Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Pyruvate kinase M2 sustains cardiac mitochondrial quality surveillance in septic cardiomyopathy by regulating prohibitin 2 abundance via S91 phosphorylation.

The endogenous mitochondrial quality control (MQC) system serves to protect mitochondria against cellular stressors. Although mitochondrial dysfunction contributes to cardiac damage during many pathological conditions, the regulatory signals influencing MQC disruption during septic cardiomyopathy (SC) remain unclear. This study aimed to investigate the involvement of pyruvate kinase M2 (PKM2) and prohibitin 2 (PHB2) interaction followed by MQC impairment in the pathogenesis of SC. We utilized LPS-induced SC models in PKM2 transgenic (PKM2TG) mice, PHB2S91D-knockin mice, and PKM2-overexpressing HL-1 cardiomyocytes. After LPS-induced SC, cardiac PKM2 expression was significantly downregulated in wild-type mice, whereas PKM2 overexpression in vivo sustained heart function, suppressed myocardial inflammation, and attenuated cardiomyocyte death. PKM2 overexpression relieved sepsis-related mitochondrial damage via MQC normalization, evidenced by balanced mitochondrial fission/fusion, activated mitophagy, restored mitochondrial biogenesis, and inhibited mitochondrial unfolded protein response. Docking simulations, co-IP, and domain deletion mutant protein transfection experiments showed that PKM2 phosphorylates PHB2 at Ser91, preventing LPS-mediated PHB2 degradation. Additionally, the A domain of PKM2 and the PHB domain of PHB2 are required for PKM2-PHB2 binding and PHB2 phosphorylation. After LPS exposure, expression of a phosphorylation-defective PHB2S91A mutant negated the protective effects of PKM2 overexpression. Moreover, knockin mice expressing a phosphorylation-mimetic PHB2S91D mutant showed improved heart function, reduced inflammation, and preserved mitochondrial function following sepsis induction. Abundant PKM2 expression is a prerequisite to sustain PKM2-PHB2 interaction which is a key element for preservation of PHB2 phosphorylation and MQC, presenting novel interventive targets for the treatment of septic cardiomyopathy.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

T-cell receptor sequencing reveals hepatocellular carcinoma immune characteristics according to Barcelona Clinic liver cancer stages within liver tissue and peripheral blood.

Analysis of T-cell receptor (TCR) repertoires in different stages of hepatocellular carcinoma (HCC) might help to elucidate its pathogenesis and progression. This study aimed to investigate TCR profiles in liver biopsies and peripheral blood mononuclear cells (PBMCs) in different Barcelona Clinic liver cancer (BCLC) stages of HCC. Ten patients in early stage (BCLC_A), 10 patients in middle stage (BCLC_B), and 10 patients in late stage (BCLC_C) cancer were prospectively enrolled. The liver tumor tissues, adjacent tissues, and PBMCs of each patient were collected and examined by TCR ß sequencing. Based on the ImMunoGeneTics (IMGT) database, we aligned the V, D, J, and C gene segments and identified the frequency of CDR3 sequences and amino acids sequence. Diversity of TCR in PBMCs was higher than in both tumor tissues and adjacent tissues, regardless of BCLC stage and postoperative recurrence. TCR clonality was increased in T cells from peripheral blood in advanced HCC, compared with the early and middle stages. No statistical differences were observed between different BCLC stages, either in tumors or adjacent tissues. TCR clonality revealed no significant difference between recurrent tumor and non-recurrent tumor, therefore PBMCs was better to be representative of TCR characteristics in different stages of HCC compared to tumor tissues. Clonal expansion of T cells was associated with low risk of recurrence in HCC patients.

Analysis of the intestinal microbiota and profiles of blood amino acids and acylcarnitines in neonates with hyperbilirubinemia.

