Research Progress on the Bone Metastasis Mechanism of Prostate Cancer and Bone-Targeted Drugs

Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.

碳纤维表面生长聚合物微球同时提高界面强度和韧性

碳纤维(CF)增强聚合物基复合材料(CFRPC)的界面性能是影响其性能和使用的关键因素,提高界面黏附强度常带来界面韧性损失。文中提出在CF表面进行点击分散聚合,原位生长功能聚合物粒子,同时提高CF-环氧复合材料界面强度和韧性。首先利用多巴胺(DA)对CF进行预处理,然后借助CF表面PDA,室温下进行巯基(-SH)-环氧(-Epoxy)在异丙醇或巯基(-SH)-异氰酸酯(-NCO)在乙醇中的原位点击分散聚合。扫描电镜(SEM)观察到,随单体用量增加,CF表面生长聚合物粒子增大、增多;红外光谱分析表明,使用等摩尔、高浓度单体,或使用过量-SH或-NCO单体,所得CF表面粒子含有残留-SH或-NCO基团,并可进一步功能化;动态接触角测试表明,单体用量增加,CF表面长出的聚合物粒子增多,表面接触角下降,表面能上升;微滴脱黏测试和SEM断面观察证实,长有粒子的CF与环氧基材的界面剪切强度和断裂韧性同时提高。

Numerical simulations and comparative analysis for two types of storm surges in the Bohai Sea using a coupled atmosphere-ocean model

The Bohai Sea is extremely susceptible to storm surges induced by extratropical storms and tropical cyclones in nearly every season. In order to relieve the impacts of storm surge disasters on structures and human lives in coastal regions, it is very important to understand the occurring of the severe storm surges. The previous research is mostly restricted to a single type of storm surge caused by extratropical storm or tropical cyclone. In present paper, a coupled atmosphere-ocean model is developed to study the storm surges induced by two types of extreme weather conditions. Two special cases happened in the Bohai Sea are simulated successively. The wind intensity and minimum sea-level pressure derived from the Weather Research and Forecasting (WRF) model agree well with the observed data. The computed time series of water level obtained from the Regional Ocean Modeling System (ROMS) also are in good agreement with the tide gauge observations. The structures of the wind fields and average currents for two types of storm surges are analyzed and compared. The results of coupled model are compared with those from the uncoupled model. The case studies indicate that the wind field and structure of the ocean surface current have great differences between extratropical storm surge and typhoon storm surge. The magnitude of storm surge in the Bohai Sea is shown mainly determined by the ocean surface driving force, but greatly affected by the coastal geometry and bathymetry.

Holocene sea level trend on the west coast of Bohai Bay,China: reanalysis and standardization

Using 110 newly revised Holocene sea level indicators categorized into three types,sediments(67),shelly cheniers(27)and oyster reefs(16),this paper firstly provides a Holocene relative sea level curve,based on multiple approaches of litho-and biostratigraphies and sedimentary faces analysis,for the west coast of Bohai Bay,China.Following considerations,including indicative meaning,the paleo tidal pattern and range and conversion from mean tidal level to mean sea level,an apparent relative mean sea level(RMSL)curve was further reconstructed.After systematical calibration using CALIB,those of the 48 reworked samples were further corrected for the residence-time effect.Similarly,the younger ages for another 35 samples were chosen at the subsample level.These result in a younger-oriented shift for about 0.5 ka.Three local spatial factors,including neotectonic subsidence(average rate about 0.1 mm/a),self-compaction of unconsolidated sediments(between a few decimeters to about 6 m)and subsidence due to groundwater withdrawal(between a few centimeters to about 2.5 m),were quantitatively corrected.Finally,the amended RMSL curve after eliminating all these local temporo-spatial factors is very likely to show non-existence of mid-Holocene highstand and imply potential influences of both ice-volume equivalent sea level and regional glacial isostatic adjustment.Although it is still unable to divide both global and regional factors,the slowdown of sea level rise,in 7.5–6.8 ka with a maximum height less than+1 m,may constrain the model effort in the near future.

