The micaceous weathered granitic soil(WGS)is frequently encountered in civil engineering worldwide,unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS.This ...The micaceous weathered granitic soil(WGS)is frequently encountered in civil engineering worldwide,unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS.This study prepares reconstituted WGS with different mica contents by removing natural mica in theWGS,and then mixes it with commercial mica powders.The geotechnical behavior as well as the microstructures of the mixtures are characterized.The addition of mica enables the physical indices of WGS to be specific combinations of coarser gradation and high permeability but high Atterberg limits.However,high mica content in WGS was found to be associated with undesirable mechanical properties,including increased compressibility,disintegration,and swelling potential,as well as poor compactability and low effective frictional angle.Microstructural analysis indicates that the influence of mica on the responses of mixtures originates from the intrinsic nature of mica as well as the particle packing being formed withinWGS.Mica exists in the mixture as stacks of plates that form a spongy structure with high compressibility and swelling potential.Pores among the plates give the soil high water retention and high Atterberg limits.Large pores are also generated by soil particles with bridging packing,which enhances the permeability and water-soil interactions upon immersion.This study provides a microlevel understanding of how mica dominates the behavior of WGS and provides new insights into the effective stabilization and improvement of micaceous soils.展开更多
Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we re...Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.展开更多
The inter-city linkage heat data provided by Baidu Migration is employed as a characterization of inter-city linkages in order to facilitate the study of the network linkage characteristics and hierarchical structure ...The inter-city linkage heat data provided by Baidu Migration is employed as a characterization of inter-city linkages in order to facilitate the study of the network linkage characteristics and hierarchical structure of urban agglomeration in the Greater Bay Area through the use of social network analysis method.This is the inaugural application of big data based on location services in the study of urban agglomeration network structure,which represents a novel research perspective on this topic.The study reveals that the density of network linkages in the Greater Bay Area urban agglomeration has reached 100%,indicating a mature network-like spatial structure.This structure has given rise to three distinct communities:Shenzhen-Dongguan-Huizhou,Guangzhou-Foshan-Zhaoqing,and Zhuhai-Zhongshan-Jiangmen.Additionally,cities within the Greater Bay Area urban agglomeration play different roles,suggesting that varying development strategies may be necessary to achieve staggered development.The study demonstrates that large datasets represented by LBS can offer novel insights and methodologies for the examination of urban agglomeration network structures,contingent on the appropriate mining and processing of the data.展开更多
Carbon storage of terrestrial ecosystems plays a vital role in advancing carbon neutrality. Better understanding of how land use changes affect carbon storage in urban agglomeration will provide valuable guidance for ...Carbon storage of terrestrial ecosystems plays a vital role in advancing carbon neutrality. Better understanding of how land use changes affect carbon storage in urban agglomeration will provide valuable guidance for policymakers in developing effective regional conservation policies. Taking the Pearl River Delta Urban Agglomeration(PRDUA) in China as an example, we examined the heterogeneous response of carbon storage to land use changes in 1990–2018 from a combined view of administrative units and physical entities. The results indicate that the primary change in land use was due to the expansion of construction land(5897.16 km2). The carbon storage in PRDUA decreased from 767.34 Tg C in 1990 to 725.42 Tg C in 2018 with a spatial pattern of high wings and the low middle. The carbon storage loss was largely attributed to construction land expansion(55.74%), followed by forest degradation(54.81%). Changes in carbon storage showed significant divergences in different sized cities and hierarchical boundaries. The coefficients of geographically weighted regression(GWR) reveal that the alteration in carbon storage in Guangzhou City was more responsive to changes in construction land(-0.11) compared to other cities, while that in Shenzhen was mainly affected by the dynamics of forest land(8.32). The change in carbon storage was primarily influenced by the conversion of farmland within urban extent(5.05) and the degradation of forest land in rural areas(5.82). Carbon storage changes were less sensitive to the expansion of construction land in the urban center, urban built-up area, and ex-urban built-up area, with the corresponding GWR coefficients of 0.19, 0.04, and 0.02. This study necessitates the differentiated protection strategies of carbon storage in urban agglomerations.展开更多
Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synt...Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells,using a synthetic lethal short hairpin RNA(shRNA) screening approach.Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183(RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF 183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA(siRNA) was used to knock down RNF183 transiently.Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay(ELISA) were used to evaluate the protein abundance. MTT assay,colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation.Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8(IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo.Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.展开更多
Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradatio...Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.展开更多
As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination ...As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination of the major alkaloids in U.rhynchophylla.In this research,a rapid quantitative analysis involving multi-components analysis by a single marker strategy coupled with core-shell column HPLC was adopted to analyse four alkaloids(corynoxeine,isocorynoxeine,isorhynchophylline,rhynchophylline)in U.rhynchophylla.Isorhynchophylline was selected as the internal reference substance,the content of which was determined by the traditional external standard method.Relative correction factors(RCF)between isorhynchophylline and the other three alkaloids were calculated respectively.The results showed that the QAMS method had good robustness under different HPLC instruments.Nineteen batches of U.rhynchophylla were tested.No significant difference was observed between the results by QAMS and EMS(Correlation coefficient>0.99,p>0.05).The QAMS method could be employed as a rapid,effective technique for the quality control of U.rhynchophylla.展开更多
Point cloud compression is critical to deploy 3D representation of the physical world such as 3D immersive telepresence,autonomous driving,and cultural heritage preservation.However,point cloud data are distributed ir...Point cloud compression is critical to deploy 3D representation of the physical world such as 3D immersive telepresence,autonomous driving,and cultural heritage preservation.However,point cloud data are distributed irregularly and discontinuously in spatial and temporal domains,where redundant unoccupied voxels and weak correlations in 3D space make achieving efficient compression a challenging problem.In this paper,we propose a spatio-temporal context-guided algorithm for lossless point cloud geometry compression.The proposed scheme starts with dividing the point cloud into sliced layers of unit thickness along the longest axis.Then,it introduces a prediction method where both intraframe and inter-frame point clouds are available,by determining correspondences between adjacent layers and estimating the shortest path using the travelling salesman algorithm.Finally,the few prediction residual is efficiently compressed with optimal context-guided and adaptive fastmode arithmetic coding techniques.Experiments prove that the proposed method can effectively achieve low bit rate lossless compression of point cloud geometric information,and is suitable for 3D point cloud compression applicable to various types of scenes.展开更多
The ever-growing pursuit of high energy density batteries has triggered extensive efforts toward developing alkali metal(Li,Na,and K)battery(AMB)technologies owing to high theoretical capacities and low redox potentia...The ever-growing pursuit of high energy density batteries has triggered extensive efforts toward developing alkali metal(Li,Na,and K)battery(AMB)technologies owing to high theoretical capacities and low redox potentials of metallic anodes.Typically,for new battery systems,the electrolyte design is critical for realizing the battery electrochemistry of AMBs.Conventional electrolytes in alkali ion batteries are generally unsuitable for sustaining the stability owing to the hyper-reactivity and dendritic growth of alkali metals.In this review,we begin with the fundamentals of AMB electrolytes.Recent advancements in concentrated and fluorinated electrolytes,as well as functional electrolyte additives for boosting the stability of Li metal batteries,are summarized and discussed with a special focus on structure-composition-performance relationships.We then delve into the electrolyte formulations for Na-and K metal batteries,including those in which Na/K do not adhere to the Li-inherited paradigms.Finally,the challenges and the future research needs in advanced electrolytes for AMB are highlighted.This comprehensive review sheds light on the principles for the rational design of promising electrolytes and offers new inspirations for developing stable AMBs with high performance.展开更多
Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities...Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 h.Transwell,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),respectively.In vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH.SK-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail vein.Totally 8 mice were randomly divided into PZH and control groups,4 mice in each group.After 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day 17.Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH.Quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq results.Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH.Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo.Furthermore,PZH played roles in inhibiting the transcriptional activity of YAP.Conclusion:PZH restrained migration,invasion and epithelialmesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.展开更多
Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.M...Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.展开更多
