DEAR EDITOR,Accurate estimation of population size is a crucial issue in wildlife population ecology and conservation.While Global Positioning System(GPS)collars are well recognized as an effective method for monitori...DEAR EDITOR,Accurate estimation of population size is a crucial issue in wildlife population ecology and conservation.While Global Positioning System(GPS)collars are well recognized as an effective method for monitoring wildlife behavior,their application in direct wildlife population size estimation remains underutilized.In this study,GPS telemetry was employed to survey a rhesus macaque(Macaca mulatta)population on Neilingding Island in Guangdong,China.From May 2021 to April 2022,32 macaques across nine groups were fitted with GPS collars,producing a dataset of 109739 location fixes.Analyzing data from all tracked individuals revealed the annual home ranges of the nine groups.展开更多
Border Gateway Protocol(BGP)is a standard inter-domain routing protocol for the Internet that conveys network layer reachability information and establishes routes to different destinations.The BGP protocol exhibits s...Border Gateway Protocol(BGP)is a standard inter-domain routing protocol for the Internet that conveys network layer reachability information and establishes routes to different destinations.The BGP protocol exhibits security design defects,such as an unconditional trust mechanism and the default acceptance of BGP route announcements from peers by BGP neighboring nodes,easily triggering prefix hijacking,path forgery,route leakage,and other BGP security threats.Meanwhile,the traditional BGP security mechanism,relying on a public key infrastructure,faces issues like a single point of failure and a single point of trust.The decentralization,anti-tampering,and traceability advantages of blockchain offer new solution ideas for constructing secure and trusted inter-domain routing mechanisms.In this paper,we summarize the characteristics of BGP protocol in detail,sort out the BGP security threats and their causes.Additionally,we analyze the shortcomings of the traditional BGP security mechanism and comprehensively evaluate existing blockchain-based solutions to address the above problems and validate the reliability and effectiveness of blockchain-based BGP security methods in mitigating BGP security threats.Finally,we discuss the challenges posed by BGP security problems and outline prospects for future research.展开更多
BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer...BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.展开更多
<b><span style="font-family:Verdana;">INTRODUCTION</span></b><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="...<b><span style="font-family:Verdana;">INTRODUCTION</span></b><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: Extracorporeal membrane oxygenation (ECMO) is commonly used for refractory cardiac or respiratory failure. There are reported cases of successful use of ECMO in patients with septic shock;however, there is a lack of evidence to prove its overall efficacy. Thus, we conducted this study to analyze the relationship between sepsis and ECMO in our own patients.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">METHODS</span></b></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">: 305 patients who were placed on ECMO between 2010 and 2020 were identified within an IRB-approved database. Their clinical outcomes were an</span><span><span style="font-family:Verdana;">alyzed with a specific focus on patients who were septic before or during ECMO, defined as a positive blood culture. Group S was composed of patients with a positive blood culture before or during ECMO, while Group N was composed of all patients without a positive blood culture before or during ECMO. The primary outcome compared between groups was </span><span style="font-family:Verdana;">ECMO</span><span style="font-family:Verdana;"> survival rate. </span><b><span style="font-family:Verdana;">RESULTS</span></b><span style="font-family:Verdana;">: Among the 305 patients on ECMO, 58 (19%) were in Group S and 247 (81%) were in Group N. ECMO survival rates were 45% in Group S and 62% in Group N (p = 0.017).</span></span></span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">CONCLUSION</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: Of our 305 patients, patients who were septic upon ECMO </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">placement or those who developed sepsis during ECMO had worse ECMO survival rates than non-septic patients. Ultimately, patients who are septic or have a high probability of becoming septic may not be indicated for ECMO placement, and cautious administration of ECMO to these patients may be necessary.</span></span></span>展开更多
AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by in...AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimalpatients with APCa as compared with GEM alone.展开更多
