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.

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.

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.

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-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.

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.

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.

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.

Temporal Immunomodulation via Wireless Programmed Electric Cues Achieves Optimized Diabetic Bone Regeneration.

Mimicking the temporal pattern of biological behaviors during the natural repair process is a promising strategy for biomaterial-mediated tissue regeneration. However, precise regulation of dynamic cell behaviors allocated in a microenvironment post-implantation remains challenging until now. Here, remote tuning of electric cues is accomplished by wireless ultrasound stimulation (US) on an electroactive membrane for bone regeneration under a diabetic background. Programmable electric cues mediated by US from the piezoelectric membrane achieve the temporal regulation of macrophage polarization, satisfying the pattern of immunoregulation during the natural healing process and effectively promoting diabetic bone repair. Mechanistic insight reveals that the controllable decrease in AKT2 expression and phosphorylation could explain US-mediated macrophage polarization. This study exhibits a strategy aimed at precisely biosimulating the temporal regenerative pattern by controllable and programmable electric output for optimized diabetic tissue regeneration and provides basic insights into bionic design-based precision medicine achieved by intelligent and external field-responsive biomaterials.

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.

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.

Novel Airflow-Field-Driven Melt Spinning 3D Printing of Tubular Scaffolds Based on Polycaprolactone Blends.

The fabrication of various 3D tissue engineering tubular scaffolds with fibrous structures, to assist the human body in rapidly repairing a variety of ailments, is receiving more and more attention. Due to the inefficiency of the majority of fibrous preparation techniques, the question of how to rapidly produce the requisite three-dimensional tubular microfiber scaffold structures has become an urgent problem. In this study, an efficient polymer fiber preparation method was developed, using a high-speed airflow drive. Melt blending of polycaprolactone (PCL), polylactic acid (PLA), and tributyl citrate (TBC), was used for the printing material, to achieve the efficient preparation of tubular microfiber scaffolds with different structures. The scaffold diameter was as small as 2 mm, the wall thickness was up to 100 µm, and the fiber injection efficiency reached 15.48 g/h. By utilizing simulations to optimize the printing parameters and by adjusting the printing settings, it was possible to achieve a controlled fiber diameter in the range of 3 µm to 15 µm. In addition, plasma treatment was applied to the microfibers' surface, to increase their wettability, and the efficiency of the hydrophilic modification was demonstrated. Furthermore, the mechanical property test demonstrated that the fibers have a tensile strength of 1.36 ± 0.16 MPa and a tensile strain of 30.8 ± 3.5%. The radial compressive strain of the tubular scaffold could reach 60% of the original scaffold's diameter. Finally, the in vitro degradation of the fibers at various pH values was tested. The results showed that, under alkaline conditions, the surface of the fibers would be severely crushed and the rate of deterioration would increase.

Neuraminidase 1 promotes renal fibrosis development in male mice.

The functions of the influenza virus neuraminidase has been well documented but those of the mammalian neuraminidases remain less explored. Here, we characterize the role of neuraminidase 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated in the fibrotic kidneys of patients and mice. Functionally, tubular epithelial cell-specific NEU1 knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, and collagen deposition in mice. Conversely, NEU1 overexpression exacerbates progressive renal fibrosis. Mechanistically, NEU1 interacts with TGFß type I receptor ALK5 at the 160-200aa region and stabilizes ALK5 leading to SMAD2/3 activation. Salvianolic acid B, a component of Salvia miltiorrhiza, is found to strongly bind to NEU1 and effectively protect mice from renal fibrosis in a NEU1-dependent manner. Collectively, this study characterizes a promotor role for NEU1 in renal fibrosis and suggests a potential avenue of targeting NEU1 to treat kidney diseases.

Uptake of heavy metals by crops near a mining field: Pathways from roots and leaves.

Metal uptake and distribution in crops have been demonstrated to be highly variable and depending on the metal of interest and the crop type. However, no consensus is reached regarding the primary factor controlling metal uptake in crops. This study thus comparably investigated Hg, As, Zn, Pb, Cd and Cu uptake and distribution in three crops grown in a watershed near a copper mining field located in Yunnan, Southwestern China. The bioconcentration factor (BCF) and translocation factor (TF) were statistically compared for the same metal across different crops. Leafy crops had a stronger propensity to accumulate Hg, As and Zn than fruit crops. The ability of grain crops to accumulate Cd and Cu was much lower than leafy and fruit crops. The three crops all tended not to accumulate Pb in their edible tissues. The DTPA extracted metal concentrations were not statistically correlated with the metal concentrations in crop edible tissues. It is thus not practical to predict metal uptake of Hg, As, Pb and Zn through their available concentrations in soils. The contents of nitrogen and phosphorus, and competing metal ions present in paddy soil decreased the accumulation of Cu and Cd in rice grains. By means of hierarchical cluster analysis, the high accumulation of Zn in the edible tissues of fruit and grain crops was mainly due to dust inputs via phloem transport from leaves. This is why BCF(Zn) was the highest among the six metals for these two crops. For leafy crops, the accumulation of Hg, Cd and Zn in leaves was mainly through soil inputs by roots. Our findings serve as a scientific basis for the selection of crops in areas with high background of heavy metals.

F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production.

BACKGROUND: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. METHODS: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. FINDINGS: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. INTERPRETATION: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. FUNDING: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).

