Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains ...under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.
In this work, we rationally designed a series of crystalline and stable dioxin‐linked metallophthalocyanine covalent organic frameworks (COFs; MPc‐TFPN COF, M=Ni, Co, Zn) under the guidance of ...reticular chemistry. As a novel single‐site catalysts (SSCs), NiPc/CoPc‐TFPN COF exhibited outstanding activity and selectivity for electrocatalytic CO2 reduction (ECR; Faradaic efficiency of CO (FECO)=99.8(±1.24) %/ 96.1(±1.25) % for NiPc/CoPc‐TFPN COF). More importantly, when coupled with light, the FECO and current density (jCO) were further improved across the applied potential range (−0.6 to −1.2 V vs. RHE) compared to the dark environment for NiPc‐TFPN COF (jCO increased from 14.1 to 17.5 A g−1 at −0.9 V; FECO reached up to ca. 100 % at −0.8 to −0.9 V). Furthermore, an in‐depth mechanism study was established by density functional theory (DFT) simulation and experimental characterization. For the first time, this work explored the application of COFs as photo‐coupled electrocatalysts to improve ECR efficiency, which showed the potential of using light‐sensitive COFs in the field of electrocatalysis.
A series of stable dioxin‐linked metallophthalocyanine covalent organic frameworks (COFs) were developed and applied for photo‐coupled electrocatalytic CO2 reduction. This work represents a new insight for the future rational design of light sensitive crystalline materials for CO2 reduction.
A strategy to covalently connect crystalline covalent organic frameworks (COFs) with semiconductors to create stable organic–inorganic Z‐scheme heterojunctions for artificial photosynthesis is ...presented. A series of COF–semiconductor Z‐scheme photocatalysts combining water‐oxidation semiconductors (TiO2, Bi2WO6, and α‐Fe2O3) with CO2 reduction COFs (COF‐316/318) was synthesized and exhibited high photocatalytic CO2‐to‐CO conversion efficiencies (up to 69.67 μmol g−1 h−1), with H2O as the electron donor in the gas–solid CO2 reduction, without additional photosensitizers and sacrificial agents. This is the first report of covalently bonded COF/inorganic‐semiconductor systems utilizing the Z‐scheme applied for artificial photosynthesis. Experiments and calculations confirmed efficient semiconductor‐to‐COF electron transfer by covalent coupling, resulting in electron accumulation in the cyano/pyridine moieties of the COF for CO2 reduction and holes in the semiconductor for H2O oxidation, thus mimicking natural photosynthesis.
Here comes the sun: A strategy to covalently connect covalent organic frameworks with semiconductors to create organic–inorganic Z‐scheme heterojunctions was developed and applied for the CO2 photoreduction with H2O. This work delivers new insights for the future design of Z‐scheme organic–inorganic heterojunctions for artificial photosynthesis.
Many experiments show that the numbers of mRNA and protein are proportional to the cell volume in growing cells. However, models of stochastic gene expression often assume constant transcription rate ...per gene and constant translation rate per mRNA, which are incompatible with these experiments. Here, we construct a minimal gene expression model to fill this gap. Assuming ribosomes and RNA polymerases are limiting in gene expression, we show that the numbers of proteins and mRNAs both grow exponentially during the cell cycle and that the concentrations of all mRNAs and proteins achieve cellular homeostasis; the competition between genes for the RNA polymerases makes the transcription rate independent of the genome number. Furthermore, by extending the model to situations in which DNA (mRNA) can be saturated by RNA polymerases (ribosomes) and becomes limiting, we predict a transition from exponential to linear growth of cell volume as the protein-to-DNA ratio increases.
Summary
The plant immune system features numerous immune receptors localized on the cell surface to monitor the apoplastic space for danger signals from a broad range of plant colonizers. Recent ...discoveries shed light on the enormous complexity of molecular signals sensed by these receptors, how they are generated and removed to maintain cellular homeostasis and immunocompetence, and how they are shaped by host‐imposed evolutionary constraints. Fine‐tuning receptor sensing mechanisms at the molecular, cellular and physiological level is critical for maintaining a robust but adaptive host barrier to commensal, pathogenic, and symbiotic colonizers alike. These receptors are at the core of any plant‐colonizer interaction and hold great potential for engineering disease resistance and harnessing beneficial microbiota to keep crops healthy.
Retinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the ...detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world.
Purpose
Openness to external knowledge has recently gained popularity as a means for firms to complement and leverage internal knowledge in the pursuit of innovation outcomes. However, conflicting ...evidence exists regarding the role of openness in external knowledge acquisition. This paper aims to propose that openness to external knowledge has a nonlinear effect on innovation performance and that this nonlinear relationship is contingent on an ambidextrous knowledge search strategy.
