Glial scar size, inhibitor concentration, and growth of regenerating axons after spinal cord transection

A mathematical model has been formulated in accordance with cell chemotaxis and relevant experimental data. A three-dimensional lattice Boltzmann method was used for numerical simulation. The present study observed the effects of glial scar size and inhibitor concentration on regenerative axonal growth following spinal cord transection. The simulation test comprised two parts： （1） when release rates of growth inhibitor and promoter were constant, the effects of glial scar size on axonal growth rate were analyzed, and concentrations of inhibitor and promoters located at the moving growth cones were recorded. （2） When the glial scar size was constant, the effects of inhibitor and promoter release rates on axonal growth rate were analyzed, and inhibitor and promoter concentrations at the moving growth cones were recorded. Results demonstrated that （1） a larger glial scar and a higher release rate of inhibitor resulted in a reduced axonal growth rate. （2） The axonal growth rate depended on the ratio of inhibitor to promoter concentrations at the growth cones. When the average ratio was 〈 1.5, regenerating axons were able to grow and successfully contact target cells.

Expansion of the South China Sea basin:Constraints from magnetic anomaly stripes,sea floor topography,satellite gravity and submarine geothermics

The widely distributed E-W-trending magnetic anomaly stripes in the central basin and the N-Etrending magnetic anomaly stripes in the southwest sub-basin provide the most important evidence for Neogene expansion of the South China Sea.The expansion mechanism remains,however,controversial because of the lack of direct drilling data,non-systematic marine magnetic survey data,and irregular magnetic anomaly stripes with two obvious directions.For example,researchers have inferred different ages and episodes of expansion for the central basin and southwest sub-basin.Major controversy centers on the order of basinal expansion and the mechanism of expansion for the entire South China Sea basin.This study attempts to constrain these problems from a comprehensive analysis of the seafloor topography,magnetic anomaly stripes,regional aeromagnetic data,satellite gravity,and submarine geothermics.The mapped seafloor terrain shows that the central basin is a north-south rectangle that is relatively shallow with many seamounts,whereas the southwest sub-basin is wide in northeast,gradually narrows to the southwest,and is relatively deeper with fewer seamounts.Many magnetic anomaly stripes are present in the central basin with variable dimensions and directions that are dominantly EWtrending,followed by the NE-,NW- and NS-trending.Conversely such stripes are few in the southwest sub-basin and mainly NE-trending.Regional magnetic data suggest that the NW-trending Ailaoshan-Red River fault extends into the South China Sea,links with the central fault zone in the South China Sea,which extends further southward to Reed Tablemount.Satellite gravity data show that both the central basin and southwest sub-basin are composed of oceanic crust.The Changlong seamount is particularly visible in the southwest sub-basin and extends eastward to the Zhenbei seamount.Also a low gravity anomaly zone coincides with the central fault zone in the sub-basin.The submarine geothermic distribution demonstrates that the southwest sub-basin has a higher geothermal value than the central basin,and that the central fault zone is defined by a low thermal anomaly.This study suggests that NW-SE expansion of the southwest subbasin is later than the N-S expansion of the central basin with the sub-basin extending into the central basin and with both expansions ending at the same time.The expansion of southwestern sub-basin,similar to the Japanese Sea,is likely caused by left-lateral strike slip on the central fault zone in the South China Sea,which may have significance for finding oil and gas in this region.

The Average Achievable Rate of Multi-Antenna Two-Way Relay Networks with Interference Alignment

The large system analysis(LSA)has recently been shown to be a very useful tool for computing the average achievable rate.In this paper,we use LSA to derive the users’average achievable rate of multi-antenna two-way relay networks with interference alignment(IA),and we then derive the rate expressions under both equal power allocation and optimal power allocation.It is shown that the obtained closed-form rate expressions are functions of the average signal-to-noise ratio(SNR)for each data stream.Extensive simulation studies show that the average achievable rate expressions derived through LSA provide accurate estimates of the average achievable rate for two-way relay networks with interference alignment.

