Survival analysis of the duration of rumors during the COVID-19 pandemic.

BACKGROUND: The emergence of the COVID-19 pandemic towards the end of 2019 triggered a relentless spread of online misinformation, which significantly impacted societal stability, public perception, and the effectiveness of measures to prevent and control the epidemic. Understanding the complex dynamics and characteristics that determine the duration of rumors is crucial for their effective management. In response to this urgent requirement, our study takes survival analysis method to analyze COVID-19 rumors comprehensively and rigorously. Our primary aim is to clarify the distribution patterns and key determinants of their persistence. Through this exploration, we aim to contribute to the development of robust rumor management strategies, thereby reducing the adverse effects of misinformation during the ongoing pandemic. METHODS: The dataset utilized in this research was sourced from Tencent's "Jiao Zhen" Verification Platform's "Real-Time Debunking of Novel Coronavirus Pneumonia" system. We gathered a total of 754 instances of rumors from January 18, 2020, to January 17, 2023. The duration of each rumor was ascertained using the Baidu search engine. To analyze these rumors, survival analysis techniques were applied. The study focused on examining various factors that might influence the rumors' longevity, including the theme of the content, emotional appeal, the credibility of the source, and the mode of presentation. RESULTS: Our study's results indicate that a rumor's lifecycle post-emergence typically progresses through three distinct phases: an initial rapid decline phase (0-25 days), followed by a stable phase (25-1000 days), and ultimately, an extinction phase (beyond 1000 days). It is observed that half of the rumors fade within the first 25 days, with an average duration of approximately 260.15 days. When compared to the baseline category of prevention and treatment rumors, the risk of dissipation is markedly higher in other categories: policy measures rumors are 3.58 times more likely to perish, virus information rumors have a 0.52 times higher risk, epidemic situation rumors are 4.86 times more likely to die out, and social current affairs rumors face a 2.02 times increased risk. Additionally, in comparison to wish rumors, bogie rumors and aggression rumors have 0.26 and 0.27 times higher risks of dying, respectively. In terms of presentation, graphical and video rumors share similar dissolution risks, whereas textual rumors tend to have a longer survival time. Interestingly, the credibility of the rumor's source does not significantly impact its longevity. CONCLUSION: The survival time of rumors is strongly linked to their content theme and emotional appeal, whereas the credibility of the source and the format of presentation have a more auxiliary influence. This study recommends that government agencies should adopt specific strategies to counter rumors. Experts and scholars are encouraged to take an active role in spreading health knowledge. It's important for the public to proactively seek trustworthy sources for accurate information. Media platforms are advised to maintain journalistic integrity, verify the accuracy of information, and guide the public towards improved media literacy. These actions, collectively, can foster a collaborative alliance between the government and the media, effectively combating misinformation.

Deciphering the age-dependent changes of pulmonary fibroblasts in mice by single-cell transcriptomics.

Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue. Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques. Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFß treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts. Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis.

Preparation of N-doped porous biochar with high specific surface area and its efficient adsorption for mercury ion from aqueous solution.

Herein, a new type of super active nitrogen-doped biochar sheet (SNBC) was prepared by two-step pyrolysis and KOH chemical activation with melamine and cherry kernel powder as precursors of nitrogen and carbon source for removing Hg2+ from wastewater. The N2 adsorption/desorption and scanning electron microscope characterization revealed that the resulted SNBC under 600 °C calcination owned huge specific surface area of 2828 m2/g and plenty of well-developed micropores, and X-ray photoelectron spectroscopy and Fourier transform-infrared spectroscopy analysis testified the existence of functional groups containing N and O, which could provide adsorption sites for Hg2+. The SNBC-600 showed high adsorption capacity for Hg2+ even at low pH, and interfering cations had little effect on the adsorption. The adsorption process was rapid and dynamic data fit the pseudo-second-order dynamic model well. The maximum adsorption capacity of Hg2+ on SNBC-600 calculated by Langmuir model was 230 mg/g. After six times of reuse, the adsorption capacity still exceeded 200 mg/g, exhibiting good reusability. The designed microfiltration membrane device base on SNBC-600 could remove low concentration of Hg2+ effectively from solution. This study provided a simple and environment-friendly method for manufacturing nitrogen-doped biochar sheet, which was of great significance in the practical application of Hg2+ pollution treatment.

Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration.

Dermal adipocyte lineage cells are highly plastic and can undergo reversible differentiation and dedifferentiation in response to various stimuli. Using single-cell RNA sequencing of developing or wounded mouse skin, we classify dermal fibroblasts (dFBs) into distinct non-adipogenic and adipogenic cell states. Cell differentiation trajectory analyses identify IL-1-NF-κB and WNT-ß-catenin as top signaling pathways that positively and negatively associate with adipogenesis, respectively. Upon wounding, activation of adipocyte progenitors and wound-induced adipogenesis are mediated in part by neutrophils through the IL-1R-NF-κB-CREB signaling axis. In contrast, WNT activation, by WNT ligand and/or ablation of Gsk3, inhibits the adipogenic potential of dFBs but promotes lipolysis and dedifferentiation of mature adipocytes, contributing to myofibroblast formation. Finally, sustained WNT activation and inhibition of adipogenesis is seen in human keloids. These data reveal molecular mechanisms underlying the plasticity of dermal adipocyte lineage cells, defining potential therapeutic targets for defective wound healing and scar formation.

Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)-induced atopic dermatitis-like model. We found that injection of a high dose of AS not only suppressed the IMQ-mediated development of T-helper 1 (Th1) and T-helper 17 (Th17) immune responses but also inhibited the IMQ-mediated recruitment and/or activation of neutrophils and macrophages. In contrast, AS injection enhanced MC903-mediated development of the T-helper 2 (Th2) immune response and neutrophil recruitment. Using an in vitro approach, we found that AS treatment inhibited Th1 but promoted Th2 polarization of primary lymphocytes, and inhibited activation of peritoneal macrophages but not bone marrow derived neutrophils. Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.

Research Advances of Bioactive Sesquiterpenoids Isolated from Marine-Derived Aspergillus sp.

Marine fungi Aspergillus sp. is an important source of natural active lead compounds with biological and chemical diversity, of which sesquiterpenoids are an extremely important class of bioactive secondary metabolites. In this paper, we review the sources, chemical structures, bioactivity, biosynthesis, and druggability evaluation of sesquiterpenoids discovered from marine fungi Aspergillus sp. since 2008. The Aspergillus species involved include mainly Aspergillus fumigatus, Aspergillus versicolor, Aspergillus flavus, Aspergillus ustus, Aspergillus sydowii, and so on, which originate from sponges, marine sediments, algae, mangroves, and corals. In recent years, 268 sesquiterpenoids were isolated from secondary metabolites of marine Aspergillus sp., 131 of which displayed bioactivities such as antitumor, antimicrobial, anti-inflammatory, and enzyme inhibitory activity. Furthermore, the main types of active sesquiterpenoids are bisabolanes, followed by drimanes, nitrobenzoyl, etc. Therefore, these novel sesquiterpenoids will provide a large number of potential lead compounds for the development of marine drugs.

Establishment of human embryonic stem cell WAe009-A-88 carrying a long QT syndrome mutation in KCNH2.

Long-QT syndrome type 2 (LQT2) is a life-threatening Mendelian disease caused by genetic variants in KCNH2. Herein, we generated a human embryonic stem cell line (WAe009-A-88) carrying a LQT2 related mutation in KCNH2, c.1720 A>G. The WAe009-A-88 line maintained stem cell-like morphology, expressed high levels of pluripotent markers, had a normal karyotype, and could differentiate into all three germ layers in vivo. The cell line can serve as valuable tools for modeling LQT2 in vitro and investigating the pathological mechanisms related to KCNH2 mutations.

Establishment of human embryonic stem cell WAe009-A-74 carrying a Long QT syndrome mutation in KCNH2.

Long-QT syndrome type 2 (LQT2) is a common malignant hereditary arrhythmia. Due to the lack of suitable animal and human models, the pathogenesis of LQT2 caused by human ether-a-go-go-related gene (hERG) deficiency is still unclear. Herein, we have generated a human embryonic stem cell line (WAe009-A-74) carrying a LQTS related mutation in KCNH2. The WAe009-A-74 line maintained stem cell like morphology, pluripotency, normal karyotype and could differentiate into all three germ layers in vivo.

Base Editing of Human Pluripotent Stem Cells for Modeling Long QT Syndrome.

Human pluripotent stem cells (hPSCs) have great potential for disease modeling, drug discovery, and regenerative medicine as they can differentiate into many different functional cell types via directed differentiation. However, the application of disease modeling is limited due to a time-consuming and labor-intensive process of introducing known pathogenic mutations into hPSCs. Base editing is a newly developed technology that enables the facile introduction of point mutations into specific loci within the genome of living cells without unwanted genome injured. We describe an optimized stepwise protocol to introduce disease-specific mutations of long QT syndrome (LQTs) into hPSCs. We highlight technical issues, especially those associated with introducing a point mutation to obtain isogenic hPSCs without inserting any resistance cassette and reproducible cardiomyocyte differentiation. Based on the protocol, we succeeded in getting hPSCs carrying LQTs pathogenic mutation with excellent efficiency (31.7% of heterozygous clones, 9.1% of homozygous clones) in less than 20 days. In addition, we also provide protocols to analyze electrophysiological of hPSC-derived cardiomyocytes using multi-electrode arrays. This protocol is also applicable to introduce other disease-specific mutations into hPSCs.

The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases.

BACKGROUND: Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. METHODS: Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. CONCLUSIONS: Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

Integrated analysis of microRNA and mRNA expression profiling identifies BAIAP3 as a novel target of dysregulated hsa-miR-1972 in age-related white matter lesions.

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis.

As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.

Mo-doped boron nitride monolayer as a promising single-atom electrocatalyst for CO2 conversion.

The design of new, efficient catalysts for the conversion of CO2 to useful fuels under mild conditions is urgent in order to reduce greenhouse gas emissions and alleviate the energy crisis. In this work, a series of transition metals (TMs), including Sc to Zn, Mo, Ru, Rh, Pd and Ag, supported on a boron nitride (BN) monolayer with boron vacancies, were investigated as electrocatalysts for the CO2 reduction reaction (CRR) using comprehensive density functional theory (DFT) calculations. The results demonstrate that a single-Mo-atom-doped boron nitride (Mo-doped BN) monolayer possesses excellent performance for converting CO2 to CH4 with a relatively low limiting potential of -0.45 V, which is lower than most catalysts for the selective production of CH4 as found in both theoretical and experimental studies. In addition, the formation of OCHO on the Mo-doped BN monolayer in the early hydrogenation steps is found to be spontaneous, which is distinct from the conventional catalysts. Mo, as a non-noble element, presents excellent catalytic performance with coordination to the BN monolayer, and is thus a promising transition metal for catalyzing CRR. This work not only provides insight into the mechanism of CRR on the single-atom catalyst (Mo-doped BN monolayer) at the atomic level, but also offers guidance in the search for appropriate earth-abundant TMs as electrochemical catalysts for the efficient conversion of CO2 to useful fuels under ambient conditions.

New dynamic viewing of mast cells in pulmonary arterial hypertension (PAH): contributors or outsiders to cardiovascular remodeling.

BACKGROUND: In patients with pulmonary arterial hypertension (PAH), mast cells (MCs) are extensively observed around pulmonary vessels. However, their temporal and spatial variation during PAH development remains obscure. This study investigated the dynamic evolution of MCs in lungs and right ventricles (RV) to illuminate their role in pulmonary vascular and RV remodeling. METHODS: The PAH model was established by a single intra-peritoneal injection of monocrotaline (MCT, 60 mg/kg) in rats. On day 0, 3, 7, 14, and 28 after MCT injection, lung and RV tissues were harvested for staining with hematoxylin and eosin (HE), Gomori aldehyde fuchsin (GAF), toluidine blue (TB) and picrosirius red (PSR). Immunohistochemistry was performed to evaluate the levels of α-SMA, CD68 and tryptase. A simple RV remolding model was produced as well by pulmonary artery banding (PAB). RV tissues were collected to determine the degree of MCs infiltration. RESULTS: After MCT challenge, elevated mean pulmonary arterial pressure (mPAP), increased RV systolic pressure (RVSP), pulmonary arterial media hypertrophy as well as distal vascular muscularization gradually occurred with time. MCs recruitment along with CD68+ macrophages accumulation was observed around distal pulmonary vessels and in alveolar septa. Excessive infiltration and degranulation of MCs were detected in MCT-treated group in lung tissues but not in RV. In addition, no exacerbation of MCs infiltration and degranulation in RV was noted in PAB-treated rats, suggesting few contributions of MCs to RV remodeling. CONCLUSIONS: Our findings implied a crucial role of MCs in the remodeling of pulmonary vessels, not RV, which probably through releasing cytokines such as tryptase. The present study enriches the knowledge about PAH, providing a potential profile of MCs as a switch for the treatment of PAH.

Rab34 regulates adhesion, migration, and invasion of breast cancer cells.

The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion, and macropinocytosis. In this study, we found that Rab34 is over-expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion, and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin ß3, and depletion of Rab34 promotes the degradation of integrin ß3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase. Accordingly, Rab34 is tyrosine phosphorylated by Src at Y247 residue. A mutant mimicking phosphorylated form of Rab34 (Rab34Y247D) promotes cell migration and invasion. Importantly, the tyrosine phosphorylation of Rab34 is inhibited in cells in suspension, and increased with the cells re-adhesion. In addition, Rab34Y247D promotes cell adhesion, and enhances integrin ß3 endocytosis and recycling. The results uncover a role of Rab34 in migration and invasion of breast cancer cells and its involvement in cancer metastasis, and provide a novel mechanism of tyrosine phosphorylation of Rab34 in regulating cell migration, invasion, and adhesion through modulating the endocytosis, stability, and recycling of integrin ß3.

Hydration effect on proton transfer in melamine-cyanuric acid complex.

Self-assembly of melamine-cyanuric acid (MC) leads to urinary tract calculi and renal failure. The hydration effects on molecular geometry, the IR spectra, the frontier molecular orbital, the energy barrier of proton transfer (PT), as well as the stability of MC were explored by density functional theory (DFT) calculations. The intramolecular PT breaks the big π-conjugated ring of melamine or converts the p-π conjugation (:N-C'=O) to π-π conjugation (O=C-N=C') of cyanuric acid. The intermolecular PT varies the coupling between melamine and cyanuric acid from pure hydrogen bonds (Na…HNd and NH…O) to the cooperation of cation…anion electrostatic interaction (NaH(+)…Nd (-)) and two NH…O hydrogen bonds. Distinct IR spectra shifts occur for Na…HNd stretching mode upon PT, i.e., blue-shift upon intramolecular PT and red-shift upon intermolecular PT. It is expected that the PT would inhibit the generation of rosette-like structure or one-dimensional tape conformer for the MC complexes. Hydration obviously effects the local geometric structure around the water binding site, as well as the IR spectra of NH…O and N…HN hydrogen bonds. Hydration decreases the intramolecular PT barrier from ~45 kcal mol(-1) in anhydrous complex to ~11.5 kcal mol(-1) in trihydrated clusters. While, the hydration effects on intermolecular PT barrier is slight. The relative stability of MC varies slightly by hydration due to the strong hydrogen bond interaction between melamine and cyanuric acid fragments. Graphical Abstract Hydration effect on proton transfer in melamine-cyanuric acid complex.

Sorting nexin 27 interacts with Fzd7 and mediates Wnt signalling.

SNX27 is the only sorting nexin (SNX) that contains a PDZ domain, which interacts with PDZ-binding motif of target proteins to regulate the trafficking of these proteins. We here showed that SNX27 interacts with Frizzled (Fzd) receptors via PDZ domain interaction. Immunofluorescence microscopy revealed that Fzd7 can be internalized and associate with SNX27-containing endosomal membrane. In addition, SNX27 enhances the endocytosis of Fzd7 and promotes the degradation of Fzd7. Further examination demonstrated that SNX27 inhibits the Wnt regulated transcription activity of TCF/LEF. Our results suggested that SNX27 interacts with Frizzled receptors to regulate the endocytosis and stability of Fzds, and consequently mediates canonical Wnt signalling.

DFT investigation on dihydrogen-bonded amine-borane complexes.

The DFT method has been employed in the exploration on dihydrogen-bonded amine-borane complexes, with a special emphasis on the dimerization and substituent group effect. Stable dihydrogen bonded complexes can be generated from these amine-borane monomers with the appearance of NH(δ+)…H(δ-)B interactions. The binding energy decreases gradually with the increase of the steric effect of the substituents. The substituent group number mainly varies the C-N bond length. The dimerization generates close H…H and influences predominantly the N-B distance. The effect of dimerization on IR and vibrational circular dichroism (VCD) spectra is stronger than that of the number of substituent groups, which leads to distinct NBO charge variation on α-C. Both the substituent group number and dimerization enhance the chemical shift difference between hydrogen atoms covalently bonded to N and B, Δδ H-H, which can be hired as an index for structural determination. It is proposed that amine-borane complexes with more substituent groups in higher degree of polymerization are potentially interesting materials for hydrogen storage. Graphical Abstract Both the number of substituent group and dimerization enhance the chemical shift difference of hydrogen atoms covalently bonded on N and B, Δδ H-H, which can be employed as an index for the structural determination.