Agarose-gel-based self-limiting synthesis of a bimetal (Fe and Co)-doped composite as a bifunctional catalyst for a zinc-air battery.

Exploring efficient noble-metal-free electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is crucial for the development of rechargeable Zn-air batteries. Herein, a self-limiting method using an agarose gel was proposed to prepare bimetallic (iron and cobalt) nitrogen-doped carbon composites (FeCo-NC). The resulting FeCo-NC catalyst has a high surface area and a hierarchical porous structure. The optimized FeCo-NC electrocatalyst exhibits a small potential difference (ΔE) = 0.72 V between the ORR half-wave potential and the OER potential at a current density of 10 mA cm-2 in alkaline media. Impressively, the FeCo-NC Zn-air battery exhibits a high open-circuit voltage, large power density, and outstanding charge-discharge cycling stability. This study provides an effective means of designing electrocatalysts and energy conversion systems.

nHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair.

Critical-sized maxillofacial bone defects have been a tough clinical challenge considering their requirements for functional and structural repair. In this study, an injectable in-situ forming double cross-linked hydrogel was prepared from gelatin (Gel), 20 mg/mL alginate dialdehyde (ADA), 4.5 mg/mL Ca2+ and borax. Improved properties of composite hydrogel might well fit and cover irregular geometric shape of facial bone defects, support facial structures and conduct masticatory force. We innovatively constructed a bioactive poly-porous structure by decoration with nano-sized hydroxyapatite (nHA). The highly ordered, homogeneous and size-confined porous surface served as an interactive osteogenic platform for communication and interplay between macrophages and bone marrow derived stem cells (BMSCs). Effective macrophage-BMSC crosstalk well explained the remarkable efficiency of nHA-loaded gelatin/alginate hydrogel (nHA@Gel/ADA) in the repair of critical-size skull bone defect. Collectively, the composite hydrogel constructed here might serve as a promising alternative in repair process of complex maxillofacial bone defects.

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.

Multi-Scale Structure and Directional Hydrophobicity of Titanium Alloy Surface Using Electrical Discharge.

Titanium alloys with special macro-micro composite structures of directional hydrophobicity are difficult to prepare due to poor thermal conductivity and good corrosion resistance, inhibiting the wide engineering applications for aerospace, marine engineering, and biomedicine. To prepare macro-micro composite structures on the surface of titanium alloys and achieve directional hydrophobicity, the sub-millimeter structures with an edge width of 150 µm, a groove width of 250 µm, and a depth of 250 µm were fabricated on the titanium alloy by wire electrical discharge machining (WEDM) technology, and high voltage-induced weak electric arc machining (HV-µEAM) was used to fabricate micro-scale feature size micro-structures on the processed macro-structure edges. The influence of process parameters on the morphology of microstructures was studied experimentally. The smooth surface of the titanium alloy is isotropically hydrophilic, and its contact angle is 68°. After processing the macrostructure on the titanium alloy surface, it shows directional hydrophobicity after being modified by low surface energy materials. The macro-micro composite structure formed by HV-µEAM realizes a directional hydrophobic surface with contact angles (CA) of 140° (parallel direction) and 130° (perpendicular direction), respectively. This surface has been modified with low surface energy to achieve contact angles of 154° and 143°. The results of the abrasion resistance test show that under the load of 100 g, it retains directional hydrophobicity at a friction distance of 700 mm with 600# sandpaper. The existence of the sub-millimeter macrostructure is the reason for the directionality of surface hydrophobicity. The microstructure can realize the transformation of the titanium alloy surface from hydrophilic to hydrophobic. Under the combined effects of the macro and micro composite structure, the surface of the titanium alloy shows obvious directional hydrophobicity.

Identification of a novel immune gene panel in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common oral cancers. Immune activity is significantly related to the initiation and progression of TSCC. Systemic analysis of the immunogenomic landscape and identification of crucial immune-related genes (IRGs) would help understanding of TSCC. Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) provide multiple TSCC cases for use in an integrated immunogenomic study. METHODS: Immune landscape of TSCC was depicted by expression microarray data from GSE13601 and GSE34105. Univariate Cox analysis, in combination with survival analysis, was applied to select candidate IRGs with significant survival value. Survival predicting models were constructed by multivariate Cox regression and logistic regression analysis. Unsupervised clustering analysis was used to construct an immune gene panel based on prognostic IRGs to distinguish TSCC subgroups with different prognostic outcomes. Finally, IHC staining was performed to validate the clinical value of this immune-gene panel. RESULTS: Differentially expressed IRGs were identified in two TSCC microarray datasets. Functional enrichment analysis revealed that ontology terms associated with variations in T cell function, were highly enriched. Infiltration status of activated CD8+ T cells, central memory CD4+ T cells and type 17 T helper cells, had great prognostic value for TSCC progression. Unsupervised clustering analysis was further performed to classify TSCC patients into three subgroups. CTSG, CXCL13, and VEGFA were finally combined together to form an immune-gene panel, todistinguish different TSCC subgroups. IHC staining of TSCC sections further validated the clinical efficiency of the immune-gene panel consisting of prognostic IRGs to distinguish TSCC patients. CONCLUSION: VEGFA, CXCL13, and CTSG, correlated with T cell infiltration and prognostic outcome. They were screened to form an immune-gene panel to identify TSCC subgroups with different prognostic outcomes. Clinical IHC further validated the efficacy of this immune-gene panel to evaluate aggressiveness of TSCC development.