Security Assessment of Distribution System with Distributed Photovoltaic

In order to evaluate the safe and stable operation of distribution network with the distributed photovoltaic (PV), the?security of distribution network is researched. On the basis of electricity supply security, voltage quality and network losses,?the index system of static security is established. The paper simulates the uncertainty and random characteristics of PV by OpenDSS. The typical scenes that PV accessed to the distribution network are designed.?The paper summarizes the results of voltage fluctuation and network losses and uses indices to quantify it under different scenes. Based on the index system, the paper proposes some recommendations on PV permeability, interconnected locations, dispersion degrees and power factors when the distributed PV accessed to the distribution network.

Process analytical technologies and self-optimization algorithms in automated pharmaceutical continuous manufacturing

The pharmaceutical industry is now paying increased attention to continuous manufacturing.While the revolution to continuous and automated manufacturing is deepening in most of the top pharma companies in the world,the advancement of automated pharmaceutical continuous manufacturing in China is relatively slow due to some key challenges including the lack of knowledge on the related technologies and shortage of qualified personnels.In this review,emphasis is given to two of the crucial technologies in automated pharmaceutical continuous manufacturing,i.e.,process analytical technology(PAT)and self-optimizing algorithm.Research work published in recent 5 years employing advanced PAT tools and self-optimization algorithms is introduced,which represents the great progress that has been made in automated pharmaceutical continuous manufacturing.

Multistep continuous flow synthesis of Erlotinib

Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction,addition and cyclization reactions. All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.

Continuous-flow enzymatic synthesis of chiral lactones in a three-dimensional microfluidic reactor

A new continuous-flow process for the enzymatic synthesis of optically pureγ-lactones,which are used as flavors and fragrances in the food and cosmetic industries,was developed in a three-dimensional microfluidic reactor.The microchannels(175 mm in length,0.9 mm in depth,and 1.72 mL in volume)were carved precisely inside a single borosilicate glass(90 mm×75 mm×12 mm)with ultrafast femtosecond laser micromachining.The flow field analysis and reaction simulation showed that the mixing of substrates and enzymes was enhanced,allowing the adjustment of residence time in a wide window.SmCR_(V4),a carbonyl reductase with excellent catalytic activity and enantioselectivity towardγ/δ-keto acids,was employed for the asymmetric synthesis of various chiral lactones.30 mmol/L(R)-γ-decalactone(3g)can be obtained in 26 s with a space-time yield(STY)up to 16,877 g L^(-1)d^(-1),which is 14.4 times higher than the highest STY of batch reaction reported previously.This continuous-flow process was applied to the synthesis of 6 chiral lactones.In addition,the scaled-up synthesis of 3g was carried out in 6 cascade microreactors continuously for 6 h,demonstrating the feasibility and stability of the 3D continuous-flow process in enzymatic synthesis of optically pure compounds.

Microfluidic separation of particles by synergistic effect of geometry-induced hydrodynamics and magnetic field

Microfluidic combined with magnetic field have been demonstrated to be the promising solutions for fast and low-damage particles separation.However,the difficulties in the precise layout of magnets and accurate prediction of particle trajectories lead to under and over separation of target particles.A novel particle separation lab-on-chip(LOC)prototype integrated with microstructures and micropolar arrays is designed and characterized.Meanwhile,a numerical model for the separation of magnetic particles by the synergistic effect of geometry-induced hydrodynamics and magnetic field is constructed.The effect of geometry and magnetic field layout on particle deflection is systematically analyzed to implement accurate prediction of particle trajectories.It is found that the separation efficiency of magnetic particles increased from 50.2%to 91.7%and decreased from 88.6%to 85.7%in the range of depth factors from 15µm to 27µm and width factors from 30µm to 60µm,respectively.In particular,the combined effect of the offset distance of permanent magnets and the distance from the main flow channel exhibits a significant difference from the conventional perception.Finally,the developed LOC prototype was generalized for extension to arbitrary systems.This work provides a new insight and robust method for the microfluidic separation of magnetic particles.

