Mechanism of agonist-induced activation of the human itch receptor MRGPRX1.

Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) are 4 primate-specific receptors that are recently reported to be responsible for many biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first identified human MRGPR, and its expression is restricted to primary sensory neurons. Due to its dual roles in itch and pain signaling pathways, MRGPRX1 has been regarded as a promising target for itch remission and pain inhibition. Here, we reported a cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 in an active conformation at an overall resolution of 3.0 Å via a NanoBiT tethering strategy. Compound 16 is a new pain-relieving compound with high potency and selectivity to MRGPRX1 over other MRGPRXs and opioid receptor. MRGPRX1 was revealed to share common structural features of the Gq-mediated receptor activation mechanism of MRGPRX family members, but the variable residues in orthosteric pocket of MRGPRX1 exhibit the unique agonist recognition pattern, potentially facilitating to design MRGPRX1-specific modulators. Together with receptor activation and itch behavior evaluation assays, our study provides a structural snapshot to modify therapeutic molecules for itch relieving and analgesia targeting MRGPRX1.

Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

BACKGROUND: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.

Comparative transcriptome analysis and identification of candidate bZIP transcription factors involved in anthraquinone biosynthesis in Rheum officinale Baill.

Rhubarb is a traditional medicinal plant in China, whose pharmacological effects derive mainly from its anthraquinones. However, the regulatory mechanism affecting anthraquinone biosynthesis in R. officinale remains poorly understood. We assembled a high-quality, full-length transcriptome using single-molecule real-time (SMRT) sequencing. 274 unigenes potentially involved in the biosynthesis of anthraquinones, including those in the shikimate, polyketide, MVA and MEP pathways, were identified based on full-length transcriptome. Differentially expressed genes (DEGs) induced by MeJA treatment and DEGs between different tissues were identified through next-generation sequencing (NGS), revealing the genes that may be involved in the biosynthesis of anthraquinones. The basic leucine zipper (bZIP) transcription factors of R. officinale were systematically identified. Key genes such as RobZIP50 and RobZIP53 were systematically identified and found to be associated with anthraquinone biosynthesis in R. officinale through differential expression, co-expression and protein interaction analyses. RobZIP50 and RobZIP53 were highly expressed in roots and rhizomes, and significantly increased after 12 h of MeJA treatment. Additionally, both RobZIP50 and RobZIP53 were localized exclusively in the nucleus, with RobZIP53 showing significant transcriptional activity. Taken together, our results suggest that RobZIP53 may play a role in regulating anthraquinone biosynthesis in R. officinale.

The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation.

Very long-chain fatty acids (VLCFAs) are fatty acids with a carbon chain length greater than 18 carbons (>C18) and exhibit various functions, such as in skin barrier formation, liver homeostasis, myelin maintenance, spermatogenesis, retinal function, and anti-inflammation. VLCFAs are absorbed by dietary or elongated from endogenous hexadecanoyl acids (C16). Similar to long-chain fatty acid synthesis, VLCFAs elongation begins with acyl-CoA and malonyl-CoA as sources, and the length of the acyl chain is extended by two carbon units in each cycle. However, the VLCFAs elongation machinery is located in ER membrane and consists of four components, FA elongase (ELOVL), 3-ketoacyl-CoA reductase (KAR), 3-hydroxyacyl-CoA dehydratase (HACD), and trans-2-enoyl-CoA reductase (TECR), which is different with the long-chain fatty acid machinery fatty acid synthase (FAS) complex. Although the critical components in the elongation cycle are identified, the detailed catalytic and regulation mechanisms are still poorly understood. Here, we focused on the structural and biochemical analysis of TECR-associated VLCFA elongation reactions. Firstly, we identified a stable complex of human HACD2-TECR based on extensive in vitro characterizations. Combining computational modeling and biochemical analysis, we confirmed the critical interactions between TECR and HACD1/2. Then, we proposed the putative substrate binding sites and catalytic residues for TECR and HACD2. Besides, we revealed the structural similarities of HACD with ELOVLs and proposed the possible competition mechanism of TECR-associated complex formation.

Minor clone of del(17p) provides a reservoir for relapse in multiple myeloma.

