In cold regions,understanding the freezing strength of the interface between soil and structure is crucial for designing frost-resistant foundations.To investigate how the content of cement powder in aeolian sand affe...In cold regions,understanding the freezing strength of the interface between soil and structure is crucial for designing frost-resistant foundations.To investigate how the content of cement powder in aeolian sand affects this strength,we conducted direct shear tests under various conditions such as different fine-grained soil content,normal stress,and initial moisture content of the soil.By analyzing parameters like soil properties,and volume of ice content,and using the Mohr-Coulomb strength theory to define interface strength,we aimed to indirectly measure the cementation strength of the interface.Our findings revealed that as the particle content increased,the interface stress-strain curves became noticeably stiffer.We also observed a positive linear relationship between freezing strength and silt content,while the initial moisture content of the soil did not significantly impact the strengthening effect of fine-grained soil on freezing strength.Moreover,we discovered that as the powder content increased,the force binding the ice to the interface decreased,while the friction angle at the interface increased.However,the cohesion force at the interface remained relatively unchanged.Overall,our analysis suggests that the increase in freezing strength due to fine-grained soil content is primarily due to the heightened friction between aeolian sand and the interface.展开更多
The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmac...The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ·mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.展开更多
Reconstruction during the catalytic process has been considered to play a key role for the performance.Here we report a RuNiPO based catalyst for efficient alkaline hydrogen evolution reaction(HER),which can benefit f...Reconstruction during the catalytic process has been considered to play a key role for the performance.Here we report a RuNiPO based catalyst for efficient alkaline hydrogen evolution reaction(HER),which can benefit from a long-term reconstruction during HER for 10 h to continuously increase the performance.The final catalyst(e-RuNiPO)shows a huge morphology change from bulk sphere to highly exposed layered structure in the electrocatalysis process,and exhibits an interesting electronic structure modification with the electron transfer from Ru to Ni for better interfacial interaction and quick charge transfer.Due to the favorable morphology with more exposed active sites and the optimized electronic structure,the final catalyst can achieve an outstanding performance with only an overpotential of 15 mV at 10 mA cm^(-2)(with a good stability more than 100 h),even outperforming the performance of benchmark 20 wt%Pt/C catalyst(18 mV at 10 mA cm^(-2))by using a much lower Ru content.展开更多
Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fev...Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fever may be the only sign of infection. If appropriate antimicrobial treatment is not given in time, infection-related mortality is high. In our study, we aimed to optimize the dosage regimen of Micafungin in children with febrile neutropenic against Candida spp. by Mote Carlo Simulation (MCS). Pharmacokinetic parameters and microbiological data of Micafungin were collected. Then we used MCS to calculate Probability of Target Attainment (PTA) and Cumulative Fraction of Response (CFR). With dosages of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, and 4 mg/kg in oral group and dosages of 100 mg, and 200 mg in intravenous administration, all have different degree of antifungal effect. But when the dosage regimen was 50 mg IV, the therapeutic effect of Micafungin against Candida spp. was not good.展开更多
Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. ...Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive candidiasis. It was recommended as first-line drugs for the treatment and prevention of mycoses. In our study, we aimed to optimise the dosage of fluconazole with gender against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of fluconazole and the MIC distribution of Candida spp. on fluconazole. We decided to evaluate the gender between males and females with the pharmacokinetics of fluconazole. Using probability of target attainment (PTA) and cumulative fraction of response (CFR) as indexes, crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae, when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%. For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml. PTA was higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64 g/ml, respectively. For the different dosage regimens 100 mg IV and 200 mg IV of fluconazole for Candida spp., it is desirable that fluconazole dosage regimens take into account both the gender of the patient.展开更多
Invasive fungal infections (IFI) have recently become increasingly more prevalent, resulting in an increased risk of morbidity and mortality. Both Candida spp. and Aspergillus spp. are major causes of IFI. In this stu...Invasive fungal infections (IFI) have recently become increasingly more prevalent, resulting in an increased risk of morbidity and mortality. Both Candida spp. and Aspergillus spp. are major causes of IFI. In this study, we aimed to evaluate the cumulative fraction of response of various dosage regimens of posaconazole against nine Candida spp. and six Aspergillus spp. in both children and adults. Monte Carlo simulation (MCS) was performed to optimize selection of posaconazole dosage regimens. For children, a dosage regimen of 120 mg/m2 posaconazole tid was sufficient to treat fungal infections caused by all six Aspergillus spp. and six of the nine Candida spp. (but was not effective against C. glabrata, C. guilliermondii and C. krusei). In contrast, a 400 mg dosage regimen of posaconazole bid achieved the target pharmacokinetic/pharmacodynamics (PK/PD) parameters against all six Aspergillus spp. and eight of the nine Candida spp. (but was not effective against C. glabrata) in the adults. Dosage regimens of 50 mg bid, 100 mg bid, or 200 mg bid were not effective. Posaconazole dosage regimens are likely to achieve their desired PK/PD targets against Candida spp. and Aspergillus spp. in both children and adults.展开更多