Continuous-flow synthesis of polysubstituted γ-butyrolactones via enzymatic cascade catalysis

Polysubstituted chiral γ-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis of these molecules faces the problems of low enzyme activity and phase separation in batch reaction, resulting in low productivity. Herein, we report a new continuous-flow process to synthesize the optically pure Nicotiana tabacum lactone(3S,4S)-4a and whisky lactone(3R,4S)-4b from α,β-unsaturatedγ-ketoesters. A new ene reductase(ER) from Swingsia samuiensi(Ss ER) and a carbonyl reductase(Ss CR)were engineered by directed evolution to improve their activity and thermostability. The continuous-flow preparative reactions were performed in two 3D microfluidic reactors, generating(3S,4S)-4a(99% ee and87% de) and(3R,4S)-4b(99% ee and 98% de) with space-time yields 3 and 7.4 times higher than those of the batch reactions. The significant enhancement in the productivity of enzyme cascade catalysis brought by cutting-edge continuous microfluidic technology will benefit the general multi-enzyme catalytic systems in the future.

Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing

Using gas-liquid segmented micromixers to prepare nanoparticles that have a homogeneous particle size, controllable shape, and monodispersity advantages. Although nanoparticle aggregation within a microfluid has been shown to be affected by the shear effect, the shear effect triggering conditions in gasliquid two-phase flow is unclear and the aggregation behavior of nanoparticles under the shear effect is difficult to predict, resulting in uncontrollable physical and chemical properties of nanoparticle aggregates. In this study, a numerical simulation of nanoparticle aggregation in gas-liquid two-phase flow under the shear effect is performed using the CFD-DEM method. Then, the effects of total flow rate,gas-liquid two-phase flow ratio, and particle volume fraction on particle aggregation were analyzed to achieve control of particle aggregation shape and size. Meanwhile, the triggering mechanism of the shear effect and the mechanism of the shear effect on the aggregation of nanoparticles were clarified. The results show that increasing the total flow rate or decreasing the gas-liquid two-phase flow rate ratio can induce the shear effect, which reduces the particle aggregation size and makes the morphology tend to be spherical. Moreover, increasing the particle volume fraction, and total flow rate or decreasing the gas-liquid two-phase flow rate ratio also increases the number of particle collisions and induce interparticle adhesion. Hence, particle adhesion and the shear effect compete with each other and together affect particle aggregation.

Micro/nano flow chemistry by Beyond Limits Manufacturing

In September 2018,we proposed the cutting-edge concept of“Beyond Limits Manufacturing”(BLM).BLM technology is based on the three-dimensional inner engraving or precise outer engraving of ultra-fast laser,to invent micro/nano scale flow chips or devices,which makes it possible for the microform,integration,economy,safety,high efficiency,green and intelligence of research,development and manufacturing process,so as to realize transformational manufacturing in the era of Industry 4.0.In this paper,we reviewed the representative results we made in the field of micro/nano flow chemistry during the implementation of the BLM major project(December 2019 to August 2023),and discussed its application prospects in micro/nano flow chemistry.

Novel seven-membered ring-fused naphthalimide derivatives with potentials for cancer theranostics

Naphthalimide derivatives have good planarity and large conjugated structure and therefore possess photophysical properties and biological activities. Previously, our group discovered seven-membered heterocyclic derivatives via modifying 4-and 5-positions of naphthalimide skeleton and found the derivatives had good water solubility and showed large stokes shift and strong fluorescence in water. In this article, we designed and synthesized more seven-membered ring-fused naphthalimide derivatives(Y1-Y16)by introducing different substitutions on the imide group. Among them, Y1, Y5, Y9 were found to show similar cytotoxic activities with Amonafide against A549 and HL60 cells, with IC50values at 10^(-6)mol/L.What is more, the asymmetry derivatives(Y1 and Y5) showed high fluorescent quantum yields in the aqueous phase(Ф = 0.47). Considering the great fluorescence quantum yields in water and the potent anti-tumor activities of the representative seven-membered ring-fused naphthalimides, they have potentials to be used as agents for cancer theranostics.

