HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s

Purpose STAT3 plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 is failure in clinic. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo. Experimental Design The expression of HAb18G/CD147, pSTAT3 and CD44s were determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 was assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot, immunofluorescence staining, immunoprecipitation, and in vivo tumor formationusing loss or gain-of-function strategies. Results Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. CyPA, a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147 dependent mechanisms. HAb18G/CD147 was associated and co-localized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high co-expression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer. Conclusions We identified HAb18G/CD147 as a novel upstream activator of STAT3 via interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies

Enhanced Photoelectrochemical Water Splitting of Hematite Multilayer Nanowires Photoanode with Tuning Surface State via Bottom-up Interfacial Engineering

The optimization of multiple interfaces in hematite (α-Fe_2O_3) based composites for photoelectrochemical water splitting to facilitate charge transport in the bulk is of paramount importance to obtain enhanced solar-to-fuel efficiency. Herein, we report the fabrication of ITO/Fe_2O_3/Fe_2TiO_5/FeNiOOH multi-layer nanowires and a series of systematic experiments designed to elucidate the mechanism underlying the interfacial coupling effect of the quaternary hematite composite. The hierarchical ITO/Fe_2O_3/Fe_2TiO_5/FeNiOOH nanowires display photocurrents that are more than an order of magnitude greater than those of pristine Fe_2O_3 nanowires (from 0.205 mA cm^(−2) to 2.2 mA cm^(−2) at 1.23 V vs. RHE and 1 Sun), and higher than those of most of the recently reported state-of-the-art hematite composites. Structural, compositional and electrochemical investigations disclose that the surface states (SS) are finely regulated via the atomic addition of an Fe_2TiO_5 layer and FeNiOOH nanodots, while the upgrading of back contact conductivity and charge donor densities originate from the epitaxial relationship and enhanced Sn doping contributed from the ITO underlayer. We attribute the superior water oxidation performance to the interfacial coupling effect of the ITO underlayer (Sn doping and back contact conductivity promoter), the atomic level Fe_2TiO_5 coating (Ti doping, surface state density and energy level modulation) and the FeNiOOH nanodot electrocatalyst (regulating surface state energy level). Our work suggests an effective pathway for rational designing of highly active and cost-effective integrated photoanodes for photoelectrochemical water splitting

Enhanced photoelectrochemical water splitting of hematite multilayer nanowire photoanodes by tuning the surface state via bottom-up interfacial engineering

The optimization of multiple interfaces in hematite (α-Fe₂O₃) based composites for photoelectrochemical water splitting to facilitate charge transport in the bulk is of paramount importance to obtain enhanced solar-to-fuel efficiency. Herein, we report the fabrication of ITO/Fe₂O₃/Fe₂TiO₅/FeNiOOH multi-layer nanowires and a series of systematic experiments designed to elucidate the mechanism underlying the interfacial coupling effect of the quaternary hematite composite. The hierarchical ITO/Fe₂O₃/Fe₂TiO₅/FeNiOOH nanowires display photocurrents that are more than an order of magnitude greater than those of pristine Fe₂O₃ nanowires (from 0.205 mAcm⁻² to 2.2 mAcm⁻² at 1.23 V vs. RHE and 1 Sun), and higher than those of most of the recently reported state-of-the-art hematite composites. Structural, compositional and electrochemical investigations disclose that the surface states (SS) are finely regulated via the atomic addition of an Fe₂TiO₅ layer and FeNiOOH nanodots, while the upgrading of back contact conductivity and charge donor densities originate from the epitaxial relationship and enhanced Sn doping contributed from the ITO underlayer. We attribute the superior water oxidation performance to the interfacial coupling effect of the ITO underlayer (Sn doping and back contact conductivity promoter), the atomic level Fe₂TiO₅ coating (Ti doping, surface state density and energy level modulation) and the FeNiOOH nanodot electrocatalyst (regulating surface state energy level). Our work suggests an effective pathway for rational designing of highly active and cost-effective integrated photoanodes for photoelectrochemical water splitting

