Search

ABSTRACTJapan’s Conscription Law of 1873 constituted a core element of the military reforms implemented by the Meiji government. The law implied an additional burden in the form of a “tax in kind” which would not be shared equally, because only a small portion of those eligible to serve were actually recruited. As the government neither alleviated the hardship nor corrected the inequalities created by the conscription system, local communities and private entrepreneurs took initiative. One response was conscription insurance. Introduced toward the end of the 19thcentury, it established itself as an important segment of Japan’s insurance industry in pre-war Japan with a performance comparable to that of the life insurance industry. Despite its success, Japan’s conscription insurance has so far not attracted the attention of international scholars. This paper takes a first step towards filling the gap. It describes the background of the major companies, evaluates their core product and analyses the performance of the industry. It argues that a major factor in the success of the industry was the ability of the companies to position themselves and their product as serving the national interest.

ABSTRACTBased on the longitudinal case study of the CHINT group for about 40 years, this paper analyses co-evolution of cluster firm innovative capabilities and its external networks; results show that firm's product and market exploratory/exploitative innovation have been improved with the continuous development of network type from manufacturing and marketing network to innovation network, and evolution of network construction by changing network relations, size and range. Then the levels of internal innovative capabilities and developments in different stages restrict and influence the characters and evolutionary path of network types and constructions. But, entrepreneurial orientation will also bring significant impacts on the co-evolution of innovation capabilities and firm's external networks.

Phase separation plays a crucial role in many natural and industrial processes, such as the formation of clouds and minerals and the distillation of crude oil. In metals and alloys, phase separation is an important approach often utilized to improve their mechanical strength for use in construction, automobile, and aerospace manufacturing. Despite its importance in many processes, the atomic details of phase separation are largely unknown. In particular, it is unclear how a different crystal phase emerges from the parent alloy. Here, using real-time in situtransmission electron microscopy, we describe the stages of the phase separation in face-centered cubic (fcc) AuRu alloy nanoparticles, resulting in a Ru phase with a hexagonal close-packed (hcp) crystal structure. Our observation reveals that the hcpRu phase forms in two steps: the spinodal decomposition of the alloy produces metastable fccRu clusters, and as they grow larger, these clusters transform into hcpRu domains. Our calculations indicate that the primary reason for the fcc-to-hcptransformation is the size-dependent competition between the interfacial and bulk energies of Ru domains. These insights into elusive, transient steps in the phase separation of alloys can aid in engineering nanomaterials with unconventional phases.

Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mineral density and a heightened risk of fractures. Therapies for OP have primarily focused on balancing bone formation and bone resorption, but enhancing the remineralization of osteoporotic bone is also a key strategy for effective repair. Recent insights into biomineralization mechanisms have highlighted the essential role of mineral-containing extracellular vesicles (EVs) secreted by osteoblasts in promoting bone marrow mesenchymal stromal/stem cell (BMSC) differentiation and initiating matrix mineralization. Drawing from these principles, we developed a biomimetic approach to replicate the structure and function of the osteoblast-derived EVs by engineering biomimetic mitochondrial minerals with bone marrow homing cell membranes (CMs). This bone-targeted biomimetic system exhibits excellent biocompatibility, enhancing osteogenic differentiation and stimulating angiogenesis by regulating cellular energy metabolism. Additionally, the CM-coated structure shows affinity for collagen fibrils, effectively enhancing intrafibrillar collagen mineralization, thereby facilitating osteoporotic bone repair. Overall, the biomimetic system offers a safe and efficient therapeutic alternative, positioning it as a platform for bone tissue engineering and regenerative medicine.

Multisensor navigation via redundancy and complementary has been widely applied to safety-critical services, such as self-driving vehicles. To improve the robustness and reliability of the multisensor navigation system in urban canyon environments, a robust Kalman filter (RKF) method enhanced by the projection statistic (PS) detector is proposed in this work. Based on a statistical consistency check, the availability of measurements from observation sensors is preevaluated by the PS criterion. The new iterative Huber’s M-estimation with the exclusion function is implemented on the linear regression model for robust state estimation. The effectiveness of the proposed algorithm was verified by a dynamic test in the representative urban canyon environment. Our approach shows significant superiority and robustness among the comparative experiments, where the 3-D root-mean-square (rms) error is limited to 3.33 m. The biased measurements can be effectively identified and removed by the PS detector with a given significance level. The new iterative Huber’s M-estimation assisted by the prior availability knowledge enables the integration solution more robust and reliable. The presented robust method is pretty suitable for multisensor navigation in urban canyon environments.

