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.

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.

Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study.

BACKGROUND: Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA. METHODS: A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age. RESULTS: In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group. CONCLUSION: The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

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.

Discovery of PlatinumIV-Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents.

Recently, artemisinin and derivatives have been revealed to possess encouraging antitumor activity. Herein, we integrated the antitumor advantages of artesunate and platinum drugs to construct novel PtIV-artesunate dual-action and triple-action complexes. Most derivatives, especially 10f, displayed broad-spectrum and potent in vitro antitumor activities against a number of cancer cell lines. Compound 10f displayed potent antimetastasis and anticlonogenic activities, efficiently induced autophagic cell death and apoptosis, and arrested the cell cycle at both S and G2/M phases. More importantly, it displayed remarkable in vivo antitumor efficacy in the A549 xenograft model (TGI = 53.4%; 6 µmol/kg) with low toxicity. In addition to the antitumor application, 10f showed potent in vivo antimalarial activity in malarial-infected mice model and obviously alleviated malarial-related multiorgan injury. This conjugation greatly improved safety, especially reducing the platinum drugs' nephrotoxicity. Taken together, this study highlighted the therapeutic potential of PtIV-artesunate complexes as antitumor and antimalarial agents.

Inspired by bis-ß-carboline alkaloids: Construction and antitumor evaluation of a novel bis-ß-carboline scaffold as potent antitumor agents.

Bis-ß-carboline alkaloids are widely distributed in natural products and represent a promising drug-like scaffold for discovering drugs and bioactive molecules. In this study, we utilized the structural simplification strategy to construct a novel bis-ß-carboline scaffold via "one-pot" condensation-Mannich reaction. The simplified bis-ß-carboline derivatives were obtained in good yield. Antitumor evaluation revealed most compounds, especially 3m, displayed potent antitumor activity (IC50 values for 3m: 0.96 µM âˆ¼ 1.52 µM). More importantly, 3m displayed valuable antitumor properties including anti-migration and anti-invasion activity against cancer cells, antiangiogenic and vascular-disrupting properties. Mechanistic studies revealed 3m potently inhibited both Top1 and Top2 activity, thus interfering with DNA synthesis in cancer cells. Taken together, this study developed a new synthetic methodology to construct a novel bis-ß-carboline scaffold, which represents a promising lead structure for antitumor drug discovery.

Discovery of potent tubulin inhibitors targeting the colchicine binding site via structure-based lead optimization and antitumor evaluation.

The colchicine binding site of tubulin is a promising target for discovering novel antitumour agents. Previously, we identified 2-aryl-4-amide-quinoline derivatives displayed moderate tubulin polymerisation inhibitory activity and broad-spectrum in vitro antitumour activity. In this study, structure based rational design and systematic structural optimisation were performed to obtain analogues C1∼J2 bearing diverse substituents and scaffolds. Among them, analogue G13 bearing a hydroxymethyl group displayed good tubulin polymerisation inhibitory activity (IC50 = 13.5 µM) and potent antiproliferative activity (IC50 values: 0.65 µM∼0.90 µM). G13 potently inhibited the migration and invasion of MDA-MB-231 cells, and displayed potent antiangiogenic activity. It efficiently increased intracellular ROS level and decreased MMP in cancer cells, and obviously induced the fragmentation and disassembly of the microtubules network. More importantly, G13 exhibited good in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).

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.

Quantitative resilience assessment of the network-level metro rail service's responses to the COVID-19 pandemic.

The metro rail system has proven to be the most efficient high-capacity carriers. During the unprecedented coronavirus disease 2019 (COVID-19) challenge, non-pharmaceutical interventions become a widely adopted strategy to limit physical movements and interactions. For situational awareness and decision support, data-driven analytics about serviceability are invaluable to metro agencies and decision-makers of cities. This paper presents a data-driven analytical framework that quantitatively evaluates COVID-19-caused resilience performance of metro rails. Several characteristics (e.g., vulnerability, robustness, rapidity, and degree to return) of the metro system's responses to the disturbance were identified and modeled with multivariate multiple regression. The applicability and rationality of the resilience evaluation model were validated by the metro transit data of the United States. The preliminary results disclosed that metro rail transit encountered more vulnerability (90.6%) in passenger trips than motorbus and light rail (around 70%). A set of statistical models were employed to disentangle the effect of socio-demographic variables and COVID-19-related factors on the metro transit. The disclosed emerging knowledge of resilience provides an in-depth understanding of mobility trends for the public and time-sensitive decision support for the policy effects, to further improve the service and management of the metro system under the spread of the epidemic.

