The Application of Diaphragm Ultrasound in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Chronic Obstructive Pulmonary Disease (COPD) is a prevalent condition that poses a significant burden on individuals and society due to its high morbidity and mortality rates. The diaphragm is the main respiratory muscle, its function has a direct impact on the quality of life and prognosis of COPD patients. This article aims to review the structural measurement and functional evaluation methods through the use of diaphragmatic ultrasound and relevant research on its application in clinical practice for COPD patients. Thus, it serves to provide valuable insights for clinical monitoring of diaphragm function in COPD patients, facilitating early clinical intervention and aiding in the recovery of diaphragm function.

Contrast-enhanced ultrasound evaluation of primary renal squamous cell carcinoma: a case report.

Renal squamous cell carcinoma (RSCC) is very rare, and there are few reports about it so far. Here we report a unique case of renal squamous cell carcinoma examined by contrast-enhanced ultrasound(CEUS), which has never been reported before. In addition, the results of CEUS showed some unique features, different from other imaging examinations. The purpose of this case report is to clarify the CEUS findings of this case and analyze its potential value in early diagnosis of RSCC.

Hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in chronic HBV infection with a normal ALT level.

Aims: To discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level. Methods: 94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis. Results: There were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p < 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p < 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p < 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone. Conclusion: The hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.

Mechanistic insights into the regulation of plant phosphate homeostasis by the rice SPX2 - PHR2 complex.

Phosphate (Pi) starvation response (PHR) transcription factors play key roles in plant Pi homeostasis maintenance. They are negatively regulated by stand-alone SPX proteins, cellular receptors for inositol pyrophosphate (PP-InsP) nutrient messengers. How PP-InsP-bound SPX interacts with PHRs is poorly understood. Here, we report crystal structures of the rice SPX2/InsP6/PHR2 complex and of the PHR2 DNA binding (MYB) domain in complex with target DNA at resolutions of 3.1 Å and 2.7 Å, respectively. In the SPX2/InsP6/PHR2 complex, the signalling-active SPX2 assembles into a domain-swapped dimer conformation and binds two copies of PHR2, targeting both its coiled-coil (CC) oligomerisation domain and MYB domain. Our results reveal that the SPX2 senses PP-InsPs to inactivate PHR2 by establishing severe steric clashes with the PHR2 MYB domain, preventing DNA binding, and by disrupting oligomerisation of the PHR2 CC domain, attenuating promoter binding. Our findings rationalize how PP-InsPs activate SPX receptor proteins to target PHR family transcription factors.

Research Progress on Diaphragm Ultrasound in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) is a common disease of the respiratory system, and its prevalence and mortality remain high. COPD results in continuous impairment of lung function, which severely affects the patient's work and life. In severe cases, there will be acute respiratory failure, which endangers the lives of patients, and respiratory muscle dysfunction is one of the main reasons for this result. As the diaphragm is the most important inspiratory muscle, its dysfunction has a great impact on the deterioration of respiratory function in COPD patients. With the development of ultrasound, more and more studies have found that diaphragm ultrasound can play an important role in the diagnosis and treatment of COPD patients. The main purpose of this article is to review the research progress on diaphragm ultrasound in COPD and briefly introduce diaphragmatic ultrasound examination methods.

A conservative pathway for coordination of cell wall biosynthesis and cell cycle progression in plants.

The mechanism that coordinates cell growth and cell cycle progression remains poorly understood; in particular, whether the cell cycle and cell wall biosynthesis are coordinated remains unclear. Recently, cell wall biosynthesis and cell cycle progression were reported to respond to wounding. Nonetheless, no genes are reported to synchronize the biosynthesis of the cell wall and the cell cycle. Here, we report that wounding induces the expression of genes associated with cell wall biosynthesis and the cell cycle, and that two genes, AtMYB46 in Arabidopsis thaliana and RrMYB18 in Rosa rugosa, are induced by wounding. We found that AtMYB46 and RrMYB18 promote the biosynthesis of the cell wall by upregulating the expression of cell wall-associated genes, and that both of them also upregulate the expression of a battery of genes associated with cell cycle progression. Ultimately, this response leads to the development of curled leaves of reduced size. We also found that the coordination of cell wall biosynthesis and cell cycle progression by AtMYB46 and RrMYB18 is evolutionarily conservative in multiple species. In accordance with wounding promoting cell regeneration by regulating the cell cycle, these findings also provide novel insight into the coordination between cell growth and cell cycle progression and a method for producing miniature plants.