Deep neural networks executing with low precision at inference time can gain acceleration and compression advantages over their high-precision counterparts, but need to overcome the challenge of accuracy degeneration as the bit-width decreases. This work focuses on under 4-bit quantization that has a significant accuracy degeneration. We start with ternarization, a balance between efficiency and accuracy that quantizes both weights and activations into ternary values. We find that the hard threshold $\Delta $ introduced in previous ternary networks for determining quantization intervals and the suboptimal solution of $\Delta $ limit the performance of the ternary model. To alleviate it, we present Soft Threshold Ternary Networks (STTN), which enables the model to automatically determine ternarized values instead of depending on a hard threshold. Based on it, we further generalize the idea of soft threshold from ternarization to arbitrary bit-width, named Soft Threshold Quantized Networks (STQN). We observe that previous quantization relies on the rounding-to-nearest function, constraining the quantization solution space and leading to a significant accuracy degradation, especially in low-bit ( $\leq3$ -bits) quantization. Instead of relying on the traditional rounding-to-nearest function, STQN is able to determine quantization intervals by itself adaptively. Accuracy experiments on image classification, object detection and instance segmentation, as well as efficiency experiments on field-programmable gate array (FPGA) demonstrate that the proposed framework can achieve a prominent tradeoff between accuracy and efficiency. Code is available at: https://github.com/WeixiangXu/STTN.

Cervical cancer is a common malignant gynecological tumor for females all over the world. Circular RNAs (circRNAs) are being found to have relevance to various human cancers, including cervical cancer. This study is designed to explore the role and mechanism of circRNA DDB1- and CUL4-associated factor 1 (circVPRBP, also known as hsa_circ_0065898) on the progression of cervical cancer. CircVPRBP, microRNA-106b-5p (miR-106b-5p), and tripartite motif-containing protein 3 (TRIM3) levels were determined by real-time quantitative PCR. Cell proliferative ability, apoptosis rate, cell cycle progression, migration, and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2′-deoxyuridine, colony formation assay, flow cytometry, and transwell assays. Protein levels of matrix metallopeptidase 2 (MMP2) and matrix MMP9, and TRIM3 were measured by western blot assay. The binding relationship between miR-106b-5p and circVPRBP or TRIM3 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA immunoprecipitation assays. The biological role of circVPRBP on cervical tumor growth was examined by the xenograft tumor model in vivo. CircVPRBP and TRIM3 were decreased, and miR-106b-5p was increased in cervical cancer tissues and cell lines. Furthermore, circVPRBP could suppress cell growth and metastasis of cervical cancer cells in vitro. Mechanically, circVPRBP could regulate TRIM3 expression by sponging miR-106b-5p. Also, circVPRBP upregulation repressed tumor growth of cervical cancer cells in vivo. CircVPRBP could inhibit the malignant biological behavior of cervical cancer cells by miR-106b-5p/TRIM3 axis, providing a promising therapeutic target for cervical cancer treatment.

Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco’s modified Eagle’s medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

ABSTRACTThe expression of circRNA_FOXO3 was found to be positively associated with the expression of Forkhead Box O3 (FOXO3), which is targeted and regulated by miR-23a. Polymorphisms in rs12196996 and rs2232365 have been reported in various diseases. In this study, we recruited intensive care unit (ICU)-acquired sepsis patients and grouped them according to their genotypes of rs12196996 and rs2232365. Quantitative real-time PCR was performed to analyze the expression of circRNA_FOXO3, FOXO3 mRNA, and miR-23a. ELISA was carried out to evaluate the abundance of cytokines and luciferase assay was used to explore the inhibitory role of miR-23a on circRNA_FOXO3 and FOXO3. Accordingly, we found that rs12196996 GG and rs2232365 AA were significantly correlated with prolonged survival of ICU-acquired sepsis patients. Rs12196996 GG and rs2232365 AA were also correlated with increased level of miR-23a, IL-10 and decreased level of TNF, IL-2, IFN, IL-6 and IL-1β in the peripheral blood cell samples of patients with ICU-acquired sepsis. The luciferase activity of wild-type (WT) circRNA_FOXO3 and FOXO3 were severely reduced by miR-23a. MiR-23a precursors could effectively suppress the expression of circRNA_FOXO3 and FOXO3 in the cells. Moreover, LPS-induced cell viability loss and dysregulation of cytokines were effectively restored by the knockdown of FOXO3 or circRNA_FOXO3 siRNA in the cells. This study revealed that the minor allele of rs12196996 polymorphism and rs2232365 polymorphism collaboratively contributed to the increased survival and suppressed severity of ICU-acquired sepsis.

