Atherosclerosis is an arterial inflammatory disease. The circulating level of the C-C chemokine ligand (CCL4) is increased in atherosclerotic patients. This study aimed to investigate whether CCL4 ...inhibition could retard the progression of atherosclerosis. In ApoE knockout mice, CCL4 antibody treatment reduced circulating interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels and improved lipid profiles accompanied with upregulation of the liver X receptor. CCL4 inhibition reduced the atheroma areas and modified the progression of atheroma plaques, which consisted of a thicker fibrous cap with a reduced macrophage content and lower matrix metalloproteinase-2 and -9 expressions, suggesting the stabilization of atheroma plaques. Human coronary endothelial cells (HCAECs) and macrophages were stimulated with TNF-α or oxidized LDL (ox-LDL). The induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were attenuated by the CCL4 antibody or CCL4 si-RNA. CCL4 inhibition reduced the adhesiveness of HCAECs, which is an early sign of atherogenesis. CCL4 blockade reduced the activity of metalloproteinase-2 and -9 and the production of TNF-α and IL-6 in stimulated macrophages. The effects of CCL4 inhibition on down-regulating adhesion and inflammation proteins were obtained through the nuclear factor kappa B (NFκB) signaling pathway. The direct inhibition of CCL4 stabilized atheroma and reduced endothelial and macrophage activation. CCL4 may be a novel therapeutic target for modulating atherosclerosis.
Microsupercapacitors (MSCs) with neutral multivalent electrolytes are safer, cheaper, and exhibit higher theoretical energy densities compared with the MSCs with acidic and alkaline electrolytes. ...Multivalent charge carriers (e.g., Mg2+, Zn2+) in the MSCs with Ti3C2Tx MXene electrodes have not been demonstrated, which could theoretically achieve higher specific capacitances and energy densities. However, because of the larger size of multivalent charge carriers, the MXene electrodes require further modifications to facilitate reversible electrochemical reactions. Herein, through spontaneous intercalation of various metal ions into MXene multilayers, twelve metal ion intercalated MXene electrodes (Mn+‐MXene) are fabricated and demonstrate improved electrochemical performance. Different nanopillar effects are observed between divalent Be2+ and trivalent Al3+ intercalants, which are systematically investigated by electrochemical impedance spectroscopy and molecular dynamics simulation. Among all Mn+‐MXene electrodes, the Be2+‐MXene electrode largely facilitates the charge‐transfer process with minimal disturbance of electrolyte diffusion rates, showing improved specific capacitances and high rate performance in univalent (Li2SO4, Na2SO4, K2SO4) and multivalent electrolytes (BeSO4, MgSO4, ZnSO4). Finally, flexible Be2+‐MXene MSCs with neural ZnSO4 gel electrolytes are fabricated, demonstrating superior areal capacitances (77.2 mF cm−2) and high energy density (3.86 μWh cm−2 at 0.12 mW cm−2) together with high user safety.
A facile metal‐ion intercalation technology is developed to enhance the electrochemical performance of Ti3C2Tx MXene in various neutral multivalent electrolytes. Twelve metal ions are intercalated into MXene electrodes. The Be2+‐intercalated MXene electrode facilitates the charge‐transfer process with minimal disturbance of electrolyte diffusion rates. Finally, Be2+‐MXene microsupercapacitors with neural ZnSO4 gel electrolytes demonstrate superior areal capacitances together with high user safety.
Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia ...(HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new SN group) and those who had undergone conization without hysterectomy (surveillance previous SP group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.
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High‐grade cervical intraepithelial neoplasia (HG‐CIN), a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines.
Flash nonvolatile memory has been widely applied in portable electronic products. However, traditional flash memory is expected to reach physical limits as its dimensions are scaled down; the charges ...stored in the floating gate can leak out more easily through a thin tunneling oxide, causing a serious reliability issue. In order to solve this problem, discrete nanocrystal memory has been proposed and is considered to be a promising candidate for the next generation of nonvolatile memories due to its high operation speed, good scalability, and superior reliability. This paper reviews the current status of research in nanocrystal memory and focuses on its materials, fabrication, structures, and treatment methods to provide an in-depth perspective of state-of-the-art nanocrystal memory.
This letter investigates the double-ended resistive switching characteristics of indium tin oxide (ITO) resistance random access memory (RRAM). Resistive switching can be achieved around both the ...active TiN electrode and the inert Pt electrode. In addition, complementary resistance switching (CRS) characteristics can be observed without current compliance during dc voltage sweep operations. Electrical measurement data fitting results indicate that the oxygen-rich ITO near top and bottom electrodes works as a double-ended resistive switching layer. Based on the analysis of the current conduction mechanism, we propose a physical model to interpret the CRS behaviors in ITO RRAM devices.
This study focuses on the interaction between the oxide layer area of a transistor and its ferroelectric layer area. An experimental comparison of transistor oxide layer area demonstrates that the ...larger the ratio of oxide to ferroelectric layers, the larger the on/off ratio, thus improving performance. A subsequent experiment aimed to further demonstrate this in different sized devices, and changing the ratio of <inline-formula> <tex-math notation="LaTeX">\text{A}_{\text {HZO}}/\text{A}_{\text {SiO2}} </tex-math></inline-formula> (the area of HfZrO x divided by oxide layer) showed the same tendency as above, but also produced an unexpected finding in that a comparison of on/off ratio exhibits an abnormal electric characteristic. This study discusses this abnormal electric characteristic and proposes an explanatory physical model.
A visible-blind ultraviolet (UV) photodetector was designed based on a three-terminal electronic device of thin-film transistor (TFT) coupled with two-terminal p–n junction optoelectronic device, in ...hope of combining the beauties of both of the devices together. Upon the uncovered back-channel surface of amorphous indium–gallium–zinc-oxide (IGZO) TFT, we fabricated PEDOT:PSS/SnO x /IGZO heterojunction structure, through which the formation of a p–n junction and directional carrier transfer of photogenerated carriers were experimentally validated. As expected, the photoresponse characteristics of the newly designed photodetector, with a photoresponsivity of 984 A/W at a wavelength of 320 nm, a UV–visible rejection ratio up to 3.5 × 107, and a specific detectivity up to 3.3 × 1014 Jones, are not only competitive compared to the previous reports but also better than those of the pristine IGZO phototransistor. The hybrid photodetector could be operated in the off-current region with low supply voltages (<0.1 V) and ultralow power dissipation (<10 nW under illumination and ∼0.2 pW in the dark). Moreover, by applying a short positive gate pulse onto the gate, the annoying persistent photoconductivity presented in the wide band gap oxide-based devices could be suppressed conveniently, in hope of improving the response rate. With the terrific photoresponsivity along with the advantages of photodetecting pixel integration, the proposed phototransistor could be potentially used in high-performance visible-blind UV photodetector pixel arrays.
TDP-43 inclusions are found in many Alzheimer's disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical ...oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ's ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.
In this study, the increment in the breakdown voltage of a SiC junction barrier Schottky (JBS) diode under negative bias stress (NBS) is investigated. However, when the SiC JBS exhibits an increase ...in breakdown voltage after NBS, its forward characteristic does not change. The variation in breakdown voltage increases under a higher stress voltage that is close to the breakdown voltage of SiC JBS without stress. Furthermore, the variation in breakdown voltage increases with a higher compliance current and at lower NBS temperature. The electric field of SiC JBS under NBS is simulated to clarify the variation in breakdown voltage under NBS. The electrical characteristics and the simulation of the electric field under NBS demonstrate that the increase in the breakdown voltage of SiC JBS after NBS is induced by the electron injection in the oxide layer of edge termination.
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