To rapidly determine the pollution extent of wastewater, the calibration models were established for deter-mination of Chemical Oxygen Demand and Biological Oxygen Demand in wastewater by partial least squares and nea...To rapidly determine the pollution extent of wastewater, the calibration models were established for deter-mination of Chemical Oxygen Demand and Biological Oxygen Demand in wastewater by partial least squares and near infrared spectrometry of 120 samples. Spectral data preprocessing and outliers’ diagnosis were also discussed. Correlation coefficients of the models were 0.9542 and 0.9652, and the root mean square error of prediction (RMSEP) were 25.24 mg?L-1 and 12.13 mg?L-1 in the predicted range of 28.40~528.0 mg?L-1 and 16.0~305.2 mg?L-1 for Chemical Oxygen Demand and Biological Oxygen Demand, respectively. By statistical significance test, the results of determination were compared with those of stan-dard methods with no significant difference at 0.05 level. The method has been applied to simultaneous de-termination of Chemical Oxygen Demand and Biological Oxygen Demand in wastewater with satisfactory results.展开更多
AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-...AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide assay.After treatment with 10 μg/mL oridonin for 24 h and 48 h,the cells were stained with acridine orange/ethidium bromide.The morphologic changes were observed under an inverted fluorescence microscope.DNA fragmen-tation(a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay.After treated with oridonin(0,1.25,2.5,5 and 10 μg/mL),HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis,and oridonin-induced apoptosis in HGC-27 cells was detected.After treatment with oridonin for 24 h,the effects of oridonin on expression of Apaf-1,Bcl-2,Bax,caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction(RT-PCR) and Western blotting.RESULTS:Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose-and time-dependent manner.The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h(1.25,2.5,5 and 10 μg/mL) were 1.78% ± 0.36%,4.96% ± 1.59%,10.35% ± 2.76% and 41.6% ± 4.29%,respectively,which showed a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%,21.57% ± 3.75%,30.31% ± 4.91% and 61.19% ± 5.81%,with a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%,31.86% ± 3.86%,48.30% ± 4.16% and 81.80% ± 6.72%,with a significant difference(P < 0.05).Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining.After treatment with oridonin,the cells became round,shrank,and developed small buds around the nuclear membrane while forming apoptotic bodies.Lactate dehydrogenase(LDH) release assay showed that after treated with 1.25 μg/mL and 20 μg/mL oridonin for 24 h,LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4%(P < 0.001).However,the change in the release of LDH caused by necrosis was insignificant,suggesting thatthe major cause of oridonin-induced HGC-27 cell death was apoptosis.Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls(P < 0.05).And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%,12.8% ± 2.53%,28.5% ± 4.23% and 49.6% ± 3.76%,which were in a dose-dependent manner(P < 0.05).After treatment for 24 h,DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dosedependent manner.RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3(0.917 ± 0.103 vs 0.357 ± 0.019,P < 0.05),cytochrome c(1.429 ± 0.111 vs 1.002 ± 0.014,P < 0.05),Apaf-1(0.688 ± 0.101 vs 0.242 ± 0.037,P < 0.05) and Bax(0.856 ± 0.101 vs 0.278 ± 0.027,P < 0.05)(P < 0.05),whereas down-regulated in Bcl-2(0.085 ± 0.012 vs 0.175 ± 0.030,P < 0.05).Western blotting analysis also confirmed this result.CONCLUSION:Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1,caspase-3 and cytochrome c,which are highly dependent upon the mitochondrial pathway.展开更多
Objective: To investigate the relationship between extracellular signal-regulated kinase (ERK) pathway, multidrug resistance gene (mdr-1), ribonucleotide recluctase M1 (RRM1) gene and their roles in gemcitabine...Objective: To investigate the relationship between extracellular signal-regulated kinase (ERK) pathway, multidrug resistance gene (mdr-1), ribonucleotide recluctase M1 (RRM1) gene and their roles in gemcitabine (GEM) chemoresistance in pancreatic cancer cell line SW1990. Methods: The GEM-resistance cell model was constructed by a stepwise method. Immunohistochemistry was used to measure the expression of ERK protein (ERK1/2) in the established cell strains in a semiquantitative way. The mRNA expression of mdr-1 and RRM1 were detected by RT-PCR. MTT assay was performed to determine the IC50 value. Results: The established GEM-resistant cell strains were able to gain stable growth and passage ability in the medium contained different concentration levels of GEM (0, 30, 60, 100, 150 and 200 nmol/L). The expression of ERK protein, mdr-1 and RRM1 gene were elevated accompanied by the increase of GEM concentration. There was a highly positive correlation between mdr-1, RRM1 expression and GEM-resistanca level (r = 0.960, P = 0.002 and r = 0.966, P = 0.002). The expression of ERK protein also correlated with the