Graphical abstract:

Efficient synthesis of chiral compounds under mild conditions is highly desirable in the chemical and pharmaceutical communities, but it often faces difficulties. Although various enzymes have been harnessed as biocatalysts in asymmetric reduction, identifying key residues that function as stereoselectivity-switches at which amino acid exchange events can be designed by rational design or directed evolution, constitutes a major challenge. Here, we address this question by using the Zn-dependent alcohol dehydrogenase from Thermoanaerobacter brockii(TbSADH) as a model enzyme in the asymmetric reduction of a difficult-to-reduce ketone (tetrahydrofuran-3-one). Following the theoretical analysis of epistatic mutational effects and investigating the results of deconvoluting multi-mutational variants, two crucial amino acid positions 294 and 295 were identified as the “switches” that specifically control the inversion of product chirality. In order to shed light on the concealed mechanistic intricacies, molecular dynamics (MD) simulations along with quantum mechanical (QM) calculations were performed on the variants, which unveiled the distinct H-bonds formed with the furan ring O-atom in pro-(S) and pro-(R) orientations of positions 294 and 295 leading to stereospecific formation of the product.

This paper develops the theory of the kth power expectile estimation and considers its relevant hypothesis tests for coefficients of linear regression models. We prove that the asymptotic covariance matrix of kth power expectile regression converges to that of quantile regression as kconverges to one and hence promise a moment estimator of asymptotic matrix of quantile regression. The kth power expectile regression is then utilized to test for homoskedasticity and conditional symmetry of the data. Detailed comparisons of the local power among the kth power expectile regression tests, the quantile regression test, and the expectile regression test have been provided. When the underlying distribution is not standard normal, results show that the optimal kare often larger than 1 and smaller than 2, which suggests the general kth power expectile regression is necessary. Finally, the methods are illustrated by a real example.

ABSTRACTBearings are widely applied in rotating machinery of nuclear power plants (NPPs). Data-driven fault diagnosis technology is critical to ensuring the reliable operation of rotating machinery. Aiming at the problem of poor model generalization ability caused by discrepant data distribution of monitoring signals under various working conditions, a deep transfer learning method based on fully categorized alignment subdomain adaptation (FCA-SAN) is proposed in this paper. Firstly, the bearing vibration signals of the source and target operating conditions are preprocessed and converted into time-frequency domain images suitable for model input. Subsequently, a pre-trained deep convolutional neural network (DCNN) model is adopted as the feature extractor, which is combined with FCA-SAN to extract transferable features across different working conditions. The subdomain adaptation method reduces the data distribution discrepancy more fine-grained by aligning the feature distribution of different working conditions, thereby effectively improving the model generalization ability. Finally, the experimental results show that, compared with the traditional method, the proposed subdomain adaptation method reaches the highest fault diagnosis accuracy in different transfer tasks, which demonstrates the potential application value in rotating machinery of NPPs.

Graphite has dominated the market of anode materials for lithium-ion batteries in applications such as consumer electronic devices and electric vehicles. As commercial graphite anodes are approaching their theoretical capacity, significant efforts have been dedicated towards higher capacity by blending capacity-enhancing additives (e.g., Si) with graphite particles. In spite of the improved gravimetric capacity, the areal capacity of such composite anodes might decrease due to excess void spaces and an incompatible material size distribution. Herein, a rational design of compact graphite/Si/SiO2ternary composites has been proposed to address the abovementioned issues. Si/SiO2clusters with an optimal particle size are homogeneously dispersed in the interstitial spaces between graphite particles to promote the packing density, leading to a higher areal capacity than that of pure graphite with equivalent mass loading or electrode thickness. By taking the full intrinsic advantages of graphite, Si, and SiO2, the composite electrodes exhibit 553.6 mAh g–1after 700 cycles with a capacity retention of 95.2%. Furthermore, the graphite/Si/SiO2electrodes demonstrate a high coulombic efficiency with an average of 99.68% from 2nd to 200th cycles and areal capacities above 1.75 mAh cm–2during 200 cycles with an areal mass loading as high as 4.04 mg cm–2. A packing model has been proposed and verified by experimental investigation as a design principle of densely compacted anodes. The effective strategy of introducing Si/SiO2clusters into the void spaces between graphite particles provides an alternative solution for implementation of graphite–Si composite anodes in next-generation Li-ion cells.

