Isolation and identification of vapA-absent Aeromonas salmonicida in diseased snakehead Channa argus in China.

Aeromonas salmonicida is the typical pathogen causing furunculosis, reported widely in salmonids. Because of multiple serotypes, the control of A. salmonicida-caused disease has increasingly received much attention. Recently, A. salmonicida infection was reported in non-salmonid fish species. Here, a pathogenic A. salmonicida, named as As-s, was isolated from cultured snakehead (Channa argus) in a local fish farm in Shandong, China. As-s displayed clear hemolysis, amylase, and positive catalase activities, and grew at a wide range of temperatures (10-37 °C) and pH values (5.5-8.5). As-s was highly sensitive to cefuroxime sodium, ceftriaxone, ceftazidime, piperacillin, and cefoperazone and also apparently sensitive to chloramphenicol, erythromycin, and 25% cinnamaldehyde. The Virulence array protein gene cloning' results suggested that As-s has this gene compared with the other two vapA-containing strains, despite a close relationship of these strains via phylogenetic analysis. Severe ulcers on skin, muscle, and abnormal liver, and hemorrhage in pectoral/ventral fins and anal region were observed, and exophthalmos were also noticed in infected juvenile snakehead, as well as necrosis and infiltration of blood cells emerged in the internal organs using pathological section. In addition, As-s caused high mortality in snakehead, consistently with its immune gene response. This study reports the first isolation of vapA-absent A. salmonicida in snakehead.

SNCA inhibits epithelial-mesenchymal transition and correlates to favorable prognosis of breast cancer.

Alpha-synuclein (SNCA) is a pathological hallmark of Parkinson's disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.

A Comparative Study of Proton Conduction Between a 2D Zinc(II) MOF and Its Corresponding Organic Ligand.

Until now, comparative studies on proton conductivity between organic ligands and related metal-organic frameworks (MOFs) have been very limited. Herein, a stable 2D Zn(II) MOF, [Zn(L)Cl]n (1), has been successfully synthesized by using a zwitterionic-type organic ligand, 2-(1-(carboxymethyl)-1H-benzo[d]imidazol-3-ium-3-yl)acetate (HL). It is found that there are a large amount of free carboxyl groups and hydrogen bonds in the solid-state structure of HL, and a large number of chlorine ions are aligned in the channels of 1, which is favorable to the efficient proton transfer. Correspondingly, the proton conductivity values of 1 and HL are almost of the same order of magnitude under the same conditions. Moreover, the optimal σ value of 1 (4.72 × 10-3 S/cm at 100 °C and 98% relative humidity) is almost four times higher than that (1.36 × 10-3 S/cm) of the HL ligand. On the basis of the crystal data, SEM images, and calculated Ea values, we discuss the differences on proton conductivities and conduction mechanisms of 1 and HL. This report provides an inspiration for the preparation of highly conductive materials with free carboxyl groups and chloride ions.

Molecular mechanisms and therapeutic applications of huaier in breast cancer treatment.

Breast cancer is one of the most common female malignant tumors today and represents a serious health risk for women. Although the survival rate and quality of life of patients with breast cancer are improving with the continuous development of medical technology, metastasis, recurrence, and drug resistance of breast cancer remain a significant problem. Huaier, a traditional Chinese medicine (TCM) fungus, is a type of Sophora embolism fungus growing on old Sophora stems. The polysaccharides of Trametes robiniophila Murr (PS-T) are the main active ingredient of Huaier. There is increasing evidence that Huaier has great potential in breast cancer treatment, and its anti-cancer mechanism may be related to a variety of biological activities, such as the inhibition of cell proliferation, metastasis, tumor angiogenesis, the promotion of cancer cell death, and regulation of tumor-specific immunity. There is growing evidence that Huaier may be effective in the clinical treatment of breast cancer. This review systematically summarizes the basic and clinical studies on the use of Huaier in the treatment of breast cancer, providing useful information to guide the clinical application of Huaier and future clinical studies.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (223Ra) combined with new-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapies remains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of 223Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bone mCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), five retrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the 223Ra+NHA combination group and the 223Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91-2.34, P = 0.66), but the incidences in both the 223Ra+NHA combination group (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01) and the 223Ra monotherapy group (OR: 2.24, 95% CI: 1.23-4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, in the meta-analysis involving only RCTs, there was no difference between the 223Ra monotherapy group and the NHA monotherapy group (OR: 1.14, 95% CI: 0.22-5.95, P = 0.88), while the difference between the 223Ra+NHA combination group and the NHA monotherapy group remained significant (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-free survival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significant difference. Our results indicate that the combination of 223Ra with NHAs was well tolerated in bone mCRPC patients compared to 223Ra monotherapy, even though the incidence of fracture was higher in patients who received 223Ra than that among those who received NHA monotherapy. More evidence is needed to explore the safety and efficiency of 223Ra combination therapies.