Opening windows in coach buses is a practical approach to improving natural ventilation and mitigating infection risk(IR).Due to human behavior and weather conditions,the intermittent window opening strategy(IWOS)is a...Opening windows in coach buses is a practical approach to improving natural ventilation and mitigating infection risk(IR).Due to human behavior and weather conditions,the intermittent window opening strategy(IWOS)is a more common practice than keeping windows constantly open.Despite its prevalence,there are no studies exploring IWOS specifically in vehicles.We employed indoor-outdoor coupled CFD simulations to assess the effects of various IWOS on pathogen-laden droplet(PLD)dispersion and IR in a coach bus that occurred a COVID-19 outbreak in Hunan,China.Results reveal that after ventilating through two skylights for 600–1800 s,opening front and rear windows(FW+RW)or FW with a wind catcher(FW+WCH)for just 40 s can reduce PLD concentration(Cave)to 5%of its initial level and the intake fraction of the infector’s neighbor(IFn)drops by 95%.Upon closing FW+RW or FW+WCH,Cave and IFn take over 580 s to return to the pre-opening level.Moreover,intermittent FW opening halves Cave and IFn within 7 min,but leads to rapid increases upon window closure.Therefore,opening FW+RW and FW+WCH intermittently have pronounced impacts on indoor PLD concentration and are applicable approaches to control respiratory disease transmission in vehicles.According to the inhaled viral dose,it is recommended to open windows when driving time is over 12 minutes to reduce infection risk.In scenarios like epidemiological surveys and risk assessments,where assessing passenger infection risk is vital,some behaviors of opening windows cannot be overlooked and necessitate extra attention.展开更多
Background: The dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symm...Background: The dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities. Methods: Three patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity. Results: Family pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on AD,4RI (c. 1325C〉G) and one recurrent mutation in ABCB6 (c. 1270T〉C), which successfully distinguished two diseases with the similar phenotype. Conclusion: Targeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.展开更多
White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”f...White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.展开更多
Model tests and numerical calculations were adopted based on the New Yuanliangshan tunnel project to investigate the water pressure resistance of lining construction joints in high-pressure and water-rich karst tunnel...Model tests and numerical calculations were adopted based on the New Yuanliangshan tunnel project to investigate the water pressure resistance of lining construction joints in high-pressure and water-rich karst tunnels.A large-scale model test was designed and conducted,innovatively transforming the external water pressure of the lining construction joint into internal water pressure.The effects of the embedded position and waterstop type on the water pressure resistance of the construction joint were analyzed,and the reliability of the model test was verified via numerical calculations.The results show that using waterstops can significantly improve the water pressure resistance of lining construction joints.The water pressure resistance of the lining construction joint is positively correlated with the lining thickness and embedded depth of the waterstop.In addition,the type of waterstop significantly influences the water pressure resistance of lining construction joints.The test results show that the water pressure resistance of the embedded transverse reinforced waterstop is similar to that of the steel plate waterstop,and both have more advantages than the rubber waterstop.The water pressure resistance of the construction joint determined via numerical calculations is similar to the model test results,indicating that the model test results have high accuracy and reliability.This study provides a reference for similar projects and has wide applications.展开更多
The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated ...The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated the effects of La and Ce on the martensitic phase transformation of Fe in terms of the driving force and minimum energy path(MEP)using the first-principles calculations.The calculations of formation energy show that the RE substitution increases the stabilization of fcc-Fe and decreases that of bcc-Fe,thus decreasing the driving force of phase transformation.Meanwhile,the analysis based on the generalized solid-state nudged elastic band(G-SSNEB)method indicates that in the RE-containing systems,an additional energy barrier appears when the phase transformation proceeds along the Bain transition path to c/a ratio of 1.14 in the FM state,which is associated with a sudden decrease in magnetization due to the hybridization between the orbits of the RE atoms and those of the nearest neighbor Fe atoms.The results of potential-energy surfaces(PES)confirm that magnetic ordering and lattice volume change simultaneously with the Bain transition,and in comparison to pure Fe,the variation between the onset and the end structural volumes of the phase transformation is slight for the REcontaining Fe systems.展开更多