The discovery of complete ammonia oxidation (comammox) has altered our understanding of nitrification, which is the rate-limiting process in the global nitrogen cycle. However, understanding the ecological role of comammox or its contribution to nitrification in both natural and artificial ecosystems is still in its infancy. Here, we investigated the community distribution and function of comammox bacteria in riparian ecosystems and analyzed interactions between comammox and other nitrogen cycling microorganisms. The comammox bacterial abundance and rate were higher in summer than in winter and higher in nonrhizosphere soils than in the rhizosphere. Fringe soils in the riparian zone comprise a comammox hotspot, where the abundance (2.58 × 108copies g–1) and rate (0.86 mg N kg–1d–1) of comammox were not only higher than at other sampling sites but also higher than those of other ammonia oxidation processes. The comammox rate correlated significantly positively with relative abundance of the comammox species Candidatus Nitrospira nitrificansbut not with that of the species Candidatus Nitrospira nitrosa. Analysis of comammox interaction with other ammonia-oxidizing processes revealed ammonia-oxidizing archaea to dominate interface soils, comammox to dominate in fringe soils, and anaerobic ammonium oxidation (anammox) to dominate in interface sediments of the riparian zone. These results indicate that comammox may constitute an important and currently underestimated process of microbial nitrification in riparian zone ecosystems.

With the rapid development of mobile crowdsensing applications, task allocation has emerged as a new problem to be solved. Many task allocation strategies have been proposed to select the proper participants to complete tasks. Those methods need participants to submit their real locations to the platform in order to realize the optimal task assignment. However, those traditional task allocation strategies have two weaknesses. First, centralized task allocations result in high computing and communications loads. Second, the exposure of real locations increases participants' concerns regarding location privacy. To address these problems, in this paper, we propose an optimal geo-indistinguishable task allocation (GITA) mechanism using mobile edge clouds. First, the new task that is received by the remote cloud is sent to the mobile edge cloud that is nearest to the task location. Then, the mobile edge clouds serve as distributed controllers to allocate the assigned tasks to the proper candidates. To protect the candidates' real locations, we utilize a geo-indistinguishable mechanism based on differential privacy to preserve location privacy. Specifically, we obfuscate the participants' real locations as disturbed locations, and realize the optimal task allocation based on these disturbed locations. Furthermore, we apply multiobjective mixed integer nonlinear optimization to solve this problem. Finally, extensive experimental results show that, compared with the traditional Laplace mechanism and another privacy-preserving task allocation strategy, the GITA mechanism that is proposed in this paper can decrease users' moving distances and raise the task completion rate. [ABSTRACT FROM AUTHOR]

Glycyrrhetinic acid (GA) sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver, however, the limitation of commonly used macromolecular GA modification approaches as well as the application gap across various vector have constrained its use. In this study, we proposed a novel perspective to break out, disulfide bonds (SS) were employed as linkage to facilitate GA modification, which allows further connections with various carriers, while provides additional glutathione (GSH)-responsive property. The superiority of GA-disulfide conjunction was validated using mesoporous silica nanoparticles (MSN) as model carriers, chemotherapeutic drug (doxorubicin) and photosensitizer (indocyanine green) were loaded into MSN-SS-GA to further achieve chemo-photothermal synergistic anti-tumor therapy. Based on results from multiple evaluations, the GA-disulfide drafted MSN (DI/MSN-SS-GA) demonstrated excepted liver tumor targeting effect and exhibited GSH-stimuli release property to reduce preleakage. Taken together, this study presents an effective chemo-photothermal therapy for liver cancer (88.26%). This study offers a potential, robust and straightforward strategy on GA application for enhancing liver targeting therapy.

Crucial for mediating inflammation and the perception of pain, the ion channel known as transient receptor potential ankyrin 1 (TRPA1) holds significant importance. It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition. By leveraging the unique advantages of liposomes, a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed, providing a new strategy for osteoarthritis (OA) drug therapy. The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate (HAMA) hydrogels to make hydrogel microspheres viamicrofluidic technology. An in vitroinflammatory chondrocyte model was established with interleukin-1β(IL-1β) to demonstrate HAMA@Lipo@HC's capabilities. A destabilization of the medial meniscus (DMM) mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA. HAMA@Lipo@HC has a uniform particle-size distribution and is injectable. The drug encapsulation rate was 64.29% ± 2.58%, with a sustained release period of 28 days. Inhibition of TRPA1 viaHC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation. In DMM model OA mice, microspheres showed good long-term sustained drug release properties, improved joint inflammation microenvironment, reduced articular cartilage damage and decreased mechanical nociceptive threshold. This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity, focusing on TRPA1 as a therapeutic target for osteoarthritis. Additionally, it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.

