Spatial immune landscapes of SARS-CoV-2 gastrointestinal infection: macrophages contribute to local tissue inflammation and gastrointestinal symptoms.

Background: In some patients, persistent gastrointestinal symptoms like abdominal pain, nausea, and diarrhea occur as part of long COVID-19 syndrome following acute respiratory symptoms caused by SARS-CoV-2. However, the characteristics of immune cells in the gastrointestinal tract of COVID-19 patients and their association with these symptoms remain unclear. Methodology: Data were collected from 95 COVID-19 patients. Among this cohort, 11 patients who exhibited gastrointestinal symptoms and underwent gastroscopy were selected. Using imaging mass cytometry, the gastrointestinal tissues of these patients were thoroughly analyzed to identify immune cell subgroups and investigate their spatial distribution. Results: Significant acute inflammatory responses were found in the gastrointestinal tissues, particularly in the duodenum, of COVID-19 patients. These alterations included an increase in the levels of CD68+ macrophages and CD3+CD4+ T-cells, which was more pronounced in tissues with nucleocapsid protein (NP). The amount of CD68+ macrophages positively correlates with the number of CD3+CD4+ T-cells (R = 0.783, p < 0.001), additionally, spatial neighborhood analysis uncovered decreased interactions between CD68+ macrophages and multiple immune cells were noted in NP-positive tissues. Furthermore, weighted gene coexpression network analysis was employed to extract gene signatures related to clinical features and immune responses from the RNA-seq data derived from gastrointestinal tissues from COVID-19 patients, and we validated that the MEgreen module shown positive correlation with clinical parameter (i.e., Total bilirubin, ALT, AST) and macrophages (R = 0.84, p = 0.001), but negatively correlated with CD4+ T cells (R = -0.62, p = 0.004). By contrast, the MEblue module was inversely associated with macrophages and positively related with CD4+ T cells. Gene function enrichment analyses revealed that the MEgreen module is closely associated with biological processes such as immune response activation, signal transduction, and chemotaxis regulation, indicating its role in the gastrointestinal inflammatory response. Conclusion: The findings of this study highlight the role of specific immune cell groups in the gastrointestinal inflammatory response in COVID-19 patients. Gene coexpression network analysis further emphasized the importance of the gene modules in gastrointestinal immune responses, providing potential molecular targets for the treatment of COVID-19-related gastrointestinal symptoms.

Comparison of clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with or without concurrent vas-deferens obstruction.

BACKGROUND: Microsurgical vasoepididymostomy is an effective surgical method for treating epididymal obstructive azoospermia but the surgical outcomes can be affected in some non-vasectomized epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction. This study aimed to explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction. STUDY DESIGN: Retrospective study. OBJECTIVE: To explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction, aiming to identify predictive factors for concurrent vas-deferens obstruction and evaluate the efficacy of microsurgical vasoepididymostomy in patients with epididymal obstructive azoospermia and concurrent short-segment vas-deferens obstruction. MATERIALS AND METHODS: A retrospective analysis of 225 epididymal obstructive azoospermia cases was conducted at the First Affiliated Hospital of Fujian Medical University from November 2016 to March 2023. All patients underwent a comprehensive preoperative evaluation. During surgery, the vas deferens were assessed to determine the presence and extent of obstruction. Depending on the obstruction length, either a standard microsurgical vasoepididymostomy was performed, or the obstructed segment was resected followed by microsurgical vasoepididymostomy. If the remaining length post-resection was insufficient for anastomosis, the procedure was discontinued. Data on patient clinical characteristics, operative findings, and outcomes were collected and analyzed. Logistic regression was used to identify predictive factors for concurrent vas-deferens obstruction, and comparative analysis assessed patency and pregnancy rates between patients with and without concurrent vas-deferens obstruction. RESULTS: Of the 225 patients in the study, 77 (34.22%) presented with epididymal obstructive azoospermia and concurrent vas-deferens obstruction. Logistic regression analysis revealed that "the history of epididymitis" was a significant predictive factor for epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction (odds ratio = 9.06, p < 0.001). The average length of vas deferens obstruction amenable to microsurgical vasoepididymostomy post-resection was 1.31 ± 0.54 cm (range from 0.50 to 2.50 cm). In contrast, cases unsuitable for microsurgical vasoepididymostomy presented an average obstruction length of 15.26 ± 5.79 cm (p < 0.001). The patency rates were 82.17% in epididymal obstructive azoospermia patients without concurrent vas-deferens obstruction and 74.14% in those with concurrent vas-deferens obstruction. The pregnancy rates followed a similar trend, at 34.11% and 34.48%, respectively. These differences were not statistically significant (p > 0.05 for both). However, epididymal obstructive azoospermia patients with vas-deferens obstruction exhibited a decreased likelihood of bilateral microsurgical vasoepididymostomy (p < 0.001). DISCUSSION AND CONCLUSION: Our study identifies a noticeable occurrence of concurrent vas-deferens obstruction in non-vasectomized epididymal obstructive azoospermia patients, with approximately one-third of the cases (34.22%) exhibiting vas-deferens obstruction during surgical interventions. Notably, a small fraction (6.67%) of these individuals chose not to proceed with any microsurgical vasoepididymostomy, even on one side, due to the extensive length of the obstruction. Through logistic analysis, we have demonstrated that "the history of epididymitis" is a critical predictive factor for the presence of vas-deferens obstruction, underscoring its significance in preoperative evaluations. Furthermore, our research confirms that microsurgical vasoepididymostomy is still an effective treatment for epididymal obstructive azoospermia patients with concurrent short-segment vas-deferens obstruction, achieving significant patency and favorable pregnancy rates compared to those patients without vas-deferens obstruction. These insights are pivotal for enhancing surgical strategies and improving fertility outcomes in this patient cohort.

