Synchronous Driving Method for Stitching Pixel Arrays Based on an Adaptive Correction Technique.

With the application of stitching technology in large-pixel-array CMOS image sensors, the problem of non-synchronized output signals from pixel array bilateral driver circuits has become progressively more serious and has led to the DC perforation of bilateral driver circuits, while conventional clock tree synchronization design methodology does not apply to stitching technology. Therefore, this paper analyses reasons for the inconsistency in the output signals of bilateral driving circuits and proposes a synchronous driving method applicable to stitching pixel arrays based on the idea of on-chip output signal delay detection and calibration. This method detects and corrects the non-synchrony of the row driver output signals on both sides according to changes in the operating environment of the chip. This method is characterized by a simple structure and high reliability. Finally, based on the 55 nm stitching process, simulations are carried out in a CMOS image sensor with a chip area of 77 mm × 84 mm to verify that this method is feasible. This large image sensor with a 150 M pixel array has a frame rate of over 10 FPS.

Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway.

Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsis-induced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLP-induced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLP-induced mice. The levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.

HAND2-AS1 associates with outcomes of acute coronary syndrome and regulates cell viability of vascular endothelial cells.

OBJECTIVE: Acute coronary syndrome (ACS) is an emergency and severe disorder of the cardiovascular system. This paper assessed the expression of plasma HAND2-AS1 in patients with ACS, researched its diagnostic and prognostic significance, and studied its possible mechanism for participating in ACS. METHODS: The concentration of HAND2-AS1 of 101 included patients with ACS was certified by qRT-PCR and its possible diagnostic function was revealed by the receiver operating characteristic (ROC) curve. All patients were followed up for 6 months after percutaneous coronary intervention (PCI) therapy and Kaplan-Meier (K-M) curve and COX regression analysis was performed to estimate the short-term prognostic value of HAND2-AS1 in ACS. The interrelationship between HAND2-AS1 and Gensini score and endothelial injury was identified via Pearson correlation. The function of HAND2-AS1 on the viability, migration, and apoptosis of human umbilical vein endothelial cells (HUVECs) was estimated by the Cell Counting Kit-8 (CCK-8), Transwell chamber, and flow cytometry. RESULTS: In ACS patients, the expression of serum HAND2-AS1 was prominently decreased and closely correlated with the Gensini score. The decreased HAND2-AS1 expression was of diagnostic significance. Declined plasma HAND2-AS1 was observed in patients with the major adverse cardio-cerebrovascular event (MACCE) and was an independent risk for the poor prognosis of ACS patients. In the cell model, upregulation of HAND2-AS1 improved cell viability and migration and inhibited cell apoptosis. CONCLUSION: HAND2-AS1 was an independent biomarker for the diagnosis and prognosis of ACS. HAND2-AS1 might be involved in ACS development by regulating endothelial damage.

MP Allosterically Activates AMPK to Enhance ABCA1 Stability by Retarding the Calpain-Mediated Degradation Pathway.

It is widely recognized that macrophage cholesterol efflux mediated by the ATP-binding cassette transporter A1 (ABCA1) constitutes the initial and rate-limiting step of reverse cholesterol transport (RCT), displaying a negative correlation with the development of atherosclerosis. Although the transcriptional regulation of ABCA1 has been extensively studied in previous research, the impact of post-translational regulation on its expression remains to be elucidated. In this study, we report an AMP-activated protein kinase (AMPK) agonist called ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((3-hydroxyphenyl) amino)-9H-purin-9-yl) tetrahydrofuran-2-yl) methyl dihydrogen phosphate (MP), which enhances ABCA1 expression through post-translational regulation rather than transcriptional regulation. By integrating the findings of multiple experiments, it is confirmed that MP directly binds to AMPK with a moderate binding affinity, subsequently triggering its allosteric activation. Further investigations conducted on macrophages unveil a novel mechanism through which MP modulates ABCA1 expression. Specifically, MP downregulates the Cav1.2 channel to obstruct the influx of extracellular Ca2+, thereby diminishing intracellular Ca2+ levels, suppressing calcium-activated calpain activity, and reducing the interaction strength between calpain and ABCA1. This cascade of events culminates in the deceleration of calpain-mediated degradation of ABCA1. In conclusion, MP emerges as a potentially promising candidate compound for developing agents aimed at enhancing ABCA1 stability and boosting cellular cholesterol efflux and RCT.

High Dynamic Pixel Structure Based on an Adaptive Integrating Capacitor.