Background:Pharyngeal packs are employed to mitigate postoperative nausea and vomiting (PONV) and have become prevalent in dental and otolaryngological surgeries. However, their clinical efficacy continues to be a topic of debate. The objective of the present study was to conduct a quantitative assessment of the impact of pharyngeal packing in dental and otolaryngological surgeries through meta-analysis. Methods:We identified relevant randomized controlled trials (RCTs) through systematic searches of online databases, including PubMed, Embase, and Cochrane Central. Potential eligible studies were evaluated using the Jadad scoring system (range 0-5 points), with only high-quality RCTs (3 points or more) being included. The incidence of PONV, morbidity, and the level of throat pain were aggregated and estimated. Publication bias was evaluated using funnel plot symmetry and the Egger test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to rate the evidence. Results:Ten high-quality RCTs comprising 1026 participants were ultimately included. Subsequent quantitative pooled estimation unveiled that the utilization of pharyngeal packing did not lead to a significant reduction in the incidence of nausea (P= .272), vomiting (P= .775), overall PONV (P= .118), or throat pain (P= .149). By contrast, the application of pharyngeal packs was found to significantly increase the level of throat pain (P= .003). No obvious publication bias was detected, and the majority of evidence was rated high or moderate. Conclusion:Based on the existing evidence, we conclude that pharyngeal packing lacks clinical benefit and is not advised for dental and otolaryngological surgeries.

Measuring and modeling the solubility of drugs in different solvent systems is helpful to guide the selection of appropriate solvents at various stages of drug formulation development. In this work, the gravimetrical method was used to determine the solubility data of oxaprozin (OXA) in different compositions of water/organic solvents (methanol and ethanol) binary mixtures within the range of 293.15 to 333.15 K. Subsequently, the differential scanning calorimetry method was used to measure the solubility of the drug in polymers (Polyethylene Glycol 6000 and Polyvinylpyrrolidone K30) at above 400 K. Then, the solubility of OXA in ultrapure water and polymer aqueous solution was acquired by UV spectrophotometry or HPLC within a temperature range of 303.15 to 323.15 K. Finally, the experimental values were compared with the calculated values from the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) to investigate the prediction accuracy of this model in different complex mixed solvent systems. The average relative deviations (ARD) were used to evaluate the model performance of PC-SAFT. Furthermore, PC-SAFT combined with solid–liquid equilibrium theory not only modeled the phase behavior between pure or mixed solvents and drugs independent of the molecular weight of the solvent but also did not require any experimental data or model parameters from the ternary system to predict the phase behavior of OXA in binary solvents. The results of this work illustrate that PC-SAFT is a beneficial model in drug development.

O3-type layered oxide cathodes are primarily limited by complex phase transitions and sluggish kinetics resulting in rapid capacity drop and poor rate capability. Even worse, its inherent air sensitivity leads to spontaneous extraction of lattice Na-ions and the deactivation of the cathode. Simultaneous modification of both the bulk phase and the surface structure is promising to offset the above deficiencies. A spinel@O3 type layered composite structure Na0.9Mn0.5Ni0.5Cu0.1O2+x(NMNCO-SL) was constructed for the design of cathodes with higher cycling, rate and air stability. The atomic-level Cu-rich spinel structure on the surface was identified by scanning transmission electron microscopy, elemental linear scanning analysis and Raman spectra. In situ charge-discharge X-ray diffraction results show that the phase transition of NMNCO-SL is significantly suppressed. Finally, the material maintains good electrochemical properties after exposure to stringent humidity environments. The results indicate that the spinel structure at the surface plays a significant role in improving ion-diffusion dynamics, enhancing structural integrity, and increasing air stability. 1 Ah pouch cell based on NMNCO-SL showed 92% capacity retention after 500 cycles of charge/discharge cycling at 1C, demonstrating the potential prospects of customizing the surface phase structure for materials engineering applications.

