High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

Development of a double antibody sandwich ELISA method for the quantitative detection of serum C-reactive protein based on nanobody.

In this study, we successfully developed a nanobody-based double antibody sandwich ELISA kit for the detection of clinical serum C-reactive protein (CRP) by using two novel CRP specific nanobodies. The developed method exhibited a linear detection range of approximately 6-200 ng/mL, with a detection limit of 1 ng/mL. Furthermore, the method demonstrated excellent specificity, as there was no cross-reactivity with interfering substances such as total bilirubin and hemoglobin and so on. To assess reproducibility, independent measurements of the samples were conducted under experimental conditions, resulting in intra- and inter-batch coefficients of variation below 10% and a recovery rate of 93%-102%. These results indicate robust reproducibility of the method. To evaluate the performance of the developed kit, we collected 90 clinical samples for correlation analysis with commercial kits. The results showed a high correlation coefficient value (R2) of 0.98, indicating accurate concordance between the developed and commercial kits. In conclusion, our study successfully developed a nanobody-based double antibody sandwich ELISA kit to detect clinical serum CRP. The utilization of nanobodies represents a significant advancement in the field of CRP immunoassay development. The developed kit demonstrates excellent performance characteristics and holds promise for clinical applications.

Identifying mechanisms of persecutory ideation maintenance with smartphone technology: Examining threat importance, certainty, rumination, and behavior change.

Previous cross-sectional and laboratory research has identified risk factors for persecutory ideation including rumination, negative affect, and safety-seeking behaviors. Questions remain about what in-the-moment factors link general negative affect to PI as well as which maintain PI over time. In the present study, N = 219 individuals completed momentary assessments of PI as well as four factors (attributing threats as certain and important, ruminating, and changing one's behavior in response) proposed to maintain PI over time. Linear mixed effects models were used to analyze multiple time-varying relationships, including these factors predicting negative affect and vice versa, as well as factors predicting maintenance of PI over time. Linear mixed effects models were used to analyze multiple time-varying relationships, examining each PI-related factor predicting negative affect, negative affect predicting each PI-related factor, as well as each factor predicting maintenance of PI over time. All four factors were associated with increases in subsequent day self-reported severity of PI, suggesting all four increased the likelihood of maintaining or worsening next-day PI. Results of this study confirm that the proposed factors are key in maintaining a cycle by which PI and negative affect are maintained over time. These factors may represent targets for momentary interventions.

Synthesis of Chiral α-Aryl Ketones by Photoredox/Nickel-Catalyzed Enantioconvergent Acyl Cross-Coupling with Organotrifluoroborate.

Photoredox/nickel-catalyzed enantioconvergent acyl cross-coupling of carboxylic derivatives with racemic secondary organotrifluoroborate was developed for the synthesis of an enolizable chiral α-aryl ketone under mild neutral conditions. Moderate to high yields and good enantioselectivities were achieved.

Identification of the protein coding capability of coronavirus defective viral genomes by mass spectrometry.

During coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA-protein pull-down assay, six DVG-encoded proteins were identified by LC-MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies.

Left-Behind Experiences and Cyberbullying Behavior in Chinese College Students: The Mediation of Sense of Security and the Moderation of Gender.

Left-behind children seem to be more sensitive in interpersonal communication, find it more difficult to establish a stable, safe relationship with surrounding people, and have fewer positive coping styles when encountering problems, thus the aim of the present study was to explore the association between left-behind experiences and cyberbullying behavior among Chinese college students through the mediation of sense of security and the moderation of gender. A questionnaire survey comprised 553 college students with left-behind experiences and 526 college students without such experiences. The results showed that, firstly, cyberbullying behavior was significantly higher in college students with left-behind experiences than those without such experiences; secondly, left-behind experiences and cyberbullying behavior in college students was partially mediated by a sense of security; and finally, that gender moderated the mediation of the sense of security between left-behind experiences and cyberbullying behavior. This study suggests the family environment is important for individual growth and illustrates how the influence of childhood left-behind experience persists in individuals.

