Contributions of T Cell Signaling for Wound Healing.

It has long been known that T cells participate in wound healing, however, it is still enigmatic about the landscape of the signaling derived from T cells in the process of wound healing. With the advantages of scRNA-seq, in combination of immunofluorescent imaging, we identified activated T cells, cytotoxic T cells (CTLs), exhausting T cells and Tregs existing in inflammation phase of wound healing. Further analysis revealed each T cell population possess distinguished signals contributed to wound healing, some are critical for improving the wound healing quality. Besides, this study discovered and validated the exhistance of exhausting T cells among the T cells accumulated in skin duing wound healing, and the molecular mechanism(s) and contribution of exhausting T cells to wound healing deserves extensive studies in the future.

TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Cascade Synthesis of Fe-N2-Fe Dual-Atom Catalysts for Superior Oxygen Catalysis.

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N2-Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm-2), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm-2 at 25 oC and -40 oC, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N2-M DACs (M= Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications.

Research on the efficient EM modeling method from multilayered anisotropic medium-metal composite targets.

The paper presents a high-frequency modeling approach tailored for the electromagnetic (EM) scattering characteristics from electrically large radar targets coated with multi-layered anisotropic mediums (MLAMs). The approach begins by deriving the plane-wave spectrum expression for the incident EM field within MLAMs. It then employs spectral domain full-wave analysis method (SDFWAM) to obtain an analytical representation of the scattering field, further leveraging saddle point evaluation (SPE) to derive asymptotic solutions in the spatial domain. By integrating principles of physical optics (PO) and the tangent plane approximation, the far-field scattering characteristics of target enveloped in the specified medium are efficiently delineated. Validations against standard structure and the Misty satellite model reveal the method's pronounced alignment with the method of moments - finite element method (MoM-FEM) hybrid numerical algorithm, underscoring its notable computational efficiency. Furthermore, in conjunction with scattering sources decomposition technique, the approach is applied to optimize the radar cross-section (RCS) of the Su-57 aircraft, achieving precise and intelligent RCS control at minimal material cost. In conclusion, this research offers pivotal technological and theoretical foundations for EM scattering prediction, stealth design, and performance assessment in radar target domains.

Laser-assisted manipulation of Volta potential pattern on the TC4 surface for improved hBMSCs osteogenesis.

The Ti6Al4V (TC4) alloy, a prevalent biomedical material in orthopedics, still faces limitation of the insufficient osseointegration. To improve the bioactivity of TC4, introducing the electric environment onto the TC4 surface may be an effective way in the view of the necessity of endogenous electric microenvironment in bone regeneration. Herein, a Volta potential pattern was engendered on the TC4 surface via parallel laser patterning, so as to promote the osteogenic differentiation of cells. A 15 W laser successfully transformed the original α + ß dual phase towards radially distributed lath-like martensite phase in the laser treated region. The atomic lattice distortion between the heterogeneous microstructures of the laser treated and untreated regions leads to a significant Volta potential fluctuation on the TC4 surface. The Volta potential pattern as well as the laser-engraved microgrooves respectively induced mutually orthogonal cell alignments. The hBMSCs osteogenic differentiation was significantly enhanced on the laser treated TC4 surfaces in comparison to the surface without the laser treatment. Moreover, a drastic Volta potential gradient on the TC4 surface (treated with 15 W power and 400 µm interval) resulted in the most pronounced osteogenic differentiation tendency compared to other groups. Modulating the electric environment on the TC4 surface by manipulating the phase transformation may provide an effective way in evoking favorable cell response of bone regeneration, thereby improving the bioactivity of TC4 implant.

A novel model for relation prediction in knowledge graphs exploiting semantic and structural feature integration.

Relation prediction is a critical task in knowledge graph completion and associated downstream tasks that rely on knowledge representation. Previous studies indicate that both structural features and semantic information are meaningful for predicting missing relations in knowledge graphs. This has led to the development of two types of methods: structure-based methods and semantics-based methods. Since these two approaches represent two distinct learning paradigms, it is difficult to fully utilize both sets of features within a single learning model, especially deep features. As a result, existing studies usually focus on only one type of feature. This leads to an insufficient representation of knowledge in current methods and makes them prone to overlooking certain patterns when predicting missing relations. In this study, we introduce a novel model, RP-ISS, which combines deep semantic and structural features for relation prediction. The RP-ISS model utilizes a two-part architecture, with the first component being a RoBERTa module that is responsible for extracting semantic features from entity nodes. The second part of the system employs an edge-based relational message-passing network designed to capture and interpret structural information within the data. To alleviate the computational burden of the message-passing network on the RoBERTa module during the sampling process, RP-ISS introduces a node embedding memory bank, which updates asynchronously to circumvent excessive computation. The model was assessed on three publicly accessible datasets (WN18RR, WN18, and FB15k-237), and the results revealed that RP-ISS surpasses all baseline methods across all evaluation metrics. Moreover, RP-ISS showcases robust performance in graph inductive learning.

A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis. RESULTS: Here, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We find that the H3K9la levels are upregulated in endothelial cells in response to VEGF stimulation. Pharmacological inhibition of glycolysis decreases H3K9 lactylation and attenuates neovascularization. CUT& Tag analysis reveals that H3K9la is enriched at the promoters of a set of angiogenic genes and promotes their transcription. Interestingly, we find that hyperlactylation of H3K9 inhibits expression of the lactylation eraser HDAC2, whereas overexpression of HDAC2 decreases H3K9 lactylation and suppresses angiogenesis. CONCLUSIONS: Collectively, our study illustrates that H3K9la is important for VEGF-induced angiogenesis, and interruption of the H3K9la/HDAC2 feedback loop may represent a novel therapeutic method for treating pathological neovascularization.

Ultraviolet technology application in urban water supply and wastewater treatment in China: Issues, challenges and future directions.

This study thoroughly explores the application of Ultraviolet (UV) water treatment technology in urban wastewater treatment and water supply in China, highlighting its crucial role in enhancing water quality safety. UV technology, with its environmentally friendly and low-carbon characteristics, is deemed more in line with the demands of sustainable development compared to traditional chemical disinfection methods. The widespread application of UV technology in urban wastewater treatment in China, particularly in the context of urban sewage treatment, is examined. However, to better promote and apply UV technology, there is a need to deepen the understanding of this technology and its application among a broad base of users and design units. The importance of gaining in-depth knowledge about the performance of UV water treatment equipment, the design calculation basis, and operational considerations, as well as the ongoing development of relevant standards, is underscored to ensure that the equipment used in projects complies with engineering design and production requirements. Furthermore, the positive trend of UV technology in the field of advanced oxidation, indicating a promising trajectory for engineering applications, is pointed out. Regarding the prospects of industrial development, a thorough analysis is conducted in the article, emphasizing the necessity for all stakeholders to collaborate and adopt a multi-level approach to promote the sustainable development and application of UV water treatment technology. This collaborative effort is crucial for providing effective safeguards for China's environment, ecology, and human health.

Additive-Free Anode with High Stability: Nb2CTx MXene Prepared by HCl-LiF Hydrothermal Etching for Lithium-Ion Batteries.

MXenes, represented by Ti3C2Tx, have been widely studied in the electrochemical energy storage fields, including lithium-ion batteries, for their unique two-dimensional structure, tunable surface chemistry, and excellent electrical conductivity. Recently, Nb2CTx, as a new type of MXene, has attracted more and more attention due to its high theoretical specific capacity of 542 mAh g-1. However, the preparation of few-layer Nb2CTx nanosheets with high-quality remains a challenge, which limits their research and application. In this work, high-quality few-layer Nb2CTx nanosheets with a large lateral size and a high conductivity of up to 500 S cm-1 were prepared by a simple HCl-LiF hydrothermal etching method, which is 2 orders of magnitude higher than that of previously reported Nb2CTx. Furthermore, from its aqueous ink, the viscosity-tunable organic few-layer Nb2CTx ink was prepared by HCl-induced flocculation and N-methyl-2-pyrrolidone treatment. When using the organic few-layer Nb2CTx ink as an additive-free anode of lithium-ion batteries, it showed excellent cycling performance with a reversible specific capacity of 524.0 mAh g-1 after 500 cycles at 0.5 A g-1 and 444.0 mAh g-1 after 5000 cycles at 1 A g-1. For rate performance, a specific capacity of 159.8 mAh g-1 was obtained at a high current density of 5 A g-1, and an excellent capacity retention rate of about 95.65% was achieved when the current density returned to 0.5 A g-1. This work presents a simple and scalable process for the preparation of high-quality Nb2CTx and its aqueous/organic ink, which demonstrates important application potential as electrodes for electrochemical energy storage devices.

