Investigate the relationship between pulsed field ablation parameters and ablation outcomes.

BACKGROUND: Pulsed field ablation (PFA) is an emerging non-thermal ablation method. The primary challenge is the control of multiple parameters in PFA, as the interplay of these parameters remains unclear in terms of ensuring effective and safe tissue ablation. PURPOSE: This study employs the response surface method (RSM) to explore the interactions between various PFA parameters and ablation outcomes, and seeks to enhance the efficacy and safety of PFA. METHODS: In vivo experiments were conducted using rabbit liver for varying PFA parameters: pulse amplitude (PA), pulse interval (PI), number of pulse trains (NT), and number of pulses in a pulse train (NP). Ablation outcomes assessed included three ablation sizes, surface temperature, and muscle contraction strength. Additionally, histological analysis was performed on the ablated tissue. We analyzed the relationship between PFA parameters and ablation outcomes, and results were then compared with those from a simulation using an electric-thermal coupling PFA finite element model. RESULTS: A linear relationship between ablation outcomes and PFA parameters was established. PA and NT exhibited extremely significant (P < 0.0001) and significant effects (P < 0.05) on all ablation outcomes, respectively. NP showed an extremely significant impact (P < 0.0001) on surface temperature and muscle contraction strength, while PI significantly influenced (P < 0.05) muscle contraction strength alone. Histological analysis revealed that PFA produces controlled, well-defined areas of liver tissue necrosis. Surface temperature results from simulations and experiments were highly consistent (R2 > 0.97). CONCLUSIONS: This study clarifies the relationship between various PFA parameters and ablation outcomes, and aims to improve the efficacy and safety of PFA.

Boosting the Faradaic Efficiency of Br--Mediated Photoelectrochemical Epoxidation by Local Acidity on α-Fe2O3.

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br-/HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe2O3, in which low concentration of Br- as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.

[Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells].

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

A novel polarity configuration for enhancing ablation depth of pulsed field ablation: Design, modeling, and in vivo validation.

BACKGROUND: Pulsed field ablation (PFA) has been increasingly used to cut off the delivery of abnormal electrical signals in the treatment of cardiac arrhythmias. A successful cut off requires forming a layer of transmural damage on the heart wall, and this layer depends on the depth of ablation by PFA. PURPOSE: This study aims to propose a novel polarity configuration of PFA to increase the ablation depth in the treatment of cardiac arrhythmias. METHOD: A novel polarity configuration was designed for a multi-electrode system, where the number of electrodes is greater than two. The polarity configuration in such multi-electrode system is called the paired-electrode interlaced configuration (PIC). The existing configuration called the single-electrode interlaced configuration (SIC) was used to compare with the PIC. To both the SIC and PIC, a full-SIC or a full-PIC is called when all electrodes (anode, cathode) in a catheter is used otherwise partial-SIC or partial-PIC is called. By the comparison between the full-SIC and full-PIC, the benefit of the PIC was exhibited as opposed to the SIC, but an extra ablation step was added in the PIC in order to form a continuous ablation zone. The other comparative study was taken between a partial-PIC and a partial-SIC with the same number of ablation step. In this study, a rabbit model was built by infusing 0.4% saline solution (at 37°C) into the rabbit's abdominal cavity which surrounds the liver. This model was considered as a biometric environment of the heart, namely cardiac-mimetic model (CMM). RESULT: The experimental results have shown that the full-PIC is superior to the full-SIC in the ablation depth, specifically in both the maximum (4.14 ± 0.55 mm vs. 3.35 ± 0.26 mm, p < 0.01) and the minimum (3.18 ± 0.29 mm vs. 2.76 ± 0.28 mm, p < 0.05), and in the ablation width, specifically only in the maximum (8.27 ± 0.76 mm vs. 7.09 ± 0.51 mm, p = 0.019) under an identical ablation time (i.e., 5 s). It is noted that the minimum ablation width did not show a significant difference between the full-PIC and full-SIC (specifically, 5.61 ± 0.86 mm vs. 4.67 ± 0.73 mm, p = 0.069). Considering the lethal electric field threshold (LEFT) to be 600 V/cm for liver tissues, the maximum and minimum ablation depth generated by the full-PIC was found larger than that by the full-SIC (3.90 vs. 3.52 mm, and 3.03 vs. 2.48 mm, respectively) in the simulation. Meanwhile, similar experiment results by comparing the partial-PIC and partial-SIC have been obtained, which shows a significant increase in both the maximum ablation depth (4.81 ± 0.87 mm vs. 3.30 ± 0.73 mm, p < 0.001) and the maximum ablation width (8.19 ± 0.85 mm vs. 6.47 ± 1.13 mm, p = 0.001). CONCLUSIONS: (1) The electric field in the PIC is concentrated around the pair of electrodes, and the pattern of the field is a significant factor in the energy delivery along the direction of the depth. (2) The increase of the ablation depth can significantly expand the range of the tissue on the heart, where the PFA can apply, and can therefore readily form a layer of transmural damage on the heart wall at positions at which the wall is thicker.