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

Biological characterization of coronavirus noncanonical transcripts in vitro and in vivo.

BACKGROUND: In addition to the well-known coronavirus genomes and subgenomic mRNAs, the existence of other coronavirus RNA species, which are collectively referred to as noncanonical transcripts, has been suggested; however, their biological characteristics have not yet been experimentally validated in vitro and in vivo. METHODS: To comprehensively determine the amounts, species and structures of noncanonical transcripts for bovine coronavirus in HRT-18 cells and mouse hepatitis virus A59, a mouse coronavirus, in mouse L cells and mice, nanopore direct RNA sequencing was employed. To experimentally validate the synthesis of noncanonical transcripts under regular infection, Northern blotting was performed. Both Northern blotting and nanopore direct RNA sequencing were also applied to examine the reproducibility of noncanonical transcripts. In addition, Northern blotting was also employed to determine the regulatory features of noncanonical transcripts under different infection conditions, including different cells, multiplicities of infection (MOIs) and coronavirus strains. RESULTS: In the current study, we (i) experimentally determined that coronavirus noncanonical transcripts were abundantly synthesized, (ii) classified the noncanonical transcripts into seven populations based on their structures and potential synthesis mechanisms, (iii) showed that the species and amounts of the noncanonical transcripts were reproducible during regular infection but regulated in altered infection environments, (iv) revealed that coronaviruses may employ various mechanisms to synthesize noncanonical transcripts, and (v) found that the biological characteristics of coronavirus noncanonical transcripts were similar between in vitro and in vivo conditions. CONCLUSIONS: The biological characteristics of noncanonical coronavirus transcripts were experimentally validated for the first time. The identified features of noncanonical transcripts in terms of abundance, reproducibility and variety extend the current model for coronavirus gene expression. The capability of coronaviruses to regulate the species and amounts of noncanonical transcripts may contribute to the pathogenesis of coronaviruses during infection, posing potential challenges in disease control. Thus, the biology of noncanonical transcripts both in vitro and in vivo revealed here can provide a database for biological research, contributing to the development of antiviral strategies.

Tunable 1D and 2D Polyacrylonitrile Nanosheet Superstructures.

Carbon superstructures are widely applied in energy and environment-related areas. Among them, the flower-like polyacrylonitrile (PAN)-derived carbon materials have shown great promise due to their high surface area, large pore volume, and improved mass transport. In this work, we report a versatile and straightforward method for synthesizing one-dimensional (1D) nanostructured fibers and two-dimensional (2D) nanostructured thin films based on flower-like PAN chemistry by taking advantage of the nucleation and growth behavior of PAN. The resulting nanofibers and thin films exhibited distinct morphologies with intersecting PAN nanosheets, which formed through rapid nucleation on existing PAN. We further constructed a variety of hierarchical PAN superstructures based on different templates, solvents, and concentrations. These PAN nanosheet superstructures can be readily converted to carbon superstructures. As a demonstration, the nanostructured thin film exhibited a contact angle of ∼180° after surface modification with fluoroalkyl monolayers, which is attributed to high surface roughness enabled by the nanosheet assemblies. This study offers a strategy for the synthesis of nanostructured carbon materials for various applications.

Using Smartphones to Identify Momentary Characteristics of Persecutory Ideation Associated With Functional Disability.