OBJECTIVE: This study aimed to discuss the distinctive features of the intestinal microbiota in neonates with hyperbilirubinemia and to comprehensively analyse the composition of the intestinal microbiota as well as the levels of free amino acids and acylcarnitines in the peripheral blood of neonates experiencing hyperbilirubinemia. RESULTS: At the phylum level, Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Chloroflexi were the five predominant microbial groups identified in both the hyperbilirubinemia and control groups. Alpha diversity analysis, encompassing seven indices, showed no statistically significant differences between the two groups. However, Beta diversity analysis revealed a significant difference in intestinal microbiota structure between the groups. Linear discriminant analysis effect size (LEfSe) indicated a significant reduction in the abundance of Gammaproteobacteria and Enterobacteriaceae within the hyperbilirubinemia group compared to that in the control group. The heatmap revealed that the control group exhibited increased abundances of Escherichia and Bifidobacterium, while the hyperbilirubinemia group exhibited increased levels of Enterococcus and Streptococcus. Regarding blood amino acids and acylcarnitines, there were greater concentrations of citrulline (Cit), arginine (Arg), ornithine (Orn), and valine (Val) in the hyperbilirubinemia group than in the control group. The hyperbilirubinemia group also exhibited significant increases in medium-chain fatty acids (C6, C8), long-chain fatty acids (C18), and free carnitine (C0). CONCLUSION: By comparing neonates with hyperbilirubinemia to those without, a significant disparity in the community structure of the intestinal microbiota was observed. The intestinal microbiota plays a crucial role in the bilirubin metabolism process. The intestinal microbiota of neonates with hyperbilirubinemia exhibited a certain degree of dysbiosis. The abundances of Bacteroides and Bifidobacterium were negatively correlated with the bilirubin concentration. Therefore, the fact that neonates with hyperbilirubinemia exhibit some variations in blood amino acid and acylcarnitine levels may provide, to a certain degree, a theoretical basis for clinical treatment and diagnosis.

Deregulation of immune response contributing to fulminant hepatitis in HEV infected pregnant women.

Hepatitis E virus (HEV) infection in pregnant women is associated with a wide spectrum of adverse consequences for both mother and fetus. The high mortality in this population appears to be associated with hormonal changes and consequent immunological changes. This study conducted an analysis of immune responses in pregnant women infected with HEV manifesting varying severity. Data mining analysis of the GSE79197 was utilized to examine differentially biological functions in pregnant women with HEV infection (P-HEV) versus without HEV infection (P-nHEV), P-HEV progressing to ALF (P-ALF) versus P-HEV, and P-HEV versus non-pregnant women with HEV infection (nP-HEV). We found cellular response to interleukin and immune response-regulating signalings were activated in P-HEV compared with P-nHEV. However, there was a significant decrease of immune responses, such as T cell activation, leukocyte cell-cell adhesion, regulation of lymphocyte activation, and immune response-regulating signaling pathway in P-ALF patient than P-HEV patient. Compared with nP-HEV, MHC protein complex binding function was inhibited in P-HEV. Further microRNA enrichment analysis showed that MAPK and T cell receptor signaling pathways were inhibited in P-HEV compared with nP-HEV. In summary, immune responses were activated during HEV infection while being suppressed when developing ALF during pregnancy, heightening the importance of immune mediation in the pathogenesis of severe outcome in HEV infected pregnant women.

Autophagy-related protein 5 (ATG5) interacts with bone marrow stromal cell antigen 2 (BST2) to stimulate HBV replication through antagonizing the antiviral activity of BST2.

Hepatitis B virus (HBV) infection is a major global health burden with 820 000 deaths per year. In our previous study, we found that the knockdown of autophagy-related protein 5 (ATG5) significantly upregulated the interferon-stimulated genes (ISGs) expression to exert the anti-HCV effect. However, the regulation of ATG5 on HBV replication and its underlying mechanism remains unclear. In this study, we screened the altered expression of type I interferon (IFN-I) pathway genes using RT² Profiler™ PCR array following ATG5 knock-down and we found the bone marrow stromal cell antigen 2 (BST2) expression was significantly increased. We then verified the upregulation of BST2 by ATG5 knockdown using RT-qPCR and found that the knockdown of ATG5 activated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. ATG5 knockdown or BST2 overexpression decreased Hepatitis B core Antigen (HBcAg) protein, HBV DNA levels in cells and supernatants of HepAD38 and HBV-infected NTCP-HepG2. Knockdown of BST2 abrogated the anti-HBV effect of ATG5 knockdown. Furthermore, we found that ATG5 interacted with BST2, and further formed a ternary complex together with HBV-X (HBx). In conclusion, our finding indicates that ATG5 promotes HBV replication through decreasing BST2 expression and interacting with it directly to antagonize its antiviral function.