Experimental validation of a new model for mandibular motions.

Long-term excessive forces loading from muscles of mastication during mandibular motions may result in disorders of temporomandibular joint (TMJ), myofascial pain, and restriction of jaw opening and closing. Current analysis of mandibular movements is generally conducted with a single opening, protrusive and lateral movements rather than composite motions that the three can be combined arbitrarily. The objective of this study was to construct theoretical equations reflecting the correlation between composite motions and muscle forces, and consequently to analyze the mandibular composite motions and the tensions of muscles of mastication in multiple dimensions. The muscle performances such as strength, power, and endurance of mandibular motions were analyzed and the effective motion range of each muscle was derived. The mandibular composite motion model was simplified by calculating muscle forces. An orthogonal rotation matrix based on muscle forces was established. A 3D printed mandible was used for in vitro simulation of mandibular motions on a robot and measurements of force were conducted. The theoretical model and forces were verified through a trajectory tracing experiment of mandibular motions driven by a 6-axis robot with force/torque sensors. Through the analysis of the mandibular composite motion model, the motion form was obtained and transferred to guide the motions of the robot. The error between the experimental data obtained by the 6-axis force/torque sensors and the theoretical data was within 0.6 N. Our system provides excellent visualization for analyzing the changes of muscle forces and locations during various mandibular movements. It is useful for clinicians to diagnose and formulate treatment for patients who suffer from (temporomandibular joint disorders) TMDs and restrict jaw movements. The system can potentially offer the comparison before and after treatment of TMDs or jaw surgery.

SMMP: A Stable-Membership-Based Auto-Tuning Multi-Peak Clustering Algorithm.

Since most existing single-prototype clustering algorithms are unsuitable for complex-shaped clusters, many multi-prototype clustering algorithms have been proposed. Nevertheless, the automatic estimation of the number of clusters and the detection of complex shapes are still challenging, and to solve such problems usually relies on user-specified parameters and may be prohibitively time-consuming. Herein, a stable-membership-based auto-tuning multi-peak clustering algorithm (SMMP) is proposed, which can achieve fast, automatic, and effective multi-prototype clustering without iteration. A dynamic association-transfer method is designed to learn the representativeness of points to sub-cluster centers during the generation of sub-clusters by applying the density peak clustering technique. According to the learned representativeness, a border-link-based connectivity measure is used to achieve high-fidelity similarity evaluation of sub-clusters. Meanwhile, based on the assumption that a reasonable clustering should have a relatively stable membership state upon the change of clustering thresholds, SMMP can automatically identify the number of sub-clusters and clusters, respectively. Also, SMMP is designed for large datasets. Experimental results on both synthetic and real datasets demonstrated the effectiveness of SMMP.

A novel method for detection of ochratoxin A in foods-Co-MOFs based dual signal ratiometric electrochemical aptamer sensor coupled with DNA walker.

Ochratoxin A (OTA) is a naturally occurring mycotoxin that poses serious threats, such as kidney damage, to human health. Therefore, we developed a DNA walker-based dual-signal electrochemical ratiometric platform for OTA detection, which could overlook the variations in environmental and instrumental factors and DNA load densities. Cobalt metal-organic frameworks (Co-MOFs) and toluidine blue were used as the electrochemical signal tag and internal reference probe, respectively. In the presence of OTA, this developed machine resulted in the DNA labelled-Co-MOFs far away from the electrode. Thus, Co-MOFs signal at -1.18 V decreased, while toluidine blue at -0.28 V increased. This proposed strategy has displayed superior sensitivity (limit of detection = 0.31 fg/mL, linear range = 1-50 ng/mL) and high reproducibility. The sensor was also applied for determining OTA content in red wine samples and the results were comparable to those of commercial enzyme-linked immunoassay kits with satisfactory results.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Response of root and root hair phenotypes of cotton seedlings under high temperature revealed with RhizoPot.

