IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents. We investigated the role of the type 2 cytokine IL-13 on SARS-CoV-2 binding/entry, replication, and host response in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 infection in vivo. IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2- expressing ciliated cells rather than by neutralization in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened disease severity in mice; the effects were mediated by eicosanoid signaling and were abolished in mice deficient in the phospholipase A2 enzyme PLA2G2D. We conclude that IL-13-induced inflammation differentially affects multiple steps of COVID-19 pathogenesis. IL-13-induced inflammation may be protective against initial SARS-CoV-2 airway epithelial infection; however, it enhances disease progression in vivo. Blockade of IL-13 and/or eicosanoid signaling may be protective against progression to severe respiratory virus-induced lung disease. RESEARCH IN CONTEXT: Evidence before this study: Prior to this study, various pieces of evidence indicated the significant role of cytokines in the pathogenesis and progression of COVID-19. Severe COVID-19 cases were marked by cytokine storm syndrome, leading to immune activation and hyperinflammation. Treatments aimed at modulating cytokine signaling, such as IL-6 receptor antagonists, had shown moderate effects in managing severe COVID-19 cases. Studies also revealed an excessive production of type 2 cytokines, particularly IL-13 and IL-4, in the plasma and lungs of COVID-19 patients, which was associated with adverse outcomes. Treatment with anti-IL-13 monoclonal antibodies improved survival following SARS-CoV-2 infection, suggesting that IL-13 plays a role in disease severity. Type 2 cytokines were observed to potentially suppress type 1 responses, essential for viral clearance, and imbalances between these cytokine types were linked to negative COVID-19 outcomes. These findings highlighted the complex interactions between cytokines and the immune response during viral infections, underscoring the importance of understanding IL-13's role in COVID-19 and related lung diseases for developing effective therapeutic interventions.Added value of this study: In this study, we explored the impact of IL-13-induced inflammation on various stages of the SARS-CoV-2 infection cycle using both murine (in vivo) and primary human airway epithelial (in vitro) culture models. Our findings indicated that IL-13 provided protection to airway epithelial cells against SARS-CoV-2 infection in vitro, partly by reducing the number of ACE2- expressing ciliated cells. Conversely, IL-13 exacerbated the severity of SARS2-N501Y MA30 -induced disease in mice, primarily through Pla2g2d-mediated eicosanoid biosynthesis. Implications of the available evidence: Current evidence indicates that PLA 2 G2D plays a crucial role in the IL-13-driven exacerbation of COVID-19 in mice, suggesting that targeting the IL-13-PLA2G2D axis could help protect against SARS-CoV-2 infection. These insights are important for clinical research, especially for studies focusing on drugs that modify IL-13 signaling or modulate eicosanoids in the treatment of asthma and respiratory virus-induced lung diseases.

SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs.

COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required. In this study, we sought to understand the spatial impact of COVID-19 on the lungs of mice infected with mouse-adapted SARS2-N501Y MA30 . Overall, infection caused a decrease in fatty acids, amino acids, and most eicosanoids. When analyzed by segment, viral loads were highest in central lung tissue, while metabolic disturbance was highest in peripheral tissue. Infected peripheral lung tissue was characterized by lower levels of fatty acids and amino acids when compared to central lung tissue. This study highlights the spatial impacts of SARS-CoV-2 and helps explain why peripheral lung tissue is most damaged by COVID-19.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

The effect of exogenous melatonin on waterlogging stress in Clematis.