Lead halide based organic–inorganic hybrid perovskite (HPVK) materials combine the advantages of solution processing, high absorption coefficient, long charge diffusion length, and high mobility of inorganic framework. The recent interest in this field is mainly focused on solution-processable HPVK for energy conversion and different types of optoelectronics. The performance of HPVK optoelectronics is rivaling now that of conventional devices, but the stability of the HPVK device is now a major challenge in the field where chemists are expected to play more active roles. This Perspective summarizes the progress in the understanding of mechanism of the HPVK formation, and various applications in different fields such as solar cells, light-emitting diodes, lasers, photodetectors, and field-effect transistors. A personal view of the past developments and future challenges is also provided.

We develop an “acceptor dimerization” strategy by a bis-diketopyrrolopyrrole (2DPP) for an ambipolar organic semiconductor. Copolymers of 2DPP and benzothiadiazole (BTz) derivatives, P2DPP-BTz and P2DPP-2FBTz, are designed and synthesized. Both of the polymers exhibit narrow optical bandgaps of ca. 1.30 eV. The strong electron-withdrawing property of 2DPP results in low-lying lowest unoccupied molecular orbital (LUMO) energy levels of the polymers, improving the electron mobilities. 2D grazing incident X-ray diffraction and atomic force microscopy indicate that the P2DPP-BTz exhibits a small π–π stacking distance of 3.59 Å and a smooth interface, thus promoting high mobility. To take full advantage of the flexibility of organic semiconductors, flexible field-effect transistors (FETs) were fabricated on poly(ethylene terephthalate) (PET) substrates. The FETs based on P2DPP-BTz show high performance with hole and electron mobilities of 1.73 and 2.58 cm2V–1s–1, respectively. Our results demonstrate that the 2DPP acceptor is a promising building block for high-mobility ambipolar polymers.

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme‐catalyzed reaction is reported to prepare magnesium‐based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo‐crosslinking. Then, the alkaline phosphatase (ALP)‐catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions. Inspired by the natural biomineralization process of bone tissue, a magnesium‐based osteoinductive microsphere, inlayed with bone mesenchymal stem cells (BMSCs), is prepared. The cell‐laden microspheres can be packed in situ and completely fill the irregular defects via the excellent shape adaptability. Benefiting from the high bioactivity, this microsphere‐based scaffold displays remarkable performance in promoting the in vivo bone regeneration.

Pharmaceutical Integrated Experiment (PIE) is a systematic and comprehensive compulsory course for undergraduates majoring in pharmacy and pharmaceutical engineering. This course mainly focuses on integrating the theoretical knowledge of various disciplines into practice, enabling students to master the key processes of drug research and production. In view of the shortcomings of traditional PIE teaching in many domestic colleges and universities, we adopted teaching reform and exploration in 2021 and 2022. Specifically, based on our experience in development of novel SIRT5 inhibitors, we presented a project-based teaching model and selected “Design, Synthesis and Biological Evaluation of Potential SIRT5 Inhibitors” as a case to implement such teaching model. In our course, students worked in a small group to participate in seven interrelated course segments. Throughout the course, we paid attention to process assessment and students’ multirole participation in course. We effectively combined the student’s course grades and survey results to evaluate students’ overall learning effect. Compared to traditional PIE course teaching, this project-based PIE course teaching model is more likely to stimulate students’ enthusiasm for self-directed learning due to the more continuous and permeable experimental content, thereby effectively improving the teaching quality of PIE courses.

Sepsis-associated acute kidney injury (AKI) is a serious clinical problem without effective drugs. Inhibition of sirtuin 5 (SIRT5) has been confirmed to protect against AKI, suggesting that SIRT5 inhibitors might be a promising therapeutic approach for AKI. Herein, structural optimization was performed on our previous compound 1(IC50= 3.0 μM), and a series of 2,4,5-trisubstituted pyrimidine derivatives have been synthesized. The structure–activity relationship (SAR) analysis led to the discovery of three nanomolar level SIRT5 inhibitors, of which the most potent compound 58(IC50= 310 nM) was demonstrated to be a substrate-competitive and selective inhibitor. Importantly, 58significantly alleviated kidney dysfunction and pathological injury in both lipopolysaccharide (LPS)- and cecal ligation/perforation (CLP)-induced septic AKI mice. Further studies revealed that 58regulated protein succinylation and the release of proinflammatory cytokines in the kidneys of septic AKI mice. Collectively, these results highlighted that targeting SIRT5 has a therapeutic potential against septic AKI.

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.