A High SNR Improvement CMOS Analog Accumulator with Charge Compensation Technique.

In this paper, a 7.75 kHz line rate analog domain time delay integration (TDI) CMOS analog accumulator with 128-stage is proposed. An adaptive compensation for the charge loss due to parasitic effects is adopted. Based on the influence mechanism of parasitic effects, alternately charging the top and bottom plates of the storage capacitor while cooperate positive feedback capacitor dynamically compensates for the charge loss of the sampling phase and the holding phase. Using the proposed circuit, after the post-layout simulation verification, the SNR of 128 stage accumulation can be improved by as much as 20.9 dB.

Metabolomics and transcriptomics unravel the mechanism of browning resistance in Agaricus bisporus.

Agaricus bisporus is widely consumed on the world market. The easy browning of mushroom surface is one of the most intuitive factors affecting consumer purchase. A certain cognition on browning mechanism has been made after years of research. At present, people slow down the browning of mushrooms mainly by improving preservation methods. In addition, breeding is also a reliable way. In the production practice, we have identified some browning-resistant varieties, and we selected a browning-resistant variety to compare with an ordinary variety to reveal the resistance mechanism. Using transcriptomics and metabolomics, the differences in gene expression and metabolite levels were revealed, respectively. The results showed that differentially expressed genes (DEGs) like AbPPO4, AbPPO3 and AbPPO2 were differently expressed and these DEGs were involved in many pathways related to browning. The expression of AbPPO expression play an important role in the browning of A. bisporus and multiple PPO family members are involved in the regulation of browning. However, the resistance to browning cannot be judged only by the expression level of AbPPOs. For metabolomics, most of the different metabolites were organic acids. These organic acids had a higher level in anti-browning (BT) than easy-browning varieties (BS), although the profile was very heterogeneous. On the contrary, the content of trehalose in BS was significantly higher than that in BT. Higher organic acids decreased pH and further inhibited PPO activity. In addition, the BS had a higher content of trehalose, which might play roles in maintaining PPO activity. The difference of browning resistance between BS and BT is mainly due to the differential regulation mechanism of PPO.

Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural optimization and antitumor evaluation.

The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 µM to 10.36 µM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 µM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.

Emergence of lesions outside of the basal ganglia and irreversible damage to the basal ganglia with severe ß-ketothiolase deficiency: A case report.

BACKGROUND: ß-ketothiolase deficiency (ß-KTD) is an inherited disease, and insufficient attention has been paid to imageology due to its lower morbidity. Therefore, few lesions outside the basal ganglia have been found before, and the persistent pathological changes have rarely been reported. CASE SUMMARY: A 10-mo-old Chinese female patient with a free previous medical history but with poor physical and athletic development had received the haemophilus influenzae vaccine and then developed a low fever 2 d prior. She was initially diagnosed with severe brain injury, central respiratory failure, metabolic acidosis complicated with respiratory alkalosis, hyper-IgE, etc. With further examination, a definite diagnosis of ß-KTD was made. Symptomatic treatment was adopted. Ten days later, the dyspnea was improved evidently and the ventilator was removed, but there were still obvious abnormalities on magnetic resonance imaging (MRI). The lesions mainly invaded the corpus striatum but were not limited to the basal ganglia. Then, the patient's disease improved and discharged approximately 1 mo later, and the abnormal lesions on MRI had partially improved. However, for about 1 year, the residual irreversible lesions were observed on MRI, the mental and physical development of the patient was obviously regressive, and extra rehabilitation training was needed. CONCLUSION: The case highlights the critical importance of one view that the range of lesions in some patients may be more extensive than previously thought in some ß-KTD patients. In addition to biochemical tests, genetic tests and magnetic resonance imaging are not only conducive to quickly diagnosing ß-KTD but also to partially evaluating the short- and long-term outcomes. Moreover, more attention should be paid to the two mutations (c.478C>G; c.951C>T) that may be associated with severe ß-KTD.