SARS-CoV-2 infection is a serious threat to human life and health all over the world,and COVID-19 is a global epidemic caused by SARS-CoV-2 infection.SARS-CoV-2 is highly infectious,strange and variable.Therefore,the ...SARS-CoV-2 infection is a serious threat to human life and health all over the world,and COVID-19 is a global epidemic caused by SARS-CoV-2 infection.SARS-CoV-2 is highly infectious,strange and variable.Therefore,the treatment of COVID-19 must be urgent and targeted.However,vaccines and currently used drugs generally do not have the above-mentioned characteristics.Although convalescent plasma of COVID-19 has shown a clinical application value in the emergency treatment of critical patients,it shows great limitations.All human recombinant multivalent neutralizing nano-antibodies may meet the deficiency of COVID-19 therapy.Gene engineering technologies have been used to develop specific neutralizing antibody(nAB)drugs for the treatment of COVID-19 worldwide.Some of the candidate nAB drugs have been entered the clinical trials and can be used for the therapy of COVID-19 shortly.In the present review,we studied and analyzed n ABs for the treatment of COVID-19 and the progress and prospect from the following five aspects:1)The biological and clinical characteristics of SARS-CoV-2 infection;2)The feasibility of plasma therapy for convalescents with COVID-19;3)The technical routes of developing n Ab drugs;4)The current status of developing global COVID-19 antibodies;5)The difficulties and clinical use.展开更多
To improve the efficiency of the steelmaking process,a system of self-rotating lance was designed,and corresponding cold simulation mechanism was developed.The influence of the self-rotating lance on the mass transfer...To improve the efficiency of the steelmaking process,a system of self-rotating lance was designed,and corresponding cold simulation mechanism was developed.The influence of the self-rotating lance on the mass transfer rate between slag and molten steel was investigated by comparing this novel system with the traditional oxygen lance.The results show that the self-rotating lance can stably rotate with a gas jet as the power source.The mass transfer rate increases with an increase in the top and bottom blow flow rates and with a decline in the lance position.Approximately 13.7% of the top blow flow rate is converted to stirring energy,which is approximately twice that of the traditional oxygen lance,and the mass transfer rate can increase by over 30%.Furthermore,the impact energy can be concentrated at different depths of the molten bath by adjusting the rotational speed.With the same energy density,the mass transfer rate produced by the self-rotating lance is higher;however,the influence of the energy density on the mass transfer rate is low when the rotational speed is 30-50 r/min.展开更多
Oxaliplatin is the common chemotherapy drug for the treatment of colorectal cancer(CRC),however,the harmful Fusobacterium nucleatum(Fn)that existed in the CRC tumor tissues leads to extreme drug resistance to oxalipla...Oxaliplatin is the common chemotherapy drug for the treatment of colorectal cancer(CRC),however,the harmful Fusobacterium nucleatum(Fn)that existed in the CRC tumor tissues leads to extreme drug resistance to oxaliplatin,which reduces the anticancer efficiency.Here we fabricated a new dendrimer-based nanocomplex with anti-tumor and antibacterial dual-functions through conjugating Pt(Ⅳ)-complex and lauric acid(LA)to the dendritic carrier PAMAM(G=3).The synthesized PAMAM-Pt-LA nanoparticle was further coated with hyaluronic acid(HA)on its surface through electrostatically interaction in order to enhance biocompatibility and tumor targeting.The biocompatibility,anti-tumor activity and antibacterial activity of PAMAM-Pt-LA@HA nanocomplex were evaluated in vitro.The results showed that the PAMAM-Pt-LA@HA nanocomplex ehxibited a good biocompatibility,high anti-colorectal cancer activity and high anti-Fn activity.This dual-functional nanocomplex provides a new method to develop anticancer nanomedicines that will be more therapeutically efficacious and less toxic than oxaliplatin for the treatment of CRC.展开更多
基金The financial supports of the National Natural Science Foundation of China(Grant No.42177148)the opening fund of State Key Laboratory of Geohazard Prevention and Geo-environment Protection(Grant No.SKLGP 2023K011)Postdoctoral Research Project of Guangzhou(Grant No.20220402)are gratefully thanked.
文摘The micaceous weathered granitic soil(WGS)is frequently encountered in civil engineering worldwide,unfortunately little information is available regarding how mica affects the physico-mechanical behaviors of WGS.This study prepares reconstituted WGS with different mica contents by removing natural mica in theWGS,and then mixes it with commercial mica powders.The geotechnical behavior as well as the microstructures of the mixtures are characterized.The addition of mica enables the physical indices of WGS to be specific combinations of coarser gradation and high permeability but high Atterberg limits.However,high mica content in WGS was found to be associated with undesirable mechanical properties,including increased compressibility,disintegration,and swelling potential,as well as poor compactability and low effective frictional angle.Microstructural analysis indicates that the influence of mica on the responses of mixtures originates from the intrinsic nature of mica as well as the particle packing being formed withinWGS.Mica exists in the mixture as stacks of plates that form a spongy structure with high compressibility and swelling potential.Pores among the plates give the soil high water retention and high Atterberg limits.Large pores are also generated by soil particles with bridging packing,which enhances the permeability and water-soil interactions upon immersion.This study provides a microlevel understanding of how mica dominates the behavior of WGS and provides new insights into the effective stabilization and improvement of micaceous soils.
