The Prognostic Biomarker RAB7A Promotes Growth and Metastasis of Liver Cancer Cells by Regulating Glycolysis and YAP1 Activation.

Activating transcription factor 6 (ATF6) and its downstream genes are involved in progression of hepatocellular carcinoma (HCC). Herein, we demonstrated that sulfhydration of Ras-related protein Rab-7a (RAB7A) was regulated by ATF6. High expression of RAB7A indicated poor prognosis of HCC patients. RAB7A overexpression contributed to proliferation, colony formation, migration, and invasion of HepG2 and Hep3B cells. Furthermore, we found that RAB7A enhanced aerobic glycolysis in HepG2 cells, indicating a higher degree of tumor malignancy. Mechanistically, RAB7A suppressed Yes-associated protein 1 (YAP1) binding to 14-3-3 and conduced to YAP1 nuclear translocation and activation, promoting its downstream gene expression, thereby promoting growth and metastasis of liver cancer cells. In addition, knocking down RAB7A attenuated the progression of orthotopic liver tumors in mice. These findings illustrate the important role of RAB7A in regulating HCC progression. Thus, RAB7A may be a potential innovative target for HCC treatment.

Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.

BACKGROUND: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. METHODS: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. RESULTS: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. CONCLUSIONS: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Reducing Calcium Dissolution in Tunnel Shotcrete: The Impact of Admixtures on Shotcrete Performance.

Groundwater infiltration into tunnels causes water to percolate through the fissure channels in the initial support shotcrete. This results in the dissolution and outflow of calcium hydroxide, a key product of cement hydration. This process significantly incurs the formation of crystallization blockages in the tunnel drainage systems. Optimizing the shotcrete mixing ratio is a feasible way to mitigate these blockages. Therefore, this study conducts calcium dissolution tests to investigate the impact of six admixtures, namely, antialkali agent, nanosilica, nanosilica carbonate, fly ash, sodium methyl silicate waterproofing agents, and silane waterproofing agents, on calcium dissolution resistance. Also, mechanical and microscopic tests are carried out to examine their impact on the strength and pore structure of the shotcrete. The objective of this study is to determine the optimal admixture for enhancing the calcium dissolution resistance of shotcrete. Results indicate that the antialkali agent significantly reduces the calcium leaching content of shotcrete. When the dosage is 14%, the calcium leaching amount is reduced by 68.4% in 28 days. Followed by nanosilica and silane waterproofing agents, with optimal dosages of 12 and 0.4%, respectively, the dissolution amount of calcium ions in shotcrete was reduced by 32.87 and 26.5%, respectively. Fly ash curing for 28 days can also reduce the calcium ion dissolution of shotcrete, while nanocalcium carbonate and sodium methyl silicate have little effect on the calcium dissolution of shotcrete. The antialkali agent with a strong calcium ion dissolution effect can improve the tensile strength of shotcrete under long-term curing conditions, which can be increased by 52%, but it compromises the growth of compressive strength. Nanosilica, fly ash, and silane waterproofing agents can improve both the compressive strength and tensile strength of shotcrete under long-term curing conditions. Specifically, at 28 days of curing, the compressive strength increased by 16.83, 28.8, and 20% and the tensile strength increased by 50.24, 60, and 64.5%. In addition, the microscopy results show that the antialkali agent, nanosilica, and silane waterproofing agents promote the hydration process of cement to form ettringite with a low and stable calcium-silicon ratio and reduce calcium hydroxide crystals. Nanosilica and silane waterproofing agents optimize the pore distribution in shotcrete by increasing beneficial pores, decreasing harmful pores, and reducing total porosity.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Fe-Co Co-Doped 1D@2D Carbon-Based Composite as an Efficient Catalyst for Zn-Air Batteries.

A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm-2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc-air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.

Activating transcription factor 6 regulates cystathionine to increase autophagy and restore memory in Alzheimer' s disease model mice.

Endoplasmic reticulum stress (ER stress) plays a crucial role in the process of Alzheimer's disease (AD). Activating transcription factor 6 (ATF6) is a crucial sensor of ER stress. In AD patients, the homeostasis of the endogenous signal H2S produced by cystathionine γ-lyase (CTH) is in disbalance. However, the role of ATF6 and CTH in AD is rarely reported. Herein, we found that ATF6 and CTH were reduced in AD patients and APP/PS1 mice by immunohistochemistry and western blots. In LN229 and U87 MG cells, knockdown of ATF6 attenuated CTH expression, whereas overexpression of ATF6 resulted in upregulation of CTH. Brain-specific ATF6 knockout mice expressed significantly down-regulated CTH in the hippocampus and cortex compared to wild-type mice. Mechanistically, ATF6 and CTH increased H2S generation and autophagy-related proteins. Further we observed that CTH promoted the sulfhydration of αSNAP. This is probably to be the specific mechanism by which AFT6 promotes autophagy. Through in vivo studies, we found that αSNAP sulfhydration expression was significantly lower in ATF6 knockout mice than in wild-type mice. Decreased ATF6 impaired spatial memory retention, while addition of CTH rescued memory loss. Together, we demonstrate that ATF6 positively regulates the expression of CTH, which is closely related to the rescue of AD. Targeting the ATF6/CTH signal pathway may provide a new strategy for the treatment of AD.