Investigation into the Phase-Activity Relationship of MnO2 Nanomaterials toward Ozone-Assisted Catalytic Oxidation of Toluene.

Manganese dioxide (MnO2 ), with naturally abundant crystal phases, is one of the most active candidates for toluene degradation. However, it remains ambiguous and controversial of the phase-activity relationship and the origin of the catalytic activity of these multiphase MnO2 . In this study, six types of MnO2 with crystal phases corresponding to α-, ß-, γ-, ε-, λ-, and δ-MnO2 are prepared, and their catalytic activity toward ozone-assisted catalytic oxidation of toluene at room temperature are studied, which follow the order of δ-MnO2  > α-MnO2  > ε-MnO2  > γ-MnO2  > λ-MnO2  > ß-MnO2 . Further investigation of the specific oxygen species with the toluene oxidation activity indicates that high catalytic activity of MnO2 is originated from the rich oxygen vacancy and the strong mobility of oxygen species. This work illustrates the important role of crystal phase in determining the oxygen vacancies' density and the mobility of oxygen species, thus influencing the catalytic activity of MnO2 catalysts, which sheds light on strategies of rational design and synthesis of multiphase MnO2 catalysts for volatile organic pollutants' (VOCs) degradation.

A Highly Linear CMOS Image Sensor Design Based on an Adaptive Nonlinear Ramp Generator and Fully Differential Pipeline Sampling Quantization with a Double Auto-Zeroing Technique.

For a complementary metal-oxide-semiconductor image sensor with highly linear, low noise and high frame rate, the nonlinear correction and frame rate improvement techniques are becoming very important. The in-pixel source follower transistor and the integration capacitor on the floating diffusion node cause linearity degradation. In order to address this problem, this paper proposes an adaptive nonlinear ramp generator circuit based on dummy pixels used in single-slope analog-to-digital converter topology for a complementary metal-oxide-semiconductor (CMOS) image sensor. In the proposed approach, the traditional linear ramp generator circuit is replaced with the new proposed adaptive nonlinear ramp generator circuit that can mitigate the nonlinearity of the pixel unit circuit, especially the gain nonlinearity of the source follower transistor and the integration capacitor nonlinearity of the floating diffusion node. Moreover, in order to enhance the frame rate and address the issue of high column fixed pattern noise, a new readout scheme of fully differential pipeline sampling quantization with a double auto-zeroing technique is proposed. Compared with the conventional readout structure without a fully differential pipeline sampling quantization technique and double auto-zeroing technique, the proposed readout scheme cannot only enhance the frame rate but can also improve the consistency of the offset and delay information of different column comparators and significantly reduce the column fixed pattern noise. The proposed techniques are simulated and verified with a prototype chip fabricated using typical 180 nm CMOS process technology. The obtained measurement results demonstrate that the overall nonlinearity of the CMOS image sensor is reduced from 1.03% to 0.047%, the efficiency of the comparator is improved from 85.3% to 100%, and the column fixed pattern noise is reduced from 0.43% to 0.019%.

Genome Survey and Transcriptome Analysis on Mycelia and Primordia of Agaricus blazei.

Agaricus blazei, a type of edible straw-rotting mushroom with somewhat sweet taste and fragrance of almonds, has attracted considerable scientific and practical attention. High-throughput Illumina PE150 and PacBio RSII platform were employed to generate a genomic sequence. De novo assembly generated 36 contigs with 38,686,133 bp in size, containing 10,119 putative predicted genes. Additionally, we also studied transcriptional regulation of the mycelia and the primordia for exploration of genes involved in fruiting body formation. Expression profiling analysis revealed that 2,164 genes were upregulated in mycelia and 1,557 in primordia. Functional enrichment showed that differentially expressed genes associated with response to stress, ribosome biogenesis, arginine biosynthesis, and steroid biosynthesis pathway were more active in fruiting body. The genome and transcriptome analysis of A. blazei provide valuable sequence resources and contribute to our understanding of genes related to the biosynthesis pathway of polysaccharide and benzaldehyde, as well as the fruiting body formation.

