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Enhanced terahertz wave generation via Stokes wave recycling in a non-synchronously picosecond pulse pump configuration has been demonstrated. It is theoretically analyzed that under the condition of high pump peak power density, the oscillation of the strong 1st order Stokes wave could benefit the higher order Stokes wave emission and terahertz wave generation. In the experiment, 5.71 times enhancement of terahertz wave generation was obtained via Stokes wave recycling in the non-synchronously picosecond pulse pumped terahertz parametric generator compared with the conventional single-pass terahertz parametric generation. The maximum terahertz wave average power was 61.7 μW under the pump power of 20 W and the cavity length of 170 mm, while the maximum power conversion efficiency was 3.085 × 10-6.

Abstract A facile and efficient palladium-catalyzed borylation of aryl (pseudo)halides at room temperature has been developed. Arylboronic esters were expeditiously assembled in good yields and with a broad substrate scope and good functional group compatibility. This approach has been successfully applied to the one-pot two-step borylation/Suzuki–Miyaura cross-coupling reaction, providing a concise access to biaryl compounds from readily available aryl halides. Furthermore, a parallel synthesis of biaryl analogs is accomplished at room temperature using the strategy, which enhances the practical usefulness of this method.

Molybdenum disulfide (MoS2), a typical member of the transition metal dichalcogenides (TMDs) group, is known for its excellent electronic performance and is considered a candidate next-generation semiconductor. The preparation of MoS2 nanoflakes for use as the core of semiconducting devices depends on mechanical exfoliation, but its quality has not yet been optimized. In this paper, a novel exfoliation method of achieving MoS2 nanoflakes is proposed. We find that the size and yield of the exfoliated flakes are improved after thermal treatment for 2 h at a temperature of 110°C followed by precooling for 10 min in ambient air. The new method has the advantage of a 152-fold larger size of obtained MoS2 flakes than traditional mechanical exfoliation. This phenomenon may be attributable to the differences in van Der Waals force and the increase in surface free energy at the interface induced by thermal treatment. In addition, a field-effect transistor (FET) was fabricated on the basis of multilayer MoS2 prepared according to a new process, and the device exhibited a typical depleted-FET performance, with an on/off ratio of ~105 and a field-effect mobility of 24.26 cm2/Vs in the saturated region when VG is 10 V, which is generally consistent with the values for devices reported previously. This implies that the new process may have potential for the standard preparation of MoS2 and even other 2D materials as well.

Supercontinuum generation has been widely applied in laser spectroscopy and few-cycle pulse generation. It is composed of complex and unmeasurable nonlinear optical effects, which influence the final broadened spectrum markedly. To describe and characterize the two key processes, the Kerr effect and ionization, we employ two nonlinear integrals, including the common B integral for the Kerr effect and a P integral for ionization or plasma effect. With these integrals, the contributions of Kerr and plasma effects in the supercontinuum generation are identified and determined quantitatively. Then we utilize machine learning to construct a multilayer perceptron neural network to obtain the solution of the propagation equation for a femtosecond pulse in a solid medium. We employ supervised and unsupervised training with both experimental and simulation data to train the neural network for a better accuracy of the calculation. The trained network can take the input and broadened spectra of the pulse to compute initial laser parameters and the B and P integrals instantly so that the contributions of Kerr and plasma effects in the supercontinuum generation may be quantified in real time, unveiling the nonlinearities behind the spectral evolution. This method provides a more accurate understanding of the physics of the entangled nonlinear optics effects and a faster and more convenient tool in the investigation of nonlinear optics.