基金supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(Grant Nos.:437b8f31,d6092dae,YHT-19064 to Chundong Yu)the National Natural Science Foundation of China(Grant Nos.:81970485,82173086 to Chundong Yu)the Natural Science Foundation of Fujian Province(Grant No.:2023J01249 to Shicong Wang).
文摘Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
文摘The inter-city linkage heat data provided by Baidu Migration is employed as a characterization of inter-city linkages in order to facilitate the study of the network linkage characteristics and hierarchical structure of urban agglomeration in the Greater Bay Area through the use of social network analysis method.This is the inaugural application of big data based on location services in the study of urban agglomeration network structure,which represents a novel research perspective on this topic.The study reveals that the density of network linkages in the Greater Bay Area urban agglomeration has reached 100%,indicating a mature network-like spatial structure.This structure has given rise to three distinct communities:Shenzhen-Dongguan-Huizhou,Guangzhou-Foshan-Zhaoqing,and Zhuhai-Zhongshan-Jiangmen.Additionally,cities within the Greater Bay Area urban agglomeration play different roles,suggesting that varying development strategies may be necessary to achieve staggered development.The study demonstrates that large datasets represented by LBS can offer novel insights and methodologies for the examination of urban agglomeration network structures,contingent on the appropriate mining and processing of the data.
基金Under the auspices of National Natural Science Foundation of China (No.42171414,41771429)the Open Fund of Guangdong Enterprise Key Laboratory for Urban SensingMonitoring and Early Warning (No.2020B121202019)。
文摘Carbon storage of terrestrial ecosystems plays a vital role in advancing carbon neutrality. Better understanding of how land use changes affect carbon storage in urban agglomeration will provide valuable guidance for policymakers in developing effective regional conservation policies. Taking the Pearl River Delta Urban Agglomeration(PRDUA) in China as an example, we examined the heterogeneous response of carbon storage to land use changes in 1990–2018 from a combined view of administrative units and physical entities. The results indicate that the primary change in land use was due to the expansion of construction land(5897.16 km2). The carbon storage in PRDUA decreased from 767.34 Tg C in 1990 to 725.42 Tg C in 2018 with a spatial pattern of high wings and the low middle. The carbon storage loss was largely attributed to construction land expansion(55.74%), followed by forest degradation(54.81%). Changes in carbon storage showed significant divergences in different sized cities and hierarchical boundaries. The coefficients of geographically weighted regression(GWR) reveal that the alteration in carbon storage in Guangzhou City was more responsive to changes in construction land(-0.11) compared to other cities, while that in Shenzhen was mainly affected by the dynamics of forest land(8.32). The change in carbon storage was primarily influenced by the conversion of farmland within urban extent(5.05) and the degradation of forest land in rural areas(5.82). Carbon storage changes were less sensitive to the expansion of construction land in the urban center, urban built-up area, and ex-urban built-up area, with the corresponding GWR coefficients of 0.19, 0.04, and 0.02. This study necessitates the differentiated protection strategies of carbon storage in urban agglomerations.
基金supported by the National Natural Science Foundation of China(Nos.81672744,81472252)Science and Technology Project of Guangdong Province(No.2016A020217007)Guangdong Esophageal Cancer Institute(No.M201606)
文摘Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells,using a synthetic lethal short hairpin RNA(shRNA) screening approach.Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183(RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF 183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA(siRNA) was used to knock down RNF183 transiently.Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay(ELISA) were used to evaluate the protein abundance. MTT assay,colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation.Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8(IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo.Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.
基金supported by the National Natural Science Foundation of China (No. 81472256, 81272638)the Guangdong Provincial Science and Technology Project (No. 2016A020215081, 2016A020217007)the National High Technology Research and Development Program of China (863 Program, No. 2012AA02A204)
文摘Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.
文摘As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination of the major alkaloids in U.rhynchophylla.In this research,a rapid quantitative analysis involving multi-components analysis by a single marker strategy coupled with core-shell column HPLC was adopted to analyse four alkaloids(corynoxeine,isocorynoxeine,isorhynchophylline,rhynchophylline)in U.rhynchophylla.Isorhynchophylline was selected as the internal reference substance,the content of which was determined by the traditional external standard method.Relative correction factors(RCF)between isorhynchophylline and the other three alkaloids were calculated respectively.The results showed that the QAMS method had good robustness under different HPLC instruments.Nineteen batches of U.rhynchophylla were tested.No significant difference was observed between the results by QAMS and EMS(Correlation coefficient>0.99,p>0.05).The QAMS method could be employed as a rapid,effective technique for the quality control of U.rhynchophylla.