mdr-1 and RRM1 level (r = -0.943, P = 0.005 and r = -0.883, P = 0.02). At the GEM-resistance level of 200 nmol/L, the grey scale value of ERK1/2 was 164.22 ±13.17, mdr-1/β-actin and RRM1/β-actin were 1.41 ±0.04 and 1.45 ± 0.18, respectively; after treated with ERK pathway inhibitor U0126, these values synchronously decreased to 186.85 ± 13.14, 0.2 3± 0.02 and 0.21 ± 0.03, respectively; inversely, the ERK1/2 grey scale value was 106.55 ± 16.45, mdr-l/β-actin and RRMl/β-actin were 1.50± 0.07 and 1.52 ± 0.12, respectively, which presented a tendency of synchronously increase after treated with ERK pathway activator EGF. The IC50 values in GEM-resistant cells of 0 nmol/L and 200 nmol/L levels were 4.104 and 10.20, respectively. After treated with U0126, these values decreased to 3.26 and 4.50, respectively; while treated with EGF, the IC50 values increased to 8.89 and 17.17, respectively. Conclusion: The ERK pathway may induce the GEM-chemoresistance in pancreatic cell line SW1990 through the participation in the regulation of the mdr-1 and RRM1 gene expression.展开更多
To investigate the principles of differentiation and prescription of traditional Chinese medicine(TCM)treatment for cancerous fever by logistic stepwise regression and literature investigation,the following databases ...To investigate the principles of differentiation and prescription of traditional Chinese medicine(TCM)treatment for cancerous fever by logistic stepwise regression and literature investigation,the following databases were searched(from inception to June 30th 2016):CNKI,CSPD,CBM,PubMed,MEDLINE,EMBASE.According to the inclusion and exclusion criteria,literatures about TCM in the treatment of cancerous fever were screened.The frequency about cancerous fever of differential syndrome types,formulas and herbs were analyzed by logistic multiple regression analysis.The model about syndrome types and formula application of cancerous fever was established.The result showed formula prescriptions used most frequently were Qing-Hao-Bie-Jia decoction,Xiao-Chai-Hu decoction,Xue-Fu-Zhu-Yu decoction,Bai-Hu decoction,San-Ren decoction.The main syndrome types of cancerous fever were as follows:Toxic heat flourishing type,Yin deficiency type,Stagnation of damp-heat type,Qi-Yin deficiency type,Liver meridian depressed-heat type,Blood stasis type and Yang deficiency type.Based on regression equation of the syndrome types,the corresponding herbs of this seven syndrome types were Radix Bupleuri,Radix Paeoniae Alba and Scutellaria Baicalensis Georgi;Radix Bupleuri and Cortex Moutan;Radix Paeoniae Rubra and Radix Angelicae Sinensis;Rhizoma Pinelliae,Cortex Lycii Radicis and Radix Paeoniae Alba;Herba Artemisiae Annuae,Gypsum Fibrosum and Poria Cocos;Rhizoma Anemarrhenae,Scutellaria Baicalensis Georgi and Radix Codonopsis;Radix Bupleuri respectively.The results of Logistic regression analysis and frequency of herbs statistics can provide reference for differentiation and treatment of cancerous fever in clinical.展开更多
Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we r...Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).展开更多
Ferroelectric tunnel junctions(FTJs)have great potential for application in high-density non-volatile memories.Recently,α-In_(2)Se_(3) was found to exhibit robust in-plane and out-of-plane ferroelectric polarizations...Ferroelectric tunnel junctions(FTJs)have great potential for application in high-density non-volatile memories.Recently,α-In_(2)Se_(3) was found to exhibit robust in-plane and out-of-plane ferroelectric polarizations at a monolayer thickness,which is ideal to serve as a ferroelectric component in miniaturized electronic devices.In this work,we design two-dimensional van der Waals heterostructures composed of anα-In_(2)Se_(3) ferroelectric and a hexagonal IV–VI semiconductor and propose an in-plane FTJ based on these heterostructures.Our first-principles calculations show that the electronic band structure of the designed heterostructures can be switched between insulating and metallic states by ferroelectric polarization.We demonstrate that the in-plane FTJ exhibits two distinct transport regimes,tunneling and metallic,for OFF and ON states,respectively,leading to a giant tunneling electroresistance effect with the OFF/ON resistance ratio exceeding 1×104.Our results provide a promising approach for the high-density ferroelectric memory based on the 2D ferroelectric/semiconductor heterostructures.展开更多