Clematis is the queen of the vines, being an ornamental plant with high economic value. Waterlogging stress reduces the ornamental value of the plant and limits its application. Melatonin plays an important role in plant resistance to abiotic stresses. In this study, the physiological responses and gene expression levels of two wild species, namely, Clematis tientaiensis and Clematis lanuginosa, and two horticultural varieties, namely, 'Sen-No-Kaze' and 'Viva Polonia,' under waterlogging stress were analyzed to determine the effect of melatonin on waterlogging tolerance. The results showed that the waterlogging tolerances of C. lanuginosa and 'Sen-No-Kaze' were relatively poor, but were significantly improved by concentrations of 100 µmol·L-1 and 50 µmol·L-1 melatonin. C. tientaiensis and 'Viva Polonia' had relatively strong tolerance to waterlogging, and this was significantly improved by 200 µmol·L-1 melatonin. Under waterlogging stress, the relative conductivity and H2O2 content of Clematis increased significantly; the photosynthetic parameters and chlorophyll contents were significantly decreased; photosynthesis was inhibited; the contents of soluble protein and soluble sugars were decreased. Effective improvement of waterlogging tolerance after exogenous melatonin spraying, the relative conductivity was decreased by 4.05%-27.44%; the H2O2 content was decreased by 3.84%-23.28%; the chlorophyll content was increased by 35.59%-103.36%; the photosynthetic efficiency was increased by 25.42%-45.86%; the antioxidant enzyme activities of APX, POD, SOD, and CAT were increased by 28.03%-158.61%; the contents of proline, soluble protein, and soluble sugars were enhanced, and cell homeostasis was improved. Transcription sequencing was performed on wild Clematis with differences in waterlogging tolerance, and nine transcription factors were selected that were highly correlated with melatonin and that had the potential to improve waterlogging tolerance, among which LBD4, and MYB4 were significantly positively correlated with the antioxidant enzyme system, and bHLH36, DOF36, and WRKY4 were significantly negatively correlated. Photosynthetic capacity was positively correlated with DOF36 and WRKY4 while being significantly negatively correlated with MYB4, MOF1, DOF47, REV1 and ABR1. Melatonin could enhance the flooding tolerance of Clematis by improving photosynthetic efficiency and antioxidant enzyme activity. This study provides an important basis and reference for the application of melatonin in waterlogging-resistant breeding of Clematis.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Perceived stress and influencing factors for the people at high risk to COVID-19 in centralized quarantine camps in Wenzhou, China.

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

Parallel processing model for low-dose computed tomography image denoising.

Low-dose computed tomography (LDCT) has gained increasing attention owing to its crucial role in reducing radiation exposure in patients. However, LDCT-reconstructed images often suffer from significant noise and artifacts, negatively impacting the radiologists' ability to accurately diagnose. To address this issue, many studies have focused on denoising LDCT images using deep learning (DL) methods. However, these DL-based denoising methods have been hindered by the highly variable feature distribution of LDCT data from different imaging sources, which adversely affects the performance of current denoising models. In this study, we propose a parallel processing model, the multi-encoder deep feature transformation network (MDFTN), which is designed to enhance the performance of LDCT imaging for multisource data. Unlike traditional network structures, which rely on continual learning to process multitask data, the approach can simultaneously handle LDCT images within a unified framework from various imaging sources. The proposed MDFTN consists of multiple encoders and decoders along with a deep feature transformation module (DFTM). During forward propagation in network training, each encoder extracts diverse features from its respective data source in parallel and the DFTM compresses these features into a shared feature space. Subsequently, each decoder performs an inverse operation for multisource loss estimation. Through collaborative training, the proposed MDFTN leverages the complementary advantages of multisource data distribution to enhance its adaptability and generalization. Numerous experiments were conducted on two public datasets and one local dataset, which demonstrated that the proposed network model can simultaneously process multisource data while effectively suppressing noise and preserving fine structures. The source code is available at https://github.com/123456789ey/MDFTN .

A Hybrid EEG-Based Stress State Classification Model Using Multi-Domain Transfer Entropy and PCANet.

