Persistent Presence Research Articles

Early corticosteroid treatment enhances recovery from SARS-CoV-2 induced loss of smell in hamster

Among the numerous long COVID symptoms, olfactory dysfunction persists in ∼10 % of patients suffering from SARS-CoV-2 induced anosmia. Among the few potential therapies, corticoid treatment has been used for its anti-inflammatory effect with mixed success in patients. In this study, we explored its impact using hamster as an animal model. SARS-CoV-2 infected hamsters lose their smell abilities and this loss is correlated with damage of the olfactory epithelium and persistent presence of innate immunity cells. We started a dexamethasone treatment 2 days post infection, when olfaction was already impacted, until 11 days post infection when it started to recover. We observed an improvement of olfactory capacities in the animals treated with corticoid compared to those treated with vehicle. This recovery was not related to differences in the remaining damage to the olfactory epithelium, which was similar in both groups. This improvement was however correlated with a reduced inflammation in the olfactory epithelium with a local increase of the mature olfactory neuron population. Surprisingly, at 11 days post infection, we observed an increased and disorganized presence of immature olfactory neurons, especially in persistent inflammatory zones of the epithelium. This unusual population of immature olfactory neurons coincided with a strong increase of olfactory epithelium proliferation in both groups. Our results indicate that persistent inflammation of the olfactory epithelium following SARS-CoV-2 infection may alter the extent and speed of regeneration of the olfactory neuron population, and that corticoid treatment is effective to limit inflammation and improve olfaction recovery following SARS-CoV-2 infection.

Biodegradation of microplastics derived from controlled release fertilizer coating: Selective microbial colonization and metabolism in plastisphere

Coated controlled-release fertilizers (CRFs) are widely used in agriculture, and the persistent presence of residual polymer coating has raised environmental concerns. This study investigates the underlying degradation dynamics of microplastics (MPs) derived from three typical materials used in CRFs, including polyethylene (PE), epoxy (EP), and polyurethane (PU), through a soil degradation test. The formation of surface biofilm, the succession process, and metabolic characteristics of microbial community are revealed by laser scanning confocal microscope, 16S rRNA sequencing, and non-targeted metabolomics analysis. The weight loss rates of PE, EP, and PU after 807 days of degradation were 16.70 %, 2.79 %, and 4.86 %, respectively. Significant secondary MPs were produced with tears and holes appeared in the coating cross sections and pyrolysis products were produced such as ethers, acids, and esters for PE; alkanes, olefins and their branched-chain derivatives for EP; and short-chain fatty acids and benzene molecules for PU. The coating surface selectively recruited the bacteria of Chujaibacter and Ralstonia and fungus of Fusarium and Penicillium, forming biofilm composed of lipids, proteins, and living cells. The metabolism of amino acids and polymers was enhanced to protect against MP-induced stress. The metabolites or intermediates of organic acids and derivatives, oxygen-contained organic compounds, and benzenoids on CRF surface increased significantly compared with soil, but there were no significant differences among different coating types. This study provides insights to the underlying mechanisms of biodegradation and microenvironmental changes of MPs in soil.

Pulmonary vein capture is a predictor for long-term success of stand-alone pulmonary vein isolation with cryoballoon ablation in patients with persistent atrial fibrillation.

The mechanisms of AF development and progression are still not completely understood. Despite the relative efficacy of ablation, the risk of AF recurrence is substantial, particularly in patients with persistent AF (perAF). At present we do not have any reliable intra-procedural electrophysiologic predictors of long-term success of AF ablation other than pulmonary vein isolation. We evaluated selected intraprocedural pulmonary vein characteristics that may be helpful in future guidance of persistent AF ablation. 390 consecutive procedures using cryoballoon for initial AF ablation were divided by clinical presentation (paroxysmal or persistent AF), and by pulmonary vein (PV) response to pacing after completion of ablation (discrete electrogram elicited with pacing-"PV capture" or not-"Control"). Patients were followed (median 20 months) for recurrent atrial arrhythmias as the primary end point of the study. PV capture was identified in 20.3% and 17.1% and patients with paroxysmal and persistent AF respectively (ns). In patients with persistent AF presence of PV capture was associated with significantly better outcomes compared to patients without PV capture (p < 0.001). In the group "persistent AF and PV capture", an initial strategy of PV isolation and reisolation of the PVs (without additional lesions) for patients with recurrent atrial arrhythmias resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with paroxysmal AF, PV capture was not associated with outcome benefits. Specific electrophysiologic characteristics of PV (PV capture cycle length: PVCCL) did not have an impact on AF recurrence, although 25% shortening of PVCCL was observed after 60 s periods of pacing at short cycle lengths. No background demographic patient characteristic differences were identified between patients with vs. without PV capture. The presence of PV capture was associated with better outcomes in patients with persistent AF. PV capture may identify those patients with persistent AF in whom cryoballoon PV isolation alone is sufficient as an initial ablation procedure and as the primary ablation strategy for recurrent AF.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties

BackgroundEnsuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants.MethodsTo demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years’ worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors’ spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI).ResultsSpatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84–42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80–63.83%). Factors’ space-scale variation explained 75.71% (68.94–81.55%), whereas time-scale variation contributed 20.25% (14.14–27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations.ConclusionsThree-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

Deltamethrin's Toxicological Impact on Freshwater Crab Barytelphusa cunicularis

The present study investigates the toxicological impact of deltamethrin, a widely used synthetic pyrethroid insecticide used in agriculture, specifically targeting the freshwater crab Barytelphusa cunicularis. The research delves into the insecticide’s mechanism of action and acute toxicity on the crab species. With the persistent presence of deltamethrin in soil disrupting microbial activity and water contamination posing threats to aquatic ecosystems. The investigation aimed to determine the lethal toxicity concentration of pesticide. The experiment reveals LC50 values at 24, 48, 72, and 96 hours, indicating concentrations of 0.0125, 0.0075, 0.006 and 0.0049 ppm respectively. The findings demonstrate a correlation between increased pesticide concentration and exposure period with a rise in percentage mortality. Adverse effects observed on B. cunicularis populations underscore the need to comprehend deltamethrins impact on non-target organisms. This research contributes significant insights into deltamethrins toxicology, offering valuable information for decision-making and in promoting sustainable pest management practices.

Benzopyrene elimination from the environment using graphitic carbon nitride-SnS nanocomposites

Benzopyrene (BaP) stands as a potent polycyclic aromatic hydrocarbon (PAH) molecule, boasting five fused aromatic rings, making its way into the human food chain through soil contamination. The persistent environmental presence of PAHs in soil, attributed to industrial exposure, is primarily due to their low molecular weight and hydrophobic nature. To preemptively address the entry of BaP into the food chain, the application of nanocomposites was identified as an effective remediation strategy. Post-synthesis, comprehensive characterization tests employing techniques such as UV-DRS, XRD, SEM-EDX, FTIR, and DLS unveiled the distinctive features of the g–C3N4–SnS nanocomposites. These nanocomposites exhibited spherical shapes embedded on layers of nanosheets, boasting particle diameters measuring 88.9 nm. Subsequent tests were conducted to assess the efficacy of eliminating benzopyrene from a combination of PAH molecules and g–C3N4–SnS nanocomposites. Varied parameters, including PAH concentration, adsorbent dosage, and suspension pH, were systematically explored. The optimized conditions for the efficient removal of BaP utilizing the g–C3N4–SnS nanocomposite involved 2 μg/mL of benzopyrene, 10 μg/mL of the nanocomposite, and a pH of 5, considering UV light as the irradiation source. The investigation into the mechanism governing BaP elimination closely aligned with batch adsorption results involved a thorough exploration of adsorption kinetics and isotherms. Photocatalytic degradation of benzopyrene was achieved, reaching a maximum of 86 % in 4 h and 36 % in 2 h, with g–C3N4–SnS nanocomposite acting as the catalyst. Further validation through HPLC data confirmed the successful removal of BaP from the soil matrix.

