AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family memb...AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.展开更多
Objective: To investigate the autophagy-inducing effect of Compound Berberine (CBBR) on CNE2 nasopharyngeal carcinoma (NPC) cells and its possible targets in P13K/AKT/mTOR signaling pathway. Methods: CNE2 cells at exp...Objective: To investigate the autophagy-inducing effect of Compound Berberine (CBBR) on CNE2 nasopharyngeal carcinoma (NPC) cells and its possible targets in P13K/AKT/mTOR signaling pathway. Methods: CNE2 cells at exponential growth phase were taken as the target cells in this study. Firstly, IC50 concentration for CBBR was determined by MTT assay. Then, 3 different concentrations of CBBR, 0.25 mg⋅mL−1, 0.50 mg⋅mL−1 and 1.00 mg⋅mL−1, around the concentration of IC50, were taken for followed intervention experiments respectively. Fluorescein labeling method was utilized to assay the inducing effect of CBBR on the autophagic activity of CNE2 cells, followed by Western blot procedure to explore the changes of key messenger molecules in the autophagy-related signaling pathway of P13K/AKT/mTOR, both combined with 3-MA block test in a comparative way and carried out by detecting the expressive levels of Beclin 1, LC3-II and LC3-I as well as the ratio of LC3-II:LC3-I. Results: IC50 of CBBR was determined at the level of 0.5 mg⋅mL−1. The inducing effect of CBBR on autophagy of CNE2 cells was shown occurring in various modes, not a simple concentration-dependent tendency, with its effect minimal at the concentration of 0.25 mg⋅mL−1 and maximal at the concentration of 0.50 mg⋅mL−1, while only slightly higher at the concentration of 1.00 mg⋅mL−1 than that of 0.5 mg⋅mL−1. Although its inducing effect was weakened a little following the pretreatment by 3-MA, the effect combined with CBBR was still significantly higher than that of simply blocked by 3-MA. Moreover, changes in the expressive levels of Beclin1, LC3-II and LC3-I as well as LC3-II:LC3-I all showed a tendency corresponding to the changed autophagic features of CNE2 cells (P Conclusions: CBBR can bring about inhibiting effect on the proliferating activity of CNE2 cells through inducing increased autophagic activity via intervening targets in P13K/AKT/mTOR signaling pathway, and this effect could not be completely blocked by the antagonist 3-MA.展开更多
In a circuit quantum electrodynamics(circuit QED) architecture, the microwave resonator could be used to couple and probe qubits. The long-range coupling and information transfer between nonlocal qubits can be perform...In a circuit quantum electrodynamics(circuit QED) architecture, the microwave resonator could be used to couple and probe qubits. The long-range coupling and information transfer between nonlocal qubits can be performed via photons trapped in a microwave resonator, promising an effective approach for scaling up solid-state qubits. A series of important advances in the hybrid system composed of a microwave resonator and semiconductor qubits have been achieved in recent years. For instance,with applications of high-impedance microwave resonators, the strong coupling regime between charge/spin qubits and a microwave resonator has been reached. Simultaneously, resonator-based dispersive readout and single-shot readout to probe the qubit state have been further improved due to the increase of the coupling strength. Here, we briefly introduce this hybrid system related to the progress and fruits in achieving the strong coupling between charge/spin qubits in double quantum dots(DQDs)and the resonator, the long-range coupling between qubits, and also the applications of the resonator for qubit state readout.展开更多
In this theoretical work,we describe a mechanism for the coupling between a plane structure consisting of four quantum dots and a resonator.We systematically study the dependence of the quadruple coupling strength and...In this theoretical work,we describe a mechanism for the coupling between a plane structure consisting of four quantum dots and a resonator.We systematically study the dependence of the quadruple coupling strength and the qubit decoherence rate and point out the optimized operating position of the hybrid system.According to the transmission given by the input-output theory,the signatures in the resonator spectrum are predicted.Furthermore,based on the parameters already achieved in previous works,we prove that the device described in this paper can achieve the strong coupling limit,i.e.,this approach can be used for system extension under the existing technical conditions.Our results show an effective and promotable approach to couple quantum dot structures in plane with the resonator and propose a meaningful extension method.展开更多