High-value Applications of Nanocellulose

Nanocelluloses, obtained from the biopolymer cellulose, are a class of renewable functional nanomaterials with excellent properties and a broad range of applications. This review mainly illustrates practical and advanced applications of nanocellulose-based materials in the following categories.(1) Fire-resistant materials: in the section on these types of materials, the fireprotection property of nanocellulose/clay hybrid composites(clay nanopaper) is illustrated; oriented montmorillonite(MTM) provides barrier properties and low thermal conductivity whereas cellulose nanofibers(CNFs) impart favorable charring.(2) Thermal insulation materials: the best way to obtain materials with good heat insulation performance is to decrease the thermal conductivity of such materials.(3) Template materials: nanocellulose can direct the deposition and patterning of materials to form nanoparticles, nanowires, or nanotubes with improved properties.

Change of substrate geometry and laminin density stimulates axon branching

Axon branching enables neurons to contact with multiple targets and respond to their microenvironment.Owing to its importance in neuronal network formation,axon branching has been studied extensively during the past decades.It is reported that ECM(Extra Cellular Matrix)components such as laminin,collagen,and tenascin regulate the morphology and motility of neuronal growth cones in culture,but the effects of their distribution and the change of density on axon branching are not well understood.We fabricated chemically homogeneous substrate by microcontact printing(μCP)and inhomogeneous substrate with different laminin density

Enhancing gene editing efficiency for cells by CRISPR/Cas9 system-loaded multilayered nanoparticles assembled via microfluidics

Most non-viral carriers for in vitro delivery of nucleic acids suffer from low efficiency of introducing m RNA and other nucleic acids,especially large m RNA.Cas9 protein is the nuclease part of the powerful gene-editing tool,CRISPR/Cas9 system,Cas9 m RNA is particularly large,thus presents a big challenge for delivery.We assembled a multilayered biodegradable nanocarrier to load Cas9 m RNA inside to protect Cas9 m RNA from degradation.We used a microfluidic chip to synthesize a small,positively charged,and degradable core to attract negatively charged Cas9 m RNA.The microfluidic assembly allows the core to be small enough to incorporate into a cationic liposome.The multilayered nanocarriers elevated the delivery efficiency of Cas9 m RNA by over 2 folds and increased the expression by over 5 folds compared to commercially used non-viral carriers.In addition,the multilayered nanocarriers do not require reduced serum medium for transfection.When using the standard complete medium for transfection,the multilayered nanocarriers could increase the expression of Cas9 m RNA by over 15 folds compared to commercially used non-viral carriers.The co-delivery of Cas9 m RNA and sg RNA via LRC elevated the gene-editing efficiency by 3 folds compared to that via commercially used non-viral carriers.Based on the higher transfection efficiency of Cas9 m RNA/sg RNA than commercially used non-viral carriers,these multilayered nanocarriers may have a good prospect as efficient commercial delivery carriers for Cas9 m RNA/sg RNA and other nucleic acids.

High-performance organic electrochemical transistors gated with 3D-printed graphene oxide electrodes

Organic electrochemical transistors(OECTs)have garnered significant interest due to their ability to facilitate both ionic and electronic transport.A large proportion of research efforts thus far have focused on investigating high-performance materials that can serve as mixed ion doping and charge transport layers.However,relatively less attention has been given to the gateelectrode materials,which play a critical role in controlling operational voltage,redox processes,and stability,especially in the context of semiconductor-based OECTs working in accumulation mode.Moreover,the demand for planarity and flexibility in modern bioelectronic devices presents significant challenges for the commonly used Ag/AgCl electrodes in OECTs.Herein,we report the construction of high-performance accumulation-mode OECTs by utilizing a gate electrode made of three-dimensional(3D)-printed graphene oxide.The 3D-printed graphene oxide electrode incorporating one-dimensional(1D)carbon nanotubes,is directly printed using an aqueous-based ink and showcases exceptional mechanical flexibility and porosity properties,enabling high-throughput preparation for both top gates and integrated planar architecture,as well as fast ion/charge transport.OECTs with high performance comparable to that of Ag/AgCl-gated OECTs are thus achieved and present promising feasibility for electrocardiograph(ECG)signal recording.This provides a promising choice for the application of flexible bioelectronics in medical care and neurological recording.