Background: Circular RNAs (circRNAs) are a class of novel RNAs with important biological functions, and aberrant expression of circRNAs has been implicated in human diseases. However, the feasibility of using blood circRNAs as disease biomarkers is largely unknown. Methods: We explored the potential of using human peripheral blood mononuclear cell (PBMC) circRNAs as marker molecules to diagnose active pulmonary tuberculosis (TB). Findings: First, we demonstrated that circRNAs are widely expressed in human PBMCs and that many are abundant enough to be detected. Second, we found that the magnitude of PBMC circRNAs in TB patients was higher than that in the paired healthy controls. Compared with host linear transcripts, the circRNAs within several pathways are disproportionately upregulated in active TB patients, including “Cytokine-cytokine receptor interaction”, “Chemokine signaling pathway”, “Neurotrophin signaling pathway”, and “Bacterial invasion of epithelial cells”. Based on the differentially expressed circRNAs within these pathways, we developed a PBMC circRNA-based molecular signature differentiating active TB patients from healthy controls. We validated the classification power of the PBMC circRNA signature in an independent cohort with the area under the receiver operating characteristic curve (AUC) at 0.946. Interpretation: Our results suggest that PBMC circRNAs are potentially reliable marker molecules in TB diagnosis.

Abstract Background Macrophages stand at the forefront of both innate and adapted immunity through their capacities to recognize, engulf, and eliminate foreign particles, and to stimulate adapted immune cells. They are also involved in controlling pro- and anti-inflammatory pathways. Macrophage activity against Mycobacterium tuberculosis (M. tuberculosis) has been shown to involve Toll-like receptor (TLR) activation and ROS production. Previous studies have shown that lipopolysaccharide (LPS), through TLR4, could activate macrophages, improve their bactericidal ROS production, and facilitate anti-infective immune responses. We sought to better understand the role of the TLR4-NOX2 axis in macrophage activation during M. tuberculosis infection. Methods THP-1 macrophages and PMA primed THP-1 macrophages [THP-1(A)] were treated with LPS and infected by M. tuberculosis. Cells were analyzed by flow cytometry for TLR4 expression, ROS production, phagocytosis, and killing of M. tuberculosis. Western blotting was used to analyze NOX2 expression. Inhibitors of the TLR4-NOX2 pathway were used to assess this pathway’s role in these processes, and their role in LPS activation of macrophages. Results We found that THP1-derived macrophages or PMA primed THP-1 macrophages exhibit higher surface TLR4 levels and increased NOX2 expression levels following LPS treatment. M. tuberculosis infection reduced these levels, but LPS was able to limit the negative effects of M.tb. Additionally, LPS increases THP-1(A) cells’ bactericidal activities including phagocytosis, ROS production, and destruction of M. tuberculosis. Significantly, all of these activities are impaired when TLR4 or NOX2 are inhibited. Conclusion These studies demonstrate the importance of the TLR4-NOX2 axis in M. tuberculosis elimination by macrophages and may lead to novel therapies for tuberculosis and other bacterial infections.

Four-wave-mixing microscopy is widely researched in both biology and medicine. In this paper, we present a simplified near-degenerate four-wave-mixing microscopy (SNDFWM). An ultra-steep long-pass filter is utilized to produce an ultra-steep edge on the spectrum of a femtosecond pulse, and a super-sensitive four-wave-mixing (FWM) signal can be generated via an ultra-steep short-pass filter. Compared with the current state-of-the-art FWM microscopy, this SNDFWM microscopy has the advantages of simpler experimental apparatus, lower cost, and easier operation. We demonstrate that this SNDFWM microscopy has high sensitivity and high spatial resolution in both nanowires and biological tissues. We also show that the SNDFWM microscopy can achieve an ultra-sensitive detection based on the electron-resonance effect. This method might find an important application in tracking of nano drugs in vivo.

