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.

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.

In-depth understanding of the effects of different molecular weight pullulan interacting with protein and starch on dough structure and application properties.

This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into dough system to explore their intervention effects on structural and technological properties of dough as well as physical and digestion properties of biscuits. Results showed that HPL (pullulan with molecule weight of 100- 300 kDa) could increase the intermolecular collisions, prompt the protein aggregation and limit the water migration in dough system, resulting in an integrate, continuous and dense network structure of the gel with strengthened elasticity and weakened extensibility, which caused an increase in biscuit thickness, hardness and crispness. On the contrary, LPL (pullulan with molecule weight of 3- 100 kDa) could go against the formation of stable and elastic dough through breaking down cross-linkage between protein and starch so as to provide biscuits with decreased hardness and crispness during baking. Both HPL and LPL delayed starch pasting and retrogradation process while HPL had the stronger retarding effect on starch digestibility of biscuits than LPL. These findings dedicated to a better understanding of pullulan function in dough system and provide suggestions for fractionation applications of pullulan in food field.

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.

Secreted salt and hydrodynamic factors combine to affect dynamic fluctuations of microplastics on mangrove leaves.

Mangrove leaves have been acknowledged as crucial sink for coastal microplastics (MPs). Whereas, the temporal dynamics of MPs intercepted by mangrove leaves have remained poorly understood. Here, we detected MPs intercepted by submerged and non-submerged mangrove leaves over time and the potential driving factors. Abundance and characteristics of MPs interception by mangrove leaves exhibited dynamic fluctuations, with the coefficient of variation (CV) of submerged mangrove leaves (CV = 0.604; 1.76 n/g to 15.45 n/g) being approximately twofold higher than non-submerged mangrove leaves (CV = 0.377; 0.74 n/g to 3.28 n/g). Partial least squares path model (PLS-PM) analysis further illustrated that MPs abundance on submerged mangrove leaves were negative correlated to hydrodynamic factors (i.e., current velocity and tidal range). Intriguingly, secreted salt as a significantly driver of MPs intercepted by mangrove leaves. Results of this work highlights that MPs intercepted by mangrove leaves is characterized by dynamic fluctuations and reveals the importance of hydrodynamic factors and secreted salt. Overall, this work identifies the pivotal buffering role played by mangrove leaves in intercepting MPs, which provides basic knowledge for better understanding of microplastic pollution status and control from mangrove plants.

Heterojunction-Induced Rapid Transformation of Ni3+/Ni2+ Sites which Mediates Urea Oxidation for Energy-Efficient Hydrogen Production.

Water electrolysis is an environmentally-friendly strategy for hydrogen production but suffers from significant energy consumption. Substituting urea oxidation reaction (UOR) with lower theoretical voltage for water oxidation reaction adopting nickel-based electrocatalysts engenders reduced energy consumption for hydrogen production. The main obstacle remains strong interaction between accumulated Ni3+ and *COO in the conventional Ni3+-catalyzing pathway. Herein, a novel Ni3+/Ni2+ mediated pathway for UOR via constructing a heterojunction of nickel metaphosphate and nickel telluride (Ni2P4O12/NiTe), which efficiently lowers the energy barrier of UOR and avoids the accumulation of Ni3+ and excessive adsorption of *COO on the electrocatalysts, is developed. As a result, Ni2P4O12/NiTe demonstrates an exceptionally low potential of 1.313 V to achieve a current density of 10 mA cm-2 toward efficient urea oxidation reaction while simultaneously showcases an overpotential of merely 24 mV at 10 mA cm-2 for hydrogen evolution reaction. Constructing urea electrolysis electrolyzer using Ni2P4O12/NiTe at both sides attains 100 mA cm-2 at a low cell voltage of 1.475 V along with excellent stability over 500 h accompanied with nearly 100% Faradic efficiency.

Large electronegativity differences between adjacent atomic sites activate and stabilize ZnIn2S4 for efficient photocatalytic overall water splitting.

Photocatalytic overall water splitting into hydrogen and oxygen is desirable for long-term renewable, sustainable and clean fuel production on earth. Metal sulfides are considered as ideal hydrogen-evolved photocatalysts, but their component homogeneity and typical sulfur instability cause an inert oxygen production, which remains a huge obstacle to overall water-splitting. Here, a distortion-evoked cation-site oxygen doping of ZnIn2S4 (D-O-ZIS) creates significant electronegativity differences between adjacent atomic sites, with S1 sites being electron-rich and S2 sites being electron-deficient in the local structure of S1-S2-O sites. The strong charge redistribution character activates stable oxygen reactions at S2 sites and avoids the common issue of sulfur instability in metal sulfide photocatalysis, while S1 sites favor the adsorption/desorption of hydrogen. Consequently, an overall water-splitting reaction has been realized in D-O-ZIS with a remarkable solar-to-hydrogen conversion efficiency of 0.57%, accompanying a ~ 91% retention rate after 120 h photocatalytic test. In this work, we inspire an universal design from electronegativity differences perspective to activate and stabilize metal sulfide photocatalysts for efficient overall water-splitting.

Peanut oil odor enhances the immunomodulatory effect on immunosuppressed mice by regulating the cAMP signaling pathway via the brain-spleen axis.

The role of sniffing relative to immune function has attracted considerable attention. The present study investigated the immunomodulatory effects of peanut oil odor on cyclophosphamide (CTX)-induced immunosuppressed mice. The subset of mice subjected to prolonged (8 h) sniffing peanut oil odor (PL) demonstrated significantly elevated levels of agouti-related peptide, neuropeptide Y, and glutamate (p < 0.05), whereas it significantly down-regulated the level of γ-aminobutyric acid in the brain (p < 0.05). Furthermore, immunohistochemistry results indicated significantly increased expression of mGluR1/5 and decreased expression of GABABR in the hippocampus and hypothalamus (p < 0.05) of the PL group. Additionally, the PL group had significantly up-regulated expression levels of cAMP, Epac, Rap1, ERK1/2 and PKA (p < 0.05) and remarkably increased phosphorylation of CREB in the cAMP signaling pathway (p < 0.05), which influenced the central nervous system. Moreover, compared with CTX-induced mice, the percentages of peripheral blood T lymphocytes (CD3+CD4+ and CD3+CD8+) and the levels of splenic cytokines (IL-2, IL-4, and TNF-α) were significantly increased following PL treatment (p < 0.05). The PL group also showed significantly up-regulated expression levels of cAMP, p-p65, and p-IκBα in the spleen (p < 0.05) by western blot analysis. In summary, PL intervention significantly up-regulated the expression levels of cAMP in the brain (p < 0.05), with subsequent transfer of cAMP to the spleen which promoted phosphorylation of p65 and IκBα. This series of events enhanced the immunity of mice, which confirmed the regulatory effect of PL on the cAMP signaling pathway, thereby enhancing immune function via the brain-spleen axis.

Cancer stem cell biomarkers and related signalling pathways.

Cancer stem cells (CSCs) represent a distinct subset of neoplastic cells characterised by their heightened capacity for tumorigenesis. These cells are implicated in the facilitation of cancer metastasis, recurrence, and resistance to conventional therapeutic interventions. Extensive scientific research has been devoted to the identification of biomarkers and the elucidation of molecular mechanisms in order to improve targeted therapeutic approaches. Accurate identification of cancer stem cells based on biomarkers can provide a theoretical basis for drug combinations of malignant tumours. Targeted biomarker-based therapies also offer a silver lining for patients with advanced malignancies. This review aims comprehensively to consolidate the latest findings on CSCs biomarkers, targeted agents as well as biomarkers associated signalling pathways in well-established cancer types, thereby contributing to improved prognostic outcomes.

Insight into the role of niche concept in deciphering the ecological drivers of MPs-associated bacterial communities in mangrove forest.