Perceived Importance of Breast Cancer Risk Factors: A Survey on 386 Physicians in China.

There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience.  This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.

MRI magnetic compatible electrical neural interface: From materials to application.

Neural electrical interfaces are important tools for local neural stimulation and recording, which potentially have wide application in the diagnosis and treatment of neural diseases, as well as in the transmission of neural activity for brain-computer interface (BCI) systems. At the same time, magnetic resonance imaging (MRI) is one of the effective and non-invasive techniques for recording whole-brain signals, providing details of brain structures and also activation pattern maps. Simultaneous recording of extracellular neural signals and MRI combines two expressions of the same neural activity and is believed to be of great importance for the understanding of brain function. However, this combination makes requests on the magnetic and electronic performance of neural interface devices. MRI-compatibility refers here to a technological approach to simultaneous MRI and electrode recording or stimulation without artifacts in imaging. Trade-offs between materials magnetic susceptibility selection and electrical function should be considered. Herein, prominent trends in selecting materials of suitable magnetic properties are analyzed and material design, function and application of neural interfaces are outlined together with the remaining challenge to fabricate MRI-compatible neural interface.

Phenotypic plasticity of stomatal and photosynthetic features of four Picea species in two contrasting common gardens.

Global climate change is expected to affect mountain ecosystems significantly. Phenotypic plasticity, the ability of any genotype to produce a variety of phenotypes under different environmental conditions, is critical in determining the ability of species to acclimate to current climatic changes. Here, to simulate the impact of climate change, we compared the physiology of species of the genus Picea from different provenances and climatic conditions and quantified their phenotypic plasticity index (PPI) in two contrasting common gardens (dry vs. wet), and then considered phenotypic plastic effects on their future adaptation. The mean PPI of the photosynthetic features studied was higher than that of the stomatal features. Species grown in the arid and humid common gardens were differentiated: the stomatal length (SL) and width (SW) on the adaxial surface, the transpiration rate (Tr) and leaf mass per area (LMA) were more highly correlated with rainfall than other traits. There were no significant relationships between the observed plasticity and the species' original habitat, except in P. crassifolia (from an arid habitat) and P. asperata (from a humid habitat). Picea crassifolia exhibited enhanced instantaneous efficiency of water use (PPI = 0.52) and the ratio of photosynthesis to respiration (PPI = 0.10) remained constant; this species was, therefore, considered to the one best able to acclimate when faced with the effects of climate change. The other three species exhibited reduced physiological activity when exposed to water limitation. These findings indicate how climate change affects the potential roles of plasticity in determining plant physiology, and provide a basis for future reforestation efforts in China.

The use of a double-layer platinum black-conducting polymer coating for improvement of neural recording and mitigation of photoelectric artifact.

The impedance of electrode and photostimulation artifacts (short-duration and high-amplitude spikes) are still hindering the employment of silicon-based neural probe in optogenetics. A fiber-based optrode modified with a double-layer platinum black-poly (3,4ethylenedioxythiophene) PEDOT/poly (4-styrenesulfonate) PSS (Pt-PP) coating has been developed for improvement of neural recording quality and mitigation of photoelectric artifact simultaneously. The Pt-PP coating was made by layer-by-layer electrochemical deposition followed by the ultrasonication and Cyclic Voltammetry (CV) scanning to verify its mechanical and electrochemical stability. Both in-vitro and in-vivo experiments demonstrated that Pt-PP coated optrode had outstanding recording performance (high signal-to-noise ratio about 9.64) and low photoelectric amplitude (850 µV). The artifact recovery time of Pt-PP coated optrode (0.3 ms) after photostimulation was significantly decreased when compared to platinum black (6 ms) or PEDOT/PSS (0.7 ms) coated one which has potential to retain high-quality neural signals in animal experiments. At last, the optogenetics experiments revealed the capability of Pt-PP coated optrode to record the change in neural spike rate with certain spatial resolution and shorter artifact recovery time. These results suggest that Pt-PP coating has great potential for neural electrodes in the application of neuroscience.