Bio-inspired Adaptive and Responsive Protein-based Materials.

In nature, the inherent adaptability and responsiveness of proteins play a crucial role in the survival and reproduction of organisms, enabling them to adjust to ever-changing environments. A comprehensive understanding of protein structure and function is essential for unraveling the complex biological adaptive processes, providing new insights for the design of protein-based materials in advanced fields. Recently, materials derived from proteins with specific properties and functions have been engineered. These protein-based materials, distinguished by their engineered adaptability and responsiveness, range from the nanoscale to the macroscale through meticulous control of protein structure. First, the review introduces the natural adaptability and responsiveness of proteins in organisms, encompassing biological adhesion and the responses of organisms to light, magnetic fields, and temperature. Next, it discusses the achievements in protein-engineered adaptability and adhesion through protein assembly and nanotechnology, emphasizing precise control over protein bioactivity. Finally, the review briefly addresses the application of protein engineering techniques and the self-assembly capabilities of proteins to achieve responsiveness in protein-based materials to humidity, light, magnetism, temperature, and other factors. We hope this review will foster a multidimensional understanding of protein adaptability and responsiveness, thereby advancing the interdisciplinary integration of biomedical science, materials science, and biotechnology.

Molybdenum and Vanadium-Codoped Cobalt Carbonate Nanosheets Deposited on Nickel Foam as a High-Efficient Bifunctional Catalyst for Overall Alkaline Water Splitting.

To address issues of global energy sustainability, it is essential to develop highly efficient bifunctional transition metal-based electrocatalysts to accelerate the kinetics of both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, the heterogeneous molybdenum and vanadium codoped cobalt carbonate nanosheets loaded on nickel foam (VMoCoCOx@NF) are fabricated by facile hydrothermal deposition. Firstly, the mole ratio of V/Mo/Co in the composite is optimized by response surface methodology (RSM). When the optimized composite serves as a bifunctional catalyst, the water-splitting current density achieves 10 mA cm-2 and 100 mA cm-2 at cell voltages of 1.54 V and 1.61 V in a 1.0 M KOH electrolyte with robust stability. Furthermore, characterization is carried out using field emission scanning electron microscopy-energy dispersive spectroscopy (FESEM-EDS), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Density functional theory (DFT) calculations reveal that the fabricated VMoCoCOx@NF catalyst synergistically decreases the Gibbs free energy of hydrogen and oxygen-containing intermediates, thus accelerating OER/HER catalytic kinetics. Benefiting from the concerted advantages of porous NF substrates and clustered VMoCoCOx nanosheets, the fabricated catalyst exhibits superior electrocatalytic performance. This work presents a novel approach to developing transition metal catalysts for overall water splitting.

BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

Identification of the Ilex macrocarpa anthracnose pathogen and the antifungal potential of the cell-free supernatant of Bacillus velezensis against Colletotrichum fioriniae.

Introduction: Anthracnose is a significant fungal disease that affects tree growth and development, with Colletotrichum spp. exhibiting host non-specificity and targeting various organs, making disease control challenging. Methods: This study aimed to identify the pathogenic species causing anthracnose in Ilex macrocarpa in Nanchong, Sichuan Province, and screen effective fungicides, particularly biological ones. The pathogen was identified as Colletotrichum fioriniae through morphological observation, pathogenicity assays, and molecular biological methods. Three biological and five chemical fungicides were evaluated for their effects on the mycelial growth and spore germination rate of the pathogen. Results: The results indicated that prochloraz was the most effective chemical fungicide, while the cell-free supernatant (CFS) of Bacillus velezensis had the most significant inhibitory effect among the biological fungicides. Transcriptome analysis revealed that the CFS of B. velezensis significantly reduced the expression of genes associated with ribosomes, genetic information processing, membrane lipid metabolism, and sphingolipid biosynthesis in C. fioriniae. Additionally, the glutathione pathway's expression of various genes, including key genes such as GST, GFA, Grx, TRR, and POD, was induced. Furthermore, the expression of 17 MFS transporters and 9 ABC transporters was increased. Autophagy-related ATGs were also affected by the B. velezensis CFS. Discussion: These findings suggest that the B. velezensis CFS may inhibit C. fioriniae through interference with ribosomes, genetic information processing, cell membrane metabolism, and energy metabolism. These results provide potential target genes for the B. velezensis CFS and insights into the antifungal mechanism by which B. velezensis inhibits C. fioriniae.

Biogenic derived nanoparticles modulate mitochondrial function in cardiomyocytes.

Preservation of mitochondrial functionality is essential for heart hemostasis and cardiovascular diseases treatment. However, the current nanomedicines including liposomes, polymers and inorganic nanomaterials are severely hindered by poor stability, high manufacturing costs and potential biotoxicity. In this research, we present novel polyphenolic nanoparticles (NPs) derived from naturally occurring pomegranate peel (PP, labelled as PPP NPs), which exhibit potent antioxidative and anti-inflammatory properties, serving as a modulator of mitochondrial function. PPP NPs have been identified to improve survival rates in models of mitochondrial depletion through enhancement of cardiomyocyte proliferation and the reduction of DNA damage. Moreover, PPP NPs can effectively inhibit the production of reactive oxygen species and inflammatory mediators in lipopolysaccharide (LPS)-induced mitochondrial damage. Utilizing human engineered heart tissue and mice models, PPP NPs were found to significantly improve contractile function and alleviate inflammation activities after LPS treatment. Mechanically, PPP NPs regulated inflammatory responses via a m6A dependent manner, as determined using RNA-seq and MeRIP-seq analyses. Collectively, these insights underscore the potential of PPP NPs as a novel therapeutic approach for mitochondrial dysfunction.

Inferring Novel Cells in Single-Cell RNA-Sequencing Data.

Single-cell RNA-sequencing (scRNA-seq) is a powerful technology that allows researchers to study gene expression heterogeneity within a tissue or cell population. One of the major advantages of scRNA-seq is that it allows researchers to identify and characterize novel cell types or subpopulations within a tissue that may be missed by traditional bulk RNA-sequencing methods. Although many existing methods have been developed to recognize known cell types, inferring novel cells may still be challenging in routine scRNA-seq analysis. Here we describe three lines of methods for inferring novel cells: unsupervised and outlier-detection-based methods, supervised and semi-supervised methods, and copy number variation (CNV)-based methods, as well as the corresponding situations that each method applies. We also provide implementation code and example usages to illustrate the available methods.

CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages.

AIMS: Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. METHODS AND RESULTS: Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE-/- mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions. CONCLUSIONS: Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.

Discovery of Potent and Selective c-Met Degraders for Hepatocellular Carcinoma Treatment.