Abstract Background Pathways directing endogenous stem/progenitor cells to restore normal architecture and function of damaged/diseased lungs remain underexplored. Published data have revealed that alveolar progenitor type II cell (ATIIC)-derived signaling promotes re-epithelialization of injured alveoli, yet the underlying mechanism is unknown. Here we aim to define the role of ATIIC-derived exosome miRNA signaling in controlling ATIIC-specific proliferation or differentiation in response to injury. Methods Pluripotent stem cell-derived cultures, which contain early lung stem/progenitor populations that can subsequently differentiate into ATIICs, were used as a model for unbiased screening and identification of ATIIC phenotype-specific exosome miRNA signaling, and human induced pluripotent stem cell-derived ATIICs (hiPSC-ATIICs) were employed to examine the molecular basis of key exosome miRNA signaling in promoting ATIIC-specific proliferation. QRT-PCR was performed to examine expression pattern of ATIIC-derived key exosome miRNA in an alveolar injury model and in injured human lungs. Results We show that human ATIIC line (A549)-derived exosome miR-371b-5p promotes ATIIC-specific proliferation, but not differentiation, in differentiating cultures of pluripotent stem cells. Using 3′UTR-driven luciferase reporters, we identified PTEN as a direct target of miR-371b-5p. Transfection of miR-371b-5p mimic into hiPSC-ATIICs leads to significantly decreased expression of endogenous PTEN, which stimulates phosphorylation of Akt and its downstream substrates, GSK3β and FOXOs, promoting cell proliferation. While not expressed in normal ATIIC phenotypes, the exosome miR-371b-5p expression is significantly induced after hiPSC-ATIICs or hATIICs (human primary ATIICs) are subjected to bleomycin-induced injury. To rule out that the ATIIC-derived exosome-miRNAs are merely a cell culture phenomenon, we transplanted hiPSC-ATIICs into bleomycin-challenged lungs of mice, and found that the transplanted hiPSC-ATIICs engraft and express exosome miR-371b-5p, along with additional survival of numerous mouse ATIICs in bleomycin-injured lungs. Consistent with these findings, significant levels of exosome miR-371b-5p were also detected in lavage samples of patients with acute pneumonia, but not in those from patients without pulmonary disorders. Conclusions Collectively, our data strongly suggest that ATIIC-derived exosome miR-371b-5p may serve as a niche signaling to augment ATIIC survival/proliferation, promoting re-epithelialization of injured alveoli, and thus provide a promising novel target to develop treatment for currently incurable lung diseases.

Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.

The NO gas adsorption properties of the monolayer, bilayer and trilayer MoS _2 has been studied based on the first-principles calculation. The interaction between NO and MoS _2 layers is weak physical adsorption, which is evidenced by the large distance (>3 Å), small adsorption energies (

We present our research on the high energy picosecond laser operating at a repetition rate of 1 kHz and the high average power picosecond laser running at 100 kHz based on bulk Nd-doped crystals. With diode-pumped solid state (DPSS) hybrid amplifiers consisting of a picosecond oscillator, a regenerative amplifier, end-pumped single-pass amplifiers, and a side-pumped amplifier, an output energy of 64.8 mJ at a repetition rate of 1 kHz was achieved. An average power of 37.5 W at a repetition rate of 100 kHz pumped by continuous wave laser diodes was obtained. Compact, stable and high power DPSS laser amplifier systems with good beam qualities are excellent picosecond sources for high power optical parametric chirped pulse amplification (OPCPA) and high-efficiency laser processing.

Biological structures have excellent mechanical performances including lightweight, high stiffness, etc. However, these are difficult to apply directly to some given complex structures, such as automobile frame, control arm, etc. In this study, a novel bionic design method for skeleton structures with complex features is proposed by the bio-inspired idea of “main-branch and sub-branch”. The envelope model of a given part is established by analyzing the structural functions and working conditions, and the load path is extracted by the load-transferred law as the structural main-branch. Then, the selection criterion of bionic prototype is established from three aspects: load similarity, structural similarity and manufacturability. The cross-sections with high similarities are selected as the structural sub-branch. Finally, the multi-objective size optimization is carried out and a new model is established. The bionic design of a control arm is carried out by the method: structural main-branch is obtained by the load path analysis and structural sub-branch is occupied by the fish-bone structure. The design result shows that the structural stiffness is increased by 62.3%, while the weight is reduced by 24.75%. The method can also be used for other fields including automobile, aerospace and civil engineering.