Detection of Coastal Erosion and Progradation in the Colombian ‘Atrato River’ Delta by Using Sentinel-1 Synthetic Aperture Radar Data

This paper presents a methodology to detect the coastal erosion and progradation effects in the ‘Atrato River’ delta, located in the Gulf of Urabá in Colombia, using SAR (Synthetic Aperture Radar) images. Erosion is the physical–mechanical loss of the soil that affects its functions and ecosystem services while producing a reduction in its productive capacity. Progradation is the deposition of layers in the basinward direction while moving coastward. Other studies have investigated these two phenomena using optical images, encountering difficulties due to the persistent presence of clouds in this region. In order to avoid the cloud effects, in this study, we used 16 Sentinel 1 SAR images with two different polarizations between 2016 and 2023. First, each image was rescaled from 0 to 255, then the image was despeckled by a deep learning (DL) model. Afterwards, a single RGB image was composed with the filtered polarizations. Next, a classifier with 99% accuracy based on Otsu’s method was used to determine whether each pixel was water or not. Then, the classified image was registered to a reference one using Oriented FAST and Rotated BRIEF (ORB) descriptor. Finally, a multitemporal analysis was performed by comparing every image to the previous one to identify the studied phenomena, calculating areas. Also, all images were integrated to obtain a heatmap that showed the overall changes across eight years (2016–2023) in a single image. The multitemporal analysis performed found that the newly created mouth is the most active area for these processes, coinciding with other studies. In addition, a comparison of these findings with the Oceanic Niño Index (ONI) showed a relative delayed coupling to the erosion process and a coupling of progradation with dry and wet seasons.

Discerning the influence of climate variability modes, regional weather features and time series persistence on streamflow using Bayesian networks and multiple linear regression

AbstractA large literature on the sensitivity of streamflow response to climate variations has emerged over the past several decades, but the underlying mechanisms are not fully understood. The usual approaches to this problem have been simple and do not fully address its complexity, which involves the individual and joint effects of large‐scale climate modes and smaller‐scale weather features on streamflow volumes, the presence of persistence in these time series and their effects on antecedent conditions. Ongoing improvements in observational and reanalysis datasets and online access allow for better quantification of the connections between streamflow response, climate variability modes and regional weather features. The purpose of this paper is to determine whether Bayesian networks can be used to better identify key factors and their associated pathways leading to streamflow generation. A Markov blanket approach is described and illustrated using monthly streamflow series recorded at eight gauging stations within or immediately adjacent to the coastal region of eastern mainland Australia. The method is compared and contrasted with conventional multiple linear regression with discussion around this type of approach as part of a growing interest in machine learning applications. One example is used to illustrate the application of both approaches to a streamflow series exhibiting strong non‐stationarity. Results for the other streamflow series are included in a concise synthesis. Overall, the results suggest that Bayesian networks have several desirable features in terms of transparency, interpretability and explanatory insight. The findings from this study lend support to the use of Bayesian networks for modelling connections between streamflow volume and the variability of climate and regional weather. This improved understanding of the key controls of streamflow variability is intended to help address growing needs around informing social, cultural, economic and ecological aspects of water planning and management.

Green and effective remediation of heavy metals contaminated water using CaCO3 vaterite synthesized through biomineralization

Heavy metal pollution has attracted significant attention due to its persistent presence in aquatic environments. A novel vaterite-based calcium carbonate adsorbent, named biogenic CaCO3, was synthesized utilizing a microbially induced carbonate precipitation (MICP) method to remediate heavy metal-contaminated water. The maximum Cd2+ removal capacity of biogenic CaCO3 was 1074.04 mg Cd2+/g CaCO3 with a high Cd2+ removal efficiency greater than 90% (initial Cd2+ concentration 400 mg/L). Furthermore, the biogenic CaCO₃ vaterite, induced by microbial-induced calcium carbonate precipitation (MICP) process, demonstrated a prolonged phase transformation to calcite and enhanced stability. This resulted in a sustained high effectiveness (greater than 96%) following six consecutive recycling tests. Additionally, X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses revealed that the semi-stable vaterite type of biogenic CaCO3 spontaneously underwent dissolution and recrystallization to form thermodynamic stable calcite in aquatic environments. However, the presence of Cd2+ leads to the transformation of vaterite into CdCO3 rather than undergoing direct converting to calcite. This transformation is attributed to the relatively low solubility of CdCO3 compared to calcite. Meanwhile, the biogenic CaCO3 proved to be an efficient and viable method for the removal of Pb2+, Cu2+, Zn2+, Co2+, Ni2+ and Mn2+ from water samples, surpassing the performance of previously reported adsorbents. Overall, the efficient and promising adsorbent demonstrates potential for practical in situ remediation of heavy metals-contaminated water.