Targeting c-Met is a clinical trend for the precise treatment of HCC, but the potential issue of acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease treatment and overcoming drug resistance due to its special mechanism of action. In this study, we designed and synthesized two series of novel c-Met degraders and conducted a systematic biological evaluation of the optimal compound H11. H11 exhibited good c-Met degradation activity and anti-HCC activity. Importantly, H11 also demonstrated more potent inhibitory activity against Ba/F3-TPR-MET-D1228N and Ba/F3-TPR-MET-Y1230H cell lines than did tepotinib. In summary, H11 displayed potent anti-HCC activity as a degrader and may overcome resistance to type Ib inhibitors, making it a new therapeutic strategy for HCC with MET alterations.

Identification and molecular characterization of Wanghe virus: A novel member of the Solinviviridae family from mosquitoes, China.

Arboviruses have always been a significant public health concern. Metagenomic surveillance has expanded the number of novel, often unclassified arboviruses, especially mosquito-borne and mosquito-specific viruses. This report presents the first description of a novel single-stranded RNA virus, Wanghe virus, identified from mosquitoes that were collected in Shandong Province in 2022. In this study, a total of 4,795 mosquitoes were collected and then divided into 105 pools according to location and species. QRT-PCR and nested PCR were performed to confirm the presence of Wanghe virus, and its genomic features and phylogenetic relationships were further analyzed. Our results revealed that Wanghe virus was detected in 9 out of the 105 mosquito pools, resulting in a minimum infection rate (MIR) of 0.19 % (9/4,795). One complete genome sequence and three viral partial sequences were obtained from the Wanghe virus-positive pools. Pairwise distance analysis indicated that these amplified sequences shared high nucleotide identity. Phylogenetic analysis demonstrated that Wanghe virus is most closely related to Guiyang Solinvi-like virus 3, which belongs to Solinviviridae. Further analyses indicated that Wanghe virus is a new, unclassified member of Solinviviridae.

Regulation and microbial response mechanism of nitric oxide to copper-containing swine wastewater treated by Pistia stratiotes.

As a signaling molecule, Nitric oxide (NO) has been widely used in abiotic stress mitigation studies.Pistia stratiotes showed a good synergistic removal effect on heavy metals, nitrogen and phosphorus, but the high concentration of copper(Cu) in swine wastewater inhibited the comprehensive removal ability of Pistia stratiotes. At present, it is not clear how the addition of NO regulates the stress resistance mechanism of Pistia stratiotes to copper in swine wastewater, and the microbial response mechanism accompanying this process is not yet clear. Therefore, in the concentration range of 0.31∼4 mg·L-1Cu2+ and NO concentration of 0,0.05 and 0.1 mg L-1, the removal effect of Pistia stratiotes on copper from swine wastewater was studied. The results showed as follows: The treatment of non-available copper in groups M and H increased by 10.67% and 22.31%, respectively, compared with that in group L. The critical point of inhibiting effect of NO on growth rate was 2.03 mg·L-1Cu. By measuring three-dimensional fluorescence spectrum, combined with parallel factor analysis and principal component analysis, it was confirmed that exogenous addition of NO affected the humification degree of dissolved organic matter(DOM) and promoted the chelation of organic matter with copper. With the increase of Cu concentration, the Reyranella and Prosthecobacter with certain copper resistance gradually gained advantages. Redundancy analysis(RDA) showed that Emiticicia had a strong correlation with the removal rates of ammonia nitrogen, total phosphorus and copper in swine wastewater, while hgcI_clade had a strong correlation with the removal rates of total nitrogen. In conclusion, controlling the dosage of NO can effectively improve the tolerance and removal effect of Pistia stratiotes on copper in swine wastewater, which is of great significance for promoting the treatment and resource transformation of swine wastewater.

Aberrant baseline brain activity and disrupted functional connectivity in patients with vascular cognitive impairment due to cerebral small vessel disease.

Objective: This study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI). Materials and methods: A total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7 ± 6.9 years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6 ± 5.5 years; male, 58.5%). Additionally, 53 age-, gender-, and education-matched healthy subjects were recruited as normal controls (NC) (mean age, 54.9 ± 7.9 years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden. Results: VCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients. Conclusion: Abnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI.

Tris(pentafluoro)phenylborane electrolyte additive regulates the highly stable and uniform CEI membrane components to improve the high-voltage behaviors of NCM811 lithium-ion batteries.

