Adaptive higher-order singular value decomposition clutter filter for ultrafast Doppler imaging of coronary flow under non-negligible tissue motion.

BACKGROUND AND OBJECTIVE: With the development of advanced clutter-filtering techniques by singular value decomposition (SVD) and leveraging favorable acquisition settings such as open-chest imaging by a linear high-frequency probe and plane waves, several studies have shown the feasibility of cardiac flow measurements during the entire cardiac cycle, ranging from coronary flow to myocardial perfusion. When applying these techniques in a routine clinical setting, using transthoracic ultrasound imaging, new challenges emerge. Firstly, a smaller aperture is needed that can fit between ribs. Consequently, diverging waves are employed instead of plane waves to achieve an adequate field of view. Secondly, to ensure imaging at a larger depth, the maximum pulse repetition frequency has to be reduced. Lastly, in comparison to the open-chest scenario, tissue motion induced by the heartbeat is significantly stronger. The latter complicates substantially the distinction between clutter and blood signals. METHODS: This study investigates a strategy to overcome these challenges by diverging wave imaging with an optimal number of tilt angles, in combination with dedicated clutter-filtering techniques. In particular, a novel, adaptive, higher-order SVD (HOSVD) clutter filter, which utilizes spatial, temporal, and angular information of the received ultrasound signals, is proposed to enhance clutter and blood separation. RESULTS: When non-negligible tissue motion is present, using fewer tilt angles not only reduces the decorrelation between the received waveforms but also allows for collecting more temporal samples at a given ensemble duration, contributing to improved Doppler performance. The addition of a third angular dimension enables the application of HOSVD, providing greater flexibility in selecting blood separation thresholds from a 3-D tensor. This differs from the conventional threshold selection method in a 2-D spatiotemporal space using SVD. Exhaustive threshold search has shown a significant improvement in Contrast and Contrast-to-Noise ratio for Power Doppler images filtered with HOSVD compared to the SVD-based clutter filter. CONCLUSION: With the improved settings, the obtained Power Doppler images show the feasibility of measuring coronary flow under the influence of non-negligible tissue motion in both in vitro and ex vivo.

Bilateral Focal Choroidal Excavation and Central Serous Chorioretinopathy Coexisting in a Male Patient.

Background: Here, we report a case of a male patient with bilateral focal choroidal excavation (FCE) and central serous chorioretinopathy (CSC). A 33-year-old man complained of mild blurring of vision in the right eye. Optical coherence tomography (OCT) revealed FCE in both eyes, with subretinal fluid in both eyes and serous pigment epithelial detachment in the right eye. Standard laser fluence (50 J/cm2) was used in the right eye, and a subthreshold micropulse laser (SML) was simultaneously used in the left eye. Follow-up visits were recommended. At his last visit (5 months after treatment), the visual acuity was 16/20 in the right eye and 20/20 in the left eye and OCT showed a completed resolution of SRF. Conclusion: FCE is defined as a localized depression of the choroid detected by OCT. It may be congenital or acquired secondarily. We present a case of uncommon focal choroidal excavation and central serous chorioretinopathy (CSC) coexisting in both eyes at a relatively young age in which visual acuity was improved and subretinal fluid (SRF) completely resolved with laser treatment. Timely treatment can promote SRF absorption and improve vision.

Puerarin attenuates remifentanil­induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1.

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

Ultrasound Viscoelastography by Acoustic Radiation Force: A State-of-the-Art Review.

Ultrasound elastography (USE) is a promising tool for tissue characterization as several diseases result in alterations of tissue structure and composition, which manifest as changes in tissue mechanical properties. By imaging the tissue response to an applied mechanical excitation, USE mimics the manual palpation performed by clinicians to sense the tissue elasticity for diagnostic purposes. Next to elasticity, viscosity has recently been investigated as an additional, relevant, diagnostic biomarker. Moreover, since biological tissues are inherently viscoelastic, accounting for viscosity in the tissue characterization process enhances the accuracy of the elasticity estimation. Recently, methods exploiting different acquisition and processing techniques have been proposed to perform ultrasound viscoelastography. After introducing the physics describing viscoelasticity, a comprehensive overview of the currently available USE acquisition techniques is provided, followed by a structured review of the existing viscoelasticity estimators classified according to the employed processing technique. These estimators are further reviewed from a clinical usage perspective, and current outstanding challenges are discussed.

Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion: Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Screening of natural inhibitors against peptidyl arginine deiminase 4 from herbal extracts by a high-performance liquid chromatography ultraviolet-visible based method.

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.

Extraction, purification, structural characteristics and biological properties of the polysaccharides from Armillaria mellea (Vahl) P. Kumm.: A review.

Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.

Detection of Clostridium perfringens in donor milk at a human breast milk bank: a case report.

BACKGROUND: The breast milk bank is a professional organization that collects donor human milk (DHM) for special medical needs by recruiting qualified breast milk donors. Such organizations are also responsible for the disinfection, processing, testing, storage, distribution, and use of breast milk. As DHM is a biological product, it may get contaminated. Microbiological testing is the final step to determine microbial contamination of DHM. However, a universal method for the microbiological analysis of DHM in breast milk banks globally is lacking.DHM without strict screening may become a potential carrier of pathogens and seriously threaten the health of infants. Clostridium perfringens, a gram-positive anaerobic bacterium, is capable of causing wound infections, including gas gangrene, enteritis/enterocolitis, and enterotoxemia. Here, the first case of C. perfringens detected in DHM has been reported to facilitate the identification of such contamination in breast milk banks. CASE PRESENTATION: A breastfeeding mother donated 3000 mL of milk to the breast milk bank of the First Affiliated Hospital of the Army Medical University(over 2900 beds and patient receiving capacity of over 132,000), Chongqing, China. The milk sample was subjected to microbiological screening using liquid enrichment, followed by anaerobic and aerobic culturing. The results revealed the growth of C. perfringens in the anaerobic culture medium, but no bacteria or yeast-like fungi were observed in the aerobic culture medium. The donor did not exhibit any clinical symptoms, and her routine blood results and body temperature were normal. However, the infant fed with her milk had recurrent bloody stools. Breast milk bank infection control emergency handling as well as environmental sampling and investigation revealed that the cause was contamination of the donor's home-use breast pump with C. perfringens. The infant no longer experienced bloody stool once the donor changed the breast pump. CONCLUSIONS: C. perfringens can enter breast milk from contaminated pumping environments or devices, thus causing illness in infants. The microbiological testing of DHM in breast milk banks can be accomplished using liquid enrichment, along with anaerobic and aerobic culture, which is of immense significance in improving the standards for microbiological screening, DHM safety, and infant health.

Design and synthesis of ligustrazine derivatives as potential anti-Alzheimer's agents.

A novel series of ligustrazine derivatives was designed, synthesized, and evaluated as acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitors for the treatment of Alzheimer's disease (AD). In vitro studies displayed that some of the synthesized compounds revealed promising AChE and BuChE inhibitory effects. Particularly, compounds E12 and E27, indicated highly AChE inhibitory activity with IC50 values of 1.85 µM and 0.98 µM, respectively and showed noteworthy protective effects against on glutamate-induced SH-SY5Y cells damage at 1 µM and 10 µM concentrations. Furthermore, molecular simulation docking elucidates compounds E12 and E27 interacting with residues in the binding site of AChE (PDB code: 4EY7) and BuChE (PDB code: 1P0I), emphasizing the protein residues that participate in the main interactions with the two targets. Taken together, these results revealed that compounds E12 and E27 might be potential lead compounds for further structure optimization in the drug-discovery process against AD.

Conduction system pacing is superior to biventricular pacing in patients with heart failure: Insights from the pooled clinical studies.

Background: The effects of conduction system pacing (CSP) compared with conventional biventricular pacing (BVP) on heart function in patients with heart failure remain elusive. Methods: PubMed, Embase, Cochrane's Library and Web of science databases were searched up to 1 October 2022 for pertinent controlled studies. Random or fixed-effect model were used to synthesize the clinical outcomes. Subgroup analysis was performed to screen the potential confounding factors. Results: Fifteen studies including 1,347 patients were enrolled. Compared with BVP, CSP was significantly associated with shortened QRS duration [WMD -22.51 ms; p = 0.000], improved left ventricular ejection fraction [WMD 5.53%; p = 0.000], improved NYHA grade [WMD -0.42; p = 0.000], higher response rate and lower heart failure rehospitalization rate. CSP resulted in better clinical outcomes in higher male proportion group than lower one compared with BVP. No significant differences of clinical outcomes were observed between left bundle branch area pacing (LBBaP) and his bundle pacing (HBP) except the pacing threshold. The pacing threshold of LBBaP was significantly lower than those in BVP and HBP. Conclusion: This study suggests that CSP might be superior to conventional BVP for HF patients. In a higher male proportion group, CSP may be associated with more benefits than BVP. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355991; Identifier: CRD42022355991.