Engineering grain boundaries at the 2D limit for the hydrogen evolution reaction

Atom-thin transition metal dichalcogenides (TMDs) have emerged as fascinating materials and key structures for electrocatalysis. So far, their edges, dopant heteroatoms and defects have been intensively explored as active sites for the hydrogen evolution reaction (HER) to split water. However, grain boundaries (GBs), a key type of defects in TMDs, have been overlooked due to their low density and large structural variations. Here, we demonstrate the synthesis of wafer-size atom-thin TMD films with an ultra-high-density of GBs, up to ~1012 cm−2. We propose a climb and drive 0D/2D interaction to explain the underlying growth mechanism. The electrocatalytic activity of the nanograin film is comprehensively examined by micro-electrochemical measurements, showing an excellent hydrogen-evolution performance (onset potential: −25 mV and Tafel slope: 54 mV dec−1), thus indicating an intrinsically high activation of the TMD GBs

Investigations into sensing characteristics of circular thin-plate electrostatic sensors for gas path monitoring

Circular thin-plate electrostatic sensors are promising in gas path monitoring due to their advantages of non-intrusiveness and easy installation. The spatial sensitivity and filtering effect are two important performance parameters. In this paper, an analytically mathematical model of induced charge on a circular thin-plate electrode is first derived. Then the spatial sensitivity and filtering effect of the circular electrostatic sensor are investigated by numerical calculations. Finally, experimental studies are performed to testify the theoretical results. Both theoretical and experimental results demonstrate that circular thin-plate electrostatic sensors act as a low-pass filter in the spatial frequency domain, and both the spatial filtering effect and the temporal frequency response characteristics depend strongly on the spatial position and velocity of the charged particle. These conclusions can provide guidelines for the optimal design of circular thin-plate electrostatic sensors

Theoretical analysis and finite element method simulations on dynamic sensitivity of hemisphere-shaped electrostatic sensors

Electrostatic sensors are key components of electrostatic monitoring systems. Their sensitivity characteristics have a direct influence on monitoring accuracy. In previous studies, spatial sensitivity, which is called static sensitivity here, was used to describe the sensitivity characteristics. However, it only reflects a basic relationship between static charged particles and induced charges on an electrostatic sensor’s probe. Besides, as a three-dimensional defined parameter, it is difficult to build a unified model if actual boundary conditions are considered. Thus, it is not quite proper for applications that detect moving particles. To solve this problem, dynamic sensitivity is proposed in this article. As for a hemisphere-shaped electrostatic sensor, first, a more accurate model of static sensitivity is built. Based on it, dynamic sensitivity is defined and modeled analytically. Then, a calibration method is proposed to improve the model’s accuracy under actual boundary conditions. In the end, finite element method simulations are done for validations. The results demonstrate that dynamic sensitivity reflects a relationship between moving charged particles and the actual output signals of a sensor, thus it is direct and practical for moving particles. And the theoretical results are highly consistent with the simulated ones. Moreover, the dynamic sensitivity indicates localized sensing characteristics of hemisphere-shaped electrostatic sensors

Transfusion-Associated HIV Infection in Pediatric Leukemia Patients (Two Case Reports)

Background: Leukemia is the second most malignant tumor in children. The chemotherapy induced anemia (CIA) and hemorrhage are the most popular side-effects due to the myelosuppression of chemotherapy. So far, multitransfusion is still the timely and effective measure in curing these complications. The acquisition of HIV infection and subsequent development of AIDS by component transfusion from donors at risk is well known, and prognosis of HIV infection is particularly severe in patients with leukemia. Case Presentation: We report two leukemic cases that were infected with HIV through transfusion. The first patient was totally transfused with 16 U RBC, 20 U platelets and 820 ml fresh frozen plasma, and later test showed that his first used FFP carried the HIV. For the second 2 U RBC, 5 U platelets and 1500 ml fresh frozen plasma were transfused to her. Late test of her used blood products showed that the fourth RBC carried the HIV. Both results were confirmed by the local Center for Disease Control (CDC). They were not transfused before the diagnosis of leukemia. Their parents were healthy with negative HIV-Ab Conclusion: Since the two leukemic patients suffered transfusion-associated HIV with poor prognosis, we must take more efforts to utilize blood products judiciously, manage blood donors, test blood samples etiologically, shorten HIV testing "window periods" and develop preventive vaccination against HIV to reduce the incidence as low as possible