Three-dimensional drivable optrode array for high-resolution neural stimulations and recordings in multiple brain regions.

The brain-computer interface (BCI) devices are of prime important for study of nervous system as well as diagnosis and treatment of neurological disorders. To meet the needs of the BCI devices in high-density integration and multi-functionalization, 3-dimensional (3D) drivable optrode array with laser diodes (LDs) coupled waveguides was developed. The unique device realizes the 3D integration of the optrodes and avoids fiber tangle and tissue heating by adopting LD coupled waveguide structure. Besides, the postoperative position adjustment of the optrode array was achieved by integrating with a 3D printed micro-drive. Most importantly, high-resolution neural stimulations and recordings were achieved for study of working memory related neural circuits in four brain regions of mice including prelimbic cortex (PrL), mediodorsal thalamic nucleus (MD), dorsal medial caudate nucleus (dmCP) and posterior motor cortex 2 (pM2). The results indicate that this novel device is promising for the research of complex neural networks.

Direct electrodeposition of Graphene enhanced conductive polymer on microelectrode for biosensing application.

Engineering of neural interface with nanomaterials for high spatial resolution neural recording and stimulation is still hindered by materials properties and modification methods. Recently, poly(3,4-ethylene-dioxythiophene) (PEDOT) has been widely used as an electrode-tissue interface material for its good electrochemical property. However, cracks and delamination of PEDOT film under pulse stimulation are found which restrict its long-term applications. This paper develops a flexible electrochemical method about the co-deposition of graphene with PEDOT on microelectrode sites to enhance the long-term stability and improve the electrochemical properties of microelectrode. This method is unique and profound because it co-deposits graphene with PEDOT on microelectrode sites directly and avoids the harmful post reduction process. And, most importantly, significantly improved electrochemical performances of the modified microelectrodes (compared to PEDOT-GO) are demonstrated due to the large effective surface area, good conductivity and excellent mechanical property of graphene. Furthermore, the good mechanical stability of the composites is verified by ultrasonication and CV scanning tests. In-vivo acute implantation of the microelectrodes reveals the modified microelectrodes show higher recording performance than the unmodified ones. These findings suggest the composites are excellent candidates for the applications of neural interface.

Progress in Research of Flexible MEMS Microelectrodes for Neural Interface.

With the rapid development of Micro-electro-mechanical Systems (MEMS) fabrication technologies, many microelectrodes with various structures and functions have been designed and fabricated for applications in biomedical research, diagnosis and treatment through electrical stimulation and electrophysiological signal recording. The flexible MEMS microelectrodes exhibit excellent characteristics in many aspects beyond stiff microelectrodes based on silicon or metal, including: lighter weight, smaller volume, better conforming to neural tissue and lower fabrication cost. In this paper, we reviewed the key technologies in flexible MEMS microelectrodes for neural interface in recent years, including: design and fabrication technology, flexible MEMS microelectrodes with fluidic channels and electrode⁻tissue interface modification technology for performance improvement. Furthermore, the future directions of flexible MEMS microelectrodes for neural interface were described, including transparent and stretchable microelectrodes integrated with multi-functional aspects and next-generation electrode⁻tissue interface modifications, which facilitated electrode efficacy and safety during implantation. Finally, we predict that the relationships between micro fabrication techniques, and biomedical engineering and nanotechnology represented by flexible MEMS microelectrodes for neural interface, will open a new gate to better understanding the neural system and brain diseases.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface.

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

Higher thermal acclimation potential of respiration but not photosynthesis in two alpine Picea taxa in contrast to two lowland congeners.