The high-speed rail(HSR)network in China has experienced rapid development since the 2000s.In 2016,the State Council of the People’s Republic of China issued a revised version of the“Mid-and Long-term Railway Networ...The high-speed rail(HSR)network in China has experienced rapid development since the 2000s.In 2016,the State Council of the People’s Republic of China issued a revised version of the“Mid-and Long-term Railway Network Plan”,detailing the expansion of the railway network and construction of an HSR system.In the future,the HSR construction efforts in China will further increase,which is considered to impact regional development and air pollutant emissions.Therefore,in this paper,we apply a transportation network-multiregional computable general equilibrium(CGE)model to estimate the dynamic effects of HSR projects on economic growth,regional disparities,and air pollutant emissions in China.The results indicate that HSR system improvement could generate a positive economic impact but could also increase emissions.The gross domestic product(GDP)growth per unit investment cost stimulated by HSR investment is found to be the largest in eastern China but the smallest in the northwest regions.Conversely,HSR investment in Northwest China contributes to a substantial reduction in regional disparities in terms of the GDP per capita.In regard to air pollution emissions,HSR construction in South-Central China results in the largest increase in CO_(2) and NO_(X) emissions,while for CO,SO_(2),and fine particulate matter(PM_(2.5))emissions,the largest increase occurs due to HSR construction in Northwest China.At the regional level,the provinces with large changes in accessibility also experience large changes in their air pollutant emissions.展开更多
20E-hydroxyecdysone(20E)plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response.Insect metamorphosis is a highly successful strategy for environme...20E-hydroxyecdysone(20E)plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response.Insect metamorphosis is a highly successful strategy for environmental adaptation and is the most vulnerable stage during which the insect is susceptible to various pathogens.20E regulates a series of antimicrobial peptides(AMPs)through the immunodeficiency(IMD)pathway activation in Drosophila;nevertheless,whether other immune pathways are involved in 20E-regulated insect immunity is unknown.Our previous studies showed that BmMD-2A is a member of the MD-2-related lipid recognition(ML)family of proteins that are involved in the Bombyx mori innate immunity Toll signaling pathway.In this study,we further demonstrate that BmMD-2A is also positively regulated by 20E,and the BmMD-2A neutralization experiment suggested that 20E activates some downstream immune effect factors,the AMP genes against Escherichia coli and Staphylococcus aureus,through the regulation of BmMD-2A in larval metamorphosis,implying that B.mori may use the Toll-ML signaling pathway to maintain innate immune balance in the larval-pupal metamorphosis stage,which is a different innate immunity pathway regulated by 20E compared to the IMD pathway in Drosophila.展开更多
Electronic devices that are transparent and flexible have a wide range of applications in the domains of vital sign parameter monitoring,health management,and so on.Ferroelectric memory is a revolutionary nonvolatile ...Electronic devices that are transparent and flexible have a wide range of applications in the domains of vital sign parameter monitoring,health management,and so on.Ferroelectric memory is a revolutionary nonvolatile memory that is ideal for data storage and processing in transparent flexible electronic systems.In this study,Ce-doped hafnium oxide ferroelectric thin film is manufactured on mica substrate by the chemical solution deposition with transparent indium tin oxide(ITO)thin films as the bottom electrodes.The transmittance of mica/ITO/Hf_(0.85)Ce_(0.15)O_(2)thin film is over 80%.The 2Pr of the transparent flexible Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film is increased by about 22.4%and the Ec is reduced by 26.7%compared with those of Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film grown on p+-Si substrate.The transparent flexible Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film can remain keeping good quality when being bent under±2.5 mm bending radius.Additionally,degradation of polarization,retention,and endurance performance was not obvious even at a bending radius of 5.0 mm after 104 bending cycles.This research provides a new strategy and an important experimental basis for the development and implementation of transparent flexible ferroelectric memories.展开更多
基金supported by the Forestry Administration of Guangdong Province(33000-42090019)Shenzhen Science and Technology Innovation Committee(Basic Research 20180285)+1 种基金Nature Science Foundation of Guangdong,China(2021A 1515010641)Neilingding-Futian National Nature Reserve。
文摘DEAR EDITOR,Accurate estimation of population size is a crucial issue in wildlife population ecology and conservation.While Global Positioning System(GPS)collars are well recognized as an effective method for monitoring wildlife behavior,their application in direct wildlife population size estimation remains underutilized.In this study,GPS telemetry was employed to survey a rhesus macaque(Macaca mulatta)population on Neilingding Island in Guangdong,China.From May 2021 to April 2022,32 macaques across nine groups were fitted with GPS collars,producing a dataset of 109739 location fixes.Analyzing data from all tracked individuals revealed the annual home ranges of the nine groups.