Beyond time: Enhancing corrosion resistance of geopolymer concrete and BFRP bars in seawater

To improve the durability of Basalt fiber reinforced polymer (BFRP) bars reinforced geopolymer concrete (GPC), it is important to study the time-dependent variation of the corrosion resistance ability of GPC and BFRP in a seawater environment. This paper presents an experimental investigation to study the time-dependent mechanical properties and durability of BFRP bars and geopolymer materials synthesized by granulated blast furnace slag (GGBFS), fly ash, and silica fume. The resulting GPC and Portland cement (PC) concrete were exposed to artificial seawater. The mechanical properties of GPC were evaluated by analyzing and comparing the volume expansion and strength loss rates of GPC and PC concrete in an artificial seawater environment. The corrosion resistance of geopolymer (GP) mortar and PC mortar was evaluated by studying the migration ability and pore structure in corrosive ions attack (Cl−, SO42−, Mg2+) in artificial seawater. Moreover, the time-dependent tensile strength of BFRP was comparatively investigated by immersing in different solutions (tap water, artificial seawater, and alkaline simulated seawater). In addition, the dual interface transition zones (ITZs) characteristics of BFRP reinforced GPC under artificial seawater were also investigated by SEM and BSE tests. The results showed that the volume expansion rate and strength loss rate of GPC decreased by 77.6% and 8.7%, respectively, after 360 days of seawater corrosion compared with PC concrete. This enabled the development of a time-dependent strength model of GPC in marine environments. The coefficient of ions diffusion in GP mortar is much lower than that of PC mortar, and GP mortar shows excellent resistance to ion migration. In addition, the effect of seawater corrosion on the tensile strength of BFRP bars increases with the increase of bars' diameter, and the ultimate strengths of BFRP bars with diameters of 6 mm and 8 mm were 695 MPa and 663 MPa, respectively. The tensile strength degradation model of BFRP bars in geopolymer concrete under seawater corrosion was established. After 360 days of seawater immersion, the average porosity of the ITZ between geopolymer and aggregates, and the average porosity of the ITZ between geopolymer and BFRP bars increased insignificantly compared to that of PC concrete. This research can provide a theoretical basis for the service life prediction of BFRP reinforced geopolymer concrete within marine environments

The effectiveness of blinatumomab in clearing measurable residual disease in pediatric B‐cell acute lymphoblastic leukemia patients detected by next‐generation sequencing

Abstract Background Blinatumomab improved survival outcomes in B‐cell acute lymphoblastic leukemia (B‐ALL) patients with measurable residual disease (MRD) <10−4. However, data on blinatumomab clearing MRD with high sensitivity of 10−6 remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating extremely low level (up to <10−6) of MRD, as detected by next‐generation sequencing (NGS), in children with B‐ALL. Methods Patients (n = 19) whose MRD was undetectable by multiparameter flow cytometry (MFC) (sensitivity of 10−4) but detectable by NGS after chemotherapy and followed by blinatumomab consolidation were included retrospectively. Results After one course of blinatumomab, 13/19 patients (68%) successfully achieved NGS‐MRD clearance (undetectable). With a median follow‐up of 13.3 months, three of patients who were NGS‐MRD positive relapsed within 1.8 months, while another three remained complete remission. Conclusions Our study was the first to demonstrate that blinatumomab could further eradicate MRD after patients achieve MFC‐MRD undetectable in B‐ALL patients

Comparative study of biomarkers for the early identification of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in infectious mononucleosis

Abstract Background and aim Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. Methods We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. Results Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. Conclusions IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations