BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We per...BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points.RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point.CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.展开更多
Randomness and fluctuations in wind power output may cause changes in important parameters(e.g.,grid frequency and voltage),which in turn affect the stable operation of a power system.However,owing to external factors...Randomness and fluctuations in wind power output may cause changes in important parameters(e.g.,grid frequency and voltage),which in turn affect the stable operation of a power system.However,owing to external factors(such as weather),there are often various anomalies in wind power data,such as missing numerical values and unreasonable data.This significantly affects the accuracy of wind power generation predictions and operational decisions.Therefore,developing and applying reliable wind power interpolation methods is important for promoting the sustainable development of the wind power industry.In this study,the causes of abnormal data in wind power generation were first analyzed from a practical perspective.Second,an improved complete ensemble empirical mode decomposition with adaptive noise(ICEEMDAN)method with a generative adversarial interpolation network(GAIN)network was proposed to preprocess wind power generation and interpolate missing wind power generation sub-components.Finally,a complete wind power generation time series was reconstructed.Compared to traditional methods,the proposed ICEEMDAN-GAIN combination interpolation model has a higher interpolation accuracy and can effectively reduce the error impact caused by wind power generation sequence fluctuations.展开更多
The mechanical properties of Portland cement differ from the weakly consolidated shallow formation in deep water.This results in undesired abrupt changes in the compressive strength and elastic modulus at the cement–...The mechanical properties of Portland cement differ from the weakly consolidated shallow formation in deep water.This results in undesired abrupt changes in the compressive strength and elastic modulus at the cement–formation interface.In this study,a water-borne epoxy resin was applied as a strengthening material to reinforce the weakly consolidated shallow formation and protect the cement sheath from potential failure.The mechanical properties of the unconsolidated clay were tested,including their changes with increases in the temperature and curing time.In addition,the effects of the seawater,cement slurry alkaline filtrate,and saltwater drilling fluid were evaluated.As confirmed by the results,the strengthening fluid was excellent at reinforcing the unconsolidated clay,with a compressive strength of 2.49 MPa(after curing for 7 days),even at a dosage of 5%.A cement slurry filtrate with a high pH was suitable to produce the required strengthening of the formation,especially its early age strength.It should also be pointed out that the used fluid exhibited good compatibility with the saltwater drilling fluid and seawater behaved well as a diluent for the strengthening fluid.展开更多
Perforation and fracturing are typically associated with the development of coalbed methane wells.As the cement sheath is prone to failure during this process,in this work,the effects of the casing pressure,elastic mo...Perforation and fracturing are typically associated with the development of coalbed methane wells.As the cement sheath is prone to failure during this process,in this work,the effects of the casing pressure,elastic modulus of the cement,elastic modulus of the formation,and casing eccentricity on the resulting stresses are analyzed in the frame of a finite element method.Subsequently,sensitivity response curves of the cement sheath stress are plotted by normalizing all factors.The results show that the maximum circumferential stress and Mises stress of the cement sheath increase with the casing internal pressure,elastic modulus of the cement and casing eccentricity.As the elastic modulus of the formation increases,the maximum circumferential stress of the cement sheath decreases,and its maximum Mises stress increases slightly.The cement sheath undergoes tensile failure during coalbed methane fracturing.The stress sensitivity of the cement sheath to the influential parameters is in the following order:casing internal pressure>elastic modulus of cement sheath>casing eccentricity>elastic modulus of formation.展开更多
Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly...Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Hart Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes lp21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL 1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS's molecular etiology and generate a list of interesting candidate regions for further studies.展开更多
The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which e...The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.展开更多
Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly desired.As an alternative,liquid metals(LMs),a nontraditional family of metal materials...Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly desired.As an alternative,liquid metals(LMs),a nontraditional family of metal materials,have piqued the interest of biomedical researchers and made significant advances in biomed-ical areas,owing to their shape transformability,self-healing capability,excellent electrical,and thermal conductivities.In particular,many functionalized strategies for the preparation and modification of LMs or LMs-based composites to achieve extended biomedical applications have been investigated in recent years.These findings provided inspiring while constructive reference for the fabrication and engineering of novel LMs-based composites.Herein,in this topic review,we elaborate on the recent advances of LMs-based functional materials,with particular focuses on the synthesis,modification,and bio-applications,especially in antitumor therapy,antibacterial,contrast agent for imaging,bone repair,electronic skin sen-sor,and nerve connection agent.Further on,the current challenges and future prospects of LMs-based composites are carefully discussed.展开更多
A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical prop...A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical properties and in vitro degradation behavior were all evaluated.The adhesion and proliferation of Schwann cells(SCs)were observed.In the in vivo experiment,MC@Col NGC and other conduits including Col,chitosan(CST)and polycaprolactone(PCL)conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect.Histological analyses,morphological analyses,electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks.The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC.In vitro cytocompatibility evaluation revealed that the SCs had good viability,attachment and proliferation in the MC@Col.In in vivo results,the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects,but superior to those by Col,CST and PCL conduits.The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration,thus showing great promising potential as a new type of conduit in clinical applications.展开更多
The authors regret that the last name and first name of all authors are reversed in the original article.The correct writing is as follows:Le Jiang,a,b#;Zhongqun Liu,a,b#;Zhaoyan Wang,d,e,f;Yijun Su,a,b;Yingjin Wang,a...The authors regret that the last name and first name of all authors are reversed in the original article.The correct writing is as follows:Le Jiang,a,b#;Zhongqun Liu,a,b#;Zhaoyan Wang,d,e,f;Yijun Su,a,b;Yingjin Wang,a,b;Yaojie Wei,a,b;Yanan Jiang,c;Zhanrong Jia,c;Chunyang Ma,a,b;Fangli Gang,a,b;Nan Xu,a,b;Lingyun Zhao,a,b;Xiumei Wang,a,b;Qiong Wu,d,e,f;Xiong Lu,c,*and Xiaodan Sun,a,b,*a.State Key Laboratory of New Ceramics and Fine Processing,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;b.Key Laboratory of Advanced Materials of Ministry of Education of China,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;c.Key Lab of Advanced Technologies of Materials of Ministry of Education,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu 610031,People’s Republic of China d.MOE Key Laboratory of Bioinformatics,Tsinghua University,Beijing,100084,People’s Republic of China e.Center for Synthetic and Systems Biology,Tsinghua University,Beijing,100084,People’s Republic of China f.School of Life Sciences,Tsinghua University,Beijing,100084,People’s Republic of China.展开更多
Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging...Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes (IOMS NCs) via the integration of MoS2 (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a 3?2 relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.展开更多
Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for oste...Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe_3O_4 nanoparticles into chitosan/polyethylene glycol(PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field(AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells(MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.展开更多
Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen(DO),representing an ideal state for maintaining good water quality,and conducive to the biomineralization of organic matter.Water l...Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen(DO),representing an ideal state for maintaining good water quality,and conducive to the biomineralization of organic matter.Water lifting aerators(WLAs)can extend the periods of complete mixing and increase the initial mixing temperature.To evaluate the influence of artificial-induced continuously mixing on dissolved organic matter(DOM)removal performance,the variations of DOM concentrations,optical characteristic,environmental factors were studied after approaching the total mixing status via WLAs operation.During this process,the dissolved organic carbon reduced by 39.18%,whereas the permanganate index decreased by 20.47%.The optical properties indicate that the DOM became more endogenous and its molecular weight decreased.Based on the results of the Biolog Eco Plates,the microorganisms were maintained at a relatively high metabolic activity in the early stage of induced mixing when the mixing temperature was relatively high,whereas DOM declined at a high rate.With the continuous decrease in the water temperature,both the metabolic capacity and the diversity of aerobic microorganisms significantly decreased,and the rate of organic matter mineralization slowed down.The results of this study demonstrate that the artificial induced mixing largely enhanced the removal DOM performance by providing a long period of aerobic conditions and higher initial temperature.展开更多
Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment u...Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)4-CONH2). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.展开更多
Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of deve...Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.展开更多
Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles (NPs) as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential t...Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles (NPs) as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential toxicity in synthesis, the lack of general methods for the controlled synthesis of various kinds of magnetic NP (MNP)@conjugated polymer NPs, and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics. We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole (PPy) NPs with balanced, prominent magneto-optical properties. MNP@PPy NPs with an adjustable size, different shapes, and a controlled shell thickness were obtained using this method. The method was extended to synthesize other MNP-conjugated polymer core-shell NPs, such as MNP@polyaniline and MNP@poly(3,4-ethylenedioxythiophene):poly(4- styrenesulfonate) (PEDOT:PSS). We discuss the formation mechanism of the proposed method according to our experimental results. Finally, using the optical and magnetic properties of the obtained MNP@PEDOT:PSS NPs, in vivo multimodal imaging-guided hyperthermia was induced in mice, achieving an excellent tumor-ablation therapeutic effect. Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.展开更多
Amphipathic polymer pullulan acetate (PA)-coated magnetic nanoparticles were prepared and characterized by various physicochemical means. The cytotoxicity and cellular uptake of the magnetic nanoparticles were examine...Amphipathic polymer pullulan acetate (PA)-coated magnetic nanoparticles were prepared and characterized by various physicochemical means. The cytotoxicity and cellular uptake of the magnetic nanoparticles were examined. The hyperthermic effect of the magnetic nanoparticles on tumor cells was evaluated. Transmission electron microscopy (TEM) showed that the PA coated magnetic nanoparticles (PAMNs) had spherical morphology. Dynamic light scattering (DLS) showed that the size distribution of PAMNs was unimodal,with an average diameter of 25.8 nm ± 6.1 nm. The presence of the adsorbed layer of PA on the magnetite surface was confirmed by Fourier transform infrared (FTIR) spectroscopy. Magnetic measurements revealed that the saturation magnetization of the PAMNs reached 51.9 emu/g and the nanoparticles were superparamagnetic. Thermogravimetric analysis (TGA) showed that the Fe_(3)O_(4) particles constituted 75 wt% of the PAMNs. The PAMNs had good heating properties in an alternating magnetic field. Cytotoxicity assay showed that PAMNs exhibited no significant cytotoxicity against L929 cells. TEM results showed that a large number of PAMNs were internalized into KB cells. PAMNs have good hyperthermia effect on KB cells in vitro by magnetic field induced hyperthermia. These novel magnetic nanoparticles have great potential as magnetic hyperthermia mediators.展开更多
With tremendous research advances in biomedical application,liquid metals(LM)also offer fantastic chemistry for synthesis of novel nano-composites.Herein,as a pioneering trial,litchi-shaped heterogeneous eutectic gall...With tremendous research advances in biomedical application,liquid metals(LM)also offer fantastic chemistry for synthesis of novel nano-composites.Herein,as a pioneering trial,litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles(EGaIn-Au NPs),served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy,have been successfully prepared using in situ interfacial galvanic replacement reaction.The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium(EGaIn)NPs surface.Most importantly,the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs.Inspired by this approach,in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities.展开更多
The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained in...The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.展开更多
基金supported by the Health and Medical Research Fund of the Food and Health Bureau of the Hong Kong Special Administrative Region(Project No.19201161)Seed Fund from the University of Hong Kong.
文摘BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points.RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point.CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.
基金supported by the Undergraduate Teaching Innovation Project of Guangxi Higher Education(grant numbers 2021JGB286,Guangxi Zhuang Autonomous Region Department of Education,China).
基金We gratefully acknowledge the support of National Natural Science Foundation of China(NSFC)(Grant No.51977133&Grant No.U2066209).