Driven by the increase in its frequency and duration, high temperature weather is increasingly seriously affecting crop development. High temperature inhibits the leaf development, flowering, and pollination of cotton, but its effects on the roots and root hair phenotypes and lifespans remain unclear. Thus, this study selected the two cotton varieties Nongda 601 (ND) and Guoxin 9 (GX) as materials and adopted the RhizoPot, an in situ root observation system, to investigate the effects of high temperature (38°C day and 32°C night) on the growth dynamics of the aboveground parts and root phenotypes of cotton at the seedling stage. The results showed that high temperature reduced the net photosynthetic rate and chlorophyll content, decreased the dry matter accumulation and transfer to the root, and lowered the root-shoot ratio (R/S ratio). The root phenotypes changed significantly under high temperature. After 7 d of high temperature stress, the root lengths of ND and GX decreased by 78.14 mm and 59.64 mm, respectively. Their specific root lengths increased by 79.60% and 66.11%, respectively. Their specific root surface areas increased by 418.70 cm2·g-1 and 433.42 cm2·g-1, respectively. Their proportions of very fine roots increased to 99.26% and 97.16%, respectively. After the removal of high temperature (RHT), their root lengths tended to increase, and their proportions of very fine roots continued to increase. The root hairs of ND and GX were also significantly affected by high temperature. In particular, the root hair densities of ND and GX decreased by 52.53% and 56.25%, respectively. Their average root hair lengths decreased by 96.62% and 74.29%, respectively. Their root hair lifespans decreased by 7 d and 10 d, respectively. After the RHT, their average root hair lengths failed to recover. A principal component analysis indicated that the root architectures were significantly affected by root hair density, average root hair length, specific root length, and specific root surface area under high temperatures. In summary, cotton adapts to high temperature environments by increasing the specific root length, specific root surface area, and the proportions of very fine roots, and reducing the lifespan of root hairs.

Differences in Microbial Communities Stimulated by Malic Acid Have the Potential to Improve Nutrient Absorption and Fruit Quality of Grapes.

Malic acid is a component of the rhizosphere exudate and is vital for crop growth. However, little information is available about the effects of external applications of malic acid on the nutrient absorption and quality of grape fruit, and few studies have been performed on the relationship between the changes in the rhizosphere microbial community and nutrient absorption and fruit quality of grapes after adding malic acid. Here, the LM (low concentration of malic acid) and HM (high concentration of malic acid) treatments comprised 5% and 10% malic acid (the ratio of acid to the total weight of the fertilizer) combined with NPK fertilizer, respectively. Applying malic acid changed the grape rhizosphere microbial community structure and community-level physiological profile (CLPP) significantly, and HM had a positive effect on the utilization of substrates. The microbial community structure in the rhizosphere of the grapes with added malic acid was closely related to the CLPP. The N and P content in the leaves and fruits increased after applying malic acid compared to the control, while K content in the fruits increased significantly. In addition, malic acid significantly reduced the weight per fruit, significantly increased soluble sugar content (SSC) and vitamin C content of the fruit, and significantly improved the fruit sugar-acid ratio and grape tasting score. Moreover, the principal component analysis and grape nutrient and fruit quality scores showed that grape nutrients and fruit quality were significantly affected by malic acid and ranked as 5% malic acid > 10% malic acid > control. Pearson's correlation heatmap of microbial composition, nutrient absorption and fruit quality of the grapes showed that the grape microbial community was closely related to grape nutrients and fruit quality. Adding malic acid was positively correlated to Planococcaceae, Bacillaceae, Woeseiaceae and Rhodobacteraceae. Furthermore, Planococcaceae, Bacillaceae, Woeseiaceae and Rhodobacteraceae were closely related to grape nutrient absorption and fruit quality. Bacillaceae and Woeseiaceae were positively correlated with total soluble sugar, while Planococcaceae and Rhodobacteraceae were positively correlated with titratable acid. Hence, Bacillaceae and Woeseiaceae were the key bacteria that played a major role in grape fruit quality and nutrient absorption after applying malic acid water-soluble fertilizer.

Gomphocantharellus, a new genus of Gomphales.

The genus Gomphocantharellus and species Gomphocantharellus cylindrosporus are proposed as new based on morphological assessments and molecular phylogenetic evidence inferred from nucleotide sequences of mitochondrial (mt) adenosine triphosphate (ATPase) subunit 6 (atp6) and mt small subunit rDNA (mtSSU). Basidiomes of G. cylindrosporus are characterized by the peach to pinkish orange color, cantharelloid habit with a gill-like hymenophore with obtuse edges, smooth and cylindrical to allantoid basidiospores, and cylindrical to narrowly clavate flexuous pleurocystidia. The species resembles a species of Cantharellus but differs from the latter by the cylindrical basidiospores. Phylogenetic analyses confirm the placement of Gomphocantharellus as an independent lineage within the order Gomphales.