Infrared image sensing technology has received widespread attention due to its advantages of not being affected by the environment, good target recognition, and high anti-interference ability. However, with the improvement of the integration of the infrared focal plane, the dynamic range of the photoelectric system is difficult to improve, that is, the restrictive trade-off between noise and full well capacity is particularly prominent. Since the capacitance of the inversion MOS capacitor changes with the gate-source voltage adaptively, the inversion MOS capacitor is used as the capacitor in the infrared pixel circuit, which can solve the contradiction between noise in low light and full well capacity in high light. To this end, a highly dynamic pixel structure based on adaptive capacitance is proposed, so that the capacitance of the infrared image sensor can automatically change from 6.5 fF to 37.5 fF as the light intensity increases. And based on 55 nm CMOS process technology, the performance parameters of an infrared image sensor with a 12,288 × 12,288 pixel array are studied. The research results show that a small-size pixel of 5.5 µm × 5.5 µm has a large full well capacity of 1.31 Me- and a variable conversion gain, with a noise of less than 0.43 e- and a dynamic range of more than 130 dB.

Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.

Energy landscape quantifications of histone H3.3 recognition by chaperone DAXX reveal an uncoupled binding specificity and affinity.

Histone variant H3.3 differs from the canonical histone H3.1 by only five amino acids, yet its chaperone death domain-associated protein (DAXX) can specifically recognize H3.3 over H3.1, despite having a large DAXX-interacting surface on the H3.3-H4 heterodimer common to that on the H3.1-H4 complex. This observation gives rise to the question of, from the binding energy point view, how high binding specificity may be achieved with small differences of the overall binding energy for protein-protein interactions in general. Here we investigate the mechanism of coupling of binding specificity and affinity in protein-protein interactions using the DAXX-H3.3-H4 complex as a model. Using a multi-scale method, we found that the hydrophobic interactions between DAXX and the H3.3-specific region contributed to their initial binding process. And the structural flexibility of the interacting partners contributed to the binding affinity after their encounter. By quantifying the free energy landscape, we revealed that the interaction between the specific residues of H3.3 and DAXX decreased the encounter barrier height while the folding of H3.3-H4 and DAXX increased the depth of the free energy basin of the final binding state. The encounter barrier height, which is not coupled to the thermodynamic stability of the final binding state, had a marked effect on the initial binding rate of flexible histones and chaperones. Based on the energy landscape theory, we found that the intrinsic binding energy funnel of this uncoupled recognition process was affected by the structural flexibility and the flexibility modulated the degree of coupling between binding specificity and affinity. Our work offers a biophysical explanation of the specific recognition between the histones and their chaperones, and also extends the use of energy landscape theory for understanding molecular recognitions in general.

Dual roles of the Arabidopsis PEAT complex in histone H2A deubiquitination and H4K5 acetylation.

Histone H2A monoubiquitination is associated with transcriptional repression and needs to be removed by deubiquitinases to facilitate gene transcription in eukaryotes. However, the deubiquitinase responsible for genome-wide H2A deubiquitination in plants has yet to be identified. In this study, we found that the previously identified PWWP-EPCR-ARID-TRB (PEAT) complex components interact with both the ubiquitin-specific protease UBP5 and the redundant histone acetyltransferases HAM1 and HAM2 (HAM1/2) to form a larger version of PEAT complex in Arabidopsis thaliana. UBP5 functions as an H2A deubiquitinase in a nucleosome substrate-dependent manner in vitro and mediates H2A deubiquitination at the whole-genome level in vivo. HAM1/2 are shared subunits of the PEAT complex and the conserved NuA4 histone acetyltransferase complex, and are responsible for histone H4K5 acetylation. Within the PEAT complex, the PWWP components (PWWP1, PWWP2, and PWWP3) directly interact with UBP5 and are necessary for UBP5-mediated H2A deubiquitination, while the EPCR components (EPCR1 and EPCR2) directly interact with HAM1/2 and are required for HAM1/2-mediated H4K5 acetylation. Collectively, our study not only identifies dual roles of the PEAT complex in H2A deubiquitination and H4K5 acetylation but also illustrates how these processes collaborate at the whole-genome level to regulate the transcription and development in plants.

Intermetallic Compound with CuNi Sites for Enhancing the Selectivity of Electrochemical CO2 Conversion.

