Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles

Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.

Sustainable Use of Agricultural Land in Zhoukou City Based on Emergy Analysis

Taking Zhoukou City in Henan Province as an example,we select the statistics during the period 2000-2009,and use emergy analysis method to research the sustainable use of agricultural land in Zhoukou City. The study results show that: ( i) The agricultural input is mainly based on resources purchase input,which accounts for more than 90% of total emergy input; the industrial energy input is to a large extent dependent on the input of chemical fertilizer and pesticide; precipitation significantly affects the input of renewable environmental resources. ( ii) The agricultural output is mainly based on farming and animal husbandry,with the proportion reaching 99% ; the proportion of fishery and forestry is too low; the agricultural output structure is relatively simple. ( iii) The use of agricultural land has achieved initial success in terms of economic sustainability,but in terms of ecological sustainability and social sustainability,it is at a low level; the sustainable use index shows the great vitality and development potential of agricultural system; unsustainability is reflected in considerable input of chemical fertilizer and pesticide,and simple agricultural output structure.

0.04 degree-per-hour MEMS disk resonator gyroscope with high-quality factor (510 k) and long decaying time constant(74.9 s)

The disk resonator gyroscope is an attractive candidate for high-performance MEMS gyroscopes.This gyroscope consists of a sensor and readout electronics,and the characteristics of the sensor directly determine the performance.For the sensor,a high-quality factor and long decaying time constant are the most important characteristics required to achieve high performance.We report a disk resonator gyroscope with a measured quality factor of 510 k and decaying time constant of 74.9 s,which is a record for MEMS silicon disk resonator gyroscopes,to the best of our knowledge.To improve the quality factor of the DRG,the quality factor improvement mechanism is first analyzed,and based on this mechanism two stiffness-mass decoupled methods,i.e.,spoke length distribution optimization and lumped mass configuration design,are proposed and demonstrated.A disk resonator gyroscope prototype is fabricated based on these design strategies,and the sensor itself shows an angle random walk as low as 0.001°/√h,demonstrating true potential to achieve navigation-grade performance.The gyroscope with readout electronics shows an angle random walk of 0.01°/√h and a bias instability of 0.04°/h at room temperature without compensation,revealing that the performance of the gyroscope is severely limited by the readout electronics,which should be further improved.We expect that the quality factor improvement methods can be used in the design of other MEMS gyroscopes and that the newly designed DRG can be further improved to achieve navigation-grade performances for high-end industrial,transportation,aerospace,and automotive applications.

0.79 ppm scale-factor nonlinearity whole-angle microshell gyroscope realized by real-time calibration of capacitive displacement detection

Whole-angle gyroscopes have broad prospects for development with inherent advantages of excellent scale factor,wide bandwidth and measurement range,which are restrictions on rate gyroscopes.Previous studies on the whole-angle mode are based mostly on the linear model of Lynch,and the essential nonlinearity of capacitive displacement detection is always neglected,which has significant negative effects on the performance.In this paper,a novel realtime calibration method of capacitive displacement detection is proposed to eliminate these nonlinear effects.This novel method innovatively takes advantage of the relationship between the first and third harmonic components of detective signals for calibration.Based on this method,the real-time calibration of capacitive displacement detection is achieved and solves the problems of traditional methods,which are usually related to the vibration amplitude,environmental variations and other factors.Furthermore,this novel calibration method is embedded into a whole-angle control system to restore the linear capacitive response in real time and then combined with a microshell resonator for the first time to exploit the enormous potential of an ultrahigh Q factor and symmetric structure.The effectiveness is proven because the angle drift is reduced significantly to improve the scale-factor nonlinearity by 14 times to 0.79 ppm with 0.0673/h bias instability and a 0.0017s rate threshold,which is the best reported performance of the MEMS whole-angle gyroscope thus far.More importantly,this novel calibration method can be applied for all kinds of resonators with the requirement of a linear capacitive response even under a large resonant amplitude.

Comparison of UV and UV-LED activated sodium percarbonate for the degradation of O-desmethylvenlafaxine