Constructing a high-density linkage map for Gossypium hirsutum × Gossypium barbadense and identifying QTLs for lint percentage

To introgress the good fiber quality and yield from Gossypium barbadense into a commercial Upland cotton variety, a high‐density simple sequence repeat （SSR） genetic linkage map was developed from a BC1F1 population of Gossypium hirsutum × Gossypium barbadense. The map com-prised 2,292 loci and covered 5115.16 centiMorgan （cM） of the cotton AD genome, with an average marker interval of 2.23 cM. Of the marker order for 1,577 common loci on this new map, 90.36% agrees well with the marker order on the D genome sequence genetic map. Compared with five pub-lished high‐density SSR genetic maps, 53.14% of marker loci were newly discovered in this map. Twenty‐six quantitative trait loci （QTLs） for lint percentage （LP） were identified on nine chromosomes. Nine stable or common QTLs could be used for marker‐assisted selection. Fifty percent of the QTLs were from G. barbadense and increased LP by 1.07%–2.41%. These results indicated that the map could be used for screening chromosome substitution segments from G. barbadense in the Upland cotton background, identifying QTLs or genes from G. barbadense, and further developing the gene pyramiding effect for improving fiber yield and quality.

NCL-based mitochondrial-targeting fluorescent probe for the detection of Glutathione in living cells

Glutathione(GSH) plays a critical role in maintaining cellular redox homeostasis in biological system.Mitochondrion is a pivotal organelle for cellular aerobic respiration and its disorder is associated with impaired redox balance, leading to cell death. In this work, we designed and synthesized a non-invasive“off-on” mitochondrial-targeting fluorescent probe QZ for the detection of GSH in living cells. Based on the mechanism of native chemical ligation(NCL) and fluorescence resonance energy transfer(FRET), a rhodamine B derivative, QZ was prepared, by choosing aromatic thioester bond as the selective reaction site. QZ exhibited excellent detection capability for GSH over Cys and Hcy. Upon addition of GSH to QZ solution, a remarkably enhanced fluorescence was observed with a limit of detection of 2.98 μmol/L.Furthermore, QZ was found to possess the specific mitochondrial localization ability in cell imaging experiments. Moreover, with exogenous and endogenous stimulations, QZ could image GSH in living cells.

Surgical treatment of ovarian cancer liver metastasis

In addition to hepatocellular carcinoma,metastatic liver cancer(MLC)is another focus of hepatic surgeon.Good outcome of patients with liver metastasis(LM)from colorectal cancer or neuroendocrine tumor have been achieved.Ovarian cancer liver metastasis(OCLM)has its unique oncological characteristics and a variety of metastasis patterns,which brings a challenge to hepatic surgeon.Hepatic surgeons hold different views and techniques from gynecologists,which makes differences in the evaluation and treatment of the disease.We reviewed recent studies and,in combination with our own clinical experience,attempted to introduce the progress of surgical treatment of liver metastases from OC.In our experience,both preoperative imaging and surgical procedures are based on the assurance of R0 resection.R0 cytoreductive surgery(CRS)is the most favorable determinant for the prognosis of OC patients,and R0 liver resection(LR)is a component of R0 CRS.Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively.During the operation,regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule,liver parenchymal infiltration(LPI)or liver parenchymal metastasis(LPM),1–2 cm resection margin should be emphasized.For patients with liver portal lymph node metastasis(LPLNM),hepatic portal skeletonization should be performed,rather than portal lymph node dissection.The operation should be as radical as possible to ensure the patients to achieve good prognosis.

Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy

Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.