Atrazine exposure promotes cardiomyocyte pyroptosis to exacerbate cardiotoxicity by activating NF-κB pathway

Atrazine is a ubiquitous herbicide with persistent environmental presence and accumulation in the food chain, posing potential health hazards to organisms. Increasing evidence suggests that atrazine may have detrimental effects on various organ systems, including the nervous, digestive, and immune systems. However, the specific toxicity and underlying mechanism of atrazine-induced cardiac injury remain obscure. In this study, 4-week-old male C57BL/6 mice were administered atrazine via intragastric administration at doses of 50 and 200 mg/kg for 4 and 8 weeks, respectively. Our findings showed that atrazine exposure led to cardiac fibrosis, as evidenced by elevated heart index and histopathological scores, extensive myofiber damage, and interstitial collagen deposition. Moreover, atrazine induced cardiomyocyte apoptosis, macrophage infiltration, and excessive production of inflammatory factors. Importantly, atrazine upregulated the expressions of crucial pyroptosis proteins, including NLRP3, ASC, CASPASE1, and GSDMD, via the activation of NF-κB pathway, thus promoting cardiomyocyte pyroptosis. Collectively, our findings provide novel evidence demonstrating that atrazine may exacerbate myocardial fibrosis by inducing cardiomyocyte pyroptosis, highlighting its potential role in the development of cardiac fibrosis.

The characteristics of acute macular neuroretinopathy following COVID-19 infection

BackgroundIn this study, we report a case series of acute macular neuroretinopathy (AMN) associated with COVID-19 infection.MethodsThis retrospective observational study was conducted at Beijing Tongren Hospital. We reviewed patients who were diagnosed with AMN within one month of testing positive for COVID-19 using real-time reverse transcription-polymerase chain reaction (RT-PCR).ResultsA total of 11 AMN patients (20 eyes) were included in the study. The mean age was 33.8 ± 12.6 years. The average interval between a positive COVID-19 PCR test and the onset of ocular symptoms was 2.8 ± 2.5 days. The mean follow-up period for the patients was 12.5 ± 3.8 weeks. Imaging characteristics of AMN patients following COVID-19 infection included areas of low reflectivity on near-infrared reflectance (NIR) imaging, hyperreflective lesions at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) B-scans. Visual field examinations revealed parafoveal scotomas that closely corresponded to the clinical lesions. Optical coherence tomography angiography (OCT-A) demonstrated impaired perfusion in the deep retinal vascular plexus. Fluorescein angiography (FA), indocyanine green angiography (ICGA), and spontaneous fundus autofluorescence showed no significant abnormalities. During follow-up, partial improvement in retinal lesions was observed in NIR imaging and SD-OCT in some patients, but a proportion of patients still exhibited persistent retinal damage and no improvement in visual field scotomas.ConclusionCOVID-19-related AMN share similar clinical and imaging features with AMN due to other causes, as evidenced by the persistent presence of visual field scotomas over a longer duration.Trail registrationhttps://www.chictr.org.cn/; identifier: ChiCTR2100044365

Helicobacter pylori infection in humans and phytotherapy, probiotics, and emerging therapeutic interventions: a review.

The global prevalence of Helicobacter pylori (H. pylori) infection remains high, indicating a persistent presence of this pathogenic bacterium capable of infecting humans. This review summarizes the population demographics, transmission routes, as well as conventional and novel therapeutic approaches for H. pylori infection. The prevalence of H. pylori infection exceeds 30% in numerous countries worldwide and can be transmitted through interpersonal and zoonotic routes. Cytotoxin-related gene A (CagA) and vacuolar cytotoxin A (VacA) are the main virulence factors of H. pylori, contributing to its steep global infection rate. Preventative measures should be taken from people's living habits and dietary factors to reduce H. pylori infection. Phytotherapy, probiotics therapies and some emerging therapies have emerged as alternative treatments for H. pylori infection, addressing the issue of elevated antibiotic resistance rates. Plant extracts primarily target urease activity and adhesion activity to treat H. pylori, while probiotics prevent H. pylori infection through both immune and non-immune pathways. In the future, the primary research focus will be on combining multiple treatment methods to effectively eradicate H. pylori infection.

Microbial associates of the elm leaf beetle: uncovering the absence of resident bacteria and the influence of fungi on insect performance.