Shear-Wave Particle-Velocity Estimation and Enhancement Using a Multi-Resolution Convolutional Neural Network.

OBJECTIVE: Tissue mechanical properties are valuable markers for tissue characterization, aiding in the detection and staging of pathologies. Shear wave elastography (SWE) offers a quantitative assessment of tissue mechanical characteristics based on the SW propagation profile, which is derived from the SW particle motion. Improving the signal-to-noise ratio (SNR) of the SW particle motion would directly enhance the accuracy of the material property estimates such as elasticity or viscosity. METHODS: In this paper, we present a 3-D multi-resolution convolutional neural network (MRCNN) to perform improved estimation of the SW particle velocity Vz. Additionally, we propose a novel approach to generate training data from real acquisitions, providing high SNR ground truth target data, one-to-one paired to inputs that are corrupted with real-world noise and disturbances. DISCUSSION: By testing the network on in vitro data acquired from a commercial breast elastography phantom, we show that the MRCNN outperforms Loupas' autocorrelation algorithm with an improved SNR of 4.47 dB for the Vz signals, a two-fold decrease in the standard deviation of the downstream elasticity estimates, and a two-fold increase in the contrast-to-noise ratio of the elasticity maps. The generalizability of the network was further demonstrated with a set of ex vivo porcine liver data. CONCLUSION: The proposed MRCNN outperforms the standard autocorrelation method, in particular in low SNR regimes.

Acorus calamus var. angustatus Besser: Insight into current research on ethnopharmacological use, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

A. calamus var. angustatus Besser is an important traditional medicinal herb commonly used in China and other Asian countries. This study is the first systematic review of the literature to thoroughly analyze the ethnopharmacological application, phytochemistry, pharmacology, toxicology and pharmacokinetic properties of A. calamus var. angustatus Besser and provides a rationale for future research and prospects for application in clinical treatment. Information on relevant studies investigating A. calamus var. angustatus Besser was collected from SciFinder, the Web of Science, PubMed, CNKI, Elsevier, ResearchGate, ACS, Flora of China, and Baidu Scholar, etc. up to December 2022. In addition, information was also obtained from Pharmacopeias, books on Chinese herbal classics, local books, as well as PhD and MS dissertations. A. calamus var. angustatus Besser has played an important role in the herbal treatment of coma, convulsion, amnesia, and dementia for thousands of years. Studies investigating the chemical constituents of A. calamus var. angustatus Besser have isolated and identified 234 small-molecule compounds and a few polysaccharides. Among them, simple phenylpropanoids represented by asarone analogues and lignans are the two main active ingredients, which can be considered characteristic chemotaxonomic markers of this herb. In vitro and in vivo pharmacological studies indicated that crude extracts and active compounds from A. calamus var. angustatus Besser display a wide range of pharmacological activities, especially as treatment for Alzheimer's disease (AD), and anticonvulsant, antidepressant-like, anxiolytic-like, anti-fatigue, anti-Parkinson, neuroprotection, and brain protection properties, providing more evidence to explain the traditional medicinal uses and ethnopharmacology. The clinical therapeutic dose of A. calamus var. angustatus Besser does not present any toxic effects, but its main active ingredients α-asarone and ß-asarone at excessive dose may lead to toxicity, and in particular, their respective epoxide metabolites may exert potential toxicity to the liver. This review provides a reference and further information for the future development and clinical application of A. calamus var. angustatus Besser.

Reducing disulfide bonds as a robust strategy to facilitate the self-assembly of cod protein fabricating potential active ingredients-nanocarrier.