Engineering oxygen vacancies and localized amorphous regions in CuO-ZnO separately boost catalytic reactivity and selectivity

Generating different types of defects in heterogeneous catalysts for synergetic promotion of the reactivity and selectivity in catalytic reactions is highly challenging due to the lack of effective theoretical guidance.Herein,we demonstrate a facile strategy to introduce two types of defects into the CuO-ZnO model catalyst,namely oxygen vacancies(OVs)induced by H2 partial reduction and localized amorphous regions(LARs)generated via the ball milling process.Using industrially important Rochow–Müller reaction as a representative,we found OVs predominantly improved the target product selectivity of dimethyldichlorosilane,while LARs significantly increased the conversion of reactant Si.The CuO-ZnO catalyst with optimized OVs and LARs contents achieved the best catalytic property.Theoretical calculation further revealed that LARs promote the generation of the Cu3Si active phase,and OVs impact the electronic structure of the Cu3Si active phase.This work provides a new understanding of the roles of different catalyst defects and a feasible way of engineering the catalyst structure for better catalytic performances.

Electronic exoneuron based on liquid metal for the quantitative sensing of the augmented somatosensory system

The increasing demands in augmented somatosensory have promoted quantitative sensing to be an emerging need for athletic training/performance evaluation and physical rehabilitation.Neurons for the somatosensory system in the human body can capture the information of movements in time but only qualitatively.This work presents an electronic Exo-neuron(EEN)that can spread throughout the limbs for realizing augmented somatosensory by recording both muscular activity and joint motion quantitatively without site constraints or drift instability,even in strenuous activities.Simply based on low-cost liquid metal and clinically used adhesive elastomer,the EEN could be easily fabricated in large areas for limbs.It is thin(~120μm),soft,stretchable(>500%),and conformal and further shows wide applications in sports,rehabilitation,health care,and entertainment.

Gold nanorods core/AgPt alloy nanodots shell： A novel potent antibacterial nanostructure

In the light of the current problems of silver nanoparticles （Ag NPs） in terms of antibacterial performance, we have designed a novel trimetallic corelshell nanostructure with AgPt alloy nanodots epitaxially grown on gold nanorods （Au@PtAg NRs） as a potential antibacterial agent. Both Escherichia coli （E. coli） and Staphylococcus aureus （S. aureus） were studied. The antibacterial activity exhibits an obvious composition-dependence. On increasing the Ag fraction in the alloy shell up to 80%, the antibacterial activity gradually increases, demonstrating a flexible way to tune this activity. At 80% Ag, tile antibacterial activity is better than that of a pure Ag shell. The improved antibacterial ability mainly results from the high exposure of silver on the shell surface due to the dot morphology. We thus demonstrate that forming alloys is an effective way to improve antibacterial activity while retaining high chemical stability for Ag-based nanomaterials. Furthermore, due to the tunable localized surface plasmonic response in the near-infrared （NIR） spectral region, additional control over antibacterial activity using light--such as photothermal killing and photo- triggered silver ion release--is expected. As a demonstration, highly enhanced antibacterial activity is shown by utilizing the NIR photothermal effect of the nanostructures. Our results indicate that such tailored nanostructures will find a role in the future fight against bacteria, including the challenge of the increasing severity of multidrug resistance.