Perfluorocarbon Nanodroplets with Deep Tumor Penetration and Controlled Drug Delivery for Ultrasound/Fluorescence Imaging Guided Breast Cancer Therapy.

Some impediments, including insufficient drug release, poor tumor penetration, and lack of real-time imaging guidance, still limited the therapeutic efficiency of nanotechnology-based drug delivery systems. Here, light-responsive perfluoropentane (PFP) based nanodroplets as doxorubicin (DOX) nanocarriers that could achieve deep tumor delivery under multimodal imaging guidance were developed. Triggered by laser irradiation, the liquid PFP with low boiling point could go through small-to-big size change and liquid-to-gas phase transformation. At the same time, the accompanied cavitation effect led to not only the disruption of dense extracellular matrix for deep penetration but also the disruption of endo-/lysosome for nucleus delivery of released DOX. Furthermore, different from many imaging approaches which were always "on", only upon laser stimulation could the nanodroplets act as ultrasound/fluorescence probes due to the echogenic PFP bubbles and the recovered fluorescence of DOX itself after released from nanodroplets, which was highly desirable to indicate the DOX state in real time. Therefore, such PFP nanodroplets with phase/size tunable properties enable site-specific drug delivery efficiently and exhibit their potent in cancer theranostics.

Increased photodynamic therapy sensitization in tumors using a nitric oxide-based nanoplatform with ATP-production blocking capability.

Photodynamic therapy (PDT) efficacy in cancer cells is affected by sub-physiological hypoxia caused by dysregulated and "chaotic" tumor microvasculature. However, current traditional O2-replenishing strategies are undergoing their own intrinsic deficiencies. In addition, resistance mechanisms activated during PDT also lead the present situation far from satisfactory. Methods: We propose a nitric oxide (NO)-based theranostic nanoplatform by using biocompatible poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) as carriers, in which the outer polymeric layer embeds chlorin e6 (Ce6) and incorporates L-Arginine (L-Arg). This nanoplatform (L-Arg@Ce6@P NPs) can reduce hyperactive O2 metabolism of tumor cells by NO-mediated mitochondrial respiration inhibition, which should raise endogenous O2 tension to counteract hypoxia. Furthermore, NO can also hinder oxidative phosphorylation (OXPHOS) which should cause intracellular adenosine triphosphate (ATP) depletion, inhibiting tumor cells proliferation and turning cells more sensitive to PDT. Results: When the L-Arg@Ce6@P NPs accumulate in solid tumors by the enhanced permeability and retention (EPR) effect, locally released L-Arg is oxidized by the abundant H2O2 to produce NO. In vitro experiments suggest that NO can retard hypoactive O2 metabolism and save intracellular O2 for enhancing PDT efficacy under NIR light irradiation. Also, lower intracellular ATP hinders proliferation of DNA, improving PDT sensitization. PDT phototherapeutic efficacy increased by combining these two complementary strategies in vitro/in vivo. Conclusion: We show that this NO-based nanoplatform can be potentially used to alleviate hypoxia and sensitize tumor cells to amplify the efficacy of phototherapy guided by photoacoustic (PA) imaging.

A measurement method of knee joint space width by ultrasound: a large multicenter study.

BACKGROUND: Although plain radiology is the primary method for assessing joint space width (JSW), it has poor sensitivity to change over time in regards to determining longitudinal progression. We, therefore, developed a new ultrasound (US) measurement method of knee JSW and aimed to provide a monitoring method for the change of JSW in the future. METHODS: A multicenter study was promoted by the Professional Committee of Musculoskeletal Ultrasound, the Ultrasound Society, and the Chinese Medical Doctor Association. US study of knee specimens determined the landmarks for ultrasonic measurement of knee JSW. The US of 1,272 participants from 27 centers was performed to discuss the feasibility and possible influencing factors of knee JSW. The landmarks for US measurement of knee JS, the inflection point of medial femoral epicondyle and the proximal end of the tibia, were determined. RESULTS: The mean knee JSW1 (medial knee JSW) was 8.57±1.95 mm in females and 9.52±2.31 mm in males. The mean knee JSW2 (the near medial knee JSW) was 9.07±2.24 mm in females and 10.17±2.35 mm in males. The JSW values of males were significantly higher than those of females, with a statistical difference. JSW values were negatively correlated with age and body mass index (BMI) to different degrees and positively correlated with height. CONCLUSIONS: The novel US measurement method can be used to measure knee JSW.