Objective: Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (ESCC)...Objective: Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (ESCC) for a long term. tubeimoside I (TBMS1) is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells. Methods: Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins' expression and location. Results: Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMS1-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B1/cdc2 complex-related G2/M cell cycle arrest. Conclusions: Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC.展开更多
BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors d...BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.展开更多
Although different types of drugs are available for postmenopausal osteoporosis,the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis...Although different types of drugs are available for postmenopausal osteoporosis,the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents.Here,we defined that norlichexanthone(NOR),a natural product,is a ligand of estrogen receptor-alpha(ERα)and revealed its therapeutic potential for postmenopausal osteoporosis.We used mammalian-one hybrid assay to screen for ERαmodulators from crude extracts of several plant endophytes.As a result,NOR purified from the extract of endophyte ARL-13 was identified as a selective ERαmodulator.NOR directly bound to ERαwith an affinity in nanomolar range,revealing that it is a natural ligand of ERα.NOR induced osteoblast formation in MC3T3-E1 precursor cells.Conversely,NOR inhibited receptor activator of nuclear factor-kappa B ligand(RANKL)-induced osteoclast formation in both RAW264.7 macrophages and mouse primary monocytes.Mechanistically,NOR inhibited RANKL-induced association of ERαand TRAF6 to prevent ERα-mediated TRAF6 activation via Lys63-linked ubiquitination.Importantly,NOR exhibited potent anti-osteoporosis efficacy in an ovariectomized mouse model.Comparing to estrogen,NOR was of much less capability in stimulating endometrial hyperplasia and promoting mammalian cancer cell proliferation.Taken together,our study identified NOR as a natural and high affinity ligand of ERαwith substantial anti-osteoporosis but less estrogenic activity.展开更多
AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible stud...AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios(HRs) values and 95% confidence intervals(CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval(published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746(66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count(PLT) before therapy significantly increased the probability of postoperative recurrence(HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence(HR = 1.49, 95%CI: 1.25-1.77). Subgroupand meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.展开更多
AIM: To investigate the effects of single nucleotide polymorphisms(SNPs) in glutathione S-transferase(GST) genes on survival of hepatocellular carcinoma(HCC) patients.METHODS: Twelve tagging SNPs in GST genes(includin...AIM: To investigate the effects of single nucleotide polymorphisms(SNPs) in glutathione S-transferase(GST) genes on survival of hepatocellular carcinoma(HCC) patients.METHODS: Twelve tagging SNPs in GST genes(including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom Mass ARRAY i PLEX genotyping method in a cohort of 214 Chinese patients with resected HCC.The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome.Additionally, stratified analysis was performed at each level of the demographic and clinical variables.An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.RESULTS: Two SNPs(GSTO2 : rs7085725 and GSTP1 : rs4147581) were significantly associated with overall survival in HCC patients(P = 0.035 and 0.042, respectively).In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis.We further investigated cumulative effects of these two SNPs on overall survival in HCC patients.Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death(P < 0.001).The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis(HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001).Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variantalleles of rs7085725(HR = 2.07, 95%CI: 1.13-3.76, P = 0.018).The distributions of GSTO2 : rs7085725 and GSTP1 : rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.展开更多