In this study, a novel method was developed to encapsulate hydrophobic compounds by self-assembly of cod protein (CP) triggered by breaking disulfide bonds. Curcumin (Cur), a representative lipid-soluble polyphenol, was selected as a model to evaluate the potential of CP nanoparticles as novel and accessible nanocarriers. Results showed that the protein structure gradually unfolded with increasing dithiothreitol (DTT) concentration, indicating that S-S cleavage was conducive to forming a looser structure. The resultant unfolded CP exposed more hydrophobic sites, facilitating its interaction with hydrophobic compounds. The encapsulation efficiency (EE) of formed CP-Cur nanoparticles was relatively high, reaching 99.09%, 98.8%, and 89.77% when the mass ratios of CP to Cur were 20:1, 10:1, and 5:1 (w/v), respectively. The hydrophobic interaction, weak van der Waals, and hydrogen bond were the forces contributing to the formation of CP-Cur nanoparticles, whereas the hydrophobic interaction played a crucial role. The CP-Cur complex exhibited increased stability and a homogeneous-stable structural phase. Thus, this research not only proposed a novel and simple encapsulation method of hydrophobic bioactive compounds but also provided a theoretical reference for the application of reductants in food or pharmacy system.

Synergistic effects of defocus-incorporated multiple segments and atropine in slowing the progression of myopia.

Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have revealed the treatment effects of defocus-incorporated multiple segments (DIMS) and topical atropine (ATP) on myopia control. However, no study has evaluated these two interventions together. In this retrospective study, we aimed to determine whether the combination of DIMS lenses and 0.01% ATP can slow the progression of myopia compared with DIMS lenses or single vision (SV) lenses alone. We included 107 children with myopia who were treated with DIMS and 0.01% ATP combination (DIMS + ATP group), DIMS monotherapy (DIMS group), or a control group (SV group). We compared treatment effects among three groups in axial length and myopia progression. After a 1-year follow-up, the DIMS + ATP group showed a smaller change in axial length and myopia progression than the DIMS and SV groups (P < 0.05). Hence, combination treatment with DIMS and 0.01% ATP might be a better choice for children with myopia.

Solanum nigrum Linn.: An Insight into Current Research on Traditional Uses, Phytochemistry, and Pharmacology.

Solanum nigrum Linn., is a common edible medicinal herb of the Solanaceae family which is native to Southeast Asia and is now widely distributed in temperate to tropical regions of Europe, Asia, and America. Traditionally, it has been used to treat various cancers, acute nephritis, urethritis, leucorrhea, sore throat, toothache, dermatitis, eczema, carbuncles, and furuncles. Up to now, 188 chemical constituents have been identified from S. nigrum. Among them, steroidal saponins, alkaloids, phenols, and polysaccharides are the major bioactive constituents. Investigations of pharmacological activities of S. nigrum revealed that this edible medicinal herb exhibits a wide range of therapeutic potential, including antitumor, anti-inflammatory, antioxidant, antibacterial, and neuroprotective activities both in vivo and in vitro. This article presents a comprehensive and systematic overview of the botanical, traditional uses, phytochemical compositions, pharmacological properties, clinical trials, and toxicity of S. nigrum to provide the latest information for further exploitation and applications of S. nigrum in functional foods and medicines.

Isodon rubescens (Hemls.) Hara.: A Comprehensive Review on Traditional Uses, Phytochemistry, and Pharmacological Activities.

Isodon rubescens is a medicinal and food plant, often eaten as a wild vegetable in ancient China, and has been widely used for decades to treat sore throats, tonsillitis, colds and headaches, bronchitis, chronic hepatitis, joint rheumatism, snake and insect bites, and various cancers. This comprehensive and systematic review of the ethnomedicinal uses, phytochemical composition, pharmacological activity, quality control and toxicology of I. rubescens provides updated information for the further development and application in the fields of functional foods and new drugs research. To date, a total of 324 substances have been isolated and identified from the plant, including terpenoids, flavonoids, polyphenols, alkaloids, amino acids, and volatile oils. Among these substances, diterpenoids are the most important and abundant bioactive components. In the past decades pharmacological studies have shown that I. rubescens has significant biological activities, especially in the modulation of antitumor and multidrug resistance. However, most of these studies have been conducted in vitro. In-depth in vivo studies on the quality control of its crude extracts and active ingredients, as well as on metabolite identification are still very limited. Therefore, more well-designed preclinical and clinical studies are needed to confirm the reported therapeutic potential of I. rubescens.

Development and Validation of a Novel Prognostic Nomogram Combined With Desmoplastic Reaction for Synchronous Colorectal Peritoneal Metastasis.