The deletion of chromosome 17p (del(17p)) is considered a crucial prognostic factor at the time of diagnosis in patients with multiple myeloma (MM). However, the impact of del(17p) on survival at different clonal sizes at relapse, as well as the patterns of clonal evolution between diagnosis and relapse and their prognostic value, has not been well described. To address these issues, we analyzed the interphase fluorescence in situ hybridization (iFISH) results of 995 newly diagnosed MM (NDMM) patients and 293 patients with MM at their first relapse. Among these patients, 197 had paired iFISH data at diagnosis and first relapse. Our analysis of paired iFISH revealed that a minor clone of del(17p) at relapse but not at diagnosis was associated with poor prognosis in MM (hazard ratio for median overall survival 1.64 vs. 1.44). Fifty-six and 12 patients developed one or more new cytogenetic abnormalities at relapse, mainly del(17p) and gain/amp(1q), respectively. We classified the patients into six groups based on the change patterns in the clonal size of del(17p) between the two time points. Patients who did not have del(17p) during follow-up showed the best outcomes, whereas those who acquired del(17p) during their disease course, experienced compromised survival (median overall survival: 61.3 vs. 49.4 months; hazard ratio =1.64; 95% confidence interval: 1.06-2.56; P<0.05). In conclusion, our data confirmed the adverse impact of a minor clone of del(17p) at relapse and highlighted the importance of designing optimal therapeutic strategies to eliminate high-risk cytogenetic abnormalities (clinicaltrials gov. identifier: NCT04645199).

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients. OBJECTIVE: The aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment. METHODS: DIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels. RESULTS: Proteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1ß) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1ß showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031). CONCLUSIONS: Local ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1ß may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients.

T(11;14) with multiple myeloma: Standard risk survival but slow and poor response.

We described 790 patients with newly diagnosed multiple myeloma, including 224 (28.4%) standard risk (SR) patients without t(11;14), 99 (12.5%) patients with t(11;14)alone, 58 (7.3%) with t(11;14) + HR, and 409 (51.8%) in the high-risk cytogenetic abnormality (HRCA) group including t(4;14), t(14;16), t(14;20), C1A1 and/or del(17p) but without t(11;14), to evaluate the impact of t(11;14) in NDMM patients on response rate, response kinetics and survival. Our study showed that NDMM patients in the t(11;14)alone group had similar PFS (49.3 vs. 50.7 months; P = 0.392) and OS (112.4 vs. NR months; P = 0.982) as those in the SR group. However, the t(11;14)alone group exhibited a significantly poorer depth of response compared to the SR group, particularly with a lower MRD negativity rate (60.0% vs. 76.0%, P = 0.009). In the t(11;14)alone group, MRD status did not significantly impact PFS or OS, which was in contrast to the other groups. Response kinetics analyses showed that the t(11;14)alone group had a slower response rate than the other subgroups (t(11;14)alone vs. SR vs. HRCA: median time to MRD negativity = 9.19 vs. 4.25 vs. 4.27 months; P < 0.001). Our study showed that t(11;14)alone was characterized by survival comparable to standard risk cytogenetics despite exhibiting the slowest timing of response onset and lowest plateau of remission, which suggested a relatively indolent clinical course.

Loss of Gst1 enhances resistance to MMS by reprogramming the transcription of DNA damage response genes in a Rad53-dependent manner in Candida albicans.

The DNA damage response is a highly conserved protective mechanism that enables cells to cope with various lesions in the genome. Extensive studies across different eukaryotic cells have identified the crucial roles played by components required for response to DNA damage. When compared to the essential signal transducers and repair factors in the DNA damage response circuitry, the negative regulators and underlying mechanisms of this circuitry have been relatively under-examined. In this study, we investigated Gst1, a putative glutathione transferase in the fungal pathogen Candida albicans. We found that under stress caused by the DNA damage agent MMS, GST1 expression was significantly upregulated, and this upregulation was further enhanced by the loss of the checkpoint kinases and DNA repair factors. Somewhat counterintuitively, deletion of GST1 conferred increased resistance to MMS, potentially via enhancing the phosphorylation of Rad53. Furthermore, overexpression of RAD53 or deletion of GST1 resulted in upregulated transcription of DNA damage repair genes, including CAS1, RAD7, and RAD30, while repression of RAD7 transcription in the GST1 deletion reversed the strain's heightened resistance to MMS. Finally, Gst1 physically interacted with Rad53, and their interaction weakened in response to MMS-induced stress. Overall, our findings suggest a negative regulatory role for GST1 in DNA damage response in C. albicans, and position Gst1 within the Rad53-mediated signaling pathway. These findings hold significant implications for understanding the mechanisms underlying the DNA damage response in this fungal pathogen and supply new potential targets for therapeutic intervention.

Parasitic behaviour and developmental morphology of Anastatus japonicus reared on the factitious host Antheraea pernyi.