We demonstrate a broadband degenerate femtosecond optical parametric oscillator (OPO) around 2060 nm. Synchronically pumped by a commercially available 75.6 MHz Yb:KGW femtosecond laser, it is able to generate self-phase-locked 2 μm pulses with 82 mW output power and 3 dB bandwidth of 105 nm. The degenerate operation is naturally stable in free-running condition, with only 0.8% rms fluctuation in 3.5 hours. We also obtain broadband spectrum extending from 1600 nm to 2500 nm with the 3 dB bandwidth of 452 nm by increasing the intracavity power density.

We demonstrate the first Kerr-lens mode-locked operation in a diode-pumped Yb:GdYSiO5 oscillator. Under a diode pump power of 5 W, 141 fs pulses with an average power of 237 mW were obtained at a repetition rate of 118 MHz. The central wavelength was at 1094 nm with a bandwidth of 10.1 nm. Shorter pulses were obtained by adjusting the cavity to operate at a shorter wavelength, resulting in 55 fs pulse duration at the central wavelength of 1054 nm with a bandwidth of 23.5 nm.

Abstract.: Tanshinone IIA, one of the main active components from the Chinese herb Danshen, is widely used to treat cardiovascular diseases in Asian countries, especially in China. To further elucidate its heart rate–reducing and anti-ischemic mechanisms, here we investigated the effects of tanshinone IIA on hyperpolarization-activated cyclic nucleotide–modulated (HCN) channels expressed in Xenopus oocytes using two-electrode voltage clamp techniques. When applied to the extracellular solution, 100 μM tanshinone IIA caused a slowing of activation and deactivation and an increase of minimum open probabilities (from 0.06 ± 0.01 to 0.29 ± 0.03, P

Emergencies, especially major ones, happen fast, randomly, as well as unpredictably, and generally will bring great harm to people’s life and the economy. Therefore, governments and lots of professionals devote themselves to taking effective measures and providing optimal evacuation plans. This paper establishes two different emergency evacuation models on the basis of the maximum flow model (MFM) and the minimum-cost maximum flow model (MC-MFM), and proposes corresponding algorithms for the evacuation from one source node to one designated destination (one-to-one evacuation). Ulteriorly, we extend our evaluation model from one source node to many designated destinations (one-to-many evacuation). At last, we make case analysis of evacuation optimization and planning in Beijing, and obtain the desired evacuation routes and effective traffic control measures from the perspective of sufficiency and practicability. Both analytical and numerical results support that our models are feasible and practical.

PURPOSE:The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). MATERIALS/METHODS:Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. RESULTS:All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, D mean, D median, D98% and D min) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p

This paper establishes VMI-APIOBPCS II model by extending VMI-APIOBPCS model from serial supply chain to distribution supply chain. Then TPL is introduced to this VMI distribution supply chain, and operational framework and process of VMI&TPL integrated supply chain are analyzed deeply. On this basis VMI-APIOBPCS II model is then changed to VMI&TPL-APIOBPCS model and VMI&TPL integrated operation mode is simulated. Finally, compared with VMI-APIOBPCS model, the TPL’s important role of goods consolidation and risk sharing in VMI&TPL integrated supply chain is analyzed in detail from the aspects of bullwhip effect, inventory level, service level, and so on.

This paper investigates the dynamic pricing and supply chain coordination in a decentralized system that consists of one supplier and one manufacturer, in which both the market demand and production yield are stochastic. We show that the centralized expected profit is jointly concave in the production quantity and order quantity when the price is ex-ante selected. We also derive the equilibrium strategies in the decentralized system and prove that the entire profit of supply chain is inevitably lower than that under centralized system. Based on this, we propose a reimbursement contract to coordinate the decentralized supply chain so as to achieve the maximized profit. It is worth mentioning that, under reimbursement contract, the equilibrium production and order quantities are irrelevant to the manufacturer's risk sharing coefficient but are only determined by the supplier’s risk sharing coefficient.