages and assessed the effects of this switch on apoptosis resistance in hepatocytes. For this purpose, human and mouse macrophages were isolated and polarized into M0, M(IFN-γ), M(IFN-γ→IL-4), M(IL-4) or M(IL-4→IFN-γ) subsets. Conditioned media (CM) from these subsets were applied to human and mouse hepatocytes followed by apoptosis induction. Cell apoptosis was evaluated by immunostaining for cleaved caspase-3. As a result, M(IFN-γ) or M(IL-4) macrophages switched their phenotype into M(IFN-γ→IL-4) or M(IL-4→IFN-γ) through reprogramming with IL-4 or IFN-γ, respectively. Importantly, hepatocytes pre-treated with M(IFN-γ→IL-4) CMs exhibited much weaker expression of cleaved caspase-3, compared to those pre-treated with M(IFN-γ) CM, and vice versa. Together, phenotypic switch of macrophages toward M(IL-4) phenotype confers hepatocytes enhanced resistance to apoptosis.

The unsteady bearing forces of a propeller can be significantly affected by external transverse excitations. This paper numerically studies the unsteady variation characteristics of the bearing forces of a three-blade conventional propeller with external transverse excitations or without excitations. The dynamic mesh method combined with the RANS turbulence model is employed. The numerical simulation shows the frequency response in the frequency domain of KT, KQunder external transverse excitations. The frequency of the response is found always equal to twice of the excitation frequency. If the amplitude of the external transverse excitation keeps constant, the amplitude of the response increases with the increase of the excitation frequency. If the excitation frequency keeps constant, the amplitude of the response increases with the increase of the excitation amplitude, in a power-law relationship. The pressure distribution can be significantly affected by the external transverse excitation, leading to a high irregularity of the flow field.