Multi-Scale Engineered 2D Carbon Polyhedron Array with Enhanced Electrocatalytic Performance.

Electrocatalyst engineering from the atomic to macroscopic level of electrocatalysts is one of the most powerful routes to boost the performance of electrochemical devices. However, multi-scale structure engineering mainly focuses on the range of atomic-to-particle scale such as hierarchical porosity engineering, while catalyst engineering at the macroscopic level, such as the arrangement configuration of nanoparticles, is often overlooked. Here, a 2D carbon polyhedron array with a multi-scale engineered structure via facile chemical etching, ice-templating induced self-assembly, and high-temperature pyrolysis processes is reported. Controlled phytic acid etching of the carbon precursor introduces homogeneous atomic phosphorous and nitrogen doping, as well as a well-defined mesoporous structure. Subsequent ice-templated self-assembly triggers the formation of a 2D particle array superstructure. The atomic-level doping gives rise to high intrinsic activity, while the well-engineered porous structure and particle arrangement addresses the mass transport limitations at the microscopic particle level and macroscopic electrode level. As a result, the as-prepared electrocatalyst delivers outstanding performance toward oxygen reduction reaction in both acidic and alkaline media, which is better than recently reported state-of-the-art metal-free electrocatalysts. Molecular dynamics simulation together with extensive characterizations indicate that the performance enhancement originates from multi-scale structural synergy.

PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.

Pain is a common annoying non-motor symptom in Parkinson's disease (PD) that causes distress to patients. Treatment for PD pain remains a big challenge, as its underlying mechanisms are elusive. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1-R play important roles in regulating a variety of pathophysiological processes. In this study, we investigated whether PACAP/PAC1-R signaling was involved in the mechanisms of PD pain. 6-hydroxydopamine (6-OHDA)-induced PD model was established in rats. Behavioral tests, electrophysiological and Western blotting analysis were conducted 3 weeks later. We found that 6-OHDA rats had significantly lower mechanical paw withdrawal 50% threshold in von Frey filament test and shorter tail flick latency, while mRNA levels of Pacap and Adcyap1r1 (gene encoding PAC1-R) in the spinal dorsal horn were significantly upregulated. Whole-cell recordings from coronal spinal cord slices at L4-L6 revealed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in dorsal horn neurons was significantly increased, which was reversed by application of a PAC1-R antagonist PACAP 6-38 (250 nM). Furthermore, we demonstrated that intrathecal microinjection of PACAP 6-38 (0.125, 0.5, 2 µg) dose-dependently ameliorated the mechanical and thermal hyperalgesia in 6-OHDA rats. Inhibition of PACAP/PAC1-R signaling significantly suppressed the activation of Ca2+/calmodulin-dependent protein kinase II and extracellular signal-regulated kinase (ERK) in spinal dorsal horn of 6-OHDA rats. Microinjection of pAAV-Adcyap1r1 into L4-L6 spinal dorsal horn alleviated hyperalgesia in 6-OHDA rats. Intrathecal microinjection of ERK antagonist PD98059 (10 µg) significantly alleviated hyperalgesia in 6-OHDA rats associated with the inhibition of sEPSCs in dorsal horn neurons. In addition, we found that serum PACAP-38 concentration was significantly increased in PD patients with pain, and positively correlated with numerical rating scale score. In conclusion, activation of PACAP/PAC1-R induces the development of PD pain and targeting PACAP/PAC1-R is an alternative strategy for treating PD pain.

Daytime radiative cooling multilayer films designed by a machine learning method and genetic algorithm.

Recently, there has been growing interest and attention towards daytime radiative cooling. This cooling technology is considered a potentially significant alternative to traditional cooling methods because of its neither energy consumption nor harmful gas emission during operation. In this paper, a daytime radiative cooling emitter (DRCE) consisting of polydimethylsiloxane, silicon dioxide, and aluminum nitride from top to bottom on a silver-silicon substrate was designed by a machine learning method (MLM) and genetic algorithm to achieve daytime radiative cooling. The optimal DRCE had 94.43% average total hemispherical emissivity in the atmospheric window wavelength band and 98.25% average total hemispherical reflectivity in the solar radiation wavelength band. When the ambient temperature was 30°C, and the power of solar radiation was about 900W/m 2, the net cooling power of the optimal DRCE could achieve 140.38W/m 2. The steady-state temperature of that could be approximately 9.08°C lower than the ambient temperature. This paper provides a general research strategy for MLM-driven design of DRCE.

Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells.

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

FAEE exerts a protective effect against osteoporosis by regulating the MAPK signalling pathway.