Design of few-layer carbon nitride/BiFeO3 composites for efficient organic pollutant photodegradation.

Heterojunction-driven photocatalysis can degrade various organic pollutants, and developing carbon nitride-based composite photocatalysts is of great significance and gains growing interest. In this study, a two-dimensional graphitic carbon nitride nanosheets/BiFeO3 (GCNNs/BiFeO3) Z-scheme heterojunction has been synthesized through the electrostatic spinning and post-calcination The obtained GCNNs/BiFeO3 nanofibers show large surface contact between GCNNs the and BiFeO3 nanostructures. The Z-scheme heterojunction shows a remarkably enhanced photocatalytic performance, which could degrade 94% of tetracycline (TC) and 88% of Rhodamine B (RhB) under LED visible light irradiation in 150 min. Radical trapping experiments demonstrate the effective construction of Z-scheme heterojunctions, and •O2- and h+ are the main active species in the photocatalytic degradation process. This study realizes a novel nanostructured GCNNs/BiFeO3 heterojunction for photodegradation applications, which would guide the design of next-generation efficient photocatalysts.

Neuraminidase 1 is a driver of experimental cardiac hypertrophy.

AIMS: Despite considerable therapeutic advances, there is still a dearth of evidence on the molecular determinants of cardiac hypertrophy that culminate in heart failure. Neuraminidases are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids. This study sought to characterize the role of neuraminidases in pathological cardiac hypertrophy and identify pharmacological inhibitors targeting mammalian neuraminidases. METHODS AND RESULTS: Neuraminidase 1 (NEU1) was highly expressed in hypertrophic hearts of mice and rats, and this elevation was confirmed in patients with hypertrophic cardiomyopathy (n = 7) compared with healthy controls (n = 7). The increased NEU1 was mainly localized in cardiomyocytes by co-localization with cardiac troponin T. Cardiomyocyte-specific NEU1 deficiency alleviated hypertrophic phenotypes in response to transverse aortic constriction or isoproterenol hydrochloride infusion, while NEU1 overexpression exacerbated the development of cardiac hypertrophy. Mechanistically, co-immunoprecipitation coupled with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated that NEU1 translocated into the nucleus and interacted with GATA4, leading to Foetal gene (Nppa and Nppb) expression. Virtual screening and experimental validation identified a novel compound C-09 from millions of compounds that showed favourable binding affinity to human NEU1 (KD = 0.38 µM) and effectively prevented the development of cardiac remodelling in cellular and animal models. Interestingly, anti-influenza drugs zanamivir and oseltamivir effectively inhibited mammalian NEU1 and showed new indications of cardio-protection. CONCLUSIONS: This work identifies NEU1 as a critical driver of cardiac hypertrophy and inhibition of NEU1 opens up an entirely new field of treatment for cardiovascular diseases.

Metal-Organic Framework Assembled on Oriented Nanofiber Arrays for Field-Effect Transistor and Gas Sensor-Based Applications.

Metal-organic framework (MOF) films are essential for numerous sensor and device applications. However, metal-organic framework materials have poor machinability due to their predominant powder-like nature, and their presence as the active layer in a device can seriously affect the performance and utility of the device. Herein, active layers of field-effect transistor (FETs) devices and chemiresistor gas sensors with high performance were constructed by loading Cu3(HITP)2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene) in situ-axial anchoring on oriented nanofiber arrays prepared via electrospinning. The strong interaction between polar groups on the polymer chains and metal ions promotes the nucleation of Cu3(HITP)2, steric hindrance makes particles of Cu3(HITP)2 with uniform size, morphology, and good crystallinity during nucleation by liquid phase epitaxial growth (LPE). Influences of differently-oriented Cu3(HITP)2 NFAs-based FETs on the electrical properties were studied, optimally oriented Cu3(HITP)2 NFAs-based FETs showed good mobility of 5.09 cm2/V·s and on/off ratio of 9.6 × 103. Moreover, excellent gas sensing response characteristics were exhibited in sensing volatile organic compounds (VOCs). Chemiresistor gas sensors with high response value, faster response and recovery are widely suited for VOCs. It brings new inspirations for the design and utilization of electrically conductive MOFs as an active layer for FETs and sensor units for chemiresistor gas sensors.