Design/methodology/approach
Based on original large-scale survey of 246 interfirm collaborations in the high-technology industry, it is found that the impact of openness to external knowledge on innovation performance exhibits an inverted-U shape and that this relationship is affected by an ambidextrous knowledge search strategy.
Findings
The results indicate that an ambidextrous knowledge strategy that addresses the depth and breadth of external knowledge significantly influences a firm’s ability to derive benefits from increased openness to external knowledge. Empirically, the authors provide an original contribution to high-technology firms by exploring how and why an ambidextrous knowledge strategy can be a critical catalyst spurring innovation performance.
Research limitations/implications
The research scope is limited to a single industry. Further research could extend the theoretical framework to multiple industries, which may increase the likelihood of innovation theory development.
Practical implications
The results suggest that firms opening up the boundaries of their innovation activity to engage in external knowledge are able to leverage their in-house innovation to enhance their innovation performance. The authors advocate that in innovation management domains, greater emphasis is needed on how openness to external knowledge has more positive impacts not only on innovation performance but also on innovation implemented management.
Originality/value
This study is among the first to investigate the ambidextrous knowledge search effect on the external knowledge of high-technology firms. This paper contributes to the theoretical and practical literature concerning openness innovation and knowledge management by reflecting on the ambidextrous knowledge search strategy.
Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. ...However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).
The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and
bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.
Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7
CD45RA
CD45RO
CD95
effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like
and
and by upregulating genes like
, and
(
). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.
HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.
.
Yield stress materials flow if a sufficiently large shear stress is applied. Although such materials are ubiquitous and relevant for industry, there is no accepted microscopic description of how they ...yield, even in the simplest situations in which temperature is negligible and in which flow inhomogeneities such as shear bands or fractures are absent. Here we propose a scaling description of the yielding transition in amorphous solids made of soft particles at zero temperature. Our description makes a connection between the Herschel–Bulkley exponent characterizing the singularity of the flow curve near the yield stress Σ c, the extension and duration of the avalanches of plasticity observed at threshold, and the density P ( x ) of soft spots, or shear transformation zones, as a function of the stress increment x beyond which they yield. We argue that the critical exponents of the yielding transition may be expressed in terms of three independent exponents, θ, d f, and z , characterizing, respectively, the density of soft spots, the fractal dimension of the avalanches, and their duration. Our description shares some similarity with the depinning transition that occurs when an elastic manifold is driven through a random potential, but also presents some striking differences. We test our arguments in an elasto-plastic model, an automaton model similar to those used in depinning, but with a different interaction kernel, and find satisfying agreement with our predictions in both two and three dimensions.
Significance Yield stress solids flow if a sufficiently large shear stress is applied. Although such materials are ubiquitous and relevant for industry, there is no accepted microscopic description of how they yield. Here we propose a scaling description of the yielding transition that relates the flow curve, the statistics of the avalanches of plasticity observed at threshold, and the density of local zones that are about to yield. Our description shares some similarity with the depinning transition that occurs when an elastic manifold is driven through a random potential, but also presents some striking differences. Numerical simulations on a simple elasto-plastic model find good agreement with our predictions.
Summary
The S‐domain‐type receptor‐like kinase (SD‐RLK) LIPOOLIGOSACCHARIDE‐SPECIFIC REDUCED ELICITATION (LORE) from Arabidopsis thaliana is a pattern recognition receptor that senses medium‐chain ...3‐hydroxy fatty acids, such as 3‐hydroxydecanoic acid (3‐OH‐C10:0), to activate pattern‐triggered immunity. Here, we show that LORE homomerization is required to activate 3‐OH‐C10:0‐induced immune signaling.
Fluorescence lifetime imaging in Nicotiana benthamiana demonstrates that AtLORE homomerizes via the extracellular and transmembrane domains. Co‐expression of AtLORE truncations lacking the intracellular domain exerts a dominant negative effect on AtLORE signaling in both N. benthamiana and A. thaliana, highlighting that homomerization is essential for signaling.
Screening for 3‐OH‐C10:0‐induced reactive oxygen species production revealed natural variation within the Arabidopsis genus. Arabidopsis lyrata and Arabidopsis halleri do not respond to 3‐OH‐C10:0, although both possess a putative LORE ortholog. Both LORE orthologs have defective extracellular domains that bind 3‐OH‐C10:0 to a similar level as AtLORE, but lack the ability to homomerize. Thus, ligand binding is independent of LORE homomerization. Analysis of AtLORE and AlyrLORE chimera suggests that the loss of AlyrLORE homomerization is caused by several amino acid polymorphisms across the extracellular domain.
Our findings shed light on the activation mechanism of LORE and the loss of 3‐OH‐C10:0 perception within the Arabidopsis genus.