Conerent photon source is an important element that has been widely used in spectroscopy,imaging,detection,and teleportation in quantum optics.However,it is still a challenge to realize micro-scale coherent emitters i...Conerent photon source is an important element that has been widely used in spectroscopy,imaging,detection,and teleportation in quantum optics.However,it is still a challenge to realize micro-scale coherent emitters in semiconductor systems.We report the observation of gain in a cavity-coupled GaAs double quantum dot system with a voltage bias across the device.By characterizing and analyzing the cavity responses to different quantum dot behaviors,we distinguish the microwave photon emission from the signal gain.This study provides a possibility to realize micro-scale amplifiers or coherent microwave photon sources in circuit quantum electrodynamics(cQED) hybrid systems.展开更多
BACKGROUND Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer(EC or EJC).Postoperative anastomotic leakage(AL)remains problematic.The use of fibrin sealant(FS)may ...BACKGROUND Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer(EC or EJC).Postoperative anastomotic leakage(AL)remains problematic.The use of fibrin sealant(FS)may improve the strength of esophageal anastomosis and reduce the incidence of AL.AIM To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC.METHODS In this single-arm,phase II trial(Clinicaltrial.gov identifier:NCT03529266),we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0.An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis.After performing the anastomosis,2.5 mL of porcine FS was applied circumferentially.The primary endpoint was the proportion of patients with AL within 3 mo.RESULTS From June 4,2018,to December 29,2018,57 patients were enrolled.At the data cutoff date(June 30,2019),three(5.3%)of the 57 patients had developed AL,including two(3.5%)with esophagogastric AL and one(1.8%)with gastric fistula.The incidence of anastomotic stricture and other major postoperative complications was 1.8%and 17.5%,respectively.The median time needed to resume oral feeding after operation was 8 d(Interquartile range:7.0-9.0 d).No adverse events related to FS were recorded.No deaths occurred within 90 d after surgery.CONCLUSION Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC.Further phase III studies are warranted.展开更多
Interactions between water and solid substrates are of fundamental importance to various processes in nature and industry.Electric control is widely used to modify interfacial water,where the influence of surface char...Interactions between water and solid substrates are of fundamental importance to various processes in nature and industry.Electric control is widely used to modify interfacial water,where the influence of surface charges is inevitable.Here we obtain positively and negatively charged surfaces using Li Ta O_(3) crystals and observe that a large net surface charge up to 0.1 C/m;can nominally change the contact angles of pure water droplets comparing to the same uncharged surface.However,even a small amount of surface charge can efficiently increase the water contact angle in the presence of aerosols.Our results indicate that such surface charges can hardly affect the structure of interfacial water molecular layers and the morphology of the macroscopic droplet,while adsorption of a small amount of organic contaminants from aerosols with the help of Coulomb attraction can notably decrease the wettability of solid surface.Our results not only provide a fundamental understanding of the interactions between charged surfaces and water,but also help to develop new techniques on electric control of wettability and microfluidics in real aerosol environments.展开更多
HfO_(2)-based ferroelectrics have evoked considerable interest owing to the complementary metal-oxide semiconductor compatibility and robust ferroelectricity down to a few unit cells.However,the unique wake-up effect ...HfO_(2)-based ferroelectrics have evoked considerable interest owing to the complementary metal-oxide semiconductor compatibility and robust ferroelectricity down to a few unit cells.However,the unique wake-up effect of HfO_(2)-based ferroelectric films severely restricts the improvement of their performance.In particular,the domain structure is an important characteristic of ferroelectric materials,which still has not been well understood in HfO_(2)-based ferroelectrics.In this work,a Hf_(0.5)Zr_(0.5)O_(2) ferroelectric thin film is grown on a typical Si substrate