Graphene quantum dots (GQDs) and silver nanocubes (AgNCs) were synthesized successfully and characterized by UV-vis and fluorescence (FL) spectra, Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The GQDs and AgNCs modified gold electrode (GE) possesses good conductivity shown by electrochemical impedance spectroscopy (EIS). The Chit–GQDs/AgNCs/GE displays a good electrocatalytic activity towards the reduction of hydrogen peroxide (H2O2), and can be used as a novel and sensitive enzyme-free H2O2sensor. According to the amperometric experiments, the sensor exhibits a rapid response, a wide linear range from 10 μM to 7.38 mM, a low detection limit of 0.15 μM and high selectivity, as well as a good repeatability for H2O2determination.

Localized surface plasmon resonance (LSPR) of doped Si nanocrystals (NCs) is critical to the development of Si-based plasmonics. We now experimentally show that LSPR can be obtained from both B- and P-doped Si NCs in the mid-infrared region. Both experiments and calculations demonstrate that the Drude model can be used to describe the LSPR of Si NCs if the dielectric screening and carrier effective mass of Si NCs are considered. When the doping levels of B and P are similar, the LSPR energy of B-doped Si NCs is higher than that of P-doped Si NCs because B is more efficiently activated to produce free carriers than P in Si NCs. We find that the plasmonic coupling between Si NCs is effectively blocked by oxide at the NC surface. The LSPR quality factors of B- and P-doped Si NCs approach those of traditional noble metal NCs. We demonstrate that LSPR is an effective means to gain physical insights on the electronic properties of doped Si NCs. The current work on the model semiconductor NCs, i.e., Si NCs has important implication for the physical understanding and practical use of semiconductor NC plasmonics.

The purpose of this paper is to further understand the dependence of the electrochemical activity of a boron-doped diamond (BDD) film electrode on its surface boron doping concentration and the pretreatment applied to its surface. An electrochemically cathodic polarization ([?]3 V vs. SCE) with a varying polarization duration (5-50 min) was carried separately out to three types of BDDs with a boron doping level of 700, 2500, 8000 ppm in 0.5 M H2SO4 solution. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to evaluate surface activity of the BDDs with and without cathodic polarizations by using 1.0 mM Fe(CN)63[?]/4[?]. Moreover, the surface activity of the polarized BDD electrodes was examined further by using anodic stripping voltammetry to detect a series of known concentrations of Pb2+. Our results indicated that the applied cathodic polarization significantly improved the surface activity of the as-received BDD, and exhibited more active effect on the surface of a higher boron doping level BDD compared to a lower boron doping level BDD, thereby improving the ability of the polarized BDDs to detect trace Pb(II) in aqueous solutions by anodic stripping voltammetry.

Concept maps are an important tool to organize, represent, and share knowledge. Building a concept map involves creating text-based concepts and specifying their relationships with line-based links. Current concept map tools usually impose specific task structures for text and link construction, and may increase cognitive burden to generate and interact with concept maps. While pen-based devices (e.g., tablet PCs) offer users more freedom in drawing concept maps with a pen or stylus more naturally, the support for hand-drawn concept map creation and manipulation is still limited, largely due to the lack of methods to recognize the components and structures of hand-drawn concept maps. This article proposes a method to understand hand-drawn concept maps. Our algorithm can extract node blocks, or concept blocks, and link blocks of a hand-drawn concept map by combining dynamic programming and graph partitioning, recognize the text content of each concept node, and build a concept-map structure by relating concepts and links. We also design an algorithm for concept map retrieval based on hand-drawn queries. With our algorithms, we introduce structure-based intelligent manipulation techniques and ink-based retrieval techniques to support the management and modification of hand-drawn concept maps. Results from our evaluation study show high structure recognition accuracy in real time of our method, and good usability of intelligent manipulation and retrieval techniques.

Due to the specific structure of natural bone, most of the therapeutics are incapable to be delivered into the targeted site with effective concentrations. Nanotechnology has provided a good way to improve this issue, cell membrane mimetic nanoparticles (NPs) have been emerging as an ideal nanomaterial which integrates the advantages of natural cell membranes with synthetic NPs to significantly improve the biocompatibility as well as achieving long-lasting circulation and targeted delivery. In addition, functionalized modifications of the cell membrane facilitate more precise targeting and therapy. Here, an overview of the preparation of cell membrane-coated NPs and the properties of cell membranes from different cell sources has been given to expatiate their function and potential applications. Strategies for functionalized modification of cell membranes are also briefly described. The application of cell membrane-coated NPs for bone therapy is then presented according to the function of cell membranes. Moreover, the prospects and challenges of cell membrane-coated NPs for translational medicine have also been discussed.