The egg parasitoid Anastatus japonicus is a key natural enemy in the biological control of various agricultural and forestry pests. It is particularly used against the brown marmorated stink bug Halyomorpha halys and the emerging defoliator pest Caligula japonica in East Asia. It has been proved that the eggs of Antheraea pernyi can be used as a factitious host for the mass production of A. japonicus. This study systematically documented the parasitic behaviour and developmental morphology exhibited by A. japonicus on the eggs of A. pernyi. The parasitic behaviour of A. japonicus encompassed ten steps including searching, antennation, locating, digging, probing, detecting, oviposition, host-feeding, grooming, and resting. Oviposition, in particular, was observed to occur in three stages, with the parasitoids releasing eggs during the second stage when the body remained relatively static. Among all the steps of parasitic behaviour, probing accounted for the longest time, constituting 33.1% of the whole time. It was followed by digging (19.3%), oviposition (18.5%), antennation (9.6%), detecting (7.4%), and the remaining steps, each occupying less than 5.0% of the total event time. The pre-emergence of adult A. japonicus involves four stages: egg (0 to 2nd day), larva (3rd to 9th day), pre-pupa (10th to 13th day), pupa (14th to 22nd day), and subsequent development into an adult. Typically, it takes 25.60 ± 0.30 days to develop from an egg to an adult at 25℃. This information increases the understanding of the biology of A. japonicus and may provide a reference for optimising reproductive devices.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

Engineering Sandwiched Nanochannel Aptasensor for Efficiently Screening Cancer Cells.

Cancer cells are a class of important tumor biomarkers and are closely related to tumorous progression. It is urgent to develop a sensitive and highly efficient method for the rapid and accurate detection of cancer cells. Herein, an aptamer sandwiched nanochannel electrochemical sensor was established for the highly selective determination of cancer cells. By virtue of the porous nanochannels as the filter platform and immobilized with DNA aptamers for specifically capturing the cancer cells, the nanochannel-based electrochemical sensor denotes excellent performance for MCF-7 screening, and allowing a low limit of detection of 36 cells mL-1 . The nanochannels-based sandwich structure aptasensor not only presents an efficacious and reliable approach for cancer cell detection but also provides great advantage for preventing electrode passivation in the process of biomarkers analysis.

Bioinspired Hydrogen Peroxide-Activated Nanochannels and Their Applications in Cancer Cell Analysis.

Bioinspired nanochannels that manipulate ion transport have shown great potential for understanding complex physiological processes. Herein, inspired by the gating function of the biological ion channels, we designed and constructed artificial hydrogen peroxide (H2O2)-activated nanochannels by decorating the inner pore surface with 4-(phenoxymethyl) benzeneboronic acid pinacol ester (PBAE). Benefiting from the specific hydrolysis reaction between H2O2 and PBAE in the confined nanochannels, the functionalized artificial nanochannels exhibited a highly selective and sensitive response toward H2O2. The system could switch between open/closed states in the presence/absence of H2O2 by the ionic current test. Meanwhile, comsol simulations were carried out to evidence the mechanism of hydrogen peroxide triggered regulation of ion transport by the nanochannels. It was found that the surface charge density of the nanochannels changed along with the addition of H2O2. Furthermore, based on the sensing strategy, the PBAE-functionalized nanochannel membrane was applied in the detection of H2O2 in the tumor microenvironment, which achieved highly selective distinguishing of cancerous cells from normal cells. This work provides a versatile method to construct bioinspired nanochannel-based platforms for detecting small reactive molecules and offers prospects for the application of disease diagnosis and prognosis.

High-Yield, Magnetic Harvesting of Extracellular Outer-Membrane Vesicles from Escherichia coli.

Extracellular outer-membrane vesicles (OMVs) are attractive for use as drug nanocarriers, because of their high biocompatibility and ability to enter cells. However, widespread use is hampered by low yields. Here, a high-yield method for magnetic harvesting of OMVs from Escherichia coli is described. To this end, E. coli are grown in the presence of magnetic iron-oxide nanoparticles (MNPs). Uptake of MNPs by E. coli is low and does not increase secretion of OMVs. Uptake of MNPs can be enhanced through PEGylation of MNPs. E. coli growth in the presence of PEGylated MNPs increases bacterial MNP-uptake and OMV-secretion, accompanied by upregulation of genes involved in OMV-secretion. OMVs containing MNPs can be magnetically harvested at 60-fold higher yields than achieved by ultracentrifugation. Functionally, magnetically-harvested OMVs and OMVs harvested by ultracentrifugation are both taken-up in similar numbers by bacteria. Uniquely, in an applied magnetic field, magnetically-harvested OMVs with MNPs accumulate over the entire depth of an infectious biofilm. OMVs harvested by ultracentrifugation without MNPs only accumulate near the biofilm surface. In conclusion, PEGylation of MNPs is essential for their uptake in E. coli and yields magnetic OMVs allowing high-yield magnetic-harvesting. Moreover, magnetic OMVs can be magnetically targeted to a cargo delivery site in the human body.