Ballistic Performance of Polyurea-Reinforced Ceramic/Metal Armor Subjected to Projectile Impact.

Although polyurea has attracted extensive attention in impact mitigation due to its protective characteristics during intensive loading, the ballistic performance of polyurea-reinforced ceramic/metal armor remains unclear. In the present study, polyurea-reinforced ceramic/metal armor with different structures was designed, including three types of coating positions of the polyurea. The ballistic tests were conducted with a ballistic gun; the samples were subjected to a tungsten projectile formed into a cylinder 8 mm in diameter and 30 mm in length, and the deformation process of the tested targets was recorded with a high-speed camera. The ballistic performance of the polyurea-reinforced ceramic/metal armor was evaluated according to mass efficiency. The damaged targets were investigated in order to determine the failure patterns and the mechanisms of interaction between the projectile and the target. A scanning electron microscope (SEM) was used to observe the microstructure of polyurea and to understand its failure mechanisms. The results showed that the mass efficiency of the polyurea-coated armor was 89% higher than that of ceramic/metal armor, which implies that polyurea-coated ceramic armor achieved higher ballistic performance with lighter mass quality than that of ceramic/metal armor. The improvement of ballistic performance was due to the energy absorbed by polyurea during glass transition. These results are promising regarding further applications of polyurea-reinforced ceramic/metal armor.

High platelet count predicts poor prognosis in HCC patients undergoing TACE: a propensity score-matched analysis.

BACKGROUND: The aim of this study was to retrospectively evaluate the prognostic value of the pretreatment platelet (PLT) count in patients with hepatitis B virus (HBV)-related intermediate-advanced hepatocellular carcinoma (HCC) complicated with cirrhosis undergoing transcatheter arterial chemoembolization (TACE). RESEARCH DESIGN AND METHODS: We assessed 362 patients with HBV-related intermediate-advanced HCC complicated with cirrhosis undergoing TACE. Patients were divided into low (≤96 × 109/L) and high (>96 × 109/L) PLT groups. Propensity score matching (PSM) was performed to eliminate the imbalance in potential confounding factors. The endpoint was time to progression (TTP). RESULTS: After PSM, the high and low PLT groups had 97 patients each. The TTP was significantly longer in the low PLT group than in the high PLT group (log-rank test, p < 0.001). A high pretreatment PLT count was an independent predictor of poor tumor response (OR 4.724; 95% CI 1.889-11.815; P = 0.001) and short TTP (HR = 3.598; 95% CI: 2.570-5.036; P < 0.001). Subgroup analysis showed that a high PLT count increased the risk of progression across almost all subgroups. CONCLUSIONS: The pretreatment PLT count has potential value in predicting the prognosis of patients with intermediate-advanced HCC undergoing TACE.

Elevation Matters More than Season in Shaping the Heterogeneity of Soil and Root Associated Ectomycorrhizal Fungal Community.

Ectomycorrhizal (EcM) fungi play important roles in forest ecosystems, and their richness and composition can change along with elevation and season changes. However, no study has estimated the relative importance of altitudinal and seasonal heterogeneity in predicting the distribution of EcM fungal communities by simultaneously considering different sample types (root versus soil). In this study, we collected root and soil samples along a > 1,500-m elevation gradient during wet and dry seasons from Baima Snow Mountain, located in "the Mountains of Southwest China," one of the 34 biodiversity hot spots, and we analyzed them using next-generation sequencing. Regardless of the sample type, similar EcM fungal richness pattern with increasing elevation (decline in the forest zone, and an increase at the alpine meadow zone) and strong community turnovers among different elevational zones and between two seasons were detected, and changes of EcM fungal community similarity on 400-m altitude gradient were equivalent to the community turnover between dry and wet seasons. Elevation and edaphic factors were shown to have the largest effects on EcM fungal community. The heterogeneity of richness and community composition was stronger among different elevational zones than across different seasons, mainly because the elevation variations in the EcM fungal community were shaped by the combined effects of different environmental factors, while seasonal changes were mainly controlled by temperature and fast-changing soil nutrients. IMPORTANCE Altitude and season represent two important environmental gradients that shape the structure of biome, including the heterogeneity of EcM fungi. Previous studies have separately considered the influences of altitude and season on EcM fungal communities, but the relative importance of altitude and season is still unknown. The present study revealed that elevation influences the heterogeneity of EcM fungal community more than season; this may be because the variability of environmental factors is higher across different elevations than that across seasons.