Herceptin-decorated paclitaxel-loaded poly(lactide-co-glycolide) nanobubbles: ultrasound-facilitated release and targeted accumulation in breast cancers.

Ultrasound can promote the drug release from drug-loaded substances and alter the tumor local microenvironment to facilitate the transport of drug carriers into the tumor tissues. Based on the altered tumor microenvironment, nanobubbles (NBs) as drug carriers with surfaces functionalized with targeting ligands can reach the tumor sites, thereby increasing the efficacy of chemotherapy. Herein, paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) NBs are prepared as drug carriers with covalently conjugated herceptin (anti-HER2 monoclonal antibody) on the surface to guide the target. The effect of ultrasound on the drug release and targeting of the herceptin-conjugated drug-loaded nanobubbles (PTX-NBs-HER) on the cancerous cells is determined. The use of ultrasound significantly improves the cell targeting capability in vitro, and efficiency of enhanced permeability and retention in vivo. The combination of PTX-NBs-HER and ultrasound facilitates the release of PTX, as well as the uptake and cell apoptosis in vitro. The in vivo application of both PTX-NBs-HER and ultrasound enhances the PTX targeting and accumulation in breast cancers while reducing the transmission and distribution of PTX in healthy organs. The combination of ultrasound with PTX-NBs-HER as contrast agents and drug carriers affords an image-guided drug delivery system for the precise targeted therapy of tumors.

Delineation of pentatricopeptide repeat codes for target RNA prediction.

Members of the pentatricopeptide repeat (PPR) protein family are sequence-specific RNA-binding proteins that play crucial roles in organelle RNA metabolism. Each PPR protein consists of a tandem array of PPR motifs, each of which aligns to one nucleotide of the RNA target. The di-residues in the PPR motif, which are referred to as the PPR codes, determine nucleotide specificity. Numerous PPR codes are distributed among the vast number of PPR motifs, but the correlation between PPR codes and RNA bases is poorly understood, which hinders target RNA prediction and functional investigation of PPR proteins. To address this issue, we developed a modular assembly method for high-throughput construction of designer PPRs, and by using this method, 62 designer PPR proteins containing various PPR codes were assembled. Then, the correlation between these PPR codes and RNA bases was systematically explored and delineated. Based on this correlation, the web server PPRCODE (http://yinlab.hzau.edu.cn/pprcode) was developed. Our study will not only serve as a platform for facilitating target RNA prediction and functional investigation of the large number of PPR family proteins but also provide an alternative strategy for the assembly of custom PPRs that can potentially be used for plant organelle RNA manipulation.

Diagnostic performance of two-dimensional shear wave elastography for evaluating tibial nerve stiffness in patients with diabetic peripheral neuropathy.

OBJECTIVES: To evaluate the stiffness of the tibial nerve with two-dimensional shear wave elastography (2D-SWE) and to determine whether 2D-SWE can be used to diagnose diabetic peripheral neuropathy (DPN). METHODS: The study included 70 consecutive diabetic patients with DPN or without DPN and 20 healthy volunteers. The tibial nerve stiffness measured with 2D-SWE was studied. The differences in stiffness values among patients with DPN, patients with clinically defined DPN, patients without DPN, and healthy volunteers based on clinical features and electrodiagnostic tests were evaluated with the Mann-Whitney U test and the Kruskal-Wallis test. Inter- and intraobserver variability was evaluated, and a receiver operator characteristic curve analysis was performed. RESULTS: The tibial nerve stiffness based on mean (EMean), minimum (EMin), and maximum (EMax) shear elasticity indices was significantly higher in patients with DPN and clinically defined DPN than that in patients without DPN and control subjects (p < 0.05). The area under the curve (AUC) for the SWE measurements of EMean, EMin, and EMax was 0.846, 0.867, and 0.821, respectively. An EMin cutoff value of 45.7 kPa had a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 74.0%, 87.6%, 6.0, and 0.3, respectively. The inter- and intraobserver agreements were excellent for the SWE measurements. CONCLUSIONS: Tibial nerve stiffness is significantly higher in diabetic patients with DPN and clinically defined DPN. The EMean and EMin have a good accuracy for identifying DPN. Minor degree of peripheral nerve lesions appear to might exist in patients with clinically defined DPN, not detectable by electrophysiology. 2D-SWE has a potential use for cases with clinically defined DPN and can be detected with 2D-SWE. KEY POINTS: • 2D-SWE elastography is a noninvasive method that can be used to evaluate precise nerve stiffness for diagnosing DPN. • Minor degree of neurologic lesion might exist early in patients with clinically defined DPN and can be detected by 2D-SWE. • E Min and E Mean of SWE elasticity indices have better diagnostic accuracies than E Max for identifying DPN.