This paper proposes a new hybrid model for classifying stress states using EEG signals, combining multi-domain transfer entropy (TrEn) with a two-dimensional PCANet (2D-PCANet) approach. The aim is to create an automated system for identifying stress levels, which is crucial for early intervention and mental health management. A major challenge in this field lies in extracting meaningful emotional information from the complex patterns observed in EEG. Our model addresses this by initially applying independent component analysis (ICA) to purify the EEG signals, enhancing the clarity for further analysis. We then leverage the adaptability of the fractional Fourier transform (FrFT) to represent the EEG data in time, frequency, and time-frequency domains. This multi-domain representation allows for a more nuanced understanding of the brain's activity in response to stress. The subsequent stage involves the deployment of a two-layer 2D-PCANet network designed to autonomously distill EEG features associated with stress. These features are then classified by a support vector machine (SVM) to determine the stress state. Moreover, stress induction and data acquisition experiments are designed. We employed two distinct tasks known to trigger stress responses. Other stress-inducing elements that enhance the stress response were included in the experimental design, such as time limits and performance feedback. The EEG data collected from 15 participants were retained. The proposed algorithm achieves an average accuracy of over 92% on this self-collected dataset, enabling stress state detection under different task-induced conditions.

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.

Photocatalytic Chemoselective Cyclic Oxysulfonylation of 2,3-Allenoic Acids.

Photoinduced cyclization of 2,3-allenoic acids with sulfonyl chloride providing an efficient synthesis of 4-sulfonylated furan-2(5H)-ones under mild reaction conditions has been achieved. The reaction enjoys a high chemoselectivity and tolerates a wide range of functional groups. The catalytic cycle has been validated through control experiments, cyclic voltammetry studies, and Stern-Volmer quenching studies.

Impact of butylparaben on growth dynamics and microcystin-LR production in Microcystis aeruginosa.

The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.

Growth Stage-Dependent Variation in Soil Quality and Microbial Diversity of Ancient Gleditsia sinensis.

The environment monitoring of forest is vital for the ecosystem sustainable management, especially soil quality. Ancient Gleditsia sinensis is one of the most distributed ancient trees in Shaanxi. Comprehensive soil evaluate is important for the ancient tree protection. In this study, we selected the most distributed ancient tree Gleditsia sinensis and immature tree to compare the effect of growth stage to soil quality and soil bacteria. Most ancient tree soil nutrients were in good condition compared with immature tree. The bacterial community were composed with Proteobacteria (27.55%), Acidobacteriota (16.82%), Actinobacteriota (15.77%), Gemmatimonadota (6.82%), Crenarchaeota (4.61%), Bacteroidota (4.41%), Firmicutes (4.32%), Chloroflexi (4.28%), Planctomycetota (3.24%) and Verrucomicrobiota (3.04%). The level 2 ancient tree (300-400 years old) was different in bacterial community diversity. SOC and STN were important to level 2 (300-400 years old Gleditsia sinensis), and other levels were opposite. Our results suggested that the ancient tree management should not be lumped together.

Preoperative blood urea nitrogen-to-serum albumin ratio for prediction of in-hospital mortality in patients who underwent emergency surgery for acute type A aortic dissection.

The study aimed to assess the predictive value of blood urea nitrogen (BUN)-to-albumin ratio (BA-R) for in-hospital mortality in patients undergoing emergency surgery for acute type A aortic dissection (ATAAD). Patients who were diagnosed with ATAAD and underwent emergency surgery within 48 hours of onset at our hospital between January 2015 and December 2021 were included in this study. The primary endpoint of this study was postoperative in-hospital mortality (POIM). The data of the survivors and non-survivors were retrospectively compared analyses. A total of 557 ATAAD patients were included, with 505 survivors and 52 non-survivors. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (P < 0.001). Univariate regression analysis showed that preoperative BA-R, serum creatinine level, SA level, D-dimer level, age, myocardial ischemia, cerebral ischemia, and aortic clamp time were risk factors for POIM. In addition, multivariable regression analysis showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). Receiver operating characteristic curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (area under the curve =0.874). The sensitivity and specificity of preoperative BA-R in predicting the POIM of patients who underwent emergency surgery for ATAAD were 84.6% and 71.3%, respectively (95% confidence interval, 0.829-0.919; P < 0.001). In conclusion, Preoperative BA-R is a simple, rapid, and potentially useful prognostic indicator of POIM in patients with ATAAD. BAR: Blood urea nitrogen-to-albumin ratio, BUN: Blood urea nitrogen, SA: Serum albumin, REF: Reference. The aim of this study was to evaluate the prognostic value of BA-R for the prediction of postoperative in-hospital mortality in patients who underwent emergency surgery for ATAAD. A total of 557 patients with ATAAD were enrolled, and 505 survived while 52 did not. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (0.27 [0.18, 0.46] vs. 0.12 [0.10, 0.16]mmol/g; P < 0.001). The study showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). ROC curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (AUC = 0.874) and the sensitivity and specificity were 84.6% and 71.3%, respectively (95% CI, 0.829-0.919; P < 0.001). We believe that our study makes a significant contribution to the literature because we found preoperative BA-R to be a simple, rapid, and potentially useful prognostic indicator of postoperative in-hospital mortality in patients with ATAAD.