buffered with TiN electrode.The 90°domains of the Pca21 ferroelectric phase with head-to-tail and tail-to-tail structures can be observed by Cs-corrected scanning transmission electron microscope under their pristine condition.After waking up,the 180°domain is displayed in the ferroelectric phase.The remarkable differences in domain walls for 90°and 180°domains are characterized by qualitatively mapping the polarization distributions at the atomic scale.The domain wall changes from the[101]of the Hf_(0.5)Zr_(0.5)O_(2) film to the[001]of the Hf_(0.5)Zr_(0.5)O_(2) film.This result provides fundamental information for understanding the domain structure of HfO_(2)-based ferroelectrics.展开更多
A magnetic biochar adsorbent(BM–OH–BC)was prepared through NaOH–ball milling co-modification with walnut shells as the raw material,and its oil adsorption characteristics were investigated.The adsorption properties...A magnetic biochar adsorbent(BM–OH–BC)was prepared through NaOH–ball milling co-modification with walnut shells as the raw material,and its oil adsorption characteristics were investigated.The adsorption properties of oil pollutants were compared before and after the NaOH-ball-milling co-modification,and the mechanism of NaOH-ball-milling on oil pollutants was investigated by scanning electron microscope-energy dispersive X-ray spectroscopy,BET,X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy.The experimental results showed that the oil adsorption capacity of BM–OH–BC can reach 2.75 g/g,which is 129%higher than that of unmodified biochar.Moreover,after five adsorption and desorption cycles,the adsorption rate of BM–OH–BC only decreased by 5.9%,which was because the oil adsorption of BM–OH–BC is mainly chemical adsorption.The adsorption processes involving single layer,heterogeneous phase and multilayer made BM–OH–BC have excellent adsorption properties.After biochar co-modification,the specific surface area of BM–OH–BC increased to 466 m^(2)/g,the total pore volume increased to 0.245 cm^(3)/g,the average pore size decreased to1.90 nm,and the number of hydrophobic non-polar functional groups increased,leading to the enhancement of its oil absorption capacity.This study provides a reference for the treatment of oil-contaminated water bodies.展开更多
To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three decades.Tandem...To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three decades.Tandem stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 months.More than two decades after its introduction,trials exploring the utility of tandem transplants have yielded mixed results.The role of tandem ASCT in multiple myeloma(MM)remains unclear and controversial.In the EMN02/HOVON95 study.展开更多
Phase transitions involving oxygen ion extraction within the framework of the crystallographic relevance have been widely exploited for sake of superconductivity,ferromagnetism,and ion conductivity in perovskiterelate...Phase transitions involving oxygen ion extraction within the framework of the crystallographic relevance have been widely exploited for sake of superconductivity,ferromagnetism,and ion conductivity in perovskiterelated oxides.However,atomic-scale pathways of phase transitions and ion extraction threshold are inadequately understood.Here we investigate the atomic structure evolution of LaCoO_(3) films upon oxygen extraction and subsequent Co migration,focusing on the key role of epitaxial strain.The brownmillerite to Ruddlesden-Popper phase transitions are discovered to stabilize at distinct crystal orientations in compressive-and tensile-strained cobaltites,which could be attributed to in-plane and out-of-plane Ruddlesden-Popper stacking faults,respectively.A two-stage process from exterior to interior phase transition is evidenced in compressive-strained LaCoO_(2.5),while a single-step nucleation process leaving bottom layer unchanged in tensile-strained situation.Strain analyses reveal that the former process is initiated by an expansion in Co layer at boundary,whereas the latter one is associated with an edge dislocation combined with antiphase boundary.These findings provide a chemomechanical perspective on the structure regulation of perovskite oxides and enrich insights into strain-dependent phase diagram in epitaxial oxides films.展开更多
基金Supported by the Science and Technology Program of Guangzhou(No.201803010066)the High-level Hospital Construction Project,Zhongshan Ophthalmic Center,Sun Yat-sen University(No.303010202).
文摘AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.