A lysosomal targeting fluorescent probe and its zinc imaging in SH-SY5Y human neuroblastoma cells

Zinc plays a significant role in oxidative balance and central nervous systems. Herein, we reported a highly sensitive fluorescent probe DR, bearing a morpholine group and a BPEN ligand in the naphthalimide fluorophore. Upon Zn2+binding, DR exhibited remarkable fluorescence enhancement, and showed high sensitivity to Zn2+with the association constant of 4.9 ? 108 L/mol, and the detection limit of15 nmol/L. Confocal imaging experiments indicated that DR was able to localize to lysosomes in MCF-7 cells. Moreover, upon H2 O2 stimulation in SH-SY5 Y cells, endogenous release of Zn2+was observed.

Programmed co-assembly of DNA-peptide hybrid microdroplets by phase separation

Biopolymers, including DNA and peptides have been used as excellent self-assembling building blocks for programmable single-component or hybrid materials, due to their controlled molecular interactions.However, combining two assembling principles of DNA-based programmability and peptide-based specific molecular interactions for hybrid structures to microscale has not yet been achieved. In this study,we describe a hybrid microsystem that emerges from the co-assembly of DNA origami structure and short elastin-like polypeptide conjugated oligonucleotides, and initiates liquid-liquid phase separation to generate microdroplets upon heating above the transition temperature. Moreover, the hybrid microdroplets are capable for guest molecule trapping and perform bi-/tri-enzymatic cascades with rate enhancements as open “microreactors”. Our programmed assembled DNA-peptide microsystem represents a new combination of DNA nanotechnology and peptide science and opens potential application routes toward lifeinspired biomaterials.

A highly sensitive fluorescent probe for tracking intracellular zinc ions and direct imaging of prostatic tissue in mice

A highly sensitive fluorescent sensor ZnDN was designed,synthesized and used for tracking intracellular zinc ions in various living cells and direct imaging of prostatic tissue in mice.ZnDN was prepared from the heterocyclic-fused naphthalimide fluorophore,and the zinc receptor,N,N-bis(2-pyridylmethyl)ethylenediamine(BPEN).Upon addition of Zn2+to the solutions of ZnDN,a remarkable fluorescence enhancement was observed,which could be attributed to the photo-induced electron transfer(PET)mechanism.Since ZnDN exhibited high sensitivity toward Zn2+in phosphate buffer solution,with a limit of detection of 4.0 x 10-9 mol/L,it was further applied for the imaging of exogenous and endogenous Zn21 in different living cells.Living cells imaging experiments suggested that ZnDN could image the changes of intracellular free zinc ions,and could be used for two-photon imaging.Moreover,flow cytometry suggested that ZnDN could distinguish cancerous prostate cells from normal cells.Animal experiments indicated that ZnDN had the potential in imaging prostate tissue in vivo.

Forward link outage performance of aeronautical broadband satellite communications

High-throughput satellites(HTSs) play an important role in future millimeter-wave(mm Wave) aeronautical communication to meet high speed and broad bandwidth requirements. This paper investigates the outage performance of an aeronautical broadband satellite communication system’s forward link, where the feeder link from the gateway to the HTS uses free-space optical(FSO) transmission and the user link from the HTS to aircraft operates at the mm Wave band. In the user link, spot beam technology is exploited at the HTS and a massive antenna array is deployed at the aircraft. We first present a location-based beamforming(BF) scheme to maximize the expected output signal-to-noise ratio(SNR) of the forward link with the amplify-and-forward(AF) protocol,which turns out to be a phased array. Then, by supposing that the FSO feeder link follows Gamma-Gamma fading whereas the mm Wave user link experiences shadowed Rician fading, we take the influence of the phase error into account, and derive the closed-form expression of the outage probability(OP) for the considered system. To gain further insight, a simple asymptotic OP expression at a high SNR is provided to show the diversity order and coding gain. Finally, numerical simulations are conducted to confirm the validity of the theoretical analysis and reveal the effects of phase errors on the system outage performance.