文摘Point cloud compression is critical to deploy 3D representation of the physical world such as 3D immersive telepresence,autonomous driving,and cultural heritage preservation.However,point cloud data are distributed irregularly and discontinuously in spatial and temporal domains,where redundant unoccupied voxels and weak correlations in 3D space make achieving efficient compression a challenging problem.In this paper,we propose a spatio-temporal context-guided algorithm for lossless point cloud geometry compression.The proposed scheme starts with dividing the point cloud into sliced layers of unit thickness along the longest axis.Then,it introduces a prediction method where both intraframe and inter-frame point clouds are available,by determining correspondences between adjacent layers and estimating the shortest path using the travelling salesman algorithm.Finally,the few prediction residual is efficiently compressed with optimal context-guided and adaptive fastmode arithmetic coding techniques.Experiments prove that the proposed method can effectively achieve low bit rate lossless compression of point cloud geometric information,and is suitable for 3D point cloud compression applicable to various types of scenes.
基金financial support from Natural Science Foundation of Inner Mongolia(No.2019MS05068)Inner Mongolia scientific and technological achievements transformation project(CGZH2018132)+3 种基金Inner Mongolia major science and technology project(2020ZD0024)the research project of Inner Mongolia Electric Power(Group)Co.,Ltd for post-doctoral studies,the Hong Kong Polytechnic University start-up funding,National Nature Science Foundation of China(No.51872157)Shenzhen Key Laboratory on Power Battery Safety Research(No.ZDSYS201707271615073)financial support from the Australian Research Council(DE190100445).
文摘The ever-growing pursuit of high energy density batteries has triggered extensive efforts toward developing alkali metal(Li,Na,and K)battery(AMB)technologies owing to high theoretical capacities and low redox potentials of metallic anodes.Typically,for new battery systems,the electrolyte design is critical for realizing the battery electrochemistry of AMBs.Conventional electrolytes in alkali ion batteries are generally unsuitable for sustaining the stability owing to the hyper-reactivity and dendritic growth of alkali metals.In this review,we begin with the fundamentals of AMB electrolytes.Recent advancements in concentrated and fluorinated electrolytes,as well as functional electrolyte additives for boosting the stability of Li metal batteries,are summarized and discussed with a special focus on structure-composition-performance relationships.We then delve into the electrolyte formulations for Na-and K metal batteries,including those in which Na/K do not adhere to the Li-inherited paradigms.Finally,the challenges and the future research needs in advanced electrolytes for AMB are highlighted.This comprehensive review sheds light on the principles for the rational design of promising electrolytes and offers new inspirations for developing stable AMBs with high performance.
基金Supported by Joint Funds for Innovation of Science and Technology,Fujian Province(No.2019Y9047)Joint Funds for Innovation of Science and Technology of Fujian Province(No.2017Y9117)+3 种基金Young and Middle-Aged Talent Training Project of Fujian Provincial Health and Family Planning Commission(No.2020GGA072)Natural Science Foundation of Fujian Province(No.2020J011164,2020J011170)Startup Fund for Scientific Research,Fujian Medical University(No.2019QH1298)Science and Technology Plan Project of Fuzhou(No.2019-S-87)。
文摘Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 h.Transwell,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),respectively.In vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH.SK-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail vein.Totally 8 mice were randomly divided into PZH and control groups,4 mice in each group.After 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day 17.Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH.Quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq results.Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH.Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo.Furthermore,PZH played roles in inhibiting the transcriptional activity of YAP.Conclusion:PZH restrained migration,invasion and epithelialmesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.
文摘Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.
基金supported by the National Natural Science Foundation of China(No.42175095,No.42005069,and No.42175180)support from Guangdong Major Project of Basic and Applied Basic Research(2020B0301030004,2021B0301030007)the UK GCRF Rapid Response Grant on“Transmission of SARS-CoV-2 virus in crowded indoor environment”,and the Innovation Group Project of the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(No.311020001)are also gratefully acknowledged.