文摘Objective: To investigate the autophagy-inducing effect of Compound Berberine (CBBR) on CNE2 nasopharyngeal carcinoma (NPC) cells and its possible targets in P13K/AKT/mTOR signaling pathway. Methods: CNE2 cells at exponential growth phase were taken as the target cells in this study. Firstly, IC50 concentration for CBBR was determined by MTT assay. Then, 3 different concentrations of CBBR, 0.25 mg⋅mL−1, 0.50 mg⋅mL−1 and 1.00 mg⋅mL−1, around the concentration of IC50, were taken for followed intervention experiments respectively. Fluorescein labeling method was utilized to assay the inducing effect of CBBR on the autophagic activity of CNE2 cells, followed by Western blot procedure to explore the changes of key messenger molecules in the autophagy-related signaling pathway of P13K/AKT/mTOR, both combined with 3-MA block test in a comparative way and carried out by detecting the expressive levels of Beclin 1, LC3-II and LC3-I as well as the ratio of LC3-II:LC3-I. Results: IC50 of CBBR was determined at the level of 0.5 mg⋅mL−1. The inducing effect of CBBR on autophagy of CNE2 cells was shown occurring in various modes, not a simple concentration-dependent tendency, with its effect minimal at the concentration of 0.25 mg⋅mL−1 and maximal at the concentration of 0.50 mg⋅mL−1, while only slightly higher at the concentration of 1.00 mg⋅mL−1 than that of 0.5 mg⋅mL−1. Although its inducing effect was weakened a little following the pretreatment by 3-MA, the effect combined with CBBR was still significantly higher than that of simply blocked by 3-MA. Moreover, changes in the expressive levels of Beclin1, LC3-II and LC3-I as well as LC3-II:LC3-I all showed a tendency corresponding to the changed autophagic features of CNE2 cells (P Conclusions: CBBR can bring about inhibiting effect on the proliferating activity of CNE2 cells through inducing increased autophagic activity via intervening targets in P13K/AKT/mTOR signaling pathway, and this effect could not be completely blocked by the antagonist 3-MA.
基金supported by the National Key Research and Development Program of China(Grant No.2016YFA0301700)the National Natural Science Foundation of China(Grant Nos.61922074,12074368,and12034018)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302300)。
文摘In a circuit quantum electrodynamics(circuit QED) architecture, the microwave resonator could be used to couple and probe qubits. The long-range coupling and information transfer between nonlocal qubits can be performed via photons trapped in a microwave resonator, promising an effective approach for scaling up solid-state qubits. A series of important advances in the hybrid system composed of a microwave resonator and semiconductor qubits have been achieved in recent years. For instance,with applications of high-impedance microwave resonators, the strong coupling regime between charge/spin qubits and a microwave resonator has been reached. Simultaneously, resonator-based dispersive readout and single-shot readout to probe the qubit state have been further improved due to the increase of the coupling strength. Here, we briefly introduce this hybrid system related to the progress and fruits in achieving the strong coupling between charge/spin qubits in double quantum dots(DQDs)and the resonator, the long-range coupling between qubits, and also the applications of the resonator for qubit state readout.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.92265113,12074368,and 12034018).
文摘In this theoretical work,we describe a mechanism for the coupling between a plane structure consisting of four quantum dots and a resonator.We systematically study the dependence of the quadruple coupling strength and the qubit decoherence rate and point out the optimized operating position of the hybrid system.According to the transmission given by the input-output theory,the signatures in the resonator spectrum are predicted.Furthermore,based on the parameters already achieved in previous works,we prove that the device described in this paper can achieve the strong coupling limit,i.e.,this approach can be used for system extension under the existing technical conditions.Our results show an effective and promotable approach to couple quantum dot structures in plane with the resonator and propose a meaningful extension method.
基金supported by the Natural Science Foundation of Fujian Province of China (No. 2011J05098)the Fundamental Research Funds for the Central Universities (No. 2011121055)+1 种基金Grants from the National Natural Science Foundation of China (No. 81202956)SRF for ROCS, SEM [2011]1568 and NSFC (No. 81102332)
文摘Objective: Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (ESCC) for a long term. tubeimoside I (TBMS1) is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells. Methods: Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins' expression and location. Results: Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMS1-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B1/cdc2 complex-related G2/M cell cycle arrest. Conclusions: Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC.