Film-Forming Capability and Antibacterial Activity of Surface-Deacetylated Chitin Nanocrystals: Role of Degree of Deacetylation.

Developing sustainable food-active packaging materials is a major issue in food preservation applications. Chitin nanocrystals (ChNCs) are regarded as unique bioderived nanomaterials due to their inherent nitrogen moiety. By tuning the chemical functionality of this nanomaterial, it is possible to affect its properties, such as film-forming capability and antibacterial activity. In this work, surface-deacetylated chitin nanocrystals (D-ChNCs) with different degrees of deacetylation (DDs) were prepared by partial deacetylation of native chitin and subsequent acid hydrolysis, and their film-forming capability and antibacterial activity were studied systematically. The D-ChNCs showed favorable film-forming ability and antibacterial activity, which are closely related to their DD. With the increase in DD (from 5.7% to 45.4%), the formed transparent films based on ChNCs showed gradually increased elongation at break (from 0.5% to 2.5%) and water contact angle (from 25.5° to 87.0°), but decreased break strength (from 3.13 to 0.89 MPa), Young's modulus (from 0.84 to 0.24 MPa), and water vapor permeability (from 4.7 × 10-10 to 4.1 × 10-10g/m s Pa). Moreover, the antibacterial activity of the D-ChNCs against E. coli and S. aureus also increased with the increase of DD. This study also found that the depolarization and potential dissipation of the bacterial cell membrane induced by the contact between amino-rich D-ChNCs and bacteria through electrostatic attraction are the possible mechanisms causing bacterial cell death. This study provides a basis for understanding the effects of DD on the film-forming capability and antibacterial activity of ChNCs, which is conducive to the design of novel active packaging films based on ChNCs.

Suppression of female fertility in Aedes aegypti with a CRISPR-targeted male-sterile mutation.

Aedes aegypti spread devastating viruses such as dengue, which causes disease among 100 to 400 million people annually. A potential approach to control mosquito disease vectors is the sterile insect technique (SIT). The strategy involves repeated release of large numbers of sterile males, which reduces insect populations because the sterile males mate and thereby suppress the fertility of females that would otherwise mate with fertile males. While SIT has been successful in suppressing certain agricultural pests, it has been less effective in depressing populations of Ae. aegypti This limitation is in part because of the fitness effects resulting from mutagenizing the mosquitoes nonspecifically. Here, we introduced and characterized the impact on female fertility of an Ae. aegypti mutation that disrupts a gene that is specifically expressed in testes. We used CRISPR/Cas9 to generate a null mutation in the Ae. aegypti ß2-tubulin (B2t) gene, which eliminates male fertility. When we allowed wild-type females to first mate with B2t mutant males, most of the females did not produce progeny even after being subsequently exposed to wild-type males. We also introduced B2t mutant and wild-type males simultaneously with wild-type females and found that a larger number of B2t mutant males relative to the wild-type males was effective in significantly suppressing female fertility. These results raise the possibility of employing B2t sterile males to improve the efficacy of SIT in suppressing populations of Ae. aegypti through repeated releases and thereby reduce the transmission of viruses by these invasive mosquitoes.

Internal representations of the canonical real-world distance of objects.

In the real world, every object has its canonical distance from observers. For example, airplanes are usually far away from us, whereas eyeglasses are close to us. Do we have an internal representation of the canonical real-world distance of objects in our cognitive system? If we do, does the canonical distance influence the perceived size of an object? Here, we conducted two experiments to address these questions. In Experiment 1, we first asked participants to rate the canonical distance of objects. Participants gave consistent ratings to each object. Then, pairs of object images were presented one by one in a trial, and participants were asked to rate the distance of the second object (i.e., a priming paradigm). We found that the rating of the perceived distance of the target object was modulated by the canonical real-world distance of the prime. In Experiment 2, participants were asked to judge the perceived size of canonically near or far objects that were presented at the converging end (i.e., far location) or the opening end (i.e., near location) of a background image with converging lines. We found that regardless of the presentation location, participants perceived the canonically near object as smaller than the canonically far object even though their retinal and real-world sizes were matched. In all, our results suggest that we have an internal representation of the canonical real-world distance of objects, which affects the perceived distance of subsequent objects and the perceived size of the objects themselves.

Rhizosphere shapes the associations between protistan predators and bacteria within microbiomes through the deterministic selection on bacterial communities.

The assembly of bacterial communities in the rhizosphere is well-documented and plays a crucial role in supporting plant performance. However, we have limited knowledge of how plant rhizosphere determines the assembly of protistan predators and whether the potential associations between protistan predators and bacterial communities shift due to rhizosphere selection. To address this, we examined bacterial and protistan taxa from 443 agricultural soil samples including bulk and rhizosphere soils. Our results presented distinct patterns of bacteria and protistan predators in rhizosphere microbiome assembly. Community assembly of protistan predators was determined by a stochastic process in the rhizosphere and the diversity of protistan predators was reduced in the rhizosphere compared to bulk soils, these may be attributed to the indirect impacts from the altered bacterial communities that showed deterministic process assembly in the rhizosphere. Interestingly, we observed that the plant rhizosphere facilitates more close interrelationships between protistan predators and bacterial communities, which might promote a healthy rhizosphere microbial community for plant growth. Overall, our findings indicate that the potential predator-prey relationships within the microbiome, mediated by plant rhizosphere, might contribute to plant performance in agricultural ecosystems.

CePP2C19 confers tolerance to drought by regulating the ABA sensitivity in Cyperus esculentus.

BACKGROUND: Tiger nut (Cyperus esculentus) is widely known as an additional source of food, oil and feed worldwide. The agricultural production of tiger nut has been greatly hindered by drought stress, reducing both yield and quality. Protein phosphatase 2 C (PP2Cs) plays an important role in plant responses to drought stress however, the molecular mechanism of PP2Cs in tiger nuts still unclear. RESULTS: In this study, we identified a putative group A PP2C-encoding gene (CePP2C19) from tiger nut using transcriptome analysis, which is highly induced by drought stress. The transient expression assay suggested that CePP2C19 was localized to nucleus. Furthermore, the interaction between CePP2C19 and CePYR1, a coreceptor for ABA signaling, was first detected using a yeast two-hybrid assay and then verified using a bimolecular fluorescence complementation (BiFC) analysis. In addition, the transgenic Arabidopsis lines overexpressing CePP2C19 exhibited extreme tolerance to ABA and mannitol stresses during seed germination and root growth. At the mature stage, overexpression of CePP2C19 resulted in a higher tolerance to drought stress in transgenic Arabidopsis, as confirmed by a visible phenotype and several physiological parameters. Noticeably, the silencing of CePP2C19 by virus-induced gene silencing (VIGS) showed obvious reduction in drought tolerance in tiger nut plants. CONCLUSIONS: The CePP2C19 emerges as a pivotal gene involved in the ABA signaling pathway, which likely reduce ABA sensitivity and thus enhances drought tolerance in Cyperus esculentus.

Hepatitis E virus infection activates NOD-like receptor family pyrin domain-containing 3 inflammasome antagonizing interferon response but therapeutically targetable.

BACKGROUND AND AIMS: HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting. APPROACH AND RESULTS: We measured IL-1ß secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL-1ß production. A profound increase of IL-1ß secretion was further observed in HEV-infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF-κB signaling activation as a key upstream event of HEV-induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross-interference. CONCLUSIONS: HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.

Standardizing image assessment in optical diffraction tomography.

Optical diffraction tomography (ODT) has gradually become a popular label-free imaging technique that offers diffraction-limited resolution by mapping an object's three-dimensional (3D) refractive index (RI) distribution. However, there is a lack of comprehensive quantitative image assessment metrics in ODT for studying how various experimental conditions influence image quality, and subsequently optimizing the experimental conditions. In this Letter, we propose to standardize the image assessment in ODT by proposing a set of metrics, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and structural distinguishability (SD). To test the feasibility of the metrics, we performed experiments on angle-scanning ODT by varying the number of illumination angles, RI contrast of samples, sample feature sizes, and sample types (e.g., standard polystyrene beads and 3D printed structures) and evaluated the RI tomograms with SNR, CNR, and SD. We further quantitatively studied how image quality can be improved, and tested the image assessment metrics on subcellular structures of living cells. We envision the proposed image assessment metrics may greatly benefit end-users for assessing the RI tomograms, as well as experimentalists for optimizing ODT instruments.

SAR Image Simulations of Ocean Scenes Based on the Improved Facet TSM.

The facet-based two scale model (FTSM) is widely applied in SAR image simulations of the anisotropic ocean surface. However, this model is sensitive to the cutoff parameter and facet size, and the choice of these two parameters is arbitrary. We propose to make an approximation of the cutoff invariant two scale model (CITSM) to improve the simulation efficiency while remaining the robustness to cutoff wavenumbers. Meanwhile, the robustness to facet sizes is obtained by correcting the geometrical optics (GO) solution, taking into account the slope probability density function (PDF) correction induced by the spectrum within an individual facet. The new FTSM, with less dependence on cutoff parameters and facet sizes, is proved to be reasonable in the comparisons with advanced analytical models and experimental data. Finally, SAR images of the ocean surface and ship wakes with various facet sizes are provided to prove the operability and applicability of our model.

Genome-Wide Identification of MADS-Box Family Genes in Safflower (Carthamus tinctorius L.) and Functional Analysis of CtMADS24 during Flowering.

Safflower is an important economic crop with a plethora of industrial and medicinal applications around the world. The bioactive components of safflower petals are known to have pharmacological activity that promotes blood circulation and reduces blood stasis. However, fine-tuning the genetic mechanism of flower development in safflower is still required. In this study, we report the genome-wide identification of MADS-box transcription factors in safflower and the functional characterization of a putative CtMADS24 during vegetative and reproductive growth. In total, 77 members of MADS-box-encoding genes were identified from the safflower genome. The phylogenetic analysis divided CtMADS genes into two types and 15 subfamilies. Similarly, bioinformatic analysis, such as of conserved protein motifs, gene structures, and cis-regulatory elements, also revealed structural conservation of MADS-box genes in safflower. Furthermore, the differential expression pattern of CtMADS genes by RNA-seq data indicated that type II genes might play important regulatory roles in floral development. Similarly, the qRT-PCR analysis also revealed the transcript abundance of 12 CtMADS genes exhibiting tissue-specific expression in different flower organs. The nucleus-localized CtMADS24 of the AP1 subfamily was validated by transient transformation in tobacco using GFP translational fusion. Moreover, CtMADS24-overexpressed transgenic Arabidopsis exhibited early flowering and an abnormal phenotype, suggesting that CtMADS24 mediated the expression of genes involved in floral organ development. Taken together, these findings provide valuable information on the regulatory role of CtMADS24 during flower development in safflower and for the selection of important genes for future molecular breeding programs.

Black garlic melanoidins inhibit in vitro α-amylase and α-glucosidase activity: the role of high-molecular-weight fluorescent compounds.

BACKGROUND: Black garlic (Allium sativum L.) melanoidins (MLDs) are produced by Maillard reaction under high temperature and high humidity, and has a variety of biological activities. The aim of this study was to analyze the structural characteristics and investigate α-amylase and α-glucosidase in vitro inhibitory activity of black garlic MLDs. RESULTS: Spectroscopic and chemical analysis revealed that black garlic MLDs were heterogeneous macromolecular polymers with a skeletal structure similar to sugar chains. Molecular weight distribution and 3DEEM fluorescence showed that black garlic MLDs were composed of high-molecular-weight colorants with strong fluorescence properties. The polarity of black garlic MLDs was related to the fluorescence groups. The results of physicochemical properties proved that the polarity difference of black garlic MLDs was related to the elemental composition, resulting in differences in fluorescence, thermodynamic and apparent characteristics. MLDs with higher levels of fluorescent intensity (BG20 and BG40) had stronger inhibitory effects on α-amylase and α-glucosidase than BGW, and hydrolysis of fluorescent groups attenuated the inhibitory activity. The median inhibitory concentration (IC50 ) of black garlic MLDs against enzymes was positively correlated with the concentration, and the kinetic results detected non-competitive and mixed types of inhibition. CONCLUSION: High-molecular-weight fluorescent components of black garlic MLDs played a crucial role in the inhibitory activities of α-amylase and α-glucosidase, and the inhibitory ability was positively correlated with concentration. Black garlic MLDs had the potential to block postprandial glucose rise. © 2023 Society of Chemical Industry.