Human-induced changes in recent sedimentation rates in Bohai Bay, China： Implications for coastal development

In many countries, coastal planners strive to balance the demands between civil, commercial strategy and environmental conversation interests for future development, particularly given the sea level rise in the 21 st century. Achieving a sustainable balance is often a dilemma, especially in low-lying coastal areas where dams in inland river basin are trapping significant amounts of fluvial sediments. We recently investigated the shore of Bohai Bay in northern China where there has been a severe increase in sea level following a program of large-scale coastal reclamation and infrastructure development over the last five decades. To investigate this trend, we obtained sediment cores from near-shore in Bohai Bay, which were dated by ^(137)Cs and ^(210)Pb radionuclides to determine the sedimentation rates for the last 50 years. The average sedimentation rates of Bohai Bay exceeded 10 mm yr^(-1) before 1963, which was much higher than the rate of local sea-level rise. However, our results showed an overall decreasing sedimentation rate after 1963, which was not able to compensate for the increasing relative sea-level rise in that period. In addition, our results revealed that erosion occurred after the 1980 s in the shallow sea area of Bohai Bay. We suggest that this situation places the Bohai Bay coast at a greater risk of inundation and erosion within the next few decades than previously thought, especially in the large new reclamation area. This study may be a case study for many other shallow sea areas of the muddy coast if the sea level continues to rise rapidly and the sediment delivered by rivers continues to decrease.

A Nano-and Micro-Integrated Protein Chip Based on Quantum Dot Probes and a Microfluidic Network

A novel nano-and micro-integrated protein chip(NMIPC)that can detect proteins with ultrahigh sensitivity has been fabricated.A microfl uidic network(μFN)was used to construct the protein chips,which allowed facile patterning of proteins and subsequent biomolecular recognition.Aqueous phase-synthesized,water-soluble fl uorescent CdTe/CdS core-shell quantum dots(aqQDs),having high quantum yield and high photostability,were used as the signaling probe.Importantly,it was found that aqQDs were compatible with microfluidic format assays,which afforded highly sensitive protein chips for cancer biomarker assays.

The construction of drug-resistant cancer cell lines by CRISPR/Cas9 system for drug screening

Cancer therapy is often hampered by the rapid emergence of drug resistance. Drug-resistant cellular models are essential for understanding the drug resistance and developing new therapeutics. The low efficiency and long time required in creating these models are major obstacles hindering drug resistance research and drug screening. Herein, we report an approach that can accelerate(shortening the time from years to 3 weeks) the establishment of cancer cell line-based, inheritable drug resistance models by specific knockout of MED12 gene using CRISPR/Cas9 system. The resultant MED12^(KO) A375(melanoma)cell line was resistant to inhibitors of B-Raf proto-oncogene, serine/threonine kinase(BRAF), whereas the resultant MED12^(KO) PC9(non-small cell lung cancer) cell line was resistant to inhibitors of epidermal growth factor receptor(EGFR). Evaluation of anti-cancer drugs and their combinations shows that certain combinations of BRAF inhibitors and TGF-β receptor(TGF-βR) inhibitors are active in suppressing the growth of MED12^(KO) A375 cells, and a few combinations of EGFR inhibitors and TGF-βR inhibitors were active in suppressing the growth of MED12^(KO) PC9 cells. The drug-resistant models will be useful in screening novel drugs and drug combinations for multi-drug-resistant cancer therapy.

Aggregation-Induced Fluorogens in Bio-Detection,Tumor Imaging,and Therapy:A Review

Aggregation-induced emission(AIE)fluorogens produce strong,stable fluorescence upon aggregation,thus enabling a new frontier in bio-detection,cell imaging,and other biomedical applications.In this review,we summarize the recent developments of AIE fluorogen design strategy,bio-detection,cell imaging,tumor imaging,vascular imaging,and image-guided tumor therapy.We highlight a section on the microfluidic approach to synthesize AIE nanoparticles(NPs)and current challenges and potentials of AIE NPs.