Enantioselective determination of econazole in rat plasma and its application to a pharmacokinetic study.

Econazole is a widely used chiral antifungal drug. In this paper, an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of econazole enantiomers in rat plasma for the first time. After addition of the internal standard (IS) clotrimazole, plasma samples were extracted by liquid-liquid extraction with n-hexane:2-propanol (98.5:1.5, v/v). Baseline separation of the enantiomers was achieved on a Chiralpak® IC column (250 mm × 4.6 mm, 5 µm) using acetonitrile-ammonium acetate buffer (5 mM) (85:15, v/v) as mobile phase. The detection of the analytes was performed in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 381.07 â†’ 124.92 and 276.78 â†’ 164.92 were monitored for econazole enantiomers and clotrimazole, respectively. The linear range was 0.20-50.00 ng/mL with the lower limit of quantification of 0.20 ng/mL for both econazole enantiomers in plasma. The intra-day and inter-day precisions were not exceeding 10.2% and the accuracies were within ±15.0%. The validated method was successfully applied to the stereoselective pharmacokinetic study of econazole enantiomers in rat plasma after transdermal administration of racemic econazole nitrate cream. Significant differences were observed in Cmax, AUC and CL/F of econazole enantiomers, indicating the enantioselective pharmacokinetic behavior of econazole in rats.

Correction to: H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

The original article can be found online.

H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth. Comparisons of matched DIPG xenografts with and without K27M knockdown allowed identification of mutation-specific effects on the transcriptome and epigenome. The resulting transcriptional changes recapitulate expression signatures from K27M primary DIPG tumors and are strongly enriched for genes associated with nervous system development. Integrated analysis of ChIP-seq and expression data showed that genes upregulated by the mutation are overrepresented in apparently bivalent promoters. Many of these targets are associated with more immature differentiation states. Expression profiles indicate K27M knockdown decreases proliferation and increases differentiation within lineages represented in DIPG. These data suggest that K27M-mediated loss of H3K27me3 directly regulates a subset of genes by releasing poised promoters, and contributes to tumor phenotype and growth by limiting differentiation. The delayed tumor growth associated with knockdown of H3 K27M provides evidence that this highly recurrent mutation is a relevant therapeutic target.

Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC.

1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological activities between the enantiomers. In the present study, enantioseparation of seventeen DHP structural analogues, consisting of either pharmacologically active or newly synthesized derivatives, (M2-4, MD5, HM2, HM10, CE5, N11, N10, N7, M11, MC6-8, MC13, MD23, and 42IIP) by high-performance liquid chromatography was investigated using immobilized polysaccharide-based chiral stationary phase, Chiralpak IC column. Due to the solvent versatility of the covalently immobilized chiral stationary phase in enantiomer separation, multiple elution modes including standard normal phase, nonstandard mobile phase, and reversed phase were used to expand the possibility to find the optimum enantioselective conditions for the tested analytes. Under appropriate separation conditions, complete enantiomeric separation was obtained for nearly all compounds except MC6-8 and MC13 which contained two chiral centers. Additionally, the effects of the polar modifier, the additive, and column temperature on the chiral recognition were evaluated. The thermodynamic parameters calculated according to the linear van't Hoff equation indicated that the chiral separations in this study were enthalpy-driven or entropy-driven. Some parameters of method validation such as linearity, limit of quantitation, and repeatability were also measured for all studied compounds to prove the reliability of the method.

Neutrophil Elastase Regulates Emergency Myelopoiesis Preceding Systemic Inflammation in Diet-induced Obesity.

Inflammation plays a significant role in the development of obesity-related complications, but the molecular events that initiate and propagate such inflammation remain unclear. Here, we report that mice fed a high-fat diet (HFD) for as little as 1-3 days show increased differentiation of myeloid progenitors into neutrophils and monocytes but reduced B lymphocyte production in the bone marrow. Levels of neutrophil elastase (NE) and the nuclear factors CCAAT/enhancer-binding protein α (C/EBPα) and growth factor-independent 1 (GFI-1) are elevated in hematopoietic stem and progenitor cells from HFD-fed mice, but mice lacking either NE or C/EBPα are resistant to HFD-induced myelopoiesis. NE deletion increases expression of the inhibitory isoform of p30 C/EBPα, impairs the transcriptional activity of p42 C/EBPα, and reduces expression of the C/EBPα target gene GFI-1 in hematopoietic stem and progenitor cells, suggesting a mechanism by which NE regulates myelopoiesis. Furthermore, NE deletion prevents HFD-induced vascular leakage. Thus, HFD feeding rapidly activates bone marrow myelopoiesis through the NE-dependent C/EBPα-GFI-1 pathway preceding vascular damage and systemic inflammation.