As an active metabolite of venlafaxine and emerging antidepressant,Odesmethylvenlafaxine(ODVEN) was widely detected in different water bodies,which caused potential harm to human health and environmental safety.In this study,the comparative work on the ODVEN degradation by UV(254 nm) and UV-LED(275 nm) activated sodium percarbonate(SPC) systems was systematically performed.The higher removal rate of ODVEN can be achieved under UV-LED direct photolysis(14.99%) than UV direct photolysis(4.57%) due to the higher values of photolysis coefficient at the wavelength 275nm.Significant synergistic effects were observed in the UV/SPC(80.38%) and UV-LED/SPC(53.57%) systems and the former exhibited better performance for the elimination of ODVEN.The degradation of ODVEN all followed the pseudo-first-order kinetics well in these processes,and the pseudo-first-order rate constant(kobs) increased with increasing SPC concentration.Radicals quenching experiments demonstrated that both ·OH and CO_(3)·-were involved in the degradation of ODVEN and the second-order rate constant of ODVEN with CO_(3)·-(1.58 × 10^(8)(mol/L)-1sec-1) was reported for the first time based on competitive kinetic method.The introduction of HA,Cl-,NO_(3)-and HCO_(3)-inhibited the ODVEN degradation to varying degrees in the both processes.According to quantum chemical calculation,radical addition at the ortho-position of the phenolic hydroxyl group was confirmed to be the main reaction pathways for the oxidation of ODVEN by·OH.In addition,the oxidation of ODVEN may involve the demethylation,H-abstraction,OH^(-)addition and C-N bond cleavage.Eventually,the UV-LED/SPC process was considered to be more cost-effective compared to the UV/SPC process,although the UV/SPC process possessed a higher removal rate of ODVEN.

Removal of the rate table:MEMS gyrocompass with virtual maytagging

High-performance micro-electro-mechanical system(MEMS)gyrocompasses for north-finding systems have been very popular for decades.In this paper,a MEMS north-finding system(NFS)based on virtual maytagging(VM)is presented for the first time.In stark contrast to previous schemes of MEMS-based NFSs(e.g.,carouseling,maytagging)and the abandoning rate table,we developed a honeycomb disk resonator gyroscope(HDRG)and two commercial accelerometers for azimuth detection.Instead of the physical rotation of the integrated turntable in traditional NFSs,the vibratory working modes of the HDRG are rotated periodically with electronic control to reduce the uncertainty in the azimuth.After systematically analyzing the principle of NFSs with VM,we designed tests to verify the practicability at the sensor level.A bias instability of 0.0078°/h can be obtained during one day with VM in an HDRG.We also implemented comparative north-finding experiments to further check our strategy at the system level.The accuracy in the azimuth can reach 0.204°for 5 min at 28.2°latitude with VM and 0.172°with maytagging.The results show that without any mechanical turning parts,VM technology makes it possible to develop high-precision handheld MEMS NFSs.

Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy

Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.

Kinetics of oxidation of dimethyl trisulfide by potassium permanganate in drinking water

Metabolites of algae such as geosmin, 2- methylisoborneol etc. are reported to induce pungent odors into drinking water and attract additional scientifc attention. Recently, in China, taste and odor outbreaks in drinking water supply have become increasingly common. In source water affected by eutrophication, dimethyl trisulfide, speculated to be produced by decayed algae, was found to be the source of taste and odor issues and can be removed effectively by usual oxidation agents. In this experimental study, batch scale tests were carried out focusing on the removal of dimethyl trisulfide. Reaction kinetics of dimethyl trisulfide oxidized by potassium permanganate in water had been studied; influence factors such as pH, organic substrate, other existed taste, and odor contaminant in equivalent concentration were also dis- cussed. Results showed that dimethyl trisulfide can be removed by potassium permanganate efficiently; the ratio can reach more than 70% with oxidant dosage of 4 mg. L~ and contact time prolonged to 120 min. The dimethyl trisulfide decomposition followed a second-order kinetics pattern with a rate constant k -- 0.00213 L.（min.mg）-1. Typically, the degradation rate of dimethyl trisulfide was increased with the increasing KMnO4 dosage, but dramatically dropped with the increasing levels of humic acid （1.8-4.5 mg. L-1） and other odor-causing compounds （e.g. fl-cyclocitral, 0-1886.0 pg.L-1）. Solution pH （5.2- 9.0） and initial dimethyl trisulfide concentration did not significantly affected the degradation. This study demon- strates that KMnO4 oxidation is an effective option to remove dimethyl trisulfide from water.

High-resolution and large-size stretchable electrodes based on patterned silver nanowires composites

Electrodes based on composites of silver nanowires(AgNWs)and elastic polymers have been widely studied and applied in various stretchable electronic devices.However,due to the high aspect ratio of nanowires,the patterning of AgNW-based composite electrodes remains a huge challenge,especially for high-resolution complex circuit wiring on large-size elastic substrates.In this paper,we propose a method for preparing large-size stretchable circuit boards with high-resolution electrodes by the combination of screen printing and vacuum filtration of AgNWs/polydimethylsiloxane(PDMS)composite.The as-prepared stretchable electrodes have smooth edges with patterning resolution up to-50 μm.The conductivity of the composite electrode can be precisely controlled by varying deposition densities of AgNWs and have reached to 1.07 x 10^(4) S/cm when the deposition density was 2.0 mg/cm^(2).In addition,the uniformity of conductivity and the resistance-strain characteristics of composite electrodes were systematically evaluated with different AgNWs deposition densities.The composite electrodes have been successfully employed to construct a large-size programmable display system and an 18-channel surface electromyography(EMG)recording,showing great potentials for some strain-insensitive stretchable circuits in wearable and health-related electronic applications.