Broadening the charging and discharging voltage window of high nickel cathode material NCM811 is the most expected method to improve the high specific energy density of batteries currently, yet the cathode-electrolyte interface (CEI) formed by the oxidized and decomposed products of carbonate-based electrolyte under high voltage are always so unsatisfied. Therefore, a voltage-stabilizer, TPFPB (Tris(pentafluoro)phenylborane), added into baseline electrolyte (1 M LiPF6 in EC:EMC:DMC=1:1:1 vol%) to promote the electrochemical performance of the battery at 4.5 V. The results interpret that the TPFPB-contained NCM811-Li half-cells exhibit high specific capacity (167.10 mAh/g), excellent capacity retention rate (CRR) (75.37 %), and high rate performance (173.3 mAh/g at 5C) during 4.5 V. Meanwhile, through the analysis of the physical characterization techniques. the B- and F-rich interfacial layer, named as CEI film, existing at the interface between the cathode and the electrolyte, produced under 4.5 V, is superior, resulting in impeding the structural collapse of the cathode material and the continued dissolution of transition metal ions (TMn+) from the cathode material, as well as, ameliorate the electrochemical polarization of the battery, ultimately, it can stabilize the electrochemical performance of the battery under high voltage. Therein, the present work elucidate a new and substantial approach to enhance the high-voltage performances of rich-Ni cathode materials.

Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband's spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Estimating the contribution of setting-specific contacts to SARS-CoV-2 transmission using digital contact tracing data.

While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%-12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%-5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.

2D Reconfigurable Memory Device Enabled by Defect Engineering for Multifunctional Neuromorphic Computing.

In this era of artificial intelligence and Internet of Things, emerging new computing paradigms such as in-sensor and in-memory computing call for both structurally simple and multifunctional memory devices. Although emerging two-dimensional (2D) memory devices provide promising solutions, the most reported devices either suffer from single functionalities or structural complexity. Here, this work reports a reconfigurable memory device (RMD) based on MoS2/CuInP2S6 heterostructure, which integrates the defect engineering-enabled interlayer defects and the ferroelectric polarization in CuInP2S6, to realize a simplified structure device for all-in-one sensing, memory and computing. The plasma treatment-induced defect engineering of the CuInP2S6 nanosheet effectively increases the interlayer defect density, which significantly enhances the charge-trapping ability in synergy with ferroelectric properties. The reported device not only can serve as a non-volatile electronic memory device, but also can be reconfigured into optoelectronic memory mode or synaptic mode after controlling the ferroelectric polarization states in CuInP2S6. When operated in optoelectronic memory mode, the all-in-one RMD could diagnose ophthalmic disease by segmenting vasculature within biological retinas. On the other hand, operating as an optoelectronic synapse, this work showcases in-sensor reservoir computing for gesture recognition with high energy efficiency.

Ion-Exchanging Lead-Free Perovskite with Tunable Emission Wavelengths for Chemical and Fluorescent Double-Modal Anticounterfeiting Application.

Novel and covert fluorescence is quite desirable for fluorescent anticounterfeiting application. Here, Cs2InCl5·H2O/Sb and Cs2NaInCl6/Sb with high photoluminescence quantum yields (PLQYs) of 99.61 and 99.9%, respectively, were achieved. Considering the excellent optical performances together with the high similarity of the two crystal structures, we tried to realize the crystal structure transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb by an ion-exchange method. It was well done by just adding the NaCl precursor with different concentrations in the Cs2InCl5·H2O/Sb product. Interestingly, a gradual color change from yellow to orange, warm white, white, cool white, and blue was achieved in the process of crystal structure transition. The energy-transfer dynamic models of Cs2InCl5·H2O/Sb, the white product, and Cs2NaInCl6/Sb were identified. The chemical reaction and UV fluorescence properties made it possible for application in chemical and fluorescent double-modal anticounterfeiting and highly decreased the possibility of being cracked and copied. Especially, when salt for daily cooking was used to replace NaCl, a similar phenomenon happened as that of the 99.9% NaCl precursor, which made it easy to be applicated. The combination of chemical and optical verifications provides two levels of security and unbreakable encryption. The results demonstrate that the transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb is highly promising in fluorescent anticounterfeiting application.

Optimal harvest period and quality control markers of cultivated Flos Chrysanthemi Indici using untargeted/targeted metabolomics, chemometric analysis and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating. AIM OF THE STUDY: To explore quality control markers of FCI based on the optimal harvest period. MATERIALS AND METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI. RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis. CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.