基金Supported by the National Natural Science Foundation of China,No.81773128 and No.81871998the Natural Science Basic Research Plan in Shaanxi Province of China,No.2018JM7013 and No.2017JM8039+1 种基金the Research Fund for Young Star of Science and Technology in Shaanxi Province,No.2018KJXX-022China Postdoctoral Science Foundation,No.2018M641000
文摘BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
基金supported by the National Natural Science Foundation of China(Grant Nos.31770811,31471318 and 31271453)the Fundamental Research Funds for the Central Universities(Grant No.20720190082,China)+1 种基金the Regional Demonstration of Marine Economy Innovative Development Project(Grant No.16PYY007SF17,China)the Fujian Provincial Science&Technology Department(Grant No.2017YZ0002-1,China)
文摘Although different types of drugs are available for postmenopausal osteoporosis,the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents.Here,we defined that norlichexanthone(NOR),a natural product,is a ligand of estrogen receptor-alpha(ERα)and revealed its therapeutic potential for postmenopausal osteoporosis.We used mammalian-one hybrid assay to screen for ERαmodulators from crude extracts of several plant endophytes.As a result,NOR purified from the extract of endophyte ARL-13 was identified as a selective ERαmodulator.NOR directly bound to ERαwith an affinity in nanomolar range,revealing that it is a natural ligand of ERα.NOR induced osteoblast formation in MC3T3-E1 precursor cells.Conversely,NOR inhibited receptor activator of nuclear factor-kappa B ligand(RANKL)-induced osteoclast formation in both RAW264.7 macrophages and mouse primary monocytes.Mechanistically,NOR inhibited RANKL-induced association of ERαand TRAF6 to prevent ERα-mediated TRAF6 activation via Lys63-linked ubiquitination.Importantly,NOR exhibited potent anti-osteoporosis efficacy in an ovariectomized mouse model.Comparing to estrogen,NOR was of much less capability in stimulating endometrial hyperplasia and promoting mammalian cancer cell proliferation.Taken together,our study identified NOR as a natural and high affinity ligand of ERαwith substantial anti-osteoporosis but less estrogenic activity.
基金Supported by National Natural Science Foundation of China,No.81272644 and No.81072051
文摘AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios(HRs) values and 95% confidence intervals(CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval(published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746(66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count(PLT) before therapy significantly increased the probability of postoperative recurrence(HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence(HR = 1.49, 95%CI: 1.25-1.77). Subgroupand meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.
基金Supported by Grants from National Natural Science Foundation of China,No.81201549 and No.81272644the Project of Innovative Research Team for Key Science and Technology in Xi’an Jiaotong University,No.2003KCJ-23
文摘AIM: To investigate the effects of single nucleotide polymorphisms(SNPs) in glutathione S-transferase(GST) genes on survival of hepatocellular carcinoma(HCC) patients.METHODS: Twelve tagging SNPs in GST genes(including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom Mass ARRAY i PLEX genotyping method in a cohort of 214 Chinese patients with resected HCC.The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome.Additionally, stratified analysis was performed at each level of the demographic and clinical variables.An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.RESULTS: Two SNPs(GSTO2 : rs7085725 and GSTP1 : rs4147581) were significantly associated with overall survival in HCC patients(P = 0.035 and 0.042, respectively).In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis.We further investigated cumulative effects of these two SNPs on overall survival in HCC patients.Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death(P < 0.001).The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis(HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001).Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variantalleles of rs7085725(HR = 2.07, 95%CI: 1.13-3.76, P = 0.018).The distributions of GSTO2 : rs7085725 and GSTP1 : rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
基金Project supported by the National Key Research and Development Program of China(Grant No.2016YFA0301700)the National Natural Science Foundation of China(Grant Nos.61922074,11674300,61674132,11625419,and 11804327)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB24030601)the Anhui Initiative in Quantum Information Technologies,China(Grant No.AHY080000)。
文摘Conerent photon source is an important element that has been widely used in spectroscopy,imaging,detection,and teleportation in quantum optics.However,it is still a challenge to realize micro-scale coherent emitters in semiconductor systems.We report the observation of gain in a cavity-coupled GaAs double quantum dot system with a voltage bias across the device.By characterizing and analyzing the cavity responses to different quantum dot behaviors,we distinguish the microwave photon emission from the signal gain.This study provides a possibility to realize micro-scale amplifiers or coherent microwave photon sources in circuit quantum electrodynamics(cQED) hybrid systems.
