Thyroid cancer is the most common malignant neoplasm within the endocrine system and the field of head and neck surgery. Although the majority of thyroid cancers, more than 90%, are ...well-differentiated thyroid carcinomas with a favourable prognosis, the escalating incidence of this disease has contributed to an increasing number of patients with a propensity for recurrent disease, rapid disease progression, and poor or no response to conventional treatments. These clinical challenges are commonly attributed to alterations in key thyroid oncogenes or signaling pathways, thereby initiating tumour cell dedifferentiation events, accompanied by reduced or virtually absent expression of the sodium/iodine symporter (NIS). As a result, the disease evolves into iodine-refractory differentiated thyroid cancer (RAIR-DTC), an entity that is insensitive to conventional radioiodine therapy. Despite being classified as a differentiated thyroid cancer, RAIR-DTC has an extremely poor clinical prognosis, with a 10-year survival rate of less than 10%. Therefore, it is of paramount importance to comprehensively elucidate the underlying pathogenesis of RAIR-DTC and provide specific targeted interventions. As the pathogenic mechanisms of RAIR-DTC remain elusive, here we aim to review recent advances in understanding the pathogenesis of RAIR-DTC and provide valuable insights for the development of future molecularly targeted therapeutic approaches.
cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that ...specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1−/− BMDM cells and in Trex1−/− mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.
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•Astin C impairs cGAS-STING signaling and the inflammatory responses•Astin C attenuates autoinflammatory responses in Trex1−/− cells and disease model•Astin C specifically binds to STING•Astin C prevents the recruitment of IRF3 onto STING signalosome
Li et al. have characterized a small-molecule cyclopeptide, astin C, which specifically inhibits cGAS-STING signaling as well as the innate inflammatory responses. This finding provides a way to potentially manipulate STING-mediated clinical diseases.
Total-ionizing-dose (TID) effects and low-frequency noise are evaluated in 30-nm gate-length bulk and silicon-on-insulator (SOI) FinFETs for devices with fin widths of 10-40 nm. Minimal threshold ...voltage shifts are observed at 2 Mrad(SiO2), but large increases in low-frequency noise are found, and significant changes in defect-energy distributions are inferred. Radiation-induced leakage current is enhanced for narrow- and short-channel bulk FinFETs. Short-channel SOI FinFETs show enhanced degradation compared with longer-channel devices. Narrow- and short-channel SOI devices exhibit high radiation tolerance. Significant random telegraph noise (RTN) is observed in smaller devices due to prominent individual defects.
Total-ionizing-dose mechanisms are investigated in 16-nm InGaAs FinFETs with an HfO 2 /Al 2 O 3 gate-stack. Transistors are irradiated up to 500 krad(SiO 2 ) and annealed at high temperatures. ...Irradiated devices show negative threshold-voltage Vth shifts, subthreshold stretch-out, and leakage current increases. These result from positive charge trapping in the gate oxide and shallow trench insulators, and increases in the interface and border-trap charge densities. Low-frequency noise measurements at different temperatures indicate a significant increase of noise magnitude in irradiated devices at an activation energy of ~0.4 eV. Density functional theory (DFT) calculations strongly suggest that transistor Vth shifts are due primarily to hole trapping at oxygen vacancies in HfO 2 , and the increased noise is due primarily to O vacancies in Al 2 O 3 . Additional contributions to the noise from defects in the GaAs buffer layer are also likely, primarily at low temperatures.
Total-ionizing-dose (TID) effects and low-frequency noise are evaluated in advanced bulk nMOS and pMOS FinFETs with SiO 2 /HfO 2 gate dielectrics. Otherwise identical devices built with and without ...through-silicon via (TSV) integration exhibit threshold voltage shifts of less than 25 mV and changes in maximum transconductance of less than 1% up to 2 Mrad(SiO 2 ). TSV integration negligibly impacts threshold shifts and degradation of subthreshold swing and <inline-formula> <tex-math notation="LaTeX">I_{\mathrm{\scriptscriptstyle ON}}/I_{\mathrm{\scriptscriptstyle OFF}} </tex-math></inline-formula> ratios. Similar low-frequency noise magnitudes and frequency dependencies are observed before and after TID irradiation for each device type. Effective densities of the near-interfacial electron traps responsible for the noise in the nMOS devices increase as the surface potential moves toward midgap, while effective densities of the hole traps that cause the noise in the pMOS devices increase as the surface potential moves toward the valence band edge.
We evaluate the total-ionizing-dose (TID) responses of InGaAs nMOS fin field-effect transistors (FinFETs) with a modified gate-stack irradiated with 10-keV X-rays under different gate biases. This ...modified InGaAs nMOS FinFET process shows decreased subthreshold leakage current and increased hysteresis in as-processed devices, and reduced hole trapping in irradiated devices, than first-generation development-stage devices. The reduction in subthreshold leakage current is attributed to changing the buffer layer from GaAs to In 0.3 Ga 0.7 As, thereby enhancing the material quality. Both the increased hysteresis in as-processed devices and reduced hole trapping in irradiated devices are attributed primarily to thinning the Al 2 O 3 layer that separates the HfO 2 from the InGaAs layers. This facilitates charge exchange with defects at the HfO 2 /Al 2 O 3 interface and reduces the percentage of radiation-induced holes that are generated in Al 2 O 3 and trapped in HfO 2 . The removal of a tungsten layer above the TiN gate reduces the interface dose enhancement.