Bifunctional nanozyme of copper organophyllosilicate for the ultrasensitive detection of hydroquinone.

The rapid development of nanozymes for ultrasensitive detection of contaminate has resulted in considerable attention. Herein, a carboxyl- and aminopropyl-functionalized copper organophyllosilicate (Cu-CAP) was synthesized by a facile, one-pot sol-gel method. The bifunctional groups endow it with superior catalytic activity than that of natural enzyme. Besides, it possesses outstanding catalytic stability under harsh conditions such as high temperature, extremely high or low pH, and high salinity. Apart from laccase-mimetic activity, Cu-CAP also shows oxidation of the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) to the blue-colored TMBox in the presence of H2O2, which is similar to natural horseradish peroxidase (HRP). Interestingly, this colorimetric system was suppressed by hydroquinone (HQ) specifically. Inspired by this, Cu-CAP was used to develop a highly sensitive and selective colorimetric method for the determination of HQ. This assay displayed an extremely low detection limit of 23 nM and was applied for the detection of HQ in environmental water with high accuracy. This approach offers a new route for the rational design of high performance nanozymes for environmental and biosensing applications.

Cationization of neutral small molecules by site-specific carboxylation of 10-phenyl-10H-phenothiazine in laser desorption/ionization.

It is a pre-requisite to ionize analyte molecules efficiently for detection by laser desorption/ionization mass spectrometry. Here, we report a conceptual demonstration of cationizing neutral small molecules which are typically difficult to be ionized with the traditional organic matrices due to their low proton/cation affinity values. Our strategy features generating radical cations from site-specifically carboxylated 10-(4-carboxyphenyl)-10H-phenothiazine-3,7-dicarboxylic acid (PTZ(A)2-Ph(A)) with a laser, and anchoring the chlorine ion from NaCl through covalent bond-like bridging interactions with the N/S atoms in the heterocyclic structure. This "Maverick" design allows a dramatic change of the energy landscape of analyte sodiation with an enhanced efficiency. We have synthesized two families of compounds based on the model structures of phenothiazine (PTZ) and phenoxazine (PXZ) and their carboxylated derivatives, and performed comparison between them or against the traditional organic matrices in a systematic format. We have demonstrated that PTZ(A)2-Ph(A) is outstanding as a novel MALDI matrix for the detection of oligosaccharides and amino acids, with an ultra-clean background baseline and high signal-to-noise ratios (up to dozens of times better than the traditional matrices). This work provides a new method for the cationization of neutral small molecules in a distinct mechanism, inspiring the development of next-generation matrices for sensitive detection of hard-to-be-ionized molecules by MALDI MS.

Optical Coherence Tomography-Based Patient-Specific Residual Multi-Thrombus Coronary Plaque Models With Fluid-Structure Interaction for Better Treatment Decisions: A Biomechanical Modeling Case Study.

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative antithrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. in vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after antithrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based fluid-structure interaction (FSI) models with different thrombus volumes, fluid-only, and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus, and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at thrombi 1 and 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after antithrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.

Intravenous methylprednisolone or immunoglobulin for anti-glutamic acid decarboxylase 65 antibody autoimmune encephalitis: which is better?

BACKGROUND: Patients positive for anti-glutamic acid decarboxylase 65 (GAD65) antibodies have attracted increasing attention. Their clinical manifestations are highly heterogeneous and can be comorbid with tumors. Currently, there is no consensus on the therapeutic regimen for anti-GAD65-associated neurological diseases due to the clinical complexity, rarity and sporadic distribution. We reported six anti-GAD65 autoimmune encephalitis (AE) patients who received intravenous methylprednisolone (IVMP) or immunoglobulin (IVIG) or both. Then, we evaluated the therapeutic effect of both by summarizing results in previous anti-GAD65 AE patients from 70 published references. RESULTS: Our six patients all achieved clinical improvements in the short term. Unfortunately, there was no significant difference between IVMP and IVIG in terms of therapeutic response according to the previous references, and the effectiveness of IVMP and IVIG was 45.56% and 36.71%, respectively. We further divided the patients into different subgroups according to their prominent clinical manifestations. The response rates of IVMP and IVIG were 42.65% and 32.69%, respectively, in epilepsy patients; 60.00% and 77.78%, respectively, in patients with stiff-person syndrome; and 28.57% and 55.56%, respectively, in cerebellar ataxia patients. Among 29 anti-GAD65 AE patients with tumors, the response rates of IVMP and IVIG were 29.41% and 42.11%, respectively. There was no significant difference in effectiveness between the two regimens among the different subgroups. CONCLUSION: Except for stiff-person syndrome, we found that this kind of AE generally has a poor response to IVMP or IVIG. Larger prospective studies enrolling large numbers of patients are required to identify the optimal therapeutic strategy in the future.