基金the National Natural Science Foundation of China,GrantNumbers(62272007,62001007)the Natural Science Foundation of Beijing,GrantNumbers(4234083,4212018)The authors also acknowledge the support from King Khalid University for funding this research through the Large Group Project under Grant Number RGP.2/373/45.
文摘Border Gateway Protocol(BGP)is a standard inter-domain routing protocol for the Internet that conveys network layer reachability information and establishes routes to different destinations.The BGP protocol exhibits security design defects,such as an unconditional trust mechanism and the default acceptance of BGP route announcements from peers by BGP neighboring nodes,easily triggering prefix hijacking,path forgery,route leakage,and other BGP security threats.Meanwhile,the traditional BGP security mechanism,relying on a public key infrastructure,faces issues like a single point of failure and a single point of trust.The decentralization,anti-tampering,and traceability advantages of blockchain offer new solution ideas for constructing secure and trusted inter-domain routing mechanisms.In this paper,we summarize the characteristics of BGP protocol in detail,sort out the BGP security threats and their causes.Additionally,we analyze the shortcomings of the traditional BGP security mechanism and comprehensively evaluate existing blockchain-based solutions to address the above problems and validate the reliability and effectiveness of blockchain-based BGP security methods in mitigating BGP security threats.Finally,we discuss the challenges posed by BGP security problems and outline prospects for future research.
基金Supported by the National Natural Science Funds of China,No.81974448Guangdong Medical Research Foundation,No.B2019126Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324135005013.
文摘BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.
文摘<b><span style="font-family:Verdana;">INTRODUCTION</span></b><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: Extracorporeal membrane oxygenation (ECMO) is commonly used for refractory cardiac or respiratory failure. There are reported cases of successful use of ECMO in patients with septic shock;however, there is a lack of evidence to prove its overall efficacy. Thus, we conducted this study to analyze the relationship between sepsis and ECMO in our own patients.</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">METHODS</span></b></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">: 305 patients who were placed on ECMO between 2010 and 2020 were identified within an IRB-approved database. Their clinical outcomes were an</span><span><span style="font-family:Verdana;">alyzed with a specific focus on patients who were septic before or during ECMO, defined as a positive blood culture. Group S was composed of patients with a positive blood culture before or during ECMO, while Group N was composed of all patients without a positive blood culture before or during ECMO. The primary outcome compared between groups was </span><span style="font-family:Verdana;">ECMO</span><span style="font-family:Verdana;"> survival rate. </span><b><span style="font-family:Verdana;">RESULTS</span></b><span style="font-family:Verdana;">: Among the 305 patients on ECMO, 58 (19%) were in Group S and 247 (81%) were in Group N. ECMO survival rates were 45% in Group S and 62% in Group N (p = 0.017).</span></span></span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">CONCLUSION</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">: Of our 305 patients, patients who were septic upon ECMO </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">placement or those who developed sepsis during ECMO had worse ECMO survival rates than non-septic patients. Ultimately, patients who are septic or have a high probability of becoming septic may not be indicated for ECMO placement, and cautious administration of ECMO to these patients may be necessary.</span></span></span>
文摘AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimalpatients with APCa as compared with GEM alone.
文摘To rapidly determine the pollution extent of wastewater, the calibration models were established for deter-mination of Chemical Oxygen Demand and Biological Oxygen Demand in wastewater by partial least squares and near infrared spectrometry of 120 samples. Spectral data preprocessing and outliers’ diagnosis were also discussed. Correlation coefficients of the models were 0.9542 and 0.9652, and the root mean square error of prediction (RMSEP) were 25.24 mg?L-1 and 12.13 mg?L-1 in the predicted range of 28.40~528.0 mg?L-1 and 16.0~305.2 mg?L-1 for Chemical Oxygen Demand and Biological Oxygen Demand, respectively. By statistical significance test, the results of determination were compared with those of stan-dard methods with no significant difference at 0.05 level. The method has been applied to simultaneous de-termination of Chemical Oxygen Demand and Biological Oxygen Demand in wastewater with satisfactory results.