文摘Randomness and fluctuations in wind power output may cause changes in important parameters(e.g.,grid frequency and voltage),which in turn affect the stable operation of a power system.However,owing to external factors(such as weather),there are often various anomalies in wind power data,such as missing numerical values and unreasonable data.This significantly affects the accuracy of wind power generation predictions and operational decisions.Therefore,developing and applying reliable wind power interpolation methods is important for promoting the sustainable development of the wind power industry.In this study,the causes of abnormal data in wind power generation were first analyzed from a practical perspective.Second,an improved complete ensemble empirical mode decomposition with adaptive noise(ICEEMDAN)method with a generative adversarial interpolation network(GAIN)network was proposed to preprocess wind power generation and interpolate missing wind power generation sub-components.Finally,a complete wind power generation time series was reconstructed.Compared to traditional methods,the proposed ICEEMDAN-GAIN combination interpolation model has a higher interpolation accuracy and can effectively reduce the error impact caused by wind power generation sequence fluctuations.
基金supported by the Natural Science Foundation of China(51804332,51974355)Major Scientific and Technological Projects of CNPC(ZD2019-184-003)+1 种基金Provincial Geological Exploration Fund of Guizhou Province(208-9912-JBN-UTS0)Shandong Provincial Natural Science Foundation(ZR2017LEE005).
文摘The mechanical properties of Portland cement differ from the weakly consolidated shallow formation in deep water.This results in undesired abrupt changes in the compressive strength and elastic modulus at the cement–formation interface.In this study,a water-borne epoxy resin was applied as a strengthening material to reinforce the weakly consolidated shallow formation and protect the cement sheath from potential failure.The mechanical properties of the unconsolidated clay were tested,including their changes with increases in the temperature and curing time.In addition,the effects of the seawater,cement slurry alkaline filtrate,and saltwater drilling fluid were evaluated.As confirmed by the results,the strengthening fluid was excellent at reinforcing the unconsolidated clay,with a compressive strength of 2.49 MPa(after curing for 7 days),even at a dosage of 5%.A cement slurry filtrate with a high pH was suitable to produce the required strengthening of the formation,especially its early age strength.It should also be pointed out that the used fluid exhibited good compatibility with the saltwater drilling fluid and seawater behaved well as a diluent for the strengthening fluid.
基金funded by the Provincial Geological Exploration Fund of Guizhou Province(208-9912-JBN-UTS0).
文摘Perforation and fracturing are typically associated with the development of coalbed methane wells.As the cement sheath is prone to failure during this process,in this work,the effects of the casing pressure,elastic modulus of the cement,elastic modulus of the formation,and casing eccentricity on the resulting stresses are analyzed in the frame of a finite element method.Subsequently,sensitivity response curves of the cement sheath stress are plotted by normalizing all factors.The results show that the maximum circumferential stress and Mises stress of the cement sheath increase with the casing internal pressure,elastic modulus of the cement and casing eccentricity.As the elastic modulus of the formation increases,the maximum circumferential stress of the cement sheath decreases,and its maximum Mises stress increases slightly.The cement sheath undergoes tensile failure during coalbed methane fracturing.The stress sensitivity of the cement sheath to the influential parameters is in the following order:casing internal pressure>elastic modulus of cement sheath>casing eccentricity>elastic modulus of formation.
文摘Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Hart Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes lp21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL 1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS's molecular etiology and generate a list of interesting candidate regions for further studies.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.52072210 and 52111530230)Key R&D Projects of Social Development of Hainan Provincial Department of Science and Technology(Grant No.ZDYF2020137)Tsinghua University Beijing Union Medical CollegeeHospital Cooperation Project(Grant No.20191080871).
文摘The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.
基金financially supported by the National Natural Science Foundation of China (No.51971116)the UTokyo-Tsinghua Collaborative Research Fund (No.20213080033)the Open Funding Project of the State Key Laboratory of Biochemical Engineering (No.2021KF-04).
文摘Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly desired.As an alternative,liquid metals(LMs),a nontraditional family of metal materials,have piqued the interest of biomedical researchers and made significant advances in biomed-ical areas,owing to their shape transformability,self-healing capability,excellent electrical,and thermal conductivities.In particular,many functionalized strategies for the preparation and modification of LMs or LMs-based composites to achieve extended biomedical applications have been investigated in recent years.These findings provided inspiring while constructive reference for the fabrication and engineering of novel LMs-based composites.Herein,in this topic review,we elaborate on the recent advances of LMs-based functional materials,with particular focuses on the synthesis,modification,and bio-applications,especially in antitumor therapy,antibacterial,contrast agent for imaging,bone repair,electronic skin sen-sor,and nerve connection agent.Further on,the current challenges and future prospects of LMs-based composites are carefully discussed.
基金funded by the National Key R&D Program of China(No.2020YFC1107601)The Foshan-Tsinghua Innovation Special Fund(No.2020THFS05)the Key R&D Program in Shandong Province(2019JZZY011106).
文摘A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical properties and in vitro degradation behavior were all evaluated.The adhesion and proliferation of Schwann cells(SCs)were observed.In the in vivo experiment,MC@Col NGC and other conduits including Col,chitosan(CST)and polycaprolactone(PCL)conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect.Histological analyses,morphological analyses,electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks.The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC.In vitro cytocompatibility evaluation revealed that the SCs had good viability,attachment and proliferation in the MC@Col.In in vivo results,the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects,but superior to those by Col,CST and PCL conduits.The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration,thus showing great promising potential as a new type of conduit in clinical applications.
文摘The authors regret that the last name and first name of all authors are reversed in the original article.The correct writing is as follows:Le Jiang,a,b#;Zhongqun Liu,a,b#;Zhaoyan Wang,d,e,f;Yijun Su,a,b;Yingjin Wang,a,b;Yaojie Wei,a,b;Yanan Jiang,c;Zhanrong Jia,c;Chunyang Ma,a,b;Fangli Gang,a,b;Nan Xu,a,b;Lingyun Zhao,a,b;Xiumei Wang,a,b;Qiong Wu,d,e,f;Xiong Lu,c,*and Xiaodan Sun,a,b,*a.State Key Laboratory of New Ceramics and Fine Processing,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;b.Key Laboratory of Advanced Materials of Ministry of Education of China,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;c.Key Lab of Advanced Technologies of Materials of Ministry of Education,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu 610031,People’s Republic of China d.MOE Key Laboratory of Bioinformatics,Tsinghua University,Beijing,100084,People’s Republic of China e.Center for Synthetic and Systems Biology,Tsinghua University,Beijing,100084,People’s Republic of China f.School of Life Sciences,Tsinghua University,Beijing,100084,People’s Republic of China.
基金This study was supported by the National Natural Science Foundation of China (NSFC) (No. 81671829).
文摘Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes (IOMS NCs) via the integration of MoS2 (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a 3?2 relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.
基金financial support from the National Natural Science Foundation of China (81671829)the 111 Project (B17026)
文摘Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe_3O_4 nanoparticles into chitosan/polyethylene glycol(PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field(AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells(MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.
基金supported by the National Natural Science Foundation of China(No.51979217)the National Key Research and Development Program of China(No.2019YFD1100101)the Shaanxi Provincial Key Research and Development Project(Nos.2019ZDLSF06-01 and 2019ZDLSF06-02)。
文摘Naturally complete mixing promotes the spontaneous redistribution of dissolved oxygen(DO),representing an ideal state for maintaining good water quality,and conducive to the biomineralization of organic matter.Water lifting aerators(WLAs)can extend the periods of complete mixing and increase the initial mixing temperature.To evaluate the influence of artificial-induced continuously mixing on dissolved organic matter(DOM)removal performance,the variations of DOM concentrations,optical characteristic,environmental factors were studied after approaching the total mixing status via WLAs operation.During this process,the dissolved organic carbon reduced by 39.18%,whereas the permanganate index decreased by 20.47%.The optical properties indicate that the DOM became more endogenous and its molecular weight decreased.Based on the results of the Biolog Eco Plates,the microorganisms were maintained at a relatively high metabolic activity in the early stage of induced mixing when the mixing temperature was relatively high,whereas DOM declined at a high rate.With the continuous decrease in the water temperature,both the metabolic capacity and the diversity of aerobic microorganisms significantly decreased,and the rate of organic matter mineralization slowed down.The results of this study demonstrate that the artificial induced mixing largely enhanced the removal DOM performance by providing a long period of aerobic conditions and higher initial temperature.
文摘Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)4-CONH2). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.
基金the National Natural Science Foundation of China(31771056 and 81200931)the Tsinghua University Initiative Scientific Research Program(20161080091)+1 种基金the 111 Project(B17026)a special fund from Key laboratory of Neurodegenerative diseases,Ministry of Education(PXM2019_026283_000002).
文摘Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.
文摘Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles (NPs) as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential toxicity in synthesis, the lack of general methods for the controlled synthesis of various kinds of magnetic NP (MNP)@conjugated polymer NPs, and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics. We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole (PPy) NPs with balanced, prominent magneto-optical properties. MNP@PPy NPs with an adjustable size, different shapes, and a controlled shell thickness were obtained using this method. The method was extended to synthesize other MNP-conjugated polymer core-shell NPs, such as MNP@polyaniline and MNP@poly(3,4-ethylenedioxythiophene):poly(4- styrenesulfonate) (PEDOT:PSS). We discuss the formation mechanism of the proposed method according to our experimental results. Finally, using the optical and magnetic properties of the obtained MNP@PEDOT:PSS NPs, in vivo multimodal imaging-guided hyperthermia was induced in mice, achieving an excellent tumor-ablation therapeutic effect. Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.
基金This study was supported by the Beijing Municipal Science&Technology Commission(No.Z07000200540704)the China Postdoctoral Science Foundation(No.20090450417)and the Tsinghua Yuyuan Medical Fund.
文摘Amphipathic polymer pullulan acetate (PA)-coated magnetic nanoparticles were prepared and characterized by various physicochemical means. The cytotoxicity and cellular uptake of the magnetic nanoparticles were examined. The hyperthermic effect of the magnetic nanoparticles on tumor cells was evaluated. Transmission electron microscopy (TEM) showed that the PA coated magnetic nanoparticles (PAMNs) had spherical morphology. Dynamic light scattering (DLS) showed that the size distribution of PAMNs was unimodal,with an average diameter of 25.8 nm ± 6.1 nm. The presence of the adsorbed layer of PA on the magnetite surface was confirmed by Fourier transform infrared (FTIR) spectroscopy. Magnetic measurements revealed that the saturation magnetization of the PAMNs reached 51.9 emu/g and the nanoparticles were superparamagnetic. Thermogravimetric analysis (TGA) showed that the Fe_(3)O_(4) particles constituted 75 wt% of the PAMNs. The PAMNs had good heating properties in an alternating magnetic field. Cytotoxicity assay showed that PAMNs exhibited no significant cytotoxicity against L929 cells. TEM results showed that a large number of PAMNs were internalized into KB cells. PAMNs have good hyperthermia effect on KB cells in vitro by magnetic field induced hyperthermia. These novel magnetic nanoparticles have great potential as magnetic hyperthermia mediators.
基金supported by grants of the National Natural Science Foundation of China(Nos.5197116,81671829).
文摘With tremendous research advances in biomedical application,liquid metals(LM)also offer fantastic chemistry for synthesis of novel nano-composites.Herein,as a pioneering trial,litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles(EGaIn-Au NPs),served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy,have been successfully prepared using in situ interfacial galvanic replacement reaction.The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium(EGaIn)NPs surface.Most importantly,the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs.Inspired by this approach,in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities.
基金support from the National Key R&D Program of China(Nos.2020YFC1107600 and 2018YFB0704304)the National Natural Science Foundation of China(Nos.31771056 and 31771052)Shandong Province Key R&D Program of China(No.2019JZZY011106).
文摘The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.