文摘Opening windows in coach buses is a practical approach to improving natural ventilation and mitigating infection risk(IR).Due to human behavior and weather conditions,the intermittent window opening strategy(IWOS)is a more common practice than keeping windows constantly open.Despite its prevalence,there are no studies exploring IWOS specifically in vehicles.We employed indoor-outdoor coupled CFD simulations to assess the effects of various IWOS on pathogen-laden droplet(PLD)dispersion and IR in a coach bus that occurred a COVID-19 outbreak in Hunan,China.Results reveal that after ventilating through two skylights for 600–1800 s,opening front and rear windows(FW+RW)or FW with a wind catcher(FW+WCH)for just 40 s can reduce PLD concentration(Cave)to 5%of its initial level and the intake fraction of the infector’s neighbor(IFn)drops by 95%.Upon closing FW+RW or FW+WCH,Cave and IFn take over 580 s to return to the pre-opening level.Moreover,intermittent FW opening halves Cave and IFn within 7 min,but leads to rapid increases upon window closure.Therefore,opening FW+RW and FW+WCH intermittently have pronounced impacts on indoor PLD concentration and are applicable approaches to control respiratory disease transmission in vehicles.According to the inhaled viral dose,it is recommended to open windows when driving time is over 12 minutes to reduce infection risk.In scenarios like epidemiological surveys and risk assessments,where assessing passenger infection risk is vital,some behaviors of opening windows cannot be overlooked and necessitate extra attention.
基金supported by the Key Area Research and Development Program of Guangdong Province in China(2020B0202010005)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA28030202)+2 种基金the Priority Research Program of Chinese Academy of Science(XDA24020104)the Key Technologies R&D Program of Inner MongoliaChina(2021GG0300)。
基金This study was supported by grants from the National Natural Science Foundation of China,Beijing Natural Science Foundation
文摘Background: The dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities. Methods: Three patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity. Results: Family pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on AD,4RI (c. 1325C〉G) and one recurrent mutation in ABCB6 (c. 1270T〉C), which successfully distinguished two diseases with the similar phenotype. Conclusion: Targeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.
基金The authors are very grateful for the financial support by National Natural Science Foundation of China(Grant No.31900957)Shandong Provincial Natural Science Foundation(Grant No.ZR2019QC007)+4 种基金Innovation and technology program for the excellent youth scholars of higher education of Shandong province(Grant No.2019KJE015)Traditional Chinese Medicine Science and Technology Project of Shandong province(Grant No.2021Q069)Open Fund of Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid(Grant No.KTRDHA-Y201902)National College Students Innovation and Entrepreneurship Training Program of China(Grant No.S202011065041,202211065038)Zhejiang Engineering Research Center for Tissue Repair Materials(Grant No:WIUCASZZXF21004).
文摘White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.
基金the General Program of the National Natural Science Foundation of China(Grant No.51878037).
文摘Model tests and numerical calculations were adopted based on the New Yuanliangshan tunnel project to investigate the water pressure resistance of lining construction joints in high-pressure and water-rich karst tunnels.A large-scale model test was designed and conducted,innovatively transforming the external water pressure of the lining construction joint into internal water pressure.The effects of the embedded position and waterstop type on the water pressure resistance of the construction joint were analyzed,and the reliability of the model test was verified via numerical calculations.The results show that using waterstops can significantly improve the water pressure resistance of lining construction joints.The water pressure resistance of the lining construction joint is positively correlated with the lining thickness and embedded depth of the waterstop.In addition,the type of waterstop significantly influences the water pressure resistance of lining construction joints.The test results show that the water pressure resistance of the embedded transverse reinforced waterstop is similar to that of the steel plate waterstop,and both have more advantages than the rubber waterstop.The water pressure resistance of the construction joint determined via numerical calculations is similar to the model test results,indicating that the model test results have high accuracy and reliability.This study provides a reference for similar projects and has wide applications.
基金Project supported by the National Natural Science Foundation of China(5196103052161008)+3 种基金the Natural Science Foundation of Inner Mongolia(2019MS05013)Youth Innovation Talent Project of Baotouthe Innovation Fund of Inner Mongolia University of Science and Technology(2019QDL-B15)the Central Government Guides Local Science and Technology Development Fund Projects of China。
文摘The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated the effects of La and Ce on the martensitic phase transformation of Fe in terms of the driving force and minimum energy path(MEP)using the first-principles calculations.The calculations of formation energy show that the RE substitution increases the stabilization of fcc-Fe and decreases that of bcc-Fe,thus decreasing the driving force of phase transformation.Meanwhile,the analysis based on the generalized solid-state nudged elastic band(G-SSNEB)method indicates that in the RE-containing systems,an additional energy barrier appears when the phase transformation proceeds along the Bain transition path to c/a ratio of 1.14 in the FM state,which is associated with a sudden decrease in magnetization due to the hybridization between the orbits of the RE atoms and those of the nearest neighbor Fe atoms.The results of potential-energy surfaces(PES)confirm that magnetic ordering and lattice volume change simultaneously with the Bain transition,and in comparison to pure Fe,the variation between the onset and the end structural volumes of the phase transformation is slight for the REcontaining Fe systems.