Degradation of norfloxacin in aqueous solution by atmospheric-pressure non-thermal plasma: Mechanism and degradation pathways.

Norfloxacin is a synthetic antibiotics drug which is widely used in the treatment of infectious diseases and also often carelessly released into natural environment resulting in antibiotics-contaminated wastewater. In this work, we employed atmospheric-pressure non-thermal dielectric barrier discharge (DBD) to treat norfloxacin-contaminated water and investigated the degradation efficiency and mechanism for the plasma treatments under different conditions with varied working gas atmospheres. Our results showed that the DBD efficiency for norfloxacin degradation depended on reactive oxygen/nitrogen species (RONS) produced in the plasma treatment, while the plasma-induced hydroxyl radical played a critical role in the norfloxacin degradation. For O2-DBD, except for the contribution from reactive oxygen species (ROS), ozone could also play an important role. For N2-DBD, reactive nitrogen species (RNS) could work synergistically with H2O2 to enhance the degradation effect. We also checked the plasma activated liquid (PAL) effect and analyzed the degradation products so that the degradation mechanism and pathways could be elucidated. This work may therefore provide the guidance for effective and feasible application of low-temperature plasma technology in treatment of antibiotics-contaminated wastewater.

RNA editing machinery in plant organelles.

RNA editing is a type of post-transcriptional modification that includes nucleotide insertion/deletion or conversion. Different categories of RNA editing have been widely observed in distinct RNAs from divergent organisms. In flowering plants, RNA editing usually alters cytidine to uridine in plastids and mitochondria, playing important roles in various plant developmental processes, including organelle biogenesis, adaptation to environmental changes, and signal transduction. Numerous studies have demonstrated that a number of factors are involved in plant RNA editing, such as pentatricopeptide repeat (PPR) proteins, multiple organelle RNA editing factors (MORF, also known as RIP), organelle RNA recognition motif (ORRM) containing proteins, protoporphyrinogen IX oxidase 1 (PPO1) and organelle zinc finger 1 (OZ1). These factors play diverse roles in plant RNA editing due to their distinct characteristics. In this review, we discuss the functional roles of the individual editing factors and their associations in plant RNA editing.

MORF9 increases the RNA-binding activity of PLS-type pentatricopeptide repeat protein in plastid RNA editing.

RNA editing is a post-transcriptional process that modifies the genetic information on RNA molecules. In flowering plants, RNA editing usually alters cytidine to uridine in plastids and mitochondria. The PLS-type pentatricopeptide repeat (PPR) protein and the multiple organellar RNA editing factor (MORF, also known as RNA editing factor interacting protein (RIP)) are two types of key trans-acting factors involved in this process. However, how they cooperate with one another remains unclear. Here, we have characterized the interactions between a designer PLS-type PPR protein (PLS)3PPR and MORF9, and found that RNA-binding activity of (PLS)3PPR is drastically increased on MORF9 binding. We also determined the crystal structures of (PLS)3PPR, MORF9 and the (PLS)3PPR-MORF9 complex. MORF9 binding induces significant compressed conformational changes of (PLS)3PPR, revealing the molecular mechanisms by which MORF9-bound (PLS)3PPR has increased RNA-binding activity. Similarly, increased RNA-binding activity is observed for the natural PLS-type PPR protein, LPA66, in the presence of MORF9. These findings significantly expand our understanding of MORF function in plant organellar RNA editing.

Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study.

AIM: The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. MATERIALS & METHODS: Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. RESULTS: PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. CONCLUSION: These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.