CONTEXT: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported. OBJECTIVE: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK). MATERIALS AND METHODS: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo, and then histology was undertaken in combination with cytokines analyses. RESULTS: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro. In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p < 0.01). DISCUSSION AND CONCLUSIONS: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.

Particle separation induced by triangle obstacles in a straight channel.

Efficient separation of particles has ever-growing importance in both fundamental research and nanotechnological applications. However, such particles usually suffer from some fluctuations from external surroundings and outside intervention from unknown directions. Here, we numerically investigate the transport of Brownian particles in a straight channel with regular arrays of equilateral triangle obstacles. The particles can be rectified by the triangle obstacles under the action of an oscillating (square wave) force. At the given amplitude and frequency of the oscillating force, the transport is sensitively dependent on the force direction and particle size. In the cases of longitudinal and transversal oscillating force, the particles with different sizes exhibit different transport behaviors. Interestingly, under a constant force in the longitudinal direction, the phenomenon of particle separation is observed, where the particles with different radii will move in different directions. Furthermore, we also study the transport of Brownian particles driven by a tilt oscillating force. By choosing proper force directions, we can observe the gating phenomenon and transport reversal. Under different driving conditions, we can separate particles of different sizes and make them move in opposite directions.

Spontaneous rectification and absolute negative mobility of inertial Brownian particles induced by Gaussian potentials in steady laminar flows.

We study the transport of inertial Brownian particles in steady laminar flows in the presence of two-dimensional Gaussian potentials. Through extensive numerical simulations, it is found that the transport is sensitively dependent on the external constant force and the Gaussian potential. Within tailored parameter regimes, the system exhibits a rich variety of transport behaviors. There exists the phenomenon of spontaneous rectification (SR), where the directed transport of particles can occur in the absence of any external driving forces. It is found that SR of the particles can be manipulated by the spatial position of the Gaussian potential. Moreover, when the potential lies at the center of the cellular flow, the system exhibits absolute negative mobility (ANM), i.e., the particles can move in a direction opposite to the constant force. More importantly, the phenomenon of ANM induced by Gaussian potentials is robust in a wide range of system parameters and can be further strengthened with the optimized parameters, which may pave the way to the implementation of related experiments.

The Cardioprotective Effects of Remote Ischemic Conditioning in a Rat Model of Acute Myocardial Infarction.

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.

Electrical Signal Reporter, Pore-Forming Protein, for Rapid, Miniaturized, and Universal Identification of Microorganisms.

Despite recent advances in signal reporter-based assays for bacteria detection and profiling, the low-cost, ultrasensitive, accurate, and fast diagnosis remains a challenge for better patient care. Herein, we present a novel bacteria identification method based on α-hemolysin-labeled sandwich assay (HLSA). A pore-forming protein, α-hemolysin, is used as an electrical signal reporter. The assay takes advantage of the specific binding of target nucleic acid with two hybridization probes: capture probe decorated magnetic microparticles and oligonucleotides detecting probe and α-hemolysin modified gold nanoparticles. α-Hemolysin was then released by competitive gold binding peptide incubation into an electric cell with a lipid bilayer between the electrodes. The nanopores formed by α-hemolysin on the lipid layer allowed target nucleic acid concentration-dependent currents for quantification. Sandwich probes against 16S rRNAs of 10 common bacteria pathogens were designed and single cell level nucleic acid concentration detection was achieved. Compared with nanopore technique-based DNA sequencing, HLSA gives a quantitive and straightforward readout that is not dependent on an ultrasensitive and expensive instrument (Axopatch 200B amplifier), thus, is faster and requires no large-scale instruments. Also, since α-hemolysin-modified nanoparticles will be washed out before the α-hemolysin releasing step without the target nucleic acid, no current will be detected, and thus, the assay is more specific. The current strategy based on the electrical signal reporter offers a new insight for pathogen and virus diagnostics.

Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome.

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH2CH2CH2SO3)2· H2O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 µmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD50) and 90% repolarization (APD90), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (IKs), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC50 value of 201.1 µmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, IKs, thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

Coastline Detection with Gaofen-3 SAR Images Using an Improved FCM Method.