Objectives: Though often a feature of schizophrenia-spectrum disorders, persecutory ideation (PI) is also common in other psychiatric disorders as well as among individuals who are otherwise healthy. Emerging technologies allow for a more thorough understanding of the momentary phenomenological characteristics that determine whether PI leads to significant distress and dysfunction. This study aims to identify the momentary phenomenological features of PI associated with distress, dysfunction, and need for clinical care. Methods: A total of 231 individuals with at least moderate PI from 43 US states participated in a study involving 30 days of data collection using a smartphone data collection system combining ecological momentary assessment and passive sensors, wherein they reported on occurrence of PI as well as related appraisals, responses, and cooccurring states. Most (N = 120, 51.9%) participants reported never having received treatment for their PI, while 50 participants had received inpatient treatment (21.6%), and 60 (26.4%) had received outpatient care only. Results: Individuals with greater functional disability did not differ in PI frequency but were more likely at the moment to describe threats as important to them, to ruminate about those threats, to experience distress related to them, and to change their behavior in response. Groups based on treatment-seeking patterns largely did not differ in baseline measures or momentary phenomenology of PI as assessed by self-report or passive sensors. Conclusions: Smartphone data collection allows for granular assessment of PI-related phenomena. Functional disability is associated with differences in appraisals of and responses to PI at the moment.

Mechanical Properties of Full-Scale UHPC-Filled Steel Tube Composite Columns under Axial Load.

In the realm of civil engineering, ultra-high-performance concrete-filled steel tube composite columns (UCFSTCs) constitute a new type of building material and structure, exhibiting high compressive strength and commendable durability. Given their promising characteristics, the prospects of their application are highly promising and are worthy of further exploration. However, current research has primarily focused on scaled-down specimens, thereby limiting a broader understanding of UCFSTCs' full-scale mechanical properties in real-world scenarios. This study aimed to investigate the mechanical properties of full-scale UHPC-filled steel tube composite columns (FUCFSTCs) in practical engineering applications. With the steel tube strength, steel tube thickness, concrete strength, aspect ratio, and steel tube diameter used as design parameters and the finite element software ABAQUS as the analytical tool, a total of 21 FUCFSTCs were designed and analyzed. Through a comparison with experimental curves, the rationality of both the material constitutive model and finite element model was verified, and the maximum error was 6.54%. Furthermore, this study analyzed the influence of different design parameters on FUCFSTCs' ultimate bearing capacity, ductility coefficient, and the stress-strain relationship of their concrete. The ductility coefficient remained around 1.3, and the cross-sectional size had the greatest impact on the bearing capacity of the composite column, with a maximum increase of 145.90%. Additionally, this paper provides an in-depth analysis of FUCFSTCs' mechanical behavior, failure mode, and stress process under an axial load. In conclusion, this research proposes an axial compression limit bearing capacity formula for FUCFSTCs via statistical regression, with a maximum error of 3.04%, meeting engineering accuracy requirements. Consequently, this study lays a strong foundation for the future application of FUCFSTCs in practical engineering.

Al-Doped Core-Shell-Structured Ni@Mesoporous Silica for Highly Selective Hydrodeoxygenation of Lignin-Derived Aldehydes.

Selective deoxygenation of chemicals using non-noble metal-based catalysts poses a significant challenge toward upgrading biomass-derived oxygenates into advanced fuels and fine chemicals. Herein, we report a bifunctional core-shell catalyst (Ni@Al3-mSiO2) consisting of Ni nanoparticles closely encapsulated by the Al-doped mesoporous silica shell that achieves 100% vanillin conversion and >99% yield of 2-methoxy-4-methylphenol under 1 MPa H2 at 130 °C in water. Due to the unique mesoporous core-shell structure, no significant decrease in catalytic activity was observed after 10 recycles. Furthermore, incorporating Al atoms into the silica shell significantly increased the number of acidic sites. Density functional theory calculations reveal the reaction pathway of the vanillin hydrodeoxygenation process and uncover the intrinsic influence of the Al sites. This work not only provides an efficient and cost-effective bifunctional hydrodeoxygenation catalyst but also offers a new synthetic protocol to rationally design promising non-noble metal catalysts for biomass valorization or other widespread applications.

Environmentally stable and stretchable polymer electronics enabled by surface-tethered nanostructured molecular-level protection.