基金Supported by Medical and Health Research Foundation of Zhejiang Province,No. 2009B019
文摘AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide assay.After treatment with 10 μg/mL oridonin for 24 h and 48 h,the cells were stained with acridine orange/ethidium bromide.The morphologic changes were observed under an inverted fluorescence microscope.DNA fragmen-tation(a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay.After treated with oridonin(0,1.25,2.5,5 and 10 μg/mL),HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis,and oridonin-induced apoptosis in HGC-27 cells was detected.After treatment with oridonin for 24 h,the effects of oridonin on expression of Apaf-1,Bcl-2,Bax,caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction(RT-PCR) and Western blotting.RESULTS:Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose-and time-dependent manner.The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h(1.25,2.5,5 and 10 μg/mL) were 1.78% ± 0.36%,4.96% ± 1.59%,10.35% ± 2.76% and 41.6% ± 4.29%,respectively,which showed a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%,21.57% ± 3.75%,30.31% ± 4.91% and 61.19% ± 5.81%,with a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%,31.86% ± 3.86%,48.30% ± 4.16% and 81.80% ± 6.72%,with a significant difference(P < 0.05).Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining.After treatment with oridonin,the cells became round,shrank,and developed small buds around the nuclear membrane while forming apoptotic bodies.Lactate dehydrogenase(LDH) release assay showed that after treated with 1.25 μg/mL and 20 μg/mL oridonin for 24 h,LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4%(P < 0.001).However,the change in the release of LDH caused by necrosis was insignificant,suggesting thatthe major cause of oridonin-induced HGC-27 cell death was apoptosis.Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls(P < 0.05).And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%,12.8% ± 2.53%,28.5% ± 4.23% and 49.6% ± 3.76%,which were in a dose-dependent manner(P < 0.05).After treatment for 24 h,DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dosedependent manner.RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3(0.917 ± 0.103 vs 0.357 ± 0.019,P < 0.05),cytochrome c(1.429 ± 0.111 vs 1.002 ± 0.014,P < 0.05),Apaf-1(0.688 ± 0.101 vs 0.242 ± 0.037,P < 0.05) and Bax(0.856 ± 0.101 vs 0.278 ± 0.027,P < 0.05)(P < 0.05),whereas down-regulated in Bcl-2(0.085 ± 0.012 vs 0.175 ± 0.030,P < 0.05).Western blotting analysis also confirmed this result.CONCLUSION:Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1,caspase-3 and cytochrome c,which are highly dependent upon the mitochondrial pathway.
文摘Objective: To investigate the relationship between extracellular signal-regulated kinase (ERK) pathway, multidrug resistance gene (mdr-1), ribonucleotide recluctase M1 (RRM1) gene and their roles in gemcitabine (GEM) chemoresistance in pancreatic cancer cell line SW1990. Methods: The GEM-resistance cell model was constructed by a stepwise method. Immunohistochemistry was used to measure the expression of ERK protein (ERK1/2) in the established cell strains in a semiquantitative way. The mRNA expression of mdr-1 and RRM1 were detected by RT-PCR. MTT assay was performed to determine the IC50 value. Results: The established GEM-resistant cell strains were able to gain stable growth and passage ability in the medium contained different concentration levels of GEM (0, 30, 60, 100, 150 and 200 nmol/L). The expression of ERK protein, mdr-1 and RRM1 gene were elevated accompanied by the increase of GEM concentration. There was a highly positive correlation between mdr-1, RRM1 expression and GEM-resistanca level (r = 0.960, P = 0.002 and r = 0.966, P = 0.002). The expression of ERK protein also correlated with the mdr-1 and RRM1 level (r = -0.943, P = 0.005 and r = -0.883, P = 0.02). At the GEM-resistance level of 200 nmol/L, the grey scale value of ERK1/2 was 164.22 ±13.17, mdr-1/β-actin and RRM1/β-actin were 1.41 ±0.04 and 1.45 ± 0.18, respectively; after treated with ERK pathway inhibitor U0126, these values synchronously decreased to 186.85 ± 13.14, 0.2 3± 0.02 and 0.21 ± 0.03, respectively; inversely, the ERK1/2 grey scale value was 106.55 ± 16.45, mdr-l/β-actin and RRMl/β-actin were 1.50± 0.07 and 1.52 ± 0.12, respectively, which presented a tendency of synchronously increase after treated with ERK pathway activator EGF. The IC50 values in GEM-resistant cells of 0 nmol/L and 200 nmol/L levels were 4.104 and 10.20, respectively. After treated with U0126, these values decreased to 3.26 and 4.50, respectively; while treated with EGF, the IC50 values increased to 8.89 and 17.17, respectively. Conclusion: The ERK pathway may induce the GEM-chemoresistance in pancreatic cell line SW1990 through the participation in the regulation of the mdr-1 and RRM1 gene expression.