The coastline detection is one of the main applications of the Gaofen-3 satellite in the ocean field. However, the capability of Gaofen-3 SAR image in coastline detection has not yet been validated. In this paper, two Gaofen-3 SAR images, acquired in 2016, were used to extract the coastlines of the regions of Bohai and Taihu in China, respectively. The classical Fuzzy C-means (FCM) method was used in the coastline detection, but had been improved by combining the Wavelet decomposition algorithm to better suppress the inherent speckle noises of SAR image. Coastline detection results obtained from two Sentinel-1 SAR images acquired on the same regions were compared with those of the Gaofen-3 images. By using the manually delineated coastlines as the standards in the qualitative evaluations, improvements of about 12.0%, 8.3%, 23.8%, and 9.4% can be achieved by the improved FCM method with respect to the indicators of mean, RMSE, PGSD, and P90%, respectively; demonstrating that the Gaofen-3 data is superior to the Sentinel-1 data in the detection of coastline.

A new diterpenoid from the leaves of Platycladus orientalis.

A new diterpenoid, 17-methyl-8, 13-labdadien-15, 16-olid-19-oic acid methyl ester (1), along with two known compounds 2 and 3, were isolated from the leaves of Platycladus orientalis (L.) Franco. The structures were confirmed based on the analysis of HR-MS, 1D-NMR, and 2D-NMR spectra and the configuration of 1 was confirmed by the single-crystal X-ray diffraction.

Generalized Two-Temperature Model for Coupled Phonons in Nanosized Graphene.

The design of graphene-based composite with high thermal conductivity requires a comprehensive understanding of phonon coupling in nanosized graphene. We extended the two-temperature model to coupled groups of phonons. The study give new physical quantities, the phonon-phonon coupling factor and length, to characterize the couplings quantitatively. Besides, our proposed coupling length has an obvious dependence on system size. Our studies can not only observe the nonequilibrium between different groups of phonons but explain theoretically the thermal resistance inside nanosized graphene.

Effects of non-invasive remote ischemic conditioning on rehabilitation after myocardial infarction.

Recent studies have demonstrated that remote ischemic conditioning (RIC) creates cardioprotection against ischemia/reperfusion injury and myocardial infarction (MI); however, the effects of non-invasive remote ischemic conditioning (nRIC) on prognosis and rehabilitation after MI (post-MI) remain unknown. We successfully established MI models involving healthy adult male Sprague-Dawley rats. The nRIC group repeatedly underwent 5 min of ischemia and 5 min of reperfusion in the left hind limb for three cycles every other day until weeks 4, 6, and 8 after MI. nRIC improved cardiac hemodynamic function and mitochondrial respiratory function through increasing myocardial levels of mitochondrial respiratory chain complexes I, II, III, IV, and adenosine triphosphate (ATP) and decreasing the activity of nitric oxide synthase (NOS). nRIC could inhibit cardiomyocytes apoptosis and reduce myocardium injury through raising the expression of Bcl-2 and reduced the content of creatine kinase-MB, cardiac troponin I and Bax. The results indicated that long-term nRIC could accelerate recovery and improve prognosis and rehabilitation in post-MI rats.

A Series Circuit of Thermal Rectifiers: An Effective Way to Enhance Rectification Ratio.

A novel approachis proposed to enhance the thermal rectification ratio, namely, arranging two thermal rectifiers in series. Through theoretical analysis and molecular dynamics simulations on graphene/phononic crystal structures, the results show that the series thermal rectifiers enhance thermal rectification ratio significantly, compared to a single rectifier. Meanwhile, the results of theoretical prediction match well with simulation results.

Manipulating the temperature dependence of the thermal conductivity of graphene phononic crystal.

By using non-equilibrium molecular dynamics simulations, modulating the temperature dependence of thermal conductivity of graphene phononic crystals (GPnCs) is investigated. It is found that the temperature dependence of thermal conductivity of GPnCs follows ∼T (-α) behavior. The power exponents (α) can be efficiently tuned by changing the characteristic size of GPnCs. The phonon participation ratio spectra and dispersion relation reveal that the long-range phonon modes are more affected in GPnCs with larger holes (L 0). Our results suggest that constructing GPnCs is an effective method to manipulate the temperature dependence of thermal conductivity of graphene, which would be beneficial for developing GPnC-based thermal management and signal processing devices.

Boosting thermal energy transport across the interface between phase change materials and metals via self-assembled monolayers.