Stretchable polymer semiconductors (PSCs) are essential for soft stretchable electronics. However, their environmental stability remains a longstanding concern. Here we report a surface-tethered stretchable molecular protecting layer to realize stretchable polymer electronics that are stable in direct contact with physiological fluids, containing water, ions and biofluids. This is achieved through the covalent functionalization of fluoroalkyl chains onto a stretchable PSC film surface to form densely packed nanostructures. The nanostructured fluorinated molecular protection layer (FMPL) improves the PSC operational stability over an extended period of 82 days and maintains its protection under mechanical deformation. We attribute the ability of FMPL to block water absorption and diffusion to its hydrophobicity and high fluorination surface density. The protection effect of the FMPL (~6 nm thickness) outperforms various micrometre-thick stretchable polymer encapsulants, leading to a stable PSC charge carrier mobility of ~1 cm2 V-1 s-1 in harsh environments such as in 85-90%-humidity air for 56 days or in water or artificial sweat for 42 days (as a benchmark, the unprotected PSC mobility degraded to 10-6 cm2 V-1 s-1 in the same period). The FMPL also improved the PSC stability against photo-oxidative degradation in air. Overall, we believe that our surface tethering of the nanostructured FMPL is a promising approach to achieve highly environmentally stable and stretchable polymer electronics.

Early-stage predictors of deterioration among 3145 nonsevere SARS-CoV-2-infected people community-isolated in Wuhan, China: A combination of machine learning algorithms and competing risk survival analyses.

OBJECTIVE: To determine which early-stage variables best predicted the deterioration of coronavirus disease 2019 (COVID-19) among community-isolated people infected with severe acute respiratory syndrome coronavirus 2 and to test the performance of prediction using only inexpensive-to-measure variables. METHODS: Medical records of 3145 people isolated in two Fangcang shelter hospitals (large-scale community isolation centers) from February to March 2020 were accessed. Two complementary methods-machine learning algorithms and competing risk survival analyses-were used to test potential predictors, including age, gender, severity upon admission, symptoms (general symptoms, respiratory symptoms, and gastrointestinal symptoms), computed tomography (CT) signs, and comorbid chronic diseases. All variables were measured upon (or shortly after) admission. The outcome was deterioration versus recovery of COVID-19. RESULTS: More than a quarter of the 3145 people did not present any symptoms, while one-third ended isolation due to deterioration. Machine learning models identified moderate severity upon admission, old age, and CT ground-glass opacity as the most important predictors of deterioration. Removing CT signs did not degrade the performance of models. Competing risk models identified age ≥ 35 years, male gender, moderate severity upon admission, cough, expectoration, CT patchy opacity, CT consolidation, comorbid diabetes, and comorbid cardiovascular or cerebrovascular diseases as significant predictors of deterioration, while a stuffy or runny nose as a predictor of recovery. CONCLUSIONS: Early-stage prediction of COVID-19 deterioration can be made with inexpensive-to-measure variables, such as demographic characteristics, severity upon admission, observable symptoms, and self-reported comorbid diseases, among asymptomatic people and mildly to moderately symptomatic patients.

Prognostic Analysis of Lymphovascular Invasion in Stages I-III Colorectal Cancer: A Retrospective Study Based on Propensity Score Match.

INTRODUCTION: Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I-III colorectal cancer (CRC) by using propensity score matching (PSM). METHODS: This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram. RESULTS: A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728-0.845). The areas under the curve were 0.796 in the 3-year ROC. CONCLUSIONS: LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.

Neuromorphic sensorimotor loop embodied by monolithically integrated, low-voltage, soft e-skin.