Impacts of permeability and effective diffusivity of porous scaffolds on bone ingrowth: In silico and in vivo analyses.

The permeability and the effective diffusivity of a porous scaffold are critical in the bone-ingrowth process. However, design guidelines for porous structures are still lacking due to inadequate understanding of the complex physiological processes involved. In this study, a model integrating the fundamental biological processes of bone regeneration was constructed to investigate the roles of permeability and effective diffusivity in regulating bone deposition in scaffolds. The in silico analysis results were confirmed in vivo by examining bone depositions in three diamond lattice scaffolds manufactured using selective laser melting. The findings show that the scaffolds with better permeability and effective diffusivity had deeper bone ingrowth and greater bone volume. Compared to permeability, effective diffusivity exhibited greater sensitivity to the orientation of porous structures, and bone ingrowth was deeper in the directions with higher effective diffusivity in spite of identical pore size. A 4.8-fold increase in permeability and a 1.6-fold increase in effective diffusivity by changing the porous structure led to a 1.5-fold increase in newly formed bone. The effective diffusivity of the porous scaffold affects the distribution of osteogenic growth factor, which in turn impacts cell migration and bone deposition through chemotaxis effects. Therefore, effective diffusivity may be a more suitable indicator for porous scaffolds because our study shows changes in this parameter determine changes in bone distribution and bone volume.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

Shanghai Community-Based Schizophrenia Cohort (SCS): a protocol for establishing a longitudinal cohort and research database of patients with schizophrenia receiving community-based mental health treatment.

INTRODUCTION: Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue. METHODS AND ANALYSIS: This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.

Enhancing psychiatric rehabilitation outcomes through a multimodal multitask learning model based on BERT and TabNet: An approach for personalized treatment and improved decision-making.

Evaluating the rehabilitation status of individuals with serious mental illnesses (SMI) necessitates a comprehensive analysis of multimodal data, including unstructured text records and structured diagnostic data. However, progress in the effective assessment of rehabilitation status remains limited. Our study develops a deep learning model integrating Bidirectional Encoder Representations from Transformers (BERT) and TabNet through a late fusion strategy to enhance rehabilitation prediction, including referral risk, dangerous behaviors, self-awareness, and medication adherence, in patients with SMI. BERT processes unstructured textual data, such as doctor's notes, whereas TabNet manages structured diagnostic information. The model's interpretability function serves to assist healthcare professionals in understanding the model's predictive decisions, improving patient care. Our model exhibited excellent predictive performance for all four tasks, with an accuracy exceeding 0.78 and an area under the curve of 0.70. In addition, a series of tests proved the model's robustness, fairness, and interpretability. This study combines multimodal and multitask learning strategies into a model and applies it to rehabilitation assessment tasks, offering a promising new tool that can be seamlessly integrated with the clinical workflow to support the provision of optimized patient care.

Mechano-driven intervertebral bone bridging via oriented mechanical stimulus in a twist metamaterial cage: An in silico study.

Stiffer cages provide sufficient mechanical support but fail to promote bone ingrowth due to stress shielding. It remains challenging for fusion cage to satisfy both bone bridging and mechanical stability. Here we designed a fusion cage based on twist metamaterial for improved bone ingrowth, and proved its superiority to the conventional diagonal-based cage in silico. The fusion process was numerically reproduced via an injury-induced osteogenesis model and the mechano-driven bone remodeling algorithm, and the outcomes fusion effects were evaluated by the morphological features of the newly-formed bone and the biomechanical behaviors of the bone-cage composite. The twist-based cages exhibited oriented bone formation in the depth direction, in comparison to the diagonal-based cages. The axial stiffness of the bone-cage composites with twist-based cages was notably higher than that with diagonal-based cages; meanwhile, the ranges of motion of the twist-based fusion segment were lower. It was concluded that the twist metamaterial cages led to oriented bone ingrowth, superior mechanical stability of the bone-cage composite, and less detrimental impacts on the adjacent bones. More generally, metamaterials with a tunable displacement mode of struts might provide more design freedom in implant designs to offer customized mechanical stimulus for osseointegration.

Sub-MIC vancomycin enhances the antibiotic tolerance of vancomycin-intermediate Staphylococcus aureus through downregulation of protein succinylation.