Association of vitamin D receptor gene polymorphism with the risk of lung cancer: a meta-analysis.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR gene polymorphism with lung cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA genotype was associated with the risk of lung cancer in Asians. In the meta-analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were associated with lung cancer in Asians, and B allele bb genotype were associated with lung cancer risk in overall populations; furthermore, bb genotype was associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI gene polymorphism, t allele and TT genotype were associated with lung cancer in overall populations and in Caucasians. In conclusion, B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians. However, more studies should be conducted to confirm it.

The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. Results: No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. Conclusion: This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.

Fe, N, S co-doped carbon network derived from acetate-modified Fe-ZIF-8 for oxygen reduction reaction.

In this work, potassium acetate (KAc) was added during the synthesis of a Zn-Fe based metal-organic framework (Fe-ZIF-8) to increase the fixed amount of Fe while simultaneously enhancing the number of pores. Electrospinning was utilized to embed KAc-modified Fe-ZIF-8 (Fe-ZIF-8-Ac) into the polyacrylonitrile nanofiber mesh, to obtain a network composite (Fe@NC-Ac) with hierarchical porous structure. Fe@NC-Ac was co-pyrolyzed with thiourea, resulting in Fe, N, S co-doped carbon electrocatalyst. The electrochemical tests indicated that the prepared catalyst displayed relatively remarkable oxygen reduction reaction (ORR) catalytic activity, with an onset potential (Eonset) of 1.08 V (vs. reversible hydrogen electrode, RHE) and a half-wave potential (E1/2) of 0.94 V, both higher than those of the commercial Pt/C (Eonset = 0.95 V and E1/2 = 0.84 V), respectively. Assembled into Zn-air batteries, the optimized catalyst exhibited higher open circuit voltage (1.698 V) and peak power density (90 mW cm-2) than those of the commercial 20 wt% Pt/C (1.402 V and 80 mW cm-2), respectively. This work provided a straightforward manufacturing strategy for the design of hierarchical porous carbon-based ORR catalysts with desirable performance.

Wireless Electric Cues Mediate Autologous DPSC-Loaded Conductive Hydrogel Microspheres to Engineer the Immuno-Angiogenic Niche for Homologous Maxillofacial Bone Regeneration.

Stem cell therapy serves as an effective treatment for bone regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking homologous properties. Dental pulp stem cells (DPSCs) are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number and heterogenous alteration of seed cells retard further exploration of DPSC-based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, a novel DPSC-loaded conductive hydrogel microspheres integrated with wireless electric generator is fabricated. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observe that electric signal fine-tunes regenerative niche by improvement on DPSC-mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti-inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno-angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. This novel strategy of DPSC-based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration.

FD-DE: Differential Evolution with fitness deviation based adaptation in parameter control.

Differential Evolution (DE) is arguably one of the most powerful stochastic optimization algorithms for different optimization applications, however, even the state-of-the-art DE variants still have many weaknesses. In this study, a new powerful DE variant for single-objective numerical optimization is proposed, and there are several contributions within it: First, an enhanced wavelet basis function is proposed to generate scale factor F of each individual in the first stage of the evolution; Second, a hybrid trial vector generation strategy with perturbation and t-distribution is advanced to generate different trial vectors regarding different stages of the evolution; Third, a fitness deviation based parameter control is proposed for the adaptation of control parameters; Fourth, a novel diversity indicator is proposed and a restart scheme can be launched if necessary when the quality of the individuals is detected bad. The novel algorithm is validated using a large test suite containing 130 benchmarks from the universal test suites on single-objective numerical optimization, and the results approve the big improvement in comparison with several well-known state-of-the-art DE variants. Moreover, our algorithm is also validated under real-world optimization applications, and the results also support its superiority.

Mechanical behavior of an FGM-type frozen soil wall: Theory and numerical analysis.

With a laminate model foundation, we have used the complex variable function method to calculate the boundary displacement and stress of a frozen soil wall in a horizontal connecting passage. Using an actual engineering case, the effects of the number of divided layers of a functionally graded material-type frozen soil wall, the position of the freezing pipe and the section shape of the connecting passage on the displacements and tangential stresses of the frozen soil wall are discussed. The results indicate that the frozen soil wall as a temporary support structure exhibits a good supporting effect. With the increase of layers, the material strength of the frozen soil wall weakens, and the displacements and tangential stresses of the inner boundary increase. When the midline of the freezing pipe moves toward the inner boundary, the tensile area in the frozen soil wall begins to shift, and the displacements and tangential stresses of the inner boundary decrease differently. Thedistributions of internal boundary displacements and tangential stresses are significantly affected by the section shape of the frozen soil wall, and the internal boundary displacements and tangential stresses of the frozen soil wall of the small section are more uniform than those of the frozen soil wall of the large section.