Objective: The target prediction and molecular mechanism of compound Honggencao in the treatment of upper respiratory tract infection were investigated based on network pharmacology. Methods: In the database of Tradit...Objective: The target prediction and molecular mechanism of compound Honggencao in the treatment of upper respiratory tract infection were investigated based on network pharmacology. Methods: In the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, chemical composition and potential targets of compound Honggencao were mined, and the target gene of upper respiratory tract infection of compound Honggencao was extracted from GeneCards databases. The protein-protein interaction of target genes was constructed. Then, the essential genes of enrichment of KEGG pathway analysis and functional analysis were analysed. Results: Compound Honggencao had 69 kinds of active ingredients. The upper respiratory tract infection of the target gene was 186 that built compound Honggencao on the relationship between upper respiratory tract infections of protein interaction networks, which had a total of 186 nodes, 3515 sides. Fifty-six essential genes were including IL-17, EGFR and CDND1, and so on. Gene ontology analysis had 2567 items, and pathway analysis was 166 items. The main signaling pathways involved with IL-17 signaling pathways, tumour necrosis factor signal pathway and human cytomegalovirus infection, and so on. Conclusion: The pharmacological action of compound Honggencao on upper respiratory tract infection was characterized by the synergistic effect of multiple components and multiple targets, which provided an absolute theoretical basis for the research on the pharmacological direction of molecular signaling pathway and a specific theoretical basis for clinical use.展开更多
Objective: To investigate the possible mechanism of Yiqing Capsules in the treatment of upper respiratory tract infection based on network pharmacology. Methods: The main active components of Yiqing Capsules were sele...Objective: To investigate the possible mechanism of Yiqing Capsules in the treatment of upper respiratory tract infection based on network pharmacology. Methods: The main active components of Yiqing Capsules were selected on TCMSP database;the targets of upper respiratory tract infection were selected on GeneCards database. The drug-compound-target network and PPi network were constructed through STRING database and soft Cytoscape 3.7.2. Soft R was used to perform GO enrichment analysis and KEGG pathway enrichment analysis of main targets. Results: According to the screening conditions, 48 active compounds and 171 related targets were obtained. GO enrichment analysis obtained 2333 items, KEGG pathway enrichment analysis obtained 2248 items, including Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Epstein-Barr virus infection, PI3K-Akt signaling pathway, etc. Conclusion: Yiqing capsules play a therapeutic role in upper respiratory tract infection through multi-target and multi-pathway.展开更多
The importance to industry of non-contact bearings is growing rapidly as the demand for highspeed and high-precision manufacturing equipment increases.As a recently developed non-contact technology,near-field acoustic...The importance to industry of non-contact bearings is growing rapidly as the demand for highspeed and high-precision manufacturing equipment increases.As a recently developed non-contact technology,near-field acoustic levitation(NFAL)has drawn much attention for the advantages it offers,including no requirement for an external pressurized air supply,its compact structure,and its ability to adapt to its environment.In this paper,the working mechanism of NFAL is introduced in detail and compared to all existing non-contact technologies to demonstrate its versatility and potential for practical applications in industry.The fundamental theory of NFAL,including gas film lubrication theory and acoustic radiation pressure theory is presented.Then,the current stateof-the-art of the design and development of squeeze film air bearings based on NFAL is reviewed.Finally,future trends and obstacles to more widespread use are discussed.展开更多
Nano manipulation technology has great potential applications in the assembly,measurement and fabrication of nano materials,actuating and high-sensitivity sensing of biological samples,manufacture of nano sensors,deco...Nano manipulation technology has great potential applications in the assembly,measurement and fabrication of nano materials,actuating and high-sensitivity sensing of biological samples,manufacture of nano sensors,decontamination of air and water,etc. As an actuating technology which is far from being mature,the nano manipulation still faces lots of challenges in the device principles,design,scaling up,sample safety,etc.The ultrasonic nano manipulation, in which nanoscale objects are handled and actuated by controlled ultrasound,is an emerging technology to meet some of challenges in nano manipulations. The author's research team and other groups have proposed and realized a series of nano manipulation functions such as trapping,transfer, rotation and concentration since 2012, by controlled ultrasound. Compared with other nano manipulating techniques,the ultrasonic method has the merits such as very low temperature rise at the manipulation area,little selectivity to the material properties of manipulated samples,capability of being implemented on the substrates without MENS or NEMS structure,etc. This paper reviews the progresses in principles,functions,structures and characteristics of the ultrasonic devices for nano manipulations.展开更多
Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinet...Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinetic parameters and microbiological data were collected about dalbavancin. 10,000 patients with renal or hepatic impairment analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more than 90% for dalbavancin in patients with hepatic or renal impairment, except for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in patients with hepatic or renal impairment.展开更多
The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmac...The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.展开更多
Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line...Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line drugs for the treatment and prevention of invasive candidiasis. In our study, we aimed to optimize the dosage of Rezafungin against <i><i><span style="font-family:Verdana;">Candida</span></i><span> <i><span style="font-family:Verdana;">spp.</span></i><span style="font-family:Verdana;"> </span></span></i><span style="font-family:Verdana;"> based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of rezafungin and the MIC distribution of <i></i></span><i><i><span style="font-family:Verdana;">Candida</span></i><span style="font-family:Verdana;"> <i>spp</i></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">.</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> </span></span></span></i> on <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">rezafungin</span><i><span style="font-family:Verdana;">.</span></i><span style="font-family:Verdana;"> Monte Carlo simulation was used to calculate probability of target attainment and a cumulative fraction of response to assess the best dosing regimen. The optimal dosage regimen for <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span style="font-family:Verdana;"> <i>albicans</i></span> <span style="font-family:Verdana;"></span></i></span><span style="font-family:Verdana;">and <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">glabrata </span></i><span style="font-family:Verdana;"></span></span></i></span></span><span style="font-family:Verdana;">was 50 mg IV, and the optimal dosage regimen for <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">parapsilosis</span></i><span style="font-family:Verdana;"></span></span></i><span style="font-family:Verdana;"> was 100 mg IV. Lastly, rezafungin has an excellent antifungal effect on <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">albicans</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">C.</span></i> <i><span style="font-family:Verdana;">glabrata</span></i><span style="font-family:Verdana;"></span></span></i> <span style="font-family:Verdana;">and <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span style="font-family:Verdana;"> <i>parapsilosis.</i></span></i>展开更多
<b><span style="font-family:Verdana;">Objective: </span></b><span style="font-family:""><span style="font-family:Verdana;">To select the ingredien...<b><span style="font-family:Verdana;">Objective: </span></b><span style="font-family:""><span style="font-family:Verdana;">To select the ingredients and targets of Yiqing capsule in treating COVID-19 based on network pharmacology, then to explore the potential mechanism of Yiqing capsule in treating COVID-19. </span><b><span style="font-family:Verdana;">Methods:</span></b> </span><span style="font-family:Verdana;">We </span><span style="font-family:Verdana;">screened the ingredients and targets of Yiqing capsule on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and target genes for COVID-19 in GeneCards database</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> constructed drug-ingredient-target</span><span style="font-family:Verdana;"> network through software Cytoscape 3.7.2</span><span style="font-family:Verdana;">,</span><span style="font-family:""> </span><span style="font-family:Verdana;">and </span><span style="font-family:Verdana;">constructed protein protein interaction network (PPI) network through STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of key gene targets of Yiqing capsule </span><span style="font-family:Verdana;">are used to</span><span style="font-family:""><span style="font-family:Verdana;"> treat COVID-19 through software R5.3.2. </span><b><span style="font-family:Verdana;">Results</span></b></span><b><span style="font-family:Verdana;">: </span></b><span style="font-family:""><span style="font-family:Verdana;">We got 42 ingredients, 42 potential therapeutic targets, 1643 GO items and 970 pathways in our study. The main pathway including IL-17 signaling pathway, Chagas disease (American trypanosomiasis), Influenza A, and TNF signaling pathway. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">Yiqing capsule plays a role in treating COVID-19 through multiple ingredients, multiple targets and multiple pathways.展开更多
Visible light communication(VLC)based on laser diodes demonstrates great potential for high data rate maritime,terrestrial,and aerial wireless data links.Here,we design and fabricate high-speed blue laser diodes(LDs)g...Visible light communication(VLC)based on laser diodes demonstrates great potential for high data rate maritime,terrestrial,and aerial wireless data links.Here,we design and fabricate high-speed blue laser diodes(LDs)grown on c-plane gallium nitride(GaN)substrate.This was achieved through active region design and miniaturization toward a narrow ridge waveguide,short cavity length,and single longitudinal mode Fabry–Perot laser diode.The fabricated mini-LD has a low threshold current of 31 mA and slope efficiency of 1.02 W/A.A record modulation bandwidth of 5.9 GHz(−3dB)was measured from the mini-LD.Using the developed mini-LD as a transmitter,the VLC link exhibits a high data transmission rate of 20.06 Gbps adopting the bit and power loading discrete multitone(DMT)modulation technique.The corresponding bit error rate is 0.003,satisfying the forward error correction standard.The demonstrated GaN-based mini-LD has significantly enhanced data transmission rates,paving the path for energy-efficient VLC systems and integrated photonics in the visible regime.展开更多