Myriad inherent and variable environmental features are controlling the assembly and succession of bacterial communities colonizing on mangrove microplastics (MPs). However, the mechanisms governing mangrove MPs-associated bacterial responses to environmental changes still remain unknown. Here, we assessed the dissimilarities of MPs-associated bacterial composition, diversity and functionality as well as quantified the niche variations of each taxon on plastispheres along river-mangrove-ocean and mangrove landward-to-seaward gradients in the Beibu Gulf, China, respectively. The bacterial richness and diversity as well as the niche breadth on mangrove sedimentary MPs dramatically decreased from landward to seaward regions. Characterizing the niche variations linked the difference of ecological drivers of MPs-associated bacterial populations and functions between river-mangrove-ocean (microplastic properties) and mangrove landward-to-seaward plastispheres (sediment physicochemical properties) to the trade-offs between selective stress exerted by inherent plastic substrates and microbial competitive stress imposed by environmental conditions. Notably, Rhodococcus erythropolis was predicted to be the generalist species and closely associated to biogeochemical cycles of mangrove plastispheres. Our work provides a reliable pathway for tackling the hidden mechanisms of environmental factors driving MPs-associated microbe from perspectives of niches and highlights the spatial dynamic variations of mangrove MPs-associated bacteria.

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.

Undergraduate students' perceptions of using videoconferencing for EFL learning: Evidence from Tencent Meeting application.

This paper examined Chinese undergraduate students' perceptions of using videoconferencing in learning English as a foreign language (EFL) during the COVID-19 pandemic. The data were collected among 348 Chinese university students who attended sixteen-week learning of Integrated English Course through Tencent Meeting, the most widely used videoconferencing application in China. We adopted voluntary response sampling method in this cross-sectional study. Students completed an online survey on "Wenjuanxing", China's biggest online questionnaire distribution platform. A structural equation model (SEM) was constructed and analyses revealed that perceived ease of use and perceived usefulness were significant predictors of students' satisfaction and participation intention. Students' computer self-efficacy had a positive effect on their perceived ease of use, perceived usefulness, and participation intention while their frequency of using videoconferencing did not influence these variables. This study contributes to the existing literature on the acceptance of videoconferencing in the context of EFL learning and offers insights for developing up-to-date videoconferencing teaching strategies.

Assessing the utility of COVID-19 case reports as a leading indicator for hospitalization forecasting in the United States.

Identifying data streams that can consistently improve the accuracy of epidemiological forecasting models is challenging. Using models designed to predict daily state-level hospital admissions due to COVID-19 in California and Massachusetts, we investigated whether incorporating COVID-19 case data systematically improved forecast accuracy. Additionally, we considered whether using case data aggregated by date of test or by date of report from a surveillance system made a difference to the forecast accuracy. Evaluating forecast accuracy in a test period, after first having selected the best-performing methods in a validation period, we found that overall the difference in accuracy between approaches was small, especially at forecast horizons of less than two weeks. However, forecasts from models using cases aggregated by test date showed lower accuracy at longer horizons and at key moments in the pandemic, such as the peak of the Omicron wave in January 2022. Overall, these results highlight the challenge of finding a modeling approach that can generate accurate forecasts of outbreak trends both during periods of relative stability and during periods that show rapid growth or decay of transmission rates. While COVID-19 case counts seem to be a natural choice to help predict COVID-19 hospitalizations, in practice any benefits we observed were small and inconsistent.

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.

A scATAC-seq atlas of chromatin accessibility in axolotl brain regions.

Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.

Mitochondrial quality control: prime targets for antiviral therapy?

Mitochondrial quality control (MQC) plays a crucial role in maintaining mitochondrial health. Mitochondrial dynamics and mitophagy are two intricate processes of the MQC machinery acting at the organelle level to orchestrate mitochondrial homeostasis. Here, we discuss how viruses perturb these two processes to facilitate their infections and emphasize the rationale and challenges of therapeutically targeting MQC for treating viral diseases.