A rat model of cerebral small vascular disease induced by ultrasound and protoporphyrin.

Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 µm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD.

Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

A Planar-Structured Dinuclear Cobalt(II) Complex with Indirect Synergy for Photocatalytic CO2-to-CO Conversion.

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO2-to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s-1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and DFT calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two CoII ions, energetically feasible one step two-electron transfer process by Co2I,I intermediate to afford Co2II,II(CO22-) intermediate and fast mass transfer closely related with the planar structure.

Modified peroral endoscopic myotomy technique with retrograde on-demand myotomy for achalasia: a retrospective cohort study (with video).

BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.

Ba2+-doping introduced piezoelectricity and efficient Ultrasound-Triggered bactericidal activity of brookite TiO2 nanorods.

Exploring highly efficient ultrasound-triggered catalysts is pivotal for various areas. Herein, we presented that Ba2+ doped brookite TiO2 nanorod (TiO2: Ba) with polarization-induced charge separation is a candidate. The replacement of Ba2+ for Ti4+ not only induced significant lattice distortion to induce polarization but also created oxygen vacancy defects for facilitating the charge separation, leading to high-efficiency reactive oxygen species (ROS) evolution in the piezo-catalytic processes. Furthermore, the piezocatalytic ability to degrade dye wastewater demonstrates a rate constant of 0.172 min-1 and achieves a 100 % antibacterial rate at a low dose for eliminating E. coli. This study advances that doping can induce piezoelectricity and reveals that lattice distortion-induced polarization and vacancy defects engineering can improve ROS production, which might impact applications such as water disinfection and sonodynamic therapy.

An Indocyanine Green-Based Nanocluster for Imaging Orthodox Endometriosis Lesions with Negative Contrast.

Indocyanine green (ICG), as the sole near-infrared dye FDA-approved, is limited in biomedical applications because of its poor photostability, lack of targeting, and rapid removal in vivo. Herein, we presented a nanoformulation of poly-l-lysine-indocyanine green-hyaluronic acid (PIH) and demonstrated that it can image orthodox endometriosis (EM) lesions with a negative contrast. The PIH nanocluster, with an average diameter of approximately 200 nm, exhibited improved fluorescence photostability and antioxidant ability compared to free ICG. In the in vivo imaging, EM lesions were visualized, featuring apparent voids and clear boundaries. After colocalizing with the green fluorescent protein, we concluded that the contrast provided by PIH peaked at 4 h postinjection and was observable for at least 8 h. The negative contrast, clear boundaries, and enhanced observable time might be due to the low permeation of PIH to lesions and the enhanced retention on the surfaces of lesions. Thus, our findings suggest an ICG-based nanoprobe with the potential to diagnose abdominal diseases.

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.

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.

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.

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.

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.

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.