Structural basis for specific single-stranded RNA recognition by designer pentatricopeptide repeat proteins.

As a large family of RNA-binding proteins, pentatricopeptide repeat (PPR) proteins mediate multiple aspects of RNA metabolism in eukaryotes. Binding to their target single-stranded RNAs (ssRNAs) in a modular and base-specific fashion, PPR proteins can serve as designable modules for gene manipulation. However, the structural basis for nucleotide-specific recognition by designer PPR (dPPR) proteins remains to be elucidated. Here, we report four crystal structures of dPPR proteins in complex with their respective ssRNA targets. The dPPR repeats are assembled into a right-handed superhelical spiral shell that embraces the ssRNA. Interactions between different PPR codes and RNA bases are observed at the atomic level, revealing the molecular basis for the modular and specific recognition patterns of the RNA bases U, C, A and G. These structures not only provide insights into the functional study of PPR proteins but also open a path towards the potential design of synthetic sequence-specific RNA-binding proteins.

Experimental endostatin-GFP gene transfection into human retinal vascular endothelial cells using ultrasound-targeted cationic microbubble destruction.

PURPOSE: The purpose of this study was to investigate whether ultrasound-targeted cationic microbubble destruction could effectively deliver endostatin-green fluorescent protein (ES-GFP) plasmids to human retinal vascular endothelial cells (HRECs). METHODS: Cationic microbubbles (CMBs) were prepared and then compared with neutral microbubbles (NMBs) and liposomes. First, the two types of microbubbles were characterized in terms of size and zeta potential. The cell viability of the HRECs was measured using the 3-(4,5-dimthylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) assay. The transcription and expression of endostatin, VEGF, Bcl-2, and Bcl-xl were measured via quantitative real-time PCR (qPCR) and western blotting, respectively. RESULTS: CMBs differed significantly from NMBs in terms of the zeta potential, but no differences in size were detected. Following ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy, the transcription and expression of endostatin were highest in the CMB group (p<0.05), while the transcription and expression of VEGF, Bcl-2, and Bcl-xl were lowest compared with the other groups. Moreover, the inhibition of HREC growth was enhanced following treatment with CMBs compared with NMBs or liposomes in vitro (p<0.01). CONCLUSIONS: This study demonstrated that ultrasound-mediated cationic microbubbles could enhance the transfection efficiency of ES-GFP, which had obvious impacts on the inhibition of the growth process of HRECs in vitro. These results suggest that the combination of UTMD and ES-GFP compounds might be a useful tool for gene therapy targeting retinal neovascularization.

Injectable smart phase-transformation implants for highly efficient in vivo magnetic-hyperthermia regression of tumors.

A minimally invasive, highly efficient and versatile strategy is proposed for localized tumor regression by developing a smart injectable liquid-solid phase-transformation organic-inorganic hybrid composite material, i.e., magnetic-Fe-powder-dispersed PLGA (Fe/PLGA) implants for magnetic hyperthermia therapy of cancer.

Synergistic effects of ultrasound-targeted microbubble destruction and TAT peptide on gene transfection: an experimental study in vitro and in vivo.

Cell-permeable peptides (CPPs) and ultrasound-targeted microbubble destruction (UTMD) have tremendous potential for gene delivery. However, their applications are limited due to nonspecificity of CPPs and low transfection efficiency of UTMD. Here, we developed a 'smart' gene delivery system by encapsulating TAT peptide (TATp) and hepatocyte growth factor (HGF) gene within lipid microbubbles, in which TATp was protected from being enzymatically cleaved and HGF gene was protected from degradation. This new strategy had synergistic effects of UTMD and TATp on gene transfection. We investigated the efficacy and safety of HGF gene transfection mediated by the combination of UTMD and TATp in vitro and in vivo. The results from MTT assay and flow cytometry analyses indicated that the combination of UTMD and TATp could enhance HGF gene expression in HUVECs without any significant side effect on cell viability. In rat myocardial infarction models, we demonstrated that the protein and mRNA expressions of HGF in myocardium caused by the combination of UTMD and TATp were the highest. Histopathological findings demonstrated that the combination of UTMD and TATp enhanced myocardial microvasculature and ameliorated myocardial fibrosis. In conclusion, the combination of UTMD and TATp might be a safe and efficient technique for gene delivery.