Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

Nitrogen and Nod factor signaling determine Lotus japonicus root exudate composition and bacterial assembly.

Symbiosis with soil-dwelling bacteria that fix atmospheric nitrogen allows legume plants to grow in nitrogen-depleted soil. Symbiosis impacts the assembly of root microbiota, but it is unknown how the interaction between the legume host and rhizobia impacts the remaining microbiota and whether it depends on nitrogen nutrition. Here, we use plant and bacterial mutants to address the role of Nod factor signaling on Lotus japonicus root microbiota assembly. We find that Nod factors are produced by symbionts to activate Nod factor signaling in the host and that this modulates the root exudate profile and the assembly of a symbiotic root microbiota. Lotus plants with different symbiotic abilities, grown in unfertilized or nitrate-supplemented soils, display three nitrogen-dependent nutritional states: starved, symbiotic, or inorganic. We find that root and rhizosphere microbiomes associated with these states differ in composition and connectivity, demonstrating that symbiosis and inorganic nitrogen impact the legume root microbiota differently. Finally, we demonstrate that selected bacterial genera characterizing state-dependent microbiomes have a high level of accurate prediction.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Soil microbial diversity and composition response to degradation of the alpine meadow in the southeastern Qinghai-Tibet Plateau.

With the interaction between global climate change and unreasonable human utilization, the alpine meadows on the Qinghai-Tibet Plateau have suffered various weathering degrees. Uncovering the degradation mechanism and restoration strategies can be facilitated by gaining insights into the diversity of soil microflora during meadow degradation. Therefore, we used Illumina sequencing technology to investigate the patterns of soil microbial diversity, microbial community composition, and the driving factors of microbial change in all non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and severely degraded (SD) alpine meadows in the southeastern Qinghai-Tibet Plateau. Our results pointed out that with the intensification of degradation, vegetation characteristics were significantly reduced, and soil parameters significantly varied among all degraded meadows. The contents of soil organic carbon (SOC), total nitrogen (TN), available phosphorus (AN), and total phosphorous (AK) in soils decreased with the increase of degradation. The dominant bacterial phyla were the same regardless of the meadow degradation level with Actinobacteria (37.67%) and Proteobacteria (20.62%) having the highest relative abundance. Meanwhile, the dominant fungi were Ascomycota (49.9%). Based on the linear discriminant analysis (LDA) and effect size (LEfSe) method, 38 bacterial and 49 fungal species were found to be affected in the degraded alpine meadow, most of which belonged to Actinobacteria and Ascomycota, respectively. Mantel test analysis illustrated that the bacterial community was mainly significantly dependent on below-ground biomass, pH, soil organic carbon, and total nitrogen, while the fungal community was significantly dependent on soil organic carbon, total nitrogen, available nitrogen, and available potassium. These results suggest that the degeneration of alpine meadows contributes to the variability of the diversity and composition of microflora on the Tibetan plateau. Yet this effect is mainly dependent on soil factors.

Correction: Luo et al. The Effects of Different Anode Positions on the Electrical Properties of Square-Silicon Drift Detector. Micromachines 2022, 13, 1496.

In the original publication [...].

Diagnosis and treatment of diabetic foot ulcer complicated with lower extremity vasculopathy: Consensus recommendation from the Chinese Medical Association (CMA), Chinese Medical Doctor Association (CMDA).

Diabetic foot ulcer complicated with lower extremity vasculopathy is highly prevalent, slow healing and have a poor prognosis. The final progression leads to amputation, or may even be life-threatening, seriously affecting patients' quality of life. The treatment of lower extremity vasculopathy is the focus of clinical practice and is vital to improving the healing process of diabetic foot ulcers. Recently, a number of clinical trials on diabetic foot ulcers with lower extremity vasculopathy have been reported. A joint group of Chinese Medical Association (CMA) and Chinese Medical Doctor Association (CMDA) expert representatives reviewed and reached a consensus on the guidelines for the clinical diagnosis and treatment of this kind of disease. These guidelines are based on evidence from the literature and cover the pathogenesis of diabetic foot ulcers complicated with lower extremity vasculopathy and the application of new treatment approaches. These guidelines have been put forward to guide practitioners on the best approaches for screening, diagnosing and treating diabetic foot ulcers with lower extremity vasculopathy, with the aim of providing optimal, evidence-based management for medical personnel working with diabetic foot wound repair and treatment.

Infiltrating Perfluorocarbon Nanoemulsion and Sensitizing Ultrasound Cavitation to Eradicate Biofilms.

Developing strategies for the treatment of bacterial biofilms is challenging due to their complex and resilient structure, low permeability to therapeutics, and ability to protect resident pathogens. Herein, we demonstrate that a polylysine-stabilized perfluorocarbon nanoemulsion is favored for penetrating biofilms and sensitizing the cavitation effect of low-intensity ultrasound, resulting in the dispersal of extracellular polymeric substances and killing of the protected cells. Through experiments, we observed a complete penetration of the nanoemulsion in a 40 µm Pseudomonas aeruginosa biofilm and demonstrated that it was induced by the fluidic perfluorocarbon, possibly attributing to its low surface tension. Furthermore, we presented an almost complete antibiofilm effect with a low-intensity ultrasound (1 MHz, 0.75 W/cm2, 5 min) in diverse cases, including cultured biofilms, colonized urinary catheters, and chronic wounds. During the treatment process, the perfluorocarbon phase enhanced the number and imploding energy of ultrasound cavities, thoroughly divided the biofilm structure, prevented biofilm self-healing, and sterilized the resident pathogens. Thus, the penetration and sensitization of the nanoemulsion might serve as a facile and potent strategy for eradicating biofilms in various applications.

Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent.

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.

Nano-Emulsified Perfluorooctyl Bromide Can Infiltrate Gram-Negative Bacteria and Sensitize Them to Ultrasound.

Gram-negative (G-) bacterial infections remain one of the most urgent global health threats, because the distinctive envelope structure hinders the penetration of therapeutics. Here, we showed that a perfluorooctyl bromide nanoemulsion (PFOB NE) uniquely interacts with G- bacteria. After cell envelope attachment, the PFOB can infiltrate the cell and was diffused throughout. In this process, it impaired the membranes by disintegrating phospholipid molecules, enhancing the consequent ultrasonic cavitation to break the envelope. We identified through ultrasound that the NE had remarkable bactericidal effects against various antibiotic-resistant pathogens. Using in situ sterilization, this approach accelerated the recovery of bacteria-infected murine skin wounds. Thus, combining PFOB and ultrasound might be an alternative tool for conquering the growing threat of G- pathogens.

A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo.

Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short-term safety and efficacy of two novel hyaluronic acid (HA)-triethylene glycol (TEG)-coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model. It is hypothesized that HA-hydrogel-augmented microfracture (MFX) is superior to MFX in enhancing early cartilage repair, and that the molar degree of substitution and concentration of HA affects repair. Chondral full-thickness defects in the knees of adult minipigs are treated with either 1) debridement (No MFX), 2) debridement and MFX, 3) debridement, MFX, and HA hydrogel (30% molar derivatization, 30 mg mL-1 HA; F3) (MFX+F3), and 4) debridement, MFX, and HA hydrogel (40% molar derivatization, 20 mg mL-1 HA; F4) (MFX+F4). After 8 weeks postoperatively, MFX+F3 significantly improves total macroscopic and histological scores compared with all other groups without negative effects, besides significantly enhancing the individual repair parameters "defect architecture," "repair tissue surface" (compared with No MFX, MFX), and "subchondral bone" (compared with MFX). These data indicate that photopolymerizable HA hydrogels enable a favorable metastable microenvironment promoting early chondrogenesis in vivo. This work also uncovers a mechanism for effective HA-augmented cartilage repair by combining lower molar derivatization with higher concentrations.

FGF21 promotes angiotensin II-induced abdominal aortic aneurysm via PI3K/AKT/mTOR pathway.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disorder with a high mortality rate. It was previously reported that fibroblast growth factor 21 (FGF21) was highly expressed in AAA patients. Nonetheless, its underlying mechanism in AAA progression is unclarified. METHODS: Angiotensin II (Ang-II) was used to induce AAA in human aortic vascular smooth muscle cells (HASMCs) and mouse models. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Immunofluorescence staining was utilized for detecting LC3B expression in HASMCs. Elastica van Gieson staining was conducted for histological analysis of the abdominal aortas of mice. RESULTS: FGF21 displayed a high level in Ang-II-stimulated HASMCs and AAA mice. FGF21 depletion ameliorated abdominal aorta dilation and Ang-II-triggered pathological changes in mice. FGF21 silencing hindered autophagy and PI3K/AKT/mTOR pathway. CONCLUSIONS: FGF21 contributes to AAA progression by enhancing autophagy and activating PI3K/AKT/mTOR pathway.

Ultrasmall Day-Night Photocatalysts of LnYVO4:Eu3+ (Ln = Nd, Tm, and Er) Nanoparticles.

Day-night photocatalysts that can persistently generate reactive oxygen species (ROS) after ceasing light attracted intensive attention in diverse fields. However, current strategies of combining a photocatalyst and an energy storage material can hardly fulfill the demands, especially in size. We herein present a one-phase sub-5 nm day-night photocatalyst via simply doping Nd, Tm, or Er into YVO4:Eu3+ nanoparticles, efficiently producing ROS in both day and night modes. We demonstrate that the rare earth ions acted as a ROS generator, and Eu3+ and defects contributed to the long persistency. Furthermore, the ultrasmall size led to remarkable bacterial uptake and bactericidal efficacy. Our finding suggests an alternative mechanism of day-night photocatalysts that could be ultrasmall and thus may shed light on disinfection and other applications.

Erbium oxide nanoplates as a sonosensitizer devoid of photosensitivity.

Phototoxicity is an undesirable consequence of photodynamic and most sonodynamic therapies. In the current work, we showed that Er2O3 nanoplates can avoid being cytotoxic when exposed to light and could be an effective sonosensitizer.

Novel aromatic carboxamide potentially targeting fungal succinate dehydrogenase: Design, synthesis, biological activities and molecular dynamics simulation studies.

BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs) emerging in fungicide markets are widely used in crop protection. Currently, the structural modification focusing on a structurally diverse 'core' moiety (aryl) of SDHIs is being gradually identified as one of the innovative strategies for developing novel, highly effective and low resistant fungicides. RESULTS: By optimization of lead compound SCU2028, 30 novel aromatic carboxamides Ia-o and IIa-o without a pyrazol group were designed, synthesized and characterized by 1 H NMR, 13 C NMR and high resolution mass spectrum (HRMS). In vitro antifungal activities showed that most of the compounds Ia-o and IIa-o exhibited good antifungal activities against Rhizoctonia solani. Among them, compounds Ic and IIc (EC50 = 0.02 mg/L), with the 2-chloro-3-pyridyl moiety, and compounds Io (EC50 = 0.03 mg/L) and IIo (EC50 = 0.02 mg/L), with the 4-methyl-2-trifluoromethylthiazolyl moiety, all exhibited the equivalent antifungal activities against R. solani with compound SCU2028 (EC50 = 0.03 mg/L) and bixafen (EC50 = 0.04 mg/L). Additionally, in pot tests, compound IIc (EC50 = 3.63 mg/L) also had higher antifungal activity against R. solani than compound SCU2028 (EC50 = 7.63 mg/L). Furthermore, in vitro inhibitory activity against fungal SDH showed the inhibitory ability of compound IIc was equivalent with that of compound SCU2028, and molecular dynamics simulation of the SDH-compound IIc complex suggested that compound IIc could strongly bind to and interact with the binding site of SDH. CONCLUSION: Novel aromatic carboxamides without a pyrazol group have potential as a class of SDHIs, and the strategy of replacing the pyrazol group with another aryl in the 'core' moiety might offer an alternative option in discovery of SDHI fungicides. © 2023 Society of Chemical Industry.