文摘To investigate the principles of differentiation and prescription of traditional Chinese medicine(TCM)treatment for cancerous fever by logistic stepwise regression and literature investigation,the following databases were searched(from inception to June 30th 2016):CNKI,CSPD,CBM,PubMed,MEDLINE,EMBASE.According to the inclusion and exclusion criteria,literatures about TCM in the treatment of cancerous fever were screened.The frequency about cancerous fever of differential syndrome types,formulas and herbs were analyzed by logistic multiple regression analysis.The model about syndrome types and formula application of cancerous fever was established.The result showed formula prescriptions used most frequently were Qing-Hao-Bie-Jia decoction,Xiao-Chai-Hu decoction,Xue-Fu-Zhu-Yu decoction,Bai-Hu decoction,San-Ren decoction.The main syndrome types of cancerous fever were as follows:Toxic heat flourishing type,Yin deficiency type,Stagnation of damp-heat type,Qi-Yin deficiency type,Liver meridian depressed-heat type,Blood stasis type and Yang deficiency type.Based on regression equation of the syndrome types,the corresponding herbs of this seven syndrome types were Radix Bupleuri,Radix Paeoniae Alba and Scutellaria Baicalensis Georgi;Radix Bupleuri and Cortex Moutan;Radix Paeoniae Rubra and Radix Angelicae Sinensis;Rhizoma Pinelliae,Cortex Lycii Radicis and Radix Paeoniae Alba;Herba Artemisiae Annuae,Gypsum Fibrosum and Poria Cocos;Rhizoma Anemarrhenae,Scutellaria Baicalensis Georgi and Radix Codonopsis;Radix Bupleuri respectively.The results of Logistic regression analysis and frequency of herbs statistics can provide reference for differentiation and treatment of cancerous fever in clinical.
基金This work was supported by the National Key Research and Development Program during the 14th Five-year Plan Period(2023YFC2706304)the National Key R&D Program of China(2023YFC3403300)+4 种基金National Natural Science Foundation of China(82220108017,82141128,82371074)Capital Health Development Research Special Project(2024-1-2052)Beijing Science and Technology Program(Z231100004823021,Z201100005520045)Beijing Natural Science Foundation(J230031)Sanming Project of Medicine in Shenzhen(No.SZSM202311018)and Chigenovo Co.,Ltd.
文摘Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.12072307 and 12175191)the Outstanding Youth Science Foundation of Hunan Province,China(Grant No.2021JJ20041)the Research Foundation of Education Bureau of Hunan Province,China(Grant No.21A0114).The atomic structures were plotted using VESTA software.
文摘Ferroelectric tunnel junctions(FTJs)have great potential for application in high-density non-volatile memories.Recently,α-In_(2)Se_(3) was found to exhibit robust in-plane and out-of-plane ferroelectric polarizations at a monolayer thickness,which is ideal to serve as a ferroelectric component in miniaturized electronic devices.In this work,we design two-dimensional van der Waals heterostructures composed of anα-In_(2)Se_(3) ferroelectric and a hexagonal IV–VI semiconductor and propose an in-plane FTJ based on these heterostructures.Our first-principles calculations show that the electronic band structure of the designed heterostructures can be switched between insulating and metallic states by ferroelectric polarization.We demonstrate that the in-plane FTJ exhibits two distinct transport regimes,tunneling and metallic,for OFF and ON states,respectively,leading to a giant tunneling electroresistance effect with the OFF/ON resistance ratio exceeding 1×104.Our results provide a promising approach for the high-density ferroelectric memory based on the 2D ferroelectric/semiconductor heterostructures.