Analysis of factors influencing cardiopulmonary resuscitation and survival outcome in adults after in-hospital cardiac arrest:a retrospective observational study

To the Editor:Cardiopulmonary resuscitation(CPR)guidelines,especially the latest 2020 guidelines issued by the American Heart Association(AHA),have emphasized the importance of high-quality CPR.[1]The research on cardiac arrest(CA)and CPR has dramatically increased in recent years,and the international recovery guidelines are also being revised and implemented.However,the outcome of in-hospital cardiac arrest(IHCA)remains poor,and the understanding of the prognostic factors for survival outcome after IHCA is lacking,especially in China.Patients with CA are often poorly treated,and the incidence and mortality of CA are increasing yearly.[2]This study analyzed the effects of CPR,and explored the factors that affect survival outcome after IHCA in adults.

Highly Stretchable and Permeable Conductors Based on Shrinkable Electrospun Fiber Mats

Wearable on-skin electrodes or conductors should be vapor permeable,strain-insensitive,isotropically stretchable and stable under cyclic stretching.Various strategies have been proposed to prepare the required conductors up to now;however,it is a challenge to fabricate them with above properties in a simple manner.In this paper,a highly permeable and stretchable conductor based on electrospun fluorine rubber fiber mat is reported.The fibers are pre-stretched in electric field during electrospinning,and they shrink isotropically by~35-40%in area after being detached from the substrate.The obtained fiber mat conductor demonstrates high stretchability up to~170%,and the resistance changes only 0.8 under 60%strain,which is superior to many other strain-insensitive conductors.The conductor possesses high stability,no cracks or structure damage are observed after washing and cyclic stretching.Moreover,the conductor is vapor permeable with a water vapor transmission rate of~850 g m−2 day−1,which is comparable to the normal water evaporation in ambient conditions,indicating that it would not disturb the sweat evaporation when being used on skin.The conductor is successfully used as stretchable yarns and electromyography(EMG)electrodes,showing high reliability in E-textiles and on-skin applications.

Ⅳ期NSCLC原发肿瘤三维放射治疗失败模式分析

目的探讨Ⅳ期NSCLC原发肿瘤三维放疗联合药物一线治疗的失败模式特点及放疗相关因素的影响。方法选择2003年3月至2020年7月708例初诊Ⅳ期NSCLC患者,χ2检验失败模式单因素分析;Kaplan-Meier法并log-rank检验、Cox回归模型多因素生存分析。结果708例首次失败发生率71.2%,≤6个月、>6~12个月、>12~24个月、>24个月的治疗失败发生率分别为22.7%、28.8%、13.3%、6.4%,中位生存期分别为7.2、13.4、22.2、37.6个月,差异有统计学意义(χ2=226.013,P<0.001)。复发失败发生率为21.3%,寡转移和非寡转移的复发失败发生率差异无统计学意义。转移失败发生率为66.3%,从高到低依次为脑>骨>肺>胸膜腔>肝>远处淋巴结>肾上腺>其他部位,约1/2病例发生新增转移器官,约1/3病例发生原转移器官进展。转移状态、治疗失败发生时间、病理类型、性别、综合治疗强度是预后的独立影响因素。结论Ⅳ期NSCLC原发肿瘤放疗的失败模式与一线药物治疗不同,局部失败显著降低,转移失败为主,脑转移发生率最高,治疗失败发生时间越晚,OS期越长。寡转移、女性、非鳞癌、治疗失败发生时间晚、4~6个周期化疗同期放疗剂量≥63 Gy是延长生存的独立预后因子。

Strenuous exercise-tolerance stretchable dry electrodes for continuous multi-channel electrophysiological monitoring

Electrophysiological monitoring under strenuous exercise by using stretchable dry electrodes is vital for healthcare monitoring,prosthetic control,human−machine interfaces and other biomedical applications.However,the existing dry electrodes are not applicable to the strenuous exercise situation that always involves both fast moving and profuse sweating.Herein,we present a nano-thick porous stretchable dry electrode system with high stretchability and water permeability.The system attaches conformably to the skin and stretches with it under Van der Waals forces even at sweating conditions,allowing the detection of electromyogram when moving with an acceleration of 10 g at a sweating rate of 2.8 mg cm^(−2) min^(−1).It is also capable of acquiring electrocardiogram and electroencephalogram signals.The strategy proposed would enable the biomedical studies and related applications with the requirement of stably recording electrophysiological signals under strenuous exercise scenarios.