Bacteria develop tolerance after transient exposure to antibiotics, and tolerance is a significant driver of resistance. The purpose of this study is to evaluate the mechanisms underlying tolerance formation in vancomycin-intermediate Staphylococcus aureus (VISA) strains. VISA strains were cultured with sub-minimum inhibitory concentrations (sub-MICs) of vancomycin. Enhanced vancomycin tolerance was observed in VISA strains with distinct genetic lineages. Western blot revealed that the VISA protein succinylation (Ksucc) levels decreased with the increase in vancomycin exposure. Importantly, Ksucc modification, vancomycin tolerance, and cell wall synthesis were simultaneously affected after deletion of SacobB, which encodes a desuccinylase in S. aureus. Several Ksucc sites were identified in MurA, and vancomycin MIC levels of murA mutant and Ksucc-simulated (MurA(K69E) and MurA(K191E)) mutants were reduced. The vancomycin MIC levels of K65-MurA(K191E) in particular decreased to 1 mg/L, converting VISA strain K65 to a vancomycin-susceptible S. aureus strain. We further demonstrated that the enzymatic activity of MurA was dependent on Ksucc modification. Our data suggested the influence of vancomycin exposure on bacterial tolerance, and protein Ksucc modification is a novel mechanism in regulating vancomycin tolerance.

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10-30 , odds ratio = 3.12). Functional study showes that OR11H1-A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA-sequencing find that OR11H1-A63 markedly increased growth arrest and DNA-damage-inducible gamma (GADD45G) expression. Moreover, OR11H1-A63 activates the MAPK and NF-κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF-κB pathways. Collectively, this study suggests that the OR11H1-A63 missense mutation may increase susceptibility to VKH disease in a GADD45G-dependent manner.

SALW-Net: a lightweight convolutional neural network based on self-adjusting loss function for spine MR image segmentation.

Segmentation of intervertebral discs and vertebrae from spine magnetic resonance (MR) images is essential to aid diagnosis algorithms for lumbar disc herniation. Convolutional neural networks (CNN) are effective methods, but often require high computational costs. Designing a lightweight CNN is more suitable for medical sites lacking high-computing power devices, yet due to the unbalanced pixel distribution in spine MR images, the segmentation is often sub-optimal. To address this issue, a lightweight spine segmentation CNN based on a self-adjusting loss function, which is named SALW-Net, is proposed in this study. For SALW-Net, the self-adjusting loss function could dynamically adjust the loss weights of the two branches according to the differences in segmentation results and labels during the training; thus, the ability for learning unbalanced pixels is enhanced. Two separate datasets are used to evaluate the proposed SALW-Net. Specifically, the proposed SALW-Net has fewer parameter numbers than U-net (only 2%) but achieves higher evaluation scores than that of U-net (the average DSC score of SALW-Net is 0.8781, and that of U-net is 0.8482). In addition, the practicality validation for SALW-Net is also proceeding, including deploying the model on a lightweight device and producing an aid diagnosis algorithm based on segmentation results. This means our SALW-Net has clinical application potential for assisted diagnosis in low computational power scenarios.

A Lightweight Convolutional Neural Network Based on Dynamic Level-Set Loss Function for Spine MR Image Segmentation.

BACKGROUND: Spine MR image segmentation is important foundation for computer-aided diagnostic (CAD) algorithms of spine disorders. Convolutional neural networks segment effectively, but require high computational costs. PURPOSE: To design a lightweight model based on dynamic level-set loss function for high segmentation performance. STUDY TYPE: Retrospective. POPULATION: Four hundred forty-eight subjects (3163 images) from two separate datasets. Dataset-1: 276 subjects/994 images (53.26% female, mean age 49.02 ± 14.09), all for disc degeneration screening, 188 had disc degeneration, 67 had herniated disc. Dataset-2: public dataset with 172 subjects/2169 images, 142 patients with vertebral degeneration, 163 patients with disc degeneration. FIELD STRENGTH/SEQUENCE: T2 weighted turbo spin echo sequences at 3T. ASSESSMENT: Dynamic Level-set Net (DLS-Net) was compared with four mainstream (including U-net++) and four lightweight models, and manual label made by five radiologists (vertebrae, discs, spinal fluid) used as segmentation evaluation standard. Five-fold cross-validation are used for all experiments. Based on segmentation, a CAD algorithm of lumbar disc was designed for assessing DLS-Net's practicality, and the text annotation (normal, bulging, or herniated) from medical history data were used as evaluation standard. STATISTICAL TESTS: All segmentation models were evaluated with DSC, accuracy, precision, and AUC. The pixel numbers of segmented results were compared with manual label using paired t-tests, with P < 0.05 indicating significance. The CAD algorithm was evaluated with accuracy of lumbar disc diagnosis. RESULTS: With only 1.48% parameters of U-net++, DLS-Net achieved similar accuracy in both datasets (Dataset-1: DSC 0.88 vs. 0.89, AUC 0.94 vs. 0.94; Dataset-2: DSC 0.86 vs. 0.86, AUC 0.93 vs. 0.93). The segmentation results of DLS-Net showed no significant differences with manual labels in pixel numbers for discs (Dataset-1: 1603.30 vs. 1588.77, P = 0.22; Dataset-2: 863.61 vs. 886.4, P = 0.14) and vertebrae (Dataset-1: 3984.28 vs. 3961.94, P = 0.38; Dataset-2: 4806.91 vs. 4732.85, P = 0.21). Based on DLS-Net's segmentation results, the CAD algorithm achieved higher accuracy than using non-cropped MR images (87.47% vs. 61.82%). DATA CONCLUSION: The proposed DLS-Net has fewer parameters but achieves similar accuracy to U-net++, helps CAD algorithm achieve higher accuracy, which facilitates wider application. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