基金supported by funding from the National Natural Science Foundation of China(Nos.41821005 and 42077196).
文摘The high-speed rail(HSR)network in China has experienced rapid development since the 2000s.In 2016,the State Council of the People’s Republic of China issued a revised version of the“Mid-and Long-term Railway Network Plan”,detailing the expansion of the railway network and construction of an HSR system.In the future,the HSR construction efforts in China will further increase,which is considered to impact regional development and air pollutant emissions.Therefore,in this paper,we apply a transportation network-multiregional computable general equilibrium(CGE)model to estimate the dynamic effects of HSR projects on economic growth,regional disparities,and air pollutant emissions in China.The results indicate that HSR system improvement could generate a positive economic impact but could also increase emissions.The gross domestic product(GDP)growth per unit investment cost stimulated by HSR investment is found to be the largest in eastern China but the smallest in the northwest regions.Conversely,HSR investment in Northwest China contributes to a substantial reduction in regional disparities in terms of the GDP per capita.In regard to air pollution emissions,HSR construction in South-Central China results in the largest increase in CO_(2) and NO_(X) emissions,while for CO,SO_(2),and fine particulate matter(PM_(2.5))emissions,the largest increase occurs due to HSR construction in Northwest China.At the regional level,the provinces with large changes in accessibility also experience large changes in their air pollutant emissions.
基金funded by grants from the National Science Foundation of China(grant no.31970462)the Natural Science Foundation of Guangdong Province(no.2020A1515110805,no.2020A1515010867,no.2021A1515012090).
文摘20E-hydroxyecdysone(20E)plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response.Insect metamorphosis is a highly successful strategy for environmental adaptation and is the most vulnerable stage during which the insect is susceptible to various pathogens.20E regulates a series of antimicrobial peptides(AMPs)through the immunodeficiency(IMD)pathway activation in Drosophila;nevertheless,whether other immune pathways are involved in 20E-regulated insect immunity is unknown.Our previous studies showed that BmMD-2A is a member of the MD-2-related lipid recognition(ML)family of proteins that are involved in the Bombyx mori innate immunity Toll signaling pathway.In this study,we further demonstrate that BmMD-2A is also positively regulated by 20E,and the BmMD-2A neutralization experiment suggested that 20E activates some downstream immune effect factors,the AMP genes against Escherichia coli and Staphylococcus aureus,through the regulation of BmMD-2A in larval metamorphosis,implying that B.mori may use the Toll-ML signaling pathway to maintain innate immune balance in the larval-pupal metamorphosis stage,which is a different innate immunity pathway regulated by 20E compared to the IMD pathway in Drosophila.
基金supported by the National Natural Science Foundation of China(Nos.11902285 and 12072307)the Department of Education Project of Hunan Province,China(Nos.21B0112 and 19A106)+2 种基金the Science and Technology Agency Project of Hunan Province,China(No.2020JJ5526)the China Postdoctoral Science Foundation(No.2019TQ0273)the Outstanding Youth Science Foundation of Hunan Province,China(No.2021JJ20041).
文摘Electronic devices that are transparent and flexible have a wide range of applications in the domains of vital sign parameter monitoring,health management,and so on.Ferroelectric memory is a revolutionary nonvolatile memory that is ideal for data storage and processing in transparent flexible electronic systems.In this study,Ce-doped hafnium oxide ferroelectric thin film is manufactured on mica substrate by the chemical solution deposition with transparent indium tin oxide(ITO)thin films as the bottom electrodes.The transmittance of mica/ITO/Hf_(0.85)Ce_(0.15)O_(2)thin film is over 80%.The 2Pr of the transparent flexible Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film is increased by about 22.4%and the Ec is reduced by 26.7%compared with those of Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film grown on p+-Si substrate.The transparent flexible Hf_(0.85)Ce_(0.15)O_(2)ferroelectric thin film can remain keeping good quality when being bent under±2.5 mm bending radius.Additionally,degradation of polarization,retention,and endurance performance was not obvious even at a bending radius of 5.0 mm after 104 bending cycles.This research provides a new strategy and an important experimental basis for the development and implementation of transparent flexible ferroelectric memories.