The total-ionizing-dose (TID) response of indium gallium arsenide (InGaAs) MOSFETs with Al 2 O 3 gate dielectrics and several channel lengths is evaluated under different biases. DC static ...characteristics show large negative threshold voltage <inline-formula> <tex-math notation="LaTeX">V_{\text {th}} </tex-math></inline-formula> shifts and subthreshold stretchout ( SS ), indicating net positive charge trapping in the gate oxide and generation of the interface and border traps. Hysteresis and <inline-formula> <tex-math notation="LaTeX">I_{d} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">V_{\text {gs}} </tex-math></inline-formula> measurements from cryogenic to high temperatures show the important role of defects in the Al 2 O 3 gate dielectric to the TID response. Radiation-induced-hole trapping is attributed to oxygen vacancies in the Al 2 O 3 . The relatively large hysteresis in these devices is attributed primarily to dangling Al bonds in the near-interfacial Al 2 O 3 . Analysis of the temperature dependence of <inline-formula> <tex-math notation="LaTeX">V_{\text {th}} </tex-math></inline-formula> and SS suggests that the rate at which electrons leave the Al 2 O 3 during a positive-to-negative gate-bias sweep is higher than the rate at which they enter during a negative-to-positive gate-bias sweep.
Integrating hydrogen evolution reaction (HER) with hydrazine oxidation reaction (HzOR) has an encouraging prospect for the energy‐saving hydrogen production, demanding the high‐performance ...bifunctional HER/HzOR electrocatalyst. Ruthenium phosphide/doped carbon composites have exhibited superior activity toward multiple electrocatalytic reactions. To explore the decent water‐soluble precursors containing both N and P elements is highly attractive to facilely prepare metal phosphide/doped carbon composites. Herein, as one kind ecofriendly biomolecules, adenine nucleotide was first employed to selectively fabricate the highly pure RuP nanoparticles embedded into porous N,P‐codoped carbons (RuP/PNPC) with a straightforward “mix‐and‐pyrolyze” approach. The newly prepared RuP/PNPC only requires 4.0 and −83.0 mV at 10 mA/cm2 separately in alkaline HER and HzOR, outperforming most of reported electrocatalysts, together with the outstanding neutral bifunctional performance. Furthermore, the two‐electrode alkaline and neutral overall hydrazine splitting both exhibit significant power‐efficiency superiority to the corresponding overall water splitting with the voltage difference of larger than 2 V, which can be also easily driven by the fuel cells and solar cells with considerable H2 generation. Our report innovates the N‐ and P‐bearing adenine nucleotide to effortlessly synthesize the high‐quality RuP/doped carbon composite catalysts, highly potential as a universal platform for metal phosphide‐related functional materials.
As one kind ecofriendly biomolecules, nucleotide was first explored to selectively fabricate high‐quality RuP on N,P‐codoped carbon, exhibiting superior bifunctional HER and HzOR activity in alkaline and neutral conditions. The constructed overall hydrazine splitting enables energy‐saving H2 production and can be easily driven by the fuel cells and solar cells with considerable H2 yields.
We use capacitance-frequency (<inline-formula> <tex-math notation="LaTeX">C </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">f </tex-math></inline-formula>) measurements to ...provide lower bound estimates of border-trap densities in multifin MOS capacitors with high-K dielectrics built in Ge and InGaAs fin field effect transistor (FinFET) technologies before and after X-ray irradiation. The <inline-formula> <tex-math notation="LaTeX">C </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">f </tex-math></inline-formula> method is illustrated for SiO 2 -based planar MOS capacitors and compared with high-frequency capacitance-voltage measurements. Lower effective border-trap densities are found before and after irradiation for multifin capacitors built in a strained Ge <inline-formula> <tex-math notation="LaTeX">p </tex-math></inline-formula>MOS FinFET technology than for similar devices built using an early-developmental stage InGaAs MOS technology. These results show the utility of <inline-formula> <tex-math notation="LaTeX">C </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">f </tex-math></inline-formula> measurements in characterizing defect densities in MOS capacitors, particularly when large border-trap densities exist.
The Hippo pathway restricts organ size during development and its inactivation plays a crucial role in cancer. Yes-associated protein (YAP) and its paralog transcriptional coactivator with ...PSD-95/Dlg/ZO-1 (PDZ)-binding motif (TAZ) are transcription co-activators and effectors of the Hippo pathway mediating aberrant enlargement of organs and tumor growth upon Hippo pathway inactivation. It has been demonstrated that genetic inactivation of YAP could be an effective approach to inhibit tumorigenesis. In order to identify pharmacological inhibitors of YAP, we screened a library of 52,683 compounds using a YAP-specific reporter assay. In this screen we identified cyclopeptide RA-V (deoxybouvardin) as a specific inhibitor of YAP and TAZ but not other reporters. Unexpectedly, later experiments demonstrated that RA-V represses the protein but not mRNA levels of YAP target genes. Nevertheless, RA-V strongly blocks liver enlargement induced by
knockout. Furthermore, RA-V not only inhibits liver tumorigenesis induced by YAP activation, but also induces regression of established tumors. We found that RA-V inhibits dedifferentiation and proliferation, while inducing apoptosis of hepatocytes. Furthermore, RA-V also induces apoptosis and inhibits proliferation of macrophages in the microenvironment, which are essential for YAP-induced tumorigenesis. RA-V is thus a drug candidate for cancers involving YAP/TAZ activation.
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