Adhesive forces commonly exhibit a monotonic increase or a maximum with increasing relative humidity. However, anomalous behavior has been reported. Here, a numerical model of adhesive forces, comprised mainly of capi...Adhesive forces commonly exhibit a monotonic increase or a maximum with increasing relative humidity. However, anomalous behavior has been reported. Here, a numerical model of adhesive forces, comprised mainly of capillary and van der Waals forces, between a tip and a surface is established. It is described by a power law that considers the geometry, the liquid bridge wetting radius, the contact angle, and the separation distance. Capillary forces (sum of surface tension and Laplace pressure) and van der Waals forces are calculated. The latter cannot be neglected in the adhesion even at high humidity. Decrease in adhesion with increasing relative humidity can be attributed to a blunt tip shape, which is validated by experimental data. Specifically, the decrease in adhesion is attributed primarily to a transition from a rounded to a blunt tip shape. Structuring objects at the micro- or nanoscale can either increase or decrease adhesion as a function of relative humidity. This has a wide range of applications in robotic manipulation and can provide a better understanding of adhesion mechanisms in atomic force microscopy in ambient air.展开更多
Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported....Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.展开更多
A high-sensitivity all-fiber temperature sensor based on a Sagnac interferometer is demonstrated by splicing a section of polarization maintaining fiber(PMF)between two sections of standard single mode fibers(SMFs).In...A high-sensitivity all-fiber temperature sensor based on a Sagnac interferometer is demonstrated by splicing a section of polarization maintaining fiber(PMF)between two sections of standard single mode fibers(SMFs).In this sensor,the SMF-PMF-SMF structure in the Sagnac loop is bent into a circle to enhance the sensitivity.The length and curvature of the PMF in the loop are investigated and can be optimized to further increase the temperature sensitivity of the sensor. Results show that the radius of the circle has an important effect upon temperature sensitivity due to the bend-induced birefringence variation of the PMF.The SMF-PMF-SMF structure bent into a circle with a radius of 30mm exhibits a high-sensitivity temperature of 1.73nm/℃.The sensor is provided with the advantages of easy fabrication,low-insertion loss,and high sensitivity,which may find potential applications in the field of high precision temperature measurement.展开更多
We demonstrate that multiple higher-order topological transitions can be triggered via the continuous change of the geometry in kagome photonic crystals composed of three dielectric rods. By tuning a single geometry p...We demonstrate that multiple higher-order topological transitions can be triggered via the continuous change of the geometry in kagome photonic crystals composed of three dielectric rods. By tuning a single geometry parameter, the photonic corner and edge states emerge or disappear with higher-order topological transitions. Two distinct higher-order topological insulator phases and a normal insulator phase are revealed. Their topological indices are obtained from symmetry representations. A photonic analog of the fractional corner charge is introduced to distinguish the two higher-order topological insulator phases. Our predictions can be readily realized and verified in configurable dielectric photonic crystals.展开更多
Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninv...Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated.We conducted this study to access the potential link between junction plakoglobin(JUP)and HIF2αin ccRCC.Methods:Affinity purification and mass spectrometry(AP-MS)screening,glutathione-s-transferase(GST)pull-down and co-immunoprecipitation(Co-IP)assays were performed to detect the interacting proteins of HIF2α.Quantitative PCR(qPCR)and Western blotting were used to detect the expression of JUP in human ccRCC samples.Luciferase reporter assays,chromatin immunoprecipitation(ChIP),cycloheximide chase assays,and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α.Cell Counting Kit-8(CCK-8)assays,colony formation assays,transwell assays,and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.Results:We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau(VHL)and histone deacetylases 1/2(HDAC1/2)to HIF2α to regulate its stability and transactivation.JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo.Importantly,the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.Conclusion:Taken together,these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.展开更多
文摘In cold regions,understanding the freezing strength of the interface between soil and structure is crucial for designing frost-resistant foundations.To investigate how the content of cement powder in aeolian sand affects this strength,we conducted direct shear tests under various conditions such as different fine-grained soil content,normal stress,and initial moisture content of the soil.By analyzing parameters like soil properties,and volume of ice content,and using the Mohr-Coulomb strength theory to define interface strength,we aimed to indirectly measure the cementation strength of the interface.Our findings revealed that as the particle content increased,the interface stress-strain curves became noticeably stiffer.We also observed a positive linear relationship between freezing strength and silt content,while the initial moisture content of the soil did not significantly impact the strengthening effect of fine-grained soil on freezing strength.Moreover,we discovered that as the powder content increased,the force binding the ice to the interface decreased,while the friction angle at the interface increased.However,the cohesion force at the interface remained relatively unchanged.Overall,our analysis suggests that the increase in freezing strength due to fine-grained soil content is primarily due to the heightened friction between aeolian sand and the interface.