基金China Postdoctoral Science Foundation(Grant No.2020T1300011ZX)National Science and Technology Major Project(Grant No.2018ZX10712001)Key Research and Development Projects of Tianjin Science and Technology Committee(Grant No.17YFZCSY00660)。
文摘SARS-CoV-2 infection is a serious threat to human life and health all over the world,and COVID-19 is a global epidemic caused by SARS-CoV-2 infection.SARS-CoV-2 is highly infectious,strange and variable.Therefore,the treatment of COVID-19 must be urgent and targeted.However,vaccines and currently used drugs generally do not have the above-mentioned characteristics.Although convalescent plasma of COVID-19 has shown a clinical application value in the emergency treatment of critical patients,it shows great limitations.All human recombinant multivalent neutralizing nano-antibodies may meet the deficiency of COVID-19 therapy.Gene engineering technologies have been used to develop specific neutralizing antibody(nAB)drugs for the treatment of COVID-19 worldwide.Some of the candidate nAB drugs have been entered the clinical trials and can be used for the therapy of COVID-19 shortly.In the present review,we studied and analyzed n ABs for the treatment of COVID-19 and the progress and prospect from the following five aspects:1)The biological and clinical characteristics of SARS-CoV-2 infection;2)The feasibility of plasma therapy for convalescents with COVID-19;3)The technical routes of developing n Ab drugs;4)The current status of developing global COVID-19 antibodies;5)The difficulties and clinical use.
基金the National Key Research and Development Program with Project Number 2017YFB0304000the Beijing Natural Science Foundation with Project Number 2172057 in China.
文摘To improve the efficiency of the steelmaking process,a system of self-rotating lance was designed,and corresponding cold simulation mechanism was developed.The influence of the self-rotating lance on the mass transfer rate between slag and molten steel was investigated by comparing this novel system with the traditional oxygen lance.The results show that the self-rotating lance can stably rotate with a gas jet as the power source.The mass transfer rate increases with an increase in the top and bottom blow flow rates and with a decline in the lance position.Approximately 13.7% of the top blow flow rate is converted to stirring energy,which is approximately twice that of the traditional oxygen lance,and the mass transfer rate can increase by over 30%.Furthermore,the impact energy can be concentrated at different depths of the molten bath by adjusting the rotational speed.With the same energy density,the mass transfer rate produced by the self-rotating lance is higher;however,the influence of the energy density on the mass transfer rate is low when the rotational speed is 30-50 r/min.
基金financially supported by the National Natural Science Foundation of China(Nos.22075209,U20A20260 and 52103180)a distinguished professor of Tianjin,the Leading Talents Program of the Tianjin Educational Committee+2 种基金the Key program of Tianjin Municipal Natural Science Foundation(Nos.18JCZDJC37700 and 18JCQNJC72300)the Training Project of Innovation Team of Colleges and Universities in Tianjin(No.TD13-5020)the Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid(No.KTRDHA-Z201901)for the financial support。
文摘Oxaliplatin is the common chemotherapy drug for the treatment of colorectal cancer(CRC),however,the harmful Fusobacterium nucleatum(Fn)that existed in the CRC tumor tissues leads to extreme drug resistance to oxaliplatin,which reduces the anticancer efficiency.Here we fabricated a new dendrimer-based nanocomplex with anti-tumor and antibacterial dual-functions through conjugating Pt(Ⅳ)-complex and lauric acid(LA)to the dendritic carrier PAMAM(G=3).The synthesized PAMAM-Pt-LA nanoparticle was further coated with hyaluronic acid(HA)on its surface through electrostatically interaction in order to enhance biocompatibility and tumor targeting.The biocompatibility,anti-tumor activity and antibacterial activity of PAMAM-Pt-LA@HA nanocomplex were evaluated in vitro.The results showed that the PAMAM-Pt-LA@HA nanocomplex ehxibited a good biocompatibility,high anti-colorectal cancer activity and high anti-Fn activity.This dual-functional nanocomplex provides a new method to develop anticancer nanomedicines that will be more therapeutically efficacious and less toxic than oxaliplatin for the treatment of CRC.