Mussel-Inspired Flexible, Wearable, and Self-Adhesive Conductive Hydrogels for Strain Sensors.

The latest generation of wearable devices features materials that are flexible, conductive, and stretchable, thus meeting the requirements of stability and reliability. However, the metal conductors that are currently used in various equipments cannot achieve these high performance expectations. Hence, a mussel-inspired conductive hydrogel (HAC-B-PAM) is prepared with a facile approach by employing polyacrylamide (PAM), dopamine-functionalized hyaluronic acid (HAC), borax as a dynamic cross-linker agent, and Li+ and Na+ as conductive ions. HAC-B-PAM hydrogels demonstrate an excellent stretchability (up to 2800%), high tensile toughness (42.4 kPa), self-adhesive properties (adhesion strength to porcine skin of 49.6 kPa), and good self-healing properties without any stimuli at room temperature. Furthermore, the fabricated hydrogel-based strain sensor is sensitive to deformation and can detect human body motion. Multifunctional hydrogels can be assembled into flexible wearable devices with potential applications in the field of electronic skin and soft robotics.

Using optical coherence tomography and intravascular ultrasound imaging to quantify coronary plaque cap thickness and vulnerability: a pilot study.

BACKGROUND: Detecting coronary vulnerable plaques in vivo and assessing their vulnerability have been great challenges for clinicians and the research community. Intravascular ultrasound (IVUS) is commonly used in clinical practice for diagnosis and treatment decisions. However, due to IVUS limited resolution (about 150-200 µm), it is not sufficient to detect vulnerable plaques with a threshold cap thickness of 65 µm. Optical Coherence Tomography (OCT) has a resolution of 15-20 µm and can measure fibrous cap thickness more accurately. The aim of this study was to use OCT as the benchmark to obtain patient-specific coronary plaque cap thickness and evaluate the differences between OCT and IVUS fibrous cap quantifications. A cap index with integer values 0-4 was also introduced as a quantitative measure of plaque vulnerability to study plaque vulnerability. METHODS: Data from 10 patients (mean age: 70.4; m: 6; f: 4) with coronary heart disease who underwent IVUS, OCT, and angiography were collected at Cardiovascular Research Foundation (CRF) using approved protocol with informed consent obtained. 348 slices with lipid core and fibrous caps were selected for study. Convolutional Neural Network (CNN)-based and expert-based data segmentation were performed using established methods previously published. Cap thickness data were extracted to quantify differences between IVUS and OCT measurements. RESULTS: For the 348 slices analyzed, the mean value difference between OCT and IVUS cap thickness measurements was 1.83% (p = 0.031). However, mean value of point-to-point differences was 35.76%. Comparing minimum cap thickness for each plaque, the mean value of the 20 plaque IVUS-OCT differences was 44.46%, ranging from 2.36% to 91.15%. For cap index values assigned to the 348 slices, the disagreement between OCT and IVUS assignments was 25%. However, for the OCT cap index = 2 and 3 groups, the disagreement rates were 91% and 80%, respectively. Furthermore, the observation of cap index changes from baseline to follow-up indicated that IVUS results differed from OCT by 80%. CONCLUSIONS: These preliminary results demonstrated that there were significant differences between IVUS and OCT plaque cap thickness measurements. Large-scale patient studies are needed to confirm our findings.

Changes in structure and function of bacterial and fungal communities in open composting of Chinese herb residues.

In this study, dynamic changes in bacterial and fungal communities, metabolic characteristics, and trophic modes in Chinese herb residues open composting for 30 days were analyzed by using high-throughput sequencing, PICRUSt, and FUNGuild, respectively. Bacillaceae and Basidiomycota predominated at the early composting stage, while Proteobacteria and Ascomycota became the dominant phyla during the active phase. Aerobic composting had a significant effect on bacterial metabolic characteristics and fungal trophic modes over the composting time. The function of the bacterial communities changed from environmental information processing to metabolism. Fungal communities changed as well, with the pathogenic fungi decreasing and wood saprotrophs increasing. These results indicated that open composting of Chinese herb residues not only influenced microbial community structure but also changed metabolic characteristics and trophic modes, which became the internal dynamics of composting.