文摘The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ·mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.
基金supported by the National Key R&D Program of China(2020YFA0406103)the National Natural Science Foundation of China(U1932211,12205213)+2 种基金the Jiangsu Planned Projects for Postdoctoral Research Funds(7121453621)the Collaborative Innovation Center of Suzhou Nano Science&Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the 111 Project。
文摘Reconstruction during the catalytic process has been considered to play a key role for the performance.Here we report a RuNiPO based catalyst for efficient alkaline hydrogen evolution reaction(HER),which can benefit from a long-term reconstruction during HER for 10 h to continuously increase the performance.The final catalyst(e-RuNiPO)shows a huge morphology change from bulk sphere to highly exposed layered structure in the electrocatalysis process,and exhibits an interesting electronic structure modification with the electron transfer from Ru to Ni for better interfacial interaction and quick charge transfer.Due to the favorable morphology with more exposed active sites and the optimized electronic structure,the final catalyst can achieve an outstanding performance with only an overpotential of 15 mV at 10 mA cm^(-2)(with a good stability more than 100 h),even outperforming the performance of benchmark 20 wt%Pt/C catalyst(18 mV at 10 mA cm^(-2))by using a much lower Ru content.
文摘Neutropenia with fever is a special group of patients. Due to low immune function, inflammation-related clinical symptoms and signs are often not obvious, and pathogenic bacteria and infection focus are not clear. Fever may be the only sign of infection. If appropriate antimicrobial treatment is not given in time, infection-related mortality is high. In our study, we aimed to optimize the dosage regimen of Micafungin in children with febrile neutropenic against Candida spp. by Mote Carlo Simulation (MCS). Pharmacokinetic parameters and microbiological data of Micafungin were collected. Then we used MCS to calculate Probability of Target Attainment (PTA) and Cumulative Fraction of Response (CFR). With dosages of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, and 4 mg/kg in oral group and dosages of 100 mg, and 200 mg in intravenous administration, all have different degree of antifungal effect. But when the dosage regimen was 50 mg IV, the therapeutic effect of Micafungin against Candida spp. was not good.
文摘Candidemia is one of the four most common nosocomial blood infections and is the most common hospital-acquired fungemia in a recent multi-institutional study from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive candidiasis. It was recommended as first-line drugs for the treatment and prevention of mycoses. In our study, we aimed to optimise the dosage of fluconazole with gender against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of fluconazole and the MIC distribution of Candida spp. on fluconazole. We decided to evaluate the gender between males and females with the pharmacokinetics of fluconazole. Using probability of target attainment (PTA) and cumulative fraction of response (CFR) as indexes, crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae, when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%. For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml. PTA was higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64 g/ml, respectively. For the different dosage regimens 100 mg IV and 200 mg IV of fluconazole for Candida spp., it is desirable that fluconazole dosage regimens take into account both the gender of the patient.
文摘Invasive fungal infections (IFI) have recently become increasingly more prevalent, resulting in an increased risk of morbidity and mortality. Both Candida spp. and Aspergillus spp. are major causes of IFI. In this study, we aimed to evaluate the cumulative fraction of response of various dosage regimens of posaconazole against nine Candida spp. and six Aspergillus spp. in both children and adults. Monte Carlo simulation (MCS) was performed to optimize selection of posaconazole dosage regimens. For children, a dosage regimen of 120 mg/m2 posaconazole tid was sufficient to treat fungal infections caused by all six Aspergillus spp. and six of the nine Candida spp. (but was not effective against C. glabrata, C. guilliermondii and C. krusei). In contrast, a 400 mg dosage regimen of posaconazole bid achieved the target pharmacokinetic/pharmacodynamics (PK/PD) parameters against all six Aspergillus spp. and eight of the nine Candida spp. (but was not effective against C. glabrata) in the adults. Dosage regimens of 50 mg bid, 100 mg bid, or 200 mg bid were not effective. Posaconazole dosage regimens are likely to achieve their desired PK/PD targets against Candida spp. and Aspergillus spp. in both children and adults.