A mesoporous theranostic platform for ultrasound and photoacoustic dual imaging-guided photothermal and enhanced starvation therapy for cancer.

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O2) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. STATEMENT OF SIGNIFICANCE: A multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor.

Development of an innovative eugenol and borax-based orodispersible film for enhanced treatment of mouth ulcers.

Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development.

NeighborNet: Learning Intra- and Inter-Image Pixel Neighbor Representation for Breast Lesion Segmentation.

Breast lesion segmentation from ultrasound images is essential in computer-aided breast cancer diagnosis. To alleviate the problems of blurry lesion boundaries and irregular morphologies, common practices combine CNN and attention to integrate global and local information. However, previous methods use two independent modules to extract global and local features separately, such feature-wise inflexible integration ignores the semantic gap between them, resulting in representation redundancy/insufficiency and undesirable restrictions in clinic practices. Moreover, medical images are highly similar to each other due to the imaging methods and human tissues, but the captured global information by transformer-based methods in the medical domain is limited within images, the semantic relations and common knowledge across images are largely ignored. To alleviate the above problems, in the neighbor view, this paper develops a pixel neighbor representation learning method (NeighborNet) to flexibly integrate global and local context within and across images for lesion morphology and boundary modeling. Concretely, we design two neighbor layers to investigate two properties (i.e., number and distribution) of neighbors. The neighbor number for each pixel is not fixed but determined by itself. The neighbor distribution is extended from one image to all images in the datasets. With the two properties, for each pixel at each feature level, the proposed NeighborNet can evolve into the transformer or degenerate into the CNN for adaptive context representation learning to cope with the irregular lesion morphologies and blurry boundaries. The state-of-the-art performances on three ultrasound datasets prove the effectiveness of the proposed NeighborNet. The code is available at: https://github.com/fjcaoww/NeighborNet.

Dimerization activates the Inversin complex in C. elegans.

Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static "Inversin complex" or one that adopts multiple bioactive forms. Through characterization of hyperactive alleles in C. elegans , we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologs of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL-2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states-an active dimer and an inactive monomer-gates the output of the Inversin complex.

Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

Copper-catalyzed remote double functionalization of allenynes.

Addition reactions of molecules with conjugated or non-conjugated multiple unsaturated C-C bonds are very attractive yet challenging due to the versatile issues of chemo-, regio-, and stereo-selectivities. Especially for the readily available conjugated allenyne compounds, the reactivities have not been explored. The first example of copper-catalyzed 2,5-hydrofunctionalization and 2,5-difunctionalization of allenynes, which provides a facile access to versatile conjugated vinylic allenes with a C-B or C-Si bond, has been developed. This mild protocol has a broad substrate scope tolerating many synthetically useful functional groups. Due to the highly functionalized nature of the products, they have been demonstrated as platform molecules for the efficient syntheses of monocyclic products including poly-substituted benzenes, bicyclic compounds, and highly functionalized allene molecules.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.