Spectral- and Polarization-Dependent Scattering of Gold Nanobipyramids for Exogenous Contrast in Optical Coherence Tomography.

Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT's structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.

A two-miRNA signature of upregulated miR-185-5p and miR-362-5p as a blood biomarker for breast cancer.

BACKGROUND: Differentially expressed microRNAs (miRNAs) in the blood of breast cancer patients may serve as diagnostic biomarkers. METHODS: In this study, miRNA microarray of the blood of breast cancer patients and healthy controls was performed. Candidate differentially expressed miRNAs were further verified by real-time polymerase chain reaction in 68 breast cancer patients and 13 healthy controls. RESULTS: Six upregulated blood miRNAs (miR-26b-5p, miR-106b-5p, miR-142-3p, miR-142-5p, miR-185-5p, and miR-362-5p) were identified in breast cancer patients. These six miRNAs could discriminate breast cancer patients from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.8891, 0.8158, 0.8529, 0.8507, 0.9050, and 0.9333, respectively. Bioinformatic analysis showed that the six miRNAs were potentially involved in numerous cancer-related pathways, including the mitogen-activated protein kinase signaling pathway, nuclear factor-kappa B signaling pathway, and the transforming growth factor-beta signaling pathway. Importantly, two miRNAs (miR-185-5p and miR-362-5p) were used to construct a two-miRNA panel by logistic regression. The two-miRNA panel displayed a better diagnostic performance than each of the miRNAs alone, with a higher AUC (0.957), sensitivity (92.65 %), and specificity (92.31 %). Additionally, the high expression of the six miRNAs or the two-miRNA panel was associated with poor prognosis of breast cancer. CONCLUSIONS: We identified six upregulated miRNAs and a two-miRNA panel in the blood as potential biomarkers for the diagnosis and prognosis of breast cancer.

Hydroxysafflor yellow A alleviates cerebral ischemia reperfusion injury by suppressing apoptosis via mitochondrial permeability transition pore.

BACKGROUND: Mitochondria are key cellular organelles that are essential for cell fate decisions. Hydroxysafflor yellow A (HSYA) has displayed an impressively essential role in protection of cerebral ischemia/reperfusion (I/R). However, the mitochondrial effect of HSYA on Brain Microvascular Endothelial Cells (BMECs) under I/R remains to be largely unclear. PURPOSE: To evaluate the protective effects of HSYA-mediated mitochondrial permeability transition pore (mPTP) on cerebral I/R injury and its mechanism. METHODS: Cerebral I/R injury was established by the model of Middle cerebral artery occlusion (MCAO) in rats. Furthermore, to further clarify the relevant mechanism of HSYA's effects on mPTP, inhibition of extracellular regulated protein kinases (ERK) with U0126 and transfect with Cyclophilin D (CypD) SiRNA to reversely verified whether the protective effects of HSYA were exerted by regulating the Mitogen-activated protein kinase kinase (MEK)/ERK/CypD pathway. RESULTS: HSYA treatment significantly increased BMECs viability, decreased the generation of ROS, opening of mPTP and translocation of cytochrome c after OGD/R. In addition to inhibited CypD, HSYA potentiated MEK and increased phosphorylation of ERK expression in BMECs, inhibited apoptosis mediated by mitochondrial. Notably, HSYA also significantly ameliorated neurological deficits and decreased the infarct volume in rats. CONCLUSION: HSYA reduced the CytC export from mitochondrial by inhibited the open of mPTP via MEK/ERK/CypD pathway, contributing to the protection of I/R. Thus, our study not only revealed novel mechanisms of HSYA for its anti-I/R function, but also provided a template for the design of novel mPTP inhibitor for the treatment of various mPTP-related diseases.

Gold nanomaterials for optical biosensing and bioimaging.

Gold nanoparticles (AuNPs) are highly compelling nanomaterials for biomedical studies due to their unique optical properties. By leveraging the versatile optical properties of different gold nanostructures, the performance of biosensing and biomedical imaging can be dramatically improved in terms of their sensitivity, specificity, speed, contrast, resolution and penetration depth. Here we review recent advances of optical biosensing and bioimaging techniques based on three major optical properties of AuNPs: surface plasmon resonance, surface enhanced Raman scattering and luminescence. We summarize the fabrication methods and optical properties of different types of AuNPs, highlight the emerging applications of these AuNPs for novel optical biosensors and biomedical imaging innovations, and discuss the future trends of AuNP-based optical biosensors and bioimaging as well as the challenges of implementing these techniques in preclinical and clinical investigations.