文摘Objective: The target prediction and molecular mechanism of compound Honggencao in the treatment of upper respiratory tract infection were investigated based on network pharmacology. Methods: In the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, chemical composition and potential targets of compound Honggencao were mined, and the target gene of upper respiratory tract infection of compound Honggencao was extracted from GeneCards databases. The protein-protein interaction of target genes was constructed. Then, the essential genes of enrichment of KEGG pathway analysis and functional analysis were analysed. Results: Compound Honggencao had 69 kinds of active ingredients. The upper respiratory tract infection of the target gene was 186 that built compound Honggencao on the relationship between upper respiratory tract infections of protein interaction networks, which had a total of 186 nodes, 3515 sides. Fifty-six essential genes were including IL-17, EGFR and CDND1, and so on. Gene ontology analysis had 2567 items, and pathway analysis was 166 items. The main signaling pathways involved with IL-17 signaling pathways, tumour necrosis factor signal pathway and human cytomegalovirus infection, and so on. Conclusion: The pharmacological action of compound Honggencao on upper respiratory tract infection was characterized by the synergistic effect of multiple components and multiple targets, which provided an absolute theoretical basis for the research on the pharmacological direction of molecular signaling pathway and a specific theoretical basis for clinical use.
文摘Objective: To investigate the possible mechanism of Yiqing Capsules in the treatment of upper respiratory tract infection based on network pharmacology. Methods: The main active components of Yiqing Capsules were selected on TCMSP database;the targets of upper respiratory tract infection were selected on GeneCards database. The drug-compound-target network and PPi network were constructed through STRING database and soft Cytoscape 3.7.2. Soft R was used to perform GO enrichment analysis and KEGG pathway enrichment analysis of main targets. Results: According to the screening conditions, 48 active compounds and 171 related targets were obtained. GO enrichment analysis obtained 2333 items, KEGG pathway enrichment analysis obtained 2248 items, including Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Epstein-Barr virus infection, PI3K-Akt signaling pathway, etc. Conclusion: Yiqing capsules play a therapeutic role in upper respiratory tract infection through multi-target and multi-pathway.
基金the financial support from the National Natural Science Foundation of China(Nos.51575170 and 51875185)the National Key R&D Program of China(2018YFB2000100)the Foundation of Hunan Province(2018JJ1006).
文摘The importance to industry of non-contact bearings is growing rapidly as the demand for highspeed and high-precision manufacturing equipment increases.As a recently developed non-contact technology,near-field acoustic levitation(NFAL)has drawn much attention for the advantages it offers,including no requirement for an external pressurized air supply,its compact structure,and its ability to adapt to its environment.In this paper,the working mechanism of NFAL is introduced in detail and compared to all existing non-contact technologies to demonstrate its versatility and potential for practical applications in industry.The fundamental theory of NFAL,including gas film lubrication theory and acoustic radiation pressure theory is presented.Then,the current stateof-the-art of the design and development of squeeze film air bearings based on NFAL is reviewed.Finally,future trends and obstacles to more widespread use are discussed.
基金Sponsored by the State Key Lab of Mechanics and Control of Mechanical Structures(Grant No.MCMS-0314G01)and PAPD
文摘Nano manipulation technology has great potential applications in the assembly,measurement and fabrication of nano materials,actuating and high-sensitivity sensing of biological samples,manufacture of nano sensors,decontamination of air and water,etc. As an actuating technology which is far from being mature,the nano manipulation still faces lots of challenges in the device principles,design,scaling up,sample safety,etc.The ultrasonic nano manipulation, in which nanoscale objects are handled and actuated by controlled ultrasound,is an emerging technology to meet some of challenges in nano manipulations. The author's research team and other groups have proposed and realized a series of nano manipulation functions such as trapping,transfer, rotation and concentration since 2012, by controlled ultrasound. Compared with other nano manipulating techniques,the ultrasonic method has the merits such as very low temperature rise at the manipulation area,little selectivity to the material properties of manipulated samples,capability of being implemented on the substrates without MENS or NEMS structure,etc. This paper reviews the progresses in principles,functions,structures and characteristics of the ultrasonic devices for nano manipulations.
文摘Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinetic parameters and microbiological data were collected about dalbavancin. 10,000 patients with renal or hepatic impairment analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more than 90% for dalbavancin in patients with hepatic or renal impairment, except for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in patients with hepatic or renal impairment.
文摘The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.