Microbial symbionts play crucial roles in the biology of many insects. While bacteria have been the primary focus of research on insect-microbe symbiosis, recent studies suggest that fungal symbionts may be just as important. The elm leaf beetle (ELB, Xanthogaleruca luteola) is a serious pest species of field elm (Ulmus minor). Using culture-dependent and independent methods, we investigated the abundance and species richness of bacteria and fungi throughout various ELB life stages and generations, while concurrently analyzing microbial communities on elm leaves. No persistent bacterial community was found to be associated with the ELB or elm leaves. By contrast, fungi were persistently present in the beetle's feeding life stages and on elm leaves. Fungal community sequencing revealed a predominance of the genera Penicillium and Aspergillus in insects and on leaves. Culture-dependent surveys showed a high prevalence of two fungal colony morphotypes closely related to Penicillium lanosocoeruleum and Aspergillus flavus. Among these, the Penicillium morphotype was significantly more abundant on feeding-damaged compared with intact leaves, suggesting that the fungus thrives in the presence of the ELB. We assessed whether the detected prevalent fungal morphotypes influenced ELB's performance by rearing insects on (i) surface-sterilized leaves, (ii) leaves inoculated with Penicillium spores, and (iii) leaves inoculated with Aspergillus spores. Insects feeding on Penicillium-inoculated leaves gained more biomass and tended to lay larger egg clutches than those consuming surface-sterilized leaves or Aspergillus-inoculated leaves. Our results demonstrate that the ELB does not harbor resident bacteria and that it might benefit from associating with Penicillium fungi.IMPORTANCEOur study provides insights into the still understudied role of microbial symbionts in the biology of the elm leaf beetle (ELB), a major pest of elms. Contrary to expectations, we found no persistent bacterial symbionts associated with the ELB or elm leaves. Our research thus contributes to the growing body of knowledge that not all insects rely on bacterial symbionts. While no persistent bacterial symbionts were detectable in the ELB and elm leaf samples, our analyses revealed the persistent presence of fungi, particularly Penicillium and Aspergillus on both elm leaves and in the feeding ELB stages. Moreover, when ELB were fed with fungus-treated elm leaves, we detected a potentially beneficial effect of Penicillium on the ELB's development and fecundity. Our results highlight the significance of fungal symbionts in the biology of this insect.

A Perspective on Probing Coral Resilience to Climate and Environmental Changes Using Stable Isotopes of Bio‐Utilized Metal Elements

AbstractIn the face of diverse challenges like global warming, ocean acidification, and human activities, the world's coral reefs are confronting a severe ecological crisis. Understanding the historical coevolution of corals with their environment and their resilience to current climate change is crucial for protecting these ecosystems and predicting their future. In this context, metal stable isotopes in corals present a novel and alternative methodology. Their significant fractionation during coral biological processes, persistent presence in coral skeletons, and relatively straightforward sources make them a valuable tool. However, the complexity of coral biology necessitates a deeper investigation into the fundamental mechanisms behind the isotopic fractionation of these biologically utilized metal elements. A comprehensive and systematic study of the roles of metal stable elements in coral biological processes is essential. This includes examining the fractionation of metal isotopes across different parts of the corals, such as tissues, zooxanthellae, and skeletons. To achieve these goals, multidisciplinary collaborations are essential. They should focus on several key areas: interpreting metal stable isotopes data in the context of coral physiology and ecology; conducting controlled laboratory experiments on coral cultivation; engaging in comparative studies with inorganically precipitated aragonites; and developing a holistic understanding within the framework of coral biomineralization models.

Land use and occupation and pesticide contamination assessment in honey from Africanized honey bees (Hymenoptera: Apidae) using gas chromatography-mass spectrometry.

We examined pesticide contamination in honey from Africanized honey bees in two different seasons, and evaluated the concentration and incidence of these compounds in georeferenced apiaries to provide relevant information for food safety and environmental quality. The land use and occupation of the region were evaluated by selecting 15 apiaries and georeferencing three randomly selected colonies of Africanized honey bees within each apiary. Honey samples were collected during two seasons, and three organochlorine pesticides (p.p`-DDE, Mitotane and Bicyclo[2.2.1]) and four organophosphate pesticides (Ethoprophos, Methyl Parathion, Chlorpyrifos and Fenchlorphos) were analyzed in the honey using gas chromatography-mass spectrometry. 80% of the apiaries showed a predominance of agricultural land use in the foraging areas of the bees. There was a higher concentration of pesticides in samples collected during Season I compared to Season II. There were differences in the proportion of samples contaminated with pesticides between seasons. Some honey samples showed concentrations of the chlorpyrifos pesticide above the levels recommended by Brazilian legislation. Pesticide contamination of honey is not limited to specific application season, indicating the persistent presence and easy availability of pesticides, including banned pesticides not sold or prescribed by agronomists, potentially smuggled from neighboring countries.