The members of the genus Picea form a dominant component in many alpine and boreal forests which are the major sink for atmospheric CO2. However, little is known about the growth response and acclimation of CO2 exchange characteristics to high temperature stress in Picea taxa from different altitudes. Gas exchange parameters and growth characteristics were recorded from four year old seedlings of two alpine (Picea likiangensis vars. rubescens and linzhiensis) and two lowland (P. koraiensis and P. meyeri) taxa. Seedlings were grown at moderate (25°C/15°C) and high (35°C/25°C) day/night temperatures, for four months. The approximated biomass increment (ΔD2H) for all taxa decreased under high temperature stress, associated with decreased photosynthesis and increased respiration. However, the two alpine taxa exhibited lower photosynthetic acclimation and higher respiratory acclimation than either lowland taxon. Moreover, higher leaf dry mass per unit area (LMA) and leaf nitrogen content per unit area (Narea), and a smaller change in the nitrogen use efficiency of photosynthesis (PNUE) for lowland taxa indicated that these maintained higher homeostasis of photosynthesis than alpine taxa. The higher respiration rates produced more energy for repair and maintenance biomass, especially for higher photosynthetic activity for lowland taxa, which causes lower respiratory acclimation. Thus, the changes of ΔD2H for alpine spruces were larger than that for lowland spruces. These results indicate that long term heat stress negatively impact on the growth of Picea seedlings, and alpine taxa are more affected than low altitude ones by high temperature stress. Hence the altitude ranges of Picea taxa should be taken into account when predicting changes to carbon fluxes in warmer conditions.

Effects of Chai-Qin-Cheng-Qi decoction () on acute pancreatitis-associated lung injury in mice with acute necrotizing pancreatitis.

OBJECTIVE: To investigate the effects of Chai-Qin-Cheng-Qi Decoction (, CQCQD) on acute pancreatitis-associated lung injury in mice with acute necrotizing pancreatitis (ANP). METHODS: Thirty healthy mice were randomly divided into three groups: an ANP group (ANP+placebo, n=10); a treatment group (ANP+CQCQD, n=10); and a control group (normal mice+placebo, n=10). ANP was induced by intraperitoneal injection with 8% L-arginine (4 µg/kg), and the control group was injected with normal saline. The treatment group received CQCQD (20 mL/kg), and the ANP and control groups received placebo (sucrose and starch) intragastrically at 2 h intervals. After the third intragastric administration, blood, pancreatic tissues and right lung tissues were collected for measurement of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay, and the expression of heat shock protein 70 (HSP70) in lung tissue was determined by Western blot analysis. Pathological changes of pancreatic tissue and lung tissue were examined. RESULTS: Serum IL-6 was significantly higher in the ANP group compared with the control and the treatment groups (1589.63±377.28 vs. 927.46±210.42 pg/mL, P<0.05, and 1589.63±377.28 vs. 1107.73±351.62 pg/mL, P<0.05, respectively). The IL-10 concentration was significantly lower in the ANP group compared with the treatment group (920.64±101.68 vs. 1177.84±201.72 pg/mL, P<0.05), but no signififi cant difference was found between the ANP and control groups and between the treatment and control groups. The expression level of HSP70 in the ANP and control groups was signififi cantly lower than in the treatment group (0.93±0.03 vs. 1.42±0.21, P<0.01, and 0.81±0.09 vs. 1.42±0.21, P<0.01, respectively). There was no signififi cant difference in HSP70 levels between the ANP and control groups. Histological scores of pancreatic and lung tissue were significantly decreased in the treatment group compared with the ANP groups (4.50±0.54 vs. 6.20±1.65, P<0.05, and 3.00±0.63 vs. 3.87±0.83, P<0.05, respectively). CONCLUSIONS: The incidence of acute pancreatitisassociated lung injury in ANP mice correlates positively with serum IL-6 concentration. CQCQD may inhibit IL-6 induction and increase IL-10 concentration and HSP70 expression, effectively reducing lung injury.

Forward-collected simultaneous fluorescence lifetime imaging and coherent anti-Stokes Raman scattering microscopy.

We demonstrate the simultaneous collection and separation of femtosecond-laser-based forward-collected coherent anti-Stokes Raman scattering (F-CARS) and two-photon-excitation-induced fluorescence lifetime images (FLIM) using time-correlated single photon counting (TCSPC). We achieve this in a nondescanned geometry using a single multimode fiber without significant loss of light, field of view, and most importantly, TCSPC timing fidelity. In addition to showing the ability to separate CARS images from FLIM images using time gating, we also demonstrate composite multimodal epicollected FLIM imaging with fiber-collected F-CARS imaging in live cells.