基金Supported by Fundamental Research Funds for the Central Universities,No.17ykzd30National Natural Science Foundation of China,No.81972614+1 种基金Guangdong Esophageal Cancer Institute Science and Technology Program,No.M201601Health&Medical Collaborative Innovation Project of Guangzhou City,China,No.201803040018.
文摘BACKGROUND Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer(EC or EJC).Postoperative anastomotic leakage(AL)remains problematic.The use of fibrin sealant(FS)may improve the strength of esophageal anastomosis and reduce the incidence of AL.AIM To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC.METHODS In this single-arm,phase II trial(Clinicaltrial.gov identifier:NCT03529266),we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0.An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis.After performing the anastomosis,2.5 mL of porcine FS was applied circumferentially.The primary endpoint was the proportion of patients with AL within 3 mo.RESULTS From June 4,2018,to December 29,2018,57 patients were enrolled.At the data cutoff date(June 30,2019),three(5.3%)of the 57 patients had developed AL,including two(3.5%)with esophagogastric AL and one(1.8%)with gastric fistula.The incidence of anastomotic stricture and other major postoperative complications was 1.8%and 17.5%,respectively.The median time needed to resume oral feeding after operation was 8 d(Interquartile range:7.0-9.0 d).No adverse events related to FS were recorded.No deaths occurred within 90 d after surgery.CONCLUSION Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC.Further phase III studies are warranted.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12025407,11934003,9185012011774328)+1 种基金the Key R&D Program of China(Grant No.2016YFA0300902)the Chinese Academy of Sciences。
文摘Interactions between water and solid substrates are of fundamental importance to various processes in nature and industry.Electric control is widely used to modify interfacial water,where the influence of surface charges is inevitable.Here we obtain positively and negatively charged surfaces using Li Ta O_(3) crystals and observe that a large net surface charge up to 0.1 C/m;can nominally change the contact angles of pure water droplets comparing to the same uncharged surface.However,even a small amount of surface charge can efficiently increase the water contact angle in the presence of aerosols.Our results indicate that such surface charges can hardly affect the structure of interfacial water molecular layers and the morphology of the macroscopic droplet,while adsorption of a small amount of organic contaminants from aerosols with the help of Coulomb attraction can notably decrease the wettability of solid surface.Our results not only provide a fundamental understanding of the interactions between charged surfaces and water,but also help to develop new techniques on electric control of wettability and microfluidics in real aerosol environments.
基金This work is supported by the National Natural Science Foundation of China(nos.51901166,11932016,52122205,52072400,and 52025025)the Fundamental Research Funds for the Central Universities(no.QTZX22064).
文摘HfO_(2)-based ferroelectrics have evoked considerable interest owing to the complementary metal-oxide semiconductor compatibility and robust ferroelectricity down to a few unit cells.However,the unique wake-up effect of HfO_(2)-based ferroelectric films severely restricts the improvement of their performance.In particular,the domain structure is an important characteristic of ferroelectric materials,which still has not been well understood in HfO_(2)-based ferroelectrics.In this work,a Hf_(0.5)Zr_(0.5)O_(2) ferroelectric thin film is grown on a typical Si substrate buffered with TiN electrode.The 90°domains of the Pca21 ferroelectric phase with head-to-tail and tail-to-tail structures can be observed by Cs-corrected scanning transmission electron microscope under their pristine condition.After waking up,the 180°domain is displayed in the ferroelectric phase.The remarkable differences in domain walls for 90°and 180°domains are characterized by qualitatively mapping the polarization distributions at the atomic scale.The domain wall changes from the[101]of the Hf_(0.5)Zr_(0.5)O_(2) film to the[001]of the Hf_(0.5)Zr_(0.5)O_(2) film.This result provides fundamental information for understanding the domain structure of HfO_(2)-based ferroelectrics.