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivomineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+and PO43−, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivostudies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivobioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

Sn‐based materials are considered as a promising candidate for anodes of lithium‐ion batteries (LIBs). However, rapid capacity fading associated with large volume expansion during cycling impedes the commercialization of Sn‐based anodes. Herein, a yolk–shell structure is designed via a thermal reduction method and following in situ surface oxidation. In this configuration, CoSn nanoparticles covered by a conformal surface oxide layer are encapsulated in hollow carbon nanocubes. When utilized as an anode material for LIBs, the CoSn@CoSnOx@C exhibits a high discharge capacity of 1177 mAh g−1after 180 cycles at 0.2 A g−1and a capacity retention of 86.7% after 500 cycles at a higher current density of 1 A g−1. The investigation demonstrates that the outstanding electrochemical performance of the composite anodes can be attributed to the synergistic effects of the yolk–shell structure, nanosized CoSn alloy core, and conformal surface oxide layer. This elaborately designed structure can be extended to other alloy‐type anode materials to tackle the capacity decay induced by volume expansion. Herein, a yolk–shell structure is synthesized via a thermal reduction method and subsequent in situ surface oxidation. In this configuration, CoSn nanoparticles covered by a conformal surface oxide layer are encapsulated in hollow carbon nanocubes. This elaborate structure is designed to tackle the rapid capacity fading associated with large volume expansion of Sn‐based anodes during cycling.

A femtosecond light pulse at 480 nm in wavelength was generated during filamentation of an intense 808 nm femtosecond laser pulse propagating along the x axis and polarized between the y and z axes of a KTP crystal. It was proven that the parametric amplification process by a fourth-order nonlinear polarization (χ^(4)(ω_2,ω,ω,ω,−ω_1)) induces frequency generation at 480 nm, where the pump light comes from the incident laser and the seed light comes from the generated supercontinuum by filamentation. The wavelength of the generated signal could be turned from 460 to 520 nm by adjusting the propagation direction in the crystal.

Bone tissue engineering has emerged as a significant research area that provides promising novel tools for the preparation of biomimetic hydrogels applied in bone-related diseases (e.g., bone defects, cartilage damage, osteoarthritis, etc.). Herein, thermal sensitive polymers (e.g., PNIPAAm, Soluplus, etc.) were introduced into main chains to fabricate biomimetic hydrogels with injectability and compatibility for those bone defect need minimally invasive surgery. Mineral ions (e.g., calcium, copper, zinc, and magnesium), as an indispensable role in maintaining the balance of the organism, were linked with polymer chains to form functional hydrogels for accelerating bone regeneration. In the chemically triggered hydrogel section, advanced hydrogels crosslinked by different molecular agents (e.g., genipin, dopamine, caffeic acid, and tannic acid) possess many advantages, including extensive selectivity, rapid gel-forming capacity and tunable mechanical property. Additionally, photo crosslinking hydrogel with rapid response and mild condition can be triggered by different photoinitiators (e.g., I2959, LAP, eosin Y, riboflavin, etc.) under specific wavelength of light. Moreover, enzyme triggered hydrogels were also utilized in the tissue regeneration due to its rapid gel-forming capacity and excellent biocompatibility. Particularly, some key factors that can determine the therapy effect for bone tissue engineering were also mentioned. Finally, brief summaries and remaining issues on how to properly design clinical-oriented hydrogels were provided in this review.

Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. Vomeronasal type-1 receptor 5 (VN1R5) was identified as a cisplatin resistance-related protein and was highly expressed in cisplatin-resistant HNSCC cells and tissues. The long noncoding RNA (lncRNA) lnc-POP1-1 was confirmed to be a downstream target induced by VN1R5. VN1R5 transcriptionally regulated lnc-POP1-1 expression by activating the specificity protein 1 (Sp1) transcription factor via the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. VN1R5 promoted cisplatin resistance in HNSCC cells in a lnc-POP1-1-dependent manner. Mechanistically, lnc-POP1-1 bound to the minichromosome maintenance deficient 5 (MCM5) protein directly and decelerated MCM5 degradation by inhibiting ubiquitination of the MCM5 protein, which facilitated the repair of DNA damage caused by cisplatin. In summary, we identified the cisplatin resistance-related protein VN1R5 and its downstream target lnc-POP1-1. Upon upregulation by VN1R5, lnc-POP1-1 promotes DNA repair in HNSCC cells through interaction with MCM5 and deceleration of its degradation.