Comparing trained and untrained probabilistic ensemble forecasts of COVID-19 cases and deaths in the United States.

The U.S. COVID-19 Forecast Hub aggregates forecasts of the short-term burden of COVID-19 in the United States from many contributing teams. We study methods for building an ensemble that combines forecasts from these teams. These experiments have informed the ensemble methods used by the Hub. To be most useful to policymakers, ensemble forecasts must have stable performance in the presence of two key characteristics of the component forecasts: (1) occasional misalignment with the reported data, and (2) instability in the relative performance of component forecasters over time. Our results indicate that in the presence of these challenges, an untrained and robust approach to ensembling using an equally weighted median of all component forecasts is a good choice to support public health decision-makers. In settings where some contributing forecasters have a stable record of good performance, trained ensembles that give those forecasters higher weight can also be helpful.

Efficient and Selective CO2 Reduction to Formate on Pd-Doped Pb3 (CO3 )2 (OH)2 : Dynamic Catalyst Reconstruction and Accelerated CO2 Protonation.

Exploring catalyst reconstruction under the electrochemical condition is critical to understanding the catalyst structure-activity relationship as well as to design effective electrocatalysts. Herein, a PbF2 nanocluster is synthesized and its self-reconstruction under the CO2 reduction condition is investigated. F- leaching, CO2 -saturated environment, and application of a cathodic potential induce self-reconstruction of PbF2 to Pb3 (CO3 )2 (OH)2 , which effectively catalyze the CO2 reduction to formate. The in situ formed Pb3 (CO3 )2 (OH)2 discloses >80% formate Faradaic efficiencies (FEs) across a broad range of potentials and achieves a maximum formate FE of ≈90.1% at -1.2 V versus reversible hydrogen electrode (RHE). Kinetic studies show that the CO2 reduction reaction (CO2 RR) on the Pb3 (CO3 )2 (OH)2 is rate-limited at the CO2 protonation step, in which proton is supplied by bicarbonate (HCO3 - ) in the electrolyte. To improve the CO2 RR kinetics, the Pb3 (CO3 )2 (OH)2 is further doped with Pd (4 wt%) to enhance its HCO3 - adsorption, which leads to accelerated protonation of CO2 . Therefore, the Pd-Pb3 (CO3 )2 (OH)2 (4 wt%) reveals higher formate FEs of >90% from -0.8 to -1.2 V versus RHE and reaches a maximum formate FE of 96.5% at -1.2 V versus RHE with a current density of ≈13 mA cm-2 .

Enhanced Antibacterial Ability and Bioactivity of Polyetherketoneketone Modified with LL-37.

Polyetherketoneketone (PEKK) is considered to be a potential substitute material for metal bone implants because of its advantageous biocompatibility, chemical stability, and mechanical properties, but clinical application has been severely restricted due to PEKK's lack of antibacterial ability and biological activity. In this study, LL-37, a natural human antimicrobial peptide, was successfully modified on the PEKK surface with polydopamine as the intermediate layer and released continuously for more than 6 days. The results of the MTT assay, colony counts, and Live/Dead staining demonstrated that compared to unmodified PEKK, the LL-37-modified PEKK significantly inhibited the adhesion, vitality, and bacterial biofilm growth of Staphylococcus aureus and Escherichia coli in a concentration-dependent way. Furthermore, the LL-37-modified PEKK enhanced biocompatibility (cell adhesion and viability) and promoted osteogenic differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells. Our data suggested that LL-37-modified PEKK might be a promising material for use in orthopedic implants.