A sustainable layered double hydroxide-pine cone biochar (LDH/PCBC) composite for enhanced removal of ciprofloxacin from water

To address ciprofloxacin's (CPF) persistent presence in water, LDH modified PCBC is developed as an effective and sustainable adsorbent for its removal.

Application of dsRNA for Fungi Disease Management Sclerotinia sclerotiorum and Botrytis cinerea.

Sclerotinia sclerotiorum and Botrytis cinerea are two closely related necrotrophic plant pathogenic fungi that have garnered significant attention due to their broad host range and persistent environmental presence. The use of double-stranded RNA (dsRNA) to inhibit specific genes has demonstrated promising potential in disease management. Various RNA interference (RNAi) strategies have been developed and applied in disease management, including the use of dsRNA to silence specific genes, as well as other RNA-based approaches. These strategies show promise in controlling fungal diseases and have the potential for broader application in plant protection. Here, we present a protocol that outlines techniques for preparing dsRNA and spraying it directly to control fungal diseases. This protocol offers a practical and effective solution for managing plant diseases and has the potential to be widely applied in disease management.

Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3

Background and aimsDirect elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance. Approaches and resultsIn the present study, high mobility group nucleosome binding domain 1 (HMGN1) was screened out based on our biotin-avidin enrichment system. First, chromatin immunoprecipitation and fluorescent in situ hybridization assays confirmed the binding of HMGN1 with cccDNA in the nucleus. Second, functional experiments in HBV-infected cells showed that the promoting effect of HMGN1 on HBV transcription and replication depended on the functional region of the nucleosomal binding domain, while transfection of the HMGN1 mutant showed no influence on HBV compared with the vector. Third, further mechanistic exploration revealed that the silencing of HMGN1 increased the level of phosphorylase CLK2 and promoted H3 phosphorylation causing the reduced accessibility of cccDNA. Moreover, silenced HMGN1 was mimicked in HBV (r) cccDNA mouse model of HBV infection in vivo. The results showed that silencing HMGN1 inhibited HBV replication in vivo. ConclusionsIn summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes.

A Retrospective Review of Patient-reported Outcomes after Postaxial Polydactyly Ligation and Surgical Excision

Background: Interventions for type B postaxial polydactyly include suture ligation and surgical excision, yet there is a paucity of literature comparing the outcomes of these procedures. This study sought to compare patient-reported long-term outcomes of postaxial digit excision. Methods: A six-question survey was distributed from January 2021 to March 2022 to patients who underwent treatment for type B postaxial polydactyly at a single pediatric institution from 2010 to 2016. Patients were queried about the incidence of pain sensitivity, keloid healing, and/or persistent presence of bump (“nubbin”) at the treatment site. Results: A total of 158 responses accounting for 258 digits were attained for a 53% response rate. The majority of digits (67.4%, n = 174) were surgically excised. Median age at procedure was 49 days: 13.0 days for ligation, 63.0 days for surgical excision. Median age at survey was 8 [IQR 5.4–10.2] years. Short-term (&lt;30 days after procedure) complications rate was 1.6%. The rate of a raised or sensitive scar was 39.5% (ligation 51.5% versus surgery 35.4%, P &lt; 0.05). The likelihood of postoperative sensitivity (P = 0.80) was similar among groups. However, the odds of a residual bump or raised scar at the surgical site was significantly higher in the ligation group (P = 0.001). These findings remained significant in the adjusted analysis. Conclusion: This study suggests that suture ligation can be used in select cases without increasing the prevalence of long-term pain or sensitivity, albeit with greater risk of a bump or raised scar at the excision site compared with surgical excision.

First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film.

In patients with coronary artery disease treated with permanent polymer-coated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 μm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. Twenty patients with 20 lesions were treated with TIGERevolutioN®. At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up. Trial Registration: Clinical Research Information Service Identifier: KCT0005699.