文摘Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line drugs for the treatment and prevention of invasive candidiasis. In our study, we aimed to optimize the dosage of Rezafungin against <i><i><span style="font-family:Verdana;">Candida</span></i><span> <i><span style="font-family:Verdana;">spp.</span></i><span style="font-family:Verdana;"> </span></span></i><span style="font-family:Verdana;"> based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of rezafungin and the MIC distribution of <i></i></span><i><i><span style="font-family:Verdana;">Candida</span></i><span style="font-family:Verdana;"> <i>spp</i></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">.</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> </span></span></span></i> on <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">rezafungin</span><i><span style="font-family:Verdana;">.</span></i><span style="font-family:Verdana;"> Monte Carlo simulation was used to calculate probability of target attainment and a cumulative fraction of response to assess the best dosing regimen. The optimal dosage regimen for <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span style="font-family:Verdana;"> <i>albicans</i></span> <span style="font-family:Verdana;"></span></i></span><span style="font-family:Verdana;">and <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">glabrata </span></i><span style="font-family:Verdana;"></span></span></i></span></span><span style="font-family:Verdana;">was 50 mg IV, and the optimal dosage regimen for <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">parapsilosis</span></i><span style="font-family:Verdana;"></span></span></i><span style="font-family:Verdana;"> was 100 mg IV. Lastly, rezafungin has an excellent antifungal effect on <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span> <i><span style="font-family:Verdana;">albicans</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">C.</span></i> <i><span style="font-family:Verdana;">glabrata</span></i><span style="font-family:Verdana;"></span></span></i> <span style="font-family:Verdana;">and <i></i></span><i><i><span style="font-family:Verdana;">C.</span></i><span style="font-family:Verdana;"> <i>parapsilosis.</i></span></i>
文摘<b><span style="font-family:Verdana;">Objective: </span></b><span style="font-family:""><span style="font-family:Verdana;">To select the ingredients and targets of Yiqing capsule in treating COVID-19 based on network pharmacology, then to explore the potential mechanism of Yiqing capsule in treating COVID-19. </span><b><span style="font-family:Verdana;">Methods:</span></b> </span><span style="font-family:Verdana;">We </span><span style="font-family:Verdana;">screened the ingredients and targets of Yiqing capsule on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and target genes for COVID-19 in GeneCards database</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> constructed drug-ingredient-target</span><span style="font-family:Verdana;"> network through software Cytoscape 3.7.2</span><span style="font-family:Verdana;">,</span><span style="font-family:""> </span><span style="font-family:Verdana;">and </span><span style="font-family:Verdana;">constructed protein protein interaction network (PPI) network through STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of key gene targets of Yiqing capsule </span><span style="font-family:Verdana;">are used to</span><span style="font-family:""><span style="font-family:Verdana;"> treat COVID-19 through software R5.3.2. </span><b><span style="font-family:Verdana;">Results</span></b></span><b><span style="font-family:Verdana;">: </span></b><span style="font-family:""><span style="font-family:Verdana;">We got 42 ingredients, 42 potential therapeutic targets, 1643 GO items and 970 pathways in our study. The main pathway including IL-17 signaling pathway, Chagas disease (American trypanosomiasis), Influenza A, and TNF signaling pathway. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span><b><span style="font-family:Verdana;">: </span></b><span style="font-family:Verdana;">Yiqing capsule plays a role in treating COVID-19 through multiple ingredients, multiple targets and multiple pathways.
基金National Key Research and Development Program of China(2022YFB2802803)National Natural Science Foundation of China(61925104,62031011,62274042)+2 种基金Natural Science Foundation of Shanghai Municipality(21ZR1406200)China Mobile Research Institute X-NETJiangsu Provincial Key Research and Development Program(BE2021008-5).
文摘Visible light communication(VLC)based on laser diodes demonstrates great potential for high data rate maritime,terrestrial,and aerial wireless data links.Here,we design and fabricate high-speed blue laser diodes(LDs)grown on c-plane gallium nitride(GaN)substrate.This was achieved through active region design and miniaturization toward a narrow ridge waveguide,short cavity length,and single longitudinal mode Fabry–Perot laser diode.The fabricated mini-LD has a low threshold current of 31 mA and slope efficiency of 1.02 W/A.A record modulation bandwidth of 5.9 GHz(−3dB)was measured from the mini-LD.Using the developed mini-LD as a transmitter,the VLC link exhibits a high data transmission rate of 20.06 Gbps adopting the bit and power loading discrete multitone(DMT)modulation technique.The corresponding bit error rate is 0.003,satisfying the forward error correction standard.The demonstrated GaN-based mini-LD has significantly enhanced data transmission rates,paving the path for energy-efficient VLC systems and integrated photonics in the visible regime.