An immunoassay based on lab-on-a-chip for simultaneous and sensitive detection of clenbuterol and ractopamine

Both clenbuterol(CLB)and ractopamine(RAC)areβ-adrenergic agonists.After long-term excessive intake,there will be adverse reactions such as headache,chest tightness,limb numbness,and serious lifethreatening.Simultaneous detection of CLB and RAC in related samples is of great importance for human health.In this work,we outline a microfluidics-based indirect competitive immunoassay(MICI)system that can sensitively detect residual CLB and RAC in pork,swine blood and swine urine.The rapid detection of multiple samples can be achieved in one chip,which greatly improves the detection efficiency.This method has good stability and reproducibility and the microfluidic chips are easy to manufacture.The linear ranges for CLB and RAC detection by MICI are 0.1-2.5 ng/mL and 0.1-5 ng/mL,and the limits of detection(LODs)are 0.094 ng/mL and 0.091 ng/mL,respectively.This straightforward and portable immunoassay system provides a good platform for rapid detection of harmful substances in food samples.

Point-of-Care Immunoassays with Tunable Detection Range for Detecting Infection in Intensive Care Unit

One of the difficulties of a multiplexed analytical assay is matching the concentration range of different markers.Here,the authors develop an automatic,multiplexed point-of-care(POC)immunoassay that allows detecting C-reactive protein(CRP),procalcitonin(PCT),and interleukin 6(IL-6)in 50μL serum samples with limits of detection 1.87μg/mL,0.17 ng/mL,and 49.75 pg/mL,respectively.The authors use electrospun fibers and surface chemistry of gold nanoparticles(AuNPs)to adjust the detection range of different biomarkers.The authors have proposed some new diagnostic indicators(mScore and mScorePlus)that combine the results of CRP,PCT,IL-6,and complete blood counts(CBCs).The authors also tracked changes in CRP,PCT,and IL-6 of patients in an intensive care unit(ICU).The authors find that mScore and mScorePlus have advantages in improving the diagnostic accuracy and providing more analytical information.mScore and mScorePlus are effective tools to detect infections,differentiate bacterial and viral infections,and monitor disease.Integrating multiple markers into one straightforward parameter is an effective method for analytical applications.The authors believe that this method provides a general way for chemists to develop increasingly accurate detection methods and indicators.

Organic nanoparticles formed by aggregation-induced fluorescent molecules for detection of hydrogen sulfide in living cells

Hydrogen sulfide(H_2S)has been found to be the third most important endogenous gaseous signaling molecule after nitric oxide(NO)and carbonic oxide(CO)and plays crucial roles in living organisms and biological systems.Here we use aggregation-induced emission(AIE)of a small organic molecule(TPE-indo)to detect H_2S in both solution and living cells.TPE-indo can target mitochondria and aggregate to fluoresce,which can serve as a sensor for monitoring H_2S in the mitochondria.We regulate the fluorescence of AIE molecules by tuning the viscosity of the solution to form TPE-indo nanoparticles,constructing a probe for H_2S with good selectivity and high sensitivity.The nucleophilic addition of HS-to the TPE-indo is crucial for the rapid H_2S detection.The imaging and analysis of H_2S in mitochondria of living cells with the probe demonstrate potential biological applications.

Growth Behavior of Rubrene Thin Films on Hexagonal Boron Nitride in the Early Stage

Two-dimensional materials,with an in-plane ordered and dangling-bonding-free surface,are ideal substrates for fabricating high-quality crystalline thin films.Here,we show a systematic study on the growth of a benchmark organic semiconductor,rubrene,on hexagonal boron nitride(h-BN)substrate via physical vapor deposition from the initial amorphous phase to the final crystalline phase;the role of temperature in such transition and the epitaxy relationship between rubrene and h-BN are revealed.With the increase of substrate temperature,the critical thickness of amorphous-crystalline-transition decreases and the morphology of crystalline phase also evolves from porous to terrace-like.When substrate temperature reaches>100℃,the critical thickness reduces to only 0.5 nm and a precise layer-by-layer growth from the very first layer is achieved,which is quite rare for rubrene growing on other substrates.The high ordering can be attributed to the fine epitaxy relationship between rubrene films and the h-BN surface lattice,and this film demonstrates good charge transport ability with a p-type field-effect mobility of>1 cm^(2)·V^(-1)·s^(-1).