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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.

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.