Although single-metal-site (SMS) catalysts have long been explored for the electrochemical CO2 reduction reaction (EC-CO2RR), the reactivity and selectivity of SMS catalysts remain rather low due to the competing hydrogen evolution reaction (HER). To improve the selectivity, in this work, a novel intermetallic particle of CuNi is decorated on the N-doped carbon substrate, which was first precisely fabricated by scarifying the bimetal-doped metal-organic framework (MOF). Thanks to the neighboring synergistic functions of Cu and Ni sites, CuNi/NC prominently boosts the electroreduction of CO2, far more than the SMS catalysts of Cu/NC and Ni/NC. Further, CuNi/NC presents superior selectivity toward CO with faradaic efficiency over a wide range of potentials (surpassing 90% at 0.6-1.0 V vs RHE, up to 98% at 0.6 V vs RHE) and excellent durability. The experimental results and theoretical calculations reveal that the Ni species can be highly activated due to the neighboring Cu species, which considerably facilitates the formation of an intermediate of COOH* and consequently enhances the selectivity of the reduction of CO2 to CO. This work paves a general way to precisely fabricate catalysts with multiple metal species and also demonstrates the significant synergetic efficiency between the neighboring sites to improve the catalytic performance.

Mechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.

Structural insights into histone binding and nucleosome assembly by chromatin assembly factor-1.

Chromatin inheritance entails de novo nucleosome assembly after DNA replication by chromatin assembly factor-1 (CAF-1). Yet direct knowledge about CAF-1's histone binding mode and nucleosome assembly process is lacking. In this work, we report the crystal structure of human CAF-1 in the absence of histones and the cryo-electron microscopy structure of CAF-1 in complex with histones H3 and H4. One histone H3-H4 heterodimer is bound by one CAF-1 complex mainly through the p60 subunit and the acidic domain of the p150 subunit. We also observed a dimeric CAF-1-H3-H4 supercomplex in which two H3-H4 heterodimers are poised for tetramer assembly and discovered that CAF-1 facilitates right-handed DNA wrapping of H3-H4 tetramers. These findings signify the involvement of DNA in H3-H4 tetramer formation and suggest a right-handed nucleosome precursor in chromatin replication.

Endowing Nanoparticles with High Stability on the Hydrogenation Reaction by the Amino Group-Assisted Strategy.

In the field of a heterogeneous industrial catalysis process, the encapsulated structure plays a crucial role in preventing active sites from leaching during the reaction; however, related studies on the strategy to fabricate encapsulated catalysts under control remain rare. Herein, we develop an amino-assisted strategy to construct a highly stable catalyst with core-shell copper nanoparticles (NPs), namely, Cu@NC (NC represents the nitrogen-doped carbon), presenting not only excellent activity but also high durability on the hydrogenation of quinolines even in the large-scale tests, which is very vital in practical application. In contrast, in the absence of the amino group, the Cu NPs were dispersed out of the carbon surface to form Cu/NC, leading to readily lose activity in the recycling tests due to the leaching occurred during the catalytic process. This work offers a promising method to fabricate a stable catalyst to enhance durability in heterogeneous catalysis.

High-Linearity and High-Speed ROIC of Ultra-Large Array Infrared Detectors Based on Adaptive Compensation and Enhancement.

In order to solve the problem of limited linearity and frame rate in the large array infrared (IR) readout integrated circuit (ROIC), a high-linearity and high-speed readout method based on adaptive offset compensation and alternating current (AC) enhancement is proposed in this paper. The efficient correlated double sampling (CDS) method in pixels is used to optimize the noise characteristics of the ROIC and output CDS voltage to the column bus. An AC enhancement method is proposed to quickly establish the column bus signal, and an adaptive offset compensation method is used at the column bus terminal to eliminate the nonlinearity caused by the pixel source follower (SF). Based on the 55 nm process, the proposed method is comprehensively verified in an 8192 × 8192 IR ROIC. The results show that, compared with the traditional readout circuit, the output swing is increased from 2 V to 3.3 V, and the full well capacity is increased from 4.3 Me- to 6 Me-. The row time of the ROIC is reduced from 20 µs to 2 µs, and the linearity is improved from 96.9% to 99.98%. The overall power consumption of the chip is 1.6 W, and the single-column power consumption of the readout optimization circuit is 33 µW in the accelerated readout mode and 16.5 µW in the nonlinear correction mode.

Palladium particles dispersed on hollow structural support improve CO2 conversion.

Herein, an effective Pd/NHS catalyst has been designed and facilely synthesized with extraordinary CO2 fixation performance, which is superior to that of Pd/NS catalysts, owing to the hollow structures facilitating mass transfer and product release.

The prognostic role and metabolic function of GGPS1 in oral squamous cell carcinoma.