GlnR activated transcription of nitrogen metabolic pathway genes facilitates biofilm formation by mycobacterium abscessus.

OBJECTIVES: Nitrogen is indispensable for the synthesis of biomacromolecules. The correlation between nitrogen metabolism and Mycobacterium abscessus (M. abscessus) biofilm formation is unclear. This study constructed global nitrogen regulator gene GlnR (Mab_0744) knockout (ΔglnR) and complementation (ΔglnR::glnR) M. abscessus strains. METHODS: Global nitrogen regulator gene glnR (Mab_0744) knockout (ΔglnR) and complementation (ΔglnR::glnR) M. abscessus strains were constructed. Sauton's medium was used to culture M. abscessus pellicle biofilm. To test the antibiotic susceptibility of pellicle biofilm, clarithromycin, amikacin, cefoxitin or imipenem was added to the medium under biofilms after 14 days of incubation. RT-qPCR and ChIP-qPCR were performed to analyse the transcriptional regulatory function of GlnR. RESULTS: GlnR knockout decreased the growth rate of planktonic cells, reduced biofilm mass and wrinkle formation, and diminished the resistance of biofilms to antibiotics. However, the susceptibility of planktonic cells to antibiotics was not changed by glnR knockout. The growth rate of planktonic ΔglnR cells was accelerated by adding nitrogen sources to the medium; the addition of glutamine or sodium glutamate rescued ΔglnR biofilm morphology and resistance to amikacin, cefoxitin, clarithromycin and imipenem. GlnR bound the promoter region and activated the transcription of eight nitrogen metabolic pathway genes (i.e. glnA, amt, ansP, nirB, nirD, glnD, glnK and narK3), which are closely related to glutamine/glutamate biosynthesis and, thus, regulate biofilm formation. CONCLUSION: This study provides insights into the mechanisms of M. abscessus biofilm formation and its resistance to antibiotics.

A polyglutamic acid/tannic acid-based nano drug delivery system: Antibacterial, immunoregulation and sustained therapeutic strategies for oral ulcers.

Oral ulcers are a common inflammatory mucosal ulcer, and the moist and dynamic environment in the oral cavity makes topical pharmacological treatment of oral ulcers challenging. Herein, oral ulcer tissue adhesion nanoparticles were prepared by using esterification reaction between polyglutamic acid and tannic acid, and at the same time doxycycline hydrochloride was loaded into the nanoparticles. The obtained slow drug release effect of the drug-loaded nanoparticles reduced the toxicity of the drug, and by penetrating into the fine crevice region of the wound tissue and adhering to it, they could in-situ release the carried drug more effectively and thus have shown significant antibacterial effects. In addition, tannic acid in the system conferred adhesion, antioxidant and immune regulation activities to the nanocarriers. A rat oral ulcer model based on fluorescent labeling was established to investigate the retention of nanoparticles at the ulcer, and the results showed that the retention rate of drug-loaded nanoparticles at the ulcer was 17 times higher than that of pure drug. Due to the antibacterial and immune regulation effects of the drug-loaded nanoparticles, the healing of oral ulcer wounds was greatly accelerated. Such application of doxycycline hydrochloride loaded polyglutamic acid/tannic acid nanoparticles is a novel and effective treatment strategy for oral ulcer.