Purpose: The prognostic value of desmoplastic reaction (DR) has not been investigated in colorectal cancer (CRC) patients with synchronous peritoneal metastasis (SPM). The present study aimed to identify whether DR can predict overall survival (OS) and develop a novel prognostic nomogram. Methods: CRC patients with SPM were enrolled from a single center between July 2007 and July 2019. DR patterns in primary tumors were classified as mature, intermediate, or immature according to the existence and absence of keloid-like collagen or myxoid stroma. Cox regression analysis was used to identify independent factors associated with OS and a nomogram was developed subsequently. Results: One hundred ninety-eight and 99 patients were randomly allocated into the training and validation groups. The median OS in the training group was 36, 25, and 12 months in mature, intermediate, and immature DR categories, respectively. Age, T stage, extraperitoneal metastasis, differentiation, cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and DR categorization were independent variables for OS, based on which the nomogram was developed. The C-index of the nomogram in the training and validation groups was 0.773 (95% CI 0.734-0.812) and 0.767 (95% CI 0.708-0.826). The calibration plots showed satisfactory agreement between the actual outcome and nomogram-predicted OS probabilities in the training and validation cohorts. Conclusions: DR classification in the primary tumor is a potential prognostic index for CRC patients with SPM. The novel prognostic nomogram combined with DR classification has good discrimination and accuracy in predicting the OS for CRC patients with SPM.

B/A Measurement of Clear Cell Renal Cell Carcinoma versus Healthy Kidney Tissue.

The acoustic parameter of non-linearity B/A has been found capable of discriminating some types of pathological tissue from healthy tissue. The literature on the utility of B/A for cancer diagnostics is very limited, with measurements on the human breast and liver. This work expands the current research on cancer diagnostics by B/A assessment of eight slices of human clear cell renal cell carcinoma (ccRCC) from two patients and four slices of healthy kidney tissue from two healthy kidney samples. The Wilcoxon test identified the B/A distribution of malignant tissue as not significantly different from that of healthy tissue. An alternative way of defining outliers resulted in median B/A values of 8.1 for ccRCC and 6.8 for healthy tissue (p < 0.05). Acoustic attenuation at 2.1 MHz was significantly greater (p < 0.05) for ccRCC (1.7 dB/cm) than for healthy tissue (1.0 dB/cm). The observed differences in the measured values suggest that B/A and acoustic attenuation may represent potential diagnostic markers of ccRCC. More data and an improved experimental design are required to provide a definitive conclusion on the utility of B/A for cancer diagnostics.

Cyclic di-GMP regulates bacterial colonization and further biocontrol efficacy of Bacillus velezensis against apple ring rot disease via its potential receptor YdaK.

Bacillus species are among the most investigated beneficial bacteria and widely used in agricultural systems as biological control agents. Its biocontrol efficacy is controlled by diverse regulators. Cyclic diguanylate (c-di-GMP) is a nearly universal second messenger in bacteria and modulates various important physiological processes, including motility, biofilm formation, antifungal antibiotic production and host colonization. However, the impact of c-di-GMP on biocontrol efficacy of beneficial bacteria is unknown. Bacillus velezensis PG12 is an effective biocontrol strain against apple ring rot disease caused by Botryosphaeria dothidea. In this study, the contribution of c-di-GMP to biocontrol efficacy of B. velezensis PG12 was investigated. Deletion of single gene encoding diguanylate cyclase or phosphodiesterase did not affect its biocontrol efficacy against apple ring rot. However, artificial modulation of c-di-GMP level in the cells leads to a significant change of biocontrol efficacy, suggesting that c-di-GMP positively regulates biocontrol efficacy of B. velezensis PG12 against apple ring rot disease. More evidences indicate that c-di-GMP does not affect the antagonistic activity of B. velezensis PG12 against B. dothidea in vitro and in vivo, but positively regulates biofilm formation of B. velezensis PG12 and its colonization on apple fruits. Importantly, deletion of ydaK could rescue the inhibition of biofilm formation, bacterial colonization and biocontrol efficacy caused by low c-di-GMP level, indicating that YdaK is the potential c-di-GMP receptor to regulate biofilm formation, colonization and effective biological control. However, YdaK did not affect the antagonistic activity of B. velezensis PG12 against B. dothidea. Based on these findings, we propose that c-di-GMP regulates biofilm formation, subsequently the bacterial colonization on apple fruits and thus biocontrol efficacy of B. velezensis through its receptor YdaK. This is the first report showing that c-di-GMP plays a role in biocontrol efficacy of beneficial bacteria.