Background: GGPS1(geranylgeranyl diphosphate synthase 1) is a member of the prenyltransferase family. Abnormal expression of GGPS1 can disrupt the balance between protein farnesylation and geranylgeranylation, thereby affecting a variety of cellular physiologic and pathological processes. However, it is still unknown how this gene could contribute to the prognosis of oral squamous cell carcinoma (OSCC). This study aimed to explore the prognostic role of GGPS1 in OSCC and its relationship with clinical features. Methods: The RNA-seq data and clinical data were obtained from TCGA. The survival analyses, Cox regression analyses, ROC curves, nomograms, calibration curves, and gene function enrichments were established by R software. Results: The results showed that the high expression of GGPS1 in OSCC is related to poor prognosis. At the same time, multivariate Cox regression analyses showed that GGPS1 could be an independent prognostic biomarker, and its gene expression level is closely related to the histological stage of cancer. GGPS1 may promote tumorigenesis because of its metabolic function. Conclusion: This study came to a conclusion that GGPS1, whose high expression has a significantly unfavorable meaning toward the prognosis of OSCC, can act as a novel independent biomarker for OSCC.

Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase.

Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification1-3. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome4, counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1)5 to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. 6-9). The intricate biological function of PR-DUB requires accurate targeting of H2AK119ub1, but PR-DUB can deubiquitinate monoubiquitinated free histones and peptide substrates indiscriminately; the basis for its exquisite nucleosome-dependent substrate specificity therefore remains unclear. Here we report the cryo-electron microscopy structure of human PR-DUB, composed of BAP1 and ASXL1, in complex with the chromatosome. We find that ASXL1 directs the binding of the positively charged C-terminal extension of BAP1 to nucleosomal DNA and histones H3-H4 near the dyad, an addition to its role in forming the ubiquitin-binding cleft. Furthermore, a conserved loop segment of the catalytic domain of BAP1 is situated near the H2A-H2B acidic patch. This distinct nucleosome-binding mode displaces the C-terminal tail of H2A from the nucleosome surface, and endows PR-DUB with the specificity for H2AK119ub1.

High-Speed Fully Differential Two-Step ADC Design Method for CMOS Image Sensor.

The application requirements of high frame rate CMOS image sensors (CIS) in the industry have not been satisfied due to the speed limitations in traditional single-slope and serial two-step analog-to-digital converters (ADCs). In this paper, a high-speed fully differential two-step ADC design method for CIS was proposed. The proposed method was based on differential ramp and time-to-digital conversion (TDC) technology. A parallel conversion mode was formed that is different from serial conversion, and the robustness of the system was ensured due to the existence of differential ramps. Aiming at the inconsistency between traditional TDC technology and single-slope ADC, a TDC technology based on level coding was proposed. The proposed technology achieves the TDC in the last clock cycle of analog-to-digital conversion, and realized a two-step conversion process at another level. This paper presents a complete circuit design, layout design, and test verification of the proposed design method based on the 55 nm 1P4M CMOS experimental platform. Under the design environment of the analog voltage of 3.3 V, the digital voltage of 1.2 V, the clock frequency of 100 MHz, and a dynamic input range of 1.6 V, this design was a 12-bit ADC with a conversion time of 480 ns, column-level power consumption of 62 µW, differential nonlinearity (DNL) of +0.6/-0.6 LSB, and integral nonlinearity (INL) of +1.2/-1.4 LSB. Furthermore, it achieved a signal-to-noise distortion ratio (SNDR) of 70.08 dB. The proposed design provided a large area array with a high frame rate, and compared with the existing advanced single-slope ADC, its conversion speed increased by more than 52%. It provides an effective solution for the implementation of high frame frequency CIS.

Nine geranylgeranylated derivatives isolated from the roots of Rhus chinensis Mill.

Nine undescribed geranylgeranylated derivatives (chinensens A-G), including malic acid derivative (A) and phenolic derivatives (B-E), as well as two pairs of enantiomers, [(R), (S)]-chinensens F and [(R), (S)]-chinensens G, were isolated from the roots of Rhus chinensis Mill. Their structures were elucidated by UV, IR, HRESIMS, 1D and 2D NMR spectra, as well as optical rotations. The 95% EtOH extract (95% EXT, 500 mg/kg, p. o.) of the roots of Rhus chinensis and the 95% EtOH fraction (95% FRA, 500 mg/kg, p. o.) from the microporous resin column significantly alleviated indomethacin-induced or water immersion-restraint stress-induced damage in rat gastric mucosa with inhibitory rates from 53% to 89%. The racemic mixture (chinensen G) and its enantiomers [(R), (S)]-chinensens G showed weak activities against H+,K+-ATPase (20%-24%) at a concentration of 0.1 mM, respectively.