Nanoparticles that Transcytosed through Cancer Cells Can Elicit Immune Response.

Transcytosis is a crucial process that nanomedicines can experience in various delivery stages. However, little was known about whether it endows biofunctions to the nanomedicines. Here, we reported that transporting photodynamic nanoparticles across cancer cells via the endoplasmic reticulum (ER)-Golgi pathway formulated them with abundant neoantigens and damage-associated molecular patterns. The resultant nanoparticles (Tran-NPs) were potent in dendritic cell maturation and T cell activation. Meanwhile, the photodynamic Tran-NPs maintained their primary function of repolarizing immunosuppressive cells. The immune responses were observed in melanoma B16F10 tumor models. Our work suggested that the transcytosis process reprogrammed the nanoparticles with immunological properties, which might shed light on the design of nanomedicines.

The value of artificial intelligence in the diagnosis of lung cancer: A systematic review and meta-analysis.

Lung cancer is a common malignant tumor disease with high clinical disability and death rates. Currently, lung cancer diagnosis mainly relies on manual pathology section analysis, but the low efficiency and subjective nature of manual film reading can lead to certain misdiagnoses and omissions. With the continuous development of science and technology, artificial intelligence (AI) has been gradually applied to imaging diagnosis. Although there are reports on AI-assisted lung cancer diagnosis, there are still problems such as small sample size and untimely data updates. Therefore, in this study, a large amount of recent data was included, and meta-analysis was used to evaluate the value of AI for lung cancer diagnosis. With the help of STATA16.0, the value of AI-assisted lung cancer diagnosis was assessed by specificity, sensitivity, negative likelihood ratio, positive likelihood ratio, diagnostic ratio, and plotting the working characteristic curves of subjects. Meta-regression and subgroup analysis were used to investigate the value of AI-assisted lung cancer diagnosis. The results of the meta-analysis showed that the combined sensitivity of the AI-aided diagnosis system for lung cancer diagnosis was 0.87 [95% CI (0.82, 0.90)], specificity was 0.87 [95% CI (0.82, 0.91)] (CI stands for confidence interval.), the missed diagnosis rate was 13%, the misdiagnosis rate was 13%, the positive likelihood ratio was 6.5 [95% CI (4.6, 9.3)], the negative likelihood ratio was 0.15 [95% CI (0.11, 0.21)], a diagnostic ratio of 43 [95% CI (24, 76)] and a sum of area under the combined subject operating characteristic (SROC) curve of 0.93 [95% CI (0.91, 0.95)]. Based on the results, the AI-assisted diagnostic system for CT (Computerized Tomography), imaging has considerable diagnostic accuracy for lung cancer diagnosis, which is of significant value for lung cancer diagnosis and has greater feasibility of realizing the extension application in the field of clinical diagnosis.

Nanoparticle-Based Photodynamic Inhibition of Candida albicans Biofilms with Interfering Quorum Sensing.