Thermal energy storage using phase change materials (PCMs) has great potential to reduce the weather dependency of sustainable energy sources. However, the low thermal conductivity of most PCMs is a long-standing bottleneck for large-scale practical applications. In modifications to increase the thermal conductivity of PCMs, the interfacial thermal resistance (ITR) between PCMs and discrete additives or porous networks reduces the effective thermal energy transport. In this work, we investigated the ITR between a metal (gold) and a polyol solid-liquid PCM (erythritol) at various temperatures including temperatures below the melting point (300 and 350 K), near the melting point (390, 400, 410 K, etc) and above the melting point (450 and 500 K) adopting non-equilibrium molecular dynamics. Since the gold-erythritol interfacial thermal conductance (ITC) is low regardless of whether erythritol is melted or not (<40 MW m-2K-1), self-assembled monolayers (SAMs) were used to boost the interfacial thermal energy transport. The SAM with carboxyl groups was found to increase the ITC most (by a factor of 7-9). As the temperature increases, the ITC significantly increases (by ∼50 MW m-2K-1) below the melting point but decreases little above the melting point. Further analysis revealed that the most obvious influencing factor is the interfacial binding energy. This work could build on existing composite PCM solutions to further improve heat transfer efficiency of energy storage applications in both liquid and solid states.

Safety and anatomical outcome analysis after flow diverter coverage of the anterior cerebral artery.

OBJECTIVES: Few studies on ischemic complications and flow changes after a flow diverter covering the anterior cerebral artery. The purpose of the study was to explore the ischemic complications and anatomical alterations associated with the flow diverter after it covers the anterior cerebral artery. MATERIALS AND METHODS: In this single-center study, patients treated with FD covering the anterior cerebral artery at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. The primary endpoint was ischemic complications related to the anterior cerebral artery. Secondary endpoints were anatomical changes in the anterior cerebral artery postoperatively and at follow-up. RESULTS: A total of 59 patients were included in this study. Four (6.8%) patients presented with ischemic stroke symptoms. Immediately after the procedure, complete occlusion of A1 and decreased blood flow was observed in 13 (22.0%) and 21 patients (35.6%), respectively. At follow-up, A1 artery was occluded in 34 patients (57.6%) and decreased blood flow was observed in 10 patients (16.9%). Symptoms of neurological deficits related to the anterior cerebral artery were not observed in all patients at follow-up. CONCLUSION: Coverage of A1 is safe, with a low incidence of ischemic stroke, when using an FD to treat aneurysms. Risk of reduced perfusion of the anterior cerebral artery postoperatively even if the anterior communicating artery is open. In cases with A1 occlusion, the blood flow in the distal the anterior cerebral artery can be adequately compensated by opening the anterior communicating artery and good vascular anastomoses.

Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease.

Pain is a widespread non-motor symptom that presents significant treatment challenges in patients with Parkinson's disease (PD). Safinamide, a new drug recently introduced for PD treatment, has demonstrated analgesic effects on pain in PD patients, though the underlying mechanisms remain unclear. To investigate the analgesic and anti-PD effect of safinamide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used, and rasagiline as positive control on motor symptoms. Notably, only safinamide alleviated hyperalgesia in MPTP mice. Whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons revealed hyperexcitability in MPTP mice, which safinamide counteracted in a concentration-dependent manner. The voltage clamp further demonstrated that sodium current in DRG neurons of MPTP mice was enhanced and safinamide reduced sodium current density. RT-qPCR identified upregulated Nav1.7 and Nav1.8 transcripts (Scn9a and Scn10a) in DRG neurons of MPTP mice. Our results suggest that safinamide could relieve hyperalgesia by inhibiting DRG neuron hyperexcitability in MPTP mice.

Masking Strategy Constructed Metal Coordination Hydrogels with Improved Mechanical Properties for Flexible Electronic Sensors.

Metal coordination hydrogels (MC-HGs) that introduce dynamically coordinate bonds together with metal ionic conduction have attracted considerable attention in flexible electronics. However, the traditional soaking method alleged to have technical scalability faces the challenge of forming MC-HGs with a "core-shell" structure, which undoubtedly reduces the whole mechanical properties and ionic stimulation responsiveness required for flexible electronics materials. Herein, a novel strategy referred to as "masking" has been proposed based on the theory of the valence bond and coordination chemistry. By regulating the masking agents and their concentrations as well as pairing mode with the metal ions, the whole mechanical properties of the resulting composites (MC-HGsMasking) show nearly double the values of their traditional soaking samples (MC-HGsSoaking). For example, the fracture stress and toughness of Fe-HGsMasking(SA, 5.0 g/L) are 1.55 MPa and 2.14 MJ/m3, almost twice those of Fe-HGsSoaking (0.83 MPa and 0.93 MJ/m3, respectively). Microstructure characterization combined with finite element analysis, molecular dynamics, and first-principles simulations demonstrates that the masking strategy first facilitating interfacial permeation of metal complexes and then effective coordination with functional ligands (carboxylates) of the hydrogels is the mechanism to strengthen the mechanical properties of composites MC-HGsMasking, which has the potential to break through the limitations of current MC-HGs in flexible electronic sensor applications.