基金This work was financially supported by the National Natural Science Fund of China(No.42007415)the Natural Science Foundation of Shaanxi Province(No.2020SF-435)。
文摘A magnetic biochar adsorbent(BM–OH–BC)was prepared through NaOH–ball milling co-modification with walnut shells as the raw material,and its oil adsorption characteristics were investigated.The adsorption properties of oil pollutants were compared before and after the NaOH-ball-milling co-modification,and the mechanism of NaOH-ball-milling on oil pollutants was investigated by scanning electron microscope-energy dispersive X-ray spectroscopy,BET,X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy.The experimental results showed that the oil adsorption capacity of BM–OH–BC can reach 2.75 g/g,which is 129%higher than that of unmodified biochar.Moreover,after five adsorption and desorption cycles,the adsorption rate of BM–OH–BC only decreased by 5.9%,which was because the oil adsorption of BM–OH–BC is mainly chemical adsorption.The adsorption processes involving single layer,heterogeneous phase and multilayer made BM–OH–BC have excellent adsorption properties.After biochar co-modification,the specific surface area of BM–OH–BC increased to 466 m^(2)/g,the total pore volume increased to 0.245 cm^(3)/g,the average pore size decreased to1.90 nm,and the number of hydrophobic non-polar functional groups increased,leading to the enhancement of its oil absorption capacity.This study provides a reference for the treatment of oil-contaminated water bodies.
基金supported by grants from the Department of Science and Technology of the Fujian Province Project(Nos.2017I0004 and 2017Y9057)the Fujian provincial health technology project(No.2021ZD01005)+2 种基金the National Key Clinical Specialty Discipline Construction Program(No.2021-76)the Fujian Provincial Clinical Research Center for Hematological Malignancies(No.2020Y2006)the Fujian Provincial Key Clinical Specialty Discipline Construction Program.
文摘To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three decades.Tandem stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 months.More than two decades after its introduction,trials exploring the utility of tandem transplants have yielded mixed results.The role of tandem ASCT in multiple myeloma(MM)remains unclear and controversial.In the EMN02/HOVON95 study.
基金supported by the National Natural Science Foundation of China(Grant Nos.52322212,52072400,52025025,and 52250402)。
文摘Phase transitions involving oxygen ion extraction within the framework of the crystallographic relevance have been widely exploited for sake of superconductivity,ferromagnetism,and ion conductivity in perovskiterelated oxides.However,atomic-scale pathways of phase transitions and ion extraction threshold are inadequately understood.Here we investigate the atomic structure evolution of LaCoO_(3) films upon oxygen extraction and subsequent Co migration,focusing on the key role of epitaxial strain.The brownmillerite to Ruddlesden-Popper phase transitions are discovered to stabilize at distinct crystal orientations in compressive-and tensile-strained cobaltites,which could be attributed to in-plane and out-of-plane Ruddlesden-Popper stacking faults,respectively.A two-stage process from exterior to interior phase transition is evidenced in compressive-strained LaCoO_(2.5),while a single-step nucleation process leaving bottom layer unchanged in tensile-strained situation.Strain analyses reveal that the former process is initiated by an expansion in Co layer at boundary,whereas the latter one is associated with an edge dislocation combined with antiphase boundary.These findings provide a chemomechanical perspective on the structure regulation of perovskite oxides and enrich insights into strain-dependent phase diagram in epitaxial oxides films.
基金supported by the Key Research Program of Chinese Academy of Sciences(ZDBS-SSW-JSC007-2)the Project from China National Space Administration(CE5C0400YJFM00507)。
基金supported by the National Key Research and Development Program of China(2016YFA0301700)the National Natural Science Foundation of China(61922074,11674300,61674132,11625419 and 11804327)+2 种基金the Strategic Priority Research Program of the CAS(XDB24030601)the Anhui Initiative in Quantum Information Technologies(AHY080000)financial support by U.S.ARO through Grant No.W911NF1410346 and No.W911NF1710257。