Artificial skin that simultaneously mimics sensory feedback and mechanical properties of natural skin holds substantial promise for next-generation robotic and medical devices. However, achieving such a biomimetic system that can seamlessly integrate with the human body remains a challenge. Through rational design and engineering of material properties, device structures, and system architectures, we realized a monolithic soft prosthetic electronic skin (e-skin). It is capable of multimodal perception, neuromorphic pulse-train signal generation, and closed-loop actuation. With a trilayer, high-permittivity elastomeric dielectric, we achieved a low subthreshold swing comparable to that of polycrystalline silicon transistors, a low operation voltage, low power consumption, and medium-scale circuit integration complexity for stretchable organic devices. Our e-skin mimics the biological sensorimotor loop, whereby a solid-state synaptic transistor elicits stronger actuation when a stimulus of increasing pressure is applied.

In-Depth Ethical Analysis of the COVID-19 Vaccine Rollout for Migrant Workers in the Gulf Countries.

During the initial COVID-19 vaccine rollout, supplies were scarce, necessitating rationing. Gulf countries, hosting millions of migrant workers, prioritized nationals over migrants for vaccination. As it turned out, many migrant workers found themselves waiting behind nationals to get vaccinated for COVID-19. Here, we discuss the public health ethical concerns surrounding this approach and call for fair and inclusive vaccine allocation policies. First, we examine global justice through the lens of statism, where distributive justice applies only to sovereign state members, and cosmopolitanism, advocating equal justice distribution for all humans. We propose a cooperativist perspective, suggesting that new justice obligations can arise between people beyond national ties. In cases of mutually beneficial cooperation, such as migrant workers contributing to a nation's economy, equal concern for all parties is required. Second, the principle of reciprocity further supports this stance, as migrants significantly contribute to host countries' societies and economies. Additional ethical principles-equity, utilitarianism, solidarity, and nondiscrimination-are essentially violated when excluding non-nationals in vaccine distribution. Finally, we argue that prioritizing nationals over migrants is not only ethically indefensible, but it also fails to ensure full protection for nationals and hampers efforts to curb COVID-19 community spread.

Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation.

N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.

Circ_0001052 promotes cardiac hypertrophy via elevating Hipk3.

Cardiac hypertrophy (CH) is a crucial risk factor for sudden death. Circular RNAs (circRNAs) exert significant effects in various biological and pathological processes. Circ_0001052 is sourced from Hipk3 (homeodomain-interacting protein kinase 3) and is reported to aggravate myocardial fibrosis. The purpose of the current study was to clarify the role and mechanism of circ-Hipk3 in CH. Transverse aortic constriction (TAC) was used to create an in vivo CH model, and angiotensin II (Ang II) therapy was used to create an in vitro CH model in cardiomyocytes (CMs). It was uncovered that circ_0001052 exerted pro-hypertrophic effects in Ang II-treated CMs. Next, the circular characteristics of circ_0001052 were verified, and we identified that circ_0001052 positively regulated Hipk3. Hipk3 exerted the same functions as circ_0001052 did. It is significant to note that circ_0001052 acted as the ceRNA of Hipk3 by sponging miR-148a-3p and miR-124-3p. According to rescue assays, miR-148a-3p and miR-124-3p partially reversed the effects of circ_0001052. Further, we testified that circ_0001052 recruited Srsf1 to stabilize Hipk3. Finally, rescue assays demonstrated that circ_0001052 promoted CH via up-regulation of Hipk3. In conclusion, our work unveiled that circ_0001052 promoted hypertrophic effects through elevating Hipk3 via sponging miR-148a-3p and miR-124-3p and recruiting Srsf1.

Determination of adulteration, geographical origins, and species of food by mass spectrometry.

Food adulteration, mislabeling, and fraud, are rising global issues. Therefore, a number of precise and reliable analytical instruments and approaches have been proposed to ensure the authenticity and accurate labeling of food and food products by confirming that the constituents of foodstuffs are of the kind and quality claimed by the seller and manufacturer. Traditional techniques (e.g., genomics-based methods) are still in use; however, emerging approaches like mass spectrometry (MS)-based technologies are being actively developed to supplement or supersede current methods for authentication of a variety of food commodities and products. This review provides a critical assessment of recent advances in food authentication, including MS-based metabolomics, proteomics and other approaches.