The performance and reaction pathway of δ-MnO2/USY for catalytic oxidation of toluene in the presence of ozone at room temperature.

In this work, a series of δ-MnO2/USY with different contents of δ-MnO2 (0.3 wt%, 1.5 wt%, 3.0 wt%, 10.0 wt%, and 15.0 wt%) were prepared. In addition, their performances of the adsorption of toluene, degradation and mineralization of toluene, and removal of ozone (O3) were investigated. The results showed that, among all the samples, 3.0 wt% δ-MnO2/USY displayed the best performance of toluene adsorption, degradation and mineralization. Furthermore, according to the in situ DRIFTS and GC-MS analysis, the intermediate by-products during the toluene degradation progress were ascertained and the possible pathway of catalytic oxidation toluene by δ-MnO2/USY in the presence of O3 was proposed.

Synthesis of spiro-tetrahydrothiopyran-oxindoles by Michael-aldol cascade reactions: discovery of potential P53-MDM2 inhibitors with good antitumor activity.

Using proline as the catalyst, an organocatalytic Michael-aldol cascade reaction was developed for the synthesis of spiro-tetrahydrothiopyran oxindoles. The highly functionalized scaffold was assembled in moderate to good yields (51-78%) and excellent diastereoselectivities (>20 : 1 dr). Interestingly, the oxindoles displayed moderate to good in vitro antitumor activities and were validated as p53-MDM2 inhibitors, which represented promising lead compounds for antitumor drug discovery.

Organocatalytic Asymmetric Synthesis of Spiro-Tetrahydrothiophene Oxindoles Bearing Four Contiguous Stereocenters by One-Pot Michael-Henry-Cascade-Rearrangement Reactions.

Asymmetric construction of tetrahydrothiophenes with four contiguous stereocenters remains a formidable challenge. Herein, the bottleneck was addressed by an unprecedented one-pot Michael-Henry-cascade-rearrangement reaction that could simultaneously create four consecutive stereogenic centers including two tetrasubstituted carbon stereocenters. The highly functionalized chiral spirotetrahydrothiophene scaffolds were assembled in moderate to good yields (≈54-79 %), excellent diastereo- (>20:1 d.r.) and enantio-selectivities (up to 93 % ee).

iTRAQ-MS/MS Proteomic Analysis Reveals Differentially Expressed Proteins During Post-harvest Maturation of the White Button Mushroom Agaricus bisporus.

Agaricus bisporus (J. E. Lange) Imbach, well known as the common cultivated mushroom or white button mushroom, is widely cultivated all over the world. We used iTRAQ-MS/MS (i.e., isobaric tags for relative and absolute quantification-coupled two-dimensional liquid chromatography-tandem mass spectrometry) to identify protein expression changes that occur during the post-harvest maturation of Agaricus bisporus fruitbodies at 0, 6, 12, and 48 h after harvest. A total of 5878 unique peptides, representing 1063 proteins, were identified. Quantitative data were obtained from 1012 out of the 1063 proteins. A total of 102, 106, and 160 differentially expressed proteins (>twofolds differences) were identified from samples collected at 6, 12, and 48 h compared to sample from 0 h post harvest, accounting for 10.1, 10.5, and 15.8% of the total proteins identified, respectively. All identified proteins including the differentially expressed proteins among different post-harvest stages were subjected to bioinformatic analysis. Furthermore, seven representative proteins either up or down-regulated at different post-harvest stages were analyzed by real-time PCR. Three out of the seven proteins, the mismatched base pair and cruciform DNA recognition protein, hydrophobin-B and protein transporter, exhibited similar expression patterns as their corresponding proteins. The 260 differentially expressed proteins identified from our study laid a foundation for future studies aiming to understand the post-harvest maturation process of A. bisporus and eventually, might help in the development of breeding program to identify strains with extended shelf life.