Biofilm formation is a critical event in the pathogenesis and virulence of fungal infections caused by Candida albicans, giving rise to about a 1000-fold increase in the resistance to antifungal agents. Although photodynamic treatment (PDT) has been excellently implicated in bacterial infections, studies on its potential against fungal infection through the clearance of fungal biofilm formation remain at its infancy stage. Here, we have designed photodynamic nanoparticles with different sizes, modifications, and the ability of generating reactive oxygen species (ROS) to examine their effects on inhibiting biofilm formation and destructing mature biofilms of C. albicans. We found that the nanoparticles modified with oligo-chitosan exhibited a better binding efficiency for planktonic cells, leading to stronger inhibitory efficacy of the filamentation and the early-stage biofilm formation. However, for mature biofilms, the nanoparticles with the smallest size (∼15 nm) showed the fastest penetration speed and a pronounced destructing effect albeit conferring the lowest ROS-producing capability. The inhibitory effect of photodynamic nanoparticles was dependent on the disruption of fungal quorum sensing (QS) by the upregulation of QS molecules, farnesol and tyrosol, mediated through the upregulation of ARO 8 and DPP 3 expression. Our findings provide a powerful strategy of nanoparticulate PDT to combat fungal infections through the inhibition of both hyphal and biofilm formation by disrupting QS.

The Role of m6A in Osteoporosis and the Differentiation of Mesenchymal Stem Cells into Osteoblasts and Adipocytes.

Osteoporosis is a systemic disease in which bone mass decreases, leading to an increased risk of bone fragility and fracture. The occurrence of osteoporosis is believed to be related to the disruption of the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. N6-adenylate methylation (m6A) modification is the most common type of chemical RNA modification and refers to a methylation modification formed by the nitrogen atom at position 6 of adenine (A), which is catalyzed by a methyltransferase. The main roles of m6A are the post-transcriptional level regulation of the stability, localization, transportation, splicing, and translation of RNA; these are key elements of various biological activities, including osteoporosis and the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. The main focus of this review is the role of m6A in these two biological processes.

Gastric defect closure after endoscopic full-thickness resection: the closing while dissecting technique.

BACKGROUND: Complete closure of gastric wall defects is critical following endoscopic full-thickness resection (EFTR). The aim of this study was to evaluate the efficacy, safety, and clinical outcome of a new endoscopic method: closing while dissecting. METHODS: Twenty-seven patients who underwent EFTR were retrospectively analyzed between January 2020 and March 2021. Gastric defects resulting from EFTR were closed using the "interrupted-close during dissection" technique with endoclips. Tumor characteristics, en bloc resection rates, and postoperative adverse events were evaluated. RESULTS: All submucosal tumors were successfully resected and complete resection was histologically confirmed. The mean maximal tumor diameter was 1.3 cm (ranging from 0.8 to 3.0 cm). The majority of these tumors were gastrointestinal stromal tumors (n = 20), Leiomyoma (n = 3), schwannomas (n = 2), others included fibroma (n = 1) and neurogenic tumor (n = 1). There were no cases of hemorrhage, peritonitis, or delayed perforation. Four patients complained of slight abdominal pain, but no hyperpyrexia or serious elevated white blood cell count was detected in the first 24 h after treatment. All wounds were healed on follow-up endoscopy 3 months after the procedure. The mean follow-up duration was 8.5 months (ranging from 3 to 17) and no tumor recurrences were observed. CONCLUSIONS: The feasibility and safety of this interrupted-close during dissection approach allows for clinical applications in EFTR of gastric submucosal tumors.

Endoscopic fenestration combined with catheterization in the treatment of a giant colonic fecalith causing bowel obstruction: a case report.

Obstruction of the colon caused by a fecalith is not a rare condition, but endoscopic attempts at removal of the fecalith are often unsuccessful because of the size of the fecalith and its extremely hard stone-like consistency. We report a case of bowel obstruction of over two weeks' duration caused by a giant colonic fecalith. Conservative treatments including insertion of a gastric tube and enemas failed to resolve the obstruction. After an initial unsuccessful attempt at fecalith removal by colonoscopy using a snare, we successfully resolved the bowel obstruction over the course of subsequent colonoscopies with endoscopic fenestration of the fecalith and placement of a transrectal gastric tube for directed instillation of the enema fluid, and we were able to avoid surgical intervention in this case.