文摘Adhesive forces commonly exhibit a monotonic increase or a maximum with increasing relative humidity. However, anomalous behavior has been reported. Here, a numerical model of adhesive forces, comprised mainly of capillary and van der Waals forces, between a tip and a surface is established. It is described by a power law that considers the geometry, the liquid bridge wetting radius, the contact angle, and the separation distance. Capillary forces (sum of surface tension and Laplace pressure) and van der Waals forces are calculated. The latter cannot be neglected in the adhesion even at high humidity. Decrease in adhesion with increasing relative humidity can be attributed to a blunt tip shape, which is validated by experimental data. Specifically, the decrease in adhesion is attributed primarily to a transition from a rounded to a blunt tip shape. Structuring objects at the micro- or nanoscale can either increase or decrease adhesion as a function of relative humidity. This has a wide range of applications in robotic manipulation and can provide a better understanding of adhesion mechanisms in atomic force microscopy in ambient air.
基金supported by the NCI/NIH (grant number 1R21CA216770)Tobacco-Related Disease Research Program (grant number 27IR-0016)+5 种基金CDMRP Kidney Cancer Research Program (grant number W81XWH-20-1-0918)Cancer Research Coordinating Committee (grant number CRC15-380768)2021 Kure It Cancer Research Grant (www.kureit.org) to L.W.UCLA institutional support grants included the UCLA Jonsson Comprehensive Cancer Center (grant number P30CA016042)the UCLA Clinical and Translational Science Institute (grant number UL1TR001881)UCLA 3 R grant (Office of Vice Chancellor of Research) to L.W.UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Research Award Program.
文摘Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.
基金the National Natural Science Foundation of China(NSFC)(Grant Nos.61425007 and 61635007)Guangdong Natural Science Foundation(Grant Nos.2015B010105007 and 2014A030308007)+3 种基金Science and Technology Innovation Commission of Shenzhen(Grant Nos.JCYJ20170412105604705 and JCYJ20160427104925452)Development and Reform Commission of Shenzhen Municipality Foundationthe National Natural Science Foundation of China(Grant No.61565002)Guangxi Province Key Research and Development Program(Grant No.AB171129027).
文摘A high-sensitivity all-fiber temperature sensor based on a Sagnac interferometer is demonstrated by splicing a section of polarization maintaining fiber(PMF)between two sections of standard single mode fibers(SMFs).In this sensor,the SMF-PMF-SMF structure in the Sagnac loop is bent into a circle to enhance the sensitivity.The length and curvature of the PMF in the loop are investigated and can be optimized to further increase the temperature sensitivity of the sensor. Results show that the radius of the circle has an important effect upon temperature sensitivity due to the bend-induced birefringence variation of the PMF.The SMF-PMF-SMF structure bent into a circle with a radius of 30mm exhibits a high-sensitivity temperature of 1.73nm/℃.The sensor is provided with the advantages of easy fabrication,low-insertion loss,and high sensitivity,which may find potential applications in the field of high precision temperature measurement.
基金National Natural Science Foundation of China(11904060,12074281)。
文摘We demonstrate that multiple higher-order topological transitions can be triggered via the continuous change of the geometry in kagome photonic crystals composed of three dielectric rods. By tuning a single geometry parameter, the photonic corner and edge states emerge or disappear with higher-order topological transitions. Two distinct higher-order topological insulator phases and a normal insulator phase are revealed. Their topological indices are obtained from symmetry representations. A photonic analog of the fractional corner charge is introduced to distinguish the two higher-order topological insulator phases. Our predictions can be readily realized and verified in configurable dielectric photonic crystals.
基金supported by National Natural Science Foundation of China(grant number 81772721,81874089,81602236,81702522)Natural Science Foundation of Jiangxi Province of China(20202BABL216060)National Major Scientific and Technological Special Project for“Significant New Drugs Development”(2017ZX09304022).
文摘Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated.We conducted this study to access the potential link between junction plakoglobin(JUP)and HIF2αin ccRCC.Methods:Affinity purification and mass spectrometry(AP-MS)screening,glutathione-s-transferase(GST)pull-down and co-immunoprecipitation(Co-IP)assays were performed to detect the interacting proteins of HIF2α.Quantitative PCR(qPCR)and Western blotting were used to detect the expression of JUP in human ccRCC samples.Luciferase reporter assays,chromatin immunoprecipitation(ChIP),cycloheximide chase assays,and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α.Cell Counting Kit-8(CCK-8)assays,colony formation assays,transwell assays,and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.Results:We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau(VHL)and histone deacetylases 1/2(HDAC1/2)to HIF2α to regulate its stability and transactivation.JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo.Importantly,the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.Conclusion:Taken together,these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.